Displaying publications 1 - 20 of 55 in total

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  1. Abidin NZ, Sulong A, Alfizah H, Ding CH, Muttaqillah NA, Rahman MM
    Pak J Med Sci, 2015 Nov-Dec;31(6):1340-3.
    PMID: 26870093 DOI: 10.12669/pjms.316.8159
    The New Delhi metallo-β-lactamase-1 (NDM-1) enzyme is a plasmid-encoded enzyme that inactivates carbapenem antibiotics. This study aims to ascertain if the modified Hodge test (MHT) has a role in screening for NDM-1 in Enterobacteriaceae with reduced carbapenem susceptibility.
    Matched MeSH terms: Carbapenems
  2. Ng HK, Puah SM, Teh CSJ, Idris N, Chua KH
    PeerJ, 2023;11:e15304.
    PMID: 37214089 DOI: 10.7717/peerj.15304
    BACKGROUND: Acinetobacter baumannii was reported to have resistance towards carbapenems and the ability to form an air-liquid biofilm (pellicle) which contributes to their virulence. The GacSA two-component system has been previously shown to play a role in pellicle formation. Therefore, this study aims to detect the presence of gacA and gacS genes in carbapenem-resistant Acinetobacter baumannii (CRAB) isolates recovered from patients in intensive care units and to investigate their pellicle forming ability.

    METHODS: The gacS and gacA genes were screened in 96 clinical CRAB isolates using PCR assay. Pellicle formation assay was performed in Mueller Hinton medium and Luria Bertani medium using borosilicate glass tubes and polypropylene plastic tubes. The biomass of the pellicle was quantitated using the crystal violet staining assay. The selected isolates were further assessed for their motility using semi-solid agar and monitored in real-time using real-time cell analyser (RTCA).

    RESULTS: All 96 clinical CRAB isolates carried the gacS and gacA genes, however, only four isolates (AB21, AB34, AB69 and AB97) displayed the ability of pellicle-formation phenotypically. These four pellicle-forming isolates produced robust pellicles in Mueller Hinton medium with better performance in borosilicate glass tubes in which biomass with OD570 ranging from 1.984 ± 0.383 to 2.272 ± 0.376 was recorded. The decrease in cell index starting from 13 hours obtained from the impedance-based RTCA showed that pellicle-forming isolates had entered the growth stage of pellicle development.

    CONCLUSION: These four pellicle-forming clinical CRAB isolates could be potentially more virulent, therefore further investigation is warranted to provide insights into their pathogenic mechanisms.

    Matched MeSH terms: Carbapenems/pharmacology
  3. Zahra N, Zeshan B, Ishaq M
    BMC Microbiol, 2022 Dec 03;22(1):290.
    PMID: 36463105 DOI: 10.1186/s12866-022-02706-8
    Acinetobacter baumannii (A. baumannii) is one of the members of ESKAPE bacteria which is considered multidrug resistant globally. The objective of this study is to determine the protein docking of different antibiotic resistance gene (ARGs) in A. baumannii. In silico analysis of antibiotic resistance genes against carbapenem are the blaOXA-51, blaOXA-23, blaOXA-58, blaOXA-24, blaOXA-143, NMD-1 and IMP-1 in A. baumannii. The doripenem, imipenem and meropenem were docked to blaOXA-51 and blaOXA-23 using PyRx. The top docking energy was -5.5 kcal/mol by imipenem and doripenem and meropenem showed a binding score of -5. 2 kcal/mol each and blaOXA-23 energy was -4.3 kcal/mol by imipenem and meropenem showed a binding score of -2.3 kcal/mol, while doripenem showed the binding score of -3.4 kcal/mol. Similarly, doripenem imipenem and meropenem were docked to blaOXA-58, IMP-1, Rec A and blaOXA-143, with docking energy was -8.8 kcal/mol by doripenem and meropenem each while imipenem showed a binding score of -4.2 kcal/mol and with IMP-1 demonstrated their binding energies. was -5.7 kcal/mol by meropenem and doripenem showed a binding score of -5.3 kcal/mol, while imipenem showed a binding score of -4.5 kcal/mol. And docking energy was -4.9 kcal/mol by imipenem and meropenem showed binding energy of -3.6 kcal/mol each while doripenem showed a binding score of -3.9 kcal/mol in RecA and with blaOXA-143 docking energy was -3.0 kcal/mol by imipenem and meropenem showed a binding score of -1.9 kcal/mol, while doripenem showed the binding score of -2.5 kcal/mol respectively. Doripenem, imipenem, and meropenem docking findings with blaOXA-24 confirmed their binding energies. Doripenem had the highest docking energy of -5.5 kcal/mol, meropenem had a binding score of -4.0 kcal/mol, and imipenem had a binding score of -3.9 kcal/mol. PyRx was used to dock the doripenem, imipenem, and meropenem to NMD-1. Docking energies for doripenem were all - 4.0 kcal/mol, whereas meropenem had docking energy of -3.3 kcal/mol and imipenem was -1.50 kcal/mol. To the best of our knowledge the underlying mechanism of phenotypic with genotypic resistance molecular docking regarding carbapenem resistance A. baumannii is unclear. Our molecular docking finds the possible protein targeting mechanism for carbapenem-resistant A.baumannii.
    Matched MeSH terms: Carbapenems/pharmacology
  4. Katip W, Rayanakorn A, Oberdorfer P, Taruangsri P, Nampuan T
    J Infect Public Health, 2023 Aug;16(8):1249-1255.
    PMID: 37295057 DOI: 10.1016/j.jiph.2023.05.024
    BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is one of the most commonly found nosocomial infections in critically ill patients. However, the appropriate treatment period for a specific group of critically ill patients with CRAB infection is currently being debated. Therefore, our study aimed to evaluate the optimal courses of therapy for critically ill patients with CRAB infection by comparing the outcomes of colistin therapy of short duration (<14 days) versus long duration (≥ 14 days).

    METHODS: A retrospective cohort study was conducted at Nakornping Hospital on critically ill patients with CRAB infection who received either a short or long course of colistin treatment between 2015 and 2022. The primary outcome was the 30-day mortality rate while secondary outcomes were clinical response, microbiological response, and nephrotoxicity. Propensity score matching with a 1: 1 ratio was performed to reduce potential biases. Furthermore, a logistic regression model was used to estimate the odds ratio (OR).

    RESULTS: A total of 374 patients met the inclusion criteria. Two hundred and forty-eight patients were recruited after utilizing propensity scores to match patients at a 1: 1 ratio. The results from the propensity score matching analysis demonstrated that the long-course therapy group had a lower 30-day mortality rate compared to the short-course therapy group (adjusted OR (aOR) = 0.46, 95% CI: 0.26-0.83, p = 0.009). The clinical response and microbiological response rates were higher in patients who received the long course of colistin therapy compared to those receiving the short course (aOR = 3.24, 95% CI: 1.78-5.92, p = 0.001; aOR = 3.01, 95% CI: 1.63-5.57, p = 0.001). There was no significant different in the occurrence of nephrotoxicity (aOR = 1.28, 95% CI: 0.74-2.22, p = 0.368) between the two treatment groups.

    CONCLUSION: A long course of colistin therapy resulted in a lower 30-day mortality rate in critically ill patients, and better clinical and microbiological outcomes, but similar nephrotoxicity as compared to a short course of colistin therapy. Therefore, a specific subset of critically ill patients who had CRAB infection needed to be considered for a long course of therapy.

    Matched MeSH terms: Carbapenems/therapeutic use
  5. 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
  6. Gan HM, Rajasekaram G, Eng WWH, Kaniappan P, Dhanoa A
    Genome Announc, 2017 Aug 10;5(32).
    PMID: 28798179 DOI: 10.1128/genomeA.00768-17
    We report the whole-genome sequences of two carbapenem-resistant clinical isolates of Klebsiella quasipneumoniae subsp. similipneumoniae obtained from two different patients. Both strains contained three different extended-spectrum β-lactamase genes and showed strikingly high pairwise average nucleotide identity of 99.99% despite being isolated 3 years apart from the same hospital.
    Matched MeSH terms: Carbapenems
  7. Baqer AA, Nor NSM, Alagely HS, Musa M, Adnan NA
    Pol Merkur Lekarski, 2023;51(1):35-41.
    PMID: 36960898 DOI: 10.36740/Merkur202301105
    OBJECTIVE: Aim: Klebsiella pneumonia has emerged as an increasingly important cause of community-acquired nosocomial infections and many of these strains are highly virulent and exhibit a strong propensity to spread. Infections cause by K. pneumonia produces carbapen¬emase (KPC) enzyme and can be difficult to treat since only a few antibiotics are effective against them. Bacteriophage targeting this strain can be an alternative treatment. Characterisation of bacteriophage is utmost important in assisting the application of bacteriophage in phage therapy.

    PATIENTS AND METHODS: Materials and methods: In the present study, the lytic bacteriophage, k3w7, isolated by the host Klebsiella pneumoniae kP2 was characterised using transmission electron microscope (TEM), plaque assay, and restriction digestive enzyme to investigate mor¬phology, host spectrum, bacteriophage life cycle and stability accordingly.

    RESULTS: Results and conclusions: As shown by TEM, k3w7 was observed to have the characteristic of icosahedral heads 100 nm and contractile sheaths 120 nm suggesting it belongs to the family of myoviridae.The Investigation has done on the phage growth cycle showed a short latent period of 20 min and a burst size of approximately 220 plaque forming units per infected cell. Stability test showed the phage was stable over a wide range of pH and temperatures. According to restriction analysis, k3w7 had 50 -kb double-stranded DNA genome as well as the heterogeneous nature of genetic material. These findings suggest that K3W7 has a potential use in therapy against infections caused by K. pneumonia produces carbapenemase.

    Matched MeSH terms: Carbapenems
  8. 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
  9. 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
  10. Yap PS, Cheng WH, Chang SK, Lim SE, Lai KS
    Cells, 2022 Sep 26;11(19).
    PMID: 36230959 DOI: 10.3390/cells11192995
    There has been a resurgence in the clinical use of polymyxin antibiotics such as colistin due to the limited treatment options for infections caused by carbapenem-resistant Enterobacterales (CRE). However, this last-resort antibiotic is currently confronted with challenges which include the emergence of chromosomal and plasmid-borne colistin resistance. Colistin resistance in Klebsiella pneumoniae is commonly caused by the mutations in the chromosomal gene mgrB. MgrB spans the inner membrane and negatively regulates PhoP phosphorylation, which is essential for bacterial outer membrane lipid biosynthesis. The present review intends to draw attention to the role of mgrB chromosomal mutations in membrane permeability in K. pneumoniae that confer colistin resistance. With growing concern regarding the global emergence of colistin resistance, deciphering physical changes of the resistant membrane mediated by mgrB inactivation may provide new insights for the discovery of novel antimicrobials that are highly effective at membrane penetration, in addition to finding out how this can help in alleviating the resistance situation.
    Matched MeSH terms: Carbapenems/pharmacology; Carbapenems/therapeutic use
  11. 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; Carbapenems/therapeutic use
  12. Zamani A, Zueter AR, Muhd Besari A, Hasan H, Harun A, Deris ZZ
    Trop Biomed, 2020 Sep 01;37(3):783-790.
    PMID: 33612791 DOI: 10.47665/tb.37.3.783
    Reduced susceptibility in Burkholderia pseudomallei during carbapenem therapy may lead to treatment failure. We isolated a clinical strain that had developed reduced susceptibility to carbapenems while on treatment. After reviewing the patient's clinical notes, the initial isolate (BUPS01/14) was exposed to carbapenem in vitro to mimic the clinical scenario. The stability of susceptibility of the carbapenem-exposed strain (BUPS01/14R) was examined by serial subculture in antibiotic-free broth. Biochemical and morphological comparison was performed by the VITEK® system and electron microscopy. MICs increased 32-fold following carbapenem exposure and became stable in the antibiotic-free environment. On electron microscopic examination, the BUPS01/14R cells were smoother and less wrinkled compared to BUPS01/14 cells. This report highlights a potential anti-melioidosis treatment failure due to the emergence of resistance while on carbapenem monotherapy. Further study of this strain is necessary to understand the mechanism of resistance at a molecular level.
    Matched MeSH terms: Carbapenems
  13. Zaidah AR, Mohammad NI, Suraiya S, Harun A
    PMID: 28473912 DOI: 10.1186/s13756-017-0200-5
    BACKGROUND: Infections by multidrug-resistant gram-negative bacteria (MDR-GNB) have been continuously growing and pose challenge to health institution globally. Carbapenem-resistant Enterobacteriacea (CRE) was identified as one of the MDR-GNB which has limited treatment options and higher mortality compared to those of sensitive strains. We report an increased burden of CRE fecal carriage at a hospital in the North-eastern region of Malaysia.

    METHODS: A retrospective descriptive study from August 2013 to December 2015 was conducted in the Medical Microbiology & Parasitology laboratory of Hospital Universiti Sains Malaysia, which is a tertiary teaching hospital with more than 700 beds. This hospital treats patients with various medical and surgical conditions. Suspected CRE from any clinical specimens received by the laboratory was identified and confirmed using standard protocols. Polymerase chain reaction (PCR) assay was performed to determine the genotype.

    RESULTS: Altogether, 8306 Enterobacteriaceae was isolated from various clinical specimens during the study period and 477/8306 (5.74%) were CRE. Majority of the isolated CRE were Klebsiella [408/477, (85.5%)], of which Klebsiella pneumoniae was the predominant species, 388/408 (95%). CRE were mainly isolated from rectal swab (screening), 235/477 (49.3%); urine, 76/477 (15.9%); blood, 46/477 (9.6%) and about 7.1% from tracheal aspirate. One hundred and thirty-six isolates were subjected to genotype determination and., 112/136 (82.4%) showed positive detection of New Delhi metallo-β-lactamase 1 (NDM-1) gene (blaNDM1).

    CONCLUSION: The study noted a high numbers of CRE isolated especially from rectal swabs. Active screening results in significant cost pressures and therefore should be revisited and revised, especially in low resource settings.

    Matched MeSH terms: Carbapenems
  14. Gupta D, Singh A, Somvanshi P, Singh A, Khan AU
    ACS Omega, 2020 Apr 28;5(16):9356-9365.
    PMID: 32363287 DOI: 10.1021/acsomega.0c00356
    The manifestation of class D β-lactamases in the community raises significant concern as they can hydrolyze carbapenem antibiotics. Hence, it is exceptionally alluring to design novel inhibitors. Structure-based virtual screening using docking programs and molecular dynamics simulations was employed to identify two novel non-β-lactam compounds that possess the ability to block different OXA variants. Furthermore, the presence of a nonpolar aliphatic amino acid, valine, near the active site serine, was identified in all OXA variants that can be accounted to block the catalytic activity of OXA enzymes.
    Matched MeSH terms: Carbapenems
  15. Das S, Pandey AK, Morris DE, Anderson R, Lim V, Wie CC, et al.
    BMC Genomics, 2024 Apr 17;25(1):381.
    PMID: 38632538 DOI: 10.1186/s12864-024-10276-4
    Klebsiella pneumoniae is a Gram-negative Enterobacteriaceae that is classified by the World Health Organisation (WHO) as a Priority One ESKAPE pathogen. South and Southeast Asian countries are regions where both healthcare associated infections (HAI) and community acquired infections (CAI) due to extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant K. pneumoniae (CRKp) are of concern. As K. pneumoniae can also exist as a harmless commensal, the spread of resistance genotypes requires epidemiological vigilance. However there has been no significant study of carriage isolates from healthy individuals, particularly in Southeast Asia, and specially Malaysia. Here we describe the genomic analysis of respiratory isolates of K. pneumoniae obtained from Orang Ulu and Orang Asli communities in Malaysian Borneo and Peninsular Malaysia respectively. The majority of isolates were K. pneumoniae species complex (KpSC) 1 K. pneumoniae (n = 53, 89.8%). Four Klebsiella variicola subsp. variicola (KpSC3) and two Klebsiella quasipneumoniae subsp. similipneumoniae (KpSC4) were also found. It was discovered that 30.2% (n = 16) of the KpSC1 isolates were ST23, 11.3% (n = 6) were of ST65, 7.5% (n = 4) were ST13, and 13.2% (n = 7) were ST86. Only eight of the KpSC1 isolates encoded ESBL, but importantly not carbapenemase. Thirteen of the KpSC1 isolates carried yersiniabactin, colibactin and aerobactin, all of which harboured the rmpADC locus and are therefore characterised as hypervirulent. Co-carriage of multiple strains was minimal. In conclusion, most isolates were KpSC1, ST23, one of the most common sequence types and previously found in cases of K. pneumoniae infection. A proportion were hypervirulent (hvKp) however antibiotic resistance was low.
    Matched MeSH terms: Carbapenems
  16. Hwa WE, Subramaniam G, Mansor MB, Yan OS, Gracie, Anbazhagan D, et al.
    Indian J Med Res, 2010 Apr;131:578-83.
    PMID: 20424311
    Carbapenem-resistant Acinetobacter spp. have gained increasing significance as opportunistic pathogens in hospitalized patients. Carbapenem resistance is often associated with the loss and/or decrease in outer membrane proteins (OMP) and overexpression of multidrug efflux systems. However, carbapenem-hydrolysing beta-lactamases of Ambler Class B (metallo-enzymes) and Ambler Class D (oxacillinases) have also been detected in Acinetobacter spp. In this study we have investigated the role of the iron regulated outer membrane protein (IROMPs) and the loss of a 29-kDa OMP in carbapenem resistance of Acinetobacter calcoaceticus.
    Matched MeSH terms: Carbapenems/pharmacology*
  17. 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
  18. 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
  19. Gan HM, Eng WWH, Dhanoa A
    J Glob Antimicrob Resist, 2020 03;20:153-159.
    PMID: 31325618 DOI: 10.1016/j.jgar.2019.07.008
    OBJECTIVES: Despite the increasing reports of carbapenem-resistant Enterobacteriaceae in Malaysia, genomic resources for carbapenem-resistant clinical strains of Klebsiella pneumoniae (K. pneumoniae) remain unavailable. This study aimed to sequence the genomes of multiple carbapenem-resistant K. pneumoniae strains from Malaysia and to identify the genetic basis for their resistance.

    METHODS: Illumina whole genome sequencing was performed on eight carbapenem-resistant K. pneumoniae isolated from a Malaysian hospital. Genetic diversity was inferred from the assembled genomes based on in silico multilocus sequence typing (MLST). In addition, plasmid-derived and chromosome-derived contigs were predicted using the machine learning approach. After genome annotation, genes associated with carbapenem resistance were identified based on similarity searched against the ResFinder database.

    RESULTS: The eight K. pneumoniae isolates were grouped into six different sequence types, some of which were represented by a single isolate in the MLST database. Genomic potential for carbapenem-resistance was attributed to the presence of plasmid-localised blaNDM (blaNDM-1/blaNDM-5) or blaKPC (blaKPC-2/blaKPC-6) in these sequenced strains. The majority of these carbapenem resistance genes was flanked by repetitive (transposase or integrase) sequences, suggesting their potential mobility. This study also reported the first blaKPC-6-harbouring plasmid contig to be assembled for K. pneumoniae, and the second for the genus Klebsiella.

    CONCLUSION: This study reported the first genomic resources for carbapenem-resistant K. pneumoniae from Malaysia. The high diversity of carbapenem resistance genes and sequence types uncovered from eight isolates from the same hospital is worrying and indicates an urgent need to improve the genomic surveillance of clinical K. pneumoniae in Malaysia.

    Matched MeSH terms: Carbapenems
  20. 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
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