Publication:

In vitro and in vivo synergistic activity of antibiotic combinations against colistin-resistant Pseudomonas aeruginosa: a study from a tertiary care hospital in Bangladesh

Background The emergence of colistin-resistant Pseudomonas aeruginosa poses a serious therapeutic challenge, particularly in low- and middle-income countries where treatment options are limited. Combination therapy is increasingly explored to improve clinical outcomes, but in vivo validation still remains insufficient.

Methods A cross-sectional experimental study was conducted at a tertiary-care hospital in Bangladesh (2019). Clinical isolates of P. aeruginosa were identified and tested for antimicrobial susceptibility following CLSI guidelines. Colistin resistance was detected by agar dilution MIC testing and further confirmed by PCR. Molecular detection of colistin resistance–associated genes (pmr A, pmr B, pmr C, phoP, pho Q and mcr-1-5) was done by PCR. In vitro synergy of colistin–imipenem and colistin–amikacin combinations were evaluated by MIC reduction and fractional inhibitory concentration index (FICI). A murine infection model was used to assess the therapeutic efficacy.

Results Among the 63 isolates of P. aeruginosa, 12 (19.05%) were identified as colistin-resistant. Multidrug resistance was observed among all the isolates, with high-level colistin MICs (≥4 µg/ml). Chromosomally mediated resistance genes (PMR and PHO systems) were only detected instead of any plasmid-mediated mcr genes. In vitro synergy testing demonstrated 100% synergistic activity for colistin–imipenem (FICI ≤0.5), whereas colistin–amikacin showed predominantly indifferent effects. In vivo, the combination of colistin–imipenem led to complete bacterial clearance from the mice with 100% survival, whereas the colistin–amikacin combination resulted in 100% mortality, similar to untreated controls.

Conclusions The Colistin–imipenem combination demonstrates strong in vitro synergy and superior in vivo efficacy against colistin-resistant P. aeruginosa, highlighting its potential as a practical therapeutic option specially in resource-limited settings.