In vitro activity of colistin mono- and combination therapy against colistin-resistant <em>Acinetobacter baumannii,</em> mechanism of resistance, and clinical outcomes of patients infected with colistin-resistant <em>A. baumannii</em> at a Thai university hospital

Abstract

PurposeColistin is a drug of last resort for treating multidrug-resistant Acinetobacter baumannii infections. Unfortunately, colistin-resistant A. baumannii (CoR-AB) has been reported. Here, we examined the in vitro effect of mono- and combined antimicrobials against CoR-AB strains and their resistance mechanism, and evaluated the clinical outcomes of CoR-AB-infected patients.Patients and methodsSeventeen clinical CoR-AB strains were isolated from patients at Phramongkutklao hospital, 2011–2015. The mono- and synergistic activities of colistin, tigecycline, sulbactam, imipenem, meropenem, amikacin, fosfomycin, and cotrimoxazole were examined by minimum inhibitory concentration (MIC) and fractional inhibitory concentration index. Clonal relationship and resistance genes were determined by repetitive extragenic palindromic polymerase chain reaction with specific primers. The effect of carbonyl cyanide 3-chlorophenylhydrazone combined with colistin was used to test efflux pump involvement. Patient treatment outcomes were also reported.ResultsThe most prevalent infection in CoR-AB patients was pneumonia (35.3%), and all patients were administered colistin combined with another agent. The 30-day mortality was 70.6%, and the colistin MIC range and MIC50 was 16–512 μg/mL and 64 μg/mL, respectively. All CoR-AB strains were sensitive to tigecycline. Sporadic isolates were susceptible to sulbactam, imipenem, meropenem, and cotrimoxazole. A synergistic or additive effect was observed for colistin plus imipenem or meropenem (16.7%), sulbactam (66.7%), or tigecycline (66.7%). The CoR-AB isolates could be divided into four different clones (A–D) with a high prevalence of group B (47.1%). Eight isolates harbored blaOXA23, blaIMP, blaKPC, and blaNDM, and one contained blaOXA23, blaIMP, and blaKPC, while the eight remaining isolates carried only blaOXA23. The MIC values of all strains were greatly reduced for colistin plus carbonyl cyanide 3-chlorophenylhydrazone.ConclusionCoR-AB clinical isolates exhibited very high colistin resistance and a high frequency of resistance genes. The mechanism of colistin resistance appears to be mediated via an efflux pump. Thus, certain antimicrobials could be used as salvage therapy for CoR-AB infection.

Rescued chlorhexidine activity by resveratrol against carbapenem-resistant Acinetobacter baumannii via down-regulation of AdeB efflux pump

“…Due to the limitation of treatment of carbapenem-resistant A. baumannii infection, colistin is becoming frequently used as a last alternative. No colistin-resistant A. baumannii was found in our study and colistin-resistant strains have rarely been recovered among carbapenem-resistant A. baumannii isolated from Thailand [26]. Nevertheless, the emergence of this critical pathogen, carbapenem-resistant A. baumannii requires new active agents for treatment.…”

Colistin heteroresistance in carbapenem-resistant Acinetobacter baumannii clinical isolates from a Thai university hospital

“…A critical problem is the increasing prevalence of carbapenem resistance, particularly by the mechanism of carbapenemase production (Codjoe and Donkor 2017). In this study, most of the CRAB isolates harbored one or two OXA carbapenemase genes, bla OXA-23-like and/ or bla OXA-58-like , similar to previous studies from Thailand (Lertsrisatit et al 2017;Leungtongkam et al 2018). In agreement with other reports, bla OXA-23-like was the major resistance determinant (40-100%) among the CRAB isolates, indicating that carbapenem monotherapy is now no longer used as a therapeutic option against the MDR A. baumannii infections (Ezadi et al 2019;Salehi et al 2018).…”

Emergent Polymyxin Resistance: End of an Era?

“…Lertsrisatit et al has shown that colistin monotherapy is not optimal for treatment of CoRB. In this paper, all (17 of 17) CoR-AB isolates were susceptible to tigecycline and were partially susceptible to sulbactam, imipenem, meropenem, and cotrimoxazole in vitro [91]. A retrospective cohort study revealed gentamicin markedly reduced mortality caused by CoR-AB triggered sepsis, especially in urinary tract infections [63].…”