Mechanisms of resistance to ciprofloxacin, ampicillin/sulbactam and imipenem in Acinetobacter baumannii clinical isolates in Taiwan

Abstract

Nosocomial infections caused by multidrug-resistant (MDR) Acinetobacter baumannii have been increasing in recent years, posing a threat to public health worldwide. The susceptibility to eight antimicrobial agents of 35 clinical A. baumannii isolates from Taiwan was tested. Isolates were examined by polymerase chain reaction (PCR) and sequencing for beta-lactamase genes and mutations in the gyrA and parC genes. Expression of AdeB, an efflux pump protein, was evaluated by real-time quantitative PCR. The level of adeB expression correlated with resistance to ciprofloxacin and ampicillin/sulbactam in A. baumannii isolates. Almost all isolates with full resistance to ciprofloxacin had both high adeB expression and point mutations in parC and gyrA, but 4 intermediate-resistant isolates had only high adeB expression without point mutations in gyrA or parC, in contrast to 18 susceptible isolates with low adeB expression and without mutations in gyrA or parC. Sixteen isolates (45.7%) carrying a type 1 integron were MDR as well as being more resistant to imipenem, amikacin, gentamicin, ceftazidime or cefepime than those without the integron. The class 1 integron in A. baumannii carried different resistance gene cassettes, including 5'CS-bla(IMP-1)-aadA4-3'CS, 5'CS-aacA4-aadA1-3'CS and 5'CS-aacC1-aadA1-3'CS. In conclusion, expression of the adeB gene was associated with resistance to ciprofloxacin and ampicillin/sulbactam in A. baumannii. Multiple mutations in gyrA and parC also played a role in ciprofloxacin resistance. The major metallo-beta-lactamase contributing to imipenem resistance in A. baumannii in Taiwan was bla(IMP-1), which was carried by the class 1 integron. The class 1 integron was associated with the MDR phenotype in A. baumannii.