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Severe influenza increases risk of invasive pulmonary aspergillosis in the ICU

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Tue, 03/12/2019 - 18:37

Severe influenza is an independent risk factor for invasive pulmonary aspergillosis with an accompanying increased mortality in the ICU, according to a multicenter retrospective cohort study at seven tertiary centers in Belgium and the Netherlands.

Wikimedia Commons
The research study was reported by Alexander F.A.D. Schauwvlieghe, MD, of Erasmus MC University Medical Center, Rotterdam, the Netherlands, and his colleagues.

Data was collected from criteria-meeting adult patients admitted to the ICU for more than 24 hours with acute respiratory failure during the 2009-2016 influenza seasons. The included cohort of 432 patients was composed of 56% men and had a median age of 59 years; all participants were diagnosed as having severe type A or type B influenza infection according to positive airway RT-PCR results.

The full cohort was subcategorized into 117 immunocompromised and 315 as nonimmunocompromised individuals using criteria established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study group (EORTC/MSG) . To assess influenza as an independent variable in the development of invasive pulmonary aspergillosis, the 315 nonimmunocompromised influenza positive individuals were compared to an influenza-negative control group of 315 nonimmunocompromised patients admitted to the ICU that presented similar respiratory insufficiency symptoms with community-acquired pneumonia.

Determination of other independent risk factors for incidence of invasive pulmonary aspergillosis was achieved by multivariate analysis of factors such as sex, diabetes status, prednisone use, age, and acute physiology and chronic health evaluation (APACHE) II score. The mean APACHE II score was 22, with the majority of patients requiring intubation for mechanical ventilation for a median duration of 11 days.

Influenza is not considered a host factor for invasive pulmonary aspergillosis and will often miss being diagnosed when using strict interpretation of the current EORTC/MSG or AspICU algorithm criteria, according to the researchers. Consequently for patients with influenza and the noninfluenza control group with community-acquired pneumonia, the definition of invasive pulmonary aspergillosis was modified from the AspICU algorithm. Stringent mycological criteria, including bronchoaveolar lavage (BAL) culture, a positive Aspergillus culture, positive galactomannan test, and/or positive serum galactomannan tests, provided supporting diagnostics for an invasive pulmonary aspergillosis determination.

 

 


At a median of 3 days following admission to the ICU, a diagnosis of invasive pulmonary aspergillosis was determined for 19% of the 432 influenza patients. Similar incident percentages of invasive pulmonary aspergillosis occurring for type A and type B, 71/355 (20%) and 12/77 (16%) patients respectively, showed that there was no clear association of the disease development with influenza subtypes that occurred during different annual seasons.

AspICU or EORTC/MSG criteria characterized only 43% and 58% of cases as proven or possible aspergillosis, respectively. On the other hand, stringent mycological tests yielded better invasive pulmonary aspergillosis classification, with 63% of BAL cultures being positive for Aspergillus, 88% of BAL galactomannan tests being positive, and 65% of serum galactomannan tests being positive in the 81/83 patients tested.

The study found that, for influenza patients, being immunocompromised more than doubled the incidence of invasive pulmonary aspergillosis, at 32% versus the 14% of those patients who were nonimmunocompromised. In contrast only 5% in the control group developed invasive pulmonary aspergillosis.
 

 


Influenza patients who developed invasive pulmonary aspergillosis in the ICU tended to have their stays significantly lengthened from 9 days (interquartile range, 5-20 days) for those without it to 19 days (IQR, 12-38 days) for those infected (P less than .0001). Likewise, 90-day mortality significantly rose from 28% for those influenza patients without invasive pulmonary aspergillosis to 51% for those with it (P = .0001).

The authors concluded that influenza was “independently associated with invasive pulmonary aspergillosis (adjusted odds ratio, 5.19; P less than.0001) along with a higher APACHE II score, male sex, and use of corticosteroids.”

Furthermore, as influenza appears to be an independent risk factor for invasive pulmonary aspergillosis and its associated high mortality, the authors suggested that “future studies should assess whether a faster diagnosis or antifungal prophylaxis could improve the outcome of influenza-associated aspergillosis.”

The authors reported that they had no conflicts of interest.

SOURCE: Schauwvlieghe AFAD et al. Lancet Respir Med. 2018 Jul 31. doi: 10.1016/S2213-2600(18)30274-1

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Severe influenza is an independent risk factor for invasive pulmonary aspergillosis with an accompanying increased mortality in the ICU, according to a multicenter retrospective cohort study at seven tertiary centers in Belgium and the Netherlands.

Wikimedia Commons
The research study was reported by Alexander F.A.D. Schauwvlieghe, MD, of Erasmus MC University Medical Center, Rotterdam, the Netherlands, and his colleagues.

Data was collected from criteria-meeting adult patients admitted to the ICU for more than 24 hours with acute respiratory failure during the 2009-2016 influenza seasons. The included cohort of 432 patients was composed of 56% men and had a median age of 59 years; all participants were diagnosed as having severe type A or type B influenza infection according to positive airway RT-PCR results.

The full cohort was subcategorized into 117 immunocompromised and 315 as nonimmunocompromised individuals using criteria established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study group (EORTC/MSG) . To assess influenza as an independent variable in the development of invasive pulmonary aspergillosis, the 315 nonimmunocompromised influenza positive individuals were compared to an influenza-negative control group of 315 nonimmunocompromised patients admitted to the ICU that presented similar respiratory insufficiency symptoms with community-acquired pneumonia.

Determination of other independent risk factors for incidence of invasive pulmonary aspergillosis was achieved by multivariate analysis of factors such as sex, diabetes status, prednisone use, age, and acute physiology and chronic health evaluation (APACHE) II score. The mean APACHE II score was 22, with the majority of patients requiring intubation for mechanical ventilation for a median duration of 11 days.

Influenza is not considered a host factor for invasive pulmonary aspergillosis and will often miss being diagnosed when using strict interpretation of the current EORTC/MSG or AspICU algorithm criteria, according to the researchers. Consequently for patients with influenza and the noninfluenza control group with community-acquired pneumonia, the definition of invasive pulmonary aspergillosis was modified from the AspICU algorithm. Stringent mycological criteria, including bronchoaveolar lavage (BAL) culture, a positive Aspergillus culture, positive galactomannan test, and/or positive serum galactomannan tests, provided supporting diagnostics for an invasive pulmonary aspergillosis determination.

 

 


At a median of 3 days following admission to the ICU, a diagnosis of invasive pulmonary aspergillosis was determined for 19% of the 432 influenza patients. Similar incident percentages of invasive pulmonary aspergillosis occurring for type A and type B, 71/355 (20%) and 12/77 (16%) patients respectively, showed that there was no clear association of the disease development with influenza subtypes that occurred during different annual seasons.

AspICU or EORTC/MSG criteria characterized only 43% and 58% of cases as proven or possible aspergillosis, respectively. On the other hand, stringent mycological tests yielded better invasive pulmonary aspergillosis classification, with 63% of BAL cultures being positive for Aspergillus, 88% of BAL galactomannan tests being positive, and 65% of serum galactomannan tests being positive in the 81/83 patients tested.

The study found that, for influenza patients, being immunocompromised more than doubled the incidence of invasive pulmonary aspergillosis, at 32% versus the 14% of those patients who were nonimmunocompromised. In contrast only 5% in the control group developed invasive pulmonary aspergillosis.
 

 


Influenza patients who developed invasive pulmonary aspergillosis in the ICU tended to have their stays significantly lengthened from 9 days (interquartile range, 5-20 days) for those without it to 19 days (IQR, 12-38 days) for those infected (P less than .0001). Likewise, 90-day mortality significantly rose from 28% for those influenza patients without invasive pulmonary aspergillosis to 51% for those with it (P = .0001).

The authors concluded that influenza was “independently associated with invasive pulmonary aspergillosis (adjusted odds ratio, 5.19; P less than.0001) along with a higher APACHE II score, male sex, and use of corticosteroids.”

Furthermore, as influenza appears to be an independent risk factor for invasive pulmonary aspergillosis and its associated high mortality, the authors suggested that “future studies should assess whether a faster diagnosis or antifungal prophylaxis could improve the outcome of influenza-associated aspergillosis.”

The authors reported that they had no conflicts of interest.

SOURCE: Schauwvlieghe AFAD et al. Lancet Respir Med. 2018 Jul 31. doi: 10.1016/S2213-2600(18)30274-1

Severe influenza is an independent risk factor for invasive pulmonary aspergillosis with an accompanying increased mortality in the ICU, according to a multicenter retrospective cohort study at seven tertiary centers in Belgium and the Netherlands.

Wikimedia Commons
The research study was reported by Alexander F.A.D. Schauwvlieghe, MD, of Erasmus MC University Medical Center, Rotterdam, the Netherlands, and his colleagues.

Data was collected from criteria-meeting adult patients admitted to the ICU for more than 24 hours with acute respiratory failure during the 2009-2016 influenza seasons. The included cohort of 432 patients was composed of 56% men and had a median age of 59 years; all participants were diagnosed as having severe type A or type B influenza infection according to positive airway RT-PCR results.

The full cohort was subcategorized into 117 immunocompromised and 315 as nonimmunocompromised individuals using criteria established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study group (EORTC/MSG) . To assess influenza as an independent variable in the development of invasive pulmonary aspergillosis, the 315 nonimmunocompromised influenza positive individuals were compared to an influenza-negative control group of 315 nonimmunocompromised patients admitted to the ICU that presented similar respiratory insufficiency symptoms with community-acquired pneumonia.

Determination of other independent risk factors for incidence of invasive pulmonary aspergillosis was achieved by multivariate analysis of factors such as sex, diabetes status, prednisone use, age, and acute physiology and chronic health evaluation (APACHE) II score. The mean APACHE II score was 22, with the majority of patients requiring intubation for mechanical ventilation for a median duration of 11 days.

Influenza is not considered a host factor for invasive pulmonary aspergillosis and will often miss being diagnosed when using strict interpretation of the current EORTC/MSG or AspICU algorithm criteria, according to the researchers. Consequently for patients with influenza and the noninfluenza control group with community-acquired pneumonia, the definition of invasive pulmonary aspergillosis was modified from the AspICU algorithm. Stringent mycological criteria, including bronchoaveolar lavage (BAL) culture, a positive Aspergillus culture, positive galactomannan test, and/or positive serum galactomannan tests, provided supporting diagnostics for an invasive pulmonary aspergillosis determination.

 

 


At a median of 3 days following admission to the ICU, a diagnosis of invasive pulmonary aspergillosis was determined for 19% of the 432 influenza patients. Similar incident percentages of invasive pulmonary aspergillosis occurring for type A and type B, 71/355 (20%) and 12/77 (16%) patients respectively, showed that there was no clear association of the disease development with influenza subtypes that occurred during different annual seasons.

AspICU or EORTC/MSG criteria characterized only 43% and 58% of cases as proven or possible aspergillosis, respectively. On the other hand, stringent mycological tests yielded better invasive pulmonary aspergillosis classification, with 63% of BAL cultures being positive for Aspergillus, 88% of BAL galactomannan tests being positive, and 65% of serum galactomannan tests being positive in the 81/83 patients tested.

The study found that, for influenza patients, being immunocompromised more than doubled the incidence of invasive pulmonary aspergillosis, at 32% versus the 14% of those patients who were nonimmunocompromised. In contrast only 5% in the control group developed invasive pulmonary aspergillosis.
 

 


Influenza patients who developed invasive pulmonary aspergillosis in the ICU tended to have their stays significantly lengthened from 9 days (interquartile range, 5-20 days) for those without it to 19 days (IQR, 12-38 days) for those infected (P less than .0001). Likewise, 90-day mortality significantly rose from 28% for those influenza patients without invasive pulmonary aspergillosis to 51% for those with it (P = .0001).

The authors concluded that influenza was “independently associated with invasive pulmonary aspergillosis (adjusted odds ratio, 5.19; P less than.0001) along with a higher APACHE II score, male sex, and use of corticosteroids.”

Furthermore, as influenza appears to be an independent risk factor for invasive pulmonary aspergillosis and its associated high mortality, the authors suggested that “future studies should assess whether a faster diagnosis or antifungal prophylaxis could improve the outcome of influenza-associated aspergillosis.”

The authors reported that they had no conflicts of interest.

SOURCE: Schauwvlieghe AFAD et al. Lancet Respir Med. 2018 Jul 31. doi: 10.1016/S2213-2600(18)30274-1

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Key clinical point: ICU admission for severe influenza as significant a risk factor should be included in the existing diagnostic criteria for predicting incidence of invasive pulmonary aspergillosis.

Major finding: Influenza is an independent risk factor associated with invasive pulmonary aspergillosis, with 90-day mortality rising from 28% to 51% when this fungal infection occurs.

Study details: Multicenter retrospective study of 432 adult patients with confirmed severe influenza admitted to the ICU with acute respiratory failure.

Disclosures: The authors reported that they had no conflicts of interest.

Source: Schauwvlieghe AFAD et al. Lancet Respir Med. 2018 Jul 31. doi: 10.1016/S2213-2600(18)30274-1.

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NYC outbreak of Candida auris linked to 45% mortality

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Wed, 01/02/2019 - 10:14
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NYC outbreak of Candida auris linked to 45% mortality

Mortality within 90 days of infection was 45% among 51 patients diagnosed with antibiotic-resistant Candida auris infections in a multihospital outbreak in New York City from 2012 to 2017.

Transmission is ongoing in health care facilities, primarily among patients with extensive health care exposures, according to a report published in Emerging Infectious Diseases.

Shawn Lockhart/CDC
This image depicts a strain of Candida auris cultured in a petri dish.

“Intensive infection prevention and control efforts continue; the goals are delaying endemicity, preventing outbreaks within facilities, reducing transmission and geographic spread, and blunting the effect of C. auris in New York and the rest of the United States,” Eleanor Adams, MD, of the New York Health Department, and her colleagues wrote. “Among medically fragile patients in NYC who had a history of extensive contact with health care facilities, clinicians should include C. auris in the differential diagnosis for patients with symptoms compatible with bloodstream infection.”


In the intensive case-patient analysis conducted by the New York State Health Department, 21 cases were from seven hospitals in Brooklyn, 16 were from three hospitals and one private medical office in Queens, 12 were from five hospitals and one long-term acute care hospital in Manhattan, and 1 was from a hospital in the Bronx. The remaining clinical case was identified in a western New York hospital in a patient who had recently been admitted to an involved Brooklyn hospital.


Among these patients, 31 (61%) had resided in long-term care facilities immediately before being admitted to the hospital in which their infection was diagnosed, and 19 of these 31 resided in skilled nursing facilities with ventilator beds; 1 (2%) resided in a long-term acute care hospital; 5 (10%) had been transferred from another hospital; and 4 (8%) had traveled internationally within 5 years before diagnosis, according to the investigators.

Isolates from 50 patients (98%) were resistant to fluconazole and 13 (25%) were resistant to fluconazole and amphotericin B. No initial isolates were resistant to echinocandins, although subsequent isolates obtained from 3 persons who had received an echinocandin acquired resistance to it, according to the researchers. Whole-genome sequencing performed at The Centers for Disease Control and Prevention indicated that 50 of 51 isolates belonged to a South Asia clade; the remaining isolate was the only one susceptible to fluconazole.

The work was supported by the CDC. No disclosures were reported.

SOURCE: Adams E et al. Emerg Infect Dis. 2018 Sep 12; 24(10); ID: 18-0649.

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Mortality within 90 days of infection was 45% among 51 patients diagnosed with antibiotic-resistant Candida auris infections in a multihospital outbreak in New York City from 2012 to 2017.

Transmission is ongoing in health care facilities, primarily among patients with extensive health care exposures, according to a report published in Emerging Infectious Diseases.

Shawn Lockhart/CDC
This image depicts a strain of Candida auris cultured in a petri dish.

“Intensive infection prevention and control efforts continue; the goals are delaying endemicity, preventing outbreaks within facilities, reducing transmission and geographic spread, and blunting the effect of C. auris in New York and the rest of the United States,” Eleanor Adams, MD, of the New York Health Department, and her colleagues wrote. “Among medically fragile patients in NYC who had a history of extensive contact with health care facilities, clinicians should include C. auris in the differential diagnosis for patients with symptoms compatible with bloodstream infection.”


In the intensive case-patient analysis conducted by the New York State Health Department, 21 cases were from seven hospitals in Brooklyn, 16 were from three hospitals and one private medical office in Queens, 12 were from five hospitals and one long-term acute care hospital in Manhattan, and 1 was from a hospital in the Bronx. The remaining clinical case was identified in a western New York hospital in a patient who had recently been admitted to an involved Brooklyn hospital.


Among these patients, 31 (61%) had resided in long-term care facilities immediately before being admitted to the hospital in which their infection was diagnosed, and 19 of these 31 resided in skilled nursing facilities with ventilator beds; 1 (2%) resided in a long-term acute care hospital; 5 (10%) had been transferred from another hospital; and 4 (8%) had traveled internationally within 5 years before diagnosis, according to the investigators.

Isolates from 50 patients (98%) were resistant to fluconazole and 13 (25%) were resistant to fluconazole and amphotericin B. No initial isolates were resistant to echinocandins, although subsequent isolates obtained from 3 persons who had received an echinocandin acquired resistance to it, according to the researchers. Whole-genome sequencing performed at The Centers for Disease Control and Prevention indicated that 50 of 51 isolates belonged to a South Asia clade; the remaining isolate was the only one susceptible to fluconazole.

The work was supported by the CDC. No disclosures were reported.

SOURCE: Adams E et al. Emerg Infect Dis. 2018 Sep 12; 24(10); ID: 18-0649.

Mortality within 90 days of infection was 45% among 51 patients diagnosed with antibiotic-resistant Candida auris infections in a multihospital outbreak in New York City from 2012 to 2017.

Transmission is ongoing in health care facilities, primarily among patients with extensive health care exposures, according to a report published in Emerging Infectious Diseases.

Shawn Lockhart/CDC
This image depicts a strain of Candida auris cultured in a petri dish.

“Intensive infection prevention and control efforts continue; the goals are delaying endemicity, preventing outbreaks within facilities, reducing transmission and geographic spread, and blunting the effect of C. auris in New York and the rest of the United States,” Eleanor Adams, MD, of the New York Health Department, and her colleagues wrote. “Among medically fragile patients in NYC who had a history of extensive contact with health care facilities, clinicians should include C. auris in the differential diagnosis for patients with symptoms compatible with bloodstream infection.”


In the intensive case-patient analysis conducted by the New York State Health Department, 21 cases were from seven hospitals in Brooklyn, 16 were from three hospitals and one private medical office in Queens, 12 were from five hospitals and one long-term acute care hospital in Manhattan, and 1 was from a hospital in the Bronx. The remaining clinical case was identified in a western New York hospital in a patient who had recently been admitted to an involved Brooklyn hospital.


Among these patients, 31 (61%) had resided in long-term care facilities immediately before being admitted to the hospital in which their infection was diagnosed, and 19 of these 31 resided in skilled nursing facilities with ventilator beds; 1 (2%) resided in a long-term acute care hospital; 5 (10%) had been transferred from another hospital; and 4 (8%) had traveled internationally within 5 years before diagnosis, according to the investigators.

Isolates from 50 patients (98%) were resistant to fluconazole and 13 (25%) were resistant to fluconazole and amphotericin B. No initial isolates were resistant to echinocandins, although subsequent isolates obtained from 3 persons who had received an echinocandin acquired resistance to it, according to the researchers. Whole-genome sequencing performed at The Centers for Disease Control and Prevention indicated that 50 of 51 isolates belonged to a South Asia clade; the remaining isolate was the only one susceptible to fluconazole.

The work was supported by the CDC. No disclosures were reported.

SOURCE: Adams E et al. Emerg Infect Dis. 2018 Sep 12; 24(10); ID: 18-0649.

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NYC outbreak of Candida auris linked to 45% mortality
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So it’s pediatric onychomycosis. Now what?

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Fri, 01/18/2019 - 17:56

 

– Though research shows that nail fungus occurs in just 0.3% of pediatric patients in the United States, that’s not what Sheila Friedlander, MD, is seeing in her southern California practice, where it’s not uncommon to see children whose nails, toe nails in particular, have fungal involvement.

fotokostic/iStock/Getty Images
More participation in organized sports at a young age may be contributing to the increase in pediatric onychomycosis.

“I know I started out telling you fungus isn’t that common in children … but you do need to think about it,” said Dr. Friedlander during a nail-focused session at the annual summer meeting of the American Academy of Dermatology. Dr. Friedlander, professor of dermatology and pediatrics at the University of California San Diego and Rady Children’s Hospital, said that she suspects that more participation in organized sports at a young age may be contributing to the increase, with occlusive sports footwear replacing bare feet or sandals for more hours of the day, presenting more opportunities for toenail trauma in sports such as soccer.

When making the clinical call about a nail problem, bear in mind that the younger the child, the less likely a nail problem is fungal, Dr. Friedlander noted. “Little children are much less likely than older children to have nail fungus. Pediatric nails are thinner, and they are faster growing, with better blood supply to the matrix.”

And if frank onychomadesis is observed, think about the time of year, and ask about recent fevers and rashes, because coxsackievirus may be the culprit. “Be not afraid, and look everywhere if the nail is confusing to you,” she said. In all ages, the diagnosis is primarily clinical, “but I culture them, I ‘PAS’ [periodic acid-Schiff stain] them, too. If you do both, you’ll increase your yield,” Dr. Friedlander said, adding, “the beauty of PAS is you can use it to give your families an answer very soon.”

Once you’ve established that fungus is to blame for a nail problem, there’s a conundrum: There are no Food and Drug Administration-approved therapies, either topical or systemic, for pediatric onychomycosis, Dr. Friedlander said. She, along with coauthors and first author Aditya Gupta, MD, of Mediprobe Research, London, Ontario, Canada, recently published an article reviewing the safety and efficacy of antifungal agents in this age group (Pediatr Dermatol. 2018 Jun 26. doi: 10.1111/pde.13561).

Reviewing information available in the United States and Canada, Dr. Friedlander and her coauthors came up with three topical and four oral options for children, along with recommendations for dosage and duration.

In response to an audience question about the use of topical antifungal treatment for nail involvement, Dr. Friedlander responded, “I think topicals would be great for kids, but it’s for kids where there is no nail matrix involvement. Also, cost is a problem. Nobody will cover it. But some families are willing to do this to avoid systemic therapy,” and if the family budget can accommodate a topical choice, it’s a logical option, she said, noting that partial reimbursement via a coupon system is available from some pharmaceutical companies.

Where appropriate, ciclopirox 8%, efinaconazole 10%, and tavaborole 5% can each be considered. Dr. Friedlander cited one study she coauthored, which reported that 70% of pediatric participants with nonmatrix onychomycosis saw effective treatment, with a 71% mycological cure rate (P = .03), after 32 weeks of treatment with ciclopirox lacquer versus vehicle (Pediatr Dermatol. 2013 May-Jun;30[3]:316-22).

Systemic therapies – which, when studied, have been given at tinea capitis doses – could include griseofulvin, terbinafine, itraconazole, and fluconazole.

In terms of oral options, Dr. Friedlander said, griseofulvin has some practical limitations. While prolonged treatment is required in any case, terbinafine may produce results in about 3 months, whereas griseofulvin may require up to 9 months of therapy. “I always try to use terbinafine … griseofulvin takes a year and a day,” she said.

She also shared some tips to improve pediatric adherence with oral antifungals: “You can tell parents to crush terbinafine tablets and mix in peanut butter or applesauce to improve adherence. Griseofulvin can be flavored by the pharmacy, but volumes are big with griseofulvin, so it’s a challenge to get kids to take it all,” she said.

Dr. Friedlander reported that she had no relevant financial disclosures.

koakes@mdedge.com



 

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– Though research shows that nail fungus occurs in just 0.3% of pediatric patients in the United States, that’s not what Sheila Friedlander, MD, is seeing in her southern California practice, where it’s not uncommon to see children whose nails, toe nails in particular, have fungal involvement.

fotokostic/iStock/Getty Images
More participation in organized sports at a young age may be contributing to the increase in pediatric onychomycosis.

“I know I started out telling you fungus isn’t that common in children … but you do need to think about it,” said Dr. Friedlander during a nail-focused session at the annual summer meeting of the American Academy of Dermatology. Dr. Friedlander, professor of dermatology and pediatrics at the University of California San Diego and Rady Children’s Hospital, said that she suspects that more participation in organized sports at a young age may be contributing to the increase, with occlusive sports footwear replacing bare feet or sandals for more hours of the day, presenting more opportunities for toenail trauma in sports such as soccer.

When making the clinical call about a nail problem, bear in mind that the younger the child, the less likely a nail problem is fungal, Dr. Friedlander noted. “Little children are much less likely than older children to have nail fungus. Pediatric nails are thinner, and they are faster growing, with better blood supply to the matrix.”

And if frank onychomadesis is observed, think about the time of year, and ask about recent fevers and rashes, because coxsackievirus may be the culprit. “Be not afraid, and look everywhere if the nail is confusing to you,” she said. In all ages, the diagnosis is primarily clinical, “but I culture them, I ‘PAS’ [periodic acid-Schiff stain] them, too. If you do both, you’ll increase your yield,” Dr. Friedlander said, adding, “the beauty of PAS is you can use it to give your families an answer very soon.”

Once you’ve established that fungus is to blame for a nail problem, there’s a conundrum: There are no Food and Drug Administration-approved therapies, either topical or systemic, for pediatric onychomycosis, Dr. Friedlander said. She, along with coauthors and first author Aditya Gupta, MD, of Mediprobe Research, London, Ontario, Canada, recently published an article reviewing the safety and efficacy of antifungal agents in this age group (Pediatr Dermatol. 2018 Jun 26. doi: 10.1111/pde.13561).

Reviewing information available in the United States and Canada, Dr. Friedlander and her coauthors came up with three topical and four oral options for children, along with recommendations for dosage and duration.

In response to an audience question about the use of topical antifungal treatment for nail involvement, Dr. Friedlander responded, “I think topicals would be great for kids, but it’s for kids where there is no nail matrix involvement. Also, cost is a problem. Nobody will cover it. But some families are willing to do this to avoid systemic therapy,” and if the family budget can accommodate a topical choice, it’s a logical option, she said, noting that partial reimbursement via a coupon system is available from some pharmaceutical companies.

Where appropriate, ciclopirox 8%, efinaconazole 10%, and tavaborole 5% can each be considered. Dr. Friedlander cited one study she coauthored, which reported that 70% of pediatric participants with nonmatrix onychomycosis saw effective treatment, with a 71% mycological cure rate (P = .03), after 32 weeks of treatment with ciclopirox lacquer versus vehicle (Pediatr Dermatol. 2013 May-Jun;30[3]:316-22).

Systemic therapies – which, when studied, have been given at tinea capitis doses – could include griseofulvin, terbinafine, itraconazole, and fluconazole.

In terms of oral options, Dr. Friedlander said, griseofulvin has some practical limitations. While prolonged treatment is required in any case, terbinafine may produce results in about 3 months, whereas griseofulvin may require up to 9 months of therapy. “I always try to use terbinafine … griseofulvin takes a year and a day,” she said.

She also shared some tips to improve pediatric adherence with oral antifungals: “You can tell parents to crush terbinafine tablets and mix in peanut butter or applesauce to improve adherence. Griseofulvin can be flavored by the pharmacy, but volumes are big with griseofulvin, so it’s a challenge to get kids to take it all,” she said.

Dr. Friedlander reported that she had no relevant financial disclosures.

koakes@mdedge.com



 

 

– Though research shows that nail fungus occurs in just 0.3% of pediatric patients in the United States, that’s not what Sheila Friedlander, MD, is seeing in her southern California practice, where it’s not uncommon to see children whose nails, toe nails in particular, have fungal involvement.

fotokostic/iStock/Getty Images
More participation in organized sports at a young age may be contributing to the increase in pediatric onychomycosis.

“I know I started out telling you fungus isn’t that common in children … but you do need to think about it,” said Dr. Friedlander during a nail-focused session at the annual summer meeting of the American Academy of Dermatology. Dr. Friedlander, professor of dermatology and pediatrics at the University of California San Diego and Rady Children’s Hospital, said that she suspects that more participation in organized sports at a young age may be contributing to the increase, with occlusive sports footwear replacing bare feet or sandals for more hours of the day, presenting more opportunities for toenail trauma in sports such as soccer.

When making the clinical call about a nail problem, bear in mind that the younger the child, the less likely a nail problem is fungal, Dr. Friedlander noted. “Little children are much less likely than older children to have nail fungus. Pediatric nails are thinner, and they are faster growing, with better blood supply to the matrix.”

And if frank onychomadesis is observed, think about the time of year, and ask about recent fevers and rashes, because coxsackievirus may be the culprit. “Be not afraid, and look everywhere if the nail is confusing to you,” she said. In all ages, the diagnosis is primarily clinical, “but I culture them, I ‘PAS’ [periodic acid-Schiff stain] them, too. If you do both, you’ll increase your yield,” Dr. Friedlander said, adding, “the beauty of PAS is you can use it to give your families an answer very soon.”

Once you’ve established that fungus is to blame for a nail problem, there’s a conundrum: There are no Food and Drug Administration-approved therapies, either topical or systemic, for pediatric onychomycosis, Dr. Friedlander said. She, along with coauthors and first author Aditya Gupta, MD, of Mediprobe Research, London, Ontario, Canada, recently published an article reviewing the safety and efficacy of antifungal agents in this age group (Pediatr Dermatol. 2018 Jun 26. doi: 10.1111/pde.13561).

Reviewing information available in the United States and Canada, Dr. Friedlander and her coauthors came up with three topical and four oral options for children, along with recommendations for dosage and duration.

In response to an audience question about the use of topical antifungal treatment for nail involvement, Dr. Friedlander responded, “I think topicals would be great for kids, but it’s for kids where there is no nail matrix involvement. Also, cost is a problem. Nobody will cover it. But some families are willing to do this to avoid systemic therapy,” and if the family budget can accommodate a topical choice, it’s a logical option, she said, noting that partial reimbursement via a coupon system is available from some pharmaceutical companies.

Where appropriate, ciclopirox 8%, efinaconazole 10%, and tavaborole 5% can each be considered. Dr. Friedlander cited one study she coauthored, which reported that 70% of pediatric participants with nonmatrix onychomycosis saw effective treatment, with a 71% mycological cure rate (P = .03), after 32 weeks of treatment with ciclopirox lacquer versus vehicle (Pediatr Dermatol. 2013 May-Jun;30[3]:316-22).

Systemic therapies – which, when studied, have been given at tinea capitis doses – could include griseofulvin, terbinafine, itraconazole, and fluconazole.

In terms of oral options, Dr. Friedlander said, griseofulvin has some practical limitations. While prolonged treatment is required in any case, terbinafine may produce results in about 3 months, whereas griseofulvin may require up to 9 months of therapy. “I always try to use terbinafine … griseofulvin takes a year and a day,” she said.

She also shared some tips to improve pediatric adherence with oral antifungals: “You can tell parents to crush terbinafine tablets and mix in peanut butter or applesauce to improve adherence. Griseofulvin can be flavored by the pharmacy, but volumes are big with griseofulvin, so it’s a challenge to get kids to take it all,” she said.

Dr. Friedlander reported that she had no relevant financial disclosures.

koakes@mdedge.com



 

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Less is more: Nanotechnology enhances antifungal’s efficacy

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The use of nanotechnology significantly reduced the amount of efinaconazole needed to effectively treat nail fungus in a study that pitted nitric oxide–releasing nanoparticles combined with the antifungal against reference strains of Trichophyton rubrum.

Efinaconazole has demonstrated effectiveness as a topical treatment for T. rubrum, but treatment can be expensive, with a single 4-mL bottle costing $691 at a major chain pharmacy, wrote Caroline B. Costa-Orlandi, PhD, of Universidade Estadual Paulista, Sao Paulo, Brazil, and her colleagues.

In a study published in the Journal of Drugs in Dermatology, an international research team evaluated topical efinaconazole and topical terbinafine, each combined with previously characterized, nitric oxide–releasing nanoparticles (NO-np) in a checkerboard design, to attack two reference strains of T. rubrum, ATCC MYA-4438 and ATCC 28189. NO-np was combined with 10% efinaconazole or with terbinafine.

The combination of NO-np and efinaconazole reduced the minimum inhibitory concentration (MIC) of efinaconazole by 16 times compared with treatment alone against ATCC MYA-4438; by 4 times when combined against ATCC 28189. With NO-np plus terbinafine, MICs against ATCC 28189 and ATCC MYA-4438 were reduced by four- and twofold, respectively, when compared with terbinafine alone. These data follow recently published findings in a study cited by the authors that demonstrated that NO-np is superior to topical terbinafine 1% cream in clearing infection in a mouse model of deep dermal dermatophytosis, suggesting that the combination may be even more effective (Nanomedicine. 2017 Oct;13[7]:2267-70).

“What we found was that we could impart the same antifungal activity at the highest concentrations tested of either alone by combining them at a fraction of these concentrations,” corresponding author Adam Friedman, MD, professor of dermatology, George Washington University, Washington, said in a press release issued by the university. The impact of this combination, “which we visualized using electron microscopy as compared to either product alone, highlighted their synergistic damaging effects at concentrations that would be completely safe to human cells,” he added.

Other benefits of NO-np include low cost, safety, ease of use, reduced likelihood for the development of antimicrobial resistance, and proven efficacy against other dermatophyte infections, the researchers noted.

The findings support the potential value of further research to evaluate nanoparticles combined with topical antifungals in a clinical setting, they said.

Dr. Costa-Orlandi had no financial conflicts to disclose. Authors Adam Friedman, MD, and Joel Friedman, MD, are coinventors of the nitric oxide–releasing nanoparticles used in the study. Dr. Adam Friedman is on the advisory board of Dermatology News.
 

SOURCE: Costa-Orlandi C et al. J Drugs Dermatol. 2018;17(7):717-20.

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The use of nanotechnology significantly reduced the amount of efinaconazole needed to effectively treat nail fungus in a study that pitted nitric oxide–releasing nanoparticles combined with the antifungal against reference strains of Trichophyton rubrum.

Efinaconazole has demonstrated effectiveness as a topical treatment for T. rubrum, but treatment can be expensive, with a single 4-mL bottle costing $691 at a major chain pharmacy, wrote Caroline B. Costa-Orlandi, PhD, of Universidade Estadual Paulista, Sao Paulo, Brazil, and her colleagues.

In a study published in the Journal of Drugs in Dermatology, an international research team evaluated topical efinaconazole and topical terbinafine, each combined with previously characterized, nitric oxide–releasing nanoparticles (NO-np) in a checkerboard design, to attack two reference strains of T. rubrum, ATCC MYA-4438 and ATCC 28189. NO-np was combined with 10% efinaconazole or with terbinafine.

The combination of NO-np and efinaconazole reduced the minimum inhibitory concentration (MIC) of efinaconazole by 16 times compared with treatment alone against ATCC MYA-4438; by 4 times when combined against ATCC 28189. With NO-np plus terbinafine, MICs against ATCC 28189 and ATCC MYA-4438 were reduced by four- and twofold, respectively, when compared with terbinafine alone. These data follow recently published findings in a study cited by the authors that demonstrated that NO-np is superior to topical terbinafine 1% cream in clearing infection in a mouse model of deep dermal dermatophytosis, suggesting that the combination may be even more effective (Nanomedicine. 2017 Oct;13[7]:2267-70).

“What we found was that we could impart the same antifungal activity at the highest concentrations tested of either alone by combining them at a fraction of these concentrations,” corresponding author Adam Friedman, MD, professor of dermatology, George Washington University, Washington, said in a press release issued by the university. The impact of this combination, “which we visualized using electron microscopy as compared to either product alone, highlighted their synergistic damaging effects at concentrations that would be completely safe to human cells,” he added.

Other benefits of NO-np include low cost, safety, ease of use, reduced likelihood for the development of antimicrobial resistance, and proven efficacy against other dermatophyte infections, the researchers noted.

The findings support the potential value of further research to evaluate nanoparticles combined with topical antifungals in a clinical setting, they said.

Dr. Costa-Orlandi had no financial conflicts to disclose. Authors Adam Friedman, MD, and Joel Friedman, MD, are coinventors of the nitric oxide–releasing nanoparticles used in the study. Dr. Adam Friedman is on the advisory board of Dermatology News.
 

SOURCE: Costa-Orlandi C et al. J Drugs Dermatol. 2018;17(7):717-20.

The use of nanotechnology significantly reduced the amount of efinaconazole needed to effectively treat nail fungus in a study that pitted nitric oxide–releasing nanoparticles combined with the antifungal against reference strains of Trichophyton rubrum.

Efinaconazole has demonstrated effectiveness as a topical treatment for T. rubrum, but treatment can be expensive, with a single 4-mL bottle costing $691 at a major chain pharmacy, wrote Caroline B. Costa-Orlandi, PhD, of Universidade Estadual Paulista, Sao Paulo, Brazil, and her colleagues.

In a study published in the Journal of Drugs in Dermatology, an international research team evaluated topical efinaconazole and topical terbinafine, each combined with previously characterized, nitric oxide–releasing nanoparticles (NO-np) in a checkerboard design, to attack two reference strains of T. rubrum, ATCC MYA-4438 and ATCC 28189. NO-np was combined with 10% efinaconazole or with terbinafine.

The combination of NO-np and efinaconazole reduced the minimum inhibitory concentration (MIC) of efinaconazole by 16 times compared with treatment alone against ATCC MYA-4438; by 4 times when combined against ATCC 28189. With NO-np plus terbinafine, MICs against ATCC 28189 and ATCC MYA-4438 were reduced by four- and twofold, respectively, when compared with terbinafine alone. These data follow recently published findings in a study cited by the authors that demonstrated that NO-np is superior to topical terbinafine 1% cream in clearing infection in a mouse model of deep dermal dermatophytosis, suggesting that the combination may be even more effective (Nanomedicine. 2017 Oct;13[7]:2267-70).

“What we found was that we could impart the same antifungal activity at the highest concentrations tested of either alone by combining them at a fraction of these concentrations,” corresponding author Adam Friedman, MD, professor of dermatology, George Washington University, Washington, said in a press release issued by the university. The impact of this combination, “which we visualized using electron microscopy as compared to either product alone, highlighted their synergistic damaging effects at concentrations that would be completely safe to human cells,” he added.

Other benefits of NO-np include low cost, safety, ease of use, reduced likelihood for the development of antimicrobial resistance, and proven efficacy against other dermatophyte infections, the researchers noted.

The findings support the potential value of further research to evaluate nanoparticles combined with topical antifungals in a clinical setting, they said.

Dr. Costa-Orlandi had no financial conflicts to disclose. Authors Adam Friedman, MD, and Joel Friedman, MD, are coinventors of the nitric oxide–releasing nanoparticles used in the study. Dr. Adam Friedman is on the advisory board of Dermatology News.
 

SOURCE: Costa-Orlandi C et al. J Drugs Dermatol. 2018;17(7):717-20.

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Key clinical point: Adding nanoparticles to antifungal medication improved the drug’s effectiveness and reduced the amount needed.

Major finding: Efinaconazole combined with nitric oxide–releasing nanoparticles reduced the antifungal’s minimum inhibitory concentration 16-fold, compared with the antifungal alone against T. rubrum reference strains.

Study details: The data come from an in vitro analysis of nanoparticle-enhanced efinaconazole or terbinafine against T. rubrum.

Disclosures: Dr. Costa-Orlandi had no financial conflicts to disclose. Coauthors Dr. Adam Friedman and Dr. Joel Friedman are coinventors of the nitric oxide–releasing nanoparticles used in the study.

Source: Costa-Orlandi C et al. J Drugs Dermatol. 2018;17(7):717-20.

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VIDEO: Device-based therapy for onychomycosis

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Several device-based therapies are currently being evaluated as treatments for onychomycosis.

These include photodynamic therapy,
which has been studied in two clinical trials and case series, Shari Lipner, MD, PhD, said in a video interview at the annual meeting of the American Academy of Dermatology, where she presented on this topic.

“Something that we’re looking at is plasma treatment of onychomycosis basically using ionized gas,” which has been shown to inhibit the growth of Trichophyton rubrum in vitro, added Dr. Lipner of the department of dermatology, Cornell University, New York.

In a pilot study of 19 patients with onychomycosis, she and her associates found that the clinical cure with nonthermal plasma was about 50% and the mycological cure rate was 15%, “and we’re now trying to improve efficacy using this device,” she said (Clin Exp Dermatol. 2017 Apr;42[3]:295-8). With a dielectric insulator, “nonthermal plasma is created by short pulses (about 10 ns) of strong (about 20 kV/mm peak) electric field that ionizes air molecules, creating ions and electrons, as well as ozone, hydroxyl radicals and nitric oxide,” according to the description in the study.

Other device-based therapies include iontophoresis, using electrical currents to increase drug delivery, and creating small punch biopsies or using a device to create “microholes” in the nails to increase delivery of topical medication across the nail, Dr. Lipner said.

Patients often ask about another device-based treatment, laser therapy, which she pointed out is not approved by the Food and Drug Administration for cure, but for a temporary increase in clear nail in patients with onychomycosis, “very different” than the criteria used for topical and systemic medications, making it difficult to compare efficacy data between lasers and medications, she noted.

Dr. Lipner reported receiving grants/research funding from MOE Medical Devices.

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REPORTING FROM AAD 18

Several device-based therapies are currently being evaluated as treatments for onychomycosis.

These include photodynamic therapy,
which has been studied in two clinical trials and case series, Shari Lipner, MD, PhD, said in a video interview at the annual meeting of the American Academy of Dermatology, where she presented on this topic.

“Something that we’re looking at is plasma treatment of onychomycosis basically using ionized gas,” which has been shown to inhibit the growth of Trichophyton rubrum in vitro, added Dr. Lipner of the department of dermatology, Cornell University, New York.

In a pilot study of 19 patients with onychomycosis, she and her associates found that the clinical cure with nonthermal plasma was about 50% and the mycological cure rate was 15%, “and we’re now trying to improve efficacy using this device,” she said (Clin Exp Dermatol. 2017 Apr;42[3]:295-8). With a dielectric insulator, “nonthermal plasma is created by short pulses (about 10 ns) of strong (about 20 kV/mm peak) electric field that ionizes air molecules, creating ions and electrons, as well as ozone, hydroxyl radicals and nitric oxide,” according to the description in the study.

Other device-based therapies include iontophoresis, using electrical currents to increase drug delivery, and creating small punch biopsies or using a device to create “microholes” in the nails to increase delivery of topical medication across the nail, Dr. Lipner said.

Patients often ask about another device-based treatment, laser therapy, which she pointed out is not approved by the Food and Drug Administration for cure, but for a temporary increase in clear nail in patients with onychomycosis, “very different” than the criteria used for topical and systemic medications, making it difficult to compare efficacy data between lasers and medications, she noted.

Dr. Lipner reported receiving grants/research funding from MOE Medical Devices.

REPORTING FROM AAD 18

Several device-based therapies are currently being evaluated as treatments for onychomycosis.

These include photodynamic therapy,
which has been studied in two clinical trials and case series, Shari Lipner, MD, PhD, said in a video interview at the annual meeting of the American Academy of Dermatology, where she presented on this topic.

“Something that we’re looking at is plasma treatment of onychomycosis basically using ionized gas,” which has been shown to inhibit the growth of Trichophyton rubrum in vitro, added Dr. Lipner of the department of dermatology, Cornell University, New York.

In a pilot study of 19 patients with onychomycosis, she and her associates found that the clinical cure with nonthermal plasma was about 50% and the mycological cure rate was 15%, “and we’re now trying to improve efficacy using this device,” she said (Clin Exp Dermatol. 2017 Apr;42[3]:295-8). With a dielectric insulator, “nonthermal plasma is created by short pulses (about 10 ns) of strong (about 20 kV/mm peak) electric field that ionizes air molecules, creating ions and electrons, as well as ozone, hydroxyl radicals and nitric oxide,” according to the description in the study.

Other device-based therapies include iontophoresis, using electrical currents to increase drug delivery, and creating small punch biopsies or using a device to create “microholes” in the nails to increase delivery of topical medication across the nail, Dr. Lipner said.

Patients often ask about another device-based treatment, laser therapy, which she pointed out is not approved by the Food and Drug Administration for cure, but for a temporary increase in clear nail in patients with onychomycosis, “very different” than the criteria used for topical and systemic medications, making it difficult to compare efficacy data between lasers and medications, she noted.

Dr. Lipner reported receiving grants/research funding from MOE Medical Devices.

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Ibrutinib linked to invasive fungal infections

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The tyrosine kinase inhibitor ibrutinib (Imbruvica) may be associated with early-onset invasive fungal infections (IFI) in patients with hematologic malignancies, investigators caution.

French investigators identified 33 cases of invasive fungal infections occurring among patients who had been treated with ibrutinib as monotherapy or in combination with other agents. Of the 33 cases, 27 were invasive aspergillosis, and 40% of these were localized in the central nervous system. The findings were published in the journal Blood.

“IFI tend to occur within the first months of treatment and are infrequent thereafter. Whilst it seems difficult at this point to advocate for systematic antifungal prophylaxis in all patients, an increased awareness about the potential risk of IFI after initiating ibrutinib is warranted, especially when other predisposing factors are associated,” wrote David Ghez, MD, PhD, and colleagues at the Gustave Roussy Institute in Villejuif and other centers in France.

Although ibrutinib, an inhibitor of Bruton’s tyrosine kinase, is generally considered to be less immunosuppressive than other therapies, it was associated with five cases of Pneumocystis jirovecii pneumonia in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib monotherapy in a 2016 report (Blood. 2016;128:1940-3). Of these five patients, four were treatment naive, suggesting that ibrutinib itself could increase risk for invasive opportunistic infections, Dr. Ghez and his colleagues noted.

 

 

Based on this finding and on case reports of invasive infections in other patients being treated with ibrutinib, the authors conducted a retrospective survey of centers in the French Innovative Leukemia Organization CLL group.

They identified 33 cases, including 30 patients with CLL (15 of whom had deleterious 17p deletions), 1 with mantle cell lymphoma, and 2 with Waldenstrom macroglobulinemia.

Invasive aspergillosis accounted for 27 of the 33 cases, and 11 cases had CNS localization. There were four cases of disseminated cryptococcosis, and one each of mucormycosis and pneumocystis pneumonia.

The median time between the start of ibrutinib therapy and a diagnosis of invasive fungal infection was 3 months, with some cases occurring as early as 1 month, and others occurring 30 months out. However, the majority of cases – 28 – were diagnosed within 6 months of the start of therapy, including 20 that occurred within 3 months of ibrutinib initiation.
 

 

In 21 patients, the diagnosis of an invasive fungal infection led to drug discontinuation. In the remaining patients, the drug was either resumed after resolution of the IFI, or continued at a lower dose because of potential for interaction between ibrutinib and the antifungal agent voriconazole.

Dr. Ghez reported receiving a research grant from Janssen, and coauthor Loic Ysebaert, MD, PhD, reported consultancy fees from the company. All other authors declared no competing financial interests.

SOURCE: Ghez D et al., Blood. 2018 Feb 1. doi: 10.1182/blood-2017-11-818286.

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The tyrosine kinase inhibitor ibrutinib (Imbruvica) may be associated with early-onset invasive fungal infections (IFI) in patients with hematologic malignancies, investigators caution.

French investigators identified 33 cases of invasive fungal infections occurring among patients who had been treated with ibrutinib as monotherapy or in combination with other agents. Of the 33 cases, 27 were invasive aspergillosis, and 40% of these were localized in the central nervous system. The findings were published in the journal Blood.

“IFI tend to occur within the first months of treatment and are infrequent thereafter. Whilst it seems difficult at this point to advocate for systematic antifungal prophylaxis in all patients, an increased awareness about the potential risk of IFI after initiating ibrutinib is warranted, especially when other predisposing factors are associated,” wrote David Ghez, MD, PhD, and colleagues at the Gustave Roussy Institute in Villejuif and other centers in France.

Although ibrutinib, an inhibitor of Bruton’s tyrosine kinase, is generally considered to be less immunosuppressive than other therapies, it was associated with five cases of Pneumocystis jirovecii pneumonia in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib monotherapy in a 2016 report (Blood. 2016;128:1940-3). Of these five patients, four were treatment naive, suggesting that ibrutinib itself could increase risk for invasive opportunistic infections, Dr. Ghez and his colleagues noted.

 

 

Based on this finding and on case reports of invasive infections in other patients being treated with ibrutinib, the authors conducted a retrospective survey of centers in the French Innovative Leukemia Organization CLL group.

They identified 33 cases, including 30 patients with CLL (15 of whom had deleterious 17p deletions), 1 with mantle cell lymphoma, and 2 with Waldenstrom macroglobulinemia.

Invasive aspergillosis accounted for 27 of the 33 cases, and 11 cases had CNS localization. There were four cases of disseminated cryptococcosis, and one each of mucormycosis and pneumocystis pneumonia.

The median time between the start of ibrutinib therapy and a diagnosis of invasive fungal infection was 3 months, with some cases occurring as early as 1 month, and others occurring 30 months out. However, the majority of cases – 28 – were diagnosed within 6 months of the start of therapy, including 20 that occurred within 3 months of ibrutinib initiation.
 

 

In 21 patients, the diagnosis of an invasive fungal infection led to drug discontinuation. In the remaining patients, the drug was either resumed after resolution of the IFI, or continued at a lower dose because of potential for interaction between ibrutinib and the antifungal agent voriconazole.

Dr. Ghez reported receiving a research grant from Janssen, and coauthor Loic Ysebaert, MD, PhD, reported consultancy fees from the company. All other authors declared no competing financial interests.

SOURCE: Ghez D et al., Blood. 2018 Feb 1. doi: 10.1182/blood-2017-11-818286.

 

The tyrosine kinase inhibitor ibrutinib (Imbruvica) may be associated with early-onset invasive fungal infections (IFI) in patients with hematologic malignancies, investigators caution.

French investigators identified 33 cases of invasive fungal infections occurring among patients who had been treated with ibrutinib as monotherapy or in combination with other agents. Of the 33 cases, 27 were invasive aspergillosis, and 40% of these were localized in the central nervous system. The findings were published in the journal Blood.

“IFI tend to occur within the first months of treatment and are infrequent thereafter. Whilst it seems difficult at this point to advocate for systematic antifungal prophylaxis in all patients, an increased awareness about the potential risk of IFI after initiating ibrutinib is warranted, especially when other predisposing factors are associated,” wrote David Ghez, MD, PhD, and colleagues at the Gustave Roussy Institute in Villejuif and other centers in France.

Although ibrutinib, an inhibitor of Bruton’s tyrosine kinase, is generally considered to be less immunosuppressive than other therapies, it was associated with five cases of Pneumocystis jirovecii pneumonia in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib monotherapy in a 2016 report (Blood. 2016;128:1940-3). Of these five patients, four were treatment naive, suggesting that ibrutinib itself could increase risk for invasive opportunistic infections, Dr. Ghez and his colleagues noted.

 

 

Based on this finding and on case reports of invasive infections in other patients being treated with ibrutinib, the authors conducted a retrospective survey of centers in the French Innovative Leukemia Organization CLL group.

They identified 33 cases, including 30 patients with CLL (15 of whom had deleterious 17p deletions), 1 with mantle cell lymphoma, and 2 with Waldenstrom macroglobulinemia.

Invasive aspergillosis accounted for 27 of the 33 cases, and 11 cases had CNS localization. There were four cases of disseminated cryptococcosis, and one each of mucormycosis and pneumocystis pneumonia.

The median time between the start of ibrutinib therapy and a diagnosis of invasive fungal infection was 3 months, with some cases occurring as early as 1 month, and others occurring 30 months out. However, the majority of cases – 28 – were diagnosed within 6 months of the start of therapy, including 20 that occurred within 3 months of ibrutinib initiation.
 

 

In 21 patients, the diagnosis of an invasive fungal infection led to drug discontinuation. In the remaining patients, the drug was either resumed after resolution of the IFI, or continued at a lower dose because of potential for interaction between ibrutinib and the antifungal agent voriconazole.

Dr. Ghez reported receiving a research grant from Janssen, and coauthor Loic Ysebaert, MD, PhD, reported consultancy fees from the company. All other authors declared no competing financial interests.

SOURCE: Ghez D et al., Blood. 2018 Feb 1. doi: 10.1182/blood-2017-11-818286.

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Key clinical point: The tyrosine kinase inhibitor ibrutinib (Imbruvica) may be associated with early-onset invasive fungal infections.

Major finding: Of 33 identified cases, 27 were invasive aspergillosis.

Study details: Retrospective review of case reports from 16 French centers.

Disclosures: Dr. Ghez reported receiving a research grant from Janssen, and coauthor Loic Ysebaert, MD, PhD, reported consultancy fees with the company. All other authors declared no competing financial interests.

Source: Ghez D et al. Blood. 2018 Feb 1. doi: 10.1182/blood-2017-11-818286.

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VIDEO: With tinea capitis, don’t be fooled by a Wood’s lamp

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Tue, 04/30/2019 - 09:31

– When it comes to diagnosing tinea capitis, you really can’t rely on a Wood’s lamp, according to pediatric dermatologist Robert Silverman, MD.

The Wood’s lamp generally misses the most common cause of tinea capitis in urban and suburban environments today, Trichophyton tonsurans, said Dr. Silverman, a pediatric dermatologist and clinical associate professor in the department of pediatrics at Georgetown University, Washington.

The dermatoscope, which “will allow you to see what is called the black dots of tinea capitis very, very closely,” is far better, he said in an interview at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation

He explained the limitations of the Wood’s lamp in this setting, and what to look for with a dermatoscope. He had other tips to share, too, from years of experience treating the condition, including how to differentiate tinea capitis on exam from its most common mimics, why it’s best to include a counter stain when using potassium hydroxide, and how to motivate parents to wash their child’s hair more frequently to reduce spores on the hair and scalp.

Dr. Silverman disclosed relationships with Pierre Fabre, Pfizer, and Regeneron.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

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– When it comes to diagnosing tinea capitis, you really can’t rely on a Wood’s lamp, according to pediatric dermatologist Robert Silverman, MD.

The Wood’s lamp generally misses the most common cause of tinea capitis in urban and suburban environments today, Trichophyton tonsurans, said Dr. Silverman, a pediatric dermatologist and clinical associate professor in the department of pediatrics at Georgetown University, Washington.

The dermatoscope, which “will allow you to see what is called the black dots of tinea capitis very, very closely,” is far better, he said in an interview at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation

He explained the limitations of the Wood’s lamp in this setting, and what to look for with a dermatoscope. He had other tips to share, too, from years of experience treating the condition, including how to differentiate tinea capitis on exam from its most common mimics, why it’s best to include a counter stain when using potassium hydroxide, and how to motivate parents to wash their child’s hair more frequently to reduce spores on the hair and scalp.

Dr. Silverman disclosed relationships with Pierre Fabre, Pfizer, and Regeneron.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

– When it comes to diagnosing tinea capitis, you really can’t rely on a Wood’s lamp, according to pediatric dermatologist Robert Silverman, MD.

The Wood’s lamp generally misses the most common cause of tinea capitis in urban and suburban environments today, Trichophyton tonsurans, said Dr. Silverman, a pediatric dermatologist and clinical associate professor in the department of pediatrics at Georgetown University, Washington.

The dermatoscope, which “will allow you to see what is called the black dots of tinea capitis very, very closely,” is far better, he said in an interview at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation

He explained the limitations of the Wood’s lamp in this setting, and what to look for with a dermatoscope. He had other tips to share, too, from years of experience treating the condition, including how to differentiate tinea capitis on exam from its most common mimics, why it’s best to include a counter stain when using potassium hydroxide, and how to motivate parents to wash their child’s hair more frequently to reduce spores on the hair and scalp.

Dr. Silverman disclosed relationships with Pierre Fabre, Pfizer, and Regeneron.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

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REPORTING FROM SDEF HAWAII DERMATOLOGY SEMINAR

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Fungi and bacteria cooperate to form inflammatory gut biofilms

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Sat, 12/08/2018 - 14:33

 

Fungi and bacteria in the gastrointestinal tract collaboratively form biofilms that may exacerbate inflammation in patients with inflammatory bowel disease (IBD), a review article concluded.

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Fungi and bacteria in the gastrointestinal tract collaboratively form biofilms that may exacerbate inflammation in patients with inflammatory bowel disease (IBD), a review article concluded.

 

Fungi and bacteria in the gastrointestinal tract collaboratively form biofilms that may exacerbate inflammation in patients with inflammatory bowel disease (IBD), a review article concluded.

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FROM DIGESTIVE AND LIVER DISEASE

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Key clinical point: Fungi and bacteria interact in the gastrointestinal tract to form biofilms that may exacerbate inflammation, suggesting a potential role for antifungals combined with probiotics as a treatment strategy for patients with inflammatory bowel disease.

Major finding: Compared with healthy family members, patients with Crohn’s disease in one key study had higher levels of the fungus Candida tropicalis and of two bacteria, Escherichia coli and Serratia marcescens, all of which worked together to form robust biofilms.

Data source: A review article summarizing the limited number of investigations to date, most published in 2010 or later.

Disclosures: The authors declared no conflicts of interest.

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Nearly 10% of patients with candidemia had CDI

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– Nearly one in ten adults hospitalized with candidemia had Clostridium difficile coinfections in a large multistate study.

Be vigilant – look for candidemia and Clostridium difficile infection occurring together,” Sharon Tsay, MD, said at an annual scientific meeting on infectious diseases. “In patients with CDI, one in 100 developed candidemia, but in patients with candidemia, nearly one in 10 had CDI,” she said. Patients with diabetes, hemodialysis, solid organ transplantation, or a prior recent hospital stay were significantly more likely to have a CDI coinfection even after the researchers controlled for potential confounders, she reported.

Both candidemia and CDI are serious health care–associated infections that disproportionately affect older, severely ill, and immunosuppressed patients, noted Dr. Tsay, an Epidemic Intelligence Service officer in the mycotic diseases branch at the Centers for Disease Control and Prevention, Atlanta. Every year in the United States, about 50,000 individuals are hospitalized with candidemia, and about 30% die within 30 days of diagnosis. The prevalence of CDI is about tenfold higher, and 30-day mortality rates range between about 1% and 9%.

cjc2nd/Wikimedia Commons/CC ASA-3.0


To understand why candidemia and CDI occur together, consider the effects of oral vancomycin therapy, Dr. Tsay said. Antibiotic pressure disrupts normal gut flora, leading to decreased immunity and Candida colonization. Disrupting the gut microbiome also increases the risk of CDI, which can damage gut mucosa, especially in hypervirulent cases such as C. difficile ribotype 027. Vancomycin can also directly damage the gut mucosa, after which Candida can translocate into the bloodstream.

To better characterize CDI and candidemia coinfections in the United States, Dr. Tsay and her associates analyzed data from CDC’s Emerging Infections Program, which tracks infections of high public health significance in 10 states across the country. Among 2,129 patients with a positive blood culture for Candida from 2014 through 2016, 193 (9%) had a diagnosis of CDI within 90 days. Two-thirds of CDI cases preceded candidemia (median, 10 days) and one-third occurred afterward (median, 7 days). Rates of 30-day mortality rates were 25% in patients with and without CDI. For both groups, Candida albicans was the most commonly identified species, followed by C. glabrata and C. parapsilosis.

Dr. Sharon Tsay
Demographics were generally similar between candidemic patients with and without CDI. “Underlying conditions were quite common, and patients with diabetes and solid organ transplant had greater odds of CDI coinfection,” Dr. Tsay said. Diabetes and solid organ transplant were significant risk factors for CDI in univariate analyses, while liver and inflammatory bowel diseases, malignancy, pancreatitis, and HIV infection were not. Among health care risk factors, significant predictors of coinfection included hemodialysis, prior hospital stay, and central venous catheter placement.

A multivariate model identified four risk factors for CDI in patients with candidemia – solid organ transplantation (odds ratio, 3.0), hemodialysis (OR, 1.8), prior hospital stay (OR, 1.7), and diabetes (OR, 1.4). Data were limited to case report forms and did not include information about CDI severity or treatment, Dr. Tsay said.

Dr. Tsay and her associates reported having no conflicts of interest.

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– Nearly one in ten adults hospitalized with candidemia had Clostridium difficile coinfections in a large multistate study.

Be vigilant – look for candidemia and Clostridium difficile infection occurring together,” Sharon Tsay, MD, said at an annual scientific meeting on infectious diseases. “In patients with CDI, one in 100 developed candidemia, but in patients with candidemia, nearly one in 10 had CDI,” she said. Patients with diabetes, hemodialysis, solid organ transplantation, or a prior recent hospital stay were significantly more likely to have a CDI coinfection even after the researchers controlled for potential confounders, she reported.

Both candidemia and CDI are serious health care–associated infections that disproportionately affect older, severely ill, and immunosuppressed patients, noted Dr. Tsay, an Epidemic Intelligence Service officer in the mycotic diseases branch at the Centers for Disease Control and Prevention, Atlanta. Every year in the United States, about 50,000 individuals are hospitalized with candidemia, and about 30% die within 30 days of diagnosis. The prevalence of CDI is about tenfold higher, and 30-day mortality rates range between about 1% and 9%.

cjc2nd/Wikimedia Commons/CC ASA-3.0


To understand why candidemia and CDI occur together, consider the effects of oral vancomycin therapy, Dr. Tsay said. Antibiotic pressure disrupts normal gut flora, leading to decreased immunity and Candida colonization. Disrupting the gut microbiome also increases the risk of CDI, which can damage gut mucosa, especially in hypervirulent cases such as C. difficile ribotype 027. Vancomycin can also directly damage the gut mucosa, after which Candida can translocate into the bloodstream.

To better characterize CDI and candidemia coinfections in the United States, Dr. Tsay and her associates analyzed data from CDC’s Emerging Infections Program, which tracks infections of high public health significance in 10 states across the country. Among 2,129 patients with a positive blood culture for Candida from 2014 through 2016, 193 (9%) had a diagnosis of CDI within 90 days. Two-thirds of CDI cases preceded candidemia (median, 10 days) and one-third occurred afterward (median, 7 days). Rates of 30-day mortality rates were 25% in patients with and without CDI. For both groups, Candida albicans was the most commonly identified species, followed by C. glabrata and C. parapsilosis.

Dr. Sharon Tsay
Demographics were generally similar between candidemic patients with and without CDI. “Underlying conditions were quite common, and patients with diabetes and solid organ transplant had greater odds of CDI coinfection,” Dr. Tsay said. Diabetes and solid organ transplant were significant risk factors for CDI in univariate analyses, while liver and inflammatory bowel diseases, malignancy, pancreatitis, and HIV infection were not. Among health care risk factors, significant predictors of coinfection included hemodialysis, prior hospital stay, and central venous catheter placement.

A multivariate model identified four risk factors for CDI in patients with candidemia – solid organ transplantation (odds ratio, 3.0), hemodialysis (OR, 1.8), prior hospital stay (OR, 1.7), and diabetes (OR, 1.4). Data were limited to case report forms and did not include information about CDI severity or treatment, Dr. Tsay said.

Dr. Tsay and her associates reported having no conflicts of interest.

– Nearly one in ten adults hospitalized with candidemia had Clostridium difficile coinfections in a large multistate study.

Be vigilant – look for candidemia and Clostridium difficile infection occurring together,” Sharon Tsay, MD, said at an annual scientific meeting on infectious diseases. “In patients with CDI, one in 100 developed candidemia, but in patients with candidemia, nearly one in 10 had CDI,” she said. Patients with diabetes, hemodialysis, solid organ transplantation, or a prior recent hospital stay were significantly more likely to have a CDI coinfection even after the researchers controlled for potential confounders, she reported.

Both candidemia and CDI are serious health care–associated infections that disproportionately affect older, severely ill, and immunosuppressed patients, noted Dr. Tsay, an Epidemic Intelligence Service officer in the mycotic diseases branch at the Centers for Disease Control and Prevention, Atlanta. Every year in the United States, about 50,000 individuals are hospitalized with candidemia, and about 30% die within 30 days of diagnosis. The prevalence of CDI is about tenfold higher, and 30-day mortality rates range between about 1% and 9%.

cjc2nd/Wikimedia Commons/CC ASA-3.0


To understand why candidemia and CDI occur together, consider the effects of oral vancomycin therapy, Dr. Tsay said. Antibiotic pressure disrupts normal gut flora, leading to decreased immunity and Candida colonization. Disrupting the gut microbiome also increases the risk of CDI, which can damage gut mucosa, especially in hypervirulent cases such as C. difficile ribotype 027. Vancomycin can also directly damage the gut mucosa, after which Candida can translocate into the bloodstream.

To better characterize CDI and candidemia coinfections in the United States, Dr. Tsay and her associates analyzed data from CDC’s Emerging Infections Program, which tracks infections of high public health significance in 10 states across the country. Among 2,129 patients with a positive blood culture for Candida from 2014 through 2016, 193 (9%) had a diagnosis of CDI within 90 days. Two-thirds of CDI cases preceded candidemia (median, 10 days) and one-third occurred afterward (median, 7 days). Rates of 30-day mortality rates were 25% in patients with and without CDI. For both groups, Candida albicans was the most commonly identified species, followed by C. glabrata and C. parapsilosis.

Dr. Sharon Tsay
Demographics were generally similar between candidemic patients with and without CDI. “Underlying conditions were quite common, and patients with diabetes and solid organ transplant had greater odds of CDI coinfection,” Dr. Tsay said. Diabetes and solid organ transplant were significant risk factors for CDI in univariate analyses, while liver and inflammatory bowel diseases, malignancy, pancreatitis, and HIV infection were not. Among health care risk factors, significant predictors of coinfection included hemodialysis, prior hospital stay, and central venous catheter placement.

A multivariate model identified four risk factors for CDI in patients with candidemia – solid organ transplantation (odds ratio, 3.0), hemodialysis (OR, 1.8), prior hospital stay (OR, 1.7), and diabetes (OR, 1.4). Data were limited to case report forms and did not include information about CDI severity or treatment, Dr. Tsay said.

Dr. Tsay and her associates reported having no conflicts of interest.

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Key clinical point: Look for candidemia and Clostridium difficile infection occurring together.

Major finding: Among 2,129 patients with a positive blood culture for Candida, 193 (9%) had a diagnosis of CDI within 90 days. Risk factors for coinfection included solid organ transplant, hemodialysis, recent hospital stay, and diabetes.

Data source: A multistate analysis of data from the Centers for Disease Control’s Emerging Infections Program.

Disclosures: Dr. Tsay and her associates reported having no conflicts of interest.

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Wait at least 2 days to replace central venous catheters in patients with candidemia

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Sat, 12/08/2018 - 14:31

– Wait at least 2 days before replacing central venous catheters (CVC) in patients with catheter-associated candidemia, according to the results of a single-center retrospective cohort study of 228 patients.

Waiting less than 2 days to replace a CVC increased the odds of 30-day mortality nearly sixfold among patients with catheter-related bloodstream infections due to candidemia, even after controlling for potential confounders, Takahiro Matsuo, MD, said at an annual scientific meeting on infectious diseases. No other factor significantly predicted mortality in univariate or multivariate analyses, he said. “This is the first study to demonstrate the optimal timing of central venous catheter replacement in catheter-related [bloodstream infection] due to Candida.”

Invasive candidiasis is associated with mortality rates of up to 50%, noted Dr. Matsuo, who is a fellow in infectious diseases at St. Luke’s International Hospital, Tokyo. Antifungal therapy improves outcomes, and most physicians agree that removing a CVC does, too. To better pinpoint optimal timing of catheter replacement, Dr. Matsuo and his associates examined risk factors for 30-day mortality among patients with candidemia who were treated at St. Luke’s between 2004 and 2015.

Amy Karon/Frontline Medical News
Dr. Takahiro Matsuo


Among 228 patients with candidemia, 166 had CVCs, and 144 had their CVC removed. Among 71 patients who needed their CVC replaced, 15 died within 30 days. Central venous catheters were replaced less than 2 days after removal in 87% of patients who died and in 54% of survivors (P = .04). The association remained statistically significant after the researchers accounted for potential confounders (adjusted odds ratio, 5.9; 95% confidence interval, 1.2-29.7; P = .03).

Patients who died within 30 days of CVC replacement also were more likely to have hematologic malignancies (20% versus 4%), diabetes (13% vs. 11%), to be on hemodialysis (27% vs. 16%), and to have a history of recent corticosteroid exposure (20% versus 11%) compared with survivors, but none of these associations reached statistical significance. Furthermore, 30-day mortality was not associated with gender, age, Candida species, endophthalmitis, or type of antifungal therapy, said Dr. Matsuo, who spoke at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

An infectious disease consultation was associated with about a 70% reduction in the odds of mortality in the multivariate analysis, but the 95% confidence interval crossed 1.0, rendering the link statistically insignificant.

Given the small sample size and single-center design of this study, its findings ideally should be confirmed in a larger randomized controlled trial, Dr. Matsuo said. The investigators also did not track whether patients were fungemic at the time of CVC replacement, he noted.

The researchers reported having no conflicts of interest.

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– Wait at least 2 days before replacing central venous catheters (CVC) in patients with catheter-associated candidemia, according to the results of a single-center retrospective cohort study of 228 patients.

Waiting less than 2 days to replace a CVC increased the odds of 30-day mortality nearly sixfold among patients with catheter-related bloodstream infections due to candidemia, even after controlling for potential confounders, Takahiro Matsuo, MD, said at an annual scientific meeting on infectious diseases. No other factor significantly predicted mortality in univariate or multivariate analyses, he said. “This is the first study to demonstrate the optimal timing of central venous catheter replacement in catheter-related [bloodstream infection] due to Candida.”

Invasive candidiasis is associated with mortality rates of up to 50%, noted Dr. Matsuo, who is a fellow in infectious diseases at St. Luke’s International Hospital, Tokyo. Antifungal therapy improves outcomes, and most physicians agree that removing a CVC does, too. To better pinpoint optimal timing of catheter replacement, Dr. Matsuo and his associates examined risk factors for 30-day mortality among patients with candidemia who were treated at St. Luke’s between 2004 and 2015.

Amy Karon/Frontline Medical News
Dr. Takahiro Matsuo


Among 228 patients with candidemia, 166 had CVCs, and 144 had their CVC removed. Among 71 patients who needed their CVC replaced, 15 died within 30 days. Central venous catheters were replaced less than 2 days after removal in 87% of patients who died and in 54% of survivors (P = .04). The association remained statistically significant after the researchers accounted for potential confounders (adjusted odds ratio, 5.9; 95% confidence interval, 1.2-29.7; P = .03).

Patients who died within 30 days of CVC replacement also were more likely to have hematologic malignancies (20% versus 4%), diabetes (13% vs. 11%), to be on hemodialysis (27% vs. 16%), and to have a history of recent corticosteroid exposure (20% versus 11%) compared with survivors, but none of these associations reached statistical significance. Furthermore, 30-day mortality was not associated with gender, age, Candida species, endophthalmitis, or type of antifungal therapy, said Dr. Matsuo, who spoke at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

An infectious disease consultation was associated with about a 70% reduction in the odds of mortality in the multivariate analysis, but the 95% confidence interval crossed 1.0, rendering the link statistically insignificant.

Given the small sample size and single-center design of this study, its findings ideally should be confirmed in a larger randomized controlled trial, Dr. Matsuo said. The investigators also did not track whether patients were fungemic at the time of CVC replacement, he noted.

The researchers reported having no conflicts of interest.

– Wait at least 2 days before replacing central venous catheters (CVC) in patients with catheter-associated candidemia, according to the results of a single-center retrospective cohort study of 228 patients.

Waiting less than 2 days to replace a CVC increased the odds of 30-day mortality nearly sixfold among patients with catheter-related bloodstream infections due to candidemia, even after controlling for potential confounders, Takahiro Matsuo, MD, said at an annual scientific meeting on infectious diseases. No other factor significantly predicted mortality in univariate or multivariate analyses, he said. “This is the first study to demonstrate the optimal timing of central venous catheter replacement in catheter-related [bloodstream infection] due to Candida.”

Invasive candidiasis is associated with mortality rates of up to 50%, noted Dr. Matsuo, who is a fellow in infectious diseases at St. Luke’s International Hospital, Tokyo. Antifungal therapy improves outcomes, and most physicians agree that removing a CVC does, too. To better pinpoint optimal timing of catheter replacement, Dr. Matsuo and his associates examined risk factors for 30-day mortality among patients with candidemia who were treated at St. Luke’s between 2004 and 2015.

Amy Karon/Frontline Medical News
Dr. Takahiro Matsuo


Among 228 patients with candidemia, 166 had CVCs, and 144 had their CVC removed. Among 71 patients who needed their CVC replaced, 15 died within 30 days. Central venous catheters were replaced less than 2 days after removal in 87% of patients who died and in 54% of survivors (P = .04). The association remained statistically significant after the researchers accounted for potential confounders (adjusted odds ratio, 5.9; 95% confidence interval, 1.2-29.7; P = .03).

Patients who died within 30 days of CVC replacement also were more likely to have hematologic malignancies (20% versus 4%), diabetes (13% vs. 11%), to be on hemodialysis (27% vs. 16%), and to have a history of recent corticosteroid exposure (20% versus 11%) compared with survivors, but none of these associations reached statistical significance. Furthermore, 30-day mortality was not associated with gender, age, Candida species, endophthalmitis, or type of antifungal therapy, said Dr. Matsuo, who spoke at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

An infectious disease consultation was associated with about a 70% reduction in the odds of mortality in the multivariate analysis, but the 95% confidence interval crossed 1.0, rendering the link statistically insignificant.

Given the small sample size and single-center design of this study, its findings ideally should be confirmed in a larger randomized controlled trial, Dr. Matsuo said. The investigators also did not track whether patients were fungemic at the time of CVC replacement, he noted.

The researchers reported having no conflicts of interest.

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Key clinical point: Consider waiting at least 2 days to replace a central venous catheter that has been removed because of candidemia.

Major finding: Replacing a CVC that was removed because of candidemia in less than 2 days was an independent risk factor for mortality (odds ratio, 5.9; 95% confidence interval, 1.2-27.3).

Data source: A single-center retrospective cohort study of 228 patients with candidemia.

Disclosures: The researchers reported having no conflicts of interest.

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