Evaluation of the in vitro synergy of polymyxin B-based combinations against polymyxin B -resistant gram-negative bacilli

Li, You; Guo, Siwei; Li, Xin; Yu, Yunsong; Yan, Bingqian; Tian, Miaomei; Xu, Bing; Hu, Huangdu

doi:10.1016/j.micpath.2022.105517

Cited by 6 publications

(1 citation statement)

References 33 publications

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“… 22 Previous studies have shown that ceftazidime-avibactam plus polymyxin B shows synergistic effects against 69.4% (25/36) of isolates with polymyxin B MICs ≥4 mg/L. 23 In this study, polymyxin B plus ceftazidime-avibactam showed synergistic effects against 63.6% (7/11) of the strains susceptible to both drugs. Synergistic effects were also observed in the three ceftazidime-avibactam-resistant NDM producers.…”

Section: Discussionsupporting

confidence: 48%

In vitro Synergistic Activity of Ceftazidime-Avibactam in Combination with Aztreonam or Meropenem Against Clinical Enterobacterales Producing blaKPC or blaNDM

Kuai¹,

Zhang²,

Lu³

et al. 2023

IDR

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Background It is often challenging to select appropriate combination therapies to treat infections caused by carbapenem-resistant Enterobacterales (CRE) with high-level resistance to carbapenem. Methods We investigated the in vitro synergistic activity of ceftazidime-avibactam-, polymyxin- or tigecycline-, and meropenem-based combinations using checkerboard assays against 16 CRE including Klebsiella pneumoniae carrying bla KPC-2 (CR1- bla KPC-2 ) and Enterobacter cloacae carrying bla NDM-1 (CR2- bla NDM-1 ) with meropenem MICs ≥128 mg/L. Time-kill assays were used to observe synergistic bactericidal activity. Results Meropenem in combination with ertapenem, amikacin, tigecycline or polymyxin B, and tigecycline plus ceftazidime-avibactam showed weak synergistic activities against CR1- bla KPC-2 and CR2- bla NDM-1 . Polymyxin B combined with tigecycline or ceftazidime-avibactam, and ceftazidime-avibactam plus amikacin showed synergistic effects against two tigecycline-non-susceptible KPC-producers or three ceftazidime-avibactam-resistant NDM-producer, and 50% (5/10) of strains with amikacin MICs ≥4096 mg/L, respectively. Synergistic interactions of ceftazidime-avibactam plus aztreonam or meropenem in checkerboard assays were measured for 100% (16/16) and 93.8% (15/16) of strains, respectively. The time-kill assay further verified that the ceftazidime-avibactam combination had the potential to restore aztreonam susceptibility and reduced meropenem MICs to 8 mg/L. Conclusion Ceftazidime-avibactam plus aztreonam or meropenem could be an effective strategy for treating CRE infections, particularly those with high-level resistance to carbapenems and/or ceftazidime-avibactam.

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Section: Discussionsupporting

confidence: 48%