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Sneak Peak: The Hospital Leader Blog “The Impact of Hospital Design on Health – for Patients AND Providers”
I was rounding on the inpatient general medicine teaching service last weekend and offered to meet my team of students and residents in the “resident library” on Saturday morning. (Although it holds the name “library,” there were no books or periodicals to be seen.) I had not been in the library for many months and was struck by a few things as I entered. 
It is a dimly lit space, lined on three of the four walls with rickety desks and desktop computers all facing the walls. The walls are painted an off-white color with innumerable dings and nicks, presumably accumulated over the course of years. There was a string of garland in the shape of a Christmas tree pinned to the wall (P.S. It is March), the entire left side of which was sagging and misshapen. There were various tattered and coffee-stained papers scattered haphazardly throughout the room, including what appeared to be progress notes and test results printed from the EHR; a few worn ECGs; a telemetry strip; even a few (REALLY old, no doubt) chest x-ray films. Lining the fourth wall was a large foldable table, topped with crumbs and food scraps, a half-eaten chocolate Bundt cake, and scattered napkins and utensils, some of which appeared to be used. The one exterior-facing wall had a row of windows with crinkled blinds, some completely closed, others opened at awkward angles and seemingly stuck in place. There was a cadre of chairs in the room, none matching, all in various stages of disrepair, with one completely missing an armrest and another tucked in the corner, probably needing the addition of a handwritten sign “BRokEn.”
This library is a place where the students, interns, and residents go for a bit of a safe haven. They can take their coats off, sit down, have their own computer space, answer pages, and complain about their woes. They can bounce questions off each other, vent frustrations, find the humor in a situation, and just be themselves. So,But what struck me about their sanctuary is that it is totally and utterly depressing. And it was as if they didn’t even notice the chaos and filth laying everywhere around them. I find it impossible to believe that it does not have an effect on their mood and outlook. Although we are all social animals, and we have a real need to congregate and connect with one another, is this really the best environment to do that?
Read the full text of this blog post at hospitalleader.org.
Dr. Scheurer is a clinical hospitalist and the medical director of quality and safety at the Medical University of South Carolina in Charleston.
Also on The Hospital Leader…
- Should Overuse Be Considered an Adverse Event By Chris Moriates, MD
- Pulling the Welcome Mat Out from Under Our Colleagues By Brett Hendel-Paterson, MD
- The Upside of Anger By Tracy Cardin, ACNP-BC, SFHM
- Does Your Onboarding Process Really Get Folks on Board? By Leslie Flores, MH, SFHM
- A GIF Is Worth 3000 Words: Introducing #Visual Abstract for #JHMChat By Charlie Wray, DO
I was rounding on the inpatient general medicine teaching service last weekend and offered to meet my team of students and residents in the “resident library” on Saturday morning. (Although it holds the name “library,” there were no books or periodicals to be seen.) I had not been in the library for many months and was struck by a few things as I entered.
It is a dimly lit space, lined on three of the four walls with rickety desks and desktop computers all facing the walls. The walls are painted an off-white color with innumerable dings and nicks, presumably accumulated over the course of years. There was a string of garland in the shape of a Christmas tree pinned to the wall (P.S. It is March), the entire left side of which was sagging and misshapen. There were various tattered and coffee-stained papers scattered haphazardly throughout the room, including what appeared to be progress notes and test results printed from the EHR; a few worn ECGs; a telemetry strip; even a few (REALLY old, no doubt) chest x-ray films. Lining the fourth wall was a large foldable table, topped with crumbs and food scraps, a half-eaten chocolate Bundt cake, and scattered napkins and utensils, some of which appeared to be used. The one exterior-facing wall had a row of windows with crinkled blinds, some completely closed, others opened at awkward angles and seemingly stuck in place. There was a cadre of chairs in the room, none matching, all in various stages of disrepair, with one completely missing an armrest and another tucked in the corner, probably needing the addition of a handwritten sign “BRokEn.”
This library is a place where the students, interns, and residents go for a bit of a safe haven. They can take their coats off, sit down, have their own computer space, answer pages, and complain about their woes. They can bounce questions off each other, vent frustrations, find the humor in a situation, and just be themselves. So,But what struck me about their sanctuary is that it is totally and utterly depressing. And it was as if they didn’t even notice the chaos and filth laying everywhere around them. I find it impossible to believe that it does not have an effect on their mood and outlook. Although we are all social animals, and we have a real need to congregate and connect with one another, is this really the best environment to do that?
Read the full text of this blog post at hospitalleader.org.
Dr. Scheurer is a clinical hospitalist and the medical director of quality and safety at the Medical University of South Carolina in Charleston.
Also on The Hospital Leader…
- Should Overuse Be Considered an Adverse Event By Chris Moriates, MD
- Pulling the Welcome Mat Out from Under Our Colleagues By Brett Hendel-Paterson, MD
- The Upside of Anger By Tracy Cardin, ACNP-BC, SFHM
- Does Your Onboarding Process Really Get Folks on Board? By Leslie Flores, MH, SFHM
- A GIF Is Worth 3000 Words: Introducing #Visual Abstract for #JHMChat By Charlie Wray, DO
I was rounding on the inpatient general medicine teaching service last weekend and offered to meet my team of students and residents in the “resident library” on Saturday morning. (Although it holds the name “library,” there were no books or periodicals to be seen.) I had not been in the library for many months and was struck by a few things as I entered.
It is a dimly lit space, lined on three of the four walls with rickety desks and desktop computers all facing the walls. The walls are painted an off-white color with innumerable dings and nicks, presumably accumulated over the course of years. There was a string of garland in the shape of a Christmas tree pinned to the wall (P.S. It is March), the entire left side of which was sagging and misshapen. There were various tattered and coffee-stained papers scattered haphazardly throughout the room, including what appeared to be progress notes and test results printed from the EHR; a few worn ECGs; a telemetry strip; even a few (REALLY old, no doubt) chest x-ray films. Lining the fourth wall was a large foldable table, topped with crumbs and food scraps, a half-eaten chocolate Bundt cake, and scattered napkins and utensils, some of which appeared to be used. The one exterior-facing wall had a row of windows with crinkled blinds, some completely closed, others opened at awkward angles and seemingly stuck in place. There was a cadre of chairs in the room, none matching, all in various stages of disrepair, with one completely missing an armrest and another tucked in the corner, probably needing the addition of a handwritten sign “BRokEn.”
This library is a place where the students, interns, and residents go for a bit of a safe haven. They can take their coats off, sit down, have their own computer space, answer pages, and complain about their woes. They can bounce questions off each other, vent frustrations, find the humor in a situation, and just be themselves. So,But what struck me about their sanctuary is that it is totally and utterly depressing. And it was as if they didn’t even notice the chaos and filth laying everywhere around them. I find it impossible to believe that it does not have an effect on their mood and outlook. Although we are all social animals, and we have a real need to congregate and connect with one another, is this really the best environment to do that?
Read the full text of this blog post at hospitalleader.org.
Dr. Scheurer is a clinical hospitalist and the medical director of quality and safety at the Medical University of South Carolina in Charleston.
Also on The Hospital Leader…
- Should Overuse Be Considered an Adverse Event By Chris Moriates, MD
- Pulling the Welcome Mat Out from Under Our Colleagues By Brett Hendel-Paterson, MD
- The Upside of Anger By Tracy Cardin, ACNP-BC, SFHM
- Does Your Onboarding Process Really Get Folks on Board? By Leslie Flores, MH, SFHM
- A GIF Is Worth 3000 Words: Introducing #Visual Abstract for #JHMChat By Charlie Wray, DO
Procalcitonin guidance improves antibiotic stewardship
The case
A 72-year-old male with COPD presents to the emergency department with increased dyspnea and cough. He is afebrile, and oxygen saturation is 87% on room air. WBC count is 9.5 with a normal differential, and chest x-ray is read by the radiologist as atelectasis versus early consolidation in the left lower lobe. Should antibiotics be initiated?
Background
The problem: Antibiotic overuse
With the increasing prevalence of antibiotic resistance in our nation’s hospitals, the need for robust antibiotic stewardship programs has continued to rise in importance. In 2016, the CDC reported a fatal case of septic shock due to a carbapenem-resistant strain of Klebsiella resistant to all tested antibiotics.1 This case received much media coverage; moreover, this patient represented only one of the approximately 23,000 patients infected with antibiotic-resistant bacteria in the United States who die each year. Although various approaches to curbing antibiotic resistance are being pursued, judicious antibiotic use is central to success. Current evidence suggests that up to 30% of antibiotics are not optimally prescribed,2 leaving a significant opportunity for improvement.
Lower respiratory infections account for a substantial proportion of antibiotic utilization in the United States. In a recent study, acute respiratory conditions generated 221 antibiotic prescriptions per 1,000 population, but only half of these were deemed appropriate.2 The inability to reliably discern viral from bacterial etiology is a driver of excess antibiotic use.
The procalcitonin assay has been touted as a possible solution to this problem. Multiple studies have evaluated its utility as a tool to help discriminate between bacterial infection and viral or noninfectious etiologies.
What is procalcitonin?
Thyroidal c-cells convert the prohormone procalcitonin to calcitonin, which is stored in secretory granules for release in response to fluctuations in calcium levels via a classical neuroendocrine feedback loop. Alternatively, procalcitonin can be synthesized in nonthyroidal parenchymal cells, and high levels of proinflammatory mediators secreted in response to bacterial endotoxin drive increased procalcitonin production. Interestingly, interferon gamma, up-regulated in viral infections, reduces procalcitonin production. Nonthyroidal parenchymal cells lack mechanisms for efficient conversion of procalcitonin to calcitonin and do not contain secretory granules to facilitate its regulated release. Hence bacterial infections correlate with higher serum procalcitonin levels.3
Evidence
Can procalcitonin guide antibiotic therapy in patients with acute respiratory illness while reducing antibiotic utilization?
The ability of procalcitonin to selectively identify bacterial infection makes it a potentially promising tool to advance the antibiotic stewardship agenda. Multiple randomized controlled trials have explored the use of procalcitonin-guided antibiotic therapy for treatment of lower respiratory tract infections such as acute bronchitis, exacerbations of COPD, and pneumonia. Each study discussed below was done in Switzerland, involved the same key investigator (Mirjam Christ-Crain, MD, PhD), and shared a similar design in which a threshold for low procalcitonin values (less than 0.1 mcg/L) and high procalcitonin values (greater than 0.25 mcg/L) was prespecified. Antibiotic therapy was strongly discouraged for patients with low procalcitonin and encouraged for those with high procalcitonin; antibiotics were not recommended for patients with intermediate values, but the treating physician was allowed ultimate discretion (Figure 1). All studies compared a procalcitonin-guided treatment group to a standard care group, in which antibiotics were prescribed by the treating physician based on established clinical guidelines.
Figure 1. Procalcitonin treatment algorithm
Procalcitonin Level (mcg/L) | Likelihood of bacterial infection | Antibiotic treatment |
less than 0.1 | Absent | Strongly discouraged |
0.1-0.25 | Unlikely | Discouraged |
0.25-0.5 | Possible | Encouraged |
greater than 0.5 | Present | Strongly encouraged |
Figure 1. Procalcitonin treatment algorithm
In a study focusing on outpatients presenting to their primary care physicians with acute respiratory tract infection, 53 primary care physicians in Switzerland recruited 458 patients. There was no significant difference in time to symptom resolution, as determined by patient report during an interview 14 days after initial presentation; however, 97% of patients in the standard-care group received antibiotics, compared with 25% in the procalcitonin-guided group. Equal numbers of patients (30% in each group) reported persistent symptoms at 28-day follow-up. Among the cohort of patients with upper respiratory infections or acute bronchitis, procalcitonin guidance reduced antibiotic prescriptions by 80%.4
In a blinded, single-center, randomized, controlled trial of 226 patients presenting to a university hospital with a COPD exacerbation severe enough to require a change in the baseline medication regimen, procalcitonin-guided therapy allowed for an absolute reduction of antibiotic use by 32% without an impact on outcomes. Rates of clinical improvement, ICU utilization, recurrent exacerbations, hospital length of stay, and mortality did not differ between the groups.5
Limitations include the possible impact of the Hawthorne effect, as physicians knew their antibiotic usage patterns were being monitored, which may impact generalizability of the findings to a real-world setting. Similarly, it is difficult to control for a spillover effect as providers exposed to the procalcitonin-guided algorithm became more comfortable with a restrictive prescribing approach. The costs of the additional procalcitonin assay must be weighed against the benefits. Incidence and cost of other adverse effects of antibiotic use (rates of Clostridium difficile, renal insufficiency, urticarial drug eruptions, etc.) were not addressed. The rapid assay currently has limited availability in the United States, though that is changing. Finally, recent additional studies (unrelated to procalcitonin) have suggested shorter antibiotic treatment durations for patients with pneumonia.8
Is there evidence for using procalcitonin to guide treatment in the broader population of ICU patients?
While there is good evidence for using procalcitonin to guide antibiotic use in patients with acute respiratory illness, the evidence for using procalcitonin in the broader cohort of critically-ill patients with sepsis is less well established.
The most promising results were reported by the Stop Antibiotics on Procalcitonin guidance Study (SAPS). Published in July 2016, this was a prospective, multicenter, randomized, controlled, open-label study of patients admitted to the ICU (not limited to respiratory illness) in the Netherlands. A total of 1,575 patients were assigned to the procalcitonin-guided group or the standard-of-care group. In the procalcitonin-guided group, procalcitonin levels were checked daily, and physicians were given nonbinding advice to discontinue antibiotics if procalcitonin levels decreased by greater than 80% from peak levels or to below 0.5 mcg/L.
Patients received an average of 7.5 daily defined antibiotic doses in the procalcitonin-guided group versus 9.3 daily defined doses in the standard-of-care group (P less than .0001). The median duration of antibiotic treatment in the procalcitonin arm was 5 days versus 7 days in the control group (P less than .0001). Mortality at 28 days was 20% in the procalcitonin group and 25% in the control group (P = .0122). At 1 year, mortality was 36% in the procalcitonin group and 43% in the control group (P = .0188). The authors hypothesized that the unexpected decrease in mortality in the procalcitonin group may have been due to earlier consideration of alternate illness etiologies in patients with a low procalcitonin level or decreased antibiotic side effects.9While the SAPS trial supports decreased antibiotic usage in ICU patients with the use of the procalcitonin assay, there are some important limitations. First, the trial was done in the Netherlands, where baseline antibiotic usage was comparatively low. Second, daily procalcitonin level monitoring was not continued for patients transferred out of the ICU while still on antibiotics. Further, guidelines for antibiotic discontinuation were nonbinding, and in many cases physicians did not stop antibiotics based on procalcitonin guidelines suggested by the study authors.
Earlier trials regarding the procalcitonin assay in the critical care setting similarly showed some promise but also concerns. One trial reported a 25% reduction in antibiotic exposure and noninferiority of 28-day mortality, but there was a nonsignificant 3.8% absolute increase in mortality at 60 days.10 Another trial reported similar survival in the procalcitonin group but more side effects and longer ICU stays.11Ultimately, while the SAPS trial supports the potential use of procalcitonin in critically-ill patients, these patients likely have complex sepsis physiology that requires clinicians to consider a number of clinical factors when making antibiotic decisions.
Back to the case
The case illustrates a common emergency department presentation where clinical and radiographic features are not convincing for bacterial infection. This patient has an acute respiratory illness, but is afebrile and lacks leukocytosis with left shift, and x-rays are indeterminate for pneumonia. The differential diagnosis also includes COPD exacerbation, viral infection, or noninfectious triggers of dyspnea.
In this scenario, obtaining procalcitonin levels is useful in the decision to initiate or withhold antibiotic treatment. An elevated procalcitonin level suggests a bacterial infection and would favor initiation of antibiotics for pneumonia. A low procalcitonin level makes a bacterial infection less likely, and a clinician may consider withholding antibiotics and consider alternate etiologies for the patient’s presentation.
Bottom line
Procalcitonin can be safely used to guide the decision to initiate antibiotics in patients presenting with acute respiratory illness. Use of the procalcitonin assay has been shown to reduce antibiotic utilization without an increase in adverse outcomes. There is potential but less conclusive evidence for procalcitonin usage in the broader population of ICU patients with sepsis.
Bryan J. Huang, MD, FHM, and Gregory B. Seymann, MD, SFHM, are in the division of hospital medicine, University of California, San Diego.
- Key Points
- Elevated procalcitonin levels suggest the presence of bacterial infection.
- In patients presenting with acute respiratory illness, procalcitonin levels can be used to guide the decision to initiate or withhold antibiotics, improving antibiotic stewardship.
- Sequential monitoring of procalcitonin levels may help guide duration of antibiotic therapy.
- There is potential but less conclusive evidence for procalcitonin usage in the broader population of ICU patients with sepsis.
References
1. Chen L, Todd R, Kiehlbauch J, Walters M, Kallen A. Notes from the field: pan-resistant New Delhi metallo-beta-lactamase-producing Klebsiella pneumoniae – Washoe County, Nevada, 2016. MMWR Morb Mortal Wkly Rep 2017; 66(1):33.
2. Fleming-Dutra KE, Hersh AL, Shapiro DJ, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA 2016;315(17):1864-73.
3. Christ-Crain M, Muller B. Procalcitonin in bacterial infections – hype, hope, more or less? Swiss Med Wkly. 2005;135(31-32):451-60.
4. Briel M, Schuetz P, Mueller B, et al. Procalcitonin-guided antibiotic use vs. a standard approach for acute respiratory tract infections in primary care. Arch Intern Med. 2008; 168(18): 2000-7.
5. Stolz D, Christ-Crain M, Bingisser R, et al. Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest 2007;131(1): 9-19.
6. Christ-Crain M, Stolz D, Bingisser R, et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006;174(1):84-93.
7. Schuetz P, Christ-Crain M, Thomann R, et al. Effect of procalcitonin-based guidelines vs. standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009; 302(10): 1059-66.
8. Uranga A, Espana PP, Bilbao A, et al. Duration of antibiotic treatment in community-acquired pneumonia: a multicenter randomized clinical trial. JAMA Intern Med. 2016;176(9):1257-65.
9. de Jong E, van Oers JA, Beishiozen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis. 2016;16(7):819-27.
10. Bouadma L, Luyt CE, Tubach F, et al. Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010;375(9713):463-74.
11. Jensen J-U, Lundgren B, Hein L, et al. The procalcitonin and survival study (PASS) – a randomised multicenter investigator-initiated trial to investigate whether daily measurements biomarker procalcitonin and proactive diagnostic and therapeutic responses to abnormal procalcitonin levels, can improve survival in intensive care unit patients. BMC infectious diseases. 2008;8:91-100.
1. Schuetz P, Christ-Crain M, Thomann R, et al. Effect of procalcitonin-based guidelines vs. standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009;302(10):1059-66.
2. de Jong E, van Oers JA, Beishiozen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis. 2016;16(7):819-27.
3. Schuetz P, Muller B, Christ-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2012;(9):CD007498.
The case
A 72-year-old male with COPD presents to the emergency department with increased dyspnea and cough. He is afebrile, and oxygen saturation is 87% on room air. WBC count is 9.5 with a normal differential, and chest x-ray is read by the radiologist as atelectasis versus early consolidation in the left lower lobe. Should antibiotics be initiated?
Background
The problem: Antibiotic overuse
With the increasing prevalence of antibiotic resistance in our nation’s hospitals, the need for robust antibiotic stewardship programs has continued to rise in importance. In 2016, the CDC reported a fatal case of septic shock due to a carbapenem-resistant strain of Klebsiella resistant to all tested antibiotics.1 This case received much media coverage; moreover, this patient represented only one of the approximately 23,000 patients infected with antibiotic-resistant bacteria in the United States who die each year. Although various approaches to curbing antibiotic resistance are being pursued, judicious antibiotic use is central to success. Current evidence suggests that up to 30% of antibiotics are not optimally prescribed,2 leaving a significant opportunity for improvement.
Lower respiratory infections account for a substantial proportion of antibiotic utilization in the United States. In a recent study, acute respiratory conditions generated 221 antibiotic prescriptions per 1,000 population, but only half of these were deemed appropriate.2 The inability to reliably discern viral from bacterial etiology is a driver of excess antibiotic use.
The procalcitonin assay has been touted as a possible solution to this problem. Multiple studies have evaluated its utility as a tool to help discriminate between bacterial infection and viral or noninfectious etiologies.
What is procalcitonin?
Thyroidal c-cells convert the prohormone procalcitonin to calcitonin, which is stored in secretory granules for release in response to fluctuations in calcium levels via a classical neuroendocrine feedback loop. Alternatively, procalcitonin can be synthesized in nonthyroidal parenchymal cells, and high levels of proinflammatory mediators secreted in response to bacterial endotoxin drive increased procalcitonin production. Interestingly, interferon gamma, up-regulated in viral infections, reduces procalcitonin production. Nonthyroidal parenchymal cells lack mechanisms for efficient conversion of procalcitonin to calcitonin and do not contain secretory granules to facilitate its regulated release. Hence bacterial infections correlate with higher serum procalcitonin levels.3
Evidence
Can procalcitonin guide antibiotic therapy in patients with acute respiratory illness while reducing antibiotic utilization?
The ability of procalcitonin to selectively identify bacterial infection makes it a potentially promising tool to advance the antibiotic stewardship agenda. Multiple randomized controlled trials have explored the use of procalcitonin-guided antibiotic therapy for treatment of lower respiratory tract infections such as acute bronchitis, exacerbations of COPD, and pneumonia. Each study discussed below was done in Switzerland, involved the same key investigator (Mirjam Christ-Crain, MD, PhD), and shared a similar design in which a threshold for low procalcitonin values (less than 0.1 mcg/L) and high procalcitonin values (greater than 0.25 mcg/L) was prespecified. Antibiotic therapy was strongly discouraged for patients with low procalcitonin and encouraged for those with high procalcitonin; antibiotics were not recommended for patients with intermediate values, but the treating physician was allowed ultimate discretion (Figure 1). All studies compared a procalcitonin-guided treatment group to a standard care group, in which antibiotics were prescribed by the treating physician based on established clinical guidelines.
Figure 1. Procalcitonin treatment algorithm
Procalcitonin Level (mcg/L) | Likelihood of bacterial infection | Antibiotic treatment |
less than 0.1 | Absent | Strongly discouraged |
0.1-0.25 | Unlikely | Discouraged |
0.25-0.5 | Possible | Encouraged |
greater than 0.5 | Present | Strongly encouraged |
Figure 1. Procalcitonin treatment algorithm
In a study focusing on outpatients presenting to their primary care physicians with acute respiratory tract infection, 53 primary care physicians in Switzerland recruited 458 patients. There was no significant difference in time to symptom resolution, as determined by patient report during an interview 14 days after initial presentation; however, 97% of patients in the standard-care group received antibiotics, compared with 25% in the procalcitonin-guided group. Equal numbers of patients (30% in each group) reported persistent symptoms at 28-day follow-up. Among the cohort of patients with upper respiratory infections or acute bronchitis, procalcitonin guidance reduced antibiotic prescriptions by 80%.4
In a blinded, single-center, randomized, controlled trial of 226 patients presenting to a university hospital with a COPD exacerbation severe enough to require a change in the baseline medication regimen, procalcitonin-guided therapy allowed for an absolute reduction of antibiotic use by 32% without an impact on outcomes. Rates of clinical improvement, ICU utilization, recurrent exacerbations, hospital length of stay, and mortality did not differ between the groups.5
Limitations include the possible impact of the Hawthorne effect, as physicians knew their antibiotic usage patterns were being monitored, which may impact generalizability of the findings to a real-world setting. Similarly, it is difficult to control for a spillover effect as providers exposed to the procalcitonin-guided algorithm became more comfortable with a restrictive prescribing approach. The costs of the additional procalcitonin assay must be weighed against the benefits. Incidence and cost of other adverse effects of antibiotic use (rates of Clostridium difficile, renal insufficiency, urticarial drug eruptions, etc.) were not addressed. The rapid assay currently has limited availability in the United States, though that is changing. Finally, recent additional studies (unrelated to procalcitonin) have suggested shorter antibiotic treatment durations for patients with pneumonia.8
Is there evidence for using procalcitonin to guide treatment in the broader population of ICU patients?
While there is good evidence for using procalcitonin to guide antibiotic use in patients with acute respiratory illness, the evidence for using procalcitonin in the broader cohort of critically-ill patients with sepsis is less well established.
The most promising results were reported by the Stop Antibiotics on Procalcitonin guidance Study (SAPS). Published in July 2016, this was a prospective, multicenter, randomized, controlled, open-label study of patients admitted to the ICU (not limited to respiratory illness) in the Netherlands. A total of 1,575 patients were assigned to the procalcitonin-guided group or the standard-of-care group. In the procalcitonin-guided group, procalcitonin levels were checked daily, and physicians were given nonbinding advice to discontinue antibiotics if procalcitonin levels decreased by greater than 80% from peak levels or to below 0.5 mcg/L.
Patients received an average of 7.5 daily defined antibiotic doses in the procalcitonin-guided group versus 9.3 daily defined doses in the standard-of-care group (P less than .0001). The median duration of antibiotic treatment in the procalcitonin arm was 5 days versus 7 days in the control group (P less than .0001). Mortality at 28 days was 20% in the procalcitonin group and 25% in the control group (P = .0122). At 1 year, mortality was 36% in the procalcitonin group and 43% in the control group (P = .0188). The authors hypothesized that the unexpected decrease in mortality in the procalcitonin group may have been due to earlier consideration of alternate illness etiologies in patients with a low procalcitonin level or decreased antibiotic side effects.9While the SAPS trial supports decreased antibiotic usage in ICU patients with the use of the procalcitonin assay, there are some important limitations. First, the trial was done in the Netherlands, where baseline antibiotic usage was comparatively low. Second, daily procalcitonin level monitoring was not continued for patients transferred out of the ICU while still on antibiotics. Further, guidelines for antibiotic discontinuation were nonbinding, and in many cases physicians did not stop antibiotics based on procalcitonin guidelines suggested by the study authors.
Earlier trials regarding the procalcitonin assay in the critical care setting similarly showed some promise but also concerns. One trial reported a 25% reduction in antibiotic exposure and noninferiority of 28-day mortality, but there was a nonsignificant 3.8% absolute increase in mortality at 60 days.10 Another trial reported similar survival in the procalcitonin group but more side effects and longer ICU stays.11Ultimately, while the SAPS trial supports the potential use of procalcitonin in critically-ill patients, these patients likely have complex sepsis physiology that requires clinicians to consider a number of clinical factors when making antibiotic decisions.
Back to the case
The case illustrates a common emergency department presentation where clinical and radiographic features are not convincing for bacterial infection. This patient has an acute respiratory illness, but is afebrile and lacks leukocytosis with left shift, and x-rays are indeterminate for pneumonia. The differential diagnosis also includes COPD exacerbation, viral infection, or noninfectious triggers of dyspnea.
In this scenario, obtaining procalcitonin levels is useful in the decision to initiate or withhold antibiotic treatment. An elevated procalcitonin level suggests a bacterial infection and would favor initiation of antibiotics for pneumonia. A low procalcitonin level makes a bacterial infection less likely, and a clinician may consider withholding antibiotics and consider alternate etiologies for the patient’s presentation.
Bottom line
Procalcitonin can be safely used to guide the decision to initiate antibiotics in patients presenting with acute respiratory illness. Use of the procalcitonin assay has been shown to reduce antibiotic utilization without an increase in adverse outcomes. There is potential but less conclusive evidence for procalcitonin usage in the broader population of ICU patients with sepsis.
Bryan J. Huang, MD, FHM, and Gregory B. Seymann, MD, SFHM, are in the division of hospital medicine, University of California, San Diego.
- Key Points
- Elevated procalcitonin levels suggest the presence of bacterial infection.
- In patients presenting with acute respiratory illness, procalcitonin levels can be used to guide the decision to initiate or withhold antibiotics, improving antibiotic stewardship.
- Sequential monitoring of procalcitonin levels may help guide duration of antibiotic therapy.
- There is potential but less conclusive evidence for procalcitonin usage in the broader population of ICU patients with sepsis.
References
1. Chen L, Todd R, Kiehlbauch J, Walters M, Kallen A. Notes from the field: pan-resistant New Delhi metallo-beta-lactamase-producing Klebsiella pneumoniae – Washoe County, Nevada, 2016. MMWR Morb Mortal Wkly Rep 2017; 66(1):33.
2. Fleming-Dutra KE, Hersh AL, Shapiro DJ, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA 2016;315(17):1864-73.
3. Christ-Crain M, Muller B. Procalcitonin in bacterial infections – hype, hope, more or less? Swiss Med Wkly. 2005;135(31-32):451-60.
4. Briel M, Schuetz P, Mueller B, et al. Procalcitonin-guided antibiotic use vs. a standard approach for acute respiratory tract infections in primary care. Arch Intern Med. 2008; 168(18): 2000-7.
5. Stolz D, Christ-Crain M, Bingisser R, et al. Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest 2007;131(1): 9-19.
6. Christ-Crain M, Stolz D, Bingisser R, et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006;174(1):84-93.
7. Schuetz P, Christ-Crain M, Thomann R, et al. Effect of procalcitonin-based guidelines vs. standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009; 302(10): 1059-66.
8. Uranga A, Espana PP, Bilbao A, et al. Duration of antibiotic treatment in community-acquired pneumonia: a multicenter randomized clinical trial. JAMA Intern Med. 2016;176(9):1257-65.
9. de Jong E, van Oers JA, Beishiozen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis. 2016;16(7):819-27.
10. Bouadma L, Luyt CE, Tubach F, et al. Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010;375(9713):463-74.
11. Jensen J-U, Lundgren B, Hein L, et al. The procalcitonin and survival study (PASS) – a randomised multicenter investigator-initiated trial to investigate whether daily measurements biomarker procalcitonin and proactive diagnostic and therapeutic responses to abnormal procalcitonin levels, can improve survival in intensive care unit patients. BMC infectious diseases. 2008;8:91-100.
1. Schuetz P, Christ-Crain M, Thomann R, et al. Effect of procalcitonin-based guidelines vs. standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009;302(10):1059-66.
2. de Jong E, van Oers JA, Beishiozen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis. 2016;16(7):819-27.
3. Schuetz P, Muller B, Christ-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2012;(9):CD007498.
The case
A 72-year-old male with COPD presents to the emergency department with increased dyspnea and cough. He is afebrile, and oxygen saturation is 87% on room air. WBC count is 9.5 with a normal differential, and chest x-ray is read by the radiologist as atelectasis versus early consolidation in the left lower lobe. Should antibiotics be initiated?
Background
The problem: Antibiotic overuse
With the increasing prevalence of antibiotic resistance in our nation’s hospitals, the need for robust antibiotic stewardship programs has continued to rise in importance. In 2016, the CDC reported a fatal case of septic shock due to a carbapenem-resistant strain of Klebsiella resistant to all tested antibiotics.1 This case received much media coverage; moreover, this patient represented only one of the approximately 23,000 patients infected with antibiotic-resistant bacteria in the United States who die each year. Although various approaches to curbing antibiotic resistance are being pursued, judicious antibiotic use is central to success. Current evidence suggests that up to 30% of antibiotics are not optimally prescribed,2 leaving a significant opportunity for improvement.
Lower respiratory infections account for a substantial proportion of antibiotic utilization in the United States. In a recent study, acute respiratory conditions generated 221 antibiotic prescriptions per 1,000 population, but only half of these were deemed appropriate.2 The inability to reliably discern viral from bacterial etiology is a driver of excess antibiotic use.
The procalcitonin assay has been touted as a possible solution to this problem. Multiple studies have evaluated its utility as a tool to help discriminate between bacterial infection and viral or noninfectious etiologies.
What is procalcitonin?
Thyroidal c-cells convert the prohormone procalcitonin to calcitonin, which is stored in secretory granules for release in response to fluctuations in calcium levels via a classical neuroendocrine feedback loop. Alternatively, procalcitonin can be synthesized in nonthyroidal parenchymal cells, and high levels of proinflammatory mediators secreted in response to bacterial endotoxin drive increased procalcitonin production. Interestingly, interferon gamma, up-regulated in viral infections, reduces procalcitonin production. Nonthyroidal parenchymal cells lack mechanisms for efficient conversion of procalcitonin to calcitonin and do not contain secretory granules to facilitate its regulated release. Hence bacterial infections correlate with higher serum procalcitonin levels.3
Evidence
Can procalcitonin guide antibiotic therapy in patients with acute respiratory illness while reducing antibiotic utilization?
The ability of procalcitonin to selectively identify bacterial infection makes it a potentially promising tool to advance the antibiotic stewardship agenda. Multiple randomized controlled trials have explored the use of procalcitonin-guided antibiotic therapy for treatment of lower respiratory tract infections such as acute bronchitis, exacerbations of COPD, and pneumonia. Each study discussed below was done in Switzerland, involved the same key investigator (Mirjam Christ-Crain, MD, PhD), and shared a similar design in which a threshold for low procalcitonin values (less than 0.1 mcg/L) and high procalcitonin values (greater than 0.25 mcg/L) was prespecified. Antibiotic therapy was strongly discouraged for patients with low procalcitonin and encouraged for those with high procalcitonin; antibiotics were not recommended for patients with intermediate values, but the treating physician was allowed ultimate discretion (Figure 1). All studies compared a procalcitonin-guided treatment group to a standard care group, in which antibiotics were prescribed by the treating physician based on established clinical guidelines.
Figure 1. Procalcitonin treatment algorithm
Procalcitonin Level (mcg/L) | Likelihood of bacterial infection | Antibiotic treatment |
less than 0.1 | Absent | Strongly discouraged |
0.1-0.25 | Unlikely | Discouraged |
0.25-0.5 | Possible | Encouraged |
greater than 0.5 | Present | Strongly encouraged |
Figure 1. Procalcitonin treatment algorithm
In a study focusing on outpatients presenting to their primary care physicians with acute respiratory tract infection, 53 primary care physicians in Switzerland recruited 458 patients. There was no significant difference in time to symptom resolution, as determined by patient report during an interview 14 days after initial presentation; however, 97% of patients in the standard-care group received antibiotics, compared with 25% in the procalcitonin-guided group. Equal numbers of patients (30% in each group) reported persistent symptoms at 28-day follow-up. Among the cohort of patients with upper respiratory infections or acute bronchitis, procalcitonin guidance reduced antibiotic prescriptions by 80%.4
In a blinded, single-center, randomized, controlled trial of 226 patients presenting to a university hospital with a COPD exacerbation severe enough to require a change in the baseline medication regimen, procalcitonin-guided therapy allowed for an absolute reduction of antibiotic use by 32% without an impact on outcomes. Rates of clinical improvement, ICU utilization, recurrent exacerbations, hospital length of stay, and mortality did not differ between the groups.5
Limitations include the possible impact of the Hawthorne effect, as physicians knew their antibiotic usage patterns were being monitored, which may impact generalizability of the findings to a real-world setting. Similarly, it is difficult to control for a spillover effect as providers exposed to the procalcitonin-guided algorithm became more comfortable with a restrictive prescribing approach. The costs of the additional procalcitonin assay must be weighed against the benefits. Incidence and cost of other adverse effects of antibiotic use (rates of Clostridium difficile, renal insufficiency, urticarial drug eruptions, etc.) were not addressed. The rapid assay currently has limited availability in the United States, though that is changing. Finally, recent additional studies (unrelated to procalcitonin) have suggested shorter antibiotic treatment durations for patients with pneumonia.8
Is there evidence for using procalcitonin to guide treatment in the broader population of ICU patients?
While there is good evidence for using procalcitonin to guide antibiotic use in patients with acute respiratory illness, the evidence for using procalcitonin in the broader cohort of critically-ill patients with sepsis is less well established.
The most promising results were reported by the Stop Antibiotics on Procalcitonin guidance Study (SAPS). Published in July 2016, this was a prospective, multicenter, randomized, controlled, open-label study of patients admitted to the ICU (not limited to respiratory illness) in the Netherlands. A total of 1,575 patients were assigned to the procalcitonin-guided group or the standard-of-care group. In the procalcitonin-guided group, procalcitonin levels were checked daily, and physicians were given nonbinding advice to discontinue antibiotics if procalcitonin levels decreased by greater than 80% from peak levels or to below 0.5 mcg/L.
Patients received an average of 7.5 daily defined antibiotic doses in the procalcitonin-guided group versus 9.3 daily defined doses in the standard-of-care group (P less than .0001). The median duration of antibiotic treatment in the procalcitonin arm was 5 days versus 7 days in the control group (P less than .0001). Mortality at 28 days was 20% in the procalcitonin group and 25% in the control group (P = .0122). At 1 year, mortality was 36% in the procalcitonin group and 43% in the control group (P = .0188). The authors hypothesized that the unexpected decrease in mortality in the procalcitonin group may have been due to earlier consideration of alternate illness etiologies in patients with a low procalcitonin level or decreased antibiotic side effects.9While the SAPS trial supports decreased antibiotic usage in ICU patients with the use of the procalcitonin assay, there are some important limitations. First, the trial was done in the Netherlands, where baseline antibiotic usage was comparatively low. Second, daily procalcitonin level monitoring was not continued for patients transferred out of the ICU while still on antibiotics. Further, guidelines for antibiotic discontinuation were nonbinding, and in many cases physicians did not stop antibiotics based on procalcitonin guidelines suggested by the study authors.
Earlier trials regarding the procalcitonin assay in the critical care setting similarly showed some promise but also concerns. One trial reported a 25% reduction in antibiotic exposure and noninferiority of 28-day mortality, but there was a nonsignificant 3.8% absolute increase in mortality at 60 days.10 Another trial reported similar survival in the procalcitonin group but more side effects and longer ICU stays.11Ultimately, while the SAPS trial supports the potential use of procalcitonin in critically-ill patients, these patients likely have complex sepsis physiology that requires clinicians to consider a number of clinical factors when making antibiotic decisions.
Back to the case
The case illustrates a common emergency department presentation where clinical and radiographic features are not convincing for bacterial infection. This patient has an acute respiratory illness, but is afebrile and lacks leukocytosis with left shift, and x-rays are indeterminate for pneumonia. The differential diagnosis also includes COPD exacerbation, viral infection, or noninfectious triggers of dyspnea.
In this scenario, obtaining procalcitonin levels is useful in the decision to initiate or withhold antibiotic treatment. An elevated procalcitonin level suggests a bacterial infection and would favor initiation of antibiotics for pneumonia. A low procalcitonin level makes a bacterial infection less likely, and a clinician may consider withholding antibiotics and consider alternate etiologies for the patient’s presentation.
Bottom line
Procalcitonin can be safely used to guide the decision to initiate antibiotics in patients presenting with acute respiratory illness. Use of the procalcitonin assay has been shown to reduce antibiotic utilization without an increase in adverse outcomes. There is potential but less conclusive evidence for procalcitonin usage in the broader population of ICU patients with sepsis.
Bryan J. Huang, MD, FHM, and Gregory B. Seymann, MD, SFHM, are in the division of hospital medicine, University of California, San Diego.
- Key Points
- Elevated procalcitonin levels suggest the presence of bacterial infection.
- In patients presenting with acute respiratory illness, procalcitonin levels can be used to guide the decision to initiate or withhold antibiotics, improving antibiotic stewardship.
- Sequential monitoring of procalcitonin levels may help guide duration of antibiotic therapy.
- There is potential but less conclusive evidence for procalcitonin usage in the broader population of ICU patients with sepsis.
References
1. Chen L, Todd R, Kiehlbauch J, Walters M, Kallen A. Notes from the field: pan-resistant New Delhi metallo-beta-lactamase-producing Klebsiella pneumoniae – Washoe County, Nevada, 2016. MMWR Morb Mortal Wkly Rep 2017; 66(1):33.
2. Fleming-Dutra KE, Hersh AL, Shapiro DJ, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA 2016;315(17):1864-73.
3. Christ-Crain M, Muller B. Procalcitonin in bacterial infections – hype, hope, more or less? Swiss Med Wkly. 2005;135(31-32):451-60.
4. Briel M, Schuetz P, Mueller B, et al. Procalcitonin-guided antibiotic use vs. a standard approach for acute respiratory tract infections in primary care. Arch Intern Med. 2008; 168(18): 2000-7.
5. Stolz D, Christ-Crain M, Bingisser R, et al. Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest 2007;131(1): 9-19.
6. Christ-Crain M, Stolz D, Bingisser R, et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006;174(1):84-93.
7. Schuetz P, Christ-Crain M, Thomann R, et al. Effect of procalcitonin-based guidelines vs. standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009; 302(10): 1059-66.
8. Uranga A, Espana PP, Bilbao A, et al. Duration of antibiotic treatment in community-acquired pneumonia: a multicenter randomized clinical trial. JAMA Intern Med. 2016;176(9):1257-65.
9. de Jong E, van Oers JA, Beishiozen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis. 2016;16(7):819-27.
10. Bouadma L, Luyt CE, Tubach F, et al. Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010;375(9713):463-74.
11. Jensen J-U, Lundgren B, Hein L, et al. The procalcitonin and survival study (PASS) – a randomised multicenter investigator-initiated trial to investigate whether daily measurements biomarker procalcitonin and proactive diagnostic and therapeutic responses to abnormal procalcitonin levels, can improve survival in intensive care unit patients. BMC infectious diseases. 2008;8:91-100.
1. Schuetz P, Christ-Crain M, Thomann R, et al. Effect of procalcitonin-based guidelines vs. standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA 2009;302(10):1059-66.
2. de Jong E, van Oers JA, Beishiozen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis. 2016;16(7):819-27.
3. Schuetz P, Muller B, Christ-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2012;(9):CD007498.
Cutting back ICU antibiotics could significantly reduce MDRO transmissions
Cutting back on antibiotic courses in intensive care unit settings can significantly reduce the number of multidrug-resistant organism (MDRO) transmissions, according to the findings of a modeling study.
“Significant opportunities exist to optimize and reduce antibiotic usage, [but] the impact of reducing overall antibiotic usage on antibiotic resistance is not known and would be difficult to assess using traditional study designs,” wrote Sean L. Barnes, PhD, of the University of Maryland, College Park, and his colleagues. “Therefore, we applied mathematical modeling to estimate the effect of reducing antibiotic usage on antibiotic resistance.”
Using an agent-based model – which allows for a realistic prediction of interactions between patients and health care workers, while also allowing for heterogeneity in the characteristics of each distinct “person” – Dr. Barnes and his coinvestigators simulated the transmission of MDROs from health care workers to patients.
Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci were deemed “high-prevalence pathogens;” carbapenem-resistant Enterobacteriaceae, multidrug-resistant Acinetobacter baumannii, and multidrug-resistant Pseudomonas aeruginosa were deemed low-prevalence pathogens. These designations were based on transmission rates found in existing literature.
Patients on antibiotic courses were set at 75% (0.75) at baseline, which was then adjusted to determine its effect on overall MDRO transmission. The number of patients at baseline was 18, with nine nurses, two physicians, and six other health care workers. Mean length-of-stay was 3.5 days, hand hygiene rates were set at 80% for nurses and 50% for physicians, with a 0.83 (83%) efficacy rate when followed. The probability of worker-to-patient transmission was set at 0.025 (2.5%), and set at 0.075 (7.5%) for transmission going the other way.
“We simulated the transmission of the high- and low-prevalence MDROs for 1 year [and] performed 200 replications each for 33 parameter-based scenarios,” the authors said.
When the number of patients on an antibiotic course was dropped from 75% to 65% (a drop of 10%), the rate of high-prevalence MDRO transmission dropped by 11.2% (P < .001). When reduced from 75% to 50% (a drop of 25%), the high-prevalence MDRO transmission rate fell by 28.3% (P < .001), according to the model.
Low-prevalence MDROs also reduced by significant amounts when antibiotic regimens were cut back by the same percentages, with transmission rates falling by 14.3% (P < .001) and 29.8% (P < .001), respectively.
In terms of microbiome effects, the 10% reduction in antibiotics lowered high-prevalence rates by an effect of 1.5, and low-prevalence rates by 1.7; those numbers were 1.2 and 1.4, respectively, when antibiotics were dropped by 25%.
“These reductions are statistically significant and proportionally similar for both high- and low-prevalence MDROs,” the authors concluded, “and they can potentially decrease MDRO acquisition among patients who are receiving antibiotics, as well as among patients who are not receiving antibiotics.”
The National Institutes of Health and the Department of Veterans Affairs’ Health Services Research and Development Department funded the study. Dr. Barnes and his coauthors reported no relevant financial disclosures.
Cutting back on antibiotic courses in intensive care unit settings can significantly reduce the number of multidrug-resistant organism (MDRO) transmissions, according to the findings of a modeling study.
“Significant opportunities exist to optimize and reduce antibiotic usage, [but] the impact of reducing overall antibiotic usage on antibiotic resistance is not known and would be difficult to assess using traditional study designs,” wrote Sean L. Barnes, PhD, of the University of Maryland, College Park, and his colleagues. “Therefore, we applied mathematical modeling to estimate the effect of reducing antibiotic usage on antibiotic resistance.”
Using an agent-based model – which allows for a realistic prediction of interactions between patients and health care workers, while also allowing for heterogeneity in the characteristics of each distinct “person” – Dr. Barnes and his coinvestigators simulated the transmission of MDROs from health care workers to patients.
Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci were deemed “high-prevalence pathogens;” carbapenem-resistant Enterobacteriaceae, multidrug-resistant Acinetobacter baumannii, and multidrug-resistant Pseudomonas aeruginosa were deemed low-prevalence pathogens. These designations were based on transmission rates found in existing literature.
Patients on antibiotic courses were set at 75% (0.75) at baseline, which was then adjusted to determine its effect on overall MDRO transmission. The number of patients at baseline was 18, with nine nurses, two physicians, and six other health care workers. Mean length-of-stay was 3.5 days, hand hygiene rates were set at 80% for nurses and 50% for physicians, with a 0.83 (83%) efficacy rate when followed. The probability of worker-to-patient transmission was set at 0.025 (2.5%), and set at 0.075 (7.5%) for transmission going the other way.
“We simulated the transmission of the high- and low-prevalence MDROs for 1 year [and] performed 200 replications each for 33 parameter-based scenarios,” the authors said.
When the number of patients on an antibiotic course was dropped from 75% to 65% (a drop of 10%), the rate of high-prevalence MDRO transmission dropped by 11.2% (P < .001). When reduced from 75% to 50% (a drop of 25%), the high-prevalence MDRO transmission rate fell by 28.3% (P < .001), according to the model.
Low-prevalence MDROs also reduced by significant amounts when antibiotic regimens were cut back by the same percentages, with transmission rates falling by 14.3% (P < .001) and 29.8% (P < .001), respectively.
In terms of microbiome effects, the 10% reduction in antibiotics lowered high-prevalence rates by an effect of 1.5, and low-prevalence rates by 1.7; those numbers were 1.2 and 1.4, respectively, when antibiotics were dropped by 25%.
“These reductions are statistically significant and proportionally similar for both high- and low-prevalence MDROs,” the authors concluded, “and they can potentially decrease MDRO acquisition among patients who are receiving antibiotics, as well as among patients who are not receiving antibiotics.”
The National Institutes of Health and the Department of Veterans Affairs’ Health Services Research and Development Department funded the study. Dr. Barnes and his coauthors reported no relevant financial disclosures.
Cutting back on antibiotic courses in intensive care unit settings can significantly reduce the number of multidrug-resistant organism (MDRO) transmissions, according to the findings of a modeling study.
“Significant opportunities exist to optimize and reduce antibiotic usage, [but] the impact of reducing overall antibiotic usage on antibiotic resistance is not known and would be difficult to assess using traditional study designs,” wrote Sean L. Barnes, PhD, of the University of Maryland, College Park, and his colleagues. “Therefore, we applied mathematical modeling to estimate the effect of reducing antibiotic usage on antibiotic resistance.”
Using an agent-based model – which allows for a realistic prediction of interactions between patients and health care workers, while also allowing for heterogeneity in the characteristics of each distinct “person” – Dr. Barnes and his coinvestigators simulated the transmission of MDROs from health care workers to patients.
Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci were deemed “high-prevalence pathogens;” carbapenem-resistant Enterobacteriaceae, multidrug-resistant Acinetobacter baumannii, and multidrug-resistant Pseudomonas aeruginosa were deemed low-prevalence pathogens. These designations were based on transmission rates found in existing literature.
Patients on antibiotic courses were set at 75% (0.75) at baseline, which was then adjusted to determine its effect on overall MDRO transmission. The number of patients at baseline was 18, with nine nurses, two physicians, and six other health care workers. Mean length-of-stay was 3.5 days, hand hygiene rates were set at 80% for nurses and 50% for physicians, with a 0.83 (83%) efficacy rate when followed. The probability of worker-to-patient transmission was set at 0.025 (2.5%), and set at 0.075 (7.5%) for transmission going the other way.
“We simulated the transmission of the high- and low-prevalence MDROs for 1 year [and] performed 200 replications each for 33 parameter-based scenarios,” the authors said.
When the number of patients on an antibiotic course was dropped from 75% to 65% (a drop of 10%), the rate of high-prevalence MDRO transmission dropped by 11.2% (P < .001). When reduced from 75% to 50% (a drop of 25%), the high-prevalence MDRO transmission rate fell by 28.3% (P < .001), according to the model.
Low-prevalence MDROs also reduced by significant amounts when antibiotic regimens were cut back by the same percentages, with transmission rates falling by 14.3% (P < .001) and 29.8% (P < .001), respectively.
In terms of microbiome effects, the 10% reduction in antibiotics lowered high-prevalence rates by an effect of 1.5, and low-prevalence rates by 1.7; those numbers were 1.2 and 1.4, respectively, when antibiotics were dropped by 25%.
“These reductions are statistically significant and proportionally similar for both high- and low-prevalence MDROs,” the authors concluded, “and they can potentially decrease MDRO acquisition among patients who are receiving antibiotics, as well as among patients who are not receiving antibiotics.”
The National Institutes of Health and the Department of Veterans Affairs’ Health Services Research and Development Department funded the study. Dr. Barnes and his coauthors reported no relevant financial disclosures.
FROM INFECTION CONTROL & HOSPITAL EPIDEMIOLOGY
Key clinical point:
Major finding: A 10% reduction in prescribed antibiotic courses saw high-prevalence MDRO transmission drop by 11.2%, and a 25% reduction caused a drop of 28.3%; low-prevalence MDROs dropped by 14.3% and 29.8%, respectively (P < .001 for all).
Data source: An agent-based model of a single ICU with 18 patients and 17 health care workers at baseline.
Disclosures: The National Institutes of Health and the Department of Veterans Affairs’ Health Services Research and Development Department funded the study. Dr. Barnes and his coauthors reported no relevant financial disclosures.
FDA clears procalcitonin test to hone antibiotic use in LRTI, sepsis
The Food and Drug Administration has cleared the expanded use of a procalcitonin test to help determine antibiotic use in patients with lower respiratory tract infections (LRTI) and sepsis.
The Vidas Brahms PCT Assay (bioMérieux) uses procalcitonin levels to determine whether a patient with a lower respiratory tract infection (LRTI) should begin or remain on antibiotics and when antibiotics should be withdrawn in a patient with sepsis.
The test will be used primarily in hospital settings and emergency departments, according to the FDA. Test levels that are high levels suggest bacterial infection and the need for antibiotics while low levels indicate viral or noninfectious processes. However, concerns exist regarding false-positive or false-negative test results, which can prompt clinicians to prematurely stop or unnecessarily continue an antibiotic regimen in certain patients.
“Health care providers should not rely solely on PCT test results when making treatment decisions but should interpret test results in the context of a patient’s clinical status and other laboratory results,” according to the FDA statement.
The expanded use of the test was approved based on promising data from clinical trials that was presented at an FDA advisory committee meeting in November 2016. The Vidas Brahms test was already approved by the FDA for use in determining a patient’s risk of dying from sepsis. The test was cleared via the FDA 510(k) regulatory pathway, which is meant for tests or devices for which there is already something similar on the market.
Support for the test’s expanded usage comes from published prospective, randomized clinical trials that compared PCT-guided therapy with standard therapy. In those studies, patients who had received PCT-guided therapy experienced significant decreases in antibiotic use without significant affects to their safety.
The Food and Drug Administration has cleared the expanded use of a procalcitonin test to help determine antibiotic use in patients with lower respiratory tract infections (LRTI) and sepsis.
The Vidas Brahms PCT Assay (bioMérieux) uses procalcitonin levels to determine whether a patient with a lower respiratory tract infection (LRTI) should begin or remain on antibiotics and when antibiotics should be withdrawn in a patient with sepsis.
The test will be used primarily in hospital settings and emergency departments, according to the FDA. Test levels that are high levels suggest bacterial infection and the need for antibiotics while low levels indicate viral or noninfectious processes. However, concerns exist regarding false-positive or false-negative test results, which can prompt clinicians to prematurely stop or unnecessarily continue an antibiotic regimen in certain patients.
“Health care providers should not rely solely on PCT test results when making treatment decisions but should interpret test results in the context of a patient’s clinical status and other laboratory results,” according to the FDA statement.
The expanded use of the test was approved based on promising data from clinical trials that was presented at an FDA advisory committee meeting in November 2016. The Vidas Brahms test was already approved by the FDA for use in determining a patient’s risk of dying from sepsis. The test was cleared via the FDA 510(k) regulatory pathway, which is meant for tests or devices for which there is already something similar on the market.
Support for the test’s expanded usage comes from published prospective, randomized clinical trials that compared PCT-guided therapy with standard therapy. In those studies, patients who had received PCT-guided therapy experienced significant decreases in antibiotic use without significant affects to their safety.
The Food and Drug Administration has cleared the expanded use of a procalcitonin test to help determine antibiotic use in patients with lower respiratory tract infections (LRTI) and sepsis.
The Vidas Brahms PCT Assay (bioMérieux) uses procalcitonin levels to determine whether a patient with a lower respiratory tract infection (LRTI) should begin or remain on antibiotics and when antibiotics should be withdrawn in a patient with sepsis.
The test will be used primarily in hospital settings and emergency departments, according to the FDA. Test levels that are high levels suggest bacterial infection and the need for antibiotics while low levels indicate viral or noninfectious processes. However, concerns exist regarding false-positive or false-negative test results, which can prompt clinicians to prematurely stop or unnecessarily continue an antibiotic regimen in certain patients.
“Health care providers should not rely solely on PCT test results when making treatment decisions but should interpret test results in the context of a patient’s clinical status and other laboratory results,” according to the FDA statement.
The expanded use of the test was approved based on promising data from clinical trials that was presented at an FDA advisory committee meeting in November 2016. The Vidas Brahms test was already approved by the FDA for use in determining a patient’s risk of dying from sepsis. The test was cleared via the FDA 510(k) regulatory pathway, which is meant for tests or devices for which there is already something similar on the market.
Support for the test’s expanded usage comes from published prospective, randomized clinical trials that compared PCT-guided therapy with standard therapy. In those studies, patients who had received PCT-guided therapy experienced significant decreases in antibiotic use without significant affects to their safety.
Antibiotic prophylaxis for artificial joints
A 66-year-old woman 3 years status post hip replacement is seen for dental work. The dentist contacts the clinic for an antibiotic prescription. The patient has a penicillin allergy (rash). What do you recommend?
A. Clindamycin one dose before dental work.
B. Amoxicillin one dose before dental work.
C. Amoxicillin one dose before, one dose 4 hours after dental work.
D. Clindamycin one dose before dental work, one dose 4 hours after dental work.
E. No antibiotics.
Many patients with prosthetic joints will request antibiotics to take prior to dental procedures. Sometimes this request comes from the dental office.
When I ask patients why they feel they need antibiotics, they often reply that they were told by their orthopedic surgeons or their dentist that they would need to take antibiotics before dental procedures.
In an era when Clostridium difficile infection is a common and dangerous complication in the elderly, avoidance of unnecessary antibiotics is critical. In the United States, it is estimated that there are 240,000 patients infected with C. difficile annually, with 24,000 deaths at a cost of $6 billion.1
Is there compelling evidence to justify giving antibiotic prophylaxis for dental procedures to patients with prosthetic joints?
This information has called into question the wisdom of giving antibiotic prophylaxis for dental procedures when the same patients have transient bacteremias as a regular part of day-to-day life, and mouth organisms were infrequent causes of prosthetic joint infections.
The American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) released an advisory statement 20 years ago on antibiotic prophylaxis for patients with dental replacements, which concluded: “Antibiotic prophylaxis is not indicated for dental patients with pins, plates, and screws, nor is it routinely indicated for most dental patients with total joint replacements.”4
In 2003, the AAOS and the ADA released updated guidelines that stated: “Presently, no scientific evidence supports the position that antibiotic prophylaxis to prevent hematogenous infections is required prior to dental treatment in patients with total joint prostheses. The risk/benefit and cost/effectiveness ratios fail to justify the administration of routine antibiotics.”5
Great confusion arose in 2009 when the AAOS published a position paper on its website that reversed this position.6 Interestingly, the statement was done by the AAOS alone, and not done in conjunction with the ADA.
In this position paper, the AAOS recommended that health care providers consider antibiotic prophylaxis prior to invasive procedures on all patients who had prosthetic joints, regardless of how long those joints have been in place. This major change in recommendations was not based on any new evidence that had been reviewed since the 2003 guidelines.
There are two studies that address outcome of patients with prosthetic joints who have and have not received prophylactic antibiotics.
Elie Berbari, MD, and colleagues reported on the results of a prospective case-control study comparing patients with prosthetic joints hospitalized with hip or knee infections with patients who had prosthetic joints hospitalized at the same time who did not have hip or knee infections.7
There was no increased risk of prosthetic hip or knee infection for patients undergoing a dental procedure who were not receiving antibiotic prophylaxis (odds ratio, 0.8; 95% confidence interval, 0.4-1.6), compared with the risk for patients not undergoing a dental procedure (OR, 0.6; 95% CI, 0.4-1.1). Antibiotic prophylaxis in patients undergoing high and low risk dental procedures did not decrease the risk of prosthetic joint infections.
In 2012, the AAOS and the ADA published updated guidelines with the following summary recommendation: “The practitioner might consider discontinuing the practice of routinely prescribing prophylactic antibiotics for patients with hip and knee prosthetic joint implants undergoing dental procedures.”8 They referenced the Berbari study as the best available evidence.
Feng-Chen Kao, MD, and colleagues published a study this year with a design very similar to the Berbari study, with similar results.9 All Taiwanese residents who had received hip or knee replacements over a 12-year period were screened. Those who had received dental procedures were matched with individuals who had not had dental procedures. The dental procedure group was subdivided into a group that received antibiotics and one that didn’t.
There was no difference in infection rates between the group that had received dental procedures and the group that did not, and no difference in infection rates between those who received prophylactic antibiotics and those who didn’t.
I think this myth can be put to rest. There is no evidence to give patients with joint prostheses prophylactic antibiotics before dental procedures.
References
1. Steckelberg J.M., Osmon D.R. Prosthetic joint infections. In: Bisno A.L., Waldvogel F.A., eds. Infections associated with indwelling medical devices. Third ed., Washington, D.C.: American Society of Microbiology Press, 2000:173-209.
2. J Dent Res. 2004 Feb;83(2):170-4.
3. J Clin Periodontol. 2006 Feb;33(6):401-7.
4. J Am Dent Assoc. 1997 Jul;128(7):1004-8.
5. J Am Dent Assoc. 2003 Jul;134(7):895-9.
6. Spec Care Dentist. 2009 Nov-Dec;29(6):229-31.
7. Clin Infect Dis. 2010 Jan 1;50(1):8-16.
8. J Dent (Shiraz). 2013 Mar;14(1):49-52.
9. Infect Control Hosp Epidemiol. 2017 Feb;38(2):154-61.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
A 66-year-old woman 3 years status post hip replacement is seen for dental work. The dentist contacts the clinic for an antibiotic prescription. The patient has a penicillin allergy (rash). What do you recommend?
A. Clindamycin one dose before dental work.
B. Amoxicillin one dose before dental work.
C. Amoxicillin one dose before, one dose 4 hours after dental work.
D. Clindamycin one dose before dental work, one dose 4 hours after dental work.
E. No antibiotics.
Many patients with prosthetic joints will request antibiotics to take prior to dental procedures. Sometimes this request comes from the dental office.
When I ask patients why they feel they need antibiotics, they often reply that they were told by their orthopedic surgeons or their dentist that they would need to take antibiotics before dental procedures.
In an era when Clostridium difficile infection is a common and dangerous complication in the elderly, avoidance of unnecessary antibiotics is critical. In the United States, it is estimated that there are 240,000 patients infected with C. difficile annually, with 24,000 deaths at a cost of $6 billion.1
Is there compelling evidence to justify giving antibiotic prophylaxis for dental procedures to patients with prosthetic joints?
This information has called into question the wisdom of giving antibiotic prophylaxis for dental procedures when the same patients have transient bacteremias as a regular part of day-to-day life, and mouth organisms were infrequent causes of prosthetic joint infections.
The American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) released an advisory statement 20 years ago on antibiotic prophylaxis for patients with dental replacements, which concluded: “Antibiotic prophylaxis is not indicated for dental patients with pins, plates, and screws, nor is it routinely indicated for most dental patients with total joint replacements.”4
In 2003, the AAOS and the ADA released updated guidelines that stated: “Presently, no scientific evidence supports the position that antibiotic prophylaxis to prevent hematogenous infections is required prior to dental treatment in patients with total joint prostheses. The risk/benefit and cost/effectiveness ratios fail to justify the administration of routine antibiotics.”5
Great confusion arose in 2009 when the AAOS published a position paper on its website that reversed this position.6 Interestingly, the statement was done by the AAOS alone, and not done in conjunction with the ADA.
In this position paper, the AAOS recommended that health care providers consider antibiotic prophylaxis prior to invasive procedures on all patients who had prosthetic joints, regardless of how long those joints have been in place. This major change in recommendations was not based on any new evidence that had been reviewed since the 2003 guidelines.
There are two studies that address outcome of patients with prosthetic joints who have and have not received prophylactic antibiotics.
Elie Berbari, MD, and colleagues reported on the results of a prospective case-control study comparing patients with prosthetic joints hospitalized with hip or knee infections with patients who had prosthetic joints hospitalized at the same time who did not have hip or knee infections.7
There was no increased risk of prosthetic hip or knee infection for patients undergoing a dental procedure who were not receiving antibiotic prophylaxis (odds ratio, 0.8; 95% confidence interval, 0.4-1.6), compared with the risk for patients not undergoing a dental procedure (OR, 0.6; 95% CI, 0.4-1.1). Antibiotic prophylaxis in patients undergoing high and low risk dental procedures did not decrease the risk of prosthetic joint infections.
In 2012, the AAOS and the ADA published updated guidelines with the following summary recommendation: “The practitioner might consider discontinuing the practice of routinely prescribing prophylactic antibiotics for patients with hip and knee prosthetic joint implants undergoing dental procedures.”8 They referenced the Berbari study as the best available evidence.
Feng-Chen Kao, MD, and colleagues published a study this year with a design very similar to the Berbari study, with similar results.9 All Taiwanese residents who had received hip or knee replacements over a 12-year period were screened. Those who had received dental procedures were matched with individuals who had not had dental procedures. The dental procedure group was subdivided into a group that received antibiotics and one that didn’t.
There was no difference in infection rates between the group that had received dental procedures and the group that did not, and no difference in infection rates between those who received prophylactic antibiotics and those who didn’t.
I think this myth can be put to rest. There is no evidence to give patients with joint prostheses prophylactic antibiotics before dental procedures.
References
1. Steckelberg J.M., Osmon D.R. Prosthetic joint infections. In: Bisno A.L., Waldvogel F.A., eds. Infections associated with indwelling medical devices. Third ed., Washington, D.C.: American Society of Microbiology Press, 2000:173-209.
2. J Dent Res. 2004 Feb;83(2):170-4.
3. J Clin Periodontol. 2006 Feb;33(6):401-7.
4. J Am Dent Assoc. 1997 Jul;128(7):1004-8.
5. J Am Dent Assoc. 2003 Jul;134(7):895-9.
6. Spec Care Dentist. 2009 Nov-Dec;29(6):229-31.
7. Clin Infect Dis. 2010 Jan 1;50(1):8-16.
8. J Dent (Shiraz). 2013 Mar;14(1):49-52.
9. Infect Control Hosp Epidemiol. 2017 Feb;38(2):154-61.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
A 66-year-old woman 3 years status post hip replacement is seen for dental work. The dentist contacts the clinic for an antibiotic prescription. The patient has a penicillin allergy (rash). What do you recommend?
A. Clindamycin one dose before dental work.
B. Amoxicillin one dose before dental work.
C. Amoxicillin one dose before, one dose 4 hours after dental work.
D. Clindamycin one dose before dental work, one dose 4 hours after dental work.
E. No antibiotics.
Many patients with prosthetic joints will request antibiotics to take prior to dental procedures. Sometimes this request comes from the dental office.
When I ask patients why they feel they need antibiotics, they often reply that they were told by their orthopedic surgeons or their dentist that they would need to take antibiotics before dental procedures.
In an era when Clostridium difficile infection is a common and dangerous complication in the elderly, avoidance of unnecessary antibiotics is critical. In the United States, it is estimated that there are 240,000 patients infected with C. difficile annually, with 24,000 deaths at a cost of $6 billion.1
Is there compelling evidence to justify giving antibiotic prophylaxis for dental procedures to patients with prosthetic joints?
This information has called into question the wisdom of giving antibiotic prophylaxis for dental procedures when the same patients have transient bacteremias as a regular part of day-to-day life, and mouth organisms were infrequent causes of prosthetic joint infections.
The American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) released an advisory statement 20 years ago on antibiotic prophylaxis for patients with dental replacements, which concluded: “Antibiotic prophylaxis is not indicated for dental patients with pins, plates, and screws, nor is it routinely indicated for most dental patients with total joint replacements.”4
In 2003, the AAOS and the ADA released updated guidelines that stated: “Presently, no scientific evidence supports the position that antibiotic prophylaxis to prevent hematogenous infections is required prior to dental treatment in patients with total joint prostheses. The risk/benefit and cost/effectiveness ratios fail to justify the administration of routine antibiotics.”5
Great confusion arose in 2009 when the AAOS published a position paper on its website that reversed this position.6 Interestingly, the statement was done by the AAOS alone, and not done in conjunction with the ADA.
In this position paper, the AAOS recommended that health care providers consider antibiotic prophylaxis prior to invasive procedures on all patients who had prosthetic joints, regardless of how long those joints have been in place. This major change in recommendations was not based on any new evidence that had been reviewed since the 2003 guidelines.
There are two studies that address outcome of patients with prosthetic joints who have and have not received prophylactic antibiotics.
Elie Berbari, MD, and colleagues reported on the results of a prospective case-control study comparing patients with prosthetic joints hospitalized with hip or knee infections with patients who had prosthetic joints hospitalized at the same time who did not have hip or knee infections.7
There was no increased risk of prosthetic hip or knee infection for patients undergoing a dental procedure who were not receiving antibiotic prophylaxis (odds ratio, 0.8; 95% confidence interval, 0.4-1.6), compared with the risk for patients not undergoing a dental procedure (OR, 0.6; 95% CI, 0.4-1.1). Antibiotic prophylaxis in patients undergoing high and low risk dental procedures did not decrease the risk of prosthetic joint infections.
In 2012, the AAOS and the ADA published updated guidelines with the following summary recommendation: “The practitioner might consider discontinuing the practice of routinely prescribing prophylactic antibiotics for patients with hip and knee prosthetic joint implants undergoing dental procedures.”8 They referenced the Berbari study as the best available evidence.
Feng-Chen Kao, MD, and colleagues published a study this year with a design very similar to the Berbari study, with similar results.9 All Taiwanese residents who had received hip or knee replacements over a 12-year period were screened. Those who had received dental procedures were matched with individuals who had not had dental procedures. The dental procedure group was subdivided into a group that received antibiotics and one that didn’t.
There was no difference in infection rates between the group that had received dental procedures and the group that did not, and no difference in infection rates between those who received prophylactic antibiotics and those who didn’t.
I think this myth can be put to rest. There is no evidence to give patients with joint prostheses prophylactic antibiotics before dental procedures.
References
1. Steckelberg J.M., Osmon D.R. Prosthetic joint infections. In: Bisno A.L., Waldvogel F.A., eds. Infections associated with indwelling medical devices. Third ed., Washington, D.C.: American Society of Microbiology Press, 2000:173-209.
2. J Dent Res. 2004 Feb;83(2):170-4.
3. J Clin Periodontol. 2006 Feb;33(6):401-7.
4. J Am Dent Assoc. 1997 Jul;128(7):1004-8.
5. J Am Dent Assoc. 2003 Jul;134(7):895-9.
6. Spec Care Dentist. 2009 Nov-Dec;29(6):229-31.
7. Clin Infect Dis. 2010 Jan 1;50(1):8-16.
8. J Dent (Shiraz). 2013 Mar;14(1):49-52.
9. Infect Control Hosp Epidemiol. 2017 Feb;38(2):154-61.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
Small study: Drug combo achieves negative bacterial culture in all TB patients
SEATTLE – An all-oral drug combination achieved negative bacterial culture in 100% of patients with extensively drug resistant (XDR) or multidrug resistant (MDR) tuberculosis at 4 months, according to a study.
The drugs used were bedaquiline (400 mg once daily for 2 weeks followed by 200 mg three times per week), pretomanid (200 mg once daily), and linezolid (600 mg twice daily). The study, Nix-TB, was an open-label, two-site trial that examined a simplified and shortened all-oral regimen. Pretomanid is an experimental drug, while bedaquiline and linezolid are both approved medications.
The mortality rate among study participants was less than 6%.
“I was surprised at how successful this study was. These are patients who are generally very ill, with a very poor prognosis,” noted Francesca Conradie, MD, deputy director of the clinical HIV unit at the University of Witwatersrand (Johannesburg, South Africa), who presented the results at a poster session at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.
To date, the trial has enrolled 72 subjects (51% HIV positive, 65% XDR-TB, 35% MDR-TB). HIV-infected subjects had to have CD4 counts of at least 50 cell/mcL. The researchers evaluated clinical, laboratory, and sputum liquid cultures at baseline and at weeks 1, 2, 4, 6, and 8, and then every 4-6 weeks throughout the 6-month treatment period.
Forty patients have finished 6 months of therapy and 31 have completed 6-months of posttherapy follow-up.
Four patients died during the first 8 weeks of therapy. Of the survivors, 74% were culture negative at 8 weeks, and all were culture negative at 4 months. Two patients experienced relapses or reinfections at 6 months following therapy.
Twenty-seven percent of patients experienced serious adverse events, but no patients withdrew from the trials for clinical adverse events or laboratory abnormalities.
Linezolid-associated peripheral neuropathy and myelosuppression occurred, with 71% of patients having experienced at least one dose interruption as a result. Seven patients experienced grade 3 or 4 transaminitis, but all such cases resolved and those patients continued the study regimen.
Some hepatic enzyme changes were seen among patients. A total of 14.1% developed alanine transaminase levels greater than 3 times the upper limit of normal (ULN), and 7.0% had levels greater than 5 x ULN. A total of 14.9% had aspartate transaminase (AST) enzymes at greater than 3 x ULN, and 2.8% had AST levels greater than 5 x ULN. A total of 4.2% had alkaline phosphatase levels reaching greater than 3 x ULN. In all cases, the values returned to normal with a pause in therapy.
Dr. Conradie characterized these results as reassuring, in light of the fact that the STAND study of pretomanid in combination with moxifloxacin and pyrazinamide was ended prematurely because of liver safety concerns.
The linezolid side effect profile is concerning, and the study will continue with modified linezolid doses, Dr. Conradie acknowledged. “We’re looking to see if we could do a study with a lower dose” of linezolid or a study that doesn’t involve giving linezolid for the entire period of the treatment, she noted.
Dr Conradie has served on advisory boards for ViiV, Janssen, Merck, GSK, Mylan, and Sanofi Aventis. The study was funded by the TB Foundation.
SEATTLE – An all-oral drug combination achieved negative bacterial culture in 100% of patients with extensively drug resistant (XDR) or multidrug resistant (MDR) tuberculosis at 4 months, according to a study.
The drugs used were bedaquiline (400 mg once daily for 2 weeks followed by 200 mg three times per week), pretomanid (200 mg once daily), and linezolid (600 mg twice daily). The study, Nix-TB, was an open-label, two-site trial that examined a simplified and shortened all-oral regimen. Pretomanid is an experimental drug, while bedaquiline and linezolid are both approved medications.
The mortality rate among study participants was less than 6%.
“I was surprised at how successful this study was. These are patients who are generally very ill, with a very poor prognosis,” noted Francesca Conradie, MD, deputy director of the clinical HIV unit at the University of Witwatersrand (Johannesburg, South Africa), who presented the results at a poster session at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.
To date, the trial has enrolled 72 subjects (51% HIV positive, 65% XDR-TB, 35% MDR-TB). HIV-infected subjects had to have CD4 counts of at least 50 cell/mcL. The researchers evaluated clinical, laboratory, and sputum liquid cultures at baseline and at weeks 1, 2, 4, 6, and 8, and then every 4-6 weeks throughout the 6-month treatment period.
Forty patients have finished 6 months of therapy and 31 have completed 6-months of posttherapy follow-up.
Four patients died during the first 8 weeks of therapy. Of the survivors, 74% were culture negative at 8 weeks, and all were culture negative at 4 months. Two patients experienced relapses or reinfections at 6 months following therapy.
Twenty-seven percent of patients experienced serious adverse events, but no patients withdrew from the trials for clinical adverse events or laboratory abnormalities.
Linezolid-associated peripheral neuropathy and myelosuppression occurred, with 71% of patients having experienced at least one dose interruption as a result. Seven patients experienced grade 3 or 4 transaminitis, but all such cases resolved and those patients continued the study regimen.
Some hepatic enzyme changes were seen among patients. A total of 14.1% developed alanine transaminase levels greater than 3 times the upper limit of normal (ULN), and 7.0% had levels greater than 5 x ULN. A total of 14.9% had aspartate transaminase (AST) enzymes at greater than 3 x ULN, and 2.8% had AST levels greater than 5 x ULN. A total of 4.2% had alkaline phosphatase levels reaching greater than 3 x ULN. In all cases, the values returned to normal with a pause in therapy.
Dr. Conradie characterized these results as reassuring, in light of the fact that the STAND study of pretomanid in combination with moxifloxacin and pyrazinamide was ended prematurely because of liver safety concerns.
The linezolid side effect profile is concerning, and the study will continue with modified linezolid doses, Dr. Conradie acknowledged. “We’re looking to see if we could do a study with a lower dose” of linezolid or a study that doesn’t involve giving linezolid for the entire period of the treatment, she noted.
Dr Conradie has served on advisory boards for ViiV, Janssen, Merck, GSK, Mylan, and Sanofi Aventis. The study was funded by the TB Foundation.
SEATTLE – An all-oral drug combination achieved negative bacterial culture in 100% of patients with extensively drug resistant (XDR) or multidrug resistant (MDR) tuberculosis at 4 months, according to a study.
The drugs used were bedaquiline (400 mg once daily for 2 weeks followed by 200 mg three times per week), pretomanid (200 mg once daily), and linezolid (600 mg twice daily). The study, Nix-TB, was an open-label, two-site trial that examined a simplified and shortened all-oral regimen. Pretomanid is an experimental drug, while bedaquiline and linezolid are both approved medications.
The mortality rate among study participants was less than 6%.
“I was surprised at how successful this study was. These are patients who are generally very ill, with a very poor prognosis,” noted Francesca Conradie, MD, deputy director of the clinical HIV unit at the University of Witwatersrand (Johannesburg, South Africa), who presented the results at a poster session at the Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.
To date, the trial has enrolled 72 subjects (51% HIV positive, 65% XDR-TB, 35% MDR-TB). HIV-infected subjects had to have CD4 counts of at least 50 cell/mcL. The researchers evaluated clinical, laboratory, and sputum liquid cultures at baseline and at weeks 1, 2, 4, 6, and 8, and then every 4-6 weeks throughout the 6-month treatment period.
Forty patients have finished 6 months of therapy and 31 have completed 6-months of posttherapy follow-up.
Four patients died during the first 8 weeks of therapy. Of the survivors, 74% were culture negative at 8 weeks, and all were culture negative at 4 months. Two patients experienced relapses or reinfections at 6 months following therapy.
Twenty-seven percent of patients experienced serious adverse events, but no patients withdrew from the trials for clinical adverse events or laboratory abnormalities.
Linezolid-associated peripheral neuropathy and myelosuppression occurred, with 71% of patients having experienced at least one dose interruption as a result. Seven patients experienced grade 3 or 4 transaminitis, but all such cases resolved and those patients continued the study regimen.
Some hepatic enzyme changes were seen among patients. A total of 14.1% developed alanine transaminase levels greater than 3 times the upper limit of normal (ULN), and 7.0% had levels greater than 5 x ULN. A total of 14.9% had aspartate transaminase (AST) enzymes at greater than 3 x ULN, and 2.8% had AST levels greater than 5 x ULN. A total of 4.2% had alkaline phosphatase levels reaching greater than 3 x ULN. In all cases, the values returned to normal with a pause in therapy.
Dr. Conradie characterized these results as reassuring, in light of the fact that the STAND study of pretomanid in combination with moxifloxacin and pyrazinamide was ended prematurely because of liver safety concerns.
The linezolid side effect profile is concerning, and the study will continue with modified linezolid doses, Dr. Conradie acknowledged. “We’re looking to see if we could do a study with a lower dose” of linezolid or a study that doesn’t involve giving linezolid for the entire period of the treatment, she noted.
Dr Conradie has served on advisory boards for ViiV, Janssen, Merck, GSK, Mylan, and Sanofi Aventis. The study was funded by the TB Foundation.
AT CROI
Key clinical point: An oral, three-drug combination led to undetectable bacteria levels.
Major finding: All of the patients in the study were culture negative at 4 months.
Data source: Open-label trial of 72 patients at two centers.
Disclosures: Dr. Conradie has served on advisory boards for ViiV, Janssen, Merck, GSK, Mylan, and Sanofi Aventis. The study was funded by the TB Foundation.
C. auris forms biofilms, enhancing its virulence, resistance
The emerging multidrug-resistant yeast organism Candida auris forms biofilms that enhance both its resistance and its virulence, according to in vitro analyses.
C. auris first attracted attention in 2009 because of its resistance to azoles and amphotericin B. Since then, it has been identified as the cause of life-threatening invasive infections worldwide, including hospital outbreaks across Asia and South America, wrote Leighann Sherry, PhD, a medical mycologist at the University of Glasgow, and her associates.
To determine whether the pathogen has the capacity to form biofilms, the investigators propagated several different strains in the laboratory and examined their development. In three separate trials, eight samples of each strain grew biofilms, which constitute “a key driver of candida pathogenicity.” In antifungal susceptibility tests, caspofungin was completely ineffective, an unexpected finding because the agent usually is highly effective against other candida species. Amphotericin B, liposomal amphotericin B, and fluconazole also were ineffective; micafungin and chlorhexidine were the most effective at clearing C. auris.
Biofilm formation “contributes not only to C. auris virulence but also to its [resistance] in hospital environments, increasing its ability to cause outbreaks,” Dr. Sherry and her associates said (Emerg. Infect. Dis. 2017 Feb;23[2]:328-31).
“Our findings suggest it is improbable that the spread and prevalence of C. auris can be controlled with antifungal stewardship approaches alone,” they noted, adding that “infection-prevention measures targeting C. auris biofilms in patients, on medical devices, and in the hospital environment will be required,” they noted.
The emerging multidrug-resistant yeast organism Candida auris forms biofilms that enhance both its resistance and its virulence, according to in vitro analyses.
C. auris first attracted attention in 2009 because of its resistance to azoles and amphotericin B. Since then, it has been identified as the cause of life-threatening invasive infections worldwide, including hospital outbreaks across Asia and South America, wrote Leighann Sherry, PhD, a medical mycologist at the University of Glasgow, and her associates.
To determine whether the pathogen has the capacity to form biofilms, the investigators propagated several different strains in the laboratory and examined their development. In three separate trials, eight samples of each strain grew biofilms, which constitute “a key driver of candida pathogenicity.” In antifungal susceptibility tests, caspofungin was completely ineffective, an unexpected finding because the agent usually is highly effective against other candida species. Amphotericin B, liposomal amphotericin B, and fluconazole also were ineffective; micafungin and chlorhexidine were the most effective at clearing C. auris.
Biofilm formation “contributes not only to C. auris virulence but also to its [resistance] in hospital environments, increasing its ability to cause outbreaks,” Dr. Sherry and her associates said (Emerg. Infect. Dis. 2017 Feb;23[2]:328-31).
“Our findings suggest it is improbable that the spread and prevalence of C. auris can be controlled with antifungal stewardship approaches alone,” they noted, adding that “infection-prevention measures targeting C. auris biofilms in patients, on medical devices, and in the hospital environment will be required,” they noted.
The emerging multidrug-resistant yeast organism Candida auris forms biofilms that enhance both its resistance and its virulence, according to in vitro analyses.
C. auris first attracted attention in 2009 because of its resistance to azoles and amphotericin B. Since then, it has been identified as the cause of life-threatening invasive infections worldwide, including hospital outbreaks across Asia and South America, wrote Leighann Sherry, PhD, a medical mycologist at the University of Glasgow, and her associates.
To determine whether the pathogen has the capacity to form biofilms, the investigators propagated several different strains in the laboratory and examined their development. In three separate trials, eight samples of each strain grew biofilms, which constitute “a key driver of candida pathogenicity.” In antifungal susceptibility tests, caspofungin was completely ineffective, an unexpected finding because the agent usually is highly effective against other candida species. Amphotericin B, liposomal amphotericin B, and fluconazole also were ineffective; micafungin and chlorhexidine were the most effective at clearing C. auris.
Biofilm formation “contributes not only to C. auris virulence but also to its [resistance] in hospital environments, increasing its ability to cause outbreaks,” Dr. Sherry and her associates said (Emerg. Infect. Dis. 2017 Feb;23[2]:328-31).
“Our findings suggest it is improbable that the spread and prevalence of C. auris can be controlled with antifungal stewardship approaches alone,” they noted, adding that “infection-prevention measures targeting C. auris biofilms in patients, on medical devices, and in the hospital environment will be required,” they noted.
FROM EMERGING INFECTIOUS DISEASES
Key clinical point: The emerging multidrug-resistant yeast organism Candida auris forms biofilms that enhance both its resistance and its virulence.
Major finding: In three separate trials, eight samples of each strain of C. auris grew biofilms that constitute “a key driver of Candida pathogenicity.”
Data source: In-vitro analyses of C. auris growth.
Disclosures: No funding source(s) or financial disclosures were provided.
Postdischarge antibiotics for complicated pneumonia
Clinical question: Are oral antibiotics as effective as intravenous (IV) antibiotics in the treatment of complicated pneumonia after discharge to home?
Background: Pneumonia is the most common illness among hospitalized children and adolescents (excluding neonates). Among children admitted with community acquired pneumonia, 15% may develop a complicated pneumonia (one with a pleural effusion or empyema). Treatment for these complicated pneumonias may include a variety of invasive procedures, such as video-assisted thorascopic surgery or chest tube placement.
Typically, a long course of antibiotics is prescribed on discharge, which may be oral or parenterally administered via a peripherally inserted central catheter (PICC). Previous studies have shown that oral antibiotics are equivalent to parenteral antibiotics for outpatient treatment of osteomyelitis. However, little evidence exists comparing the effectiveness of the two routes in treating complicated pneumonia. 
The rate of PICC complications in complicated pneumonia also has not been well studied.
Study design: Retrospective cohort study.
Setting: Thirty-eight children’s hospitals affiliated with the Children’s Hospital Association.
Synopsis: Over 4 years, 7,820 encounters were identified with 2,123 patients ultimately being included in the cohort. Inclusion criteria were age 2 months to 18 years, and discharge diagnoses of pneumonia and pleural effusion. The authors excluded patients with chronic medical conditions, length of stay (LOS) less than 4 and more than 14 days, patients transferred to or from other institutions, and patients receiving no antibiotics on hospital day 1. The final criteria attempted to avoid inclusion of patients with nosocomial pneumonia. After application of these criteria, individual patient records were reviewed.
Patients were categorized as PICC or oral antibiotics based upon antibiotic route at their initial discharge. Treatment failure was defined as an ED revisit or rehospitalization that led to a change in antibiotic, lengthening of antibiotic course, or pleural drainage. Records were searched for evidence of PICC complications, adverse drug reactions, and other illness-related revisits. Patients in the PICC arm and oral arm were matched by age, race, insurance, LOS, positive vs. negative blood culture, ICU admission, and timing and type of pleural drainage.
Fifty-seven patients had treatment failure (2.7%). In matched analysis, there was no difference in treatment failure between PICC and oral routes (PICC treatment failure OR, 1.26 95% CI, 0.54-2.94). PICC complications were found in 7.1% of patients. Patients with PICC had significantly higher rates of adverse drug reactions (OR, 19.1 95% CI, 4.2-87.3) and illness-related revisits (OR 3.27 95% CI, 1.65-6.48), and all revisits (OR, 4.71 95% CI, 2.97-7.46).
PICC use varied markedly across geographic regions and institutions, with rates varying from less than 10% of cases to approximately 70%. Of geographic regions, the Mid-Atlantic used PICCs least often while the East North Central used them the most.
Bottom line: Treatment failure with both oral and PICC treatment of complicated pneumonia occur at the same rate, and are uncommon. Patients with PICCs had an increased rate of complications, including adverse drug reactions and revisits.
Citation: Shah SS, Srivastava R, Wu S, et al. Intravenous versus oral antibiotics for postdischarge treatment of complicated pneumonia. Pediatrics. 2016;138(6):e20161692. doi: 10.1542/peds.2016-1692.
Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. duPont Hospital for Children in Wilmington, Del., and clinical assistant professor of pediatrics at Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia.
Clinical question: Are oral antibiotics as effective as intravenous (IV) antibiotics in the treatment of complicated pneumonia after discharge to home?
Background: Pneumonia is the most common illness among hospitalized children and adolescents (excluding neonates). Among children admitted with community acquired pneumonia, 15% may develop a complicated pneumonia (one with a pleural effusion or empyema). Treatment for these complicated pneumonias may include a variety of invasive procedures, such as video-assisted thorascopic surgery or chest tube placement.
Typically, a long course of antibiotics is prescribed on discharge, which may be oral or parenterally administered via a peripherally inserted central catheter (PICC). Previous studies have shown that oral antibiotics are equivalent to parenteral antibiotics for outpatient treatment of osteomyelitis. However, little evidence exists comparing the effectiveness of the two routes in treating complicated pneumonia.
The rate of PICC complications in complicated pneumonia also has not been well studied.
Study design: Retrospective cohort study.
Setting: Thirty-eight children’s hospitals affiliated with the Children’s Hospital Association.
Synopsis: Over 4 years, 7,820 encounters were identified with 2,123 patients ultimately being included in the cohort. Inclusion criteria were age 2 months to 18 years, and discharge diagnoses of pneumonia and pleural effusion. The authors excluded patients with chronic medical conditions, length of stay (LOS) less than 4 and more than 14 days, patients transferred to or from other institutions, and patients receiving no antibiotics on hospital day 1. The final criteria attempted to avoid inclusion of patients with nosocomial pneumonia. After application of these criteria, individual patient records were reviewed.
Patients were categorized as PICC or oral antibiotics based upon antibiotic route at their initial discharge. Treatment failure was defined as an ED revisit or rehospitalization that led to a change in antibiotic, lengthening of antibiotic course, or pleural drainage. Records were searched for evidence of PICC complications, adverse drug reactions, and other illness-related revisits. Patients in the PICC arm and oral arm were matched by age, race, insurance, LOS, positive vs. negative blood culture, ICU admission, and timing and type of pleural drainage.
Fifty-seven patients had treatment failure (2.7%). In matched analysis, there was no difference in treatment failure between PICC and oral routes (PICC treatment failure OR, 1.26 95% CI, 0.54-2.94). PICC complications were found in 7.1% of patients. Patients with PICC had significantly higher rates of adverse drug reactions (OR, 19.1 95% CI, 4.2-87.3) and illness-related revisits (OR 3.27 95% CI, 1.65-6.48), and all revisits (OR, 4.71 95% CI, 2.97-7.46).
PICC use varied markedly across geographic regions and institutions, with rates varying from less than 10% of cases to approximately 70%. Of geographic regions, the Mid-Atlantic used PICCs least often while the East North Central used them the most.
Bottom line: Treatment failure with both oral and PICC treatment of complicated pneumonia occur at the same rate, and are uncommon. Patients with PICCs had an increased rate of complications, including adverse drug reactions and revisits.
Citation: Shah SS, Srivastava R, Wu S, et al. Intravenous versus oral antibiotics for postdischarge treatment of complicated pneumonia. Pediatrics. 2016;138(6):e20161692. doi: 10.1542/peds.2016-1692.
Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. duPont Hospital for Children in Wilmington, Del., and clinical assistant professor of pediatrics at Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia.
Clinical question: Are oral antibiotics as effective as intravenous (IV) antibiotics in the treatment of complicated pneumonia after discharge to home?
Background: Pneumonia is the most common illness among hospitalized children and adolescents (excluding neonates). Among children admitted with community acquired pneumonia, 15% may develop a complicated pneumonia (one with a pleural effusion or empyema). Treatment for these complicated pneumonias may include a variety of invasive procedures, such as video-assisted thorascopic surgery or chest tube placement.
Typically, a long course of antibiotics is prescribed on discharge, which may be oral or parenterally administered via a peripherally inserted central catheter (PICC). Previous studies have shown that oral antibiotics are equivalent to parenteral antibiotics for outpatient treatment of osteomyelitis. However, little evidence exists comparing the effectiveness of the two routes in treating complicated pneumonia.
The rate of PICC complications in complicated pneumonia also has not been well studied.
Study design: Retrospective cohort study.
Setting: Thirty-eight children’s hospitals affiliated with the Children’s Hospital Association.
Synopsis: Over 4 years, 7,820 encounters were identified with 2,123 patients ultimately being included in the cohort. Inclusion criteria were age 2 months to 18 years, and discharge diagnoses of pneumonia and pleural effusion. The authors excluded patients with chronic medical conditions, length of stay (LOS) less than 4 and more than 14 days, patients transferred to or from other institutions, and patients receiving no antibiotics on hospital day 1. The final criteria attempted to avoid inclusion of patients with nosocomial pneumonia. After application of these criteria, individual patient records were reviewed.
Patients were categorized as PICC or oral antibiotics based upon antibiotic route at their initial discharge. Treatment failure was defined as an ED revisit or rehospitalization that led to a change in antibiotic, lengthening of antibiotic course, or pleural drainage. Records were searched for evidence of PICC complications, adverse drug reactions, and other illness-related revisits. Patients in the PICC arm and oral arm were matched by age, race, insurance, LOS, positive vs. negative blood culture, ICU admission, and timing and type of pleural drainage.
Fifty-seven patients had treatment failure (2.7%). In matched analysis, there was no difference in treatment failure between PICC and oral routes (PICC treatment failure OR, 1.26 95% CI, 0.54-2.94). PICC complications were found in 7.1% of patients. Patients with PICC had significantly higher rates of adverse drug reactions (OR, 19.1 95% CI, 4.2-87.3) and illness-related revisits (OR 3.27 95% CI, 1.65-6.48), and all revisits (OR, 4.71 95% CI, 2.97-7.46).
PICC use varied markedly across geographic regions and institutions, with rates varying from less than 10% of cases to approximately 70%. Of geographic regions, the Mid-Atlantic used PICCs least often while the East North Central used them the most.
Bottom line: Treatment failure with both oral and PICC treatment of complicated pneumonia occur at the same rate, and are uncommon. Patients with PICCs had an increased rate of complications, including adverse drug reactions and revisits.
Citation: Shah SS, Srivastava R, Wu S, et al. Intravenous versus oral antibiotics for postdischarge treatment of complicated pneumonia. Pediatrics. 2016;138(6):e20161692. doi: 10.1542/peds.2016-1692.
Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. duPont Hospital for Children in Wilmington, Del., and clinical assistant professor of pediatrics at Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia.
In ICU, pair MRSA testing method with isolation protocol
An ICU’s method of testing for methicillin-resistant Staphylococcus aureus (MRSA) should be paired with its patient isolation policy, according to researchers at the University of Colorado at Denver.
In an ICU with all patients preemptively isolated, it is worth the added expense to opt for the polymerase chain reaction (PCR) test – which generates results in a few hours – so that patients negative for the infection can be moved out of isolation more quickly, wrote Melanie D. Whittington, PhD, and her coauthors. But if the ICU is only isolating MRSA-positive patients, the authors instead recommend the less expensive but slower chromogenic agar 24-hour testing.
The other two MRSA tests the researchers assessed – conventional culture and chromogenic agar 48-hour testing – are less expensive. But when paired with either ICU isolation policy, those tests lead to excessive inappropriate isolation costs while waiting for the results, the study investigators cautioned (Am J Infect Control. 2017 Jan 23. doi: 10.1016/j.ajic.2016.12.014).
Adding together the cost per patient of the test, the “appropriate isolation costs,” and “inappropriate isolation costs,” the universal isolation policy is least expensive per patient with PCR, at $82.51 per patient. With conventional culture, which can take several days, this cost ballooned to $290.11 per patient, with high inappropriate isolation costs.
Doing the same math with the more targeted isolation policy, the least expensive screening method was the 24-hour chromogenic agar, at $8.54 per patient, while the expense of the PCR test made it the most expensive method when paired with this isolation policy, at $30.95 per patient.
“With knowledge of the screening test that minimizes inappropriate and total costs, hospitals can maximize the efficiency of their resource use and improve the health of their patients,” Dr. Whittington and her coauthors wrote.
The authors reported no conflicts of interest.
An ICU’s method of testing for methicillin-resistant Staphylococcus aureus (MRSA) should be paired with its patient isolation policy, according to researchers at the University of Colorado at Denver.
In an ICU with all patients preemptively isolated, it is worth the added expense to opt for the polymerase chain reaction (PCR) test – which generates results in a few hours – so that patients negative for the infection can be moved out of isolation more quickly, wrote Melanie D. Whittington, PhD, and her coauthors. But if the ICU is only isolating MRSA-positive patients, the authors instead recommend the less expensive but slower chromogenic agar 24-hour testing.
The other two MRSA tests the researchers assessed – conventional culture and chromogenic agar 48-hour testing – are less expensive. But when paired with either ICU isolation policy, those tests lead to excessive inappropriate isolation costs while waiting for the results, the study investigators cautioned (Am J Infect Control. 2017 Jan 23. doi: 10.1016/j.ajic.2016.12.014).
Adding together the cost per patient of the test, the “appropriate isolation costs,” and “inappropriate isolation costs,” the universal isolation policy is least expensive per patient with PCR, at $82.51 per patient. With conventional culture, which can take several days, this cost ballooned to $290.11 per patient, with high inappropriate isolation costs.
Doing the same math with the more targeted isolation policy, the least expensive screening method was the 24-hour chromogenic agar, at $8.54 per patient, while the expense of the PCR test made it the most expensive method when paired with this isolation policy, at $30.95 per patient.
“With knowledge of the screening test that minimizes inappropriate and total costs, hospitals can maximize the efficiency of their resource use and improve the health of their patients,” Dr. Whittington and her coauthors wrote.
The authors reported no conflicts of interest.
An ICU’s method of testing for methicillin-resistant Staphylococcus aureus (MRSA) should be paired with its patient isolation policy, according to researchers at the University of Colorado at Denver.
In an ICU with all patients preemptively isolated, it is worth the added expense to opt for the polymerase chain reaction (PCR) test – which generates results in a few hours – so that patients negative for the infection can be moved out of isolation more quickly, wrote Melanie D. Whittington, PhD, and her coauthors. But if the ICU is only isolating MRSA-positive patients, the authors instead recommend the less expensive but slower chromogenic agar 24-hour testing.
The other two MRSA tests the researchers assessed – conventional culture and chromogenic agar 48-hour testing – are less expensive. But when paired with either ICU isolation policy, those tests lead to excessive inappropriate isolation costs while waiting for the results, the study investigators cautioned (Am J Infect Control. 2017 Jan 23. doi: 10.1016/j.ajic.2016.12.014).
Adding together the cost per patient of the test, the “appropriate isolation costs,” and “inappropriate isolation costs,” the universal isolation policy is least expensive per patient with PCR, at $82.51 per patient. With conventional culture, which can take several days, this cost ballooned to $290.11 per patient, with high inappropriate isolation costs.
Doing the same math with the more targeted isolation policy, the least expensive screening method was the 24-hour chromogenic agar, at $8.54 per patient, while the expense of the PCR test made it the most expensive method when paired with this isolation policy, at $30.95 per patient.
“With knowledge of the screening test that minimizes inappropriate and total costs, hospitals can maximize the efficiency of their resource use and improve the health of their patients,” Dr. Whittington and her coauthors wrote.
The authors reported no conflicts of interest.
Sterile fecal filtrate effectively treated recurrent CDI
Sterile fecal filtrate transplantation (FFT) effectively treated five cases of symptomatic chronic-relapsing Clostridium difficile infection, investigators reported.
The procedure restored normal bowel habits and eliminated symptoms through the end of the study – that is, for at least 6 months – in all patients, Stephan J. Ott, MD, and his associates wrote (Gastroenterology. 2019. doi: 10.1053/j.gastro.2016.11.010).
Proteome analyses did not identify proteins likely to explain this efficacy, but 16S rRNA gene sequencing did demonstrate diverse bacterial DNA signatures in the filtrates, and tests of virus-like particles yielded “a complex signature of macrophages,” Dr. Ott and his associates reported. Additional tests suggested that recipients’ microbiomes continued to change weeks after FFT. “This open-label series strongly suggests that FFT should be evaluated in a controlled setting in comparison with standard fecal microbiota transplantation,” the researchers concluded.
Fecal microbiota transplantation (FMT) effectively treats recurrent Clostridium difficile infection (CDI), but even “the most rigorous and costly donor screening procedures, or defined panels of bacteria, cannot exclude the risk of transferring unknown pathogens or undetectable functional characteristics within the living microorganisms to the recipient, including bacterial or viral risk factors for metabolic diseases, cancer, atopy, or autoimmunity,” the investigators wrote.
Therefore, they performed sterile FFT in five patients who were positive on at least two of three tests: enzyme-linked immunosorbent assay for C. difficile–specific glutamate dehydrogenase; C. difficile toxin enzyme-linked immunosorbent assay; and culture of toxin-producing C. difficile. Patients chose their own stool donors, who were then screened based on published guidelines (Clin Gastroenterol Hepatol. 2011;9[12]:1044-49). Next, “slurries” were prepared from donor stool and filtered with a custom-built air pressure filtration system, yielding a “light brown, clear liquid with a subjectively less unpleasant and intensive odor” than conventional FMT stool preparations. Bacterial cultures of these filtrates yielded no growth, whereas donor stool cultures showed profuse growth of aerobic and anaerobic bacterial colonies, Dr. Ott and his associates said.
Patients became symptom-free 2-4 days after undergoing FFT. Notably, one patient had previously undergone FMT, which led to acute fever and diarrhea and recurrence of baseline symptoms after 3 months. This patient did not develop fever or diarrhea after FFT, was symptom-free after 3 days, and remained symptom-free until the study ended 2 years later, the researchers said. All other patients also remained symptom-free through the end of the study, that is, for 6 months to more than 2 years.
Analyses of 16S rRNA revealed substantial longitudinal shifts after FFT that often were present by week 1 and remained stable until week 6, the investigators said. Further tests confirmed marked shifts in bacterial phylotypes and in their relative abundance over time. Repeated virus analyses of one patient also showed that the phageome shifted over time to resemble that of the donor.
Patients were between 49 and 75 years old, three were female and two were male, and all had received more than one antibiotic before their first episode of CDI. Antibiotics for CDI had included metronidazole, vancomycin, and rifaximin. Comorbidities included pseudomembranous colitis, renal failure, HIV infection, epilepsy, and chronic heart failure, and medical histories included recurrent diverticulitis with sigmoid resection, gastric carcinoma, and colon cancer.
“It is important to keep in mind that, in contrast to conventional FMT, transferring sterile FFT filtrates cannot be expected to establish a microbiota similar to that of the donor in the receiving patient,” Dr. Ott and his associates noted. Instead, bacterial DNA in the filtrate might trigger the re-establishment of the recipient microbiome, they said. Bacterial cell wall fragments or bacteriophages also might play a role, they added.
The German Excellence Cluster and CONARIS Research Institute AG supported the work. Dr. Ott reported having lectured for Allergosan. Two coinvestigators reported employment with CONARIS. A third coinvestigator reported shareholder relationships with CONARIS, Allergosan, Danone, and Nestle and lectureship compensation from Allergosan. The other eight coinvestigators had no relevant conflicts of interest.
The remarkable efficacy of fecal microbial transplant in recurrent C. difficile infection provides a compelling example of ecologic microbiome-based therapy. Its mechanism is widely considered to be the restoration of select microbial species that suppress C. difficile colonization and virulence in healthy individuals. Identification of such suppressive microbiota is still at an early stage, with empirical studies revealing effective synthetic microbial consortia, and evidence of some modes of action, such as bile salt metabolism (Nature 2015;517:205-8; PLoS Pathog. 2012;8:e1002995).
Clouding this elegant concept is the provocative new study of Dr. Ott and his colleagues. Prompted by long-term safety concerns, they evaluated the efficacy of a donor fecal microfiltrate lacking viable intact organisms. Indeed, in five patients, long-term eradication of C. difficile was achieved with a single dose. This observation indicates that the initial action of fecal transplant may not require restoration of viable organisms into the antibiotic-damaged ecosystem.
What mechanisms might account for the therapeutic action of organism-free fecal microfiltrate? First, this material is laden with a complex, potentially distinct mix of microbial products and particulates (Cell. 2016;165[5]:1106-19) from donor origin or ex vivo processing. These biologicals may induce immune processes to promote control of C. difficile directly or via changes in other commensals of the patient's microbiome. Second, the microfiltrate retains abundant and diverse bacteria-targeting viruses of the fecal stream. Perhaps certain viruses, deficient in patients, target C. difficile and/or beneficially reshape microbial composition (Cell Mol Gastroenterol Hepatol. 2015;1[1]:28-40). So, C. difficile challenges us once more into the breach with new insights ahead for the principles and practice of ecologic microbiome therapy.
Jonathan Braun, MD, PhD, is professor and chair of pathology and laboratory medicine at the University of California, Los Angeles. He has no conflicts of interest.
The remarkable efficacy of fecal microbial transplant in recurrent C. difficile infection provides a compelling example of ecologic microbiome-based therapy. Its mechanism is widely considered to be the restoration of select microbial species that suppress C. difficile colonization and virulence in healthy individuals. Identification of such suppressive microbiota is still at an early stage, with empirical studies revealing effective synthetic microbial consortia, and evidence of some modes of action, such as bile salt metabolism (Nature 2015;517:205-8; PLoS Pathog. 2012;8:e1002995).
Clouding this elegant concept is the provocative new study of Dr. Ott and his colleagues. Prompted by long-term safety concerns, they evaluated the efficacy of a donor fecal microfiltrate lacking viable intact organisms. Indeed, in five patients, long-term eradication of C. difficile was achieved with a single dose. This observation indicates that the initial action of fecal transplant may not require restoration of viable organisms into the antibiotic-damaged ecosystem.
What mechanisms might account for the therapeutic action of organism-free fecal microfiltrate? First, this material is laden with a complex, potentially distinct mix of microbial products and particulates (Cell. 2016;165[5]:1106-19) from donor origin or ex vivo processing. These biologicals may induce immune processes to promote control of C. difficile directly or via changes in other commensals of the patient's microbiome. Second, the microfiltrate retains abundant and diverse bacteria-targeting viruses of the fecal stream. Perhaps certain viruses, deficient in patients, target C. difficile and/or beneficially reshape microbial composition (Cell Mol Gastroenterol Hepatol. 2015;1[1]:28-40). So, C. difficile challenges us once more into the breach with new insights ahead for the principles and practice of ecologic microbiome therapy.
Jonathan Braun, MD, PhD, is professor and chair of pathology and laboratory medicine at the University of California, Los Angeles. He has no conflicts of interest.
The remarkable efficacy of fecal microbial transplant in recurrent C. difficile infection provides a compelling example of ecologic microbiome-based therapy. Its mechanism is widely considered to be the restoration of select microbial species that suppress C. difficile colonization and virulence in healthy individuals. Identification of such suppressive microbiota is still at an early stage, with empirical studies revealing effective synthetic microbial consortia, and evidence of some modes of action, such as bile salt metabolism (Nature 2015;517:205-8; PLoS Pathog. 2012;8:e1002995).
Clouding this elegant concept is the provocative new study of Dr. Ott and his colleagues. Prompted by long-term safety concerns, they evaluated the efficacy of a donor fecal microfiltrate lacking viable intact organisms. Indeed, in five patients, long-term eradication of C. difficile was achieved with a single dose. This observation indicates that the initial action of fecal transplant may not require restoration of viable organisms into the antibiotic-damaged ecosystem.
What mechanisms might account for the therapeutic action of organism-free fecal microfiltrate? First, this material is laden with a complex, potentially distinct mix of microbial products and particulates (Cell. 2016;165[5]:1106-19) from donor origin or ex vivo processing. These biologicals may induce immune processes to promote control of C. difficile directly or via changes in other commensals of the patient's microbiome. Second, the microfiltrate retains abundant and diverse bacteria-targeting viruses of the fecal stream. Perhaps certain viruses, deficient in patients, target C. difficile and/or beneficially reshape microbial composition (Cell Mol Gastroenterol Hepatol. 2015;1[1]:28-40). So, C. difficile challenges us once more into the breach with new insights ahead for the principles and practice of ecologic microbiome therapy.
Jonathan Braun, MD, PhD, is professor and chair of pathology and laboratory medicine at the University of California, Los Angeles. He has no conflicts of interest.
Sterile fecal filtrate transplantation (FFT) effectively treated five cases of symptomatic chronic-relapsing Clostridium difficile infection, investigators reported.
The procedure restored normal bowel habits and eliminated symptoms through the end of the study – that is, for at least 6 months – in all patients, Stephan J. Ott, MD, and his associates wrote (Gastroenterology. 2019. doi: 10.1053/j.gastro.2016.11.010).
Proteome analyses did not identify proteins likely to explain this efficacy, but 16S rRNA gene sequencing did demonstrate diverse bacterial DNA signatures in the filtrates, and tests of virus-like particles yielded “a complex signature of macrophages,” Dr. Ott and his associates reported. Additional tests suggested that recipients’ microbiomes continued to change weeks after FFT. “This open-label series strongly suggests that FFT should be evaluated in a controlled setting in comparison with standard fecal microbiota transplantation,” the researchers concluded.
Fecal microbiota transplantation (FMT) effectively treats recurrent Clostridium difficile infection (CDI), but even “the most rigorous and costly donor screening procedures, or defined panels of bacteria, cannot exclude the risk of transferring unknown pathogens or undetectable functional characteristics within the living microorganisms to the recipient, including bacterial or viral risk factors for metabolic diseases, cancer, atopy, or autoimmunity,” the investigators wrote.
Therefore, they performed sterile FFT in five patients who were positive on at least two of three tests: enzyme-linked immunosorbent assay for C. difficile–specific glutamate dehydrogenase; C. difficile toxin enzyme-linked immunosorbent assay; and culture of toxin-producing C. difficile. Patients chose their own stool donors, who were then screened based on published guidelines (Clin Gastroenterol Hepatol. 2011;9[12]:1044-49). Next, “slurries” were prepared from donor stool and filtered with a custom-built air pressure filtration system, yielding a “light brown, clear liquid with a subjectively less unpleasant and intensive odor” than conventional FMT stool preparations. Bacterial cultures of these filtrates yielded no growth, whereas donor stool cultures showed profuse growth of aerobic and anaerobic bacterial colonies, Dr. Ott and his associates said.
Patients became symptom-free 2-4 days after undergoing FFT. Notably, one patient had previously undergone FMT, which led to acute fever and diarrhea and recurrence of baseline symptoms after 3 months. This patient did not develop fever or diarrhea after FFT, was symptom-free after 3 days, and remained symptom-free until the study ended 2 years later, the researchers said. All other patients also remained symptom-free through the end of the study, that is, for 6 months to more than 2 years.
Analyses of 16S rRNA revealed substantial longitudinal shifts after FFT that often were present by week 1 and remained stable until week 6, the investigators said. Further tests confirmed marked shifts in bacterial phylotypes and in their relative abundance over time. Repeated virus analyses of one patient also showed that the phageome shifted over time to resemble that of the donor.
Patients were between 49 and 75 years old, three were female and two were male, and all had received more than one antibiotic before their first episode of CDI. Antibiotics for CDI had included metronidazole, vancomycin, and rifaximin. Comorbidities included pseudomembranous colitis, renal failure, HIV infection, epilepsy, and chronic heart failure, and medical histories included recurrent diverticulitis with sigmoid resection, gastric carcinoma, and colon cancer.
“It is important to keep in mind that, in contrast to conventional FMT, transferring sterile FFT filtrates cannot be expected to establish a microbiota similar to that of the donor in the receiving patient,” Dr. Ott and his associates noted. Instead, bacterial DNA in the filtrate might trigger the re-establishment of the recipient microbiome, they said. Bacterial cell wall fragments or bacteriophages also might play a role, they added.
The German Excellence Cluster and CONARIS Research Institute AG supported the work. Dr. Ott reported having lectured for Allergosan. Two coinvestigators reported employment with CONARIS. A third coinvestigator reported shareholder relationships with CONARIS, Allergosan, Danone, and Nestle and lectureship compensation from Allergosan. The other eight coinvestigators had no relevant conflicts of interest.
Sterile fecal filtrate transplantation (FFT) effectively treated five cases of symptomatic chronic-relapsing Clostridium difficile infection, investigators reported.
The procedure restored normal bowel habits and eliminated symptoms through the end of the study – that is, for at least 6 months – in all patients, Stephan J. Ott, MD, and his associates wrote (Gastroenterology. 2019. doi: 10.1053/j.gastro.2016.11.010).
Proteome analyses did not identify proteins likely to explain this efficacy, but 16S rRNA gene sequencing did demonstrate diverse bacterial DNA signatures in the filtrates, and tests of virus-like particles yielded “a complex signature of macrophages,” Dr. Ott and his associates reported. Additional tests suggested that recipients’ microbiomes continued to change weeks after FFT. “This open-label series strongly suggests that FFT should be evaluated in a controlled setting in comparison with standard fecal microbiota transplantation,” the researchers concluded.
Fecal microbiota transplantation (FMT) effectively treats recurrent Clostridium difficile infection (CDI), but even “the most rigorous and costly donor screening procedures, or defined panels of bacteria, cannot exclude the risk of transferring unknown pathogens or undetectable functional characteristics within the living microorganisms to the recipient, including bacterial or viral risk factors for metabolic diseases, cancer, atopy, or autoimmunity,” the investigators wrote.
Therefore, they performed sterile FFT in five patients who were positive on at least two of three tests: enzyme-linked immunosorbent assay for C. difficile–specific glutamate dehydrogenase; C. difficile toxin enzyme-linked immunosorbent assay; and culture of toxin-producing C. difficile. Patients chose their own stool donors, who were then screened based on published guidelines (Clin Gastroenterol Hepatol. 2011;9[12]:1044-49). Next, “slurries” were prepared from donor stool and filtered with a custom-built air pressure filtration system, yielding a “light brown, clear liquid with a subjectively less unpleasant and intensive odor” than conventional FMT stool preparations. Bacterial cultures of these filtrates yielded no growth, whereas donor stool cultures showed profuse growth of aerobic and anaerobic bacterial colonies, Dr. Ott and his associates said.
Patients became symptom-free 2-4 days after undergoing FFT. Notably, one patient had previously undergone FMT, which led to acute fever and diarrhea and recurrence of baseline symptoms after 3 months. This patient did not develop fever or diarrhea after FFT, was symptom-free after 3 days, and remained symptom-free until the study ended 2 years later, the researchers said. All other patients also remained symptom-free through the end of the study, that is, for 6 months to more than 2 years.
Analyses of 16S rRNA revealed substantial longitudinal shifts after FFT that often were present by week 1 and remained stable until week 6, the investigators said. Further tests confirmed marked shifts in bacterial phylotypes and in their relative abundance over time. Repeated virus analyses of one patient also showed that the phageome shifted over time to resemble that of the donor.
Patients were between 49 and 75 years old, three were female and two were male, and all had received more than one antibiotic before their first episode of CDI. Antibiotics for CDI had included metronidazole, vancomycin, and rifaximin. Comorbidities included pseudomembranous colitis, renal failure, HIV infection, epilepsy, and chronic heart failure, and medical histories included recurrent diverticulitis with sigmoid resection, gastric carcinoma, and colon cancer.
“It is important to keep in mind that, in contrast to conventional FMT, transferring sterile FFT filtrates cannot be expected to establish a microbiota similar to that of the donor in the receiving patient,” Dr. Ott and his associates noted. Instead, bacterial DNA in the filtrate might trigger the re-establishment of the recipient microbiome, they said. Bacterial cell wall fragments or bacteriophages also might play a role, they added.
The German Excellence Cluster and CONARIS Research Institute AG supported the work. Dr. Ott reported having lectured for Allergosan. Two coinvestigators reported employment with CONARIS. A third coinvestigator reported shareholder relationships with CONARIS, Allergosan, Danone, and Nestle and lectureship compensation from Allergosan. The other eight coinvestigators had no relevant conflicts of interest.
FROM GASTROENTEROLOGY
Key clinical point: Sterile fecal filtrate transplantation effectively treated symptomatic chronic-relapsing Clostridium difficile infection.
Major finding: For all patients, transplantation restored normal bowel habits within 2-4 days and eliminated symptoms for at least 6 months.
Data source: A single-center cases series of five patients with recurrent symptomatic CDI.
Disclosures: The German Excellence Cluster and CONARIS Research Institute AG supported the work. Dr. Ott reported having lectured for Allergosan. Two coinvestigators reported employment with CONARIS. A third coinvestigator reported shareholder relationships with CONARIS, Allergosan, Danone, and Nestle and lectureship compensation from Allergosan. The other eight coinvestigators had no relevant conflicts of interest.