Significant downtrend of antimicrobial resistance rate and rare β-lactamase genes and plasmid replicons carriage in clinical Pseudomonas aeruginosa in Southern China
Introduction
Pseudomonas aeruginosa is one of the most important opportunistic human pathogens causing both acute and chronic infections especially for nosocomial infections [1]. Recently, P. aeruginosa is noted for its increasing resistance rates to many kinds of antibiotics worldwide and its ability to acquire genes encoding resistance determinants [2]. As therapeutic treatment was concerned, selection of appropriate antibiotics is complicated because of the potential to acquire multiple resistance machanisms of P. aeruginosa [3]. As an important type of antibiotics, β-lactams are widely applied in P. aeruginosa infections. Considering the accumulation of multiple mechanisms of resistance will leads to multi-drug resistance, we take into account the key genes of multiple drug resistance mechanisms in this research. The major mechanism of resistance is the production of β-lactamases, followed by other important mechanisms including diminished expression of outer membrane proteins, mutations in topoisomerases, and up-regulation of efflux pumps [2]. Plasmid-mediated AmpC β-lactamases is characteristically chromosomally encoded in P. aeruginosa. Considering its contribution to the resistance mechanism to ticarcillin, piperacillin, and third-generation cephalosporins, DHA-type and CMY-type β-lactams were detected in this study [2,4]. Class A-type-β-lactamase is now emerging as a dominant extended-spectrum-β-lactams (ESBLs) type. Amongst, PER-type is common in P. aeruginosa, followed by other less common class A-type-β-lactamase (VEB-type, GES-type TEM-type, SHV-type, and CTX-M-type β-lactamase) [4,5]. Aminoglycoside-modifying enzymes (AMEs, especially ACC-type) were found to be one of the features of multidrug-resistant phenotype [6]. Other β-lactamases conferring resistance to carbapenems were emerged recently, such as KPC carbapenemases, some class D-type-β-lactamases (OXA-1-type, OXA-48-type, etc.) [7]. These sequences increase the spectrum of activity of the β-lactamases against antibiotics including ceftazidime or aztreonam. The major types of metallo-β-lactamases (MBLs, such as IMP-type and VIM-type), which are responsible for the resistance of imipenem and meropenem plus the antipseudomonal cephalosporins, including cefepime, and antipseudomonal penicillins, were also included in this study [8].
The dissemination of β-lactams resistance in Gram-negative bacteria including P. aeruginosa has been largely attributed to the horizontal transfer of β-lactamase genes by plasmids [[9], [10], [11]]. Plasmids contain genes essential for initiation and control of replication and accessory genes, and are capable of increasing bacterial gene diversity (acquiring and losing genes), horizontally transferring among bacteria by conjugation or mobilization [[12], [13], [14]]. The carriage of replicons, which contribute to the replication of plasmid, represents the acquisition of plasmids by strains. Since replication is a constant and conserved part of plasmid, replicon typing is a sensitive and specific method for identifying phylogenetically related plasmids and may provide clues to the evolution of resistance plasmids. Moreover, as surveillance on antimicrobial resistance and its determinants, as well as plasmids is of great significance for clinicians to choose therapy, study on clinical P. aeruginosa isolates may facilitate further understanding of the horizontal transfer of antimicrobial drug resistance [15,16].
In this study, we collected and analysed the antimicrobial resistance data of 2163 P. aeruginosa isolates collected in a 13-year period, with their β-lactam resistance genes and plasmid replicons carrying rates further identified.
Section snippets
Hospital setting, bacterial isolates and clinical data
A total of 2163 P. aeruginosa were isolated from the First Affiliated Hospital of Guangzhou Medical University (FAHGMU), a tertiary teaching hospital with the leading clinical laboratory on microbiology in Southern China. Containing 1500 beds, the large proportion of patients in FAHGMU are from cities in Guangdong provinces and adjacent provinces and small number of patients even from Central, East and West China. As a consequence, the surveillance investigation on P. aeruginosa in this study
Antimicrobial resistance of P. aeruginosa
According to the susceptibility results, the highest resistance rate was obtained for β-lactam (43.5%), followed by monobactams (mean 33.4%) and carbapenems (mean 33.2%), fluoroquinolones (mean 29.2%), penicillins (mean 24.2%), cephems (mean 17.9%) and aminoglycosides (mean 14.6%). Remarkably, decrease in resistance rate (>10%) during 2004–2016 was observed for tested antibiotics except for ATM and AMK (Table 1). In detail, dramatical decrease from period 1 to period 4 in CIP (>30.0%, from
Conclusion
As concluded, this study has provided comprehensive knowledge on current antimicrobial resistance, β-lactam resistance genes and plasmid replicons carriage in a large scale of clinical P. aeruginosa isolates collected during 2004–2016. Significant downtrend of resistance rate was observed for the majority of tested antibiotics, and rare identification rate was found for both major β-lactamase genes and plasmid replicons. The spreading dissemination of β-lactamase genes carrying strains and
Author statement
Zhenbo Xu: Conceptualization, Methodology, Funding acquisition. Xin Lin: Formal analysis, Writing-Original draft preparation, Writing-Review & Editing. Thanapop Soteyome: Investigation. Yanrui Ye: Visualization, Resources. Dingqiang Chen: Data curation. Ling Yang: Resources. Junyan Liu: Supervision, Writing-Review & Editing.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgement
This work was supported by the Guangdong Major Project of Basic and Applied Basic Research (2020B0301030005), Guangdong International S&T Cooperation Programme (2021A0505030007), State Key Laboratory of Applied Microbiology Southern China (Grant No. SKLAM005-2019), National Key Research and Development Program of China (No. 2017YFC1601202), Collaborative grant with AEIC (KEO-2019-0624-001-1), the 111 Project (B17018).
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