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  1. Hwa WE, Subramaniam G, Navaratnam P, Sekaran SD
    J Microbiol Immunol Infect, 2009 Feb;42(1):54-62.
    PMID: 19424559
    To detect and characterize class 1 integrons among carbapenem-resistant strains of Acinetobacter spp. at University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia.
    Matched MeSH terms: Integrons/genetics*
  2. Ibrahim N, Wajidi MF, Yusof MY, Tay ST
    Trop Biomed, 2011 Dec;28(3):668-71.
    PMID: 22433898 MyJurnal
    The increased frequency of antibiotic resistance is known to be associated with the dissemination of integrons in the Enterobacteriaceae. This study determined the prevalence and type of integrons amongst 160 extended-spectrum beta-lactamase producing enterobacterial isolates kept in our culture collection. Integrons were detected in 98(61.3%) isolates, including 28(62.2%) Escherichia coli, 34(64.2%) Klebsiella spp., 27(61.4%), Enterobacter spp. and 9(50.0%) Citrobacter spp. investigated in this study. Restriction analysis of the integron gene fragments revealed that class I integron was the principal integron detected in 92(57.5%) of our isolates. Class II integron was detected in 6(3.8%) of our isolates, while no class III integron was detected in this study. The high rates of integron prevalence particularly of the class I integron in the E. coli and Klebsiella spp. concur with previous studies in other geographical regions. The higher (≥50%) integron prevalence of Citrobacter and Enterobacter isolates comparing to previous studies suggests the potential of these isolates as sources for dissemination of resistance determinants. The finding in this study serves as a basis for further study on the antibiotic resistance mechanisms of enterobacterial species in this teaching hospital.
    Matched MeSH terms: Integrons*
  3. Khosravi Y, Tay ST, Vadivelu J
    J Med Microbiol, 2011 Jul;60(Pt 7):988-994.
    PMID: 21436370 DOI: 10.1099/jmm.0.029868-0
    In this study, 90 non-replicate imipenem-resistant Pseudomonas aeruginosa (IRPA) Malaysian isolates collected between October 2005 and March 2008 were subjected to a screening test for detection of the integron and the gene cassette. Class 1 integrons were detected in 54 IRPA clinical isolates, whilst three isolates contained class 2 integrons. Analysis of the gene cassettes associated with the class 1 integrons showed the detection of accC1 in isolates carrying bla(IMP-7) and aacA7 in isolates carrying bla(VIM-2). aadA6 was detected in two isolates carrying bla(IMP-4). Using random amplification of polymorphic DNA analysis, 14 PCR fingerprint patterns were generated from the 32 isolates carrying metallo-β-lactamase (MBL) genes (35.5 %), whilst 20 patterns were generated from the 58 non-MBL gene isolates (64.4 %). Based on the differences in the fingerprinting patterns, two clusters (A and B) were identified among the MBL-producing isolates. Cluster A comprised 18 isolates (56 %) carrying the bla(VIM) gene, whereas cluster B comprised 14 (44 %) isolates carrying the bla(IMP) gene. The non-MBL isolates were divided into clusters C and D. Cluster C comprised 22 non-MBL isolates harbouring class 1 integrons, whilst cluster D consisted of three isolates carrying class 2 integrons. These findings suggest that the class 1 integron is widespread among P. aeruginosa isolated in Malaysia and that characterization of cassette arrays of integrons will be a useful epidemiological tool to study the evolution of multidrug resistance and the dissemination of antibiotic resistance genes.
    Matched MeSH terms: Integrons/genetics*; Integrons/physiology
  4. Phoon HYP, Hussin H, Hussain BM, Thong KL
    Microb Drug Resist, 2018 Oct;24(8):1108-1116.
    PMID: 29437541 DOI: 10.1089/mdr.2017.0258
    Pseudomonas aeruginosa infections account for high morbidity and mortality rates worldwide. Increasing resistance toward β-lactams, especially carbapenems, poses a serious therapeutic challenge. However, the multilocus sequence typing (MLST) of extended-spectrum beta lactamase (ESBL)- and carbapenemase-producing clinical P. aeruginosa has not been reported in Malaysia. This study aimed to determine the antibiotic susceptibility profiles, resistance genes, pulsotypes, and sequence types (STs) of clinical P. aeruginosa from a Malaysian tertiary hospital. These characteristics were analyzed by disk diffusion, minimum inhibitory concentration, polymerase chain reaction, pulsed-field gel electrophoresis (PFGE), and MLST for 199 nonreplicate clinical strains. The susceptibility of the strains toward the carbapenems and piperacillin-tazobactam was the lowest (≤90%), while ≥90% of the strains remained susceptible to all other classes of antimicrobial agents tested. The multidrug-resistant strains displayed high level resistance to cephalosporins (48 to ≥256 mg/L) and carbapenems (4-32 mg/L). Eleven strains harbored class 1 integrons containing blaGES-13, blaVIM-2, blaVIM-6, blaOXA-10, aacA(6')-Ib, aacA(6')-II, aadA6, and gcuD gene cassettes. Extra-integron genes, blaGES-20, blaIMP-4, blaVIM-2, and blaVIM-11, were also found. Overall, the maximum likelihood tree showed concordance in the clustering of strains having the same STs and PFGE clusters. ST708 was the predominant antibiotic-susceptible clone detected from the neonatal intensive care unit. The STs 235, 809, and 1076 clonal clusters consisted of multidrug resistant strains. ST235 is a recognized international high-risk clone. This is the first report of blaGES-13 and blaGES-20 ESBL-encoding gene variants and novel STs (STs 2329, 2335, 2337, 2338, 2340, and 2341) of P. aeruginosa in Malaysia.
    Matched MeSH terms: Integrons/drug effects; Integrons/genetics
  5. Lean SS, Yeo CC
    Front Microbiol, 2017;8:1547.
    PMID: 28861061 DOI: 10.3389/fmicb.2017.01547
    Acinetobacter baumannii is a Gram-negative nosocomial pathogen that has become a serious healthcare concern within a span of two decades due to its ability to rapidly acquire resistance to all classes of antimicrobial compounds. One of the key features of the A. baumannii genome is an open pan genome with a plethora of plasmids, transposons, integrons, and genomic islands, all of which play important roles in the evolution and success of this clinical pathogen, particularly in the acquisition of multidrug resistance determinants. An interesting genetic feature seen in majority of A. baumannii genomes analyzed is the presence of small plasmids that usually ranged from 2 to 10 kb in size, some of which harbor antibiotic resistance genes and homologs of plasmid mobilization genes. These plasmids are often overlooked when compared to their larger, conjugative counterparts that harbor multiple antibiotic resistance genes and transposable elements. In this mini-review, we will examine our current knowledge of these small A. baumannii plasmids and look into their genetic diversity and phylogenetic relationships. Some of these plasmids, such as the Rep-3 superfamily group and the pRAY-type, which has no recognizable replicase genes, are quite widespread among diverse A. baumannii clinical isolates worldwide, hinting at their usefulness to the lifestyle of this pathogen. Other small plasmids especially those from the Rep-1 superfamily are truly enigmatic, encoding only hypothetical proteins of unknown function, leading to the question of whether these small plasmids are "good" or "bad" to their host A. baumannii.
    Matched MeSH terms: Integrons
  6. Benacer D, Thong KL, Watanabe H, Puthucheary SD
    J Microbiol Biotechnol, 2010 Jun;20(6):1042-52.
    PMID: 20622506
    Forty-seven Salmonella Typhimurium (33 zoonotic, 14 clinical) strains were tested for antimicrobial resistance using the standard disk diffusion method. Presence of relevant resistance genes and class 1 integrons were investigated by using PCR. Pulsed-field gel electrophoresis (PFGE) and plasmid profiling were carried out to determine the genomic diversity of Salmonella Typhimurium. Approximately 57.4% of S. Typhimurium were multidrug resistant (MDR) and showed high resistance rates to tetracycline (70.2%), sulphonamides (57.4%), streptomycin (53.1%), ampicillin (29.7%), nalidixic acid (27.6%), kanamycin (23.4%), chloramphenicol (21.2%) and trimethoprim (19.1%). Resistance towards cephalosporins was noted for cephalothin (27.6%), cephradine (21.2%), amoxicillin clavulanic acid (17.0%) and cephalexin (17.0%). Resistance genes, blaTEM, strA, aadA, sul1, sul2, tet(A), tet(B) and tet(C) were detected among the drug resistant strains. Thirty-three strains (70.2%) carried class 1 integrons, which were grouped in 9 different profiles. DNA sequencing identified sat, aadA, pse-1 and dfrA genes in variable regions on class 1 integrons. Thirty-five strains (74.4%) were subtyped to 22 different plasmid profiles, each with 1 - 6 plasmids (2.0 to 95 kb). PFGE subtyped the 47 strains into 39 profiles. In conclusion, high rates of multidrug-resistance were found among the Malaysian Salmonella Typhimurium strains. The emergence of multidrug-resistant Salmonella Typhimurium to cephalosporin antibiotics was also observed. The strains were very diverse and no persistent clone was observed. The emergence of MDR Salmonella Typhimurium is a worldwide problem and this report provides information for the better understanding of the prevalence and epidemiology of MDR S. Typhimurium in Malaysia.
    Matched MeSH terms: Integrons*
  7. Lim KT, Yasin RM, Yeo CC, Puthucheary SD, Balan G, Maning N, et al.
    J Microbiol Immunol Infect, 2009 Jun;42(3):197-209.
    PMID: 19812853
    Pseudomonas aeruginosa is the third most common pathogen causing nosocomial infections. The objective of this study was to investigate the antimicrobial resistance profiles and genetic diversity of hospital isolates of P. aeruginosa and to investigate the presence of several resistance genes and integrons.
    Matched MeSH terms: Integrons/genetics
  8. Mobasseri G, Teh CSJ, Ooi PT, Tan SC, Thong KL
    Microb Drug Resist, 2019 Sep;25(7):1087-1098.
    PMID: 30844323 DOI: 10.1089/mdr.2018.0184
    Aims:
    The high prevalence of multidrug resistance (MDR) and extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae associated with nosocomial infections has caused serious therapeutic challenges. The objectives of this study were to determine the genotypic and phenotypic characteristics of K. pneumoniae strains isolated from Malaysian swine farms and the transferability of ESBL genes by plasmids.
    Results:
    A total of 50 K. pneumoniae strains were isolated from 389 samples, which were collected from healthy and unhealthy pigs (swine rectum and oral cavities), healthy farmers (human rectum, urine, and nasal cavities), farm's environment, and animal feeds from seven Malaysian swine farms. Antimicrobial susceptibility analysis of these 50 K. pneumoniae strains showed that the majority (86%) were resistant to tetracycline, while 44% and 36% of these strains were MDR and ESBL producers, respectively. PCR and DNA sequencing of the amplicons showed the occurrence of blaTEM (15/18), blaSHV (15/18), blaCTX-M-1 group (7/18), and blaCTX-M-2 group (2/18), while only class 1 integron-encoded integrase was detected. Conjugation experiments and plasmid analysis indicated that the majority of the ESBL genes were plasmid encoded and the plasmids in 11 strains were conjugative. Genotyping by pulsed-field gel electrophoresis and repetitive extragenic palindrome-polymerase chain reaction (REP-PCR) showed that these 50 strains were genetically diverse with 44 pulsotypes and 43 REP-PCR subtypes.
    Conclusions:
    ESBL-producing K. pneumoniae strains showed high resistance to tetracycline as this antibiotic is used for prophylaxis and therapeutic purposes at the swine farms. The findings in this study have drawn attention to the issue of increasing MDR in animal husbandry and it should be taken seriously to prevent the spread and treatment failure due to antimicrobial resistance.
    Matched MeSH terms: Integrons/genetics
  9. Ghaderpour A, Ho WS, Chew LL, Bong CW, Chong VC, Thong KL, et al.
    Front Microbiol, 2015;6:977.
    PMID: 26483759 DOI: 10.3389/fmicb.2015.00977
    E.coli, an important vector distributing antimicrobial resistance in the environment, was found to be multi-drug resistant, abundant, and genetically diverse in the Matang mangrove estuaries, Malaysia. One-third (34%) of the estuarine E. coli was multi-drug resistant. The highest antibiotic resistance prevalence was observed for aminoglycosides (83%) and beta-lactams (37%). Phylogenetic groups A and B1, being the most predominant E. coli, demonstrated the highest antibiotic resistant level and prevalence of integrons (integron I, 21%; integron II, 3%). Detection of phylogenetic group B23 downstream of fishing villages indicates human fecal contamination as a source of E. coli pollution. Enteroaggregative E. coli (1%) were also detected immediately downstream of the fishing village. The results indicated multi-drug resistance among E. coli circulating in Matang estuaries, which could be reflective of anthropogenic activities and aggravated by bacterial and antibiotic discharges from village lack of a sewerage system, aquaculture farms and upstream animal husbandry.
    Matched MeSH terms: Integrons
  10. Ho WS, Yap KP, Yeo CC, Rajasekaram G, Thong KL
    Front Microbiol, 2015;6:1547.
    PMID: 26793180 DOI: 10.3389/fmicb.2015.01547
    Extraintestinal pathogenic Escherichia coli (ExPEC) that causes extraintestinal infections often harbor plasmids encoding fitness traits such as resistance and virulence determinants that are of clinical importance. We determined the complete nucleotide sequence of plasmid pEC302/04 from a multidrug-resistant E. coli EC302/04 which was isolated from the tracheal aspirate of a patient in Malaysia. In addition, we also performed comparative sequence analyses of 18 related IncFIIA plasmids to determine the phylogenetic relationship and diversity of these plasmids. The 140,232 bp pEC302/04 is a multireplicon plasmid that bears three replication systems (FII, FIA, and FIB) with subtype of F2:A1:B1. The plasmid is self-transmissible with a complete transfer region. pEC302/04 also carries antibiotic resistance genes such as bla TEM-1 and a class I integron containing sul1, cml and aadA resistance genes, conferring multidrug resistance (MDR) to its host, E. coli EC302/04. Besides, two iron acquisition systems (SitABCD and IutA-IucABCD) which are the conserved virulence determinants of ExPEC-colicin V or B and M (ColV/ColBM)-producing plasmids were identified in pEC302/04. Multiple toxin-antitoxin (TA)-based addiction systems (i.e., PemI/PemK, VagC/VagD, CcdA/CcdB, and Hok/Sok) and a plasmid partitioning system, ParAB, and PsiAB, which are important for plasmid maintenance were also found. Comparative plasmid analysis revealed only one conserved gene, the repA1 as the core genome, showing that there is an extensive diversity among the IncFIIA plasmids. The phylogenetic relationship of 18 IncF plasmids based on the core regions revealed that ColV/ColBM-plasmids and non-ColV/ColBM plasmids were separated into two distinct groups. These plasmids, which carry highly diverse genetic contents, are also mosaic in nature. The atypical combination of genetic materials, i.e., the MDR- and ColV/ColBM-plasmid-virulence encoding regions in a single ExPEC plasmid is rare but of clinical importance. Such phenomenon is bothersome when the plasmids are transmissible, facilitating the spread of virulence and resistance plasmids among pathogenic bacteria. Notably, certain TA systems are more commonly found in particular ExPEC plasmid types, indicating the possible relationships between certain TA systems and ExPEC pathogenesis.
    Matched MeSH terms: Integrons
  11. Nusrat T, Akter N, Haque M, Rahman NAA, Dewanjee AK, Ahmed S, et al.
    Pathogens, 2019 Sep 12;8(3).
    PMID: 31547453 DOI: 10.3390/pathogens8030151
    BACKGROUND: Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in intensive care units (ICU), which accounts for 25% of all ICU infection. Documenting carbapenem-resistant gram-negative bacilli is very important as these strains may often cause outbreaks in the ICU setting and are responsible for the increased mortality and morbidity or limiting therapeutic options. The classical phenotypic method cannot provide an efficient means of diagnosis of the metallo-β-lactamases (MBLs) producer. Polymerase chain reaction (PCR) assays have lessened the importance of the phenotypic approach by detecting metallo-β-lactamase resistance genes such as New Delhi metallo-β-lactamase (NDM), Imipenemase (IMP), Verona integron-encoded metallo-β-lactamase (VIM), Sao Paulo metallo-β-lactamase (SPM), Germany Imipenemase (GIM).

    OBJECTIVE: To compare the results of the Combined Disc Synergy Test (CDST) with that of the multiplex PCR to detect MBL-producing gram-negative bacilli.

    MATERIALS AND METHOD: A total of 105 endotracheal aspirates (ETA) samples were collected from the ICU of a public school in Bangladesh. This cross-sectional study was carried out in the Department of Microbiology, Chittagong for quantitative culture, CDST test, and multiplex PCR for blaIMP, blaVIM, blaNDM genes of MBL producers.

    RESULTS: Among the 105 clinically suspected VAP cases, the quantitative culture was positive in 95 (90%) and among 95 g-negative bacilli isolated from VAP patients, 46 (48.42%) were imipenem resistant, 30 (65.22%) were MBL producers by CDST, 21 (45.65%) were identified as MBL producers by multiplex PCR.

    CONCLUSION: PCR was highly sensitive and specific for the detection of MBL producers.

    Matched MeSH terms: Integrons
  12. Chuah LO, Shamila Syuhada AK, Mohamad Suhaimi I, Farah Hanim T, Rusul G
    Food Res Int, 2018 03;105:743-751.
    PMID: 29433269 DOI: 10.1016/j.foodres.2017.11.066
    We investigated the genetic relatedness, antibiotic resistance and biofilm-producing ability of 114 strains of Salmonella, belonged to three serotypes (Corvallis, Brancaster and Albany), isolated from naturally contaminated poultry and their environment in wet markets and smale-scale processing plant from northern Malaysia. Pulsed-field gel electrophoresis revealed that Salmonella strains isolated from various wet markets were clonally related, suggesting the widespread dissemination of these three serotypes in northern Malaysia. All except one strain of Salmonella were resistant to more than two classes of antibiotics, hence regarded as multidrug resistant (MDR). Resistance to sulphonamide (96.5%), ampicillin (89.5%), tetracycline (85.1%), chloramphenicol (75.4%), trimethoprim (68.4%), trimethoprim-sulfamethoxazole (67.5%), streptomycin (58.8%) and nalidixic acid (44.4%) were observed. Resistance determinants, floR, cmlA, tetA, tetB, tetG, temB, blaPSE-1, sul1, sul2, qnrA, qnrS, strA and aadA were detected by PCR among MDR Salmonella strains. Seventy-six strains (66.7%) harboured class-I integrons. The gene cassettes identified were dfrA1, dfrA12, aadA2 and an open reading frame orfC with unknown function. All Salmonella strains produced biofilm and 69.3% of them were strong biofilm-producers. Our findings suggested that most likely, persistent Salmonella colonises various sites in the processing environment by producing biofilm, which leads to their widespread dissemination in wet markets located in northern Malaysia.
    Matched MeSH terms: Integrons
  13. Kor SB, Choo QC, Chew CH
    J Med Microbiol, 2013 Mar;62(Pt 3):412-420.
    PMID: 23180481 DOI: 10.1099/jmm.0.053645-0
    This study investigated 147 multidrug-resistant Enterobacteriaceae and Pseudomonas aeruginosa isolates from hospitalized patients in Malaysia. Class 1 integrons were the most dominant class identified (45.6%). Three isolates were shown to contain class 2 integrons (2.0%), whilst one isolate harboured both class 1 and 2 integrons. No class 3 integrons were detected in this study. In addition, the sul1 gene was amplified in 35% of isolates and was significantly associated with the presence of integrase genes in an integron structure. RFLP and DNA sequencing analyses revealed the presence of 19 different cassette arrays among the detected integrons. The most common gene cassettes were those encoding resistance towards aminoglycosides (aad) and trimethoprim (dfr). As far as is known, this study is the first to identify integron-carrying cassette arrays such as aadA2-linF, aacC3-cmlA5 and aacA4-catB8-aadA1 in the Malaysian population. Patients' age was demonstrated as a significant risk factor for the acquisition of integrons (P=0.028). Epidemiological typing using PFGE also demonstrated a clonal relationship among isolates carrying identical gene cassettes in Klebsiella pneumoniae and P. aeruginosa but not in Escherichia coli isolates.
    Matched MeSH terms: Integrons/genetics*
  14. Neela V, Rankouhi SZ, van Belkum A, Goering RV, Awang R
    Int J Infect Dis, 2012 Aug;16(8):e603-7.
    PMID: 22698885 DOI: 10.1016/j.ijid.2012.04.004
    Stenotrophomonas maltophilia is a recently identified nosocomial pathogen in Malaysia. Despite limited pathogenicity, its rate of isolation has increased in recent years. The aim of this study was to investigate the antibiotic susceptibility patterns, antibiotic resistance determinants, and the epidemiology of S. maltophilia at the largest tertiary care hospital in Malaysia.
    Matched MeSH terms: Integrons
  15. Ramesh Kumar MR, Arunagirinathan N, Srivani S, Dhanasezhian A, Vijaykanth N, Manikandan N, et al.
    Microb Drug Resist, 2017 Jul;23(5):602-608.
    PMID: 27854149 DOI: 10.1089/mdr.2016.0034
    The antibiotic, trimethoprim-sulfamethoxazole (TMP-SMX), is generally used for prophylaxis in HIV individuals to protect them from Pneumocystis jiroveci infection. Long-term use of TMP-SMX develops drug resistance among bacteria in HIV patients. The study was aimed to detect the TMP-SMX resistance genes among gram-negative bacteria from HIV patients. TMP-SMX-resistant isolates were detected by the Kirby-Bauer disc diffusion method. While TMP resistance genes such as dfrA1, dfrA5, dfrA7, and dfrA17 and SMX resistance genes such as sul1 and sul2 were detected by multiplex PCR, class 1 and class 2 integrons were detected by standard monoplex PCR. Of the 151 TMP-SMX-resistant bacterial isolates, 3 were positive for sul1 alone, 48 for sul2 alone, 11 for dfrA7 alone, 21 for sul1 and sul2, 1 for sul1 and dfrA7, 23 for sul2 and dfrA7, 2 for sul2 and dfrA5, 41 for sul1, sul2, and dfrA7, and 1 for sul2, dfrA5, and dfrA7. Of 60 TMP-SMX-resistant isolates positive for integrons, 44 had class 1 and 16 had class 2 integrons. It was found that the prevalence of sul genes (n = 202; p 
    Matched MeSH terms: Integrons
  16. Lim KT, Yasin R, Yeo CC, Puthucheary S, Thong KL
    J Biomed Biotechnol, 2009;2009:165637.
    PMID: 19672454 DOI: 10.1155/2009/165637
    The emergence of Escherichia coli that produce extended spectrum beta-lactamases (ESBLs) and are multidrug resistant (MDR) poses antibiotic management problems. Forty-seven E. coli isolates from various public hospitals in Malaysia were studied. All isolates were sensitive to imipenem whereas 36 were MDR (resistant to 2 or more classes of antibiotics). PCR detection using gene-specific primers showed that 87.5% of the ESBL-producing E. coli harbored the blaTEM gene. Other ESBL-encoding genes detected were blaOXA, blaSHV, and blaCTX-M. Integron-encoded integrases were detected in 55.3% of isolates, with class 1 integron-encoded intI1 integrase being the majority. Amplification and sequence analysis of the 5'CS region of the integrons showed known antibiotic resistance-encoding gene cassettes of various sizes that were inserted within the respective integrons. Conjugation and transformation experiments indicated that some of the antibiotic resistance genes were likely plasmid-encoded and transmissible. All 47 isolates were subtyped by PFGE and PCR-based fingerprinting using random amplified polymorphic DNA (RAPD), repetitive extragenic palindromes (REPs), and enterobacterial repetitive intergenic consensus (ERIC). These isolates were very diverse and heterogeneous. PFGE, ERIC, and REP-PCR methods were more discriminative than RAPD in subtyping the E. coli isolates.
    Matched MeSH terms: Integrons
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