Dataset Information

Prevalence of carbapenemases among high-level aminoglycoside-resistant Acinetobacter baumannii isolates in a university hospital in China.

ABSTRACT: The prevalence of aminoglycoside resistant enzymes has previously been reported and extended-spectrum ?-lactamase among Acinetobacter baumannii. To track the risk of multidrug-resistant A. baumannii, the present study aimed to determine the prevalence of carbapenemases in high-level aminoglycoside resistant A. baumannii over two years. A total of 118 strains of A. baumannii were consecutively collected in the First Affiliated Hospital of Chengdu Medical College, Chengdu, China. These isolates were investigated on the genetic basis of their resistance to aminoglycosides. The results showed that 75 (63.56%) isolates were high-level resistant to aminoglycosides, including gentamicin and amikacin (minimum inhibitory concentration, ?256 µg/ml). Aminoglycoside-resistant genes ant(2?)-Ia, aac(6')-Ib, aph(3')-Ia, aac(3)-Ia, aac(3)-IIa, armA, rmtA, rmtB, rmtC, rmtD, rmtE, rmtF, rmtG, rmtH and npmA, and carbapenem-resistant genes blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, blaSIM, blaIMP, blaNDM-1 and blaKPC, were analyzed using polymerase chain reaction. The positive rate of ant(2?)-Ia, aac(6')-Ib, aph(3')-Ia, aac(3)-Ia and aac(3)-IIa was 66.95, 69.49, 42.37, 39.83 and 14.41%, respectively. armA was present in 72.0% (54/75) of A. baumannii isolates with high-level resistance to aminoglycosides. The remaining nine 16S ribosomal RNA methlyase genes (rmtA, rmtB, rmtC, rmtD, rmtE, rmtF, rmtG, rmtH and npmA) and aminoglycoside-modifying enzyme gene aac(6')-Ib-cr were not detected. Among the 54 armA-positive isolates, the prevalence of the carbapenem resistant blaOXA-23 and blaOXA-51 genes was 79.63 and 100%, respectively. armA, ant(2?)-Ia and aac(6')-Ib were positive in 43 isolates. The results of multilocus sequence typing revealed 31 sequence types (STs) in all clinical strains. Among these STs, the high-level aminoglycoside-resistant A. baumannii ST92, which mostly harbored blaOXA-23, was the predominant clone (29/75). In conclusion, A. baumannii harboring carbapenemases and aminoglycoside-resistant enzymes are extremely prevalent in western China, emphasizing the need to adopt surveillance programs to solve the therapeutic challenges that this presents.

SUBMITTER: Wang Y

PROVIDER: S-EPMC5228107 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Prevalence of carbapenemases among high-level aminoglycoside-resistant Acinetobacter baumannii isolates in a university hospital in China.

Wang Yanhong Y Shen Min M Yang Jingni J Dai Min M Chang Yaowen Y Zhang Chi C Luan Guangxin G Ling Baodong B Jia Xu X

Experimental and therapeutic medicine 20161020 6

The prevalence of aminoglycoside resistant enzymes has previously been reported and extended-spectrum β-lactamase among Acinetobacter baumannii. To track the risk of multidrug-resistant A. baumannii, the present study aimed to determine the prevalence of carbapenemases in high-level aminoglycoside resistant A. baumannii over two years. A total of 118 strains of A. baumannii were consecutively collected in the First Affiliated Hospital of Chengdu Medical College, Cheng ...[more]

PMID: 28101158

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Project description:Enzymatic modification of aminoglycosides by nucleotidyltransferases, acetyltransferases and/or phosphotransferases accounts for the majority of aminoglycoside-resistant Acinetobacter isolates. In this study, we investigated the relationship between aminoglycoside resistance and the presence of aminoglycoside-modifying enzymes in Acinetobacter baumannii clinical isolate groups with different resistance profiles. Thirty-two clinical A. baumannii isolates were included in this study. Acinetobacter isolates were divided into 4 groups according to results of susceptibility testing. The presence of genes encoding the following aminoglycoside-modifying enzymes; aph (3')-V1, aph (3')-Ia, aac (3)-Ia, aac (3) IIa, aac (6')-Ih, aac (6')-Ib and ant (2')-Ia responsible for resistance was investigated by PCR in all strains. The acetyltransferase (aac (6')-Ib, aac (3)-Ia) and phosphotransferase (aph (3')-Ia) gene regions were identified in the first group, which comprised nine imipenem, meropenem, and gentamicin-resistant isolates. The acetyltransferase (aac (6')-Ib, aac (3)-Ia), phosphotransferase (aph (3')-VI) and nucleotidyltransferase (ant2-Ia) gene regions were identified in the second group, which was composed of nine imipenem-resistant, meropenem-resistant and gentamicin-sensitive isolates. The acetyltransferase (aac (3)-Ia) and phosphotransferase (aph (3')-Ia) regions were identified in the fourth group, which comprised eight imipenem-sensitive, meropenem-sensitive and gentamicin-resistant isolates. Modifying enzyme gene regions were not detected in the third group, which was composed of six imipenem, meropenem and gentamicin-sensitive isolates. Our data are consistent with previous reports, with the exception of four isolates. Both acetyltransferases and phosphotransferases were widespread in A. baumannii clinical isolates in our study. However, the presence of the enzyme alone is insufficient to explain the resistance rates. Therefore, the association between the development of resistance and the presence of the enzyme and other components should be investigated further.

Project description:Heteroresistance is a phenomenon where a subpopulation of cells exhibits higher levels of antibiotic resistance than the general population. Analysis of tobramycin resistance in Acinetobacter baumannii AB5075 using Etest strips demonstrated that colonies with increased resistance arose at high frequency within the zone of growth inhibition. The presence of a resistant subpopulation was confirmed by population analysis profiling (PAP). The tobramycin-resistant subpopulation was cross resistant to gentamicin but not amikacin. The increased tobramycin resistance phenotype was highly unstable, and cells reverted to a less resistant population at frequencies of 60 to 90% after growth on nonselective media. Furthermore, the frequency of the resistant subpopulation was not increased by preincubation with subinhibitory concentrations of tobramycin. The tobramycin-resistant subpopulation was shown to replicate during the course of antibiotic treatment, demonstrating that these were not persister cells. In A. baumannii AB5075, a large plasmid (p1AB5075) carries aadB, a 2?-nucleotidyltransferase that confers resistance to both tobramycin and gentamicin but not amikacin. The aadB gene is part of an integron and is carried adjacent to four additional resistance genes that are all flanked by copies of an integrase gene. In isolates with increased resistance, this region was highly amplified in a RecA-dependent manner. However, in a recA mutant, colonies with unstable tobramycin resistance arose by a mechanism that did not involve amplification of this region. These data indicate that tobramycin heteroresistance occurs by at least two mechanisms in A. baumannii, and future studies to determine its effect on patient outcomes are warranted.IMPORTANCEAcinetobacter baumannii has become an important pathogen in hospitals worldwide, where the incidence of these infections has been increasing. A. baumannii infections have become exceedingly difficult to treat due to a rapid increase in the frequency of multidrug- and pan-resistant isolates. This has prompted the World Health Organization to list A. baumannii as the top priority for the research and development of new antibiotics. This study reports for the first time a detailed analysis of aminoglycoside heteroresistance in A. baumannii We define the mechanistic basis for heteroresistance, where the aadB(ant2?)Ia gene encoding an aminoglycoside adenylyltransferase becomes highly amplified in a RecA-dependent manner. Remarkably, this amplification of 20 to 40 copies occurs stochastically in 1/200 cells in the absence of antibiotic selection. In addition, we provide evidence for a second RecA-independent mechanism for aminoglycoside heteroresistance. This study reveals that aminoglycoside resistance in A. baumannii is far more complex than previously realized and has important implications for the use of aminoglycosides in treating A. baumannii infections.

Dataset Information

Prevalence of carbapenemases among high-level aminoglycoside-resistant Acinetobacter baumannii isolates in a university hospital in China.

Publications

Prevalence of carbapenemases among high-level aminoglycoside-resistant <i>Acinetobacter baumannii</i> isolates in a university hospital in China.

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