In Vitro Antimicrobial Combinations for Pan-Drug Resistant Acinetobacter Species

Abstract

Background: Pandrug resistant Gram-negative organisms (PDRGNs) have emerged, as a major threat to hospitalized patients. They have been associated with mortality rates ranging from 30 to 70%. Because of the high morbidity and mortality rates of severe pandrug resistant acinetobacter spp infections, combination therapies, as opposed to monotherapy, are suggested. A synergistic effect may be developed when antibiotics are used in combination. Through this synergistic effect, treatment efficacy can be improved and resistance can be prevented. Aim of the work: To investigate the use of in vitro antibiotic synergy test (checkerboard) for pandrug resistant acinetobacter species with a clinical feedback on the most synergistic antimicrobial combination. Materials and Methods: During this study, one hundred isolates of drug resistant acinetobacter species identified by routine culture and sensitivity using disc diffusion susceptibility test, were collected from critically ill patients admitted to Ain Shams University Internal Medicine Intensive Care Units. The isolates were subjected to: (i) Determination of MIC using Vitek 2 automated system to confirm resistance of acinetobacter species to all commercially available antibiotics, (ii) Broth micro-dilution method (BMD) for determination of tigecycline susceptibility, and (iii) Determination of antimicrobial synergy by broth micodilution (Checkerboard method). Results: Vitek 2 system results showed that, all of the 100 isolates were resistant to all antibiotics included in the study. On the other hand, 100% of the isolates were sensitive (S) to Colistin. As regards the results by Broth microdilution antibiotic susceptibility method, all 100 isolates (100%) were resistant to ampicillin/sulbactam, meropenem and ciprofloxacin, whereas 95 isolates (95%) were resistant to amikacin, whereas all 100 isolates (100%) tested were sensitive to tigecycline. The results of the antibiotic combinations were as follows; the activity of ampicillin/sulbactam in combination with amikacin showed synergy in (48%), addition in (42%) and indifference in (10%). The activity of ampicillin/sulbactam in combination with ciprofloxacin showed, synergy in (36%), addition in (52%) and indifference in (12%). The activity of meropenem in combination with amikacin showed, synergy in (26%), addition in (53%) and indifference in (21%). No antagonistic activity was detected between any of the antibiotic combinations used. Conclusion: The prevalence of XDR/PDR resistant Acinetobacter spp. was highest in blood samples (43%) followed by sputum samples (35%) recovered from critically ill patients admitted to Ain Shams University Internal Medicine Intensive Care Units. Vitek 2 system showed that, all of the 100 isolates were resistant to all antibiotics included in the study. On the other hand, 100% of the isolates were sensitive (S) to colistin. Broth microdilution antibiotic susceptibility method showed that, all 100 isolates (100%) were resistant to ampicillin/sulbactam, meropenem and ciprofloxacin, whereas 95 isolates (95%) were resistant to amikacin, whereas all 100 isolates (100%) tested were sensitive to tigecycline, indicating that acinetobacter spp. did not attain resistance to tigecycline yet. The broth microdilution antibiotic synergy test (Checkerboard method), being the reference method for assessing antimicrobial synergy, showed that the highest synergic activity belongs to ampicillin/sulbactam and amkacin (48%), and the lowest synergic activity belongs to meropenem and amikacin (26%).