title: Mutant prevention concentration of colistin alone and in combination with rifampicin for multidrug-resistant Acinetobacter baumannii.
abstract: Colistin-susceptible isolates of Acinetobacter baumannii often contain subpopulations that are resistant to colistin. Monotherapy with colistin can lead to selective growth of these subpopulations and emergence of colistin-resistant strains. Our objectives were to explore the susceptibility pattern of colistin-resistant subpopulations and investigate if combining colistin with a second antibiotic could prevent their selective growth. Four colistin-susceptible clinical isolates of A. baumannii and one reference isolate were used. The mutant prevention concentration (MPC) of colistin, i.e. the concentration required to block growth of all single-step-mutant subpopulations, was determined by plating an inoculum of 109CFU on Mueller Hinton agar (MHA)-plates containing 2-fold dilutions of colistin (0.125-128 mg/L). Susceptibility testing of colistin-resistant subpopulations, obtained in the MPC assay, was performed with Etest. The MPC of colistin, in combination with rifampicin, was determined by plating an inoculum of 109CFU on MHA-plates containing colistin (0.125-128 mg/L) and fixed concentrations of rifampicin (1.1 mg/L or 4.4 mg/L). The colistin-resistant subpopulations demonstrated increased susceptibility to a number of agents compared to their main populations. These subpopulations were even susceptible to agents that normally are inactive against gram-negative bacteria and all had rifampicin MICs of < 0.002 mg/L. The combination of colistin and rifampicin completely inhibited the growth of all colistin-resistant subpopulations and significantly lowered the MPC of colistin for A. baumannii. Combining colistin with rifampicin could be a way to prevent selective growth of colistin-resistant subpopulations of A. baumannii and possibly the emergence of colistin-resistant strains.
authors: Department of Infectious Diseases, Linköping University Hospital, Linköping, Sweden. hampus.nordqvist@sodersjukhuset.se.|Department of Infectious Diseases, Stockholm South Hospital, Stockholm, Sweden. hampus.nordqvist@sodersjukhuset.se.
authors: H
authors: http://orcid.org/0000-0002-4996-9010
authors: H
authors: Nordqvist
authors: Clinical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors: L E
authors: LE
authors: Nilsson
authors: Clinical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. carina.claesson@liu.se.
authors: C
authors: C
authors: Claesson
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000254:growth & development; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012293:Rifampin / Q000494:pharmacology*; D012641:Selection, Genetic
chemical_list: D000900:Anti-Bacterial Agents; D012293:Rifampin; D003091:Colistin