Empiric Piperacillin-Tazobactam versus Carbapenems in the Treatment of Bacteraemia Due to Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae

Abstract

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are a common cause of bacteraemia in endemic countries and may be associated with high mortality; carbapenems are considered the drug of choice. Limited data suggest piperacillin-tazobactam could be equally effective. We aimed to compare 30-day mortality of patients treated empirically with piperacillin-tazobactam versus a carbapenem in a multi-centre retrospective cohort study in Singapore. Only patients with active empiric monotherapy with piperacillin-tazobactam or a carbapenem were included. A propensity score for empiric carbapenem therapy was derived and an adjusted multivariate analysis of mortality was conducted. A total of 394 patients had ESBL-Escherichia.coli and ESBL-Klebsiella pneumoniae bacteraemia of which 23.1% were community acquired cases. One hundred and fifty-one received initial active monotherapy comprising piperacillin-tazobactam (n = 94) or a carbapenem (n = 57). Patients who received carbapenems were less likely to have health-care associated risk factors and have an unknown source of bacteraemia, but were more likely to have a urinary source. Thirty-day mortality was comparable between those who received empiric piperacillin-tazobactam and a carbapenem (29 [30.9%] vs. 17 [29.8%]), P = 0.89). Those who received empiric piperacillin-tazobactam had a lower 30-day acquisition of multi-drug resistant and fungal infections (7 [7.4%] vs. 14 [24.6%]), P<0.01). After adjusting for confounders, use of empiric piperacillin-tazobactam was not associated with increased 30-day mortality (OR 1.00, 95% CI; 0.45–2.17). Empiric piperacillin-tazobactam was not associated with increased 30-day mortality and may result in fewer multi-drug resistant and fungal infections when compared with a carbapenem.

The Use of Noncarbapenem β-Lactams for the Treatment of Extended-Spectrum β-Lactamase Infections

“…Finally, Ng and colleagues evaluated 30-day mortality comparing empiric PTZ and carbapenem in 151 patients with presumed ESBL bloodstream infections. Thirty-day mortality was no different between the groups [53]. As with previous studies that resulted in similar outcomes between the treatment groups, a minority of patients were in the ICU (<10%), the majority of patients were infected with E. coli bacteremia, and almost 70% of patients had urinary or biliary sources of bacteremia.…”

“…Existing observational data have indicated contradictory results between outcomes of patients receiving PTZ and carbapenems for the treatment of ESBL infections (Table 5) [8,47,[48][49][50][51][52][53][54]. Rodriguez-Baňo and colleagues provided some of the earliest robust data evaluating β-lactam-β-lactamase inhibitors (βL-βLIs) and carbapenems for the treatment of ESBL bacteremia by conducting a post hoc observational study of Spanish patients from 6 cohorts [47].…”

Clinical Uptake of Antimicrobial Stewardship Recommendations Following Nanosphere Verigene Blood Culture Gram-Negative Reporting

“…Of interest, we identifi ed high empiric use of carbapenem/quinolone drug classes despite low identifi cation of ESBL on the BC-GN result at the Baylor Irving site. Although carbapenems are active in this setting, these high-cost agents should be reserved for the additional coverage of drug-resistant organisms (13,14). Th e outcome of this study will allow concentration of antimicrobial stewardship eff orts at this site.…”

Efficacy of β-Lactam/β-Lactamase Inhibitor Combinations for the Treatment of Bloodstream Infection Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in Hematological Patients with Neutropenia

“…This is particularly worrisome in a scenario in which carbapenem-resistant Enterobacteriaceae (CRE) are spreading rapidly and are adversely compromising patients' outcomes (7)(8)(9)(10)(11)(12). While recent investigations have suggested that ␤-lactam/␤-lactamase inhibitors (BLBLIs) may be reliable options for the treatment of BSI due to ESBL-producing Gram-negative bacilli (ESBL-GNB), especially in nonimmunocompromised patients (13)(14)(15)(16)(17)(18)(19), other studies have found contrasting data (20,21). To date, the efficacy of BLBLIs for the treatment of BSI due to ESBL-GNB in high-risk hematological patients has not been established.…”