<i>In Vitro</i> Activity of Ceftazidime-Avibactam Alone and in Combination with Amikacin Against Colistin-Resistant Gram-Negative Pathogens

Chen, Tao; Xu, Wenchao; Yu, Kaihang; Zeng, Weiliang; Xu, Chunyan; Cao, Jianming; Zhou, Tieli

doi:10.1089/mdr.2019.0463

Cited by 10 publications

(13 citation statements)

References 29 publications

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“…Time-kill assays for ceftazidime-avibactam plus meropenem or aztreonam were carried out according to the reference. 16 Considering the high MIC values of these three antibiotics against CR1- bla KPC-2 and CR2- bla NDM-1 , the ceftazidime-avibactam plus meropenem or aztreonam combination assays were performed with each drug at the concentration of 1/4× MIC, 1/8× MIC, 1/16× MIC, 1/32× MIC, 1/64× MIC and 1/128× MIC, respectively. To determine whether the susceptible breakpoint concentration of ceftazidime-avibactam (8 mg/L) could reduce meropenem or aztreonam MICs to their respective susceptible breakpoint concentrations, the time-kill assays were examined at the concentration of 4 or 8 mg/L of ceftazidime-avibactam plus the concentration of 2, 4 or 8 mg/L of aztreonam or meropenem.…”

Section: Methodsmentioning

confidence: 99%

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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: Methodsmentioning

confidence: 99%

“…Synergistic effect was defined as a ≥2 log 10 CFU/mL reduction in colony count at 24 h compared with the most active single drugs. 16 …”

Section: Methodsmentioning

confidence: 99%

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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“…The combination therapies reduce the dosage and duration of drug treatment and the associated side effects, show maximum antimicrobial effects, and in particular prevent or alleviate the development of resistance ( Chen et al, 2021 ). Thus, it is interesting to know whether there is a synergistic relationship between Phibilin and antifungal agents.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo Activity of Phibilin Against Candida albicans

Jing

Yuan

et al. 2022

Front. Microbiol.

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The increase in the occurrence of antifungal-resistant Candida albicans infections necessitates more research to explore alternative effective and safe agents against this fungus. In this work, Phibilin, a new antimicrobial peptide obtained from Philomycus bilineatus and used in traditional Chinese medicine, effectively inhibits the growth and activities of C. albicans, including the clinical resistant strains. Phibilin is a fungicidal antimicrobial peptide that exhibited its antimicrobial effect against C. albicans mainly by disrupting the membrane and interacting with the DNA of the fungi. In particular, Phibilin induces the necrosis of C. albicans via the ROS-related pathway. Moreover, this antifungal compound inhibited the biofilm formation of C. albicans by preventing the development of hyphae in a dose-dependent manner. Furthermore, Phibilin and clotrimazole displayed a synergistic effect in inhibiting the growth of the fungi. In the mouse cutaneous infection model, Phibilin significantly inhibited the formation of skin abscesses and decreased the counts of C. albicans cells in the infected area. Overall, Phibilin is potentially an effective agent against skin infections caused by C. albicans.

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“…These findings are a salient reminder of the propensity of P. aeruginosa to undergo rapid evolution to develop novel resistance phenotypes and highlight the vital importance of microbiological cultures, susceptibility testing (as well as local and regional susceptibility patterns) and use of molecular diagnostics wherever possible to guide treatment of P. aeruginosa infections. In vitro data suggest that combining ceftazidime–avibactam with other antibiotics such as aminoglycosides or colistin may be synergistic against MDR P. aeruginosa [ 84 , 85 , 86 ].…”

Section: Role Of Ceftazidime–avibactam In the Treatment Of P Aeruginosa Infectionsmentioning

confidence: 99%

Review of Ceftazidime-Avibactam for the Treatment of Infections Caused by Pseudomonas aeruginosa

et al. 2021

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Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes a range of serious infections that are often challenging to treat, as this pathogen can express multiple resistance mechanisms, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes. Ceftazidime–avibactam is a combination antimicrobial agent comprising ceftazidime, a third-generation semisynthetic cephalosporin, and avibactam, a novel non-β-lactam β-lactamase inhibitor. This review explores the potential role of ceftazidime–avibactam for the treatment of P. aeruginosa infections. Ceftazidime–avibactam has good in vitro activity against P. aeruginosa relative to comparator β-lactam agents and fluoroquinolones, comparable to amikacin and ceftolozane–tazobactam. In Phase 3 clinical trials, ceftazidime–avibactam has generally demonstrated similar clinical and microbiological outcomes to comparators in patients with complicated intra-abdominal infections, complicated urinary tract infections or hospital-acquired/ventilator-associated pneumonia caused by P. aeruginosa. Although real-world data are limited, favourable outcomes with ceftazidime–avibactam treatment have been reported in some patients with MDR and XDR P. aeruginosa infections. Thus, ceftazidime–avibactam may have a potentially important role in the management of serious and complicated P. aeruginosa infections, including those caused by MDR and XDR strains.

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In Vitro Activity of Ceftazidime-Avibactam Alone and in Combination with Amikacin Against Colistin-Resistant Gram-Negative Pathogens

Cited by 10 publications

References 29 publications

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

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

In vitro and in vivo Activity of Phibilin Against Candida albicans

Review of Ceftazidime-Avibactam for the Treatment of Infections Caused by Pseudomonas aeruginosa

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