Calcium Potentiated Carbapenem Effectiveness Against Resistant Enterobacter Species

Abstract

Background: Antimicrobial resistance (AMR) remains a global health challenge, as bacteria display increasing resistance to last-resort antibiotics such as carbapenems. Enterobacter cloacae are evolving and developing high level of resistance to carbapenems. With increasing AMR, availability of antibiotics for treatment dwindles, hence a need to complement antibiotics to enhance activity or reduce the level of resistance. This study explored the use of calcium ions in attenuating bacterial resistance to carbapenems. Method: E. cloacae strains isolated from hospital fomites and air were subjected to antimicrobial susceptibility testing with carbapenem antibiotics (imipenem, meropenem, doripenem and ertapenem) using the disc diffusion ( E. coli ATCC 25922 as control). Growth profile, Ca-Adjusted assay and time-kill curve of the strains was determined in the presence and absence of carbapenem antibiotics following a calcium stress assay. Results: Growth profile showed that all the E. cloacae strains grew markedly well at 37°C relative to ATCC 25922 and all strains displayed 80% to 100% level of resistance to tested antibiotics. The growth rate of the strains in the presence of the antibiotics was comparable to the growth rate in the absence of carbapenems. Conditional growth stress with calcium ions showed a 50% reduction in the level of resistance with doripenem displaying the lowest level of reduction and ertapenem, the highest. Discussion: The study showed that E. cloacae strains displayed high levels of resistance to carbapenems, increasing the possibility of treatment failure. Challenging strains with calcium prior to antibiotic treatment led to a significant reduction in level of resistance, indicating that calcium ions could affect bacterial strains during antibiotic activity leading to reduction in level of resistance. Conclusion: Calcium supplement could potentiate carbapenem effectiveness and reduce bacterial AMR.