Imipenem: a potent inducer of multidrug resistance in Acinetobacter baumannii
Han-Yueh Kuo1, Kai-Chih Chang, Jai-Wei Kuo
1Department of Medicine, National Taiwan University Hospital-Hsin-Chu Branch, Hsin-Chu City, Taiwan.
Abstract:
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 β-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.
Insights
Imipenem exposure strongly promotes multidrug resistance in Acinetobacter baumannii. This resistance involves carbapenemase and efflux pump mechanisms, highlighting the need for careful carbapenem antibiotic use.
Area of Science:
- Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Acinetobacter baumannii is a significant opportunistic pathogen.
- Multidrug resistance (MDR) in A. baumannii poses a major global health threat.
- Carbapenem antibiotics are crucial for treating A. baumannii infections.
Purpose of the Study:
- To investigate how imipenem exposure influences the development of multidrug resistance in Acinetobacter baumannii.
- To identify the resistance mechanisms involved in imipenem-induced MDR.
- To compare imipenem's MDR induction potential with other antibiotics.
Main Methods:
- Generation of imipenem-selected and other antibiotic-selected mutant strains of A. baumannii.
- Phenotypic antibiotic susceptibility testing with and without efflux pump inhibitors (NMP, CCCP).
- Analysis of antimicrobial resistance gene expression profiles.
Main Results:
- Imipenem was a potent inducer of MDR in reference A. baumannii strains compared to other tested antibiotics.
- Imipenem-selected mutants exhibited altered expression of OXA-51-like carbapenemase, efflux pumps, and AmpC β-lactamase.
- Efflux pump inhibitors (NMP, CCCP) partially reversed imipenem and amikacin resistance in selected mutants and clinical isolates.
Conclusions:
- Imipenem can act as a strong inducer of multidrug resistance in A. baumannii.
- The combination of OXA-51-like carbapenemase and other resistance mechanisms contributes to MDR.
- Close monitoring of carbapenem usage is essential to curb the spread of MDR A. baumannii in healthcare settings.
Related Concept Videos
Mechanism of Antibiotic Resistance in MRSA
Development of Antibiotic Resistance
Clinical Significance of Antibiotic Resistance
Inhibitors of Gram-positive Cell Wall Synthesis
Inhibitors of Bacterial Protein Synthesis
Combined Effects of Drugs: Synergism
Such synergistic combinations...
