β-Lactam/β-lactamase inhibitors versus carbapenems for the treatment of sepsis: systematic review and meta-analysis of randomized controlled trials

Shiber, Shachaf; Yahav, Dafna; Avni, Tomer; Leibovici, Leonard; Paul, Mical

doi:10.1093/jac/dku351

Cited by 42 publications

(38 citation statements)

References 38 publications

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“…BLBLIs have been shown to be as effective as carbapenems for the treatment of diverse severe infections in randomized trials (21). The reasons for raising doubts about the efficacy of BLBLIs in the treatment of severe infections caused by ESBL-E include the fol- lowing.…”

Section: Discussionmentioning

confidence: 99%

A Multinational, Preregistered Cohort Study of β-Lactam/β-Lactamase Inhibitor Combinations for Treatment of Bloodstream Infections Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae

Gutiérrez‐Gutiérrez

Pérez-Galera

Salamanca

et al. 2016

Antimicrob Agents Chemother

145

111

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The spread of extended-spectrum-␤-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether ␤-lactam/␤-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.)

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Section: Discussionmentioning

confidence: 99%

A Multinational, Preregistered Cohort Study of β-Lactam/β-Lactamase Inhibitor Combinations for Treatment of Bloodstream Infections Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae

Gutiérrez‐Gutiérrez

Pérez-Galera

Salamanca

et al. 2016

Antimicrob Agents Chemother

145

111

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“…Nevertheless, given the low number of patients receiving targeted BLBLI therapy, we cannot draw any firm conclusion. To date, the published data on the use of BLBLIs for the treatment of infections caused by ESBL-GNB are conflicting and mainly refer to nonimmunocompromised patients (13)(14)(15)(16)(17)(18)(19)(20)(21). Our study was the first to assess the usefulness of BLBLIs for the treatment of ESBL-BSI in a severely immunosuppressed cohort of hematological patients with neutropenia.…”

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confidence: 99%

“…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.…”

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confidence: 99%

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

Gudiol

Royo-Cebrecos

Abdala

et al. 2017

Antimicrob Agents Chemother

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␤-Lactam/␤-lactamase inhibitors (BLBLIs) were compared to carbapenems in two cohorts of hematological neutropenic patients with extended-spectrum-␤-lactamase (ESBL) bloodstream infection (BSI): the empirical therapy cohort (174 patients) and the definitive therapy cohort (251 patients). The 30-day case fatality rates and other secondary outcomes were similar in the two therapy groups of the two cohorts and also in the propensity-matched cohorts. BLBLIs might be carbapenemsparing alternatives for the treatment of BSI due to ESBLs in these patients.

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“…Although some studies have proposed a combination of β‐lactam/β‐lactamase inhibitors as an alternative to carbapenems for treating these resistant strains in the general population , the usefulness of this approach for the treatment of BSI in SOT recipients has not been conclusively demonstrated. The INCREMENT‐SOT project, currently in progress, should shed light on this issue .…”

Section: Discussionmentioning

confidence: 99%

Changing trends in the aetiology, treatment and outcomes of bloodstream infection occurring in the first year after solid organ transplantation: a single-centre prospective cohort study

et al. 2017

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To analyse trends in the aetiology, treatment and outcomes of bloodstream infection (BSI) within the first year post-transplant over the last 10-year period, we prospectively recorded all episodes of BSI occurring in solid organ transplant (SOT) recipients during the first year post-transplant from 2007 to 2016. Trends of factors were analysed by 2-year periods. Of 475 consecutive episodes of BSI, 218 occurred within a year of SOT in 178 SOT recipients. Gram-positive BSI decreased over time (40.5-2.2%). In contrast, there was a steady increase in Gram-negative bacilli (GNB) BSI (54.1-93.3%; P < 0.001), mainly due to Pseudomonas aeruginosa (2.4-20.4%) and Klebsiella pneumoniae (7.1-26.5%). Multidrug-resistant (MDR) GNB (4.8-38.8%; P < 0.001) rose dramatically, especially due to extended-spectrum β-lactamase (ESBL) production (7.1-34.7%). There was a sharp rise in the use of carbapenems, both as empirical (11.9-55.3%; P < 0.001) and as targeted antibiotic treatment (11.9-46.9%; P < 0.001). In conclusion, today, GNB are the leading causative agents of BSI in SOT recipients within the first year after SOT. In addition, MDR GNB have emerged mainly due to ESBL-producing strains. In spite of these changes, length of hospital stay, days of treatment and mortality have remained stable over time.

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β-Lactam/β-lactamase inhibitors versus carbapenems for the treatment of sepsis: systematic review and meta-analysis of randomized controlled trials

Abstract: No differences in efficacy between BL/BLIs and carbapenems exist in RCTs including patient populations with a certain, albeit unknown, rate of ESBL-positive bacteria causing infections.

Cited by 42 publications

References 38 publications

A Multinational, Preregistered Cohort Study of β-Lactam/β-Lactamase Inhibitor Combinations for Treatment of Bloodstream Infections Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae

A Multinational, Preregistered Cohort Study of β-Lactam/β-Lactamase Inhibitor Combinations for Treatment of Bloodstream Infections Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae

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

Changing trends in the aetiology, treatment and outcomes of bloodstream infection occurring in the first year after solid organ transplantation: a single-centre prospective cohort study

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