Carbapenem versus Cefepime or Piperacillin-Tazobactam for Empiric Treatment of Bacteremia Due to Extended-Spectrum-β-Lactamase-Producing Escherichia coli in Patients with Hematologic Malignancy

Abstract

Infections with extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli are common in patients with hematologic malignancy. The utility of cefepime and piperacillin-tazobactam as empiric therapy for ESBL-producing E. coli bacteremia in patients with hematologic malignancy is largely unknown. We conducted a single-center, retrospective cohort review of 103 adult inpatients with leukemia and/or hematopoietic stem cell transplant (HCT) recipients with monomicrobial ESBL-producing E. coli bacteremia. No association between increased 14-day mortality and empiric treatment with cefepime (8%) or piperacillin-tazobactam (0%) relative to that with carbapenems (19%) was observed (P = 0.19 and P = 0.04, respectively). This observation was consistent in multivariate Cox proportional hazards models adjusted for confounding and an inverse probability of treatment-weighted (IPTW) Cox proportional hazards model. Both fever and persistent bacteremia were more common in patients treated empirically with cefepime or piperacillin-tazobactam. Empiric treatment with cefepime or piperacillin-tazobactam did not result in increased mortality relative to that with treatment with carbapenems in patients with hematologic malignancy and ESBL-producing E. coli bacteremia, although most patients were changed to carbapenems early in treatment. However, due to prolonged fever and persistent bacteremia, their role may be limited in this patient population.

Carbapenem-Sparing Strategies for ESBL Producers: When and How

“…The clinical studies comparing the efficacy of PTZ versus carbapenems in infections caused by ESBL-PE are depicted in Table 1 [10][11][12][13][19][20][21][22][23][24][25][26][27][28][29][30]. Most comparative studies of PTZ versus carbapenems are retrospective and difficult to be evaluated because of several disagreements [11][12][13][19][20][21][22]24,25,[27][28][29][30]. Rodríguez-Baño et al [10] in 2012 conducted a post hoc analysis of patients with blood stream infection (BSI) due to ESBL-PE derived from 6 published prospective cohorts in Spain.…”

“…Table 1. Clinical studies comparing the efficacy of piperacillin-tazobactam versus carbapenems in infections caused by ESBL-producing Enterobacterales [10][11][12][13][19][20][21][22][23][24][25][26][27][28][29][30]. BSI, blood stream infection; CRBSI, catheter-related blood stream infection; cIAI, complicated intra-abdominal infection; ESBL, extended spectrum β-lactamases; ICU, intensive care unit; NR, not reported; ns, not significant; OR, odds ratio; PTZ, piperacillin-tazobactam; SSTI, skin and soft tissue infections; UTI, urinary tract infection; vs, versus.…”

“…Although some observational data have suggested that high-dose cefepime (e.g., 2 g every eight hours) can be effective for the treatment of ESBL-producing infections as a carbapenem-sparing agent [64,65], superiority of carbapenem treatment has been highlighted regarding therapy of ESBL infections [66][67][68][69]. The clinical studies comparing the efficacy of cefepime versus carbapenems in infections caused by ESBL-PE are illustrated in Table 3 [23,27,[64][65][66][67][68][69][70][71]. Chopra et al [66] outlined in a multivariate analysis that empirical therapy with cefepime for BSI due to an ESBL-producing pathogen was associated with a trend toward an increased mortality risk, and empirical carbapenem therapy was associated with a trend toward decreased mortality risk.…”

“…In multivariate analysis, empiric treatment with cefepime was not associated with increased 14-day or 30-day mortality. However, time to defervescence (p < 0.01) and persistent bacteremia (p = 0.07) were associated with cefepime treatment, hindering the use of cefepime in this specific population [27]. Table 3.…”

Comparative efficacy and safety of β-lactam/β-lactamase inhibitors versus cabapenems for febrile neutropenia empiric therapy: A systematic review and meta analysis

“…Lan et al reported that cefoperazone/sulbactam was not signi cantly different with other comparators in mortality through pooled analysis (OR 0.96, 95% CI 0.58-1.58) [25]. Recently a single-center retrospective cohort study conducted by Benanti et al showed empiric treatment with cefepime or piperacillin-tazobactam was not associated with increased 14-day mortality in neutropenic patients with hematologic malignancy and ESBL-producing E. coli bacteremia relative to that with empiric treatment with a carbapenem [26]. These ndings favor the use of BL/BLIs in empiric treatment of febrile neutropenia.…”