Increased carbapenem use has contributed to the emergence of carbapenem-resistant Enterobacteriaceae. However, indiscriminant carbapenem use is not without consequence. The existing literature indicates that carbapenems have a relatively high rate of clinical success among patients infected with ESBL-producing organisms. ESBL-producing organisms have been associated with poorer clinical outcomes compared with more susceptible organisms, partially attributable to a delay in initiating appropriate antimicrobial therapy. Such is the case with extended-spectrum β-lactamase (ESBL)-producing bacteria. The prevalence of gram-negative bacteria resistant to broad-spectrum β-lactams has increased at a rapid pace over the past decade. (See the Editorial Commentary by Perez and Bonomo on pages 1326–9.) Our findings should not be extended to β-lactam/β-lactamase inhibitor combinations in development, as limited clinical data are available for these agents. For patients at high risk of invasive ESBL infections, early carbapenem therapy should be considered. 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).Ĭonclusions. PTZ appears inferior to carbapenems for the treatment of ESBL bacteremia. One hundred three (48%) patients received PTZ empirically and 110 (52%) received carbapenems empirically. Results. A total of 331 unique patients with ESBL bacteremia were identified. We calculated overall hazard ratios for mortality censored at 14 days using Cox proportional hazards models on an IPW-adjusted cohort. Propensity scores using inverse probability of exposure weighting (IPW) were used to estimate the probability that a patient would receive PTZ vs carbapenems empirically.
The primary outcome was time to death from the first day of bacteremia. Patients were excluded if they did not receive a carbapenem after ESBL production was identified. The primary exposure was empiric therapy, defined as antibiotic therapy administered to a patient before ESBL status was known. 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. Methods. Patients hospitalized between January 2007 and April 2014 with monomicrobial ESBL bacteremia were included. 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. Background. The effectiveness of piperacillin-tazobactam (PTZ) for the treatment of extended-spectrum β-lactamase (ESBL) bacteremia is controversial.