Invitro Antimicrobial Synergy of Carbapenem with Tigecycline and Colistin in Gram negative isolates from ICU

Lubna Parveen, Fatima Khan, Salman Shah, Abu Nadeem, Asfia Sultan, Asad U Khan


The worldwide increase in the emergence of carbapenem resistant Gram-negative (CRGN) pathogens calls for the investigation into alternative approaches for treatment. The aim of this study is to evaluate the in vitro effect of the colistin–carbapenem (including meropenem, doripenem, ertapenem and imipenem) combination and tigecycline-carbapenem combination against Carbapenem Resistant Enterobacterales (CRE) using two different techniques viz. Chequerboard and time-kill synergy method.

Methods A total of 118 CRE isolates were included to the study. The minimum inhibitory concentrations of colistin, tigecycline and carbapenem (including meropenem, doripenem, ertapenem and imipenem) were determined with broth dilution method. In addition, PCR amplifications of the most common beta lactamases contributing to carbapenem resistance were performed. Synergistic effects of tigecycline-carbapenem and colistin-carbapenem were investigated by checkerboard technique and time kill assay.

Results All of the isolates were resistant to carbapenems whereas none of the isolates were resistant to colistin and tigecycline. Synergistic effect for the colistin-carbapenem and tigecycline-carbapenem combination was observed using both methods. Additive effects were also detected in both combinations where the ΣFICI of carbapenem combined with colistin was 1.167 ± 0.354 and that of carbapenem with tigecycline was 1.106 ± 0.337. The combination of colistin-carbapenem showed better effects as compared to tigecycline-carbapenem (p < 0.05). The colistin-carbapenem and tigecycline-carbapenem combinations also showed a decrease of 2.6 and 2.8-fold, respectively. Time-kill assays additionally showed synergistic effects, and no bacterial re-growth was detected following a 24 h incubation. Synergistic effect was variable and strain-depended Supplementary issue:02 - 199 - against CRE isolates that have been tested.

Conclusion: Our study showed that the combination of carbapenems with colistin and tigecycline could be a promising antimicrobial strategy in treating CRE infections and holds great importance for management of patients who cannot afford expensive drugs for treatment.

International Journal of Human and Health Sciences Supplementary Issue 02: 2023 Page: S198-S210


Multidrug resistance, Synergy, time kill assay, chequerboard technique

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