Jennifer H. Han

Carbapenem Therapy Is Associated With Improved Survival Compared With Piperacillin-Tazobactam for Patients With Extended-Spectrum β-Lactamase Bacteremia

BACKGROUND The effectiveness of piperacillin-tazobactam (PTZ) for the treatment of extended-spectrum β-lactamase (ESBL) bacteremia is controversial. We compared 14-day mortality of PTZ vs carbapenems as empiric therapy in a cohort of patients with ESBL bacteremia who all received definitive therapy with a carbapenem. METHODS Patients hospitalized between January 2007 and April 2014 with monomicrobial ESBL bacteremia were included. A decrease of >3 doubling dilutions in the minimum inhibitory concentration for third-generation cephalosporins tested in combination with 4 µg/mL of clavulanic acid was used to confirm ESBL status. The primary exposure was empiric therapy, defined as antibiotic therapy administered to a patient before ESBL status was known. Patients were excluded if they did not receive a carbapenem after ESBL production was identified. The primary outcome was time to death from the first day of bacteremia. Propensity scores using inverse probability of exposure weighting (IPW) were used to estimate the probability that a patient would receive PTZ vs carbapenems empirically. We calculated overall hazard ratios for mortality censored at 14 days using Cox proportional hazards models on an IPW-adjusted cohort. RESULTS A total of 331 unique patients with ESBL bacteremia were identified. One hundred three (48%) patients received PTZ empirically and 110 (52%) received carbapenems empirically. The adjusted risk of death was 1.92 times higher for patients receiving empiric PTZ compared with empiric carbapenem therapy (95% confidence interval, 1.07-3.45). CONCLUSIONS PTZ appears inferior to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of invasive ESBL infections, early carbapenem therapy should be considered. Our findings should not be extended to β-lactam/β-lactamase inhibitor combinations in development, as limited clinical data are available for these agents.

A Clinical Decision Tree to Predict Whether a Bacteremic Patient Is Infected With an Extended-Spectrum β-Lactamase–Producing Organism

BACKGROUND Timely identification of extended-spectrum β-lactamase (ESBL) bacteremia can improve clinical outcomes while minimizing unnecessary use of broad-spectrum antibiotics, including carbapenems. However, most clinical microbiology laboratories currently require at least 24 additional hours from the time of microbial genus and species identification to confirm ESBL production. Our objective was to develop a user-friendly decision tree to predict which organisms are ESBL producing, to guide appropriate antibiotic therapy. METHODS We included patients ≥18 years of age with bacteremia due to Escherichia coli or Klebsiella species from October 2008 to March 2015 at Johns Hopkins Hospital. Isolates with ceftriaxone minimum inhibitory concentrations ≥2 µg/mL underwent ESBL confirmatory testing. Recursive partitioning was used to generate a decision tree to determine the likelihood that a bacteremic patient was infected with an ESBL producer. Discrimination of the original and cross-validated models was evaluated using receiver operating characteristic curves and by calculation of C-statistics. RESULTS A total of 1288 patients with bacteremia met eligibility criteria. For 194 patients (15%), bacteremia was due to a confirmed ESBL producer. The final classification tree for predicting ESBL-positive bacteremia included 5 predictors: history of ESBL colonization/infection, chronic indwelling vascular hardware, age ≥43 years, recent hospitalization in an ESBL high-burden region, and ≥6 days of antibiotic exposure in the prior 6 months. The decision trees positive and negative predictive values were 90.8% and 91.9%, respectively. CONCLUSIONS Our findings suggest that a clinical decision tree can be used to estimate a bacteremic patients likelihood of infection with ESBL-producing bacteria. Recursive partitioning offers a practical, user-friendly approach for addressing important diagnostic questions.

Cleaning Hospital Room Surfaces to Prevent Health Care–Associated Infections: A Technical Brief

The cleaning of hard surfaces in hospital rooms is critical for reducing health care-associated infections. This review describes the evidence examining current methods of cleaning, disinfecting, and monitoring cleanliness of patient rooms, as well as contextual factors that may affect implementation and effectiveness. Key informants were interviewed, and a systematic search for publications since 1990 was done with the use of several bibliographic and gray literature resources. Studies examining surface contamination, colonization, or infection with Clostridium difficile, methicillin-resistant Staphylococcus aureus, or vancomycin-resistant enterococci were included. Eighty studies were identified-76 primary studies and 4 systematic reviews. Forty-nine studies examined cleaning methods, 14 evaluated monitoring strategies, and 17 addressed challenges or facilitators to implementation. Only 5 studies were randomized, controlled trials, and surface contamination was the most commonly assessed outcome. Comparative effectiveness studies of disinfecting methods and monitoring strategies were uncommon. Future research should evaluate and compare newly emerging strategies, such as self-disinfecting coatings for disinfecting and adenosine triphosphate and ultraviolet/fluorescent surface markers for monitoring. Studies should also assess patient-centered outcomes, such as infection, when possible. Other challenges include identifying high-touch surfaces that confer the greatest risk for pathogen transmission; developing standard thresholds for defining cleanliness; and using methods to adjust for confounders, such as hand hygiene, when examining the effect of disinfecting methods.

Effect of Reduced Vancomycin Susceptibility on Clinical and Economic Outcomes in Staphylococcus aureus Bacteremia

ABSTRACT Reduced vancomycin susceptibility (RVS) may lead to poor clinical outcomes in Staphylococcus aureus bacteremia. The objective of this study was to evaluate the clinical and economic impact of RVS in patients with bacteremia due to S. aureus. A cohort study of patients who were hospitalized from December 2007 to May 2009 with S. aureus bacteremia was conducted within a university health system. Multivariable logistic regression and zero-truncated negative binomial regression models were developed to evaluate the association of RVS with 30-day in-hospital mortality, length of stay, and hospital charges. One hundred thirty-four (34.2%) of a total of 392 patients had bacteremia due to S. aureus with RVS as defined by a vancomycin Etest MIC of >1.0 μg/ml. Adjusted risk factors for 30-day in-hospital mortality included the all patient refined-diagnosis related group (APRDRG) risk-of-mortality score (odds ratio [OR], 7.11; 95% confidence interval [CI], 3.04 to 16.6), neutropenia (OR, 13.4; 95% CI, 2.46 to 73.1), white blood cell count (OR, 1.05; 95% CI, 1.01 to 1.09), immunosuppression (OR, 6.31; 95% CI, 1.74 to 22.9), and intensive care unit location (OR, 3.51; 95% CI, 1.65 to 7.49). In multivariable analyses, RVS was significantly associated with increased mortality in patients with S. aureus bacteremia as a result of methicillin-susceptible (OR, 3.90; 95% CI, 1.07 to 14.2) but not methicillin-resistant (OR, 0.53; 95% CI, 0.19 to 1.46) isolates. RVS was associated with greater 30-day in-hospital mortality in patients with bacteremia due to methicillin-susceptible S. aureus but not methicillin-resistant S. aureus. Further research is needed to identify optimal treatment strategies to reduce mortality associated with RVS in S. aureus bacteremia.

Reduced vancomycin susceptibility and staphylococcal cassette chromosome mec (SCCmec) type distribution in methicillin-resistant Staphylococcus aureus bacteraemia

OBJECTIVES Recent epidemiological evidence suggests that genotypic and phenotypic characteristics that have typically distinguished community-associated methicillin-resistant Staphylococcus aureus (MRSA) and healthcare-associated MRSA strains may be evolving. The objective of this study was to examine the association between reduced vancomycin susceptibility (RVS) and staphylococcal cassette chromosome mec (SCCmec) type in MRSA bloodstream isolates. METHODS A cohort study of patients who were hospitalized from 2007 to 2009 with S. aureus bacteraemia was conducted within a university health system. Bivariable analyses were conducted to determine the association between RVS and SCCmec type, as well as other microbiological characteristics including Panton-Valentine leucocidin, accessory gene regulator (agr) dysfunction and vancomycin heteroresistance. RESULTS A total of 188 patients with MRSA bacteraemia were identified: 116 (61.7%) and 72 (38.3%) patients had infections due to healthcare-associated MRSA and community-associated MRSA, respectively. As defined by a vancomycin Etest MIC > 1.0 mg/L, the prevalence of RVS was 40.4%. Isolates with RVS were significantly more likely to be associated with SCCmec II compared with isolates without RVS (74.7% and 47.3%, respectively, P < 0.001), but not with Panton-Valentine leucocidin (P = 0.10), agr dysfunction (P = 0.19) or healthcare-associated infection (P = 0.36). CONCLUSIONS The results of our study demonstrate important microbiological characteristics among MRSA isolates characterized by RVS, including a significant association between SCCmec II and elevated vancomycin MIC. It is clear that the clinical and molecular epidemiology of MRSA is evolving, and further understanding of factors determining virulence will be important for the elucidation of optimal treatment approaches for associated infections.

Colonization with Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella Species in Long-Term Care Facility Residents

We describe the prevalence of and risk factors for colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-EB) in the long-term care facility (LTCF) setting. Colonization prevalence differed significantly across the 3 LTCFs evaluated in the study, with recent use of levofloxacin and fecal incontinence demonstrating borderline significant associations with ESBL-EB colonization.

HIV infection and glycemic response to newly initiated diabetic medical therapy.

Objectives:Type 2 diabetes (DM2) is increasingly common in HIV-infected individuals. Antiretroviral agents and chronic inflammation may adversely affect glycemic control. However, little is known about the effectiveness of diabetic medical therapy in HIV-infected patients. The objective of this study was to compare the effectiveness of initial diabetic medical therapy in patients with and without HIV infection. Design:A retrospective cohort study was conducted among adults with DM2 initiating diabetic medications within the Centers for AIDS Research Network of Integrated Clinical Systems cohort. Methods:Generalized estimating equations were used to compare changes in hemoglobin A1c (HbA1c) through the year after initiation of therapy, controlling for baseline HbA1c and demographic and clinical covariates. Results:Two hundred and eighty-six HIV-infected patients and 858 age and sex-matched HIV-uninfected patients initiated diabetic medications during the study period. Overall, patients had an adjusted absolute mean reduction in HbA1c of 1.04% [95% confidence interval (CI) −0.87 to −1.22] during the first year of therapy. HIV-infected patients achieved significantly smaller reductions in HbA1c, with an absolute mean difference of −0.17% (95% CI −0.28 to −0.06; P = 0.003). On subanalyses, HIV-infected patients on a protease inhibitor-based regimen had significantly smaller reductions in HbA1c compared to HIV-uninfected patients (adjusted absolute difference −0.21%, 95% CI −0.35 to −0.08; P = 0.002). Conclusion:Patients with HIV infection who initiate diabetic medical therapy achieve smaller reductions in HbA1c than patients without HIV infection in the course of routine clinical care. This less robust response may in part be related to use of antiretrovirals that exacerbate insulin resistance, specifically protease inhibitors.

Comparing the Outcomes of Adults With Enterobacteriaceae Bacteremia Receiving Short-Course Versus Prolonged-Course Antibiotic Therapy in a Multicenter, Propensity Score–Matched Cohort

Background The recommended duration of antibiotic treatment for Enterobacteriaceae bloodstream infections is 7-14 days. We compared the outcomes of patients receiving short-course (6-10 days) vs prolonged-course (11-16 days) antibiotic therapy for Enterobacteriaceae bacteremia. Methods A retrospective cohort study was conducted at 3 medical centers and included patients with monomicrobial Enterobacteriaceae bacteremia treated with in vitro active therapy in the range of 6-16 days between 2008 and 2014. 1:1 nearest neighbor propensity score matching without replacement was performed prior to regression analysis to estimate the risk of all-cause mortality within 30 days after the end of antibiotic treatment comparing patients in the 2 treatment groups. Secondary outcomes included recurrent bloodstream infections, Clostridium difficile infections (CDI), and the emergence of multidrug-resistant gram-negative (MDRGN) bacteria, all within 30 days after the end of antibiotic therapy. Results There were 385 well-balanced matched pairs. The median duration of therapy in the short-course group and prolonged-course group was 8 days (interquartile range [IQR], 7-9 days) and 15 days (IQR, 13-15 days), respectively. No difference in mortality between the treatment groups was observed (adjusted hazard ratio [aHR], 1.00; 95% confidence interval [CI], .62-1.63). The odds of recurrent bloodstream infections and CDI were also similar. There was a trend toward a protective effect of short-course antibiotic therapy on the emergence of MDRGN bacteria (odds ratio, 0.59; 95% CI, .32-1.09; P = .09). Conclusions Short courses of antibiotic therapy yield similar clinical outcomes as prolonged courses of antibiotic therapy for Enterobacteriaceae bacteremia, and may protect against subsequent MDRGN bacteria.

Risk factors for the development of gastrointestinal colonization with fluoroquinolone-resistant Escherichia coli in residents of long-term care facilities.

BACKGROUND The objective of this study was to assess risk factors for the development of fluoroquinolone (FQ)-resistant Escherichia coli gastrointestinal tract colonization in long-term care facility (LTCF) residents. METHODS A prospective cohort study was conducted from 2006 to 2008 at 3 LTCFs. Residents initially colonized with FQ-susceptible E. coli were followed by means of serial fecal sampling for new FQ-resistant E. coli colonization for up to 12 months or until discharge or death. A Cox proportional hazards regression model was developed to identify risk factors for new FQ-resistant E. coli colonization, with antibiotic and device exposures modeled as time-varying covariates. RESULTS Fifty-seven (47.5%) of 120 residents became newly colonized with FQ-resistant E. coli, with a median time to colonization of 57 days. Fecal incontinence (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.04-3.06; P = .04) was significantly associated with FQ-resistant E. coli acquisition. Receipt of amoxicillin-clavulanate (HR, 6.48; 95% CI, 1.43-29.4; P = .02) and the presence of a urinary catheter (HR, 3.81; 95% CI, 1.06-13.8; P = .04) during LTCF stay increased the risk of new FQ-resistant E. coli colonization. CONCLUSIONS Acquisition of FQ-resistant E. coli was common, with nearly half of LTCF residents developing new FQ-resistant E. coli colonization. Further studies are needed on interventions to limit the emergence of FQ-resistant E. coli in LTCFs.

Risk Factors for Infection or Colonization with CTX-M Extended-Spectrum-β-Lactamase-Positive Escherichia coli

ABSTRACT There has been a significant increase in the prevalence of Enterobacteriaceae that produce CTX-M-type extended-spectrum β-lactamases. The objective of this study was to evaluate risk factors for infection or colonization with CTX-M-positive Escherichia coli. A case-control study was conducted within a university system from 1 January 2007 to 31 December 2008. All patients with clinical cultures with E. coli demonstrating resistance to extended-spectrum cephalosporins were included. Case patients were designated as those with cultures positive for CTX-M-positive E. coli, and control patients were designated as those with non-CTX-M-producing E. coli. Multivariable logistic regression analyses were performed to evaluate risk factors for CTX-M-positive isolates. A total of 83 (56.8%) of a total of 146 patients had cultures with CTX-M-positive E. coli. On multivariable analyses, there was a significant association between infection or colonization with CTX-M-type β-lactamase-positive E. coli and receipt of piperacillin-tazobactam in the 30 days prior to the culture date (odds ratio [OR], 7.36; 95% confidence interval [CI], 1.61 to 33.8; P = 0.01) and a urinary culture source (OR, 0.36; 95% CI, 0.17 to 0.77; P = 0.008). The rates of resistance to fluoroquinolones were significantly higher in isolates from case patients than in isolates from control patients (90.4 and 50.8%, respectively; P < 0.001). We found that nonurinary sources of clinical cultures and the recent use of piperacillin-tazobactam conferred an increased risk of colonization or infection with CTX-M-positive E. coli. Future studies will need to focus on outcomes associated with infections due to CTX-M-positive E. coli, as well as infection control strategies to limit the spread of these increasingly common organisms.