Background:
Carbapenems (CAR),
colistin (CST), and
tigecycline (TGC) alone or in combination
therapy has become the last-resort
antibiotics for treating
infections caused by multidrug resistant (MDR) bacteria. However, resistance to these reserve
antibiotics are increasingly being reported worldwide. Hence, the quest to find other agents that will synergistically restore the efficacy of these
antibiotics have increased. Methods: Sixty-three clinical Enterobacteriaceae isolates comprising of Klebsiella pneumoniae (n = 24), Enterobacter spp. (n = 15), Serratia marcescens (n = 12), Citrobacter freundii (n = 8), Escherichia coli (n = 2), and K. oxytoca/michiganensis (n = 2) with known
carbapenem resistance mechanisms and undescribed CST and TGC resistance mechanisms were subjected to broth microdilution and
meropenem (MEM) disc synergy test in the presence and absence of
carbonyl cyanide m-chlorophenylhydrazine (
CCCP), a H+ conductor (protonophore). Results and conclusions: Susceptibility to MEM,
imipenem (
IMP), CST, and TGC was found in only 2, 0, 17, and 9 isolates respectively. Addition of
CCCP reversed resistance to CST, TGC,
IMP, and MEM in 44, 3, 0, and 0 isolates respectively; CST had the highest mean minimum inhibitory concentration (MIC) fold change (193.12; p < 0.0001) post
CCCP compared to that of MEM (1.70),
IMP (1.49) and TGC (1.16). Eight isolates tested positive for the MEM-
CCCP disc synergy test. We concluded that
CCCP reverse CST resistance in CST-resistant Enterobacteriaceae. Although
CCCP is an experimental agent with no therapeutic value clinically, further studies are necessary to decipher the mechanisms underlying the CST-
CCCP synergy to inform the development of adjuvants that could be therapeutically effective in CST-resistant
infections.