Inappropriate Initial Therapy Research Articles

Prevalence and Outcomes of Multi-Drug Resistant Blood Stream Infections Among Nursing Home Residents Admitted to an Acute Care Hospital.

The prevalence of multi-drug resistant organism (MDRO) colonization in nursing home residents has been well documented, but little is known about the impact of MDRO bloodstream infections (BSIs). The aim of this study was to assess the prevalence, cost, and outcomes of MDRO-BSI vs. non-MDRO-BSI among nursing home residents. Retrospective cohort study. 960 bed tertiary academic medical center. Persons ≥18 years old admitted to an acute care tertiary hospital from Skilled Nursing Facilities with a diagnosis of sepsis between 2015 and 2018. Retrospective analysis of prevalence and outcomes. Among patients admitted to the study hospital with a diagnosis of sepsis during the study period, 7% were from nursing homes. The prevalence of MDRO-BSI was 47%. We identified 54 (50%) gram positive BSIs, 48 (45%) gram negative BSI and 5 (5%) fungal BSI. Thirty-one (57%) of the gram-positive infections and 14 (30%) of the gram-negative infections were with MDROs. The prevalence of BSI organisms were Staphylococcus aureus in 24%, Escherichia coli in 14%, Proteus mirabilis in 13%, Staphylococcus epidermidis in 8%, Enterococcus faecalis in 7%, and Klebsiella pneumoniae in 6%. We found that intensive care unit length of stay (7 days vs 5 days, P = .009), direct cost ($13,639 vs $9,922, P = .027), and total cost ($23,752 vs $17,900 P = .032) were significantly higher in patients with MDRO-BSI vs. non-MDRO-BSI. Patients with MDRO-BSI were twice as likely to receive inappropriate empiric antiinfective therapy (31% vs 16%, P = .006) and were more likely to die (49.1% vs 29.6%, P = .049). Nursing home residents have a high prevalence of MDRO-BSI, which is associated with higher risk of receiving inappropriate initial anti-infective therapy, higher cost, higher ICU LOS, and higher mortality. Our research adds new information about the prevalence of fungemia in this population.

A Systematic Review of the Effect of Delayed Appropriate Antibiotic Treatment on the Outcomes of Patients With Severe Bacterial Infections

Patients with severe bacterial infections often experience delay in receiving appropriate treatment. Consolidated evidence of the impact of delayed appropriate treatment is needed to guide treatment and improve outcomes. What is the impact of delayed appropriate antibacterial therapy on clinical outcomes in patients with severe bacterial infections? Literature searches of MEDLINE and Embase, conducted on July 24, 2018, identified studies published after 2007 reporting the impact of delayed appropriate therapy on clinical outcomes for hospitalized adult patients with bacterial infections. Where appropriate, results were pooled and analyzed with delayed therapy modeled three ways: delay vsno delay in receiving appropriate therapy; duration of delay; and inappropriate vsappropriate initial therapy. This article reports meta-analyses on the effect of delay and duration of delay. The eligibility criteria were met by 145 studies, of which 37 contributed data to analyses of effect of delay. Mortality was significantly lower in patients receiving appropriate therapy without delay compared with those experiencing delay (OR, 0.57; 95%CI, 0.45-0.72). Mortality was also lower in the no-delay group compared with the delay group in subgroups of studies reporting mortality at 20 to 30days, during ICU stay, or in patients with bacteremia (OR, 0.57 [95%CI, 0.43-0.76]; OR, 0.47 [95%CI, 0.27-0.80]; and OR, 0.54 [95%CI, 0.40-0.75], respectively). No difference was found in time to appropriate therapy between those who died and those who survived (P= .09), but heterogeneity between studies was high. Avoiding delayed appropriate therapy is essential to reduce mortality in patients with severe bacterial infections. PROSPERO; No.: CRD42018104669; URL: www.crd.york.ac.uk/prospero/.

Antibiotic Susceptibilities and Appropriateness of Initial Drug Selection for Community-Acquired Urinary Tract Infections (UTI) Caused by Extended-Spectrum Β-Lactamase (ESBL)-Producing Pathogens

BackgroundCommunity-acquired (CA) UTI caused by ESBL-producing pathogens pose challenges related to initial antibiotic (AB) selection. Better characterization of AB susceptibilities in CA ESBL infections may improve empiric drug selection for outpatient therapy. The objectives of this study were to describe AB susceptibilities of isolates in CA ESBL UTI and provide recommendations for appropriate treatment at our institution.MethodsAdult patients with CA ESBL UTI (cystitis) from 2009 through 2013 were retrospectively matched 1:1 with a control group of non-ESBL CA UTI based on age within 5 years, gender, and organism. The primary outcome in this phase of the study was description of AB susceptibilities in CA ESBL UTI vs. controls. Secondary outcomes were comparison of appropriate initial AB therapy (defined as concordance of initial AB with in vitro susceptibilities) and development of recommendations for initial antibiotics for CA UTI.ResultsEighty-five patients were matched into each of the ESBL and non-ESBL CA UTI groups. E. coli was the pathogen in 94% of ESBL UTIs and 96% of controls. Patients with ESBL UTI most often received ceftriaxone or oral β-lactam (BL, 31%), fluoroquinolone (FQ, 27%), trimethoprim/sulfamethoxazole (TMP/SMX, 14%), or nitrofurantoin (NF, 14%); controls were similar. Besides non-carbapenem BLs, ESBL producers were significantly more resistant to FQs (78% resistant), NF (16%), TMP/SMX (60%), gentamicin (33%), and doxycycline (78%) vs. controls (P < 0.01 for each). Ertapenem and amikacin had 100% and 96% susceptibility, respectively. Initial AB were discordant in 64% of ESBL UTI vs. 14% of controls (OR 11.0, 95% CI 5.0–24.3; P < 0.0001). FQs and TMP/SMX were discordant in 83% and 42% of ESBL UTI, respectively, while NF was concordant in 100% of patients with ESBL UTI and 89% of controls.ConclusionPatients with CA ESBL UTI were significantly more likely to receive inappropriate initial AB therapy. Although ESBL-producing strains were resistant to multiple AB classes, NF retained activity against 84% of ESBL isolates and was associated with appropriateness of initial therapy in 100% of patients with ESBL UTI. Nitrofurantoin is an appropriate oral option for treatment of CA UTI, even in patients with ESBL infection.Disclosures D. N. Fish, Merck & Co.: Grant Investigator, Research grant M. Barron, Merck & Co.: Grant Investigator, Research grant

Risk factors and molecular epidemiology of Acinetobacter baumannii bacteremia in neonates.

Acinetobacter baumannii infections in neonates are not uncommon but rarely studied. Clinical and molecular epidemiology of 40 patients with A. baumannii bacteremia in the neonatal intensive care units (NICUs) of a medical center from 2004 to 2014 was analyzed. Multi-drug resistance was found in only 3 isolates (7.5%). Sequence types (STs) of A. baumannii defined by multilocus sequencing typing were diverse, and 72.4% identified isolates belonged to novel STs. Majority of the isolates were susceptible to antibiotics tested. Among the 3 imipenem-resistant A. baumannii (IRAB) isolates, 2 (66.7%) belonged to ST684, a novel ST. All of the 3 isolates were susceptible to tigecycline and colistin. The predominant mechanism of imipenem resistance in these neonatal isolates is ISAba1-blaOXA-80, which has never been reported in Asia before. Most infected newborns were premature (95%), with very low birth weight (70%<1500g), prolonged intubation, usage of percutaneous central venous catheter (65%) and long-term usage of total parenteral nutrition or intravenous lipid (95%). IRAB infection, inappropriate initial therapy, 1-minute Apgar score and early onset infection within the first 10 days of life were found to correlate with mortality by log-rank test. Prior use of imipenem for at least 5 days and use of high frequency oscillation ventilation (HFOV) were statistically significant risk factors for acquiring IRAB infections. To reduce mortality of IRAB infection, it is crucial to consider giving effective agents, such as colistin, in 2 days for high risk neonates who has been given imipenem or used HFOV.

Invasive pneumococcal disease caused by ceftriaxone-resistant Streptococcus pneumoniae in Taiwan.

Invasive pneumococcal disease (IPD) was associated with mortality, but the risk factors associated with mortality remains controversial. A retrospective cohort study was designed. All patients with IPD from 2011 to 2013 admitted in a medical center were screened and collected for their clinical presentations and laboratory characteristics. Approximately half of the 134 IPD isolates derived from these patients belonged to three major serotypes (19A, 6A and 3), which are included in 13-valent pneumococcal conjugate vaccine (PCV13), but not in 7-valent pneumococcal conjugate vaccine (PCV7). Ceftriaxone resistance according to non-meningitis criteria was identified in 38% of the IPD isolates, and was the major independent risk factor associated with inappropriate initial therapy that subsequently contributed to mortality of the patients. Infection by serotype 6A, 15B, 19A, 19F, or 23F was the major independent risk factor associated with ceftriaxone resistance (non-meningitis criteria). 77.6% of these isolates belonged to additional PCV13 serotypes, with more than 40% expressing resistance to ceftriaxone. In terms of serotype coverage, PCV13 covered 94.1% of the IPD isolates with ceftriaxone resistance, in comparison to 21.6% only by PCV7. The increase of ceftriaxone resistance in pneumococci in part driven by PCV7 vaccination in Taiwan is worrisome. The use of PCV13 in children as well as in the elderly population is likely to offer protection from the infection caused by ceftriaxone-resistant pneumococci. It is important to give an effective drug such as penicillin, fluoroquinolones or vancomycin in 2 days for improving outcome of IPD patients.

Predominance of healthcare-associated cases among episodes of community-onset bacteraemia due to extended-spectrum β-lactamase-producing Enterobacteriaceae

Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) are endemic pathogens worldwide. Infection with ESBL-PE may be associated with inadequate antibiotic therapy and a poor outcome. However, risk factors for ESBL-PE community-acquired infections are ill-defined. An observational multicentre study was performed in 50 hospitals to identify the prevalence of and risk factors for community-acquired ESBL-PE bacteraemia. All patients presenting with community-onset Enterobacteriaceae bacteraemia were recorded over a 2-month period (between June and November 2013). Risk factors and 14-day outcomes of patients were investigated. Among 682 Enterobacteriaceae bacteraemia episodes recorded, 58 (8.5%) were caused by ESBL-PE. The most frequent species isolated were Escherichia coli (537; 76.7%) and Klebsiella spp. (68; 9.7%), of which 49 (9.1%) and 8 (11.8%), respectively, were ESBL-producers. Most ESBL-PE episodes were healthcare-associated, and only 22 (38%) were apparently community-acquired. The main risk factor for community-acquired ESBL-PE bacteraemia was a prior hospital stay of ≥5 days within the past year. The overall 14-day survival was 90%; only 4 (6.9%) of 58 patients with ESBL-PE bacteraemia died. Inadequate initial antibiotic therapy was administered to 55% of patients with ESBL-PE bacteraemia but was not associated with increased 14-day mortality. Although many patients had community-onset ESBL-PE bacteraemia, almost two-thirds of the episodes were actually healthcare-associated, and true community-acquired ESBL-PE bacteraemia remains rare. In our essentially non-severely ill population, inappropriate initial therapy was not associated with a higher risk of mortality.

Early Response in Cellulitis: A Prospective Study of Dynamics and Predictors.

Skin and soft tissue infections are common reasons for medical care. Use of broad-spectrum therapy and costs have increased. Assessment of early treatment response has been given a central role both in clinical trials and everyday practice. However, there is a paucity of data on the dynamics of response, causes of early nonresponse, and how early nonresponse affects resource use and predicts outcome. We prospectively enrolled 216 patients hospitalized with cellulitis. Clinical and biochemical response data during the first 3 days of treatment were analyzed in relation to baseline factors, antibiotic use, surgery, and outcome. Multivariable analysis included logistic lasso regression. Clinical or biochemical response was observed in the majority of patients the day after treatment initiation. Concordance between clinical and biochemical response was strongest at days 2 and 3. Female sex, cardiovascular disease, higher body mass index, shorter duration of symptoms, and cellulitis other than typical erysipelas were predictors of nonresponse at day 3. In contrast, baseline factors were not predictive of clinical failure assessed posttreatment. Among cases with antibiotic treatment escalation by day 2, 90% (37/41) had nonresponse at day 1, but only 5% (2/40) had inappropriate initial therapy. Nonresponse at day 3 was a predictor of treatment duration >14 days, but not of clinical failure. Nonpharmacological factors had a major impact on early response dynamics. Delayed response was rarely related to inappropriate therapy but strongly predictive of early treatment escalation, suggesting that broadening antibiotic treatment may often be premature.

Impact of Molecular Epidemiology and Reduced Susceptibility to Glycopeptides and Daptomycin on Outcomes of Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia.

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) bacteremia was associated with high mortality, but the risk factors associated with mortality remain controversial.MethodsA retrospective cohort study was designed. All patients with MRSA bacteremia admitted were screened and collected for their clinical presentations and laboratory characteristics. Minimum inhibitory concentration (MIC) and staphylococcal cassette chromosome mec (SCCmec) type of bacterial isolates were determined. Risk factors for mortality were analyzed.ResultsMost MRSA isolates from the 189 enrolled patients showed reduced susceptibility to antibiotics, including MIC of vancomycin ≥ 1.5 mg/L (79.9%), teicoplanin ≥ 2 mg/L (86.2%), daptomycin ≥ 0.38 mg/L (73.0%) and linezolid ≥ 1.5 mg/L (64.0%). MRSA with vancomycin MIC ≥ 1.5 mg/L and inappropriate initial therapy were the two most important risk factors for mortality (both P < 0.05; odds ratio = 7.88 and 6.78). Hospital-associated MRSA (HA-MRSA), carrying SCCmec type I, II, or III, was associated with reduced susceptibility to vancomycin, teicoplanin or daptomycin and also with higher attributable mortality (all P < 0.05). Creeping vancomycin MIC was linked to higher MIC of teicoplanin and daptomycin (both P < 0.001), but not linezolid (P = 0.759).ConclusionsGiving empirical broad-spectrum antibiotics for at least 5 days to treat catheter-related infections, pneumonia, soft tissue infection and other infections was the most important risk factor for acquiring subsequent HA-MRSA infection. Choice of effective anti-MRSA agents for treating MRSA bacteremia should be based on MIC of vancomycin, teicoplanin and daptomycin. Initiation of an effective anti-MRSA agent without elevated MIC in 2 days is crucial for reducing mortality.

Emergence in Taiwan of novel imipenem-resistant Acinetobacter baumannii ST455 causing bloodstream infection in critical patients.

Acinetobacter baumannii is one of the most important noscomial pathogens worldwide. The study aimed to use multilocus sequence typing (MLST) for epidemiological surveillance of A. baumannii isolates in Taiwan and analyze the clinical presentations and patients' outcomes. MLST according to both Bartual's PubMLST and Pasteur's MLST schemes was applied to characterize bloodstream imipenem-resistant A. baumannii (IRAB) infection in intensive care units in a medical center. A total of 39 clinical IRAB bloodstream isolates in 2010 were enrolled. We also collected 13 imipenem-susceptible A. baumannii bloodstream isolates and 30 clinical sputum isolates (24 IRAB and 6 imipenem-susceptible A. baumannii) for comparison. Clinical presentations and outcome of the patients were analyzed. We found that infection by ST455B/ST2P and inappropriate initial therapy were statistically significant risk factors for mortality. More than one third of the IRAB isolates belonged to ST455B/ST2P. Most ST455B/ST2P (80%) carried ISAba1-blaOXA-23, including 10 (66.7%) with Tn2006 (ISAba1-blaOXA-23-ISAba1) in an AbaR4-type resistance island. ST455B/ST2P appears to evolve from ST208B/ST2P of clonal complex (CC) 92B/CC2P. In this hospital-based study, A. baumannii ST455 accounted for 38.5% of IRAB bacteremia, with a high mortality of 86.7%. Approximately 85% of ST455B/ST2P bacteremia had a primary source of ventilation-associated pneumonia. We report the emergence in Taiwan of IRAB ST455B/ST2P, which is the current predominant clone of IRAB in our hospital and has been causing bacteremia with high mortality in critical patients.

Emergence in Taiwan of novel imipenem-resistant Acinetobacter baumannii ST455 causing bloodstream infection in critical patients.

Acinetobacter baumannii is one of the most important nosocomial pathogens worldwide. This study aimed to use multilocus sequence typing (MLST) for the epidemiological surveillance of A. baumannii isolates in Taiwan and analyze the clinical presentations and patients' outcome. MLST according to both Bartual's PubMLST and Pasteur's MLST schemes was applied to characterize bloodstream imipenem-resistant A. baumannii (IRAB) infection in intensive care units in a medical center. A total of 39 clinical IRAB bloodstream isolates in 2010 were enrolled. We also collected 13 imipenem-susceptible A. baumannii (ISAB) bloodstream isolates and 30 clinical sputum isolates (24 IRAB and 6 ISAB) for comparison. Clinical presentations and outcome of the patients were analyzed. We found that infection by ST455(B)/ST2(P) and inappropriate initial therapy were statistically significant risk factors for mortality. More than one-third of the IRAB isolates belonged to ST455(B)/ST2(P). Most ST455(B)/ST2(P) (80%) carried ISAba1-blaOXA-23, including 10 (66.7%) with Tn2006 (ISAba1-blaOXA-23-ISAba1) in an AbaR4-type resistance island. ST455(B)/ST2(P) appears to evolve from ST208(B)/ST2(P) of clonal complex (CC) 92(B)/CC2(P). In this hospital-based study, A. baumannii ST455 accounted for 38.5% of IRAB bacteremia, with a high mortality of 86.7%. Approximately 85% of ST455(B)/ST2(P)bacteremia had a primary source of ventilation-associated pneumonia. We report the emergence in Taiwan of IRAB ST455(B)/ST2(P), which is the current predominant clone of IRAB in our hospital and has been causing bacteremia with high mortality in critical patients.

Early empiric therapy for invasive fungal infection in the ICU

The risk of infection increases with the length of stay in the intensive care unit (ICU). Invasive fungal infections (IFI) are now responsible for a sizeable proportion of ICU infections. Candida spp. are a particular problem in the ICU, where they are not only among the most common pathogens responsible for blood stream infections (BSI), but also associated with an unexpectedly high rate of mortality. Central venous catheters, total parenteral nutrition, and increasingly, surgery, are common sources of Candida BSI. While C. albicans remains the most common species implicated in candidemia, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, and other non-albicans species are often responsible for infection, especially among older patients (e.g., > 60 years). Risk scores and prediction rules for Candida BSI are helpful, but not straightforward to apply. There is also uncertainty around the appropriate length of therapy for deep-seated Candida infections (e. g., intra-abdominal infections). Despite predictive, diagnostic, and treatment uncertainties, correct assessment of patient risk factors for nosocomial Candida infection is crucial to avoiding the poor outcomes associated with delayed or inappropriate initial therapy. The reality is that many ICU patients with Candida IFI are treated late or with fluconazole despite guidelines that an echinocandin be used as initial therapy for critically ill patients. Furthermore, not all echinocandins are equally effective, particularly when it comes to non-albicans Candida infections. The problem of antifungal agents not being interchangeable extends to treatment of invasive aspergillosis, where selecting an agent such as voriconazole gives rise to concerns about drug interactions and the need for therapeutic drug monitoring. Given the increasing problem of candidemia in the ICU and the shift to non-albicans species, especially in older patients, early empiric therapy with an echinocandin is essential, as is consideration of surgical co-intervention when urgent measures are needed. Early empiric therapy with the appropriate echinocandin and source control are the cornerstones of effective treatment for Candida BSI.

Mycobacterium tuberculosis Septic Shock

Septic shock due to Mycobacterium tuberculosis (MTB) is an uncommon but well-recognized clinical syndrome. The objective of this study was to describe the unique clinical characteristics, epidemiologic risk factors, and covariates of survival of patients with MTB septic shock in comparison with other bacterial septic shock. A retrospective nested cohort study was conducted of patients given a diagnosis of MTB septic shock derived from a trinational, 8,670-patient database of patients with septic shock between 1996 and 2007. In the database, 53 patients had been given a diagnosis of MTB shock compared with 5,419 with septic shock associated with isolation of more common bacterial pathogens. Patients with MTB and other bacterial septic shock had in-hospital mortality rates of 79.2% and 49.7%, respectively (P &lt; .0001). Of the cases of MTB shock, all but five patients had recognized respiratory tract involvement. Fifty-five percent of patients (29 of 53) were documented (by direct culture or stain) as having disseminated extrapulmonary involvement. Inappropriate and appropriate initial empirical therapy was delivered in 28 patients (52.8%) and 25 patients (47.2%); survival was 7.1% and 36.0%, respectively (P = .0114). Ten patients (18.9%) did not receive anti-MTB therapy; all died. The median time to appropriate antimicrobial therapy for MTB septic shock was 31.0 h (interquartile range, 18.9-71.9 h). Only 11 patients received anti-MTB therapy within 24 h of documentation of hypotension; six of these (54.5%) survived. Only one of 21 patients (4.8%) who started anti-MTB therapy after 24 h survived (P = .0003 vs &lt; 24 h). Survival differences between these time intervals are not significantly different from those seen with bacterial septic shock due to more common bacterial pathogens. MTB septic shock behaves similarly to bacterial septic shock. As with bacterial septic shock, early appropriate antimicrobial therapy appears to improve mortality.

Clinical impact of inappropriate initial antimicrobial therapy on outcome in bacteremic biliary tract infections

The marked increase in the incidence of biliary tract infections due to antimicrobial-resistant pathogens in recent years is of great concern, as patients infected by these isolates might initially receive antibiotics ineffective against the responsible pathogens. A retrospective cohort study including 556 episodes of bacteremic biliary tract infection was designed to evaluate the impact of inappropriate initial antimicrobial therapy on the clinical outcomes of patients with biliary tract infections. Of 556 episodes, 257 (46.2%) received inappropriate initial antimicrobial therapy. Although Escherichia coli and Klebsiella species are the most common pathogens, the pathogens that were most frequently associated with inappropriate therapy were Pseudomonas aeruginosa and Enterococcus spp. In multivariable analysis, inappropriate initial antimicrobial therapy was found to be independently associated with increased mortality (odds ratio (OR) 2.25, 95% confidence interval (CI) 1.13-4.48; p = 0.021), along with pancreaticobiliary tract cancer, liver cirrhosis, Enterobacter infection, and a high Pitt bacteremia score (All p < 0.05). Subgroup multivariate analyses showed that inappropriate initial therapy was not a significant factor associated with mortality in cases where therapeutic decompression or drainage procedures were employed (OR 1.24, 95% CI 0.43-3.54; p = 0.691) or in cases with appropriate definitive antimicrobial therapy (OR 1.61, 95% CI 0.69-3.72; p = 0.270) after adjustment for other variables. Our findings suggest that the administration of inappropriate initial antimicrobial therapy might be associated with an adverse outcome in patients experiencing bacteremic biliary tract infections, and that the impact of inappropriate therapy on the outcome may be dependent on therapeutic drainage and appropriate definitive antimicrobial therapy.

Epidemiology and Outcomes of Complicated Skin and Soft Tissue Infections in Hospitalized Patients

Complicated skin and soft tissue infections (cSSTIs) are among the most rapidly increasing reasons for hospitalization. To describe inpatients with regard to patient characteristics, cSSTI origin, appropriateness of initial antibiotics, and outcomes, we performed a retrospective cohort study in patients hospitalized for cSSTI. To identify independent predictors of outcomes, we performed multivariate analyses. Of 1,096 eligible patients, 48.7% had health care-associated (HCA) cSSTI and 51.3% had community-acquired (CA) cSSTI. After adjustment for baseline variables, hospital length of stay (LOS) was longer for HCA than for CA cSSTI (difference, 2.1 days; 95% confidence interval [CI], 0.8 to 3.5; P < 0.05). Other covariates associated with a longer LOS were need for dialysis (regression coefficient ± standard error, 4.5 ± 1.1) and diabetic wound diagnosis (2.6 ± 1.0) (all P < 0.05). In the subset with culture-positive cSSTI within 24 h of admission, the most common pathogen was Staphylococcus aureus (298/449 [66.4%]), of which 74.8% (223/298) were methicillin-resistant S. aureus (MRSA). Eighty-three patients (18.5%) received inappropriate initial antibiotics. After adjustment for other variables, the following were associated with inappropriate initial therapy: direct admission to hospital (not via emergency department), cSSTI caused by MRSA or mixed pathogens, and cSSTI caused by pathogens other than S. aureus or streptococci (all P < 0.05). We did not find an association between inappropriate therapy and outcomes, except in the subset with ulcers (adjusted odds ratio, 11.8; 95% CI, 1.3 to 111.1; P = 0.03). More studies are needed to examine the impact of HCA cSSTI and inappropriate initial therapy on outcomes.

Ertapenem in the treatment of bacteremia caused by extended-spectrum beta-lactamase-producing Escherichia coli: a propensity score analysis

This study assessed the impact of ertapenem and other carbapenems on mortality in patients with monomicrobial extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) bacteremia. This non-concurrent prospective study included adult patients with ESBL-EC bacteremia during a 2.5-year period at a 2200-bed teaching hospital. We used a multivariate logistic regression model and Cox's proportional hazards model including propensity score analysis to assess variables associated with 30-day mortality. Of 71 patients who met the study criteria, nine died within 3 days. Among the 62 remaining patients who received definitive antimicrobial therapy, 13 died within 30 days. Male gender, ICU stay, solid tumor, and primary bacteremia were independent predictors of 30-day mortality, whereas definitive antimicrobial therapy using either ertapenem or imipenem/meropenem was protective (p<0.001 and p=0.002, respectively). Adjustment by propensity score found that ertapenem appeared to exhibit more favorable outcomes, but the difference fell short of statistical significance (hazard ratio 0.02, p=0.06). Inappropriate initial therapy was not a significant predictor of mortality. ICU stay, but not initial choice of empirical antimicrobial therapy, was a major predictor of mortality. Using a carbapenem as definitive therapy was a protective factor for 30-day mortality. The choice of ertapenem is reasonable for less severely-ill patients who are at risk of ESBL-EC bacteremia and unlikely to have infection due to Pseudomonas aeruginosa.

Clinical and economic outcomes in patients with community‐acquired Staphylococcus aureus pneumonia

While the clinical and economic consequences of S. aureus pneumonia in healthcare settings have been well documented, much less is known about community-acquired S. aureus pneumonia (CAP). We retrospectively identified all patients admitted to a large US urban teaching hospital between January 2005 and May 2008 with pneumonia and positive blood or respiratory cultures for S. aureus within 48 hours of admission. Patients with suspected healthcare-associated pneumonia (HCAP) were excluded from the study sample, using established criteria (eg, recent hospitalization, admission from nursing home, hemodialysis). Patients were designated as having methicillin-resistant (MRSA) or methicillin-susceptible (MSSA) CAP based on initial S. aureus isolates. Initial therapy was designated "appropriate" vs. "inappropriate" based on expected susceptibility of the organism to the regimen received. We identified a total of 128 CAP patients with S. aureus isolates; mean (standard deviation [SD]) age was 60 (17) years. A total of 55 patients (43%) had initial cultures positive for MRSA. Patients with MRSA CAP were more likely to receive inappropriate initial therapy (24 [44%] vs. 13 [18%] for MSSA; P = 0.002). Approximately 25% of all patients underwent surgery for pneumonia, 69% received mechanical ventilation, 79% were admitted to intensive care unit (ICU), and 24% died in hospital. Mean (SD) length of stay was 17.0 (15.7) days, and total hospital charges averaged $127,922 ($154,605) per patient; there were no significant differences between patients with MRSA vs. MSSA CAP. Outcomes are poor, hospital stays are long, and costs of care are high in patients with S. aureus CAP, and do not differ between those with MRSA vs. MSSA.

Initiation of Inappropriate Antimicrobial Therapy Results in a Fivefold Reduction of Survival in Human Septic Shock

Our goal was to determine the impact of the initiation of inappropriate antimicrobial therapy on survival to hospital discharge of patients with septic shock. The appropriateness of initial antimicrobial therapy, the clinical infection site, and relevant pathogens were retrospectively determined for 5,715 patients with septic shock in three countries. Therapy with appropriate antimicrobial agents was initiated in 80.1% of cases. Overall, the survival rate was 43.7%. There were marked differences in the distribution of comorbidities, clinical infections, and pathogens in patients who received appropriate and inappropriate initial antimicrobial therapy (p < 0.0001 for each). The survival rates after appropriate and inappropriate initial therapy were 52.0% and 10.3%, respectively (odds ratio [OR], 9.45; 95% CI, 7.74 to 11.54; p < 0.0001). Similar differences in survival were seen in all major epidemiologic, clinical, and organism subgroups. The decrease in survival with inappropriate initial therapy ranged from 2.3-fold for pneumococcal infection to 17.6-fold with primary bacteremia. After adjustment for acute physiology and chronic health evaluation II score, comorbidities, hospital site, and other potential risk factors, the inappropriateness of initial antimicrobial therapy remained most highly associated with risk of death (OR, 8.99; 95% CI, 6.60 to 12.23). Inappropriate initial antimicrobial therapy for septic shock occurs in about 20% of patients and is associated with a fivefold reduction in survival. Efforts to increase the frequency of the appropriateness of initial antimicrobial therapy must be central to efforts to reduce the mortality of patients with septic shock.

Initial treatment and outcome of Candida glabrata versus Candida albicans bloodstream infection

Candida glabrata is a common cause of bloodstream infection (BSI) and exhibits decreased susceptibility to fluconazole. We sought to determine whether patients with C. glabrata infection were at increased risk of inappropriate initial therapy and mortality compared with the more fluconazole-susceptible species Candida albicans by performing a matched case-control study using the Prospective Antifungal Therapy Alliance registry of invasive fungal infections. C. glabrata BSI patients were matched to those with C. albicans BSI by age, sex, and underlying illness after screening all C. glabrata patients entered into the registry from March 2004 through September 2007. Of 161 patients with C. glabrata BSI included and matched to 161 C. albicans patients, those with C. glabrata were less likely to receive an adequate dose of fluconazole as initial therapy (12% versus 52%, P < 0.05) and more likely to receive an echinocandin (44% versus 26%, P < 0.05) or inadequately dosed fluconazole (32% versus 8%, P < 0.05) as initial therapy. Although time to initiation of therapy did not differ by species ( P = 0.2), time to receipt of adequate therapy was longer for those with C. glabrata BSI ( P < 0.001). Overall, C. glabrata patients were more likely to receive inadequate initial therapy (34% versus 11%, P < 0.05), but 4-week mortality was no different between groups (30% for C. glabrata versus 29% for C. albicans, P = 0.80). We found hematologic malignancy, age greater than 60, the presence of a central venous catheter at diagnosis, mechanical ventilation, and dialysis dependence to be independent predictors of 4-week mortality. The lack of difference in mortality between species may reflect the overriding importance of host variables and/or a difference in virulence by species: further study is needed to investigate these hypotheses.

Inappropriate initial antimicrobial therapy as a risk factor for mortality in patients with community-onset Pseudomonas aeruginosa bacteraemia

This study was performed to identify the risk factors for mortality and evaluate the effect of inappropriate initial antimicrobial therapy on the outcomes of patients with community-onset Pseudomonas aeruginosa bacteraemia in an emergency department (ER) setting. All cases with P. aeruginosa bacteraemia occurring within 48 h after ER visit from January 2000 to December 2005 were retrospectively analysed. A total of 106 community-onset P. aeruginosa bacteraemia cases in the ER were included (mean age, 57.61 +/- 14.44 years old; M:F, 58:48). Although P. aeruginosa bacteraemia was diagnosed in the ER, most of the cases of P. aeruginosa bacteraemia were healthcare-associated (88.7%). Malignancy (n = 83, 78.3%) was the most common underlying disorder. Fifty patients (47.2%) were neutropaenic and 56 patients (52.8%) had septic shock. The overall 30-day mortality rate was 26.4% (28/106). In the univariate analysis, underlying malignancy, high Charlson's weighted index of comorbidity (> or = 3), high Pitt bacteraemia score (> or = 4), indwelling central venous catheter and inappropriate initial therapy were significantly associated with 30-day mortality (all P < 0.05). In the multivariate analysis, high Pitt bacteraemia score (OR, 17.03; 95% CI, 4.60-63.15; P < 0.001) and inappropriate initial antimicrobial therapy (OR, 4.29; 95% CI, 1.39-13.24; P = 0.011) were found to be significant risk factors for 30-day mortality. The 30-day mortality rate was significantly higher in the inappropriate therapy group (18/51, 35.3%) than in the appropriate therapy group (10/55, 18.2%) (P = 0.046). This study demonstrated that inappropriate initial antimicrobial therapy was significantly associated with unfavourable outcomes in patients with community-onset P. aeruginosa bacteraemia. As P. aeruginosa bacteraemia can be a fatal infection, even when community-onset, inappropriate antimicrobial therapy should be avoided in suspected cases of P. aeruginosa bacteraemia.

Direct Susceptibility Testing of Respiratory Samples

ceptible) were seen in 0.35%, 0.16%, and 1.06% of cases, respectively. The disk diffusion technique is cheaper and delivers reliable early susceptibility results. We have not evaluated the impact of the disk diffusion technique on patient care; however, 190% of patients were receiving appropriate antimicrobial treatment when the TC result was reported. Testing blood culture isolates is easier than testing respiratory samples, because the former generally involves a single pathogen, whereas respiratory samples regularly yield 11 pathogen. Bouza et al. [1] report that, in the control group, the percentage of patients who received an adequate defined daily dose of therapy was smaller (68.3%) than in the E-test group (91.28%), a fact that could be attributed to inappropriate initial therapy in this group (which I presume Kollef [4] is referring to in his editorial). This high rate needs to be further elucidated. In a publication from Spain [5], only 8 patients with hospital-acquired pneumonia received inappropriate therapy; 152 were receiving appropriate therapy.