PMID- 36211957
OWN - NLM
STAT- MEDLINE
DCOM- 20221011
LR  - 20221012
IS  - 2235-2988 (Electronic)
IS  - 2235-2988 (Linking)
VI  - 12
DP  - 2022
TI  - Efficacy and safety of novel carbapenem-beta-lactamase inhibitor combinations: 
      Results from phase II and III trials.
PG  - 925662
LID - 10.3389/fcimb.2022.925662 [doi]
LID - 925662
AB  - OBJECTIVES: The addition of novel beta-lactamase inhibitors to carbapenems restores 
      the activity against multidrug-resistant Gram-negative bacteria. The aim of this 
      study was to summarize the evidence on the efficacy and safety of novel 
      carbapenem-beta-lactamase inhibitor combinations. METHODS: We conducted a 
      meta-analysis of clinical trials comparing novel carbapenem-beta-lactamase inhibitor 
      combinations with comparators to assess the clinical and microbiological 
      responses, mortality, and adverse events (AEs). RESULTS: A total of 1,984 
      patients were included. The pooled risk ratios (RRs) of clinical cure, 
      microbiological eradication, all-cause mortality, and 28-day mortality were 1.11 
      (95% CI: 0.98-1.26), 0.98 (95% CI: 0.82-1.16), 0.90 (95% CI: 0.49-0.94), and 0.68 
      (95% CI: 0.49-0.94) between the novel carbapenem-beta-lactamase inhibitor 
      combinations and control groups. Sensitivity analysis revealed that the phase II 
      trial of imipenem-cilastatin/relebactam (ICR) against complicated urinary tract 
      infections could be the most important factor of heterogeneity for the 
      microbiological response. The therapeutic effect of novel carbapenem-beta-lactamase 
      inhibitor combinations was better in meropenem-vaborbactam (MEV), phase III 
      trials, and number of patients less than 200. The RRs of AEs from any cause and 
      serious adverse events (SAEs) for patients receiving novel carbapenem-beta-lactamase 
      inhibitor combinations were 0.98 (95% CI: 0.93-1.04) and 1.01 (95% CI: 
      0.75-1.36), respectively. CONCLUSIONS: ICR and MEV were superior to comparators 
      for clinical cure and survival rate in the treatment of complicated infections, 
      and both were as tolerable as the comparators.
CI  - Copyright (c) 2022 Yu, Shen, Luo, Xiong and Xiao.
FAU - Yu, Wei
AU  - Yu W
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National 
      Clinical Research Center for Infectious Diseases, Collaborative Innovation Center 
      for Diagnosis and Treatment of Infectious Diseases, The First Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Shen, Ping
AU  - Shen P
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National 
      Clinical Research Center for Infectious Diseases, Collaborative Innovation Center 
      for Diagnosis and Treatment of Infectious Diseases, The First Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Luo, Qixia
AU  - Luo Q
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National 
      Clinical Research Center for Infectious Diseases, Collaborative Innovation Center 
      for Diagnosis and Treatment of Infectious Diseases, The First Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Xiong, Luying
AU  - Xiong L
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National 
      Clinical Research Center for Infectious Diseases, Collaborative Innovation Center 
      for Diagnosis and Treatment of Infectious Diseases, The First Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Xiao, Yonghong
AU  - Xiao Y
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National 
      Clinical Research Center for Infectious Diseases, Collaborative Innovation Center 
      for Diagnosis and Treatment of Infectious Diseases, The First Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
DEP - 20220923
PL  - Switzerland
TA  - Front Cell Infect Microbiol
JT  - Frontiers in cellular and infection microbiology
JID - 101585359
RN  - 0 (Carbapenems)
RN  - 0 (Drug Combinations)
RN  - 0 (beta-Lactamase Inhibitors)
RN  - 92309-29-0 (Cilastatin, Imipenem Drug Combination)
RN  - FV9J3JU8B1 (Meropenem)
SB  - IM
MH  - *Carbapenems/therapeutic use
MH  - Cilastatin, Imipenem Drug Combination/adverse effects
MH  - Clinical Trials, Phase II as Topic
MH  - Clinical Trials, Phase III as Topic
MH  - Drug Combinations
MH  - Humans
MH  - Meropenem/therapeutic use
MH  - Microbial Sensitivity Tests
MH  - *beta-Lactamase Inhibitors/therapeutic use
PMC - PMC9538188
OTO - NOTNLM
OT  - adverse effects
OT  - clinical cure
OT  - imipenem-cilastatin/relebactam
OT  - meropenem-vaborbactam
OT  - mortality
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/10/11 06:00
MHDA- 2022/10/12 06:00
PMCR- 2022/01/01
CRDT- 2022/10/10 04:03
PHST- 2022/04/21 00:00 [received]
PHST- 2022/08/26 00:00 [accepted]
PHST- 2022/10/10 04:03 [entrez]
PHST- 2022/10/11 06:00 [pubmed]
PHST- 2022/10/12 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fcimb.2022.925662 [doi]
PST - epublish
SO  - Front Cell Infect Microbiol. 2022 Sep 23;12:925662. doi: 
      10.3389/fcimb.2022.925662. eCollection 2022.