title: Molecular epidemiology and mechanisms of rifampicin resistance in Acinetobacter baumannii isolates from Italy.
abstract: Use of rifampicin (RIF) in combination with colistin (COL) has been proposed for the treatment of multidrug-resistant Acinetobacter baumannii infections owing to in vitro synergism. The aim of the present study was to evaluate the molecular epidemiology and mechanisms of RIF resistance in 57 clinical isolates of A. baumannii in two tertiary care hospitals in Naples (Italy) from 2006 to 2010. Amongst the collection, 36 isolates showed high RIF minimum inhibitory concentrations (MICs) (256 mg/L to ≥512 mg/L), 16 showed intermediate MICs (8-16 mg/L) and 5 had low MICs (4 mg/L). Of the 36 isolates with elevated RIF MICs, 35 were assigned to sequence type ST2 and 1 to ST78. Amongst the 57 isolates, 35 carried at least one mutation in rpoB, including H535L in 9 isolates and double mutations D525N and P544L in 7 isolates, whilst 22 showed no rpoB mutations. Treatment with the efflux pump inhibitor phenyl-arginine-β-naphthylamide (PAβN) of resistant isolates with no mutations in rpoB and different RIF MICs reduced the MIC by >10-fold and restored the synergism between RIF and COL in time-kill studies, whilst it had no effect on strains carrying rpoB mutations. In conclusion, the emergence of elevated RIF MICs in A. baumannii isolates from our geographical area was mostly caused by mutations in rpoB; low to intermediate RIF MICs were also caused by altered membrane permeability to the drug. The phenomenon was contributed by the selection of two prevalent clones both assigned to ST2 genotype. These data may have implications for the correct identification of cases with A. baumannii infection that would not benefit from addition of RIF to COL.
authors: Dipartimento di Scienze Mediche Preventive, Università di Napoli Federico II, Via Pansini 5, Naples, Italy.
authors: Maria
authors: M
authors: Giannouli
authors: Anna
authors: A
authors: Di Popolo
authors: Emanuele
authors: E
authors: Durante-Mangoni
authors: Mariano
authors: M
authors: Bernardo
authors: Susanna
authors: S
authors: Cuccurullo
authors: Gerardino
authors: G
authors: Amato
authors: Marie-Francoise
authors: MF
authors: Tripodi
authors: Maria
authors: M
authors: Triassi
authors: Riccardo
authors: R
authors: Utili
authors: Raffaele
authors: R
authors: Zarrilli
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy / Q000453:epidemiology; D040981:Acinetobacter baumannii / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008826:Microbial Sensitivity Tests; D017720:Molecular Epidemiology; D009154:Mutation; D012293:Rifampin / Q000494:pharmacology*; D017422:Sequence Analysis, DNA
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit; D012293:Rifampin