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Published on: April 18, 2019
Ceftazidime-Avibactam/Colistin Combination Against Carbapenem-Resistant Pseudomonas aeruginosa: In Vitro Synergy
1Department of Medical Microbiology, Faculty of Medicine, Kocaeli University, İzmit, Turkiye.
Background:
The increasing prevalence of multidrug-resistant Pseudomonas aeruginosa limits treatment options and highlights the need for new antimicrobials. Although agents such as ceftazidime-avibactam (CZA), ceftolozane-tazobactam, imipenem-relebactam, and cefiderocol have expanded therapeutic choices, resistance to these antibiotics is also emerging. Combination therapies therefore remain an important strategy. This study evaluated the in vitro synergistic activity of the CZA-colistin (COL) combination in carbapenem-resistant P. aeruginosa (CRPA) isolates.
Methods:
Twelve clinical CRPA isolates obtained from Kocaeli University Hospital (2021-2022) were included. Minimum inhibitory concentration values were determined by broth microdilution, and synergy was assessed using the checkerboard method. Synergy categories were defined as follows fractional inhibitory concentrations index (FICI) ≤ 0.5 synergism, 0.5 < FICI ≤ 1.0 partial synergism, 1.0 < FICI ≤ 4.0 indifference, and >4.0 antagonism.
Results:
All isolates were susceptible to colistin, whereas four were resistant to CZA. Checkerboard analysis showed partial synergy in nine of 12 isolates (75.0%), with no antagonism detected. Partial synergy was more frequent in CZA-resistant isolates (100%) than in CZA-susceptible ones (62.5%) and was notably associated with isolates carrying blaNDM and blaOXA-48.
Conclusions:
CZA-COL combination may offer partial synergy, especially in CZA-resistant CRPA strains; however, broader in vivo and prospective studies are needed to support clinical use.
Insights
The combination of ceftazidime-avibactam (CZA) and colistin (COL) showed partial synergy against multidrug-resistant Pseudomonas aeruginosa. This combination may be beneficial for treating CZA-resistant carbapenem-resistant P. aeruginosa (CRPA) infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Rising multidrug-resistant Pseudomonas aeruginosa necessitates novel antimicrobial strategies.
- Emerging resistance to newer agents like ceftazidime-avibactam (CZA) underscores the importance of combination therapies.
- This study investigates the in vitro synergy of CZA and colistin (COL) against carbapenem-resistant P. aeruginosa (CRPA).
Purpose of the Study:
- To evaluate the in vitro synergistic activity of the CZA-COL combination against clinical CRPA isolates.
- To determine the frequency and characteristics of synergy in CRPA strains, including those resistant to CZA.
Main Methods:
- Twelve clinical CRPA isolates were analyzed.
- Minimum inhibitory concentrations (MICs) were determined using broth microdilution.
- Synergy was assessed via checkerboard method, with synergy defined by fractional inhibitory concentration index (FICI).
Main Results:
- All isolates were susceptible to colistin; four were resistant to CZA.
- Partial synergy was observed in 75% of isolates (9/12).
- Partial synergy was more prevalent in CZA-resistant isolates (100%) and associated with blaNDM and blaOXA-48 genes.
Conclusions:
- The CZA-COL combination demonstrates potential for partial synergy, particularly against CZA-resistant CRPA.
- Further in vivo and prospective clinical studies are warranted to validate the efficacy of this combination therapy.
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