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Epidemiological Analysis of Multidrug-Resistant Acinetobacter baumannii Isolates in a Tertiary Hospital Over a 12-Year Period in China.

ABSTRACT: Acinetobacter baumannii is an important nosocomial pathogen, which is multidrug resistant (MDR). Acinetobacter baumannii has become a major threat to public health worldwide due to its ability to easily acquire resistant genes. In order to analyze its epidemiology characteristics and the genetic evolution, A. baumannii isolates obtained from a Chinese tertiary hospital in the past 12 years (2008-2019), 295 isolates of non-repetitive A. baumannii, were recovered from patients and wards environments. The resistance genes were analyzed using antimicrobial susceptibility testing. The genetic relatedness of 295 isolates was identified by multilocus sequence typing (MLST) and eBURST analysis. It was found that the antibiotic-resistant and carbapenemase-resistant genes of all the 295 MDR A. baumannii in the hospital have not changed significantly over the past 12 years; all of them were resistant to multiple antibiotics except the polymyxin E and tigecycline. The results of drug-resistant genes showed that the detection rates of carbapenemase-resistant genes bla _OXA-23, bla _TEM-1, and bla _OXA-66 were 97.6, 75.3, and 71.9%, respectively, which were detected almost every year from 2008 to 2019. Additionally, 16s rRNA methylation enzyme gene armA, aminoglycoside-resistant gene ant(3")-I, and class I integrase gene could also have a high positive rate. By MLST, these isolates were assigned to 12 sequence types (STs), including ST369, ST208, ST195, ST191, ST368, ST530, ST469, ST451, ST229, ST381, ST543, and ST1176. eBURST analysis showed that 9 STs with ST208 as the founder genotype belonged to Group 1 except for ST229, ST530, and ST1176. Therefore, most MDR A. baumannii isolates had a relatively close genetic relationship. Notably, the predominant ST208 and ST369 at the early stage changed to ST451 in 2019, indicating that the complex and diverse genetic background of the prevalence of A. baumannii isolates in the hospital. Overall, further epidemiological surveillance and genetic evolution analysis of A. baumannii are required, which can provide new strategies for the prevention and control of A. baumannii infections.

SUBMITTER: Jiang M

PROVIDER: S-EPMC8388840 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Acinetobacter baumannii is a major opportunistic pathogen causing hospital-acquired infections, and it is imperative to comprehend its evolutionary and epidemiological dynamics in hospitals to prevent and control nosocomial transmission. Here, we present a comprehensive genomic epidemiological study involving the genomic sequencing and antibiotic resistance profiling of 634 A. baumannii strains isolated from seven intensive care units (ICUs) of a Chinese general hospital over 2 consecutive years. Our study reveals that ST2 is highly dominant (90.54%) in the ICUs, with 98.90% of the ST2 exhibiting multidrug resistant or extensively drug resistant. Phylogenetic analyses of newly sequenced genomes and public data suggest that nosocomial isolates originated outside the hospital but evolved inside. The major lineages appear to be stable, with 9 of the 28 identified nosocomial epidemic clones infecting over 60% of the affected patients. However, outbreaks of two highly evolved clones have been observed in different hospitals, suggesting significant inter-hospital transmission chains. By coupling patient medical records and genomic divergence of the ST2, we found that cross-ward patient transfer played a crucial role in pathogen's nosocomial transmission. Additionally, we identified 831 potential adaptive evolutionary loci and 44 associated genes by grouping and comparing the genomes of clones with different prevalence. Overall, our study provides a comprehensive and contemporary survey on the epidemiology and genomic evolution of A. baumannii in a large Chinese general hospital. These findings shed light on the nosocomial evolution and transmission of A. baumannii and offers valuable information for transmission prevention and antibiotic therapy.IMPORTANCEThis study delved into the genomic evolution and transmission of nosocomial Acinetobacter baumannii on a large scale, spanning both an extended time period and the largest sample size to date. Through molecular epidemiological investigations based on genomics, we can directly trace the origin of the pathogen, detecting and monitoring outbreaks of infectious diseases in a timely manner, and ensuring public health safety. In addition, this study also collects a large amount of genomic and antibiotic resistance detection data, which is helpful for phenotype prediction based on genomic sequencing. It enables patients to receive personalized antibiotic treatment quickly, helps doctors select antibiotics more accurately, and contributes to reducing the use of antibiotics and lowering the risk of antibiotic resistance development.

Project description:Acinetobacter baumannii is of growing concern for global health owing to its ability to evade the immune system and develop resistance to antibiotics. We analyzed A. baumannii using the National Center for Biotechnology Information (https://www.ncbi.nlm.nih.gov/pathogens) database and observed that the ST369 strain isolated in China constituted over 50% of the globally prevalent ST369 clones. This finding highlights the significant impact of ST369 on public health in China. In this study, we examined eight strains of multidrug-resistant A. baumannii ST369 isolated from a provincial hospital in China. We conducted whole-genome sequencing, comparative genomic analysis, and phenotypic experiments, and used the Galleria mellonella infection model to achieve a comprehensive understanding of the organism. In our study, we identified two mutations, G540A and G667D, on the wzc gene of A. baumannii ST369 that can potentially affect bacterial virulence and viscosity. We also verified the impact of these mutations on virulence and resistance. In addition, we examined two proteins, AB46_0125 and AB152_03903, which may play a role in virulence. These findings establish a foundation for future studies on clinical ST369 isolates harboring such mutations. IMPORTANCE Acinetobacter baumannii is a major health threat due to its antibiotic resistance and ability to cause nosocomial infections. Epidemiological studies indicated that the majority of globally prevalent ST369 clones originated from China, indicating a significant impact on public health in the country. In this study, we conducted whole-genome sequencing, comparative genomics, and Galleria mellonella infection model on eight A. baumannii ST369 isolates collected from a provincial hospital in China to comprehensively understand the organism. We identified two mutations (G540A and G667D) on the wzc gene that can affect bacterial virulence and viscosity. We confirmed their impact on resistance and virulence. We also investigated the potential involvement of AB46_0125 and AB152_03903 proteins in virulence. This finding provides a theoretical reference for further research on A. baumannii ST369 clinical isolates with similar mutations.

Project description:Virulence profiles and innate immune responses were studied in Acinetobacter baumannii from nosocomial infections collected over one year in a tertiary care hospital in Mexico. A. baumannii were identified by VITEK 2 System followed by susceptibility tests. Carbapenemase genes, active efflux mechanism to imipenem and meropenem and outer membrane proteins profile were analyzed to evaluate their role on the activity of carbapenem resistance. All isolates were genotyped by pulsed field gel electrophoresis. The ability to form biofilm was determined on a polystyrene surface. The resistance to complement was determined with a pooled human normal serum and TNF? release by infected macrophages was determined by ELISA. The 112 isolates from this study were associated with a 52% of mortality. All were resistance to ?-lactams, fluoroquinolones, and trimethroprim-sulfamethoxal, 96 and 90% were resistant to meropenem and imipenem, respectively, but with high susceptibility to polymyxin B, colistin and tigecyclin. Isolates were classified in 11 different clones. Most isolates, 88% (99/112), were metallo-?-lactamases and carbapenemases producers, associated in 95% with the presence of blaOXA-72 gene. Only 4/99 and 1/99 of the carbapenem-resistant isolates were related to efflux mechanism to meropenem or imipenem resistance, respectively. The loss of expression of 22, 29, and/or 33-36-kDa proteins was detected in 8/11 of the clinical isolates with resistance to carbapenem. More than 96% (108/112) of the isolates were high producers of biofilms on biotic surfaces. Finally, all isolates showed variable resistance to normal human serum activity and were high inductors of TNF? release by macrophages. In summary, these results suggest that multidrug-resistant A. baumannii can persist in the hospital environment through its ability to form biofilms. The high mortality observed was due to their ability to survive normal human serum activity and capability to induce potent inflammatory immune response making this nosocomial pathogen a serious threat to hospitalized patients.

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Epidemiological Analysis of Multidrug-Resistant Acinetobacter baumannii Isolates in a Tertiary Hospital Over a 12-Year Period in China.

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