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Carbapenem and colistin resistance in Enterobacteriaceae in Southeast Asia: Review and mapping of emerging and overlapping challenges

Malchione MD, Torres LM, Hartley DM, Koch M, Goodman JL

Int J Antimicrob Agents, 2019 Oct;54(4):381-399.
PMID: 31369812 DOI: 10.1016/j.ijantimicag.2019.07.019

Carbapenem-resistant Enterobacteriaceae infections have spread globally, leaving polymyxins, including colistin, as 'last-resort treatments'. Emerging colistin resistance raises the spectre of untreatable infections. Despite this threat, data remain limited for much of the world, including Southeast Asia where only 3 of 11 nations submitted data on carbapenem and colistin resistance for recent World Health Organization (WHO) reports. To improve our understanding of the challenge, we utilised broad strategies to search for and analyse data on carbapenem and colistin resistance among Escherichia coli and Klebsiella in Southeast Asia. We found 258 studies containing 526 unique reports and document carbapenem-resistant E. coli and Klebsiella in 8 and 9 of 11 nations, respectively. We estimated carbapenem resistance proportions through meta-analysis of extracted data for nations with ≥100 representative isolates. Estimated resistance among Klebsiella was high (>5%) in four nations (Indonesia, Philippines, Thailand and Vietnam), moderate (1-5%) in two nations (Malaysia and Singapore) and low (<1%) in two nations (Cambodia and Brunei). For E. coli, resistance was generally lower but was high in two of seven nations with ≥100 isolates (Indonesia and Myanmar). The most common carbapenemases were NDM metallo-β-lactamases and OXA β-lactamases. Despite sparse data, polymyxin resistance was documented in 8 of 11 nations, with mcr-1 being the predominant genotype. Widespread presence of carbapenem and polymyxin resistance, including their overlap in eight nations, represents a continuing risk and increases the threat of infections resistant to both classes. These findings, and remaining data gaps, highlight the urgent need for sufficiently-resourced robust antimicrobial resistance surveillance.

Matched MeSH terms: Carbapenems/pharmacology*
Antimicrobial Resistance Mechanisms and Genetic Diversity of Multidrug-Resistant Acinetobacter baumannii Isolated from a Teaching Hospital in Malaysia

Biglari S, Hanafiah A, Mohd Puzi S, Ramli R, Rahman M, Lopes BS

Microb Drug Resist, 2017 Jul;23(5):545-555.
PMID: 27854165 DOI: 10.1089/mdr.2016.0130

Multidrug-resistant (MDR) Acinetobacter baumannii has increasingly emerged as an important nosocomial pathogen. The aim of this study was to determine the resistance profiles and genetic diversity in A. baumannii clinical isolates in a tertiary medical center in Malaysia. The minimum inhibitory concentrations of carbapenems (imipenem and meropenem), cephalosporins (ceftazidime and cefepime), and ciprofloxacin were determined by E-test. PCR and sequencing were carried out for the detection of antibiotic resistance genes and mutations. Clonal relatedness among A. baumannii isolates was determined by REP-PCR. Sequence-based typing of OXA-51 and multilocus sequence typing were performed. One hundred twenty-five of 162 (77.2%) A. baumannii isolates had MDR phenotype. From the 162 A. baumannii isolates, 20 strain types were identified and majority of A. baumannii isolates (66%, n = 107) were classified as strain type 1 and were positive for ISAba1-blaOXA-23and ISAba1-blaADCand had mutations in both gyrA and parC genes at positions, 83 and 80, resulting in serine-to-leucine conversion. REP-PCR analysis showed 129 REP types that generated 31 clones with a 90% similarity cutoff value. OXA-66 variant of the blaOXA-51-likegenes was predominantly detected among our A. baumannii clinical isolates belonging to ST195 (found in six clones: 1, 8, 9, 19, 27, and 30) and ST208 (found in clone 21). The study helps us in understanding the genetic diversity of A. baumannii isolates in our setting and confirms that international clone II is the most widely distributed clone in Universiti Kebangsaan Malaysia Medical Centre, Malaysia.

Matched MeSH terms: Carbapenems/pharmacology
Fulltext Acinetobacter baumannii in suspected bacterial infections: Association between multidrug resistance, virulence genes, & biofilm production

Gautam D, Dolma KG, Khandelwal B, Goyal RK, Mitsuwan W, Pereira MLG, et al.

Indian J Med Res, 2023 Oct 01;158(4):439-446.
PMID: 38006347 DOI: 10.4103/ijmr.ijmr_3470_21

BACKGROUND OBJECTIVES: Acinetobacter baumannii has emerged as a nosocomial pathogen with a tendency of high antibiotic resistance and biofilm production. This study aimed to determine the occurrence of A. baumannii from different clinical specimens of suspected bacterial infections and furthermore to see the association of biofilm production with multidrug resistance and expression of virulence factor genes in A. baumannii.
METHODS: A. baumannii was confirmed in clinical specimens by the detection of the blaOXA-51-like gene. Biofilm production was tested by microtitre plate assay and virulence genes were detected by real-time PCR.
RESULTS: A. baumannii was isolated from a total of 307 clinical specimens. The isolate which showed the highest number of A. baumannii was an endotracheal tube specimen (44.95%), then sputum (19.54%), followed by pus (17.26%), urine (7.49%) and blood (5.86%), and <2 per cent from body fluids, catheter-tips and urogenital specimens. A resistance rate of 70-81.43 per cent against all antibiotics tested, except colistin and tigecycline, was noted, and 242 (78.82%) isolates were multidrug-resistant (MDR). Biofilm was detected in 205 (66.78%) with a distribution of 54.1 per cent weak, 10.42 per cent medium and 2.28 per cent strong biofilms. 71.07 per cent of MDR isolates produce biofilm (P<0.05). Amongst virulence factor genes, 281 (91.53%) outer membrane protein A (OmpA) and 98 (31.92%) biofilm-associated protein (Bap) were detected. Amongst 100 carbapenem-resistant A. baumannii, the blaOXA-23-like gene was predominant (96%), the blaOXA-58-like gene (6%) and none harboured the blaOXA-24-like gene. The metallo-β-lactamase genes blaIMP-1 (4%) and blaVIM-1(8%) were detected, and 76 per cent showed the insertion sequence ISAba1.
INTERPRETATION CONCLUSIONS: The majority of isolates studied were from lower respiratory tract specimens. The high MDR rate and its positive association with biofilm formation indicate the nosocomial distribution of A. baumannii. The biofilm formation and the presence of Bap were not interrelated, indicating that biofilm formation was not regulated by a single factor. The MDR rate and the presence of OmpA and Bap showed a positive association (P<0.05). The isolates co-harbouring different carbapenem resistance genes were the predominant biofilm producers, which will seriously limit the therapeutic options suggesting the need for strict antimicrobial stewardship and molecular surveillance in hospitals.

Matched MeSH terms: Carbapenems/pharmacology
Fulltext A retrospective study on molecular epidemiology trends of carbapenem resistant Enterobacteriaceae in a teaching hospital in Malaysia

Kong ZX, N Karunakaran R, Abdul Jabar K, Ponnampalavanar S, Chong CW, Teh CSJ

PeerJ, 2022;10:e12830.
PMID: 35223201 DOI: 10.7717/peerj.12830

BACKGROUND: Carbapenem resistant Enterobacteriaceae (CRE) has rapidly disseminated worldwide and has become a global threat to the healthcare system due to its resistance towards "last line" antibiotics. This study aimed to investigate the prevalence of CRE and the resistance mechanism as well as the risk factors associated with in-hospital mortality.
METHODS: A total of 168 CRE strains isolated from a tertiary teaching hospital from 2014-2015 were included in this study. The presence of carbapenemase genes and minimum inhibitory concentration of imipenem, meropenem and colistin were investigated. All carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) strains were characterised by PFGE. The risk factors of patients infected by CRE associated with in-hospital mortality were determined statistically.
RESULTS: The predominant CRE species isolated was K. pneumoniae. The carbapenemases detected were blaOXA-48, blaOXA-232, blaVIM and blaNDM of which blaOXA-48 was the predominant carbapenemase detected among 168 CRE strains. A total of 40 CRE strains harboured two different carbapenemase genes. A total of seven clusters and 48 pulsotypes were identified among 140 CRKp strains. A predominant pulsotype responsible for the transmission from 2014 to 2015 was identified. Univariate statistical analysis identified that the period between CRE isolation and start of appropriate therapy of more than 3 days was statistically associated with in-hospital mortality.

Matched MeSH terms: Carbapenems/pharmacology