In Vitro Interactions of Antibiotic Combinations of Colistin, Tigecycline, and Doripenem Against Extensively Drug-Resistant and Multidrug-Resistant Acinetobacter baumannii

Abstract

BackgroundAcinetobacter baumannii infections are difficult to treat owing to the emergence of various antibiotic resistant isolates. Because treatment options are limited for multidrug-resistant (MDR) A. baumannii infection, the discovery of new therapies, including combination therapy, is required. We evaluated the synergistic activity of colistin, doripenem, and tigecycline combinations against extensively drug-resistant (XDR) A. baumannii and MDR A. baumannii.MethodsTime-kill assays were performed for 41 XDR and 28 MDR clinical isolates of A. baumannii by using colistin, doripenem, and tigecycline combinations. Concentrations representative of clinically achievable levels (colistin 2 µg/mL, doripenem 8 µg/mL) and achievable tissue levels (tigecycline 2 µg/mL) for each antibiotic were used in this study.ResultsThe colistin-doripenem combination displayed the highest rate of synergy (53.6%) and bactericidal activity (75.4%) in 69 clinical isolates of A. baumannii. Among them, thedoripenem-tigecycline combination showed the lowest rate of synergy (14.5%) and bacteri-cidal activity (24.6%). The doripenem-tigecycline combination showed a higher antagonistic interaction (5.8%) compared with the colistin-tigecycline (1.4%) combination. No antagonism was observed for the colistin-doripenem combination.ConclusionsThe colistin-doripenem combination is supported in vitro by the high rate of synergy and bactericidal activity and lack of antagonistic reaction in XDR and MDR A. baumannii. It seems to be necessary to perform synergy tests to determine the appropri-ate combination therapy considering the antagonistic reaction found in several isolates against the doripenem-tigecycline and colistin-tigecycline combinations. These findings should be further examined in clinical studies.

Prevalence and Antibiotic Resistance Pattern of Acinetobacter Isolated from Patients Admitted in ICUs in Mazandaran, Northern Iran

“…Thus, many recent studies have investigated combined therapy of two or more agents for MDR acintobacter infections. Specially combination regimen of Tigecycline or Colistin with other antibiotics have frequently been reported .Park and coworker found a high rate of in vitro synergy and bactericidal activity and lack of antagonism in combination of colistin and Doripenem (Park et al, 2016). As well as, recent study revealed a superior activity for combination of tigecycline with cefoperazone-sulbactam against MDR acintobacter (Liu et al, 2014).…”

Evaluation of the synergistic effect of a combination of colistin and tigecycline against multidrug-resistant Acinetobacter baumannii

“…The main disadvantage of tigecycline is that it achieves low peak serum concentrations after administration of a standard 100 mg loading dose, which may increase the development of resistance during therapy 22,23. Studies investigating the antibiotic susceptibility of Acinetobacter species revealed that these bacteria are most susceptible to colistin and tigecycline, and a combination of these antibiotics has the lowest antagonistic interaction when compared to combinations of colistin or tigecycline with carbapenems 2,18,19. Taken together, these results indicated that combinations with colistin and tigecycline remain the best choice for the treatment of MDR Acinetobacter infections.…”

Efficacy of nebulized colistin-based therapy without concurrent intravenous colistin for ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii

“…Furthermore, relatively low rate of synergy of imipenem and the effect of CRAB strains showing a high MIC for meropenem (MIC ≥64 mg/L) might have influenced the overall results (40)(41)(42). The possibility of unexpected antagonistic effect and suboptimal doses of other antibiotics should lead to a cautious interpretation of the results on combination therapy (43,44). Taken together, a multidisciplinary approach by physicians and microbiologists to perform routine synergy tests to determine the appropriate combination therapy should be considered.…”