Displaying publications 61 - 80 of 251 in total

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  1. Fulltext Genome Analysis of the First Extensively Drug-Resistant (XDR) Mycobacterium tuberculosis in Malaysia Provides Insights into the Genetic Basis of Its Biology and Drug Resistance
    Kuan CS, Chan CL, Yew SM, Toh YF, Khoo JS, Chong J, et al.
    PLoS One, 2015;10(6):e0131694.
    PMID: 26110649 DOI: 10.1371/journal.pone.0131694
    The outbreak of extensively drug-resistant tuberculosis (XDR-TB) has become an increasing problem in many TB-burdened countries. The underlying drug resistance mechanisms, including the genetic variation favored by selective pressure in the resistant population, are partially understood. Recently, the first case of XDR-TB was reported in Malaysia. However, the detailed genotype family and mechanisms of the formation of multiple drugs resistance are unknown. We sequenced the whole genome of the UM 1072388579 strain with a 2-kb insert-size library and combined with that from previously sequenced 500-bp-insert paired-end reads to produce an improved sequence with maximal sequencing coverage across the genome. In silico spoligotyping and phylogenetic analyses demonstrated that UM 1072388579 strain belongs to an ancestral-like, non-Beijing clade of East Asia lineage. This is supported by the presence of a number of lineage-specific markers, including fadD28, embA, nuoD and pks7. Polymorphism analysis showed that the drug-susceptibility profile is correlated with the pattern of resistance mutations. Mutations in drug-efflux pumps and the cell wall biogenesis pathway such as mmpL, pks and fadD genes may play an important role in survival and adaptation of this strain to its surrounding environment. In this work, fifty-seven putative promoter SNPs were identified. Among them, we identified a novel SNP located at -4 T allele of TetR/acrR promoter as an informative marker to recognize strains of East Asian lineage. Our work indicates that the UM 1072388579 harbors both classical and uncommon SNPs that allow it to escape from inhibition by many antibiotics. This study provides a strong foundation to dissect the biology and underlying resistance mechanisms of the first reported XDR M. tuberculosis in Malaysia.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/genetics*
  2. Fulltext Extremely high prevalence of antiseptic resistant Quaternary Ammonium Compound E gene among clinical isolates of multiple drug resistant Acinetobacter baumannii in Malaysia
    Babaei M, Sulong A, Hamat R, Nordin S, Neela V
    Ann Clin Microbiol Antimicrob, 2015;14:11.
    PMID: 25858356 DOI: 10.1186/s12941-015-0071-7
    Antiseptics are commonly used for the management of MDR (multiple drug resistance) pathogens in hospitals. They play crucial roles in the infection control practices. Antiseptics are often used for skin antisepsis, gauze dressing, preparation of anatomical sites for surgical procedure, hand sterilization before in contact with an infected person, before an invasive procedure and as surgical scrub.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
  3. Susceptibility pattern of Streptococcus pneumoniae among pre-school children in Kota Bharu, Malaysia
    Malik AS, Ismail A, Pennie RA, Naidu JV
    J Trop Pediatr, 1998 02;44(1):10-4.
    PMID: 9538599 DOI: 10.1093/tropej/44.1.10
    Streptococcus pneumoniae (S. pneumoniae) is the most common bacterial cause of pneumonia, meningitis, and otitis media, with the highest incidence among young children and the elderly. S. pneumoniae was once routinely susceptible to penicillin, but since the mid-1980s the incidence of resistance to penicillin and other antimicrobial agents has been increasing all over the world. To optimize empirical regimens and initial therapy for S. pneumoniae infections, clinical healthcare providers must be informed about the prevalence and pattern of drug resistance among the isolates in their communities. No such data are available for the Malaysian population. Therefore, this study was designed to determine the antibiotic susceptibility pattern of S. pneumoniae among colonized pre-school children in Kota Bharu, Malaysia. Pharyngeal swabs were collected from children 1 month to 6 years of age. S. pneumoniae isolates were identified according to the standard and tested for penicillin resistance with a 1-microgram oxacillin disk by the Kirby-Bauer disk diffusion methods. Of 355 nasopharyngeal specimens obtained from kindergarten students, in-patients and pediatric clinics over a period of 1 year, S. pneumoniae was isolated from 36 (10 per cent). All isolates, except one, were susceptible to penicillin. The resistant isolates was susceptible to erythromycin, chloramphenicol and cephalosporins.
    Study site: kindergarten, schools, pediatric outpatients clinics, and in-patient wards of Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia.
    Matched MeSH terms: Drug Resistance, Multiple*
  4. Envelope proteome changes driven by RamA overproduction in Klebsiella pneumoniae that enhance acquired β-lactam resistance
    Jiménez-Castellanos JC, Wan Nur Ismah WAK, Takebayashi Y, Findlay J, Schneiders T, Heesom KJ, et al.
    J Antimicrob Chemother, 2018 Jan 01;73(1):88-94.
    PMID: 29029194 DOI: 10.1093/jac/dkx345
    Objectives: In Klebsiella pneumoniae, overproduction of RamA results in reduced envelope permeability and reduced antimicrobial susceptibility but clinically relevant resistance is rarely observed. Here we have tested whether RamA overproduction can enhance acquired β-lactam resistance mechanisms in K. pneumoniae and have defined the envelope protein abundance changes upon RamA overproduction during growth in low and high osmolarity media.

    Methods: Envelope permeability was estimated using a fluorescent dye accumulation assay. β-Lactam susceptibility was measured using disc testing. Total envelope protein production was quantified using LC-MS/MS proteomics and transcript levels were quantified using real-time RT-PCR.

    Results: RamA overproduction enhanced β-lactamase-mediated β-lactam resistance, in some cases dramatically, without altering β-lactamase production. It increased production of efflux pumps and decreased OmpK35 porin production, though micF overexpression showed that OmpK35 reduction has little impact on envelope permeability. A survey of K. pneumoniae bloodstream isolates revealed ramA hyperexpression in 3 of 4 carbapenemase producers, 1 of 21 CTX-M producers and 2 of 19 strains not carrying CTX-M or carbapenemases.

    Conclusions: Whilst RamA is not a key mediator of antibiotic resistance in K. pneumoniae on its own, it is potentially important for enhancing the spectrum of acquired β-lactamase-mediated β-lactam resistance. LC-MS/MS proteomics analysis has revealed that this enhancement is achieved predominantly through activation of efflux pump production.

    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/physiology
  5. Identification of a novel SHV-β-lactamase variant (SHV-144) in a Malaysian multidrug-resistant Klebsiella pneumoniae isolate
    Al-Marzooq F, Yusof MY, Tay ST
    Jpn J Infect Dis, 2013;66(6):555-7.
    PMID: 24270152
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/genetics
  6. Fulltext Molecular characterization of multi-drug resistant Escherichia coli isolates from tropical environments in Southeast Asia
    Hara H, Yusaimi YA, Zulkeflle SNM, Sugiura N, Iwamoto K, Goto M, et al.
    J Gen Appl Microbiol, 2019 Jan 24;64(6):284-292.
    PMID: 29877296 DOI: 10.2323/jgam.2018.02.003
    The emergence of antibiotic resistance among multidrug-resistant (MDR) microbes is of growing concern, and threatens public health globally. A total of 129 Escherichia coli isolates were recovered from lowland aqueous environments near hospitals and medical service centers in the vicinity of Kuala Lumpur, Malaysia. Among the eleven antibacterial agents tested, the isolates were highly resistant to trimethoprim-sulfamethoxazole (83.7%) and nalidixic acid (71.3%) and moderately resistant to ampicillin and chloramphenicol (66.7%), tetracycline (65.1%), fosfomycin (57.4%), cefotaxime (57.4%), and ciprofloxacin (57.4%), while low resistance levels were found with aminoglycosides (kanamycin, 22.5%; gentamicin, 21.7%). The presence of relevant resistance determinants was evaluated, and the genotypic resistance determinants were as follows: sulfonamides (sulI, sulII, and sulIII), trimethoprim (dfrA1 and dfrA5), quinolones (qnrS), β-lactams (ampC and blaCTX-M), chloramphenicol (cmlA1 and cat2), tetracycline (tetA and tetM), fosfomycin (fosA and fosA3), and aminoglycosides (aphA1 and aacC2). Our data suggest that multidrug-resistant E. coli strains are ubiquitous in the aquatic systems of tropical countries and indicate that hospital wastewater may contribute to this phenomenon.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/genetics*
  7. Pulsed-field gel electrophoresis of multidrug-resistant and -sensitive strains of Pseudomonas aeruginosa from a Malaysian hospital
    Thong KL, Lai KS, Ganeswrie R, Puthucheary SD
    Jpn J Infect Dis, 2004 Oct;57(5):206-9.
    PMID: 15507777
    Over a period of 6 months from January to June 2002, an unusual increase in the isolation of highly resistant Pseudomonas aeruginosa strains was observed in the various wards and intensive care units of a large general hospital in Johor Bahru, Malaysia. An equal number of multidrug resistant (MDR) and drug-susceptible strains were collected randomly from swabs, respiratory specimens, urine, blood, cerebral spinal fluid, and central venous catheters to determine the clonality and genetic variation of the strains. Macrorestriction analysis by pulsed-field gel electrophoresis showed that the 19 MDR strains were genetically very homogenous; the majority showed the dominant profile S1 (n = 10), the rest very closely related profiles S1a (n = 1), S2 (n = 4), and S2a (n = 3), indicating the endemicity of these strains. In contrast, the 19 drug-sensitive strains isolated during the same time period were genetically more diverse, showing 17 pulsed-field profiles (F = 0.50-1.00), and probably derived from the patients themselves. The presence of the MDR clone poses serious therapeutic problems as it may become endemic in the hospital and give rise to future clonal outbreaks. There is also the potential for wider geographical spread.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/genetics*
  8. Fulltext Characterization of multiple-antimicrobial-resistant Salmonella enterica Subsp. enterica isolated from indigenous vegetables and poultry in Malaysia
    Yoke-Kqueen C, Learn-Han L, Noorzaleha AS, Son R, Sabrina S, Jiun-Horng S, et al.
    Lett Appl Microbiol, 2008 Mar;46(3):318-24.
    PMID: 18179445 DOI: 10.1111/j.1472-765X.2007.02311.x
    The aims of this communication were to study characterization of serogroups among Salmonella isolates and the relationship of antimicrobial resistance to serogroups. Multiple antimicrobial resistance (MAR) was performed on 189 Salmonella enterica isolates associated with 38 different serovars that were recovered from poultry and four types of indigenous vegetables.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
  9. Emergence of Klebsiella pneumoniae producing dual carbapenemases (NDM-1 and OXA-232) and 16S rRNA methylase (armA) isolated from a Malaysian patient returning from India
    Al-Marzooq F, Ngeow YF, Tay ST
    Int J Antimicrob Agents, 2015 Apr;45(4):445-6.
    PMID: 25631676 DOI: 10.1016/j.ijantimicag.2014.12.013
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
  10. Gut bacteria of animals living in polluted environments exhibit broad-spectrum antibacterial activities
    Akbar N, Siddiqui R, Sagathevan K, Khan NA
    Int Microbiol, 2020 Nov;23(4):511-526.
    PMID: 32124096 DOI: 10.1007/s10123-020-00123-3
    Infectious diseases, in particular bacterial infections, are the leading cause of morbidity and mortality posing a global threat to human health. The emergence of antibiotic resistance has exacerbated the problem further. Hence, there is a need to search for novel sources of antibacterials. Herein, we explored gut bacteria of a variety of animals living in polluted environments for their antibacterial properties against multi-drug resistant pathogenic bacteria. A variety of species were procured including invertebrate species, Blaptica dubia (cockroach), Gromphadorhina portentosa (cockroach), Scylla serrata (crab), Grammostola rosea (tarantula), Scolopendra subspinipes (centipede) and vertebrate species including Varanus salvator (water monitor lizard), Malayopython reticulatus (python), Cuora amboinensis (tortoise), Oreochromis mossambicus (tilapia fish), Rattus rattus (rat), Gallus gallus domesticus (chicken) and Lithobates catesbeianus (frog). Gut bacteria of these animals were isolated and identified using microbiological, biochemical, analytical profiling index (API) and through molecluar identification using 16S rRNA sequencing. Bacterial conditioned media (CM) were prepared and tested against selected Gram-positive and Gram-negative pathogenic bacteria as well as human cells (HaCaT). The results revealed that CM exhibited significant broad-spectrum antibacterial activities. Upon heat inactivation, CM retained their antibacterial properties suggesting that this effect may be due to secondary metabolites or small peptides. CM showed minimal cytotoxicity against human cells. These findings suggest that gut bacteria of animals living in polluted environments produce broad-spectrum antibacterial molecule(s). The molecular identity of the active molecule(s) together with their mode of action is the subject of future studies which could lead to the rational development of novel antibacterial(s).
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/physiology
  11. Phenotypic and genetic characterization of multidrug-resistant Staphylococcus aureus in the tropics of Southeast Asia
    Zulkeflle SNM, Yusaimi YA, Sugiura N, Iwamoto K, Goto M, Utsumi M, et al.
    Microbiology (Reading), 2016 12;162(12):2064-2074.
    PMID: 27902427 DOI: 10.1099/mic.0.000392
    Antibiotic resistance has become a major public health problem throughout the world. The presence of antibiotic-resistant bacteria such as Staphylococcus aureus and antibiotic resistance genes (ARGs) in hospital wastewater is a cause for great concern today. In this study, 276 Staph. aureus isolates were recovered from hospital wastewater samples in Malaysia. All of the isolates were screened for susceptibility to nine different classes of antibiotics: ampicillin, ciprofloxacin, gentamicin, kanamycin, erythromycin, vancomycin, trimethoprim and sulfamethoxazole, chloramphenicol, tetracycline and nalidixic acid. Screening tests showed that 100 % of Staph.aureus isolates exhibited resistance against kanamycin, vancomycin, trimethoprim and sulfamethoxazole and nalidixic acid. Additionally, 91, 87, 50, 43, 11 and 8.7 % of isolates showed resistance against erythromycin, gentamicin, ciprofloxacin, ampicillin, chloramphenicol and tetracycline, respectively. Based on these results, 100 % of isolates demonstrated multidrug-resistant (MDR) characteristics, displaying resistance against more than three classes of antibiotics. Of 276 isolates, nine exhibited resistance to more than nine classes of tested antibiotics; these were selected for antibiotic susceptibility testing and examined for the presence of conserved ARGs. Interestingly, a high percentage of the selected MDR Staph.aureus isolates did not contain conserved ARGs. These results indicate that non-conserved MDR gene elements may have already spread into the environment in the tropics of Southeast Asia, and unique resistance mechanisms against several antibiotics may have evolved due to stable, moderate temperatures that support growth of bacteria throughout the year.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
  12. Fulltext Clonal relatedness in the acquisition of intestinal carriage and transmission of multidrug resistant (MDR) Klebsiella pneumoniae and Escherichia coli and its risk factors among preterm infants admitted to the neonatal intensive care unit (NICU)
    Lee YQ, Ahmad Kamar A, Velayuthan RD, Chong CW, Teh CSJ
    Pediatr Neonatol, 2021 03;62(2):129-137.
    PMID: 33218933 DOI: 10.1016/j.pedneo.2020.10.002
    BACKGROUND: Gastrointestinal carriage of multidrug resistant (MDR) Gram-negative bacilli, especially Klebsiella pneumoniae and Escherichia coli, was highly associated with severe nosocomial infections. The main objectives of this study were to determine the clonal relatedness of intestinal carriage and transmission risk factors of MDR E. coli and K. pneumoniae amongst preterm infants admitted to the neonatal intensive care unit (NICU).

    METHODS: A prospective cohort study of preterm infants with gestational age 

    Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
  13. Detection of VIM-2-, IMP-1- and NDM-1-producing multidrug-resistant Pseudomonas aeruginosa in Malaysia
    Liew SM, Rajasekaram G, Puthucheary SD, Chua KH
    J Glob Antimicrob Resist, 2018 06;13:271-273.
    PMID: 29432937 DOI: 10.1016/j.jgar.2018.01.026
    OBJECTIVES: The increasing incidence of carbapenem-resistant Pseudomonas aeruginosa along with the discovery of novel metallo-β-lactamases (MBLs) is of concern. In this study, the isolation of MBL-producing P. aeruginosa clinical strains in Malaysia was investigated.

    METHODS: A total of 53 P. aeruginosa clinical strains were isolated from different patients in Sultanah Aminah Hospital (Johor Bahru, Malaysia) in 2015. Antimicrobial susceptibility testing was performed, and minimum inhibitory concentrations (MICs) of imipenem and meropenem were determined by Etest. Carbapenem-resistant strains were screened for MBL production by the imipenem-ethylene diamine tetra-acetic acid (IMP-EDTA) double-disk synergy test, MBL imipenem/imipenem-inhibitor (IP/IPI) Etest and PCR. Multilocus sequence typing (MLST) analysis was performed for genotyping of the isolates.

    RESULTS: Among the 53 clinical strains, 3 (5.7%) were identified as MBL-producers. Multidrug resistance was observed in all three strains, and two were resistant to all of the antimicrobials tested. Sequencing analysis confirmed that the three strains harboured carbapenemase genes (blaIMP-1, blaVIM-2 and blaNDM-1 in one isolate each). These multidrug-resistant strains were identified as sequence type 235 (ST235) and ST308.

    CONCLUSIONS: The blaIMP-1 and blaNDM-1 genes have not previously been reported in Malaysian P. aeruginosa isolates. The emergence of imipenemase 1 (IMP-1)- and New Delhi metallo-β-lactamase 1 (NDM-1)-producing P. aeruginosa in Malaysia maybe travel-associated.

    Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
  14. Fulltext Novel Polymyxin Combination with the Antiretroviral Zidovudine Exerts Synergistic Killing against NDM-Producing Multidrug-Resistant Klebsiella pneumoniae
    Lin YW, Abdul Rahim N, Zhao J, Han ML, Yu HH, Wickremasinghe H, et al.
    Antimicrob Agents Chemother, 2019 04;63(4).
    PMID: 30670431 DOI: 10.1128/AAC.02176-18
    Polymyxins are used as a last-line therapy against multidrug-resistant (MDR) New Delhi metallo-β-lactamase (NDM)-producing Klebsiella pneumoniae However, polymyxin resistance can emerge with monotherapy; therefore, novel strategies are urgently needed to minimize the resistance and maintain their clinical utility. This study aimed to investigate the pharmacodynamics of polymyxin B in combination with the antiretroviral drug zidovudine against K. pneumoniae Three isolates were evaluated in static time-kill studies (0 to 64 mg/liter) over 48 h. An in vitro one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model (IVM) was used to simulate humanized dosage regimens of polymyxin B (4 mg/liter as continuous infusion) and zidovudine (as bolus dose thrice daily to achieve maximum concentration of drug in broth [Cmax] of 6 mg/liter) against K. pneumoniae BM1 over 72 h. The antimicrobial synergy of the combination was further evaluated in a murine thigh infection model against K. pneumoniae 02. In the static time-kill studies, polymyxin B monotherapy produced rapid and extensive killing against all three isolates followed by extensive regrowth, whereas zidovudine produced modest killing followed by significant regrowth at 24 h. Polymyxin B in combination with zidovudine significantly enhanced the antimicrobial activity (≥4 log10 CFU/ml) and minimized bacterial regrowth. In the IVM, the combination was synergistic and the total bacterial loads were below the limit of detection for up to 72 h. In the murine thigh infection model, the bacterial burden at 24 h in the combination group was ≥3 log10 CFU/thigh lower than each monotherapy against K. pneumoniae 02. Overall, the polymyxin B-zidovudine combination demonstrates superior antimicrobial efficacy and minimized emergence of resistance to polymyxins.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/drug effects*
  15. 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: Drug Resistance, Multiple, Bacterial/genetics*
  16. Fulltext Partial characterization of genes encoding the ATP-binding cassette proteins of Cryptosporidium parvum
    Li LC, Mun YF
    Trop Biomed, 2005 Dec;22(2):115-22.
    PMID: 16883276
    The present study aims to explore the possible mechanisms underlying the multidrug resistance characteristic of Cryptosporidium parvum by detecting the presence of ATP-binding cassette (ABC) protein encoding genes, especially one that shows high similarity to members belonging to the multidrug resistance protein (MDR) and multidrug resistance associated protein (MRP) subfamilies. PCR using ABC-specific degenerate primers successfully amplified two unique fragments, designated Cpnbd1 and Cpnbd2, from C. parvum genomic DNA. Cpnbd1 exhibited high degree of homology (99-100%) with the nucleotide- binding domains (NBDs) at the NH2 -terminal halves of two previously reported ABC proteins (CpABC and CpABC1) of human and bovine origin C. parvum isolates. It is likely that CpABC, CpABC1 and Cpnbd1 were encoded by homologous genes of a type of ABC transporter protein found in different C. parvum isolates. However, Cpnbd2 showed moderate levels of similarities (28-49%) to the NBDs of four ABC proteins characterised in C. parvum to date. Therefore, Cpnbd2 could be a novel member of an ABC superfamily of proteins in C. parvum. Phylogenetic analyses on a list of ABC transporters known to associate with MDR phenotype has significantly linked Cpnbd1 and Cpnbd2 to these transporters, thus suggesting that Cpnbd1 and Cpnbd2 proteins may contribute to the intrinsic multidrug resistance phenotype of C. parvum.
    Matched MeSH terms: Drug Resistance, Multiple/genetics*
  17. Fulltext Functional Insights into Silymarin as an Antiviral Agent against Enterovirus A71 (EV-A71)
    Lalani S, Masomian M, Poh CL
    Int J Mol Sci, 2021 Aug 15;22(16).
    PMID: 34445463 DOI: 10.3390/ijms22168757
    Enterovirus A71 (EV-A71) is a major neurovirulent agent capable of causing severe hand, foot and mouth disease (HFMD) associated with neurological complications and death. Currently, no FDA-approved antiviral is available for the treatment of EV-A71 infections. The flavonoid silymarin was shown to exert virucidal effects, but the binding site on the capsid was unknown. In this study, the ligand interacting site of silymarin was determined in silico and validated in vitro. Moreover, the potential of EV-A71 to develop resistance against silymarin was further evaluated. Molecular docking of silymarin with the capsid of EV-A71 indicated that silymarin binds to viral protein 1 (VP1) of EV-A71, specifically at the GH loop of VP1. The in vitro binding of silymarin with VP1 of EV-A71 was validated using recombinant VP1 through ELISA competitive binding assay. Continuous passaging of EV-A71 in the presence of silymarin resulted in the emergence of a mutant carrying a substitution of isoleucine by threonine (I97T) at position 97 of the BC loop of EV-A71. The mutation was speculated to overcome the inhibitory effects of silymarin. This study provides functional insights into the underlying mechanism of EV-A71 inhibition by silymarin, but warrants further in vivo evaluation before being developed as a potential therapeutic agent.
    Matched MeSH terms: Drug Resistance, Multiple, Viral/genetics
  18. An overview of Acinetobacter baumannii pathogenesis: Motility, adherence and biofilm formation
    Mea HJ, Yong PVC, Wong EH
    Microbiol Res, 2021 Jun;247:126722.
    PMID: 33618061 DOI: 10.1016/j.micres.2021.126722
    The Gram-negative opportunistic pathogen Acinetobacter baumannii has gain notoriety in recent decades, primarily due to its propensity to cause nosocomial infections in critically ill patients. Its global spread, multi-drug resistance features and plethora of virulence factors make it a serious threat to public health worldwide. Though much effort has been expended in uncovering its successes, it continues to confound researchers due to its highly adaptive nature, mutating to meet the needs of a given environment. Its persistence in the clinical setting allows it to be in close proximity to a potential host, where contact can be made facilitating infection and colonization. In this article, we aim to provide a current overview of the bacterial virulence factors, specifically focusing on factors involved in the initial stages of infection, highlighting the role of adaptation facilitated by two-component systems and biofilm formation. Finally, the study of host-pathogen interactions using available animal models, their suitability, notable findings and some perspectives moving forward are also discussed.
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial/drug effects
  19. Improving shared decision-making in adolescents through antibiotic education
    Ngadimon IW, Islahudin F, Mohamed Shah N, Md Hatah E, Makmor-Bakry M
    Int J Clin Pharm, 2017 Feb;39(1):120-125.
    PMID: 27905077 DOI: 10.1007/s11096-016-0407-1
    Background Shared decision-making is vital in achieving desired drug therapy goals, especially with antibiotics, in view of the potential long-term reduction in drug resistance. However, shared decision-making is rarely practiced with adolescent patients. Objectives The aim of the study was to identify the effect antibiotic education has on willingness to engage in shared decision-making among adolescents in Malaysia. Setting Participants from secondary schools in Malaysia were enrolled with ethical approval. Method The adolescents answered a validated questionnaire, which included demographics, antibiotic knowledge, attitude towards antibiotic use, and the Control Preference Scale, which measures willingness to engage in shared decision-making. Afterwards, antibiotic education was delivered to participating students. Main outcome measure Knowledge about and attitude toward antibiotics were investigated. Results A total of 510 adolescents participated in the study. Knowledge of antibiotics significantly increased post education (pre 3.2 ± 1.8 vs. post 6.8 ± 2.1, p 
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
  20. Pharmaceutical waste and antimicrobial resistance
    Ahmad A, Patel I, Khan MU, Babar ZU
    Lancet Infect Dis, 2017 06;17(6):578-579.
    PMID: 28555576 DOI: 10.1016/S1473-3099(17)30268-2
    Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
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