Ceftazidime–Avibactam/Colistin Combination Against Carbapenem-Resistant Pseudomonas aeruginosa: In Vitro Synergy Indicating a Possible Therapeutic Approach

Abstract

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 bla_NDM and bla_OXA-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.