Displaying publications 1 - 20 of 172 in total

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  1. Pharmacological importance of TG12 from tachykinin and its toxicological behavior against multidrug-resistant bacteria Klebsiella pneumonia
    Raju SV, Sarkar P, Pasupuleti M, Saraswathi NT, Arasu MV, Al-Dhabi NA, et al.
    Comp Biochem Physiol C Toxicol Pharmacol, 2021 Jul;245:108974.
    PMID: 33465517 DOI: 10.1016/j.cbpc.2021.108974
    Development of antimicrobial drugs against multidrug-resistant (MDR) bacteria is a great focus in recent years. TG12, a short peptide molecule used in this study was screened from tachykinin (Tac) protein of an established teleost Channa striatus (Cs) transcriptome. Tachykinin cDNA has 345 coding sequence, that denotes a protein contained 115 amino acids; in which a short peptide (TG12) was identified at 83-94. Tachykinin mRNA upregulated in C. striatus treated with Aeromonas hydrophila and Escherichia coli lipopolysaccharide (LPS). The mRNA up-regulation was studied using real-time PCR. The up-regulation tachykinin mRNA pattern confirmed the immune involvement of tachykinin in C. striatus during infection. Further, the identified peptide, TG12 was synthesized and its toxicity was demonstrated in hemolytic and cytotoxic assays using human erythrocytes and human dermal fibroblast cells, respectively. The toxicity study exhibited that the toxicity of TG12 was similar to negative control, phosphate buffer saline (PBS). Moreover, the antibiogram of TG12 was active against Klebsiella pneumonia ATCC 27736, a major MDR bacterial pathogen. Further, the antimicrobial activity of TG12 against pathogenic bacteria was screened using minimum inhibitory concentration (MIC) and anti-biofilm assays, altogether TG12 showed potential activity against K. pneumonia. Fluorescence assisted cell sorter flow cytometer analysis (FACS) and field emission scanning electron microscopy (FESEM) was carried on TG12 with K. pneumonia; the results showed that TG12 significantly reduced K. pneumonia viability as well as TG12 disrupt its membrane. In conclusion, TG12 of CsTac is potentially involved in the antibacterial immune mechanisms, which has a prospectus efficiency in pharma industry against MDR strains, especially K. pneumonia.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/drug effects*
  2. Virulence properties and pathogenicity of multidrug-resistant Vibrio harveyi associated with luminescent vibriosis in Pacific white shrimp, Penaeus vannamei
    Nurhafizah WWI, Lee KL, Laith A AR, Nadirah M, Danish-Daniel M, Zainathan SC, et al.
    J Invertebr Pathol, 2021 11;186:107594.
    PMID: 33878330 DOI: 10.1016/j.jip.2021.107594
    Global high demand for Pacific white shrimp Penaeus vannamei has led to intensified cultivation and a wide range of disease problems, including bacterial diseases due to vibrios. Three presumptive luminescent Vibrio harveyi strains (Vh5, Vh8 and Vh10) were isolated from the hepatopancreas (Vh5) and haemolymph (Vh8 and Vh10) of diseased growout Pacific white shrimp from a farm in Setiu, Terengganu, Malaysia, using Vibrio harveyi agar (VHA) differential medium. All three strains were identified as V. harveyi by biochemical characteristics. 16S rRNA gene-based phylogenetic analyses by neighbour-joining, maximum likelihood and maximum parsimony methods showed all three strains in the V. harveyi cluster. All three strains were β-haemolytic and positive for motility, biofilm formation and extracellular products (caseinase, gelatinase, lipase, DNase, amylase and chitinase). Vh10 was subjected to pathogenicity test in Pacific white shrimp by immersion challenge and determined to have a LC50 of 6.0 × 108 CFU mL-1 after 168 h of exposure. Antibiotic susceptibility tests showed that all strains were resistant to oxytetracycline (OXT30), oleandomycin (OL15), amoxicillin (AML25), ampicillin (AMP10) and colistin sulphate (CT25) but sensitive to doxycycline (DO30), flumequine (UB30), oxolinic acid (OA2), chloramphenicol (C30), florfenicol (FFC30), nitrofurantoin (F5) and fosfomycin (FOS50). Each strain was also resistant to a slightly different combination of eight other antibiotics, with an overall multiple antibiotic resistance (MAR) index of 0.40, suggesting prior history of heavy exposure to the antibiotics. Vh10 infection resulted in pale or discoloured hepatopancreas, empty guts, reddening, necrosis and luminescence of uropods, as well as melanised lesions in tail muscle. Histopathological examination showed necrosis of intertubular connective tissue and tubule, sloughing of epithelial cells in hepatopancreatic tubule, haemocytic infiltration, massive vacuolation and loss of hepatopancreatic tubule structure.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
  3. Fulltext Exploring Cefiderocol Resistance Mechanisms in Burkholderia pseudomallei
    Hall CM, Somprasong N, Hagen JP, Nottingham R, Sahl JW, Webb JR, et al.
    Antimicrob Agents Chemother, 2023 Jun 15;67(6):e0017123.
    PMID: 37133377 DOI: 10.1128/aac.00171-23
    Cefiderocol is a siderophore cephalosporin designed mainly for treatment of infections caused by β-lactam and multidrug-resistant Gram-negative bacteria. Burkholderia pseudomallei clinical isolates are usually highly cefiderocol susceptible, with in vitro resistance found in a few isolates. Resistance in clinical B. pseudomallei isolates from Australia is caused by a hitherto uncharacterized mechanism. We show that, like in other Gram-negatives, the PiuA outer membrane receptor plays a major role in cefiderocol nonsusceptibility in isolates from Malaysia.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/genetics
  4. Prevalence of multi-antimicrobial resistant non-typhoidal Salmonella isolated from filth flies at wet markets in Klang, Malaysia, and their survival in the simulated gastric fluid
    Sandrasaigaran P, Mohan S, Segaran NS, Lee TY, Radu S, Hasan H
    Int J Food Microbiol, 2023 Dec 16;407:110390.
    PMID: 37722349 DOI: 10.1016/j.ijfoodmicro.2023.110390
    Filth flies at wet markets can be a vector harbouring multiple antimicrobial-resistant (MAR) nontyphoidal Salmonella (NTS), and such strains are a significant threat to public health as they may cause severe infections in humans. This study aims to investigate the prevalence of antimicrobial-resistant NTS, especially Salmonella Enteritidis and S. Typhimurium harboured by filth flies at wet markets, and investigate their survival in the simulated gastric fluid (SGF). Filth flies (n = 90) were captured from wet markets in Klang, Malaysia, and processed to isolate Salmonella spp. The isolates (n = 16) were identified using the multiplex-touchdown PCR and assessed their antimicrobial susceptibility against 11 antimicrobial agents. Finally, three isolates with the highest MAR index were subjected to SGF survival tests. It was observed that 17.8 % of flies (n = 16/90) harbouring Salmonella, out of which 10 % (n = 9/90) was S. Enteritidis, 2.2 % (n = 2/90) was S. Typhimurium, and 5.6 % was unidentified serotypes of Salmonella enterica subsp. I. 43.8 % (n = 7/16) were confirmed as MAR, and they were observed to be resistant against ampicillin, chloramphenicol, kanamycin, streptomycin, and nalidixic acid. Three strains, F35, F75, and F85 demonstrated the highest MAR index and were able to survive (>6-log10) in the SGF (180 min), indicating their potential virulence and invasiveness. This study provides significant insights into the prevalence and severity of MAR nontyphoidal Salmonella harboured by filth flies in wet markets, which may help inform strategies for controlling the spread and outbreak of foodborne disease.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial
  5. Fulltext Effects of phenylpyruvate feeding with polymyxin B in Klebsiella pneumoniae
    Wong, A. S-L., Nusaibah Abdul Rahim
    Malaysian Journal of Medicine and Health Sciences, 2019;15(102):5-5.
    MyJurnal
    Introduction: Polymyxin B (PMB) is one of the remaining antibiotics that is effective against multidrug resistant (MDR) Gram-negative bacteria. However, PMB monotherapy is not able to achieve sustained killing hence, combination with other antibiotics are usually employed. Besides antibiotics, studies are now moving towards non-antibiotic alternatives such as metabolite feeding against MDR pathogens. This study aimed to investigate the susceptibility
    and bacterial killing of PMB in combination with metabolite phenylpyruvate against Klebsiella pneumoniae isolates. Methods: Broth microdilution was used to determine PMB minimum inhibitory concentration (MIC) alone and with phenylpyruvate against two Klebsiella pneumoniae isolates. Time kill studies were performed over 24 h (initial inoculum: ~106 CFU/mL), using PMB 2 mg/L and phenylpyruvate 2 mmol/L, alone and in combination, against the
    PMB-resistant isolate. Microbiological responses were examined using the log-change method. Results: The MIC of PMB was reduced by phenylpyruvate in both isolates. In the time kill studies, during the first hour, PMB monotherapy demonstrated the highest bacterial killing activity even compared to the combination. Phenylpyruvate monotherapy showed negligible activity against K. pneumoniae. A significant reduction in bacterial burden was seen at 1 h following PMB monotherapy and combination therapy but an equally rapid regrowth was seen at 4 h. Notably at 24 h, the regrowth following combination therapy was >1-log10 CFU/mL less than PMB monotherapy. Conclusion: Our results suggest that phenylpyruvate increased PMB susceptibility in K. pneumoniae and may minimise the emergence of resistance to PMB. Future studies investigating phenylpyruvate at higher concentrations against more isolates are
    warranted.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial
  6. Fulltext War against COVID-19: looming threat of XDR typhoid battle in Pakistan
    Tanveer M, Ahmed A, Siddiqui A, Rehman IU, Hashmi FK
    Public Health, 2021 09;198:e15-e16.
    PMID: 34187703 DOI: 10.1016/j.puhe.2021.05.019
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial
  7. Fulltext Global genome comparative analysis reveals insights of resistome and life-style adaptation of Pseudomonas putida strain T2-2 in oral cavity
    Chan XY, Chua KO, How KY, Yin WF, Chan KG
    ScientificWorldJournal, 2014;2014:930727.
    PMID: 25436236 DOI: 10.1155/2014/930727
    Most Pseudomonas putida strains are environmental microorganisms exhibiting a wide range of metabolic capability but certain strains have been reported as rare opportunistic pathogens and some emerged as multidrug resistant P. putida. This study aimed to assess the drug resistance profile of, via whole genome analysis, P. putida strain T2-2 isolated from oral cavity. At the same time, we also compared the nonenvironmental strain with environmentally isolated P. putida. In silico comparative genome analysis with available reference strains of P. putida shows that T2-2 has lesser gene counts on carbohydrate and aromatic compounds metabolisms, which suggested its little versatility. The detection of its edd gene also suggested T2-2's catabolism of glucose via ED pathway instead of EMP pathway. On the other hand, its drug resistance profile was observed via in silico gene prediction and most of the genes found were in agreement with drug-susceptibility testing in laboratory by automated VITEK 2. In addition, the finding of putative genes of multidrug resistance efflux pump and ATP-binding cassette transporters in this strain suggests a multidrug resistant phenotype. In summary, it is believed that multiple metabolic characteristics and drug resistance in P. putida strain T2-2 helped in its survival in human oral cavity.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/genetics*
  8. Fulltext Computational, crystallographic studies, cytotoxicity and anti-tubercular activity of substituted 7-methoxy-indolizine analogues
    Venugopala KN, Chandrashekharappa S, Pillay M, Abdallah HH, Mahomoodally FM, Bhandary S, et al.
    PLoS One, 2019;14(6):e0217270.
    PMID: 31163040 DOI: 10.1371/journal.pone.0217270
    Indolizines are heteroaromatic compounds, and their synthetic analogues have reportedly showed promising pharmacological properties. In this study, a series of synthetic 7-methoxy-indolizine derivatives were synthesised, characterised and evaluated for in vitro whole-cell anti-tuberculosis (TB) screening against susceptible (H37Rv) and multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB) using the resazurin microplate assay method. The cytotoxicity was evaluated using the MTT assay. In silico molecular-docking study was conducted for compounds 5a-j against enoyl-[acyl-carrier] protein reductase, a key enzyme of the type II fatty acid synthesis that has attracted much interest for the development of novel anti-TB compounds. Thereafter, molecular dynamic (MD) simulation was undertaken for the most active inhibitors. Compounds 5i and 5j with the methoxy functional group at the meta position of the benzoyl group, which was at the third position of the indolizine nucleus, demonstrated encouraging anti-TB activity against MDR strains of MTB at 16 μg/mL. In silico studies showed binding affinity within the range of 7.07-8.57 kcal/mol, with 5i showing the highest binding affinity. Hydrogen bonding, π-π- interactions, and electrostatic interactions were common with the active site. Most of these interactions occurred with the catalytic amino acids (Pro193, Tyr158, Phe149, and Lys165). MD simulation showed that 5j possessed the highest binding affinity toward the enzyme, according to the two calculation methods (MM/PBSA and MM/GBSA). The single-crystal X-ray studies of compounds 5c and 5d revealed that the molecular arrangements in these two structures were mostly guided by C-H···O hydrogen-bonded dimeric motifs and C-H···N hydrogen bonds, while various secondary interactions (such as π···π and C-H···F) also contributed to crystal formation. Compounds 5a, 5c, 5i, and 5j exhibited no toxicity up to 500 μg/mL. In conclusion, 5i and 5j are promising anti-TB compounds that have shown high affinity based on docking and MD simulation results.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/drug effects*
  9. The global prevalence of multidrug-resistance among Acinetobacter baumannii causing hospital-acquired and ventilator-associated pneumonia and its associated mortality: A systematic review and meta-analysis
    Mohd Sazlly Lim S, Zainal Abidin A, Liew SM, Roberts JA, Sime FB
    J Infect, 2019 12;79(6):593-600.
    PMID: 31580871 DOI: 10.1016/j.jinf.2019.09.012
    OBJECTIVE: The objective of this works was to assess the global prevalence of multidrug-resistance among A. baumannii causing hospital-acquired (HAP) and ventilator-associated pneumonia (VAP), and describe its associated mortality.

    METHODS: We performed a systematic search of four databases for relevant studies. Meta-analysis was done based on United Nations geoscheme regions, individual countries and study period. We used a random-effects model to calculate pooled prevalence and mortality estimates with 95% confidence intervals (CIs), weighted by study size.

    RESULTS: Among 6445 reports screened, we identified 126 relevant studies, comprising data from 29 countries. The overall prevalence of multidrug-resistance among A. baumannii causing HAP and VAP pooled from 114 studies was 79.9% (95% CI 73.9-85.4%). Central America (100%) and Latin America and the Caribbean (100%) had the highest prevalence, whereas Eastern Asia had the lowest (64.6%; 95% CI, 50.2-77.6%). The overall mortality estimate pooled from 27 studies was 42.6% (95% CI, 37.2-48.1%).

    CONCLUSIONS: We observed large amounts of variation in the prevalence of multidrug-resistance among A. baumannii causing HAP and VAP and its mortality rate among regions and lack of data from many countries. Data from this review can be used in the development of customized strategies for infection control and antimicrobial stewardship.

    Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
  10. An Overview of the Activities of Cefiderocol Against Sensitive and Multidrug- Resistant (MDR) Bacteria
    AlMatar M, Albarri O, Makky EA, Var I, Köksal F
    Mini Rev Med Chem, 2020;20(18):1908-1916.
    PMID: 32811410 DOI: 10.2174/1389557520666200818211405
    The need for new therapeutics and drug delivery systems has become necessary owing to the public health concern associated with the emergence of multidrug-resistant microorganisms. Among the newly discovered therapeutic agents is cefiderocol, which was discovered by Shionogi Company, Japan as an injectable siderophore cephalosporin. Just like the other β-lactam antibiotics, cefiderocol exhibits antibacterial activity via cell wall synthesis inhibition, especially in Gram negative bacteria (GNB); it binds to the penicillin-binding proteins, but its unique attribute is that it crosses the periplasmic space of bacteria owing to its siderophore-like attribute; it also resists the activity of β-lactamases. Among all the synthesized compounds with the modified C-7 side chain, cefiderocol (3) presented the best and well-balanced activity against multi-drug resistant (MDR) Gram negative bacteria, including those that are resistant to carbapenem. İn this article, an overview of the recent studies on cefiderocol was presented.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/drug effects*
  11. Antibiotic dosing for multidrug-resistant pathogen pneumonia
    Abdul-Aziz MH, Lipman J, Roberts JA
    Curr. Opin. Infect. Dis., 2017 Apr;30(2):231-239.
    PMID: 28030371 DOI: 10.1097/QCO.0000000000000348
    PURPOSE OF REVIEW: Nosocomial pneumonia caused by multidrug-resistant pathogens is increasing in the ICU, and these infections are negatively associated with patient outcomes. Optimization of antibiotic dosing has been suggested as a key intervention to improve clinical outcomes in patients with nosocomial pneumonia. This review describes the recent pharmacokinetic/pharmacodynamic data relevant to antibiotic dosing for nosocomial pneumonia caused by multidrug-resistant pathogens.

    RECENT FINDINGS: Optimal antibiotic treatment is challenging in critically ill patients with nosocomial pneumonia; most dosing guidelines do not consider the altered physiology and illness severity associated with severe lung infections. Antibiotic dosing can be guided by plasma drug concentrations, which do not reflect the concentrations at the site of infection. The application of aggressive dosing regimens, in accordance to the antibiotic's pharmacokinetic/pharmacodynamic characteristics, may be required to ensure rapid and effective drug exposure in infected lung tissues.

    SUMMARY: Conventional antibiotic dosing increases the likelihood of therapeutic failure in critically ill patients with nosocomial pneumonia. Alternative dosing strategies, which exploit the pharmacokinetic/pharmacodynamic properties of an antibiotic, should be strongly considered to ensure optimal antibiotic exposure and better therapeutic outcomes in these patients.

    Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
  12. Fulltext Virulence-associated genes and antibiotic resistance patterns of Vibrio spp. isolated from cultured marine fishes in Malaysia
    Mohamad N, Amal MNA, Saad MZ, Yasin ISM, Zulkiply NA, Mustafa M, et al.
    BMC Vet Res, 2019 May 28;15(1):176.
    PMID: 31138199 DOI: 10.1186/s12917-019-1907-8
    BACKGROUND: Vibriosis is an important bacterial disease of cultured marine fishes worldwide. However, information on the virulence and antibiotic resistance of Vibrio spp. isolated from fish are scarce. This study investigates the distribution of virulence associated genes and antibiotic resistance patterns of Vibrio spp. isolated from cage-cultured marine fishes in Malaysia.

    RESULTS: A total of 63 Vibrio spp. isolated from 62 cultured marine fishes in various geographical regions in Peninsular Malaysia were analysed. Forty-two of the isolates (66.7%) were positive for all chiA, luxR and vhpA, the virulence genes produced by pathogenic V. harveyi. A total of 62 Vibrio isolates (98%) had tlh gene of V. parahaemolyticus, while flaC gene of V. anguillarum was detected in 43 of isolates (68%). Other virulence genes, including tdh, trh, hlyA and toxRvc were absent from any of the isolates. Multiple antibiotic resistance (MAR) was exhibited in all strains of Harveyi clade, particularly against ampicillin, penicillin, polypeptides, cephems and streptomycin. The MAR index ranged between 0.06 and 0.56, and 75% of the isolates have MAR index of higher than 0.20. Host species and geographical origin showed no correlation with the presence of virulence genes and the antibiotic resistance patterns of Vibrio spp.

    CONCLUSIONS: The study indicates that majority of Vibrio spp. isolated from cultured marine fishes possess virulence genes, but were not associated with human pathogen. However, the antibiotics resistance is a real concern and warrants ongoing surveillance. These findings represent an updated knowledge on the risk of Vibrio spp. to human health, and also provides valuable insight on alternative approaches to combat vibriosis in cultured fish.

    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/genetics*
  13. Fulltext The role of hospital environment in transmissions of multidrug-resistant gram-negative organisms
    Chia PY, Sengupta S, Kukreja A, S L Ponnampalavanar S, Ng OT, Marimuthu K
    Antimicrob Resist Infect Control, 2020 02 11;9(1):29.
    PMID: 32046775 DOI: 10.1186/s13756-020-0685-1
    Infections by multidrug-resistant (MDR) Gram-negative organisms (GN) are associated with a high mortality rate and present an increasing challenge to the healthcare system worldwide. In recent years, increasing evidence supports the association between the healthcare environment and transmission of MDRGN to patients and healthcare workers. To better understand the role of the environment in transmission and acquisition of MDRGN, we conducted a utilitarian review based on literature published from 2014 until 2019.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/drug effects*
  14. Fulltext Silver Nanoparticles Synthesized by Using the Endophytic Bacterium Pantoea ananatis are Promising Antimicrobial Agents against Multidrug Resistant Bacteria
    Monowar T, Rahman MS, Bhore SJ, Raju G, Sathasivam KV
    Molecules, 2018 Dec 06;23(12).
    PMID: 30563220 DOI: 10.3390/molecules23123220
    Antibiotic resistance is one of the most important global problems currently confronting the world. Different biomedical applications of silver nanoparticles (AgNPs) have indicated them to be promising antimicrobial agents. In the present study, extracellular extract of an endophytic bacterium, Pantoea ananatis, was used for synthesis of AgNPs. The synthesized AgNPs were characterized by UV⁻Vis spectroscopy, FTIR, transmission electron microscopy (TEM), scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), and Zeta potential. The antimicrobial potential of the AgNPs against pathogenic Staphylococcus aureus subsp. aureus (ATCC 11632), Bacillus cereus (ATCC 10876), Escherichia coli (ATCC 10536), Pseudomonas aeruginosa (ATCC 10145) and Candida albicans (ATCC 10231), and multidrug resistant (MDR) Streptococcus pneumoniae (ATCC 700677), Enterococcus faecium (ATCC 700221) Staphylococcus aureus (ATCC 33592) Escherichia coli (NCTC 13351) was investigated. The synthesized spherical-shaped AgNPs with a size range of 8.06 nm to 91.32 nm exhibited significant antimicrobial activity at 6 μg/disc concentration against Bacillus cereus (ATCC 10876) and Candida albicans (ATCC 10231) which were found to be resistant to conventional antibiotics. The synthesized AgNPs showed promising antibacterial efficiency at 10 µg/disc concentration against the MDR strains. The present study suggests that AgNPs synthesized by using the endophytic bacterium P. ananatis are promising antimicrobial agent.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/drug effects*
  15. Exploration of the diversity of multi-drug resistant Mycobacterium tuberculosis complex in Lagos, Nigeria using WGS: Distribution of lineages, drug resistance patterns and genetic mutations
    Noorizhab MNF, Zainal Abidin N, Teh LK, Tang TH, Onyejepu N, Kunle-Ope C, et al.
    Tuberculosis (Edinb), 2023 May;140:102343.
    PMID: 37080082 DOI: 10.1016/j.tube.2023.102343
    Multidrug-resistant (MDR) or extensively drug-resistant (XDR) Tuberculosis (TB) is a major challenge to global TB control. Therefore, accurate tracing of in-country MDR-TB transmission are crucial for the development of optimal TB management strategies. This study aimed to investigate the diversity of MTBC in Nigeria. The lineage and drug-resistance patterns of the clinical MTBC isolates of TB patients in Southwestern region of Nigeria were determined using the WGS approach. The phenotypic DST of the isolates was determined for nine anti-TB drugs. The sequencing achieved average genome coverage of 65.99X. The most represented lineages were L4 (n = 52, 83%), L1 (n = 8, 12%), L2 (n = 2, 3%) and L5 (n = 1, 2%), suggesting a diversified MTB population. In term of detection of M/XDR-TB, while mutations in katG and rpoB genes are the strong predictors for the presence of M/XDR-TB, the current study also found the lack of good genetic markers for drug resistance amongst the MTBC in Nigeria which may pose greater problems on local tuberculosis management efforts. This high-resolution molecular epidemiological data provides valuable insights into the mechanistic for M/XDR TB in Lagos, Nigeria.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/genetics
  16. Epidemiology of multidrug-resistant Klebsiella pneumoniae infection in clinical setting in South-Eastern Asia: a systematic review and meta-analysis
    Salawudeen A, Raji YE, Jibo GG, Desa MNM, Neoh HM, Masri SN, et al.
    Antimicrob Resist Infect Control, 2023 Dec 07;12(1):142.
    PMID: 38062531 DOI: 10.1186/s13756-023-01346-5
    The rising prevalence of multidrug-resistant (MDR) and extended-spectrum beta lactamase-resistant (ESBL) Klebsiella pneumoniae (K. pneumoniae) is an important global public health challenge. This threat is even more pertinent in clinical settings. Morbidity and mortality associated with this condition are alarming particularly in the developing regions of the world. A comprehensive evaluation of the epidemiology of this phenomenon will assist towards the global effort of reducing its burden. So, this systematic review and meta-analysis was conducted to evaluate the epidemiology of MDR K. pneumoniae in South-Eastern Asia (SEA). The study was done under the PRISMA guidelines and was preceded by the development of a priori protocol. The protocol was then registered in PROSPERO-the public registry for systematic reviews. Seven important outcomes which include the assessment of the overall MDR K. pneumoniae prevalence were designed to be evaluated. A literature search was carried out in five selected electronic databases and 4389 were screened. Of these articles, 21 studies that met the eligibility criteria were included in the review. Relevant data were extracted from the included studies. By conducting a quality effect meta-analysis, the pooled prevalence for MDR and ESBL K. pneumoniae in SEA was estimated at 55% (CI 9-96) and 27% (CI 32-100) respectively. The review also identified ESBL genes types of allodemic situations occurring mostly in respiratory tract infections. The high prevalence of MDR and ESBL K. pneumoniae in this subregion is highly significant and of both public health and clinical relevance. Overall, the findings of this review will assist in the effective prevention and control of this threat in SEA.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/genetics
  17. Fulltext Complete Genome Sequencing of Acinetobacter baumannii AC1633 and Acinetobacter nosocomialis AC1530 Unveils a Large Multidrug-Resistant Plasmid Encoding the NDM-1 and OXA-58 Carbapenemases
    Alattraqchi AG, Mohd Rani F, A Rahman NI, Ismail S, Cleary DW, Clarke SC, et al.
    mSphere, 2021 Jan 27;6(1).
    PMID: 33504662 DOI: 10.1128/mSphere.01076-20
    Carbapenem-resistant Acinetobacter spp. are considered priority drug-resistant human-pathogenic bacteria. The genomes of two carbapenem-resistant Acinetobacter spp. clinical isolates obtained from the same tertiary hospital in Terengganu, Malaysia, namely, A. baumannii AC1633 and A. nosocomialis AC1530, were sequenced. Both isolates were found to harbor the carbapenemase genes blaNDM-1 and blaOXA-58 in a large (ca. 170 kb) plasmid designated pAC1633-1 and pAC1530, respectively, that also encodes genes that confer resistance to aminoglycosides, sulfonamides, and macrolides. The two plasmids were almost identical except for the insertion of ISAba11 and an IS4 family element in pAC1633-1, and ISAba11 along with relBE toxin-antitoxin genes flanked by inversely orientated pdif (XerC/XerD) recombination sites in pAC1530. The blaNDM-1 gene was encoded in a Tn125 composite transposon structure flanked by ISAba125, whereas blaOXA-58 was flanked by ISAba11 and ISAba3 downstream and a partial ISAba3 element upstream within a pdif module. The presence of conjugative genes in plasmids pAC1633-1/pAC1530 and their discovery in two distinct species of Acinetobacter from the same hospital are suggestive of conjugative transfer, but mating experiments failed to demonstrate transmissibility under standard laboratory conditions. Comparative sequence analysis strongly inferred that pAC1633-1/pAC1530 was derived from two separate plasmids in an IS1006-mediated recombination or transposition event. A. baumannii AC1633 also harbored three other plasmids designated pAC1633-2, pAC1633-3, and pAC1633-4. Both pAC1633-3 and pAC1633-4 are cryptic plasmids, whereas pAC1633-2 is a 12,651-bp plasmid of the GR8/GR23 Rep3-superfamily group that encodes the tetA(39) tetracycline resistance determinant in a pdif module.IMPORTANCE Bacteria of the genus Acinetobacter are important hospital-acquired pathogens, with carbapenem-resistant A. baumannii listed by the World Health Organization as the one of the top priority pathogens. Whole-genome sequencing of carbapenem-resistant A. baumannii AC1633 and A. nosocomialis AC1530, which were isolated from the main tertiary hospital in Terengganu, Malaysia, led to the discovery of a large, ca. 170-kb plasmid that harbored genes encoding the New Delhi metallo-β-lactamase-1 (NDM-1) and OXA-58 carbapenemases alongside genes that conferred resistance to aminoglycosides, macrolides, and sulfonamides. The plasmid was a patchwork of multiple mobile genetic elements and comparative sequence analysis indicated that it may have been derived from two separate plasmids through an IS1006-mediated recombination or transposition event. The presence of such a potentially transmissible plasmid encoding resistance to multiple antimicrobials warrants vigilance, as its spread to susceptible strains would lead to increasing incidences of antimicrobial resistance.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/genetics
  18. Antibacterial mechanism of Pseudomonas aeruginosa UKMP14T rhamnolipids against multidrug resistant Acinetobacter baumannii
    Firdose A, Maeda T, Sukri MAM, Yasin NHM, Sabturani N, Aqma WS
    Microb Pathog, 2024 Aug;193:106743.
    PMID: 38879138 DOI: 10.1016/j.micpath.2024.106743
    Rhamnolipids, a major category of glycolipid biosurfactant, have recently gained enormous attention in medical field because of their relevance as effective antibacterial agents against a wide variety of pathogenic bacteria. Our previous studies have shown that rhamnolipids from an environmental isolate of Pseudomonas aeruginosa UKMP14T possess antibacterial, anti-adhesive and anti-biofilm activity against multidrug-resistant ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter sp.) pathogens. However, the mechanism of their antibacterial action remains unclear. Thus, this study aimed to elucidate the mechanism of the antibacterial action of P. aeruginosa UKMP14T rhamnolipids by studying the changes in cells of one of the ESKAPE pathogens, Acinetobacter baumannii, which is the most difficult strain to kill. Results revealed that rhamnolipid treatment rendered A. baumannii cells more hydrophobic as evaluated through contact angle measurements. It also induced the release of cellular proteins measuring 510 μg/mL at a rhamnolipid concentration of 1000 μg/mL. In addition, rhamnolipids were found to be bactericidal in their action as they could permeate the inner membranes, leading to a leak-out of nucleotides. More than 50 % of the cells were found to be killed upon 1000 μg/mL rhamnolipid treatment as observed through fluorescence microscopy. Other cellular changes such as irregular shape and size, membrane perturbations, clumping, shrinkage and physical damage were clearly visible in SEM, FESEM and laser micrographs. Furthermore, rhamnolipid treatment inhibited the levels of acyl-homoserine lactones (AHLs) in A. baumannii, which are vital for their biofilm formation and virulence. The obtained results indicate that P. aeruginosa UKMP14T rhamnolipids target outer and inner bacterial membranes through permeation, including physical damage to the cells, leading to cell leakage. Furthermore, AHL inhibition appears to be the mechanism behind their anti-biofilm action. All these observations can be correlated to rhamnolipids' antibacterial effect against A. baumannii.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
  19. Appropriateness of empirical antibiotics: risk factors of adult patients with sepsis in the ICU
    Al-Sunaidar KA, Prof Abd Aziz N, Prof Hassan Y
    Int J Clin Pharm, 2020 Apr;42(2):527-538.
    PMID: 32144611 DOI: 10.1007/s11096-020-01005-4
    Background The appropriateness of antibiotics is the basis for improving the survival of patients with sepsis. Objective This study aimed to determine the appropriateness of empirical antibiotics, reasons for non-appropriate empirical antibiotics, risk factors of mortality, length of stay in intensive care unit (ICU-LOS) and Acute Physiology And Chronic Health Evaluation II (APACHE II) score predictors in adult patients with sepsis. Setting An adult ICU of a tertiary hospital in  Malaysia. Methods A retrospective cohort study was conducted amongst patients with sepsis. Data were retrieved from the patients' files and computer system. Each case was reviewed for the appropriateness of empirical antibiotics based on ICU local guidelines, bacterial sensitivity, dose, frequency, creatinine clearance and time of administration of empirical antibiotics. Multivariable logistic and Cox regression modelling were performed to compute the adjusted association of receiving appropriate or inappropriate empirical antibiotics with ICU mortality. Multivariable linear regression modelling was performed using ICU-LOS and APACHE II scores. Main outcome measures were ICU mortality, severity score (APACHE II scores) and ICU-LOS. Results The total mortality rate amongst the 228 adult ICU patients was 84.6%. Males showed a higher mortality rate (119 [52.2%]) than females (74 [32.5%]). Inappropriate empirical antibiotics were significantly associated with mortality and ICU-LOS (P 
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/drug effects*; Drug Resistance, Multiple, Bacterial/physiology
  20. Comparison of Clinical Isolates of Aeromonas from Singapore and Malaysia with Regard to Molecular Identification, Virulence, and Antimicrobial Profiles
    Khor WC, Puah SM, Koh TH, Tan JAMA, Puthucheary SD, Chua KH
    Microb Drug Resist, 2018 May;24(4):469-478.
    PMID: 29461928 DOI: 10.1089/mdr.2017.0083
    OBJECTIVE: The objective of this study was to examine the species distribution, genetic relatedness, virulence gene profiles, antimicrobial sensitivities, and resistance gene distribution of clinical Aeromonas strains from Singapore and Malaysia.

    METHODS: A total of 210 Aeromonas clinical isolates were investigated: 116 from Singapore General Hospital and 94 archived clinical isolates from University of Malaya Medical Center, Malaysia. The isolates were genetically identified based on the gcat gene screening and the partial sequences of the rpoD housekeeping gene. Genetic relatedness, distribution of 15 virulence genes and 4 beta-lactamase resistance genes, and susceptibility patterns to 11 antimicrobial agents were compared.

    RESULTS: Of the 210 Aeromonas isolates, A. dhakensis-94 (45%) was the dominant species in Singapore and Malaysia. Species composition was similar and enterobacterial repetitive intergenic consensus-PCR did not show genetic relatedness between strains from the two countries. Of the 15 virulence genes, A. dhakensis and A. hydrophila harbored the most compared with other species. Different combinations of 9 virulence genes (exu, fla, lip, eno, alt, dam, hlyA, aexU, and ascV) were present in A. dhakensis, A. hydrophila, and A. veronii from both the countries. Distribution of virulence genes was species and anatomic site related. Majority (>80%) of the strains were susceptible to all antimicrobial agents tested, except amoxicillin and cephalothin. A. dhakensis strains from Malaysia significantly harbored the cphA gene compared with A. dhakensis from Singapore. Multidrug resistance was mostly detected in strains from peritoneal fluids of dialysis patients.

    CONCLUSION: This study revealed A. dhakensis as the dominant species isolated in both geographic regions, and that it carried a high number of virulence genes. It also highlights the geographic-related differences of virulence gene distribution and antimicrobial resistance profiles of clinical Aeromonas strains from Singapore and Malaysia.

    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/drug effects; Drug Resistance, Multiple, Bacterial/genetics
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