Heteroresistance to colistin in oxacillinase-producing carbapenem-resistant Acinetobacter baumannii clinical isolates from Gorgan, Northern Iran

Abstract

Objectives: Colistin resistance rates are rising globally among multidrug-resistant Gram-negative bacilli, including Acinetobacter baumannii (A. baumannii). A new type of resistance - heteroresistance - has also been reported to colistin in clinical A. baumannii isolates. This study investigated the presence of colistin heteroresistance in carbapenem-resistant A. baumannii clinical isolates.

Methods: Different clinical specimens from hospitalised patients were investigated for A. baumannii. The MICs to imipenem, meropenem and colistin were determined by broth microdilution. PCR was performed to detect OXA-type carbapenemase genes (bla_OXA-23-like, bla_OXA-24/40-like, bla_OXA-51-like, bla_OXA-58-like, and bla_OXA-143-like). Heteroresistance to colistin was examined using the population analysis profiles method. Genotypic relatedness of the isolates was analysed by enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR).

Results: Overall, 71 A. baumannii isolates were recovered from clinical specimens. Of these, 27 (38.03%) and 44 (61.97%) isolates were carbapenem-susceptible and carbapenem-resistant, respectively. In addition, 67 (94.36%) isolates were susceptible to colistin, with MICs between 0.25-2 μg/mL. Among the 44 selected carbapenem-resistant colistin-susceptible isolates, the frequency of bla_OXA-51-like, bla_OXA-23-like and bla_OXA-24/40-like genes was 100%, 77.27% and 43.18%, respectively. Nine of 44 (20.45%) isolates were characterised as colistin-heteroresistant with subpopulations growing at 6-8 μg/mL, whereas two of 44 (4.54%) presented heterogeneous subpopulations growing at up to 1 μg/mL of colistin. ERIC‑PCR typing clustered A. baumannii isolates to 10 common types (CT1-CT10) containing isolates from different hospitals and 12 single types (ST1-ST12).

Conclusions: A. baumannii with a colistin heteroresistance phenotype was common. This could be of great concern since colistin is often used as a last-resort drug for treating A. baumannii infections, highlighting that care is necessary with colistin monotherapy. In addition, more effective strategies and surveillance are required to confine and prevent the inter-hospital and/or intra-hospital dissemination of A. baumannii between therapeutic centres.

Keywords: Acinetobacter baumannii; Colistin; Enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR); Heteroresistance; bla(OXA).