Abstract
Due to the wide use of tigecycline in the treatment of severe infections caused by multidrug-resistant (MDR) bacteria, clinical resistance to tigecycline has increased in recent years. Here, we investigated the relationship between tigecycline resistance and the expression of efflux pumps. Clinical isolates of Acinetobacter baumannii and Klebsiella pneumoniae were consecutively collected from hospitalized patients in three hospitals. The minimum inhibitory concentration (MIC) of tigecycline was determined using the broth microdilution method. Expression levels of efflux pump genes and regulators were examined by quantitative real-time reverse transcription polymerase chain reaction. The correlations between tigecycline MICs and gene expression levels were analyzed. Overall, 1,026 A. baumannii and 725 K. pneumoniae strains were collected. Most strains were isolated from sputum. The tigecycline resistance rate was 13.4% in A. baumannii isolates and 6.5% in K. pneumoniae isolates. Overexpression of AdeABC and AcrAB-TolC efflux systems was observed found in clinical tigecycline-resistant isolates. The tigecycline MIC had a linear relationship with the adeB expression level in A. baumannii isolates, but not with the acrB expression level in K. pneumoniae isolates. There were significant linear trends in the overexpression of ramA as the tigecycline MIC increased in K. pneumoniae isolates. Tigecycline resistance in A. baumannii and K. pneumoniae was strongly associated with the overexpression of efflux systems. More studies are needed to elucidate whether there are other regulators that affect the expression of adeB in A. baumannii and how ramA affects the expression of acrB in K. pneumoniae.
Highlights
Due to the wide use of tigecycline in the treatment of severe infections caused by multidrug-resistant (MDR) bacteria, clinical resistance to tigecycline has increased in recent years
Of the A. baumannii strains, 70% were isolated from sputum, 17% were isolated from wounds, and the remaining strains were isolated from urine, blood, cerebrospinal fluid, and other sources
Of the K. pneumoniae strains, 42.3% were isolated from sputum, 24% were isolated from blood, 18% were isolated from urine, and the remaining strains were isolated from wounds, cerebrospinal fluid, or other sources
Summary
Due to the wide use of tigecycline in the treatment of severe infections caused by multidrug-resistant (MDR) bacteria, clinical resistance to tigecycline has increased in recent years. We investigated the relationship between tigecycline resistance and the expression of efflux pumps. The tigecycline resistance rate was 13.4% in A. baumannii isolates and 6.5% in K. pneumoniae isolates. The tigecycline MIC had a linear relationship with the adeB expression level in A. baumannii isolates, but not with the acrB expression level in K. pneumoniae isolates. There were significant linear trends in the overexpression of ramA as the tigecycline MIC increased in K. pneumoniae isolates. Conclusions: Tigecycline resistance in A. baumannii and K. pneumoniae was strongly associated with the overexpression of efflux systems. Nosocomial infections caused by multidrug-resistant (MDR) Gram-negative bacteria represent a great threat to public health worldwide.
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