Shachaf Shiber1, Dafna Yahav2, Tomer Avni3, Leonard Leibovici4, Mical Paul5. 1. Emergency Department, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel. 2. Unit of Infectious Diseases, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel dafna.yahav@gmail.com. 3. Medicine E, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel. 4. Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel Medicine E, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel. 5. Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel Unit of Infectious Diseases, Rambam Health Care Center, Haifa, Israel.
Abstract
BACKGROUND: Data on the relative efficacy of β-lactam/β-lactamase inhibitors (BL/BLIs) versus carbapenems are scant. METHODS: This is a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing any BL/BLI versus any carbapenem for the treatment of sepsis. The primary outcome was all-cause mortality. A broad search was conducted with no restrictions on language, publication status or date. Two reviewers independently applied the inclusion criteria and extracted the data. Assessment of risk of bias was performed using the domain-based approach. Subgroup analyses were used to investigate heterogeneity and focus on patient groups more likely to harbour ESBL-positive bacteria. Risk ratios (RRs) with 95% CIs were calculated and pooled. RESULTS: Thirty-one RCTs were included. There was no difference between BL/BLIs and carbapenems in terms of mortality (RR 0.98, 95% CI 0.79-1.20), without heterogeneity. No differences were observed with regard to clinical or microbiological failure and bacterial superinfections. The results were not affected by risk of bias. No differences were detected in the subgroups of patients with nosocomial infections, Gram-negative infections and neutropenic fever. Adverse events requiring discontinuation were more common with BL/BLIs, on account of an increased incidence of diarrhoea. However, Clostridium difficile-associated diarrhoea (RR 0.29, 95% CI 0.10-0.87) was more frequent with carbapenems and seizures were more frequent with imipenem (RR 0.21, 95% CI 0.05-0.93). CONCLUSIONS: 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.
BACKGROUND: Data on the relative efficacy of β-lactam/β-lactamase inhibitors (BL/BLIs) versus carbapenems are scant. METHODS: This is a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing any BL/BLI versus any carbapenem for the treatment of sepsis. The primary outcome was all-cause mortality. A broad search was conducted with no restrictions on language, publication status or date. Two reviewers independently applied the inclusion criteria and extracted the data. Assessment of risk of bias was performed using the domain-based approach. Subgroup analyses were used to investigate heterogeneity and focus on patient groups more likely to harbour ESBL-positive bacteria. Risk ratios (RRs) with 95% CIs were calculated and pooled. RESULTS: Thirty-one RCTs were included. There was no difference between BL/BLIs and carbapenems in terms of mortality (RR 0.98, 95% CI 0.79-1.20), without heterogeneity. No differences were observed with regard to clinical or microbiological failure and bacterial superinfections. The results were not affected by risk of bias. No differences were detected in the subgroups of patients with nosocomial infections, Gram-negative infections and neutropenic fever. Adverse events requiring discontinuation were more common with BL/BLIs, on account of an increased incidence of diarrhoea. However, Clostridium difficile-associated diarrhoea (RR 0.29, 95% CI 0.10-0.87) was more frequent with carbapenems and seizures were more frequent with imipenem (RR 0.21, 95% CI 0.05-0.93). CONCLUSIONS: 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.
Authors: Belén Gutiérrez-Gutiérrez; Salvador Pérez-Galera; Elena Salamanca; Marina de Cueto; Esther Calbo; Benito Almirante; Pierluigi Viale; Antonio Oliver; Vicente Pintado; Oriol Gasch; Luis Martínez-Martínez; Johann Pitout; Murat Akova; Carmen Peña; José Molina; Alicia Hernández; Mario Venditti; Nuria Prim; Julia Origüen; German Bou; Evelina Tacconelli; Mario Tumbarello; Axel Hamprecht; Helen Giamarellou; Manel Almela; Federico Pérez; Mitchell J Schwaber; Joaquín Bermejo; Warren Lowman; Po-Ren Hsueh; Marta Mora-Rillo; Clara Natera; Maria Souli; Robert A Bonomo; Yehuda Carmeli; David L Paterson; Alvaro Pascual; Jesús Rodríguez-Baño Journal: Antimicrob Agents Chemother Date: 2016-06-20 Impact factor: 5.191
Authors: Kelly Roveran Genga; Tadanaga Shimada; John H Boyd; Keith R Walley; James A Russell Journal: J Innate Immun Date: 2018-05-15 Impact factor: 7.349