Genotypic patterns of multidrug-resistant Acinetobacter baumannii: A systematic review
Golnar Rahimzadeh, Mohammad S Rezai, Fereshteh Farshidi
Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
|Date of Submission||19-Dec-2022|
|Date of Acceptance||01-Feb-2023|
|Date of Web Publication||21-Mar-2023|
Prof. Mohammad S Rezai
Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari - 4815838477
Source of Support: None, Conflict of Interest: None
Acinetobacter baumannii (A. baumannii) is one of the most common bacteria in nosocomial infections. Inappropriate usage of antibiotics has led to expanding emergence resistance to A. baumannii as a multidrug-resistant (MDR) strain. Empirical antibiotic therapy is necessary to evaluate the resistant gene pattern of MDR A. baumannii. For this purpose, the present study evaluated the resistance genes pattern of MDR A. baumannii collected from hospitalized patients using a genotypic diagnostic technique. To find evidence related to the study objectives, databases were searched such as Google Scholar, Web of Science, Science Direct, PubMed, and Scopus from 2000 to 2022, with specified keywords in the title and text of the articles. Articles were included based on inclusion and exclusion criteria. The mentioned database displayed 284 articles. After screening, 65 eligible articles were included. The results showed that various b-lactamases genes, aminoglycoside-modifying enzymes (AMEs) genes, and pump-expressing genes are resistance gene patterns in MDR A. baumannii isolates. MDR A. baumannii has significantly become resistant to b-lactams, carbapenems, and aminoglycosides.
Keywords: Acinetobacter baumannii, molecular diagnostic, multidrug-resistant, systematic review
|How to cite this article:|
Rahimzadeh G, Rezai MS, Farshidi F. Genotypic patterns of multidrug-resistant Acinetobacter baumannii: A systematic review. Adv Biomed Res 2023;12:56
|How to cite this URL:|
Rahimzadeh G, Rezai MS, Farshidi F. Genotypic patterns of multidrug-resistant Acinetobacter baumannii: A systematic review. Adv Biomed Res [serial online] 2023 [cited 2023 Jun 7];12:56. Available from: https://www.advbiores.net/text.asp?2023/12/1/56/372184
| Introduction|| |
Acinetobacter baumannii (A. baumannii) is one of the most common bacteria in nosocomial infections, which causes many infections including skin and soft tissues, wound infections, bacteremia, endocarditis, urinary tract infections (UTIs), meningitis, and pneumonia. The mortality rate of ventilator-associated pneumonia (VAP) and infected blood caused by A. baumannii are reported from 40% to 70% and 28% to 43%, respectively.,
Currently, A. baumannii has been recognized as a multidrug-resistant (MDR) strain. According to the guidelines, MDR strains are known to be resistant to more than two different antibiotic classes containing carbapenems, aminoglycosides, ampicillin–sulbactam, cephalosporins, and fluoroquinolones. The principal mechanisms of resistance are membrane alterations, overexpression of efflux pumps, over expression of antibiotic-modifying enzymes, and modifications of target sites for antimicrobial agents.
B-lactamases have made A. baumannii resistant to b-lactam antibiotics. Carbapenems were recommended as the most effective drug for the treatment of A. baumannii infections., However, this strain acquired metallo-beta-lactamases (MBLs), and oxacilinases, and has limited the effectiveness of this drug. Furthermore, the emergence of colistin-resistant A. baumannii (Col-R-Ab) strain is reported. This resistance occurs due to changes in the structure of the lipopolysaccharide (LPS) and the presence of plasmid-carrying genes (mcr-1, mcr-2, mcr-3, and mcr-4.3).
The prevalence of antibiotic resistance and experimental prescription of antibiotics has increased without knowing the antibiotic resistance genes pattern in various countries. To detect the antibiotic resistance gene patterns in various countries and choose the correct antibiotics, screening the antibiotic resistance genes pattern of MDR A. baumannii over time may provide valuable data.
During the past two decades, molecular approaches have been introduced as a valuable technique to detect antibiotic resistance gene patterns in MDR A. baumannii isolates.,,,,,,, For this purpose, this study is to evaluate the antibiotic resistance gene patterns of MDR A. baumannii isolates using a genotypic diagnostic technique.
| Materials and Methods|| |
To find evidence related to the study purpose objectives, databases such as Google Scholar, Web of Science, Science Direct, PubMed, and Scopus were searched from 2000 to 2022, with keywords specified in the title and text of the articles. The specified keywords for searching English language databases included “MDR A. baumannii,” “PCR,” “RT PCR,” “multiplex PCR,” “b-lactamases,” “efflux pumps,” and “aminoglycoside-modifying enzymes,” which were used by the MeSH strategy.
The inclusion criteria included studies published in English, genotypic diagnostic techniques, and MDR A. baumannii isolates. The exclusion criteria included studies published in Persian, articles that were presented at national and international congresses, letters to editors, review articles, and phenotypic diagnostic techniques.
Finally, studies were identified and reviewed after excluding duplicates during primary screening. In the secondary screening, the full text of the articles was evaluated [Figure 1]. Data were extracted and recorded, including first author, duration isolation of MDR A. baumannii, country, number of samples, resistant gene patterns, and genotypic diagnostic technique, resistance to antibiotics [Table 1].
| Results|| |
The mentioned databases displayed 284 articles. After the exclusion of duplicate articles, 268 articles were reviewed. Finally, 65 articles were selected based on the exclusion and inclusion criteria [Figure 1]. The results showed different classes or subclasses of b-lactamases, AMEs, and efflux pumps genes were isolated from MDR A. baumannii isolates from the wound, blood, urine, catheter tips, soft tissue, bronchial aspirates, sputum, vascular catheter, stool, and cerebrospinal fluid (CSF).
| Discussion|| |
This study systematically reviewed 65 published English studies in various countries from 2000 to 2022 and evaluated the antibiotic resistance gene pattern of MDR A. baumannii, which were isolated from the wound, blood, urine, catheter tips, soft tissue, bronchial aspirates, sputum, vascular catheter, stool, and CSF. Out of 65 studies, 55 studies showed resistance to b-lactams, aminoglycosides, and fluoroquinolones.
Resistance to b-lactams can due to the expression of oxacillinases, MBLs, b-lactamases genes. Higgins et al.,, and other studies detected oxacillinases and MBLs such as blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, blaOXA-143, bla IMP, blaVIM, bla GIM, bla SMP, and bla NDM in MDR A. baumannii.,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,
Oxacillinases significantly hydrolyze some antibiotics belonging to cephalosporins such as methicillin and amoxicillin. They are part of the epidemiological problem of the resistant A. baumannii strains. Its expression considerably increases the resistance to carbapenems and cephalosporins., blaOXA-58 confers the antibiotics resistance mechanism to penicillin, imipenem, and oxacillin, whereas it cannot hydrolysis expanded-spectrum cephalosporins blaOXA-23-like hydrolyze ticarcillin, meropenem, amoxicillin, and imipenem. In the study by Higgins and other studies, the blaOXA-23 gene was detected in MDR A. baumannii.,,,,,,,,,,,,,,,,,,,,
The blaOXA-40-like weakly hydrolyzes cephalosporins and carbapenems such as imipenem and ceftazidime. This enzyme is resistant to tazobactam and sulbactam clavulanic acid., Qureshiand Hammoudi reported A. baumannii isolates were resistant to b-lactams and tazobactam by detection of blaOXA-40-like.
In previous reports, the incidence rate of MDR A. baumannii was reported to be 74%. The prevalence of MDR A. baumannii has increased from 50% in 2001–2007 to 74% in 2010–2015 in Iran. Reasons for such an increase are uncontrolled and overuse of antimicrobial agents, trade among nations, lack of surveillance of MDR strains, lack of use of sensitive techniques for MDR detection in clinical labs, and a rising number of patients with prolonged hospitalization.,
The antibiotic choice for treating MDR A. baumannii infections is restricted, and lipopeptides can be an alternative treatment option. Polymyxin B and colistin can be effective in the treatment of urinary tract infections, infected wounds, and blood infections. However, nephrotoxicity is a detriment to their utilization., Previous studies showed a combination of imipenem with aminoglycosides, glycylcyclines, ampicillin, rifampicin, aztreonam, sulbactam, and lipopeptides can produce a synergistic effect against MDR A. baumannii. Combination therapies can significantly enhance bactericidal activity from 8.4–26.4 to 60.3–86.7%. A previous meta-analysis reported combinations of colistin–glycopeptide and polymyxin–carbapenem to have synergistic effect for 70% of isolates with relatively low toxicity.
Other mechanisms of enzymatic resistance include AME expression. Mak et al. and other studies detected aacC1, orfX, orfX', and aadA1 genes in MDR A. baumannii isolates.,,,
In the present study, 10 studies showed that overexpression of an efflux system can be an efficient mechanism for drug resistance in A. baumannii isolates,,,,,,,,, The corresponding structural efflux pump genes are part of plasmids, transposons, or resistance islands, which MDR A. baumannii acquires in hospital units such as intensive care units (ICU) and burns units or from the environment. Efflux pumps with other antibiotic resistance mechanisms allow bacteria to reach high-level resistance; moreover, they weakly increase the MICs. Five superfamilies of efflux systems are associated with drug resistance: ATP-binding cassette (ABC) transporters, small multidrug resistance (SMR), and multidrug and toxic compound extrusion (MATE) families, major facilitator superfamily (MFS), and the resistance-nodulation-cell division (RND) family, which are the most clinically relevant.
Efflux pumps confer multidrug resistance to gram-negative bacteria. AdeABC is the first characterized RND system in A. baumannii. AdeABC extrudes aminoglycosides, b-lactams, fluoroquinolones, tetracycline, tigecycline, macrolides, chloramphenicol, and trimethoprim. Overexpression of AdeABC significantly causes higher-level carbapenem resistance. Beheshti et al., and other studies reported resistance to the mentioned antibiotics and detected adeA, adeB, adeC, adeJ, and abeM genes.,,,,,, AdeIJK is the second RND efflux system, which contributes to intrinsic resistance to b-lactams.
According to data in [Table 1], antibiotic resistance gene pattern in MDR isolates is different in various countries even in different hospitals in the same country. Antibiotic resistance gene pattern, through rapid genotypic diagnostics technique (PCR, RT.PCR), can avoid or reduce the risk of clinical response failure, guide antibiotic prescribing for MDR isolates, and reduce the socioeconomic burden associated with antibiotic-resistant infections in the community. Detection of antibiotic resistance gene patterns in various regions causes the development of a better understanding of the relationship between antibiotic prescribing levels and significant non-development of antibiotic resistance in the community. Although matrix-assisted laser desorption ionization-time of flight (MALDI-TOF), next-generation sequencing (NGS), and whole-genome sequencing (WGS) are rapid and new genotypic diagnostic techniques to detect MDR isolates, in the present study, we did not investigate these methods to detect antibiotic resistance genes pattern in MDR isolates.
| Conclusion|| |
MDR A. baumannii isolates are about many times more likely to resist than other bacteria related to hospital infections. MDR A. baumannii has widely become resistant to b-lactam antibiotics. Significant resistance to oxacillins has become part of the epidemiological problem of MDR A. baumannii isolates.
The authors would like to thank the Pediatric Infectious Diseases Research Center at Bou-Ali Sina hospital in Sari.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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