RESUMEN
This study investigated the progression of multidrug resistance upon exposure to imipenem in Acinetobacter baumannii. Eighteen A. baumannii strains, including two reference strains (ATCC 19606 and ATCC 17978), four clinical strains (AB56, AB242, AB273 and AB279) and 12 antibiotic-selected mutant strains, were used in this study. Imipenem-selected mutants were generated from imipenem-susceptible strains (ATCC 19606, ATCC 17978 and AB242) by multistep selection resistance. Amikacin-, ciprofloxacin-, colistin-, meropenem- and ceftazidime-selected mutants were also generated from the two reference strains and were used for comparison. Antibiotic susceptibilities in the absence and presence of the efflux pump inhibitors carbonyl cyanide m-chlorophenylhydrazone (CCCP) and 1-(1-naphthylmethyl)-piperazine (NMP) were examined in the three imipenem-selected mutants and the three clinical multidrug-resistant (MDR) isolates. Expression profiles of the antimicrobial resistance genes in the imipenem-selected mutants and their parental strains were also determined. The results showed that imipenem was more likely, compared with the other antibiotics, to induce a MDR phenotype in the two reference strains. Differences in OXA-51-like carbapenemase, efflux pumps or/and AmpC ß-lactamase expression were observed in the three imipenem-selected mutants. Moreover, a reduction in imipenem or amikacin resistance was observed when the imipenem-selected mutants and clinical isolates were exposed to NMP and CCCP. This study concluded that imipenem might be a potent inducer of multidrug resistance in A. baumannii strains. OXA-51-like carbapenemase combined with other resistance mechanisms may contribute to the development of multidrug resistance in A. baumannii. Monitoring the use of carbapenems is required to reduce the spread of MDR A. baumannii in hospitals.
Asunto(s)
Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Regulación Bacteriana de la Expresión Génica , Imipenem/farmacología , Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/genética , Acinetobacter baumannii/aislamiento & purificación , Acinetobacter baumannii/metabolismo , Proteínas Bacterianas/metabolismo , Carbapenémicos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Proteínas Nucleares , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Selección Genética , beta-Lactamasas/genética , beta-Lactamasas/metabolismoRESUMEN
We investigated the molecular epidemiology, antibiotic susceptibility, and antimicrobial resistant gene determinants of 23 multidrug-resistant (MDR) Acinetobacter baumannii samples that were collected from 5 proximal hospitals in Taiwan during April and May 2009. Major antibiotic resistance varied from 82.6 to 100%. Fivw pulsotypes were observed to spread clonally among the 5 hospitals. PCR screening revealed high distributions of intI1 (91%), bla(OXA-23) (57%), bla(ampC) (100%), adeB (100%), adeJ (100%), and abeM (100%) genes, which were prevalent in the MDR A. baumannii isolates. Resistance gene expression was examined by reverse transcription-PCR, and showed that increased ampC expression was associated with ceftazidime resistance, but expression of adeB, adeJ, or abeM did not guarantee antimicrobial resistance phenotypes. In addition, imipenem resistance in some A. baumannii strains may be mainly modulated by genes other than bla(OXA-51-like). This is the first direct evidence indicating local spread of MDR A. baumannii in Taiwan. The resistance gene determinants are widely distributed in clonal and nonclonal-related isolates.