Displaying publications 21 - 40 of 55 in total

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  1. Fulltext Molecular Characterization of Carbapenem Resistant Klebsiella pneumoniae in Malaysia Hospital
    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
  2. Fulltext Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit
    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
  3. Antimicrobial stewardship for acute-care hospitals: An Asian perspective
    Apisarnthanarak A, Kwa AL, Chiu CH, Kumar S, Thu LTA, Tan BH, et al.
    Infect Control Hosp Epidemiol, 2018 10;39(10):1237-1245.
    PMID: 30227898 DOI: 10.1017/ice.2018.188
    Inappropriate use of antibiotics is contributing to a serious antimicrobial resistance problem in Asian hospitals. Despite resource constraints in the region, all Asian hospitals should implement antimicrobial stewardship (AMS) programs to optimize antibiotic treatment, improve patient outcomes, and minimize antimicrobial resistance. This document describes a consensus statement from a panel of regional experts to help multidisciplinary AMS teams design programs that suit the needs and resources of their hospitals. In general, AMS teams must decide on appropriate interventions (eg, prospective audit and/or formulary restriction) for their hospital, focusing on the most misused antibiotics and problematic multidrug-resistant organisms. This focus is likely to include carbapenem use with the goal to reduce carbapenem-resistant gram-negative bacteria. Rather than initially trying to introduce a comprehensive, hospital-wide AMS program, it would be practical to begin by pilot testing a simple program based on 1 achievable core intervention for the hospital. AMS team members must work together to determine the most suitable AMS interventions to implement in their hospitals and how best to put them into practice. Continuous monitoring and feedback of outcomes to the AMS teams, hospital administration, and prescribers will enhance sustainability of the AMS programs.
    Matched MeSH terms: Carbapenems
  4. Fulltext Antimicrobial susceptibility and virulence genes of clinical and environmental isolates of Pseudomonas aeruginosa
    Liew SM, Rajasekaram G, Puthucheary SA, Chua KH
    PeerJ, 2019;7:e6217.
    PMID: 30697478 DOI: 10.7717/peerj.6217
    Background: Pseudomonas aeruginosa is ubiquitous, has intrinsic antibiotic resistance mechanisms, and is associated with serious hospital-associated infections. It has evolved from being a burn wound infection into a major nosocomial threat. In this study, we compared and correlated the antimicrobial resistance, virulence traits and clonal relatedness between clinical and fresh water environmental isolates of P. aeruginosa.

    Methods: 219 P. aeruginosa isolates were studied: (a) 105 clinical isolates from 1977 to 1985 (n = 52) and 2015 (n = 53), and (b) 114 environmental isolates from different fresh water sources. All isolates were subjected to ERIC-PCR typing, antimicrobial susceptibility testing and virulence factor genes screening.

    Results: Clinical and environmental isolates of P. aeruginosa were genetically heterogenous, with only four clinical isolates showing 100% identical ERIC-PCR patterns to seven environmental isolates. Most of the clinical and environmental isolates were sensitive to almost all of the antipseudomonal drugs, except for ticarcillin/clavulanic acid. Increased resistant isolates was seen in 2015 compared to that of the archived isolates; four MDR strains were detected and all were retrieved in 2015. All clinical isolates retrieved from 1977 to 1985 were susceptible to ceftazidime and ciprofloxacin; but in comparison, the clinical isolates recovered in 2015 exhibited 9.4% resistance to ceftazidime and 5.7% to ciprofloxacin; a rise in resistance to imipenem (3.8% to 7.5%), piperacillin (9.6% to 11.3%) and amikacin (1.9% to 5.7%) and a slight drop in resistance rates to piperacillin/tazobactam (7.7% to 7.5%), ticarcillin/clavulanic acid (19.2% to 18.9%), meropenem (15.4% to 7.5%), doripenem (11.5% to 7.5%), gentamicin (7.7% to 7.5%) and netilmicin (7.7% to 7.5%). Environmental isolates were resistant to piperacillin/tazobactam (1.8%), ciprofloxacin (1.8%), piperacillin (4.4%) and carbapenems (doripenem 11.4%, meropenem 8.8% and imipenem 2.6%). Both clinical and environmental isolates showed high prevalence of virulence factor genes, but none were detected in 10 (9.5%) clinical and 18 (15.8%) environmental isolates. The exoT gene was not detected in any of the clinical isolates. Resistance to carbapenems (meropenem, doripenem and imipenem), β-lactamase inhibitors (ticarcillin/clavulanic acid and piperacillin/tazobactam), piperacillin, ceftazidime and ciprofloxacin was observed in some of the isolates without virulence factor genes. Five virulence-negative isolates were susceptible to all of the antimicrobials. Only one MDR strain harbored none of the virulence factor genes.

    Conclusion: Over a period of 30 years, a rise in antipseudomonal drug resistance particularly to ceftazidime and ciprofloxacin was observed in two hospitals in Malaysia. The occurrence of resistant environmental isolates from densely populated areas is relevant and gives rise to collective anxiety to the community at large.

    Matched MeSH terms: Carbapenems
  5. Fulltext Ertapenem-induced neurotoxicity in an end-stage renal disease patient on intermittent haemodialysis: a case report
    Shahar S, Arimuthu DA, Mazlan SA
    BMC Nephrol, 2022 Nov 08;23(1):360.
    PMID: 36348388 DOI: 10.1186/s12882-022-02980-8
    BACKGROUND: Carbapenem-induced neurotoxicity is an unusual side effect, with seizure being the most commonly reported symptom. Among the carbapenems, imipenem-cilastin is classically associated with the most severe neurotoxicity side effects. Carbapenem is mainly excreted by the kidney and its half-life is significantly increased in patients with chronic kidney disease (CKD). Therefore, dose adjustment is necessary in such patients. Ertapenem-associated neurotoxicity is increasingly being reported in CKD patients, but rarely seen in patients with recommended dose adjustment.

    CASE PRESENTATION: We report a case of a 56-year-old male patient with chronic kidney disease 5 on dialysis(CKD 5D). The patient presented with a history of fever, chills and rigours during a session of haemodialysis (HD). He was diagnosed with Enterobacter cloacae catheter-related blood stream infection and was started on ertapenem. After 13 days of ertapenem, he experienced an acute confusional state and progressed to having auditory and visual hallucinations. His blood investigations and imaging results revealed no other alternative diagnosis. Hence a diagnosis of ertapenem-induced neurotoxicity was made. He had complete resolution of symptoms after 10 days' discontinuation of ertapenem.

    CONCLUSION: Our case draws attention to the risk of potentially serious toxicity of the central nervous system in HD patients who receive the current recommended dose of ertapenem. It also highlights that renal dosing in CKD 5D patients' needs to be clinically studied to ensure antibiotic safety.

    Matched MeSH terms: Carbapenems
  6. Antimicrobial Susceptibility Patterns of an Emerging Multidrug Resistant Nosocomial Pathogen: Acinetobacter baumannii
    Tewari R, Chopra D, Wazahat R, Dhingra S, Dudeja M
    Malays J Med Sci, 2018 May;25(3):129-134.
    PMID: 30899194 DOI: 10.21315/mjms2018.25.3.13
    Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) bacterium, a nosocomial pathogen associated with a high mortality rate and limited therapeutic options have emerged as a serious problem throughout the world. The present study aimed to assess the current levels of antibiotic susceptibility among the isolates of Acinetobacter species. The sensitivity patterns were analysed from various clinical specimens obtained from both in-patients and outpatients of a teaching hospital. Isolation was performed on 5% sheep blood agar and MacConkey agar. Urine samples were inoculated into CLED agar. Antibiotic susceptibility was performed by the disc diffusion method. A total of 16,452 samples were collected. The total number of samples positive for Acinetobacter species was 67 (0.4%). The highest number of isolates 26 (38.8%) were obtained from urine. Majority 80.3% of the isolates exhibited resistance to three or more classes of antibiotics. All isolates were susceptible to colistin (100%). The susceptibility rate of A. baumannii isolates was 80% for tigecycline and 53.3% for carbapenem. Combination therapies including colistin and tigecycline seem to be the rational treatment for MDR A. baumannii until new alternatives come forward.
    Matched MeSH terms: Carbapenems
  7. Interaction of LysM BON family protein domain with carbapenems: A putative mechanism of carbapenem resistance
    Ali A, Kumar R, Khan A, Khan AU
    Int J Biol Macromol, 2020 Oct 01;160:212-223.
    PMID: 32464197 DOI: 10.1016/j.ijbiomac.2020.05.172
    Carbapenem resistance in Gram-negative pathogens has become a global concern for health workers worldwide. In one of our earlier studies, a Klebsiella pneumoniae-carbapenemase-2 producing strain was induced with meropenem to explore differentially expressed proteins under induced and uninduced conditions. There is, LysM domain BON family protein, was found over 12-fold expressed under the induced state. A hypothesis was proposed that LysM domain protein might have an affinity towards carbapenem antibiotics making them unavailable to bind with their target. Hence, we initiated a study to understand the binding mode of carbapenem with LysM domain protein. MICs of imipenem and meropenem against LysM clone were increased by several folds as compared to NP-6 clinical strain as well as DH5 α (PET-28a KPC-2) clone. This study further revealed a strong binding of both antibiotics to LysM domain protein. Molecular simulation studies of LysM domain protein with meropenem and imipenem for 80 ns has also showed stable structure. We concluded that overexpressed LysM domain under induced condition interacted with carbapenems, leading to enhanced resistance as proved by high MIC values. Hence, the study proved the proposed hypothesis that the LysM domain plays a significant role in the putative mechanism of antibiotics resistance.
    Matched MeSH terms: Carbapenems/pharmacology*
  8. The FloR master regulator controls flotation, virulence and antibiotic production in Serratia sp. ATCC 39006
    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
  9. Fulltext Identification of IncA/C Plasmid Replication and Maintenance Genes and Development of a Plasmid Multilocus Sequence Typing Scheme
    Hancock SJ, Phan MD, Peters KM, Forde BM, Chong TM, Yin WF, et al.
    Antimicrob Agents Chemother, 2017 02;61(2).
    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
  10. Carbapenem-resistant Pseudomonas aeruginosa in malaysia producing IMP-7 beta-lactamase
    Ho SE, Subramaniam G, Palasubramaniam S, Navaratnam P
    Antimicrob Agents Chemother, 2002 Oct;46(10):3286-7.
    PMID: 12234862
    We have isolated and identified a carbapenem-resistant Pseudomonas aeruginosa strain from Malaysia that produces an IMP-7 metallo-beta-lactamase. This isolate showed high-level resistance to meropenem and imipenem, the MICs of which were 256 and 128 micro g/ml, respectively. Isoelectric focusing analyses revealed pI values of >9.0, 8.2, and 7.8, which indicated the possible presence of IMP and OXA. DNA sequencing confirmed the identity of the IMP-7 determinant.
    Matched MeSH terms: Carbapenems/pharmacology*
  11. Pharmacodynamic Analysis of Meropenem and Fosfomycin Combination Against Carbapenem-Resistant Acinetobacter baumannii in Patients with Normal Renal Clearance: Can It Be a Treatment Option?
    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
  12. Semi-mechanistic PK/PD modelling of meropenem and sulbactam combination against carbapenem-resistant strains of Acinetobacter baumannii
    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*
  13. Fulltext Detection of blaIMP4 and blaNDM1 harboring Klebsiella pneumoniae isolates in a university hospital in Malaysia
    Hamzan NI, Yean CY, Rahman RA, Hasan H, Rahman ZA
    Emerg Health Threats J, 2015;8:26011.
    PMID: 25765342 DOI: 10.3402/ehtj.v8.26011
    Background : Antibiotic resistance among Enterobacteriaceae posts a great challenge to the health care service. The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) is attracting significant attention due to its rapid and global dissemination. The infection is associated with significant morbidity and mortality, thus creating challenges for infection control and managing teams to curb the infection. In Southeast Asia, there have been limited reports and subsequent research regarding CRKP infections. Thus, the study was conducted to characterize CRKP that has been isolated in our setting. Methods : A total of 321 K. pneumoniae were included in the study. Each isolate went through an identification process using an automated identification system. Phenotypic characterization was determined using disk diffusion, modified Hodge test, Epsilometer test, and inhibitor combined disk test. Further detection of carbapenemase genes was carried out using polymerase chain reaction and confirmed by gene sequence analysis. Results : All together, 13 isolates (4.05%) were CRKP and the majority of them were resistant to tested antibiotics except colistin and tigercycline. Among seven different carbapenemase genes studied (blaKPC, bla IMP, bla SME, bla NDM, bla IMI, bla VIM, and bla OXA), only two, bla IMP4 (1.87%) and bla NDM1 (2.18%), were detected in our setting. Conclusion : Evidence suggests that the prevalence of CRKP in our setting is low, and knowledge of Carbapenem-resistant Enterobacteriaceae and CRKP has improved and become available among clinicians.
    Matched MeSH terms: Carbapenems/pharmacology*
  14. 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*
  15. Non-polymyxin-based combinations as potential alternatives in treatment against carbapenem-resistant Acinetobacter baumannii infections
    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
  16. Fulltext Spread of carbapenem-resistant Acinetobacter baumannii global clone 2 in Asia and AbaR-type resistance islands
    Kim DH, Choi JY, Kim HW, Kim SH, Chung DR, Peck KR, et al.
    Antimicrob Agents Chemother, 2013 Nov;57(11):5239-46.
    PMID: 23939892 DOI: 10.1128/AAC.00633-13
    In this surveillance study, we identified the genotypes, carbapenem resistance determinants, and structural variations of AbaR-type resistance islands among carbapenem-resistant Acinetobacter baumannii (CRAB) isolates from nine Asian locales. Clonal complex 92 (CC92), corresponding to global clone 2 (GC2), was the most prevalent in most Asian locales (83/108 isolates; 76.9%). CC108, or GC1, was a predominant clone in India. OXA-23 oxacillinase was detected in CRAB isolates from most Asian locales except Taiwan. blaOXA-24 was found in CRAB isolates from Taiwan. AbaR4-type resistance islands, which were divided into six subtypes, were identified in most CRAB isolates investigated. Five isolates from India, Malaysia, Singapore, and Hong Kong contained AbaR3-type resistance islands. Of these, three isolates harbored both AbaR3- and AbaR4-type resistance islands simultaneously. In this study, GC2 was revealed as a prevalent clone in most Asian locales, with the AbaR4-type resistance island predominant, with diverse variants. The significance of this study lies in identifying the spread of global clones of carbapenem-resistant A. baumannii in Asia.
    Matched MeSH terms: Carbapenems/pharmacology*
  17. The emerging problems of Klebsiella pneumoniae infections: carbapenem resistance and biofilm formation
    Chung PY
    FEMS Microbiol Lett, 2016 10;363(20).
    PMID: 27664057
    Klebsiella pneumoniae is an opportunistic pathogen that commonly causes nosocomial infections in the urinary tract, respiratory tract, lung, wound sites and blood in individuals with debilitating diseases. Klebsiella pneumoniae is still a cause of severe pneumonia in alcoholics in Africa and Asia, and the predominant primary pathogen of primary liver abscess in Taiwan and Southeast Asia, particularly in Asian and Hispanic patients, and individuals with diabetes mellitus. In the United States and Europe, K. pneumoniae infections are most frequently associated with nosocomial infections. The emergence of antibiotic-resistant strains of K. pneumoniae worldwide has become a cause of concern where extended-spectrum β-lactamases (ESBLs) and carbapenemase-producing strains have been isolated with increasing frequency. The pathogen's ability to form biofilms on inserted devices such as urinary catheter has been proposed as one of the important mechanisms in nosocomially acquired and persistent infections, adding to the increased resistance to currently used antibiotics. In this review, infections caused by K. pneumoniae, antibiotic resistance and formation of biofilm will be discussed.
    Matched MeSH terms: Carbapenems/therapeutic use*
  18. Fulltext Disruption of KPC-producing Klebsiella pneumoniae membrane via induction of oxidative stress by cinnamon bark (Cinnamomum verum J. Presl) essential oil
    Yang SK, Yusoff K, Ajat M, Thomas W, Abushelaibi A, Akseer R, et al.
    PLoS One, 2019;14(4):e0214326.
    PMID: 30939149 DOI: 10.1371/journal.pone.0214326
    Klebsiella pneumoniae (KP) remains the most prevalent nosocomial pathogen and carries the carbapenemase (KPC) gene which confers resistance towards carbapenem. Thus, it is necessary to discover novel antimicrobials to address the issue of antimicrobial resistance in such pathogens. Natural products such as essential oils are a promising source due to their complex composition. Essential oils have been shown to be effective against pathogens, but the overall mechanisms have yet to be fully explained. Understanding the molecular mechanisms of essential oil towards KPC-KP cells would provide a deeper understanding of their potential use in clinical settings. Therefore, we aimed to investigate the mode of action of essential oil against KPC-KP cells from a proteomic perspective by comparing the overall proteome profile of KPC-KP cells treated with cinnamon bark (Cinnamomum verum J. Presl) essential oil (CBO) at their sub-inhibitory concentration of 0.08% (v/v). A total of 384 proteins were successfully identified from the non-treated cells, whereas only 242 proteins were identified from the CBO-treated cells. Proteins were then categorized based on their biological processes, cellular components and molecular function prior to pathway analysis. Pathway analysis showed that CBO induced oxidative stress in the KPC-KP cells as indicated by the abundance of oxidative stress regulator proteins such as glycyl radical cofactor, catalase peroxidase and DNA mismatch repair protein. Oxidative stress is likely to oxidize and disrupt the bacterial membrane as shown by the loss of major membrane proteins. Several genes selected for qRT-PCR analysis validated the proteomic profile and were congruent with the proteomic abundance profiles. In conclusion, KPC-KP cells exposed to CBO undergo oxidative stress that eventually disrupts the bacterial membrane possibly via interaction with the phospholipid bilayer. Interestingly, several pathways involved in the bacterial membrane repair system were also affected by oxidative stress, contributing to the loss of cells viability.
    Matched MeSH terms: Carbapenems/adverse effects
  19. Molecular Characterization of Extended-Spectrum Beta Lactamase- and Carbapenemase-Producing Pseudomonas aeruginosa Strains from a Malaysian Tertiary Hospital
    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
  20. Fulltext Disruption of adeB gene has a greater effect on resistance to meropenems than adeA gene in Acinetobacter spp. isolated from University Malaya Medical Centre
    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
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