Linezolid

Linezolid (Zyvox), an oxazolidinone approved in 2000, has been touted for its oral bioavailability, twice‐daily dosing, gram‐positive coverage, and unique mechanism of action. Like several other antimicrobials, linezolid inhibits bacterial protein synthesis. The drug binds to the 50S ribosomal subunit near its site of interaction with the 30S subunit, preventing formation of the 70S initiation complex.5 This site of action on the 50S subunit is unique to linezolid; as a result, cross‐resistance between linezolid and other antimicrobials that act at the 50S subunit (eg, chloramphenicol, macrolides, aminoglycosides, and tetracycline) does not occur.6

The oxazolidinones have excellent bacteriostatic activity against all pathogenic gram‐positive bacteria. The U.S. Food and Drug Administration (FDA) approved linezolid for the treatment of serious infections due to vancomycin‐resistant enterococci (VRE), including bacteremia, complicated skin and soft‐tissue infections (cSSTIs) due to Staphylococcus aureus (including MRSA), and nosocomial pneumonia due to Staphylococcus aureus (including MRSA) or penicillin‐susceptible Streptococcus pneumoniae (Table 1).

In retrospective analyses of SSTIs due to MRSA, linezolid was as effective as vancomycin, resulting in higher clinical cure rates and shorter hospitalizations.7 As a result, linezolid has established a role in the treatment of community‐acquired MRSA SSTIs. Evidence limited to case reports and case series suggest that linezolid may also have a role in the treatment of bone and joint infections. In these cases, linezolid was often used because treatment with other agents had failed, the administration of other antibiotics was not indicated due to resistance patterns, the patient refused intravenous therapy, or the patient did not tolerate vancomycin. When such conditions exist, linezolid may be a consideration in cases of osteomyelitis or prosthetic joint infection.8

Potential side effects of linezolid may limit its use, especially for patients who require prolonged therapy (Table 1). Of note, as a reversible, relatively weak nonselective inhibitor of monoamine oxidase, linezolid may interact with adrenergic and serotonergic agents. Concomitant of a serotonin agent such as a selective serotonin‐reuptake inhibitor (SSRI) and linezolid should be approached with caution. Subsequent serotonin syndrome is characterized by autonomic dysfunction (eg, diaphoresis, tachycardia, hypertension) and neuromuscular hyperactivity (eg, muscle rigidity, clonus, hyperreflexia). Though infrequent, cases of reversible myelosuppression have been reported with linezolid use.9 Patients who will receive this drug for more than 2 weeks should be monitored for myelosuppression with a weekly complete blood count. Isolated reports suggest that the prolonged administration of linezolid (>28 days) may be associated with peripheral neuropathy and optic neuropathy. While prompt discontinuation of the drug often results in resolution of symptoms, peripheral or optic nerve injury can be permanent. The mechanism of injury is unclear, though mitochondrial toxicity is suspected.10

Daptomycin

Daptomycin (Cubicin), a cyclic lipopeptide, was discovered in the early 1980s, but skeletal muscle toxicity led to the discontinuation of early clinical trials. When a change from twice‐daily to once‐daily dosing in 2003 resulted in fewer adverse events, the FDA approved daptomycin to treat complicated skin and skin‐structure infections.11 Daptomycin binds to the cell membrane via a calcium‐dependent process, eventually disrupting the cell membrane potential. The bactericidal effect is limited to gram‐positive organisms.12

Daptomycin is effective against almost all gram‐positive organisms including methicillin‐susceptible Staphylococcus aureus (MSSA), MRSA, and VRE.12 As a result, it has FDA approval for the treatment of cSSTIs. While beta‐lactams remain the standard of care for MSSA bacteremia, daptomycin has FDA approval for bloodstream infections and right‐sided endocarditis due to MSSA or MRSA (Table 1).13 Daptomycin has poor penetration into alveolar fluid14 and is inhibited by pulmonary surfactants; as a consequence, it is not indicated for patients with pneumonia.15

Of note, daptomycin is mainly excreted via the kidneys and should be dose‐adjusted for patients with a creatinine clearance <30 mL/minute. A reversible myopathy may occur with daptomycin, requiring intermittent monitoring of creatinine kinase if prolonged use is anticipated. Caution should be used with the coadministration of medications that can also cause a myopathy, such as statins.

Tigecycline

Tigecycline (Tygacil) was approved for use by the FDA in 2005. The first in a class of new tetracycline analogs, the glycylcyclines, tigecycline is notable for its activity against several multidrug‐resistant (MDR) organisms, including MRSA, VRE, and Enterobacteriaceae carrying extended‐spectrum beta‐lactamases (ESBL). Tigecycline impairs bacterial protein synthesis by binding to the 30S ribosomal subunit. Due to steric hindrance from an N‐alkyl‐glycylamido group at position 9, tigecycline cannot be removed by most bacterial efflux mechanisms.16

Tigecycline has been approved for the therapy of cSSTIs, including those due to MSSA and MRSA. In a pooled analysis of 2 international, multicenter, phase III randomized, double‐blind trials, tigecycline was not inferior to vancomycin plus aztreonam in the treatment of cSSTIs. Of note, MRSA eradication rates were similar between patients treated with tigecycline and vancomycin plus aztreonam (78.1% and 75.8%, respectively).17

Dalbavancin

Dalbavancin (Zeven), a new, semisynthetic lipoglycopeptide, was approved by the FDA in late 2007; however, it has not been cleared for marketing. Though dalbavancin is derived from teicoplanin, its lipophilic anchor to the bacterial cell membrane makes the drug more potent than its predecessor. Dalbavancin interferes with bacterial cell wall synthesis by binding to the C‐terminal D‐alanyl‐D alanine of the growing peptidoglycan chains.18 Enhanced pharmacokinetic properties of dalbavancin (half‐life 149‐250 hours) allow it to be dosed once‐weekly, a novel concept in antimicrobial use.19

Like other glycopeptides, dalbavancin maintains in vitro activity against most gram‐positive aerobic organisms, including MRSA and penicillin‐susceptible and penicillin‐resistant strains of Streptococcus pneumoniae. Notably, when compared to vancomycin in vitro, the agent is more active against Enterococcus faecium and Enterococcus faecalis isolates. In a recent phase III double‐blind trial, dalbavancin was compared to linezolid for the treatment of cSSTIs. Dalbavancin was not inferior to linezolid (clinical success rate 90% vs. 92%). Of note, 51% of study patients with SSTI had infection due to MRSA. Microbiological response to dalbavancin paralleled the clinical success rate; MRSA eradication rates after dalbavancin and linezolid were 91% and 89%, respectively.20

Given its once‐weekly dosing, dalbavancin may be an attractive agent in the outpatient treatment of gram‐positive bacteremia. In a phase II study, dalbavancin administered as a single 1‐g dose, followed by a 500‐mg dose 1 week later, was comparable to 14 days of vancomycin for the treatment of catheter‐related bloodstream infections (CRBSI) due to coagulase‐negative staphylococci or S. aureus (including MRSA).21 Phase III studies are underway. At present, there is no evidence to support the use of dalbavancin for the treatment of pneumonia or bone and joint infections.

Despite the administration of vancomycin, the patient continues to experience fever and chills. Blood cultures drawn in the emergency department are now growing Enterococcus species. You review the patient's medical record and notice that she was colonized with VRE on a prior admission. You consider the antibiotic options for serious infections due to VRE.

Though rates of VRE have remained fairly stable in recent years,22 the pathogen continues to present a challenge to hospital epidemiologists. A national survey in 2004 suggested that nearly 30% of enterococci in U.S. intensive care units display vancomycin resistance.1 Additional U.S. surveillance data reveals that VRE accounts for 10% to 26% of enterococci hospital‐wide.23, 24 In 2005, a meta‐analysis noted that bloodstream infections due to VRE resulted in higher mortality rates than those due to vancomycin‐susceptible enterococci.25 This discrepancy is most evident among neutropenia patients.26 Unfortunately, the options for the treatment of serious infections due to VRE are limited. The advantages and disadvantages of linezolid, quinupristin‐dalfopristin, tigecycline, and daptomycin in the treatment for VRE are discussed below.

Linezolid

Currently, linezolid is the only oral drug that is FDA‐approved for the treatment of infections due to VRE, including bacteremia. Notably, linezolid therapy resulted in the cure of 77% of 22 cases of vancomycin‐resistant enterococcal endocarditis.27 Current guidelines by the Infectious Disease Society of America (IDSA) support the use of linezolid in cases of endocarditis due to ampicillin‐resistant and vancomycin‐resistant Enterococcus faecium.28 Unfortunately, recent reports highlight the emergence of linezolid‐resistant VRE,29 suggesting use of this drug should be limited to circumstances in which other alternatives do not exist.

Quinupristin‐Dalfopristin

Quinupristin‐dalfopristin (Synercid) was approved by the FDA in 1999. It is used in the treatment of infections caused by gram‐positive organisms and is a combination of 2 semisynthetic pristinamycin derivatives. They diffuse into bacteria and bind to different areas on the 50S ribosomal subunit, thereby inhibiting protein synthesis. Individually, quinupristin and dalfopristin are bacteriostatic but together they are bactericidal.30

Quinupristin‐dalfopristin has activity against Staphylococcus aureus (including MRSA), Streptococcus pneumoniae, gram‐positive anaerobes, and vancomycin‐sensitive and resistant Enterococcus faecium. It has little activity against Enterococcus faecalis.31 FDA‐approved uses of quinupristin‐dalfopristin are limited, but include the treatment of serious infections caused by vancomycin‐resistant E. faecium (VREF).32 In a study of 396 patients with VREF the clinical success rate of quinupristin‐dalfopristin was 73.6%.33 The drug also has FDA approval for the use in cSSTIs due to group A streptococci or MSSA.32 The use of this agent is limited due to its toxicity profile. In cases of serious VRE‐related infection, quinupristin‐dalfopristin is often only utilized if linezolid cannot be tolerated.

Daptomycin

In vitro studies suggest that daptomycin is active against enterococci, including vancomycin‐resistant isolates.34 However, clinical data on the use of this agent in the treatment of infections due to VRE are lacking. FDA approval for the use of daptomycin in cSSTI included the treatment of 45 patients infected with Enterococcus faecalis.13 In addition, several reports have detailed the successful treatment of VRE bloodstream infections with daptomycin,35, 36 including a case series of VRE endocarditis.37 To determine the role of this agent in the treatment of invasive infections due to VRE, further study is needed.

You decide to discontinue vancomycin and administer linezolid. The patient's vascular catheter is removed; catheter‐tip cultures grow >1000 colonies of VRE. Blood cultures the following day are negative and a new catheter is placed. You ask the patient to continue oral linezolid to complete a 2‐week course. A review of her medication list reveals that she is not taking SSRIs or monoamine oxidase inhibitors (MAOIs).

While linezolid has retained its FDA indication for VRE bacteremia, empiric use in suspected cases of CRBSI or catheter site infection is not advised. In an open‐label trial among seriously ill patients with intravascular catheter‐related infections, linezolid use was associated with a higher mortality when compared to vancomycin/oxacillin. Interestingly, mortality among linezolid‐treated patients included those with CRBSI due to gram‐negative pathogens, due to both gram‐negative and gram‐positive pathogens, or due to an identifiable pathogen; mortality rates did not differ among patients with gram‐positive infections only.38

Doripenem

In October 2007, the FDA approved the use of doripenem (Doribax), a much‐anticipated carbapenem. In structure, doripenem resembles meropenem and does not require a renal dehydropeptidase I inhibitor (eg, cilastatin).44 Similar to other beta‐lactams, doripenem binds to penicillin‐binding proteins (PBPs), inhibiting PBP‐directed cell wall synthesis.

Like imipenem and meropenem, doripenem has broad‐spectrum antimicrobial activity. It demonstrates in vitro activity against most gram‐positive pathogens including MSSA and ampicillin‐sensitive enterococci. Doripenem also has in vitro activity against most gram‐negative pathogens (including ESBL‐producing Enterobacteriaceae) and most anaerobes, including Bacteriodes fragilis. Most notably, when compared to other carbapenems, doripenem has demonstrated better in vitro activity against Pseudomonas aeruginosa.45 However, clinical implications of this in vitro activity are unclear.

When compared to meropenem or levofloxacin for the treatment of complicated UTIs, doripenem is an effective alternative. Clinical response rates among affected patients were 95% to 96% with doripenem, 89% with meropenem, and 90% with levofloxacin.46, 47 Doripenem was not inferior to meropenem in patients with serious lower respiratory tract infections, and comparable to imipenem‐cilastin and pipercillin‐tazobactam for the treatment of nosocomial or ventilator‐associated pneumonia (VAP).48, 49 Finally, for the treatment of complicated intraabdominal infections, doripenem was not inferior to meropenem; both drugs achieved microbiologic cure rates of >84%.50

Currently, doripenem is FDA‐approved for the treatment of complicated intraabdominal infections (eg, appendicitis, pancreatitis, cholecystitis, peritonitis) and complicated lower UTIs or pyelonephritis (Table 1). Given its expanded spectrum of activity, use of doripenem should be limited to circumstances in which a MDR pathogen is highly suspected or confirmed.

Colistin

Colistin (Coly‐Mycin M) falls within the family of polymyxin antibiotics, which were discovered in 1947. Colistin has been available for almost 50 years for the treatment of infections caused by gram‐negative bacteria, including Pseudomonas spp. However, early use of colistin was associated with significant nephrotoxicity. Its use decreased markedly with the advent of new antibiotics that had the same antimicrobial spectrum and a better side effect profile. With the emergence of MDR gram‐negative bacteria, colistin has returned to limited clinical use.51 As a polymyxin, colistin is a cell membrane detergent. It disrupts the cell membrane, causing leakage of bacterial cell content and ultimately cell death.52

Colistin has bactericidal activity against most gram‐negative bacteria including Acinetobacter spp, and members of the family Enterobacteriaceae (eg, Klebsiella spp, Escherichia coli, Enterobacter spp), including those producing ESBLs.53 Colistin is not active against several predominant gram‐negative pathogens including Proteus spp, Providencia spp, or Serratia spp (Table 1).

In 2007, several studies suggested that colistin monotherapy was effective for patients with VAP due to MDR P. aeruginosa or A. baumannii isolate.54, 55 A third trial that year suggested that colistin may have a role in the treatment of MDR P. aeruginosa among neutropenic patients. In that study, infected patients receiving colistin monotherapy experienced higher rates of clinical and microbiologic response than those receiving other antipseudomonal agents (eg, beta‐lactams or fluoroquinolones if active against the isolate).56 While uncontrolled studies suggest that the use of colistin in combination with other antimicrobials (including carbapenems, ampicillin‐sulbactam, aminoglycosides, and rifampin) may have some success in the treatment of VAP due to MDR A. baumannii,57, 58 further trials are needed.

Currently, colistin has FDA approval only for the treatment of acute infections due to gram‐negative bacteria that have demonstrated susceptibility to the drug and is therefore administered on a case by case basis. Although it has been used via the inhalation route to treat infections in cystic fibrosis patients, colistin does not have FDA approval for this indication.

Tigecycline

Tigecycline is approved for the treatment of complicated intraabdominal infections based on the results of 2 international, multicenter, phase III, randomized, double‐blind trials. In this pooled analysis, tigecycline was as effective and as safe as imipenem/cilastatin. Notably, study patients were not severely ill (baseline APACHE II score of 6.0).59 FDA approval suggests tigecycline use be focused on intraabdominal infections due to members of the family Enterobacteriaceae (eg, Klebsiella spp, Escherichia coli, Enterobacter spp), including those producing ESBLs, vancomycin‐sensitive enterococci, and/or MSSA. Notably, tigecycline lacks significant in vitro activity against Pseudomonas spp, Proteus spp, or Providencia spp. It has demonstrated in vitro activity against MDR strains of Acinetobacter spp (Table 1).

Given its bacteriostatic activity, tigecycline's effectiveness in the treatment bacteremia is unclear.

In addition, as no published studies have addressed its activity among seriously ill patients, tigecycline is considered a second‐line or third‐line agent for SSTI and complicated intraabdominal infections. Evidence for use of tigecycline for the treatment of UTIs is lacking and, as a rule, its use should be limited to scenarios in which alternatives for the proven or suspected pathogens do not exist.

The urine isolate is identified as Escherichia coli. You review the susceptibility profile and determine that this isolate is an ESBL‐producing strain. In addition, the patient's isolate demonstrates resistance to the fluoroquinolones and trimethoprim‐sulfamethoxazole. You consider other options for treatment of this ESBL‐producing E. coli.

According to national surveillance data, more than 20% of Klebsiella isolates in U.S. intensive care units produced ESBLs in 2003, a 47% increase when compared to 1998.39 Bloodstream infections due to ESBL‐producing isolates have led to increased length of hospital stay,60, 61 increased hospital costs,4 improper antibiotic use,5 and, most notably, increased mortality.61‐63 Of concern, ESBLs have been demonstrated within community Enterobacteriaceae isolates, most notably due to CTX‐M beta‐lactamase production among E. coli. In addition to ESBL production, these community E. coli isolates tend to express fluoroquinolone and trimethoprim‐sulfamethoxazole resistance.64 Carbapenems remain the mainstay of therapy for serious infections due to ESBL‐producing organisms. The once‐daily dosing of ertapenem makes this agent an attractive alternative for outpatient management.

Ertapenem

Ertapenem (Invanz) obtained FDA approval for use in the United States in 2001 and in the European Union in 2002.65 Similar to doripenem, ertapenem blocks cell wall synthesis by binding to specific penicillin‐binding proteins (PBPs).

Ertapenem has activity against numerous gram‐positive and gram‐negative bacteria as well as some anaerobic microorganisms. The FDA‐approved indications include complicated intraabdominal infections, cSSTIs, acute pelvic infections, complicated UTIs, and community‐acquired pneumonias (Table 1).66 Of note, in contrast to other carabapenems, ertapenem does not have activity against Pseudomonas aeruginosa or Acinetobacter spp.67

Ertapenem is approved as a single daily dose of 1 g and can be administered intravenously or intramuscularly. Changes in dosing must also be considered for critically ill patients. When administered to patients with VAP, ertapenem achieved a lower maximum concentration and area under the curve.68 In such patients, it is recommended that the dosage interval be decreased or that a continuous infusion of ertapenem be administered.

The patient's symptoms improve on meropenem. A peripherally‐inserted central catheter is placed for the administration of intravenous antibiotics at home. You prescribe ertapenem (1 g/day) for the remainder of a 14‐day course.

Linezolid

Linezolid (Zyvox), an oxazolidinone approved in 2000, has been touted for its oral bioavailability, twice‐daily dosing, gram‐positive coverage, and unique mechanism of action. Like several other antimicrobials, linezolid inhibits bacterial protein synthesis. The drug binds to the 50S ribosomal subunit near its site of interaction with the 30S subunit, preventing formation of the 70S initiation complex.5 This site of action on the 50S subunit is unique to linezolid; as a result, cross‐resistance between linezolid and other antimicrobials that act at the 50S subunit (eg, chloramphenicol, macrolides, aminoglycosides, and tetracycline) does not occur.6

The oxazolidinones have excellent bacteriostatic activity against all pathogenic gram‐positive bacteria. The U.S. Food and Drug Administration (FDA) approved linezolid for the treatment of serious infections due to vancomycin‐resistant enterococci (VRE), including bacteremia, complicated skin and soft‐tissue infections (cSSTIs) due to Staphylococcus aureus (including MRSA), and nosocomial pneumonia due to Staphylococcus aureus (including MRSA) or penicillin‐susceptible Streptococcus pneumoniae (Table 1).

In retrospective analyses of SSTIs due to MRSA, linezolid was as effective as vancomycin, resulting in higher clinical cure rates and shorter hospitalizations.7 As a result, linezolid has established a role in the treatment of community‐acquired MRSA SSTIs. Evidence limited to case reports and case series suggest that linezolid may also have a role in the treatment of bone and joint infections. In these cases, linezolid was often used because treatment with other agents had failed, the administration of other antibiotics was not indicated due to resistance patterns, the patient refused intravenous therapy, or the patient did not tolerate vancomycin. When such conditions exist, linezolid may be a consideration in cases of osteomyelitis or prosthetic joint infection.8

Potential side effects of linezolid may limit its use, especially for patients who require prolonged therapy (Table 1). Of note, as a reversible, relatively weak nonselective inhibitor of monoamine oxidase, linezolid may interact with adrenergic and serotonergic agents. Concomitant of a serotonin agent such as a selective serotonin‐reuptake inhibitor (SSRI) and linezolid should be approached with caution. Subsequent serotonin syndrome is characterized by autonomic dysfunction (eg, diaphoresis, tachycardia, hypertension) and neuromuscular hyperactivity (eg, muscle rigidity, clonus, hyperreflexia). Though infrequent, cases of reversible myelosuppression have been reported with linezolid use.9 Patients who will receive this drug for more than 2 weeks should be monitored for myelosuppression with a weekly complete blood count. Isolated reports suggest that the prolonged administration of linezolid (>28 days) may be associated with peripheral neuropathy and optic neuropathy. While prompt discontinuation of the drug often results in resolution of symptoms, peripheral or optic nerve injury can be permanent. The mechanism of injury is unclear, though mitochondrial toxicity is suspected.10

Daptomycin

Daptomycin (Cubicin), a cyclic lipopeptide, was discovered in the early 1980s, but skeletal muscle toxicity led to the discontinuation of early clinical trials. When a change from twice‐daily to once‐daily dosing in 2003 resulted in fewer adverse events, the FDA approved daptomycin to treat complicated skin and skin‐structure infections.11 Daptomycin binds to the cell membrane via a calcium‐dependent process, eventually disrupting the cell membrane potential. The bactericidal effect is limited to gram‐positive organisms.12

Daptomycin is effective against almost all gram‐positive organisms including methicillin‐susceptible Staphylococcus aureus (MSSA), MRSA, and VRE.12 As a result, it has FDA approval for the treatment of cSSTIs. While beta‐lactams remain the standard of care for MSSA bacteremia, daptomycin has FDA approval for bloodstream infections and right‐sided endocarditis due to MSSA or MRSA (Table 1).13 Daptomycin has poor penetration into alveolar fluid14 and is inhibited by pulmonary surfactants; as a consequence, it is not indicated for patients with pneumonia.15

Of note, daptomycin is mainly excreted via the kidneys and should be dose‐adjusted for patients with a creatinine clearance <30 mL/minute. A reversible myopathy may occur with daptomycin, requiring intermittent monitoring of creatinine kinase if prolonged use is anticipated. Caution should be used with the coadministration of medications that can also cause a myopathy, such as statins.

Tigecycline

Tigecycline (Tygacil) was approved for use by the FDA in 2005. The first in a class of new tetracycline analogs, the glycylcyclines, tigecycline is notable for its activity against several multidrug‐resistant (MDR) organisms, including MRSA, VRE, and Enterobacteriaceae carrying extended‐spectrum beta‐lactamases (ESBL). Tigecycline impairs bacterial protein synthesis by binding to the 30S ribosomal subunit. Due to steric hindrance from an N‐alkyl‐glycylamido group at position 9, tigecycline cannot be removed by most bacterial efflux mechanisms.16

Tigecycline has been approved for the therapy of cSSTIs, including those due to MSSA and MRSA. In a pooled analysis of 2 international, multicenter, phase III randomized, double‐blind trials, tigecycline was not inferior to vancomycin plus aztreonam in the treatment of cSSTIs. Of note, MRSA eradication rates were similar between patients treated with tigecycline and vancomycin plus aztreonam (78.1% and 75.8%, respectively).17

Dalbavancin

Dalbavancin (Zeven), a new, semisynthetic lipoglycopeptide, was approved by the FDA in late 2007; however, it has not been cleared for marketing. Though dalbavancin is derived from teicoplanin, its lipophilic anchor to the bacterial cell membrane makes the drug more potent than its predecessor. Dalbavancin interferes with bacterial cell wall synthesis by binding to the C‐terminal D‐alanyl‐D alanine of the growing peptidoglycan chains.18 Enhanced pharmacokinetic properties of dalbavancin (half‐life 149‐250 hours) allow it to be dosed once‐weekly, a novel concept in antimicrobial use.19

Like other glycopeptides, dalbavancin maintains in vitro activity against most gram‐positive aerobic organisms, including MRSA and penicillin‐susceptible and penicillin‐resistant strains of Streptococcus pneumoniae. Notably, when compared to vancomycin in vitro, the agent is more active against Enterococcus faecium and Enterococcus faecalis isolates. In a recent phase III double‐blind trial, dalbavancin was compared to linezolid for the treatment of cSSTIs. Dalbavancin was not inferior to linezolid (clinical success rate 90% vs. 92%). Of note, 51% of study patients with SSTI had infection due to MRSA. Microbiological response to dalbavancin paralleled the clinical success rate; MRSA eradication rates after dalbavancin and linezolid were 91% and 89%, respectively.20

Given its once‐weekly dosing, dalbavancin may be an attractive agent in the outpatient treatment of gram‐positive bacteremia. In a phase II study, dalbavancin administered as a single 1‐g dose, followed by a 500‐mg dose 1 week later, was comparable to 14 days of vancomycin for the treatment of catheter‐related bloodstream infections (CRBSI) due to coagulase‐negative staphylococci or S. aureus (including MRSA).21 Phase III studies are underway. At present, there is no evidence to support the use of dalbavancin for the treatment of pneumonia or bone and joint infections.

Despite the administration of vancomycin, the patient continues to experience fever and chills. Blood cultures drawn in the emergency department are now growing Enterococcus species. You review the patient's medical record and notice that she was colonized with VRE on a prior admission. You consider the antibiotic options for serious infections due to VRE.

Though rates of VRE have remained fairly stable in recent years,22 the pathogen continues to present a challenge to hospital epidemiologists. A national survey in 2004 suggested that nearly 30% of enterococci in U.S. intensive care units display vancomycin resistance.1 Additional U.S. surveillance data reveals that VRE accounts for 10% to 26% of enterococci hospital‐wide.23, 24 In 2005, a meta‐analysis noted that bloodstream infections due to VRE resulted in higher mortality rates than those due to vancomycin‐susceptible enterococci.25 This discrepancy is most evident among neutropenia patients.26 Unfortunately, the options for the treatment of serious infections due to VRE are limited. The advantages and disadvantages of linezolid, quinupristin‐dalfopristin, tigecycline, and daptomycin in the treatment for VRE are discussed below.

Linezolid

Currently, linezolid is the only oral drug that is FDA‐approved for the treatment of infections due to VRE, including bacteremia. Notably, linezolid therapy resulted in the cure of 77% of 22 cases of vancomycin‐resistant enterococcal endocarditis.27 Current guidelines by the Infectious Disease Society of America (IDSA) support the use of linezolid in cases of endocarditis due to ampicillin‐resistant and vancomycin‐resistant Enterococcus faecium.28 Unfortunately, recent reports highlight the emergence of linezolid‐resistant VRE,29 suggesting use of this drug should be limited to circumstances in which other alternatives do not exist.

Quinupristin‐Dalfopristin

Quinupristin‐dalfopristin (Synercid) was approved by the FDA in 1999. It is used in the treatment of infections caused by gram‐positive organisms and is a combination of 2 semisynthetic pristinamycin derivatives. They diffuse into bacteria and bind to different areas on the 50S ribosomal subunit, thereby inhibiting protein synthesis. Individually, quinupristin and dalfopristin are bacteriostatic but together they are bactericidal.30

Quinupristin‐dalfopristin has activity against Staphylococcus aureus (including MRSA), Streptococcus pneumoniae, gram‐positive anaerobes, and vancomycin‐sensitive and resistant Enterococcus faecium. It has little activity against Enterococcus faecalis.31 FDA‐approved uses of quinupristin‐dalfopristin are limited, but include the treatment of serious infections caused by vancomycin‐resistant E. faecium (VREF).32 In a study of 396 patients with VREF the clinical success rate of quinupristin‐dalfopristin was 73.6%.33 The drug also has FDA approval for the use in cSSTIs due to group A streptococci or MSSA.32 The use of this agent is limited due to its toxicity profile. In cases of serious VRE‐related infection, quinupristin‐dalfopristin is often only utilized if linezolid cannot be tolerated.

Daptomycin

In vitro studies suggest that daptomycin is active against enterococci, including vancomycin‐resistant isolates.34 However, clinical data on the use of this agent in the treatment of infections due to VRE are lacking. FDA approval for the use of daptomycin in cSSTI included the treatment of 45 patients infected with Enterococcus faecalis.13 In addition, several reports have detailed the successful treatment of VRE bloodstream infections with daptomycin,35, 36 including a case series of VRE endocarditis.37 To determine the role of this agent in the treatment of invasive infections due to VRE, further study is needed.

You decide to discontinue vancomycin and administer linezolid. The patient's vascular catheter is removed; catheter‐tip cultures grow >1000 colonies of VRE. Blood cultures the following day are negative and a new catheter is placed. You ask the patient to continue oral linezolid to complete a 2‐week course. A review of her medication list reveals that she is not taking SSRIs or monoamine oxidase inhibitors (MAOIs).

While linezolid has retained its FDA indication for VRE bacteremia, empiric use in suspected cases of CRBSI or catheter site infection is not advised. In an open‐label trial among seriously ill patients with intravascular catheter‐related infections, linezolid use was associated with a higher mortality when compared to vancomycin/oxacillin. Interestingly, mortality among linezolid‐treated patients included those with CRBSI due to gram‐negative pathogens, due to both gram‐negative and gram‐positive pathogens, or due to an identifiable pathogen; mortality rates did not differ among patients with gram‐positive infections only.38

Doripenem

In October 2007, the FDA approved the use of doripenem (Doribax), a much‐anticipated carbapenem. In structure, doripenem resembles meropenem and does not require a renal dehydropeptidase I inhibitor (eg, cilastatin).44 Similar to other beta‐lactams, doripenem binds to penicillin‐binding proteins (PBPs), inhibiting PBP‐directed cell wall synthesis.

Like imipenem and meropenem, doripenem has broad‐spectrum antimicrobial activity. It demonstrates in vitro activity against most gram‐positive pathogens including MSSA and ampicillin‐sensitive enterococci. Doripenem also has in vitro activity against most gram‐negative pathogens (including ESBL‐producing Enterobacteriaceae) and most anaerobes, including Bacteriodes fragilis. Most notably, when compared to other carbapenems, doripenem has demonstrated better in vitro activity against Pseudomonas aeruginosa.45 However, clinical implications of this in vitro activity are unclear.

When compared to meropenem or levofloxacin for the treatment of complicated UTIs, doripenem is an effective alternative. Clinical response rates among affected patients were 95% to 96% with doripenem, 89% with meropenem, and 90% with levofloxacin.46, 47 Doripenem was not inferior to meropenem in patients with serious lower respiratory tract infections, and comparable to imipenem‐cilastin and pipercillin‐tazobactam for the treatment of nosocomial or ventilator‐associated pneumonia (VAP).48, 49 Finally, for the treatment of complicated intraabdominal infections, doripenem was not inferior to meropenem; both drugs achieved microbiologic cure rates of >84%.50

Currently, doripenem is FDA‐approved for the treatment of complicated intraabdominal infections (eg, appendicitis, pancreatitis, cholecystitis, peritonitis) and complicated lower UTIs or pyelonephritis (Table 1). Given its expanded spectrum of activity, use of doripenem should be limited to circumstances in which a MDR pathogen is highly suspected or confirmed.

Colistin

Colistin (Coly‐Mycin M) falls within the family of polymyxin antibiotics, which were discovered in 1947. Colistin has been available for almost 50 years for the treatment of infections caused by gram‐negative bacteria, including Pseudomonas spp. However, early use of colistin was associated with significant nephrotoxicity. Its use decreased markedly with the advent of new antibiotics that had the same antimicrobial spectrum and a better side effect profile. With the emergence of MDR gram‐negative bacteria, colistin has returned to limited clinical use.51 As a polymyxin, colistin is a cell membrane detergent. It disrupts the cell membrane, causing leakage of bacterial cell content and ultimately cell death.52

Colistin has bactericidal activity against most gram‐negative bacteria including Acinetobacter spp, and members of the family Enterobacteriaceae (eg, Klebsiella spp, Escherichia coli, Enterobacter spp), including those producing ESBLs.53 Colistin is not active against several predominant gram‐negative pathogens including Proteus spp, Providencia spp, or Serratia spp (Table 1).

In 2007, several studies suggested that colistin monotherapy was effective for patients with VAP due to MDR P. aeruginosa or A. baumannii isolate.54, 55 A third trial that year suggested that colistin may have a role in the treatment of MDR P. aeruginosa among neutropenic patients. In that study, infected patients receiving colistin monotherapy experienced higher rates of clinical and microbiologic response than those receiving other antipseudomonal agents (eg, beta‐lactams or fluoroquinolones if active against the isolate).56 While uncontrolled studies suggest that the use of colistin in combination with other antimicrobials (including carbapenems, ampicillin‐sulbactam, aminoglycosides, and rifampin) may have some success in the treatment of VAP due to MDR A. baumannii,57, 58 further trials are needed.

Currently, colistin has FDA approval only for the treatment of acute infections due to gram‐negative bacteria that have demonstrated susceptibility to the drug and is therefore administered on a case by case basis. Although it has been used via the inhalation route to treat infections in cystic fibrosis patients, colistin does not have FDA approval for this indication.

Tigecycline

Tigecycline is approved for the treatment of complicated intraabdominal infections based on the results of 2 international, multicenter, phase III, randomized, double‐blind trials. In this pooled analysis, tigecycline was as effective and as safe as imipenem/cilastatin. Notably, study patients were not severely ill (baseline APACHE II score of 6.0).59 FDA approval suggests tigecycline use be focused on intraabdominal infections due to members of the family Enterobacteriaceae (eg, Klebsiella spp, Escherichia coli, Enterobacter spp), including those producing ESBLs, vancomycin‐sensitive enterococci, and/or MSSA. Notably, tigecycline lacks significant in vitro activity against Pseudomonas spp, Proteus spp, or Providencia spp. It has demonstrated in vitro activity against MDR strains of Acinetobacter spp (Table 1).

Given its bacteriostatic activity, tigecycline's effectiveness in the treatment bacteremia is unclear.

In addition, as no published studies have addressed its activity among seriously ill patients, tigecycline is considered a second‐line or third‐line agent for SSTI and complicated intraabdominal infections. Evidence for use of tigecycline for the treatment of UTIs is lacking and, as a rule, its use should be limited to scenarios in which alternatives for the proven or suspected pathogens do not exist.

The urine isolate is identified as Escherichia coli. You review the susceptibility profile and determine that this isolate is an ESBL‐producing strain. In addition, the patient's isolate demonstrates resistance to the fluoroquinolones and trimethoprim‐sulfamethoxazole. You consider other options for treatment of this ESBL‐producing E. coli.

According to national surveillance data, more than 20% of Klebsiella isolates in U.S. intensive care units produced ESBLs in 2003, a 47% increase when compared to 1998.39 Bloodstream infections due to ESBL‐producing isolates have led to increased length of hospital stay,60, 61 increased hospital costs,4 improper antibiotic use,5 and, most notably, increased mortality.61‐63 Of concern, ESBLs have been demonstrated within community Enterobacteriaceae isolates, most notably due to CTX‐M beta‐lactamase production among E. coli. In addition to ESBL production, these community E. coli isolates tend to express fluoroquinolone and trimethoprim‐sulfamethoxazole resistance.64 Carbapenems remain the mainstay of therapy for serious infections due to ESBL‐producing organisms. The once‐daily dosing of ertapenem makes this agent an attractive alternative for outpatient management.

Ertapenem

Ertapenem (Invanz) obtained FDA approval for use in the United States in 2001 and in the European Union in 2002.65 Similar to doripenem, ertapenem blocks cell wall synthesis by binding to specific penicillin‐binding proteins (PBPs).

Ertapenem has activity against numerous gram‐positive and gram‐negative bacteria as well as some anaerobic microorganisms. The FDA‐approved indications include complicated intraabdominal infections, cSSTIs, acute pelvic infections, complicated UTIs, and community‐acquired pneumonias (Table 1).66 Of note, in contrast to other carabapenems, ertapenem does not have activity against Pseudomonas aeruginosa or Acinetobacter spp.67

Ertapenem is approved as a single daily dose of 1 g and can be administered intravenously or intramuscularly. Changes in dosing must also be considered for critically ill patients. When administered to patients with VAP, ertapenem achieved a lower maximum concentration and area under the curve.68 In such patients, it is recommended that the dosage interval be decreased or that a continuous infusion of ertapenem be administered.

The patient's symptoms improve on meropenem. A peripherally‐inserted central catheter is placed for the administration of intravenous antibiotics at home. You prescribe ertapenem (1 g/day) for the remainder of a 14‐day course.

Linezolid

Linezolid (Zyvox), an oxazolidinone approved in 2000, has been touted for its oral bioavailability, twice‐daily dosing, gram‐positive coverage, and unique mechanism of action. Like several other antimicrobials, linezolid inhibits bacterial protein synthesis. The drug binds to the 50S ribosomal subunit near its site of interaction with the 30S subunit, preventing formation of the 70S initiation complex.5 This site of action on the 50S subunit is unique to linezolid; as a result, cross‐resistance between linezolid and other antimicrobials that act at the 50S subunit (eg, chloramphenicol, macrolides, aminoglycosides, and tetracycline) does not occur.6

The oxazolidinones have excellent bacteriostatic activity against all pathogenic gram‐positive bacteria. The U.S. Food and Drug Administration (FDA) approved linezolid for the treatment of serious infections due to vancomycin‐resistant enterococci (VRE), including bacteremia, complicated skin and soft‐tissue infections (cSSTIs) due to Staphylococcus aureus (including MRSA), and nosocomial pneumonia due to Staphylococcus aureus (including MRSA) or penicillin‐susceptible Streptococcus pneumoniae (Table 1).

In retrospective analyses of SSTIs due to MRSA, linezolid was as effective as vancomycin, resulting in higher clinical cure rates and shorter hospitalizations.7 As a result, linezolid has established a role in the treatment of community‐acquired MRSA SSTIs. Evidence limited to case reports and case series suggest that linezolid may also have a role in the treatment of bone and joint infections. In these cases, linezolid was often used because treatment with other agents had failed, the administration of other antibiotics was not indicated due to resistance patterns, the patient refused intravenous therapy, or the patient did not tolerate vancomycin. When such conditions exist, linezolid may be a consideration in cases of osteomyelitis or prosthetic joint infection.8

Potential side effects of linezolid may limit its use, especially for patients who require prolonged therapy (Table 1). Of note, as a reversible, relatively weak nonselective inhibitor of monoamine oxidase, linezolid may interact with adrenergic and serotonergic agents. Concomitant of a serotonin agent such as a selective serotonin‐reuptake inhibitor (SSRI) and linezolid should be approached with caution. Subsequent serotonin syndrome is characterized by autonomic dysfunction (eg, diaphoresis, tachycardia, hypertension) and neuromuscular hyperactivity (eg, muscle rigidity, clonus, hyperreflexia). Though infrequent, cases of reversible myelosuppression have been reported with linezolid use.9 Patients who will receive this drug for more than 2 weeks should be monitored for myelosuppression with a weekly complete blood count. Isolated reports suggest that the prolonged administration of linezolid (>28 days) may be associated with peripheral neuropathy and optic neuropathy. While prompt discontinuation of the drug often results in resolution of symptoms, peripheral or optic nerve injury can be permanent. The mechanism of injury is unclear, though mitochondrial toxicity is suspected.10

Daptomycin

Daptomycin (Cubicin), a cyclic lipopeptide, was discovered in the early 1980s, but skeletal muscle toxicity led to the discontinuation of early clinical trials. When a change from twice‐daily to once‐daily dosing in 2003 resulted in fewer adverse events, the FDA approved daptomycin to treat complicated skin and skin‐structure infections.11 Daptomycin binds to the cell membrane via a calcium‐dependent process, eventually disrupting the cell membrane potential. The bactericidal effect is limited to gram‐positive organisms.12

Daptomycin is effective against almost all gram‐positive organisms including methicillin‐susceptible Staphylococcus aureus (MSSA), MRSA, and VRE.12 As a result, it has FDA approval for the treatment of cSSTIs. While beta‐lactams remain the standard of care for MSSA bacteremia, daptomycin has FDA approval for bloodstream infections and right‐sided endocarditis due to MSSA or MRSA (Table 1).13 Daptomycin has poor penetration into alveolar fluid14 and is inhibited by pulmonary surfactants; as a consequence, it is not indicated for patients with pneumonia.15

Of note, daptomycin is mainly excreted via the kidneys and should be dose‐adjusted for patients with a creatinine clearance <30 mL/minute. A reversible myopathy may occur with daptomycin, requiring intermittent monitoring of creatinine kinase if prolonged use is anticipated. Caution should be used with the coadministration of medications that can also cause a myopathy, such as statins.

Tigecycline

Tigecycline (Tygacil) was approved for use by the FDA in 2005. The first in a class of new tetracycline analogs, the glycylcyclines, tigecycline is notable for its activity against several multidrug‐resistant (MDR) organisms, including MRSA, VRE, and Enterobacteriaceae carrying extended‐spectrum beta‐lactamases (ESBL). Tigecycline impairs bacterial protein synthesis by binding to the 30S ribosomal subunit. Due to steric hindrance from an N‐alkyl‐glycylamido group at position 9, tigecycline cannot be removed by most bacterial efflux mechanisms.16

Tigecycline has been approved for the therapy of cSSTIs, including those due to MSSA and MRSA. In a pooled analysis of 2 international, multicenter, phase III randomized, double‐blind trials, tigecycline was not inferior to vancomycin plus aztreonam in the treatment of cSSTIs. Of note, MRSA eradication rates were similar between patients treated with tigecycline and vancomycin plus aztreonam (78.1% and 75.8%, respectively).17

Dalbavancin

Dalbavancin (Zeven), a new, semisynthetic lipoglycopeptide, was approved by the FDA in late 2007; however, it has not been cleared for marketing. Though dalbavancin is derived from teicoplanin, its lipophilic anchor to the bacterial cell membrane makes the drug more potent than its predecessor. Dalbavancin interferes with bacterial cell wall synthesis by binding to the C‐terminal D‐alanyl‐D alanine of the growing peptidoglycan chains.18 Enhanced pharmacokinetic properties of dalbavancin (half‐life 149‐250 hours) allow it to be dosed once‐weekly, a novel concept in antimicrobial use.19

Like other glycopeptides, dalbavancin maintains in vitro activity against most gram‐positive aerobic organisms, including MRSA and penicillin‐susceptible and penicillin‐resistant strains of Streptococcus pneumoniae. Notably, when compared to vancomycin in vitro, the agent is more active against Enterococcus faecium and Enterococcus faecalis isolates. In a recent phase III double‐blind trial, dalbavancin was compared to linezolid for the treatment of cSSTIs. Dalbavancin was not inferior to linezolid (clinical success rate 90% vs. 92%). Of note, 51% of study patients with SSTI had infection due to MRSA. Microbiological response to dalbavancin paralleled the clinical success rate; MRSA eradication rates after dalbavancin and linezolid were 91% and 89%, respectively.20

Given its once‐weekly dosing, dalbavancin may be an attractive agent in the outpatient treatment of gram‐positive bacteremia. In a phase II study, dalbavancin administered as a single 1‐g dose, followed by a 500‐mg dose 1 week later, was comparable to 14 days of vancomycin for the treatment of catheter‐related bloodstream infections (CRBSI) due to coagulase‐negative staphylococci or S. aureus (including MRSA).21 Phase III studies are underway. At present, there is no evidence to support the use of dalbavancin for the treatment of pneumonia or bone and joint infections.

Despite the administration of vancomycin, the patient continues to experience fever and chills. Blood cultures drawn in the emergency department are now growing Enterococcus species. You review the patient's medical record and notice that she was colonized with VRE on a prior admission. You consider the antibiotic options for serious infections due to VRE.

Though rates of VRE have remained fairly stable in recent years,22 the pathogen continues to present a challenge to hospital epidemiologists. A national survey in 2004 suggested that nearly 30% of enterococci in U.S. intensive care units display vancomycin resistance.1 Additional U.S. surveillance data reveals that VRE accounts for 10% to 26% of enterococci hospital‐wide.23, 24 In 2005, a meta‐analysis noted that bloodstream infections due to VRE resulted in higher mortality rates than those due to vancomycin‐susceptible enterococci.25 This discrepancy is most evident among neutropenia patients.26 Unfortunately, the options for the treatment of serious infections due to VRE are limited. The advantages and disadvantages of linezolid, quinupristin‐dalfopristin, tigecycline, and daptomycin in the treatment for VRE are discussed below.

Linezolid

Currently, linezolid is the only oral drug that is FDA‐approved for the treatment of infections due to VRE, including bacteremia. Notably, linezolid therapy resulted in the cure of 77% of 22 cases of vancomycin‐resistant enterococcal endocarditis.27 Current guidelines by the Infectious Disease Society of America (IDSA) support the use of linezolid in cases of endocarditis due to ampicillin‐resistant and vancomycin‐resistant Enterococcus faecium.28 Unfortunately, recent reports highlight the emergence of linezolid‐resistant VRE,29 suggesting use of this drug should be limited to circumstances in which other alternatives do not exist.

Quinupristin‐Dalfopristin

Quinupristin‐dalfopristin (Synercid) was approved by the FDA in 1999. It is used in the treatment of infections caused by gram‐positive organisms and is a combination of 2 semisynthetic pristinamycin derivatives. They diffuse into bacteria and bind to different areas on the 50S ribosomal subunit, thereby inhibiting protein synthesis. Individually, quinupristin and dalfopristin are bacteriostatic but together they are bactericidal.30

Quinupristin‐dalfopristin has activity against Staphylococcus aureus (including MRSA), Streptococcus pneumoniae, gram‐positive anaerobes, and vancomycin‐sensitive and resistant Enterococcus faecium. It has little activity against Enterococcus faecalis.31 FDA‐approved uses of quinupristin‐dalfopristin are limited, but include the treatment of serious infections caused by vancomycin‐resistant E. faecium (VREF).32 In a study of 396 patients with VREF the clinical success rate of quinupristin‐dalfopristin was 73.6%.33 The drug also has FDA approval for the use in cSSTIs due to group A streptococci or MSSA.32 The use of this agent is limited due to its toxicity profile. In cases of serious VRE‐related infection, quinupristin‐dalfopristin is often only utilized if linezolid cannot be tolerated.

Daptomycin

In vitro studies suggest that daptomycin is active against enterococci, including vancomycin‐resistant isolates.34 However, clinical data on the use of this agent in the treatment of infections due to VRE are lacking. FDA approval for the use of daptomycin in cSSTI included the treatment of 45 patients infected with Enterococcus faecalis.13 In addition, several reports have detailed the successful treatment of VRE bloodstream infections with daptomycin,35, 36 including a case series of VRE endocarditis.37 To determine the role of this agent in the treatment of invasive infections due to VRE, further study is needed.

You decide to discontinue vancomycin and administer linezolid. The patient's vascular catheter is removed; catheter‐tip cultures grow >1000 colonies of VRE. Blood cultures the following day are negative and a new catheter is placed. You ask the patient to continue oral linezolid to complete a 2‐week course. A review of her medication list reveals that she is not taking SSRIs or monoamine oxidase inhibitors (MAOIs).

While linezolid has retained its FDA indication for VRE bacteremia, empiric use in suspected cases of CRBSI or catheter site infection is not advised. In an open‐label trial among seriously ill patients with intravascular catheter‐related infections, linezolid use was associated with a higher mortality when compared to vancomycin/oxacillin. Interestingly, mortality among linezolid‐treated patients included those with CRBSI due to gram‐negative pathogens, due to both gram‐negative and gram‐positive pathogens, or due to an identifiable pathogen; mortality rates did not differ among patients with gram‐positive infections only.38

Doripenem

In October 2007, the FDA approved the use of doripenem (Doribax), a much‐anticipated carbapenem. In structure, doripenem resembles meropenem and does not require a renal dehydropeptidase I inhibitor (eg, cilastatin).44 Similar to other beta‐lactams, doripenem binds to penicillin‐binding proteins (PBPs), inhibiting PBP‐directed cell wall synthesis.

Like imipenem and meropenem, doripenem has broad‐spectrum antimicrobial activity. It demonstrates in vitro activity against most gram‐positive pathogens including MSSA and ampicillin‐sensitive enterococci. Doripenem also has in vitro activity against most gram‐negative pathogens (including ESBL‐producing Enterobacteriaceae) and most anaerobes, including Bacteriodes fragilis. Most notably, when compared to other carbapenems, doripenem has demonstrated better in vitro activity against Pseudomonas aeruginosa.45 However, clinical implications of this in vitro activity are unclear.

When compared to meropenem or levofloxacin for the treatment of complicated UTIs, doripenem is an effective alternative. Clinical response rates among affected patients were 95% to 96% with doripenem, 89% with meropenem, and 90% with levofloxacin.46, 47 Doripenem was not inferior to meropenem in patients with serious lower respiratory tract infections, and comparable to imipenem‐cilastin and pipercillin‐tazobactam for the treatment of nosocomial or ventilator‐associated pneumonia (VAP).48, 49 Finally, for the treatment of complicated intraabdominal infections, doripenem was not inferior to meropenem; both drugs achieved microbiologic cure rates of >84%.50

Currently, doripenem is FDA‐approved for the treatment of complicated intraabdominal infections (eg, appendicitis, pancreatitis, cholecystitis, peritonitis) and complicated lower UTIs or pyelonephritis (Table 1). Given its expanded spectrum of activity, use of doripenem should be limited to circumstances in which a MDR pathogen is highly suspected or confirmed.

Colistin

Colistin (Coly‐Mycin M) falls within the family of polymyxin antibiotics, which were discovered in 1947. Colistin has been available for almost 50 years for the treatment of infections caused by gram‐negative bacteria, including Pseudomonas spp. However, early use of colistin was associated with significant nephrotoxicity. Its use decreased markedly with the advent of new antibiotics that had the same antimicrobial spectrum and a better side effect profile. With the emergence of MDR gram‐negative bacteria, colistin has returned to limited clinical use.51 As a polymyxin, colistin is a cell membrane detergent. It disrupts the cell membrane, causing leakage of bacterial cell content and ultimately cell death.52

Colistin has bactericidal activity against most gram‐negative bacteria including Acinetobacter spp, and members of the family Enterobacteriaceae (eg, Klebsiella spp, Escherichia coli, Enterobacter spp), including those producing ESBLs.53 Colistin is not active against several predominant gram‐negative pathogens including Proteus spp, Providencia spp, or Serratia spp (Table 1).

In 2007, several studies suggested that colistin monotherapy was effective for patients with VAP due to MDR P. aeruginosa or A. baumannii isolate.54, 55 A third trial that year suggested that colistin may have a role in the treatment of MDR P. aeruginosa among neutropenic patients. In that study, infected patients receiving colistin monotherapy experienced higher rates of clinical and microbiologic response than those receiving other antipseudomonal agents (eg, beta‐lactams or fluoroquinolones if active against the isolate).56 While uncontrolled studies suggest that the use of colistin in combination with other antimicrobials (including carbapenems, ampicillin‐sulbactam, aminoglycosides, and rifampin) may have some success in the treatment of VAP due to MDR A. baumannii,57, 58 further trials are needed.

Currently, colistin has FDA approval only for the treatment of acute infections due to gram‐negative bacteria that have demonstrated susceptibility to the drug and is therefore administered on a case by case basis. Although it has been used via the inhalation route to treat infections in cystic fibrosis patients, colistin does not have FDA approval for this indication.

Tigecycline

Tigecycline is approved for the treatment of complicated intraabdominal infections based on the results of 2 international, multicenter, phase III, randomized, double‐blind trials. In this pooled analysis, tigecycline was as effective and as safe as imipenem/cilastatin. Notably, study patients were not severely ill (baseline APACHE II score of 6.0).59 FDA approval suggests tigecycline use be focused on intraabdominal infections due to members of the family Enterobacteriaceae (eg, Klebsiella spp, Escherichia coli, Enterobacter spp), including those producing ESBLs, vancomycin‐sensitive enterococci, and/or MSSA. Notably, tigecycline lacks significant in vitro activity against Pseudomonas spp, Proteus spp, or Providencia spp. It has demonstrated in vitro activity against MDR strains of Acinetobacter spp (Table 1).

Given its bacteriostatic activity, tigecycline's effectiveness in the treatment bacteremia is unclear.

In addition, as no published studies have addressed its activity among seriously ill patients, tigecycline is considered a second‐line or third‐line agent for SSTI and complicated intraabdominal infections. Evidence for use of tigecycline for the treatment of UTIs is lacking and, as a rule, its use should be limited to scenarios in which alternatives for the proven or suspected pathogens do not exist.

The urine isolate is identified as Escherichia coli. You review the susceptibility profile and determine that this isolate is an ESBL‐producing strain. In addition, the patient's isolate demonstrates resistance to the fluoroquinolones and trimethoprim‐sulfamethoxazole. You consider other options for treatment of this ESBL‐producing E. coli.

According to national surveillance data, more than 20% of Klebsiella isolates in U.S. intensive care units produced ESBLs in 2003, a 47% increase when compared to 1998.39 Bloodstream infections due to ESBL‐producing isolates have led to increased length of hospital stay,60, 61 increased hospital costs,4 improper antibiotic use,5 and, most notably, increased mortality.61‐63 Of concern, ESBLs have been demonstrated within community Enterobacteriaceae isolates, most notably due to CTX‐M beta‐lactamase production among E. coli. In addition to ESBL production, these community E. coli isolates tend to express fluoroquinolone and trimethoprim‐sulfamethoxazole resistance.64 Carbapenems remain the mainstay of therapy for serious infections due to ESBL‐producing organisms. The once‐daily dosing of ertapenem makes this agent an attractive alternative for outpatient management.

Ertapenem

Ertapenem (Invanz) obtained FDA approval for use in the United States in 2001 and in the European Union in 2002.65 Similar to doripenem, ertapenem blocks cell wall synthesis by binding to specific penicillin‐binding proteins (PBPs).

Ertapenem has activity against numerous gram‐positive and gram‐negative bacteria as well as some anaerobic microorganisms. The FDA‐approved indications include complicated intraabdominal infections, cSSTIs, acute pelvic infections, complicated UTIs, and community‐acquired pneumonias (Table 1).66 Of note, in contrast to other carabapenems, ertapenem does not have activity against Pseudomonas aeruginosa or Acinetobacter spp.67

Ertapenem is approved as a single daily dose of 1 g and can be administered intravenously or intramuscularly. Changes in dosing must also be considered for critically ill patients. When administered to patients with VAP, ertapenem achieved a lower maximum concentration and area under the curve.68 In such patients, it is recommended that the dosage interval be decreased or that a continuous infusion of ertapenem be administered.

The patient's symptoms improve on meropenem. A peripherally‐inserted central catheter is placed for the administration of intravenous antibiotics at home. You prescribe ertapenem (1 g/day) for the remainder of a 14‐day course.

A: Assess Housing Situation

Hospitals are not required to collect homelessness data. Where such data are collected, they are often inaccurate and internally inconsistent. In 1 survey of inpatients at a public hospital, over 25% of inpatients met strict criteria for homelessness.18 Effective discharge planning begins on admission.15 Hospitalists should ask specifically about housing status at the onset of hospitalization.19 This should be done in a direct, yet sensitive, manner. Given the recent economic downturn, increasing numbers of individuals and families are marginally housed; these patients may not show outward signs of homelessness and may not volunteer this information during the initial encounter. Be aware that some patients may become homeless during hospitalization,18 often as a result of inability to work or attend to financial matters during an inpatient stay. Resultant medical debt is a common cause of personal bankruptcy and homelessness following discharge.

Although it is accepted that a patient should be medically stable prior to discharge and that the decision to discharge should be based on medical, not financial considerations,20, 21 other standards for discharge vary from provider to provider. Hospitalists may be more cautious in discharging a patient without a stable home,4 yet facilitating outpatient follow‐up care or arranging transfer to a sheltered, structured environment can lengthen the hospital stay. Many cities offer formal medical respite care in a number of forms well described in the literature, including free‐standing2225 or shelter‐based units,25, 26 or skilled nursing facilities that contract directly with hospitals for short stays. One innovative model is the hoptel, or hospital hotel,27 a temporary housing facility proximate to the hospital to which self‐sufficient homeless patients may be discharged for recuperation. Some hospitals distribute motel vouchers at discharge.22, 25 All of these options provide opportunities for rest and recovery. Some facilities are staffed with a nurse who can check vital signs and provide wound care. Respite discharge may decrease early readmission and death rates23 and decrease repeat hospitalizations,24 particularly in human immunodeficiency virus (HIV) patients.

The National Health Care for the Homeless Council (NHCHC) maintains a national map and directory of respite care programs and services (see Table 2). Hospital providers should develop familiarity with all programs offered in a given geographic area and work closely with case managers and social workers to ensure that a homeless patient is considered for all programs for which he or she is eligible.

S: Screening and Prevention

In addition to treating the presenting condition, a hospitalist should evaluate homeless patients for disease processes common in indigence. A full physical examination, preferably unclothed, is also recommended.28 Homelessness markedly increases an individual's risk of chronic medical conditions. Reactive airway disease and chronic obstructive pulmonary disease (COPD) occur at higher rates as a result of tobacco and inhalational drug abuse. Diabetes mellitus, hypertension, and chronic liver and renal disease may remain undetected for years, with end‐organ effects commonly seen at presentation. Peripheral vascular disease is 10 to 15 times more frequent than in the general population.16, 28, 29 Tuberculosis, with prevalence rates greater than 30 times the national average,30 and other communicable diseases, including HIV, hepatitis B, and hepatitis C,16 are exceedingly prevalent and in some cases endemic.12 Infestations are also common. One out of 5 Health Care for the Homeless clients has an infectious or communicable disease.16 Up to two‐thirds of homeless individuals are HIV‐positive, with younger, Hispanic, and black populations at highest risk.29 Systemic infections may be traced to poor dentition, common in this population. Poor vision and skin conditions, also rampant,30 are easily overlooked in acute care encounters. The rate of drug and alcohol abuse in the homeless population may be as high as 8 times that of the general population.31 In 1 survey of homeless adults, the majority identified substance abuse as a major factor in ongoing homelessness.32 Mental illness prevalence in the may be as high as 80% to 95%33 and street violence is commonplace; more than 50% of homeless women have been sexually assaulted.11

There is a paucity of data on the effectiveness of inpatient health interventions for the homeless. In a 2005 systematic review of 45 studies evaluating the impact of various programs on homeless health, only 1 targeted an inpatient population.34 Furthermore, the literature suggests that street‐based or shelter‐based delivery of preventative services is most effective for undomiciled patients.35 Understanding these limitations, inpatient admission remains an opportunity to offer services that may decrease morbidity.

Evidence‐based preventative measures (Table 3) include vaccination against hepatitis A and hepatitis B in the intravenous drugusing homeless population. An accelerated hepatitis B vaccine administration schedule, with doses at 0, 7, and 21 days and a booster at 12 months, has been shown to increase completion rates.36 Drug users should be advised to utilize needle exchange programs and avoid sharing equipment. Sexually active homeless patients should be counseled regarding safe sexual practices and condom use. Consider tuberculosis screening with purified protein derivative (PPD) testing and spot sputum check, which have been shown in a shelter‐based intervention to detect an infection rate of 3.1%.37 Notably, within that cohort, symptom‐based screening was not found to be helpful. Influenza, diphtheria, tetanus, and pneumococcal vaccinations are also recommended, but have not been studied in regard to secondary decrease of infection rates in the homeless.

Admission to the hospital should be considered a treatable moment for substance abuse. In focus groups of homeless smokers, 76% of participants expressed intention to quit within 6 months and all were interested in using pharmacotherapy and behavioral treatments.38 In another study comparing admitted homeless vs. domiciled substance‐using adults, a higher percentage of the homeless patients were found to be in the action stage of change, as compared with the precontemplative or contemplative stage.39 When ongoing use is likely, recommended strategies include advocating for safer routes or patterns or use and praising small successes on the continuum to abstinence.40 Where such services are available, the hospitalist should coordinate with primary care providers (PCPs) and social workers to refer patients for drug treatment and rehabilitation. Likewise, mental health follow‐up should be confirmed and ongoing care coordinated with the patient's mental health case worker, if one exists.

A: Address Primary Care Issues

The inpatient setting is often a homeless patient's only ongoing source of medical care, but may not meet all of his or her healthcare needs. During an admission for congestive heart failure (CHF), for example, he or she may receive diuresis and afterload reduction but not outpatient interventions such lipid and blood pressure management. Chronic diagnoses, such as malignancy, may be viewed as secondary and remain unaddressed. Questions about extent of a hospitalist's obligations to provide primary care arise in cases where a patient has failed to establish (and the system failed to provide) an outpatient medical home.

Just as emergency department physicians have become de facto primary care providers for underserved patients, hospitalists can expect to provide routine care for patients facing homelessness. Some interventions traditionally considered outpatient services, such as pneumococcal vaccination or counseling regarding smoking cessation, are now identified as inpatient core quality measures. Whether sexually transmitted disease or colon cancer screening or evaluation of cardiac risk status, for example, should become inpatient services for medically indigent patients is open for debate. Whenever possible, our goal is to facilitate screening and specialty consultations in the inpatient setting when this will not unnecessarily prolong hospitalization.

F: Follow‐Up Care

Ideally, transfer of care occurs smoothly between the hospitalist and a PCP or specialist who will provide a patient's ongoing medical care. Because many homeless patients lack or cannot identify a consistent outpatient provider, they may require additional assistance to ensure they receive medical care after discharge. If the patient has a PCP, the hospitalist should initiate contact with this individual at admission and discharge, forwarding relevant records in a timely fashion, including a faxed or electronic discharge summary. We often provide patients with a hard copy of the discharge summary and ask them to hand‐carry it to any follow‐up appointments. When a patient has no PCP, the hospitalist should attempt to expedite establishment of primary care. Unfortunately, many communities have limited primary care availability for patients who lack health insurance, posing challenges for hospital providers and patients.

At our institution, follow‐up appointments are often made by a clerk or nurse who later relays the appointment date and time to the patient. Some clinics collect contact information and call the patient themselves. There are frequent lapses in this scheduling system; some patients never receive a follow‐up appointment because they have no means of contact. Providing a scheduled follow‐up date and time prior to discharge may circumvent this problem.41

It is also optimal if some options for follow‐up care do not require a previously scheduled appointment. At our institution, a postdischarge aftercare clinic fills this need for patients without an established PCP, until such a relationship can be established. Aftercare appointments are designed to address specific, time‐critical, clinical issues (eg, assessing response to antibiotics, follow‐up creatinine in patient on diuretics, etc). To the degree that it is possible, selecting a site for follow‐up care that minimizes transportation (eg, a shelter‐based clinic) may improve the likelihood of follow‐up. It is wise to ask the patient when and where he or she would prefer to be seen. Consider that evening appointments may be best for day workers.28 Some authors have advocated that providers consider dispensing fewer numbers of medications at any given time, in order to enhance compliance with the follow‐up appointments,28 even if this may not reflect optimal medical management.

Careful consideration should be given before ordering tests for which results may not be available prior to anticipated discharge. These may include microbiological cultures, pathology reports, or sexually transmitted disease screening, including HIV testing. Note that even when a patient does have an established PCP, the hospitalist's liability for medical care may persist after hospital discharge. Emergency room physicians, for example, have been found liable for lack of postdischarge communication of radiologic findings.42

Timely and thorough documentation is critical. In many cases, a hospitalist is the only physician aware of a homeless patient's active medical issues. On admission, records should be thoroughly reviewed to ensure that pressing concerns, even those not traditionally requiring hospitalization, are addressed in a timely fashion. Detailed discharge documentation helps to ensure that ongoing issues are not lost during follow‐up. It may be useful to provide a given patient with a portable summary of his or her medical history for self‐reference and facilitation of ongoing care, particularly for those with a history of seeking healthcare at multiple facilities.28

E: End‐of‐Life Discussions

Given the increased mortality and decreased life expectancy of the homeless population, an acute care hospitalization provides an excellent opportunity to discuss end‐of‐life preferences, particularly if the patient does not have an established PCP. Focus groups have noted little difference in the range of end‐of‐life preferences of the homeless as compared with the general population, yet a common fear among the homeless is that of an anonymous death, or a life without remembrance.43 Many homeless patients believe that physicians would use deceit in withdrawing life‐sustaining support or that their body might be disposed of without consent. They identify advance directives as a way to regain control over their lives.44 It is important to obtain and update emergency contacts for friends and family on each admission. Notably, homeless people often designate an unrelated friend or associate as their decision maker, rather than family, and express that it is less important to have family present at their death as it is to be cared for compassionately and respectfully by those who are present.44

D: Discharge Instructions Simple and Realistic

Health illiteracy profoundly affects homeless patients. In the predischarge narratives of 21 low‐income urban medical inpatients, almost one‐half believed it would be impossible to follow medical advice at discharge.45 Healthcare providers may overestimate a patient's ability to understand discharge instructions46 and to provide self‐care at the time of discharge.47 Homeless patients are at high risk for disease relapse following discharge, given chaotic living conditions and lack of social support.1 The presence of community support has been shown to decrease the likelihood of rehospitalization.48

Medication compliance poses a particular challenge. In 1 study, one‐third of homeless patients reported inability to comply with medications.2 Cost, storage capability, and complexity of regimen are common obstacles. Side effects should be considered when medications are selected, since common side effects like gastrointestinal upset or diarrhea, or desired effects like diuresis, may be intolerable if a patient cannot reliably access a restroom. Physicians should also weigh the possibility that discharge medications and supplies may be abused or stolen on the streets. Difficulty accessing routine meals can be particularly problematic in homeless patients with diabetes, who must eat on a regular schedule in order to avoid hypoglycemia. Diabetic goals may be adjusted accordingly to minimize risk. Diet may also be an issue if a patient must take a medication with food, as with some antiretrovirals. The physician must anticipate an erratic diet and, whenever possible, dose medications accordingly. Directly observed therapy for diseases such as tuberculosis is optimal if the ability to comply is in question.28 The NHCHC has developed guidelines for adaptations of care in homeless patients with a variety of clinical conditions, including diabetes mellitus, HIV, cardiovascular disease, and asthma; these are available for reference and download on their website (Table 2).

Illiteracy and low educational level also impact compliance. In 1 sample of indigent psychiatric patients, 76% read at or below the seventh grade level.49 Aftercare instructions should be easy to understand by those with lower levels of education (fourth grade level or less), written down in simple language, and reviewed verbally by nurse, pharmacist, and physician. Consider initiating projects within your hospital to streamline discharge instruction forms.50 The use of pictorial or video‐assisted discharge instructions for common diagnoses is an area of promise.17, 51, 52

Of note, there is no body of literature addressing the extent to which hospitalists or other inpatient physicians alter treatment goals at the time of discharge for homeless patients, but this may be a common occurrence and warrants further study.

C: Communication Methods After Discharge

Before discharge, clarify how a patient can be contacted for additional test results or information regarding follow‐up appointments. Although some homeless patients maintain mobile phones, telephone‐based methods used by some hospitalists for postdischarge follow‐up53, 54 may be unreliable in this population. Some shelters or respite facilities will accept messages for clients who reside there; others will provide clients with access to voicemail or e‐mail. For those patients who are technologically savvy, free e‐mail accounts can readily be obtained and accessed at public facilities, such as the public library. Contact information for a case manager can also be very useful. We occasionally ask patients to return to the hospital to retrieve test results or a message from their physician at a predetermined time and place. Where safe and appropriate, providing patients with direct physician contact information (rather than general hospital information) may minimize communication barriers.

The Big Picture: Systems‐Based Approaches to the Discharge of Homeless Patients

The discharge of homeless patients is suited to a comprehensive, interdisciplinary approach. There are many challenges to effective discharge planning: lack of time, lack of process ownership at the institutional level, financial constraints, and perhaps most significantly, lack of consensus regarding best practices.19 There is growing acknowledgement of the need to develop policies and standardize practice in this area. Hospitalists are uniquely situated to contribute to the development of new initiatives at the institutional, local, and national level.

Interventions (Table 4) may be as simple as the identification of a dedicated social worker for all homeless discharges15, 21, 55 or creation of a hospital‐wide discharge planning committee or inpatient homeless consultation service.15, 21 The distribution of discharge planning guides for patients and resource lists to providers is also gaining in popularity.21, 56 Some innovations specifically target clinicians, such as training seminars that teach communication skills and motivational interviewing and build familiarity with safety‐net services within the community.21, 57 Community‐based programs include medical respite care services, previously discussed, and the facilitation of preferred provider relationships directed by hospitals toward skilled nursing facilities willing to accept homeless and other challenging clients.15

Homelessness has also been identified as an area of focus by state governments, with many states funding initiatives to improve training and assistance to homeless providers, policies for discharge planning from public institutions, and homeless needs assessments. Some states have gone so far as to determine that discharge to an emergency shelter is not appropriate.19 On the national level, large advocacy organizations such as the NHCHC and National Coalition for the Homeless have spearheaded Housing First efforts on behalf of homeless patients and providers throughout the country. Such programs have been shown to decrease healthcare expenditures, emergency department visits, and hospitalizations in certain homeless populations.58, 59 Check the NHCHC website for consolidated discharge planning program development resources for healthcare institutions (http://www.nhchc.org; see Table 2 for additional links).

Commentary

Homeless patients frequently require more energy and services at the time of service in order to achieve standard medical care. Optimally, a patient assumes full responsibility for his or her health, but there may be limits to this responsibility for selected patients,60 especially in light of limited access to primary care. Understandably, homeless patients may focus more on immediate physical needs (eg, food, shelter, safety) than on chronic medical problems. In addition, they may experience a sense of unwelcomeness from healthcare providers that they perceive as discrimination; this may dissuade them from seeking care.61 The inpatient physician should aim to build trust with each encounter. As suggested by 1 author, it is important to promise only what can be delivered and deliver what is promised.62 Involving the patient in care and decision‐making is the most important first step in accomplishing this goal.

It is important in caring for homeless patients to reframe one's notion of a successful outcome.16 Ideally, on resolution of his or her acute medical issues, a homeless patient would be discharged to permanent housing with substance abuse and mental health treatment. This scenario is unfortunately rare. The hospitalist often has little ability to arrange stable, on‐demand housing at discharge. He or she is best advised to focus on optimizing acute care delivery at the point of care and maximize opportunities for future health.

It has been suggested that the discontinuity inherent in the hospitalist model may confer a special obligation on hospital medicine providers to abide by a more rigorous standard of care42; one might argue that this obligation becomes even more compelling when applied to this vulnerable population. In 1 study, a disturbing 27% of an American cohort of homeless adults had no healthcare contacts in the year prior to death, underscoring this group's underutilization of health services. Armed with this knowledge, hospitalists should seize every healthcare interaction as an opportunity to offer therapies with potential for longer‐term benefit.

A: Assess Housing Situation

Hospitals are not required to collect homelessness data. Where such data are collected, they are often inaccurate and internally inconsistent. In 1 survey of inpatients at a public hospital, over 25% of inpatients met strict criteria for homelessness.18 Effective discharge planning begins on admission.15 Hospitalists should ask specifically about housing status at the onset of hospitalization.19 This should be done in a direct, yet sensitive, manner. Given the recent economic downturn, increasing numbers of individuals and families are marginally housed; these patients may not show outward signs of homelessness and may not volunteer this information during the initial encounter. Be aware that some patients may become homeless during hospitalization,18 often as a result of inability to work or attend to financial matters during an inpatient stay. Resultant medical debt is a common cause of personal bankruptcy and homelessness following discharge.

Although it is accepted that a patient should be medically stable prior to discharge and that the decision to discharge should be based on medical, not financial considerations,20, 21 other standards for discharge vary from provider to provider. Hospitalists may be more cautious in discharging a patient without a stable home,4 yet facilitating outpatient follow‐up care or arranging transfer to a sheltered, structured environment can lengthen the hospital stay. Many cities offer formal medical respite care in a number of forms well described in the literature, including free‐standing2225 or shelter‐based units,25, 26 or skilled nursing facilities that contract directly with hospitals for short stays. One innovative model is the hoptel, or hospital hotel,27 a temporary housing facility proximate to the hospital to which self‐sufficient homeless patients may be discharged for recuperation. Some hospitals distribute motel vouchers at discharge.22, 25 All of these options provide opportunities for rest and recovery. Some facilities are staffed with a nurse who can check vital signs and provide wound care. Respite discharge may decrease early readmission and death rates23 and decrease repeat hospitalizations,24 particularly in human immunodeficiency virus (HIV) patients.

The National Health Care for the Homeless Council (NHCHC) maintains a national map and directory of respite care programs and services (see Table 2). Hospital providers should develop familiarity with all programs offered in a given geographic area and work closely with case managers and social workers to ensure that a homeless patient is considered for all programs for which he or she is eligible.

S: Screening and Prevention

In addition to treating the presenting condition, a hospitalist should evaluate homeless patients for disease processes common in indigence. A full physical examination, preferably unclothed, is also recommended.28 Homelessness markedly increases an individual's risk of chronic medical conditions. Reactive airway disease and chronic obstructive pulmonary disease (COPD) occur at higher rates as a result of tobacco and inhalational drug abuse. Diabetes mellitus, hypertension, and chronic liver and renal disease may remain undetected for years, with end‐organ effects commonly seen at presentation. Peripheral vascular disease is 10 to 15 times more frequent than in the general population.16, 28, 29 Tuberculosis, with prevalence rates greater than 30 times the national average,30 and other communicable diseases, including HIV, hepatitis B, and hepatitis C,16 are exceedingly prevalent and in some cases endemic.12 Infestations are also common. One out of 5 Health Care for the Homeless clients has an infectious or communicable disease.16 Up to two‐thirds of homeless individuals are HIV‐positive, with younger, Hispanic, and black populations at highest risk.29 Systemic infections may be traced to poor dentition, common in this population. Poor vision and skin conditions, also rampant,30 are easily overlooked in acute care encounters. The rate of drug and alcohol abuse in the homeless population may be as high as 8 times that of the general population.31 In 1 survey of homeless adults, the majority identified substance abuse as a major factor in ongoing homelessness.32 Mental illness prevalence in the may be as high as 80% to 95%33 and street violence is commonplace; more than 50% of homeless women have been sexually assaulted.11

There is a paucity of data on the effectiveness of inpatient health interventions for the homeless. In a 2005 systematic review of 45 studies evaluating the impact of various programs on homeless health, only 1 targeted an inpatient population.34 Furthermore, the literature suggests that street‐based or shelter‐based delivery of preventative services is most effective for undomiciled patients.35 Understanding these limitations, inpatient admission remains an opportunity to offer services that may decrease morbidity.

Evidence‐based preventative measures (Table 3) include vaccination against hepatitis A and hepatitis B in the intravenous drugusing homeless population. An accelerated hepatitis B vaccine administration schedule, with doses at 0, 7, and 21 days and a booster at 12 months, has been shown to increase completion rates.36 Drug users should be advised to utilize needle exchange programs and avoid sharing equipment. Sexually active homeless patients should be counseled regarding safe sexual practices and condom use. Consider tuberculosis screening with purified protein derivative (PPD) testing and spot sputum check, which have been shown in a shelter‐based intervention to detect an infection rate of 3.1%.37 Notably, within that cohort, symptom‐based screening was not found to be helpful. Influenza, diphtheria, tetanus, and pneumococcal vaccinations are also recommended, but have not been studied in regard to secondary decrease of infection rates in the homeless.

Admission to the hospital should be considered a treatable moment for substance abuse. In focus groups of homeless smokers, 76% of participants expressed intention to quit within 6 months and all were interested in using pharmacotherapy and behavioral treatments.38 In another study comparing admitted homeless vs. domiciled substance‐using adults, a higher percentage of the homeless patients were found to be in the action stage of change, as compared with the precontemplative or contemplative stage.39 When ongoing use is likely, recommended strategies include advocating for safer routes or patterns or use and praising small successes on the continuum to abstinence.40 Where such services are available, the hospitalist should coordinate with primary care providers (PCPs) and social workers to refer patients for drug treatment and rehabilitation. Likewise, mental health follow‐up should be confirmed and ongoing care coordinated with the patient's mental health case worker, if one exists.

A: Address Primary Care Issues

The inpatient setting is often a homeless patient's only ongoing source of medical care, but may not meet all of his or her healthcare needs. During an admission for congestive heart failure (CHF), for example, he or she may receive diuresis and afterload reduction but not outpatient interventions such lipid and blood pressure management. Chronic diagnoses, such as malignancy, may be viewed as secondary and remain unaddressed. Questions about extent of a hospitalist's obligations to provide primary care arise in cases where a patient has failed to establish (and the system failed to provide) an outpatient medical home.

Just as emergency department physicians have become de facto primary care providers for underserved patients, hospitalists can expect to provide routine care for patients facing homelessness. Some interventions traditionally considered outpatient services, such as pneumococcal vaccination or counseling regarding smoking cessation, are now identified as inpatient core quality measures. Whether sexually transmitted disease or colon cancer screening or evaluation of cardiac risk status, for example, should become inpatient services for medically indigent patients is open for debate. Whenever possible, our goal is to facilitate screening and specialty consultations in the inpatient setting when this will not unnecessarily prolong hospitalization.

F: Follow‐Up Care

Ideally, transfer of care occurs smoothly between the hospitalist and a PCP or specialist who will provide a patient's ongoing medical care. Because many homeless patients lack or cannot identify a consistent outpatient provider, they may require additional assistance to ensure they receive medical care after discharge. If the patient has a PCP, the hospitalist should initiate contact with this individual at admission and discharge, forwarding relevant records in a timely fashion, including a faxed or electronic discharge summary. We often provide patients with a hard copy of the discharge summary and ask them to hand‐carry it to any follow‐up appointments. When a patient has no PCP, the hospitalist should attempt to expedite establishment of primary care. Unfortunately, many communities have limited primary care availability for patients who lack health insurance, posing challenges for hospital providers and patients.

At our institution, follow‐up appointments are often made by a clerk or nurse who later relays the appointment date and time to the patient. Some clinics collect contact information and call the patient themselves. There are frequent lapses in this scheduling system; some patients never receive a follow‐up appointment because they have no means of contact. Providing a scheduled follow‐up date and time prior to discharge may circumvent this problem.41

It is also optimal if some options for follow‐up care do not require a previously scheduled appointment. At our institution, a postdischarge aftercare clinic fills this need for patients without an established PCP, until such a relationship can be established. Aftercare appointments are designed to address specific, time‐critical, clinical issues (eg, assessing response to antibiotics, follow‐up creatinine in patient on diuretics, etc). To the degree that it is possible, selecting a site for follow‐up care that minimizes transportation (eg, a shelter‐based clinic) may improve the likelihood of follow‐up. It is wise to ask the patient when and where he or she would prefer to be seen. Consider that evening appointments may be best for day workers.28 Some authors have advocated that providers consider dispensing fewer numbers of medications at any given time, in order to enhance compliance with the follow‐up appointments,28 even if this may not reflect optimal medical management.

Careful consideration should be given before ordering tests for which results may not be available prior to anticipated discharge. These may include microbiological cultures, pathology reports, or sexually transmitted disease screening, including HIV testing. Note that even when a patient does have an established PCP, the hospitalist's liability for medical care may persist after hospital discharge. Emergency room physicians, for example, have been found liable for lack of postdischarge communication of radiologic findings.42

Timely and thorough documentation is critical. In many cases, a hospitalist is the only physician aware of a homeless patient's active medical issues. On admission, records should be thoroughly reviewed to ensure that pressing concerns, even those not traditionally requiring hospitalization, are addressed in a timely fashion. Detailed discharge documentation helps to ensure that ongoing issues are not lost during follow‐up. It may be useful to provide a given patient with a portable summary of his or her medical history for self‐reference and facilitation of ongoing care, particularly for those with a history of seeking healthcare at multiple facilities.28

E: End‐of‐Life Discussions

Given the increased mortality and decreased life expectancy of the homeless population, an acute care hospitalization provides an excellent opportunity to discuss end‐of‐life preferences, particularly if the patient does not have an established PCP. Focus groups have noted little difference in the range of end‐of‐life preferences of the homeless as compared with the general population, yet a common fear among the homeless is that of an anonymous death, or a life without remembrance.43 Many homeless patients believe that physicians would use deceit in withdrawing life‐sustaining support or that their body might be disposed of without consent. They identify advance directives as a way to regain control over their lives.44 It is important to obtain and update emergency contacts for friends and family on each admission. Notably, homeless people often designate an unrelated friend or associate as their decision maker, rather than family, and express that it is less important to have family present at their death as it is to be cared for compassionately and respectfully by those who are present.44

D: Discharge Instructions Simple and Realistic

Health illiteracy profoundly affects homeless patients. In the predischarge narratives of 21 low‐income urban medical inpatients, almost one‐half believed it would be impossible to follow medical advice at discharge.45 Healthcare providers may overestimate a patient's ability to understand discharge instructions46 and to provide self‐care at the time of discharge.47 Homeless patients are at high risk for disease relapse following discharge, given chaotic living conditions and lack of social support.1 The presence of community support has been shown to decrease the likelihood of rehospitalization.48

Medication compliance poses a particular challenge. In 1 study, one‐third of homeless patients reported inability to comply with medications.2 Cost, storage capability, and complexity of regimen are common obstacles. Side effects should be considered when medications are selected, since common side effects like gastrointestinal upset or diarrhea, or desired effects like diuresis, may be intolerable if a patient cannot reliably access a restroom. Physicians should also weigh the possibility that discharge medications and supplies may be abused or stolen on the streets. Difficulty accessing routine meals can be particularly problematic in homeless patients with diabetes, who must eat on a regular schedule in order to avoid hypoglycemia. Diabetic goals may be adjusted accordingly to minimize risk. Diet may also be an issue if a patient must take a medication with food, as with some antiretrovirals. The physician must anticipate an erratic diet and, whenever possible, dose medications accordingly. Directly observed therapy for diseases such as tuberculosis is optimal if the ability to comply is in question.28 The NHCHC has developed guidelines for adaptations of care in homeless patients with a variety of clinical conditions, including diabetes mellitus, HIV, cardiovascular disease, and asthma; these are available for reference and download on their website (Table 2).

Illiteracy and low educational level also impact compliance. In 1 sample of indigent psychiatric patients, 76% read at or below the seventh grade level.49 Aftercare instructions should be easy to understand by those with lower levels of education (fourth grade level or less), written down in simple language, and reviewed verbally by nurse, pharmacist, and physician. Consider initiating projects within your hospital to streamline discharge instruction forms.50 The use of pictorial or video‐assisted discharge instructions for common diagnoses is an area of promise.17, 51, 52

Of note, there is no body of literature addressing the extent to which hospitalists or other inpatient physicians alter treatment goals at the time of discharge for homeless patients, but this may be a common occurrence and warrants further study.

C: Communication Methods After Discharge

Before discharge, clarify how a patient can be contacted for additional test results or information regarding follow‐up appointments. Although some homeless patients maintain mobile phones, telephone‐based methods used by some hospitalists for postdischarge follow‐up53, 54 may be unreliable in this population. Some shelters or respite facilities will accept messages for clients who reside there; others will provide clients with access to voicemail or e‐mail. For those patients who are technologically savvy, free e‐mail accounts can readily be obtained and accessed at public facilities, such as the public library. Contact information for a case manager can also be very useful. We occasionally ask patients to return to the hospital to retrieve test results or a message from their physician at a predetermined time and place. Where safe and appropriate, providing patients with direct physician contact information (rather than general hospital information) may minimize communication barriers.

The Big Picture: Systems‐Based Approaches to the Discharge of Homeless Patients

The discharge of homeless patients is suited to a comprehensive, interdisciplinary approach. There are many challenges to effective discharge planning: lack of time, lack of process ownership at the institutional level, financial constraints, and perhaps most significantly, lack of consensus regarding best practices.19 There is growing acknowledgement of the need to develop policies and standardize practice in this area. Hospitalists are uniquely situated to contribute to the development of new initiatives at the institutional, local, and national level.

Interventions (Table 4) may be as simple as the identification of a dedicated social worker for all homeless discharges15, 21, 55 or creation of a hospital‐wide discharge planning committee or inpatient homeless consultation service.15, 21 The distribution of discharge planning guides for patients and resource lists to providers is also gaining in popularity.21, 56 Some innovations specifically target clinicians, such as training seminars that teach communication skills and motivational interviewing and build familiarity with safety‐net services within the community.21, 57 Community‐based programs include medical respite care services, previously discussed, and the facilitation of preferred provider relationships directed by hospitals toward skilled nursing facilities willing to accept homeless and other challenging clients.15

Homelessness has also been identified as an area of focus by state governments, with many states funding initiatives to improve training and assistance to homeless providers, policies for discharge planning from public institutions, and homeless needs assessments. Some states have gone so far as to determine that discharge to an emergency shelter is not appropriate.19 On the national level, large advocacy organizations such as the NHCHC and National Coalition for the Homeless have spearheaded Housing First efforts on behalf of homeless patients and providers throughout the country. Such programs have been shown to decrease healthcare expenditures, emergency department visits, and hospitalizations in certain homeless populations.58, 59 Check the NHCHC website for consolidated discharge planning program development resources for healthcare institutions (http://www.nhchc.org; see Table 2 for additional links).

Commentary

Homeless patients frequently require more energy and services at the time of service in order to achieve standard medical care. Optimally, a patient assumes full responsibility for his or her health, but there may be limits to this responsibility for selected patients,60 especially in light of limited access to primary care. Understandably, homeless patients may focus more on immediate physical needs (eg, food, shelter, safety) than on chronic medical problems. In addition, they may experience a sense of unwelcomeness from healthcare providers that they perceive as discrimination; this may dissuade them from seeking care.61 The inpatient physician should aim to build trust with each encounter. As suggested by 1 author, it is important to promise only what can be delivered and deliver what is promised.62 Involving the patient in care and decision‐making is the most important first step in accomplishing this goal.

It is important in caring for homeless patients to reframe one's notion of a successful outcome.16 Ideally, on resolution of his or her acute medical issues, a homeless patient would be discharged to permanent housing with substance abuse and mental health treatment. This scenario is unfortunately rare. The hospitalist often has little ability to arrange stable, on‐demand housing at discharge. He or she is best advised to focus on optimizing acute care delivery at the point of care and maximize opportunities for future health.

It has been suggested that the discontinuity inherent in the hospitalist model may confer a special obligation on hospital medicine providers to abide by a more rigorous standard of care42; one might argue that this obligation becomes even more compelling when applied to this vulnerable population. In 1 study, a disturbing 27% of an American cohort of homeless adults had no healthcare contacts in the year prior to death, underscoring this group's underutilization of health services. Armed with this knowledge, hospitalists should seize every healthcare interaction as an opportunity to offer therapies with potential for longer‐term benefit.

A: Assess Housing Situation

Hospitals are not required to collect homelessness data. Where such data are collected, they are often inaccurate and internally inconsistent. In 1 survey of inpatients at a public hospital, over 25% of inpatients met strict criteria for homelessness.18 Effective discharge planning begins on admission.15 Hospitalists should ask specifically about housing status at the onset of hospitalization.19 This should be done in a direct, yet sensitive, manner. Given the recent economic downturn, increasing numbers of individuals and families are marginally housed; these patients may not show outward signs of homelessness and may not volunteer this information during the initial encounter. Be aware that some patients may become homeless during hospitalization,18 often as a result of inability to work or attend to financial matters during an inpatient stay. Resultant medical debt is a common cause of personal bankruptcy and homelessness following discharge.

Although it is accepted that a patient should be medically stable prior to discharge and that the decision to discharge should be based on medical, not financial considerations,20, 21 other standards for discharge vary from provider to provider. Hospitalists may be more cautious in discharging a patient without a stable home,4 yet facilitating outpatient follow‐up care or arranging transfer to a sheltered, structured environment can lengthen the hospital stay. Many cities offer formal medical respite care in a number of forms well described in the literature, including free‐standing2225 or shelter‐based units,25, 26 or skilled nursing facilities that contract directly with hospitals for short stays. One innovative model is the hoptel, or hospital hotel,27 a temporary housing facility proximate to the hospital to which self‐sufficient homeless patients may be discharged for recuperation. Some hospitals distribute motel vouchers at discharge.22, 25 All of these options provide opportunities for rest and recovery. Some facilities are staffed with a nurse who can check vital signs and provide wound care. Respite discharge may decrease early readmission and death rates23 and decrease repeat hospitalizations,24 particularly in human immunodeficiency virus (HIV) patients.

The National Health Care for the Homeless Council (NHCHC) maintains a national map and directory of respite care programs and services (see Table 2). Hospital providers should develop familiarity with all programs offered in a given geographic area and work closely with case managers and social workers to ensure that a homeless patient is considered for all programs for which he or she is eligible.

S: Screening and Prevention

In addition to treating the presenting condition, a hospitalist should evaluate homeless patients for disease processes common in indigence. A full physical examination, preferably unclothed, is also recommended.28 Homelessness markedly increases an individual's risk of chronic medical conditions. Reactive airway disease and chronic obstructive pulmonary disease (COPD) occur at higher rates as a result of tobacco and inhalational drug abuse. Diabetes mellitus, hypertension, and chronic liver and renal disease may remain undetected for years, with end‐organ effects commonly seen at presentation. Peripheral vascular disease is 10 to 15 times more frequent than in the general population.16, 28, 29 Tuberculosis, with prevalence rates greater than 30 times the national average,30 and other communicable diseases, including HIV, hepatitis B, and hepatitis C,16 are exceedingly prevalent and in some cases endemic.12 Infestations are also common. One out of 5 Health Care for the Homeless clients has an infectious or communicable disease.16 Up to two‐thirds of homeless individuals are HIV‐positive, with younger, Hispanic, and black populations at highest risk.29 Systemic infections may be traced to poor dentition, common in this population. Poor vision and skin conditions, also rampant,30 are easily overlooked in acute care encounters. The rate of drug and alcohol abuse in the homeless population may be as high as 8 times that of the general population.31 In 1 survey of homeless adults, the majority identified substance abuse as a major factor in ongoing homelessness.32 Mental illness prevalence in the may be as high as 80% to 95%33 and street violence is commonplace; more than 50% of homeless women have been sexually assaulted.11

There is a paucity of data on the effectiveness of inpatient health interventions for the homeless. In a 2005 systematic review of 45 studies evaluating the impact of various programs on homeless health, only 1 targeted an inpatient population.34 Furthermore, the literature suggests that street‐based or shelter‐based delivery of preventative services is most effective for undomiciled patients.35 Understanding these limitations, inpatient admission remains an opportunity to offer services that may decrease morbidity.

Evidence‐based preventative measures (Table 3) include vaccination against hepatitis A and hepatitis B in the intravenous drugusing homeless population. An accelerated hepatitis B vaccine administration schedule, with doses at 0, 7, and 21 days and a booster at 12 months, has been shown to increase completion rates.36 Drug users should be advised to utilize needle exchange programs and avoid sharing equipment. Sexually active homeless patients should be counseled regarding safe sexual practices and condom use. Consider tuberculosis screening with purified protein derivative (PPD) testing and spot sputum check, which have been shown in a shelter‐based intervention to detect an infection rate of 3.1%.37 Notably, within that cohort, symptom‐based screening was not found to be helpful. Influenza, diphtheria, tetanus, and pneumococcal vaccinations are also recommended, but have not been studied in regard to secondary decrease of infection rates in the homeless.

Admission to the hospital should be considered a treatable moment for substance abuse. In focus groups of homeless smokers, 76% of participants expressed intention to quit within 6 months and all were interested in using pharmacotherapy and behavioral treatments.38 In another study comparing admitted homeless vs. domiciled substance‐using adults, a higher percentage of the homeless patients were found to be in the action stage of change, as compared with the precontemplative or contemplative stage.39 When ongoing use is likely, recommended strategies include advocating for safer routes or patterns or use and praising small successes on the continuum to abstinence.40 Where such services are available, the hospitalist should coordinate with primary care providers (PCPs) and social workers to refer patients for drug treatment and rehabilitation. Likewise, mental health follow‐up should be confirmed and ongoing care coordinated with the patient's mental health case worker, if one exists.

A: Address Primary Care Issues

The inpatient setting is often a homeless patient's only ongoing source of medical care, but may not meet all of his or her healthcare needs. During an admission for congestive heart failure (CHF), for example, he or she may receive diuresis and afterload reduction but not outpatient interventions such lipid and blood pressure management. Chronic diagnoses, such as malignancy, may be viewed as secondary and remain unaddressed. Questions about extent of a hospitalist's obligations to provide primary care arise in cases where a patient has failed to establish (and the system failed to provide) an outpatient medical home.

Just as emergency department physicians have become de facto primary care providers for underserved patients, hospitalists can expect to provide routine care for patients facing homelessness. Some interventions traditionally considered outpatient services, such as pneumococcal vaccination or counseling regarding smoking cessation, are now identified as inpatient core quality measures. Whether sexually transmitted disease or colon cancer screening or evaluation of cardiac risk status, for example, should become inpatient services for medically indigent patients is open for debate. Whenever possible, our goal is to facilitate screening and specialty consultations in the inpatient setting when this will not unnecessarily prolong hospitalization.

F: Follow‐Up Care

Ideally, transfer of care occurs smoothly between the hospitalist and a PCP or specialist who will provide a patient's ongoing medical care. Because many homeless patients lack or cannot identify a consistent outpatient provider, they may require additional assistance to ensure they receive medical care after discharge. If the patient has a PCP, the hospitalist should initiate contact with this individual at admission and discharge, forwarding relevant records in a timely fashion, including a faxed or electronic discharge summary. We often provide patients with a hard copy of the discharge summary and ask them to hand‐carry it to any follow‐up appointments. When a patient has no PCP, the hospitalist should attempt to expedite establishment of primary care. Unfortunately, many communities have limited primary care availability for patients who lack health insurance, posing challenges for hospital providers and patients.

At our institution, follow‐up appointments are often made by a clerk or nurse who later relays the appointment date and time to the patient. Some clinics collect contact information and call the patient themselves. There are frequent lapses in this scheduling system; some patients never receive a follow‐up appointment because they have no means of contact. Providing a scheduled follow‐up date and time prior to discharge may circumvent this problem.41

It is also optimal if some options for follow‐up care do not require a previously scheduled appointment. At our institution, a postdischarge aftercare clinic fills this need for patients without an established PCP, until such a relationship can be established. Aftercare appointments are designed to address specific, time‐critical, clinical issues (eg, assessing response to antibiotics, follow‐up creatinine in patient on diuretics, etc). To the degree that it is possible, selecting a site for follow‐up care that minimizes transportation (eg, a shelter‐based clinic) may improve the likelihood of follow‐up. It is wise to ask the patient when and where he or she would prefer to be seen. Consider that evening appointments may be best for day workers.28 Some authors have advocated that providers consider dispensing fewer numbers of medications at any given time, in order to enhance compliance with the follow‐up appointments,28 even if this may not reflect optimal medical management.

Careful consideration should be given before ordering tests for which results may not be available prior to anticipated discharge. These may include microbiological cultures, pathology reports, or sexually transmitted disease screening, including HIV testing. Note that even when a patient does have an established PCP, the hospitalist's liability for medical care may persist after hospital discharge. Emergency room physicians, for example, have been found liable for lack of postdischarge communication of radiologic findings.42

Timely and thorough documentation is critical. In many cases, a hospitalist is the only physician aware of a homeless patient's active medical issues. On admission, records should be thoroughly reviewed to ensure that pressing concerns, even those not traditionally requiring hospitalization, are addressed in a timely fashion. Detailed discharge documentation helps to ensure that ongoing issues are not lost during follow‐up. It may be useful to provide a given patient with a portable summary of his or her medical history for self‐reference and facilitation of ongoing care, particularly for those with a history of seeking healthcare at multiple facilities.28

E: End‐of‐Life Discussions

Given the increased mortality and decreased life expectancy of the homeless population, an acute care hospitalization provides an excellent opportunity to discuss end‐of‐life preferences, particularly if the patient does not have an established PCP. Focus groups have noted little difference in the range of end‐of‐life preferences of the homeless as compared with the general population, yet a common fear among the homeless is that of an anonymous death, or a life without remembrance.43 Many homeless patients believe that physicians would use deceit in withdrawing life‐sustaining support or that their body might be disposed of without consent. They identify advance directives as a way to regain control over their lives.44 It is important to obtain and update emergency contacts for friends and family on each admission. Notably, homeless people often designate an unrelated friend or associate as their decision maker, rather than family, and express that it is less important to have family present at their death as it is to be cared for compassionately and respectfully by those who are present.44

D: Discharge Instructions Simple and Realistic

Health illiteracy profoundly affects homeless patients. In the predischarge narratives of 21 low‐income urban medical inpatients, almost one‐half believed it would be impossible to follow medical advice at discharge.45 Healthcare providers may overestimate a patient's ability to understand discharge instructions46 and to provide self‐care at the time of discharge.47 Homeless patients are at high risk for disease relapse following discharge, given chaotic living conditions and lack of social support.1 The presence of community support has been shown to decrease the likelihood of rehospitalization.48

Medication compliance poses a particular challenge. In 1 study, one‐third of homeless patients reported inability to comply with medications.2 Cost, storage capability, and complexity of regimen are common obstacles. Side effects should be considered when medications are selected, since common side effects like gastrointestinal upset or diarrhea, or desired effects like diuresis, may be intolerable if a patient cannot reliably access a restroom. Physicians should also weigh the possibility that discharge medications and supplies may be abused or stolen on the streets. Difficulty accessing routine meals can be particularly problematic in homeless patients with diabetes, who must eat on a regular schedule in order to avoid hypoglycemia. Diabetic goals may be adjusted accordingly to minimize risk. Diet may also be an issue if a patient must take a medication with food, as with some antiretrovirals. The physician must anticipate an erratic diet and, whenever possible, dose medications accordingly. Directly observed therapy for diseases such as tuberculosis is optimal if the ability to comply is in question.28 The NHCHC has developed guidelines for adaptations of care in homeless patients with a variety of clinical conditions, including diabetes mellitus, HIV, cardiovascular disease, and asthma; these are available for reference and download on their website (Table 2).

Illiteracy and low educational level also impact compliance. In 1 sample of indigent psychiatric patients, 76% read at or below the seventh grade level.49 Aftercare instructions should be easy to understand by those with lower levels of education (fourth grade level or less), written down in simple language, and reviewed verbally by nurse, pharmacist, and physician. Consider initiating projects within your hospital to streamline discharge instruction forms.50 The use of pictorial or video‐assisted discharge instructions for common diagnoses is an area of promise.17, 51, 52

Of note, there is no body of literature addressing the extent to which hospitalists or other inpatient physicians alter treatment goals at the time of discharge for homeless patients, but this may be a common occurrence and warrants further study.

C: Communication Methods After Discharge

Before discharge, clarify how a patient can be contacted for additional test results or information regarding follow‐up appointments. Although some homeless patients maintain mobile phones, telephone‐based methods used by some hospitalists for postdischarge follow‐up53, 54 may be unreliable in this population. Some shelters or respite facilities will accept messages for clients who reside there; others will provide clients with access to voicemail or e‐mail. For those patients who are technologically savvy, free e‐mail accounts can readily be obtained and accessed at public facilities, such as the public library. Contact information for a case manager can also be very useful. We occasionally ask patients to return to the hospital to retrieve test results or a message from their physician at a predetermined time and place. Where safe and appropriate, providing patients with direct physician contact information (rather than general hospital information) may minimize communication barriers.

The Big Picture: Systems‐Based Approaches to the Discharge of Homeless Patients

The discharge of homeless patients is suited to a comprehensive, interdisciplinary approach. There are many challenges to effective discharge planning: lack of time, lack of process ownership at the institutional level, financial constraints, and perhaps most significantly, lack of consensus regarding best practices.19 There is growing acknowledgement of the need to develop policies and standardize practice in this area. Hospitalists are uniquely situated to contribute to the development of new initiatives at the institutional, local, and national level.

Interventions (Table 4) may be as simple as the identification of a dedicated social worker for all homeless discharges15, 21, 55 or creation of a hospital‐wide discharge planning committee or inpatient homeless consultation service.15, 21 The distribution of discharge planning guides for patients and resource lists to providers is also gaining in popularity.21, 56 Some innovations specifically target clinicians, such as training seminars that teach communication skills and motivational interviewing and build familiarity with safety‐net services within the community.21, 57 Community‐based programs include medical respite care services, previously discussed, and the facilitation of preferred provider relationships directed by hospitals toward skilled nursing facilities willing to accept homeless and other challenging clients.15

Homelessness has also been identified as an area of focus by state governments, with many states funding initiatives to improve training and assistance to homeless providers, policies for discharge planning from public institutions, and homeless needs assessments. Some states have gone so far as to determine that discharge to an emergency shelter is not appropriate.19 On the national level, large advocacy organizations such as the NHCHC and National Coalition for the Homeless have spearheaded Housing First efforts on behalf of homeless patients and providers throughout the country. Such programs have been shown to decrease healthcare expenditures, emergency department visits, and hospitalizations in certain homeless populations.58, 59 Check the NHCHC website for consolidated discharge planning program development resources for healthcare institutions (http://www.nhchc.org; see Table 2 for additional links).

Commentary

Homeless patients frequently require more energy and services at the time of service in order to achieve standard medical care. Optimally, a patient assumes full responsibility for his or her health, but there may be limits to this responsibility for selected patients,60 especially in light of limited access to primary care. Understandably, homeless patients may focus more on immediate physical needs (eg, food, shelter, safety) than on chronic medical problems. In addition, they may experience a sense of unwelcomeness from healthcare providers that they perceive as discrimination; this may dissuade them from seeking care.61 The inpatient physician should aim to build trust with each encounter. As suggested by 1 author, it is important to promise only what can be delivered and deliver what is promised.62 Involving the patient in care and decision‐making is the most important first step in accomplishing this goal.

It is important in caring for homeless patients to reframe one's notion of a successful outcome.16 Ideally, on resolution of his or her acute medical issues, a homeless patient would be discharged to permanent housing with substance abuse and mental health treatment. This scenario is unfortunately rare. The hospitalist often has little ability to arrange stable, on‐demand housing at discharge. He or she is best advised to focus on optimizing acute care delivery at the point of care and maximize opportunities for future health.

It has been suggested that the discontinuity inherent in the hospitalist model may confer a special obligation on hospital medicine providers to abide by a more rigorous standard of care42; one might argue that this obligation becomes even more compelling when applied to this vulnerable population. In 1 study, a disturbing 27% of an American cohort of homeless adults had no healthcare contacts in the year prior to death, underscoring this group's underutilization of health services. Armed with this knowledge, hospitalists should seize every healthcare interaction as an opportunity to offer therapies with potential for longer‐term benefit.