Displaying publications 1 - 20 of 54 in total

Abstract:
Sort:
  1. Gan HM, Lean SS, Suhaili Z, Thong KL, Yeo CC
    J Bacteriol, 2012 Nov;194(21):5979-80.
    PMID: 23045494 DOI: 10.1128/JB.01466-12
    Acinetobacter baumannii is a major cause of nosocomial infection worldwide. We report the draft genome sequence of A. baumannii AC12, a multidrug-resistant nosocomial strain with additional resistance to carbapenems and polymyxin. The genome data will provide insights into the genetic basis of antimicrobial resistance and its adaptive mechanism.
    Matched MeSH terms: Carbapenems/pharmacology
  2. Heng PY, Sulong A, Ali UKS, Wong KK
    Malays J Pathol, 2019 Aug;41(2):139-148.
    PMID: 31427549
    INTRODUCTION: OXA-48, a carbapenem-hydrolysing class D β-lactamase, and its variant, OXA-181, are increasingly reported worldwide. This study aimed to describe the prevalence and distribution of OXA-48 and OXA-181 carbapenem-resistant Enterobacteriaceae (CRE) in a tertiary medical centre in Malaysia.

    MATERIALS & METHODS: A total of 13,098 Enterobacteriaceae isolates from various clinical samples were sent to our laboratory between January 2011 and December 2012. Of these, 90 demonstrated reduced susceptibility to at least one carbapenem and were included in this study. Only 88 isolates were successfully subcultured on blood agar (BA). Another 2 isolates failed to grow and were excluded. Of the 88, 2 isolates had the same identification number (repetitive isolates); therefore, 1 isolate was excluded from further analyses. Only 87 isolates were subjected to molecular detection of the blaOXA-48 and blaOXA-181 genes by polymerase chain reaction.

    RESULTS: Eighty-seven non-repetitive isolates grew following subculture on BA. Of these, 9 (10.34%) were positive for OXA-48 (7 Klebsiella pneumoniae, 2 Escherichia coli). Each isolate originated from different patients. All patients had a history of treatment with at least one cephalosporin and/or carbapenem prior to the isolation of OXA-48 CRE. OXA-181 was detected in one (1.15%) out of the 87 isolates; CONCLUSIONS: The prevalence of OXA-48 and OXA-181 CRE among all Enterobacteriaceae isolates in our institution is 0.069% and 0.008%, respectively. Nevertheless, our findings suggest that OXA-48 and OXA-181 carbapenemases appear to be important and possibly under-recognised causes of carbapenem resistance in Malaysia.

    Matched MeSH terms: Carbapenems
  3. Chua WC, Mazlan MZ, Ali S, Che Omar S, Wan Hassan WMN, Seevaunnantum SP, et al.
    IDCases, 2017;9:91-94.
    PMID: 28725564 DOI: 10.1016/j.idcr.2017.05.002
    We report a fatal case of post-partum streptococcal toxic shock syndrome in a patient who was previously healthy and had presented to the emergency department with an extensive blistering ecchymotic lesions over her right buttock and thigh associated with severe pain. The pregnancy had been uncomplicated, and the mode of delivery had been spontaneous vaginal delivery with an episiotomy. She was found to have septicemic shock requiring high inotropic support. Subsequently, she was treated for necrotizing fasciitis, complicated by septicemic shock and multiple organ failures. A consensus was reached for extensive wound debridement to remove the source of infection; however, this approach was abandoned due to the patient's hemodynamic instability and the extremely high risks of surgery. Both the high vaginal swab and blister fluid culture revealed Group A beta hemolytic streptococcus infection. Intravenous carbapenem in combination with clindamycin was given. Other strategies attempted for streptococcal toxic removal included continuous veno-venous hemofiltration and administration of intravenous immunoglobulin. Unfortunately, the patient's condition worsened, and she succumbed to death on day 7 of hospitalization.
    Matched MeSH terms: Carbapenems
  4. Ho WS, Balan G, Puthucheary S, Kong BH, Lim KT, Tan LK, et al.
    Microb Drug Resist, 2012 Aug;18(4):408-16.
    PMID: 22394084 DOI: 10.1089/mdr.2011.0222
    The emergence of Escherichia coli resistant to extended-spectrum cephalosporins (ESCs) is of concern as ESC is often used to treat infections by Gram-negative bacteria. One-hundred and ten E. coli strains isolated in 2009-2010 from children warded in a Malaysian tertiary hospital were analyzed for their antibiograms, carriage of extended-spectrum beta-lactamase (ESBL) and AmpC genes, possible inclusion of the beta-lactamase genes on an integron platform, and their genetic relatedness. All E. coli strains were sensitive to carbapenems. About 46% of strains were multidrug resistant (MDR; i.e., resistant to ≥3 antibiotic classes) and almost half (45%) were nonsusceptible to ESCs. Among the MDR strains, high resistance rates were observed for ampicillin (98%), tetracycline (75%), and trimethoprim/sulfamethoxazole (73%). Out of 110 strains, bla(TEM-1) (49.1%), bla(CTX-M) (11.8%), and bla(CMY-2) (6.4%) were detected. Twenty-one strains were ESBL producers. CTX-M-15 was the predominant CTX-M variant found and this is the first report of a CTX-M-27-producing E. coli strain from Malaysia. Majority (3.1%) of the strains harbored class 1 integron-encoded integrases with a predominance of aadA and dfr genes within the integron variable region. No gene cassette encoding ESBL genes was found and integrons were not significantly associated with ESBL or non-ESBL producers. Possible clonal expansion was observed for few CTX-M-15-positive strains but the O25-ST131 E. coli clone known to harbor CTX-M-15 was not detected while CMY-2-positive strains were genetically diverse.
    Matched MeSH terms: Carbapenems/pharmacology
  5. Lean SS, Yeo CC, Suhaili Z, Thong KL
    Front Microbiol, 2015;6:1445.
    PMID: 26779129 DOI: 10.3389/fmicb.2015.01445
    Acinetobacter baumannii is a Gram-negative nosocomial pathogen of importance due to its uncanny ability to acquire resistance to most antimicrobials. These include carbapenems, which are the drugs of choice for treating A. baumannii infections, and polymyxins, the drugs of last resort. Whole genome sequencing was performed on two clinical carbapenem-resistant A. baumannii AC29 and AC30 strains which had an indistinguishable ApaI pulsotype but different susceptibilities to polymyxin. Both genomes consisted of an approximately 3.8 Mbp circular chromosome each and several plasmids. AC29 (susceptible to polymyxin) and AC30 (resistant to polymyxin) belonged to the ST195 lineage and are phylogenetically clustered under the International Clone II (IC-II) group. An AbaR4-type resistance island (RI) interrupted the comM gene in the chromosomes of both strains and contained the bla OXA-23 carbapenemase gene and determinants for tetracycline and streptomycin resistance. AC29 harbored another copy of bla OXA-23 in a large (~74 kb) conjugative plasmid, pAC29b, but this gene was absent in a similar plasmid (pAC30c) found in AC30. A 7 kb Tn1548::armA RI which encodes determinants for aminoglycoside and macrolide resistance, is chromosomally-located in AC29 but found in a 16 kb plasmid in AC30, pAC30b. Analysis of known determinants for polymyxin resistance in AC30 showed mutations in the pmrA gene encoding the response regulator of the two-component pmrAB signal transduction system as well as in the lpxD, lpxC, and lpsB genes that encode enzymes involved in the biosynthesis of lipopolysaccharide (LPS). Experimental evidence indicated that impairment of LPS along with overexpression of pmrAB may have contributed to the development of polymyxin resistance in AC30. Cloning of a novel variant of the bla AmpC gene from AC29 and AC30, and its subsequent expression in E. coli also indicated its likely function as an extended-spectrum cephalosporinase.
    Matched MeSH terms: Carbapenems
  6. 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: Carbapenems/pharmacology
  7. Yap PSX, Ahmad Kamar A, Chong CW, Ngoi ST, Teh CSJ
    Microb Drug Resist, 2020 Mar;26(3):190-203.
    PMID: 31545116 DOI: 10.1089/mdr.2019.0199
    Background:
    Klebsiella pneumoniae is a major opportunistic pathogen frequently associated with nosocomial infections, and often poses a major threat to immunocompromised patients. In our previous study, two K. pneumoniae (K36 and B13), which displayed resistance to almost all major antibiotics, including colistin, were isolated. Both isolates were not associated with infection and isolated from the stools of two preterm neonates admitted to the neonatal intensive care unit (NICU) during their first week of life.
    Materials and Methods:
    In this study, whole genome sequencing was performed on these two clinical multidrug resistant K. pneumoniae. We aimed to determine the genetic factors that underline the antibiotic-resistance phenotypes of these isolates.
    Results:
    The strains harbored blaSHV-27, blaSHV-71, and oqxAB genes conferring resistance to cephalosporins, carbapenems, and fluoroquinolones, respectively, but not harboring any known plasmid-borne colistin resistance determinants such as mcr-1. However, genome analysis discovered interruption of mgrB gene by insertion sequences gaining insight into the development of colistin resistance.
    Conclusion:
    The observed finding that points to a scenario of potential gut-associated resistance genes to Gram negative (K. pneumoniae) host in the NICU environment warrants attention and further investigation.
    Matched MeSH terms: Carbapenems/pharmacology
  8. Lau MY, Teng FE, Chua KH, Ponnampalavanar S, Chong CW, Abdul Jabar K, et al.
    Pathogens, 2021 Mar 02;10(3).
    PMID: 33801250 DOI: 10.3390/pathogens10030279
    The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great concern, as carbapenems are the last-line therapy for multidrug-resistant Gram-negative bacteria infections. This study aims to report the epidemiology of CRKP in a teaching hospital in Malaysia based on the molecular genotypic and clinical characteristics of the isolates. Sixty-three CRKP strains were isolated from a tertiary teaching hospital from January 2016 until August 2017. Carbapenemase genes were detected in 55 isolates, with blaOXA-48 (63.5%) as the predominant carbapenemase gene, followed by blaNDM (36.5%). At least one porin loss was detected in nine isolates. Overall, 63 isolates were divided into 30 clusters at similarity of 80% with PFGE analysis. Statistical analysis showed that in-hospital mortality was significantly associated with the usage of central venous catheter, infection or colonization by CRKP, particularly NDM-producers. In comparison, survival analysis using Cox proportional hazards regression identified a higher hazard ratio for patients with a stoma and patients treated with imipenem but a lower hazard ratio for patients with NDM-producing CRKP. OXA-48 carbapenemase gene was the predominant carbapenemase gene in this study. As CRKP infection could lead to a high rate of in-hospital mortality, early detection of the isolates was important to reduce their dissemination.
    Matched MeSH terms: Carbapenems
  9. 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
  10. Yap PSX, Chong CW, Ponnampalavanar S, Ramli R, Harun A, Tengku Jamaluddin TZM, et al.
    PeerJ, 2023;11:e16393.
    PMID: 38047021 DOI: 10.7717/peerj.16393
    BACKGROUND: The high burden of extended-spectrum beta-lactamase-producing (ESBL)-producing Enterobacterales worldwide, especially in the densely populated South East Asia poses a significant threat to the global transmission of antibiotic resistance. Molecular surveillance of ESBL-producing pathogens in this region is vital for understanding the local epidemiology, informing treatment choices, and addressing the regional and global implications of antibiotic resistance.

    METHODS: Therefore, an inventory surveillance of the ESBL-Escherichia coli (ESBL-EC) isolates responsible for infections in Malaysian hospitals was conducted. Additionally, the in vitro efficacy of flomoxef and other established antibiotics against ESBL-EC was evaluated.

    RESULTS: A total of 127 non-repetitive ESBL-EC strains isolated from clinical samples were collected during a multicentre study performed in five representative Malaysian hospitals. Of all the isolates, 33.9% were isolated from surgical site infections and 85.8% were hospital-acquired infections. High rates of resistance to cefotaxime (100%), cefepime (100%), aztreonam (100%) and trimethoprim-sulfamethoxazole (100%) were observed based on the broth microdilution test. Carbapenems remained the most effective antibiotics against the ESBL-EC, followed by flomoxef. Antibiotic resistance genes were identified by PCR. The blaCTX-M-1 was the most prevalent ESBL gene, with 28 isolates (22%) harbouring blaCTX-M-1 only, 27 isolates (21.3%) co-harbouring blaCTX-M-1 and blaTEM, and ten isolates (7.9%) co-harbouring blaCTX-M-1, blaTEM and blaSHV. A generalised linear model showed significant antibacterial activity of imipenem against different types of infection. Besides carbapenems, this study also demonstrated a satisfactory antibacterial activity of flomoxef (81.9%) on ESBL-EC, regardless of the types of ESBL genes.

    Matched MeSH terms: Carbapenems/therapeutic use
  11. Harris PN, Yin M, Jureen R, Chew J, Ali J, Paynter S, et al.
    PMID: 25932324 DOI: 10.1186/s13756-015-0055-6
    Extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae are often susceptible in vitro to β-lactam/β-lactamase inhibitor (BLBLI) combination antibiotics, but their use has been limited by concerns of clinical inefficacy. We aimed to compare outcomes between patients treated with BLBLIs and carbapenems for bloodstream infection (BSI) caused by cefotaxime non-susceptible (likely ESBL- or AmpC β-lactamase-producing) Escherichia coli and Klebsiella pneumoniae.
    Matched MeSH terms: Carbapenems
  12. Abdul-Aziz MH, Abd Rahman AN, Mat-Nor MB, Sulaiman H, Wallis SC, Lipman J, et al.
    Antimicrob Agents Chemother, 2016 01;60(1):206-14.
    PMID: 26482304 DOI: 10.1128/AAC.01543-15
    Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a 1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CL(CR)), such that a 30-ml/min increase in the estimated CL(CR) would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CL(CR) of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CL(CR) of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved.
    Matched MeSH terms: Carbapenems/blood; Carbapenems/pharmacokinetics*; Carbapenems/pharmacology
  13. Mohd Sazlly Lim S, Naicker S, Ayfan AK, Zowawi H, Roberts JA, Sime FB
    Int J Antimicrob Agents, 2020 Oct;56(4):106115.
    PMID: 32721600 DOI: 10.1016/j.ijantimicag.2020.106115
    Due to limited therapeutic options, combination therapy has been used empirically to treat carbapenem-resistant Acinetobacter baumannii (CRAB). Polymyxin-based combinations have been widely studied and used in the clinical setting. However, the use of polymyxins is often limited due to nephrotoxicity and neurotoxicity. This study aimed to evaluate the activity of non-polymyxin-based combinations relative to polymyxin-based combinations and to identify potential synergistic and bactericidal two-drug non-polymyxin-based combinations against CRAB. In vitro activity of 14 two-drug combinations against 50 A. baumannii isolates was evaluated using the checkerboard method. Subsequently, the two best-performing non-polymyxin-based combinations from the checkerboard assay were explored in static time-kill experiments. Concentrations of antibiotics corresponding to the fractional inhibitory concentrations (FIC) and the highest serum concentration achievable clinically were tested. The most synergistic combinations were fosfomycin/sulbactam (synergistic against 37/50 isolates; 74%), followed by meropenem/sulbactam (synergistic against 28/50 isolates; 56%). No antagonism was observed for any combination. Both fosfomycin/sulbactam and meropenem/sulbactam combinations exhibited bactericidal and synergistic activity against both isolates at the highest clinically achievable concentrations in the time-kill experiments. The meropenem/sulbactam combination displayed synergistic and bactericidal activity against one of two strains at concentrations equal to the FIC. Non-polymyxin-based combinations such as fosfomycin/sulbactam and meropenem/sulbactam may have a role in the treatment of CRAB. Further in vivo and clinical studies are required to scrutinise these activities further.
    Matched MeSH terms: Carbapenems/pharmacology
  14. Mohd Sazlly Lim S, Heffernan AJ, Roberts JA, Sime FB
    Microb Drug Resist, 2021 Apr;27(4):546-552.
    PMID: 32898467 DOI: 10.1089/mdr.2020.0197
    Background and Objective: Combination therapy may be a treatment option against carbapenem-resistant Acinetobacter baumannii (CR-AB) infections. In this study, we explored the utility of fosfomycin in combination with meropenem (FOS/MEM) against CR-AB isolates. Materials and Methods: Screening of synergistic activity of FOS/MEM was performed using the checkerboard assay. A pharmacokinetic/pharmacodynamic analysis was performed for various FOS/MEM regimens using Monte Carlo simulations. Results: The minimum inhibitory concentration (MIC) required to inhibit the growth of 50% of the isolates (MIC50) and MIC required to inhibit the growth of 90% of the isolates (MIC90) of FOS and MEM were reduced fourfold and twofold, respectively. The combination was synergistic against 14/50 isolates. No antagonism was observed. Sixteen out of fifty isolates had MEM MICs of ≤8 mg/L when subjected to combination therapy, compared to none with monotherapy. Forty-one out of 50 isolates had FOS MICs of ≤128 mg/L when subjected to combination therapy, compared to 17/50 isolates with monotherapy. The cumulative fraction response for MEM and FOS improved from 0% to 40% and 40% to 80%, with combination therapy, respectively. Conclusions: Addition of MEM improved the in vitro activity of FOS against the CR-AB isolates. FOS/MEM could be a plausible option to treat CR-AB for a small fraction of isolates.
    Matched MeSH terms: Carbapenems/pharmacology
  15. Mohd Sazlly Lim S, Heffernan AJ, Zowawi HM, Roberts JA, Sime FB
    Eur J Clin Microbiol Infect Dis, 2021 Sep;40(9):1943-1952.
    PMID: 33884516 DOI: 10.1007/s10096-021-04252-z
    Due to limited treatment options for carbapenem-resistant Acinetobacter baumannii (CR-AB) infections, antibiotic combinations are commonly used. In this study, we explored the potential efficacy of meropenem-sulbactam combination (MEM/SUL) against CR-AB. The checkerboard method was used to screen for synergistic activity of MEM/SUL against 50 clinical CR-AB isolates. Subsequently, time-kill studies against two CR-AB isolates were performed. Time-kill data were described using a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Subsequently, Monte Carlo simulations were performed to estimate the probability of 2-log kill, 1-log kill or stasis at 24-h following combination therapy. The MEM/SUL demonstrated synergy against 28/50 isolates. No antagonism was observed. The MIC50 and MIC90 of MEM/SUL were decreased fourfold, compared to the monotherapy MIC. In the time-kill studies, the combination displayed synergistic killing against both isolates at the highest clinically achievable concentrations. At concentrations equal to the fractional inhibitory concentration, synergism was observed against one isolate. The PK/PD model adequately delineated the data and the interaction between meropenem and sulbactam. The effect of the combination was driven by sulbactam, with meropenem acting as a potentiator. The simulations of various dosing regimens revealed no activity for the monotherapies. At best, the MEM/SUL regimen of 2 g/4 g every 8 h demonstrated a probability of target attainment of 2-log10 kill at 24 h of 34%. The reduction in the MIC values and the achievement of a moderate PTA of a 2-log10 reduction in bacterial burden demonstrated that MEM/SUL may potentially be effective against some CR-AB infections.
    Matched MeSH terms: Carbapenems/pharmacology*
  16. 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: Carbapenems/metabolism; Carbapenems/pharmacology
  17. Wong EW, Yusof MY, Mansor MB, Anbazhagan D, Ong SY, Sekaran SD
    Singapore Med J, 2009 Aug;50(8):822-6.
    PMID: 19710984
    The AdeABC pump of Acinetobacter spp. confers resistance to various antibiotic classes. This pump is composed of the AdeA, AdeB, and AdeC proteins where AdeB is a member of the resistance-nodulation-division efflux pump superfamily. The adeA, adeB, and adeC genes are contiguous and adjacent to adeS and adeR, which are transcribed in the opposite direction and which specify proteins homologous to sensors and regulators of two-component systems, respectively. In this study, an attempt is made to elucidate the role of the AdeABC efflux pump in carbapenem resistance in Acinetobacter spp.
    Matched MeSH terms: Carbapenems/pharmacology
  18. Hancock SJ, Phan MD, Peters KM, Forde BM, Chong TM, Yin WF, et al.
    PMID: 27872077 DOI: 10.1128/AAC.01740-16
    Plasmids of incompatibility group A/C (IncA/C) are becoming increasingly prevalent within pathogenic Enterobacteriaceae They are associated with the dissemination of multiple clinically relevant resistance genes, including blaCMY and blaNDM Current typing methods for IncA/C plasmids offer limited resolution. In this study, we present the complete sequence of a blaNDM-1-positive IncA/C plasmid, pMS6198A, isolated from a multidrug-resistant uropathogenic Escherichia coli strain. Hypersaturated transposon mutagenesis, coupled with transposon-directed insertion site sequencing (TraDIS), was employed to identify conserved genetic elements required for replication and maintenance of pMS6198A. Our analysis of TraDIS data identified roles for the replicon, including repA, a toxin-antitoxin system; two putative partitioning genes, parAB; and a putative gene, 053 Construction of mini-IncA/C plasmids and examination of their stability within E. coli confirmed that the region encompassing 053 contributes to the stable maintenance of IncA/C plasmids. Subsequently, the four major maintenance genes (repA, parAB, and 053) were used to construct a new plasmid multilocus sequence typing (PMLST) scheme for IncA/C plasmids. Application of this scheme to a database of 82 IncA/C plasmids identified 11 unique sequence types (STs), with two dominant STs. The majority of blaNDM-positive plasmids examined (15/17; 88%) fall into ST1, suggesting acquisition and subsequent expansion of this blaNDM-containing plasmid lineage. The IncA/C PMLST scheme represents a standardized tool to identify, track, and analyze the dissemination of important IncA/C plasmid lineages, particularly in the context of epidemiological studies.
    Matched MeSH terms: Carbapenems/pharmacology
  19. Quintero-Yanes A, Lee CM, Monson R, Salmond G
    Environ Microbiol, 2020 07;22(7):2921-2938.
    PMID: 32352190 DOI: 10.1111/1462-2920.15048
    Serratia sp. ATCC 39006 produces intracellular gas vesicles to enable upward flotation in water columns. It also uses flagellar rotation to swim through liquid and swarm across semi-solid surfaces. Flotation and motility can be co-regulated with production of a β-lactam antibiotic (carbapenem carboxylate) and a linear tripyrrole red antibiotic, prodigiosin. Production of gas vesicles, carbapenem and prodigiosin antibiotics, and motility are controlled by master transcriptional and post-transcriptional regulators, including the SmaI/SmaR-based quorum sensing system and the mRNA binding protein, RsmA. Recently, the ribose operon repressor, RbsR, was also defined as a pleiotropic regulator of flotation and virulence factor elaboration in this strain. Here, we report the discovery of a new global regulator (FloR; a DeoR family transcription factor) that modulates flotation through control of gas vesicle morphogenesis. The floR mutation is highly pleiotropic, down-regulating production of gas vesicles, carbapenem and prodigiosin antibiotics, and infection in Caenorhabditis elegans, but up-regulating flagellar motility. Detailed proteomic analysis using TMT peptide labelling and LC-MS/MS revealed that FloR is a physiological master regulator that operates through subordinate pleiotropic regulators including Rap, RpoS, RsmA, PigU, PstS and PigT.
    Matched MeSH terms: Carbapenems/biosynthesis
  20. Dasgupta C, Rafi MA, Salam MA
    Pak J Med Sci, 2020 9 25;36(6):1297-1302.
    PMID: 32968397 DOI: 10.12669/pjms.36.6.2943
    Objectives: Urinary tract infections due to multi drug resistant bacteria have been on the rise globally with serious implications for public health. The objective of this study was to explore the prevalence of multi drug resistant uropathogens and to correlate the urinary tract infections with some demographic and clinical characteristics of patients admitted in a tertiary care hospital in Bangladesh.

    Methods: A cross sectional prospective study was conducted at Shaheed Ziaur Rahman Medical College Hospital, Bogura, Bangladesh among clinically suspected urinary tract infection patients from January to December, 2018. Clean-catch midstream or catheter-catch urine samples were subjected to bacteriological culture using chromogenic agar media. Antimicrobial susceptibility testing of the isolates was done by Kirby-Bauer disk diffusion method following Clinical and Laboratory Standards Institute guidelines. Descriptive statistical methods were used for data analysis.

    Results: Culture yielded a total of 537 (42.8%) significant bacterial growths including 420 (78.2%) multi drug resistant uropathogens from 1255 urine samples. Escherichia coli was the most common isolate (61.6%) followed by Klebsiella spp. (22.5%), Pseudomonas spp. (7.8%), Staphylococcus aureus (5.4%) and Enterobacter spp. (2.6%) with multi drug resistance frequency of 77.6%, 71.9%, 90.5%, 86.2% and 92.9% respectively. There was female preponderance (M:F; 1:1.97; P=0.007) but insignificant differences between paediatric and adult population (43.65% vs. 42.57%) and also among different age groups. Diabetes, chronic renal failure, fever and supra-pubic pain had significant association as co-morbidities and presentations of urinary tract infections (P<0.05). Multi drug resistance ranged from 3.7 to 88.1% including moderate to high resistance found against commonly used antibiotics like ciprofloxacin, cephalosporin, azithromycin, aztreonam, cotrimoxazole and nalidixic acid (28.6 to 92.9%). Isolates showed 2.4 to 32.2% resistance to nitrofurantoin, amikacin, netilmicin and carbapenems except Pseudomonas spp. (66.7% resistance to nitrofurantoin) and Enterobacter spp. (28.6 to 42.9% resistance to carbapenems).

    Conclusion: There is very high prevalence of multi drug resistant uropathogens among hospitalized patients and emergence of carbapenem resistance is an alarming situation. Antibiotic stewardship program is highly recommended for hospitals to combat antimicrobial resistance.

    Matched MeSH terms: Carbapenems
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links