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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.
Frequency and predictors of inappropriate medication dosages for cardiovascular disease prevention in chronic kidney disease patients: A retrospective cross-sectional study in a Malaysian primary care clinic

Jamaluddin J, Mohamed-Yassin MS, Jamil SN, Mohamed Kamel MA, Yusof MY

Heliyon, 2023 Apr;9(4):e14998.
PMID: 37025791 DOI: 10.1016/j.heliyon.2023.e14998

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular events. This study aimed to assess the frequency of inappropriate medication dosages (IMD) for cardiovascular disease prevention among patients with CKD and its predictors in an urban academic primary care clinic in Selangor, Malaysia. All patients who attended the clinic from April to June 2019 and fulfilled the inclusion criteria were included in this cross-sectional study, except for those with an estimated glomerular filtration rate (eGFR) of more than 90 ml/min, diagnosed with urinary tract infection, pregnant or were on dialysis for end stage renal disease. Their prescriptions on the electronic medical record (EMR) system were evaluated for appropriateness using the dose adjustment recommendations based on the 2018 Malaysian Clinical Practice Guidelines on management of CKD. A total of 362 medical records were included in this study. 16.6% (95% Confidence Interval [CI]: 12.9-20.8) or 60 out of 362 of the patient records analysed contained medications prescribed with inappropriate dosages. Patients with higher stages of CKD were associated with higher odds of IMD, namely CKD stage G3b (adjusted Odds Ratio [aOR] 10.41; 95% CI: 2.31-46.88) and CKD stage 4-5 (aOR 15.76; 95% CI: 3.22-77.28). Other predictors of IMD were diagnosis of diabetes mellitus (aOR 6.40; 95% CI: 2.15-19.01), number of prescribed medications of 5 or more (aOR 4.69; 95% CI: 1.55-14.20), and eGFR reduction of more than 25% over one year (aOR 2.82; 95% CI: 1.41-5.65). Within the limitations of this study, we conclude that the occurrence of IMD for CVD prevention was low in CKD patients in this primary care clinic. Medications with inappropriate dosages identified in this study include simvastatin, fenofibrate, hydrochlorothiazide, spironolactone, metformin, gliclazide, sitagliptin, dapagliflozin and empagliflozin. Clinicians should consider the predictors of inappropriate medication dosages listed above when prescribing to patients with CKD to reduce the risk of medications-related toxicities and adverse effects. Limitations of this study should be considered when interpreting the findings presented.
Fulltext Evidence of Bacterial Biofilms among Infected and Hypertrophied Tonsils in Correlation with the Microbiology, Histopathology, and Clinical Symptoms of Tonsillar Diseases

Alasil SM, Omar R, Ismail S, Yusof MY, Dhabaan GN, Abdulla MA

Int J Otolaryngol, 2013;2013:408238.
PMID: 24454384 DOI: 10.1155/2013/408238

Diseases of the tonsils are becoming more resistant to antibiotics due to the persistence of bacteria through the formation of biofilms. Therefore, understanding the microbiology and pathophysiology of such diseases represent an important step in the management of biofilm-related infections. We have isolated the microorganisms, evaluated their antimicrobial susceptibility, and detected the presence of bacterial biofilms in tonsillar specimens in correlation with the clinical manifestations of tonsillar diseases. Therefore, a total of 140 palatine tonsils were collected from 70 patients undergoing tonsillectomy at University Malaya Medical Centre. The most recovered isolate was Staphylococcus aureus (39.65%) followed by Haemophilus influenzae (18.53%). There was high susceptibility against all selected antibiotics except for cotrimoxazole. Bacterial biofilms were detected in 60% of patients and a significant percentage of patients demonstrated infection manifestation rather than obstruction. In addition, an association between clinical symptoms like snore, apnea, nasal obstruction, and tonsillar hypertrophy was found to be related to the microbiology of tonsils particularly to the presence of biofilms. In conclusion, evidence of biofilms in tonsils in correlation with the demonstrated clinical symptoms explains the recalcitrant nature of tonsillar diseases and highlights the importance of biofilm's early detection and prevention towards better therapeutic management of biofilm-related infections.
Fulltext APSIC Guidelines for environmental cleaning and decontamination

Ling ML, Apisarnthanarak A, Thu le TA, Villanueva V, Pandjaitan C, Yusof MY

Antimicrob Resist Infect Control, 2015;4:58.
PMID: 26719796 DOI: 10.1186/s13756-015-0099-7

This document is an executive summary of APSIC Guidelines for Environmental Cleaning and Decontamination. It describes best practices in routine cleaning and decontamination in healthcare facilities as well as in specific settings e.g. management of patients with isolation precautions, food preparation areas, construction and renovation, and following a flood. It recommends the implementation of environmental hygiene program to keep the environment safe for patients, staff and visitors visiting a healthcare facility. Objective assessment of cleanliness and quality is an essential component of this program as a method for identifying quality improvement opportunities. Recommendations for safe handling of linen and bedding; as well as occupational health and safety issues are included in the guidelines. A training program is vital to ensure consistent adherence to best practices.
Intestinal carriage of multidrug-resistant gram-negative bacteria in preterm-infants during hospitalization in neonatal intensive care unit (NICU)

Yap PS, Ahmad Kamar A, Chong CW, Yap IK, Thong KL, Choo YM, et al.

Pathog Glob Health, 2016 Sep;110(6):238-246.
PMID: 27650884

The prevalence and antibiotic susceptibility of intestinal carriage of Gram-negative bacteria among preterm infants admitted to the neonatal intensive care unit (NICU) in a tertiary teaching hospital in Malaysia were determined. A total of 34 stool specimens were obtained from preterm infants upon admission and once weekly up to two weeks during hospitalization. The presumptive colonies of Escherichia coli and Klebsiella pneumoniae were selected for identification, antibiotic susceptibility testing, and subtyping by using pulsed-field gel electrophoresis (PFGE). Out of 76 Gram-negative isolates, highest resistance was detected for amoxicillin/clavulanate (30.8%, n = 16), ceftriaxone (42.3%, n = 22), ceftazidime (28.8%, n = 15), cefoxitin (28.8%, n = 15), aztreonam (36.5%, n = 19), and polymyxin B (23.1%, n = 12). Three colistin resistant K. pneumoniae have also been detected based on E-test analysis. Thirty-nine isolates of K. pneumoniae and 20 isolates of E. coli were resistant to more than three antimicrobial classes and were categorized as multidrug resistant (MDR). PFGE analysis revealed a higher diversity in pulsotypes for K. pneumoniae (18 pulsotypes) in comparison to E. coli (four pulsotypes). In addition, a total of fifteen pulsotypes was observed from 39 MDR K. pneumoniae. The risk factors for antibiotic resistance were assessed using random forest analysis. Gender was found to be the most important predictor for colistin resistant while length, OFC, and delivery mode were showing greater predictive power in the polymyxin B resistance. This study revealed worrying prevalence rates of intestinal carriage of multidrug-resistant K. pneumoniae and E. coli of hospitalized preterm infants in Malaysia, particularly high resistance to polymyxins.
A large exposure to Brucella melitensis in a diagnostic laboratory

Sam IC, Karunakaran R, Kamarulzaman A, Ponnampalavanar S, Syed Omar SF, Ng KP, et al.

J Hosp Infect, 2012 Apr;80(4):321-5.
PMID: 22237130 DOI: 10.1016/j.jhin.2011.12.004

Brucella species are easily transmitted by aerosols and can be acquired in the laboratory.
Fulltext Antimicrobial Activity of Novel Synthetic Peptides Derived from Indolicidin and Ranalexin against Streptococcus pneumoniae

Jindal HM, Le CF, Mohd Yusof MY, Velayuthan RD, Lee VS, Zain SM, et al.

PLoS One, 2015;10(6):e0128532.
PMID: 26046345 DOI: 10.1371/journal.pone.0128532

Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics in order to defeat multidrug-resistant bacteria such as Streptococcus pneumoniae. In this study, thirteen antimicrobial peptides were designed based on two natural peptides indolicidin and ranalexin. Our results revealed that four hybrid peptides RN7-IN10, RN7-IN9, RN7-IN8, and RN7-IN6 possess potent antibacterial activity against 30 pneumococcal clinical isolates (MIC 7.81-15.62µg/ml). These four hybrid peptides also showed broad spectrum antibacterial activity (7.81µg/ml) against S. aureus, methicillin resistant S. aureus (MRSA), and E. coli. Furthermore, the time killing assay results showed that the hybrid peptides were able to eliminate S. pneumoniae within less than one hour which is faster than the standard drugs erythromycin and ceftriaxone. The cytotoxic effects of peptides were tested against human erythrocytes, WRL-68 normal liver cell line, and NL-20 normal lung cell line. The results revealed that none of the thirteen peptides have cytotoxic or hemolytic effects at their MIC values. The in silico molecular docking study was carried out to investigate the binding properties of peptides with three pneumococcal virulent targets by Autodock Vina. RN7IN6 showed a strong affinity to target proteins; autolysin, pneumolysin, and pneumococcal surface protein A (PspA) based on rigid docking studies. Our results suggest that the hybrid peptides could be suitable candidates for antibacterial drug development.
Fulltext Antibiotics in surgical wards: use or misuse? A newly industrialized country's perspective

Lim MK, Lai PSM, Ponnampalavanar SS, Syed Omar SF, Taib NA, Yusof MY, et al.

J Infect Dev Ctries, 2015 Nov 30;9(11):1264-71.
PMID: 26623636 DOI: 10.3855/jidc.6731

INTRODUCTION: Studies exploring the appropriateness of therapeutic antibiotic use among surgical patients are limited, particularly in developing countries. Therefore, the aim of our study was to determine the appropriateness of antibiotics prescribed in a surgical setting in Malaysia.
METHODOLOGY: A prospective observational study was conducted in two surgical wards at a tertiary hospital in Malaysia from November 2012-July 2013. Data was collected using a case report form. The appropriateness of antibiotic therapy was based on compliance with either the Malaysian National Antibiotic Guidelines 2008 or International Clinical Practice Guidelines and determined by an expert panel (consisting of two infectious disease consultants and a pharmacist).
RESULTS: Over the study period, a total of 593 antibiotic courses were prescribed for 129 patients (4.6±3.4 antibiotics/patient). Only 34 (26.4%) patients received appropriate antibiotic therapy, whilst 95 (73.6%) patients received at least one course of inappropriate antibiotic therapy. The prevalence of inappropriate antibiotic use was 214 (66.3%) and 55 (42.0%) for prophylactic and therapeutic purposes, respectively. The most common causes of inappropriate prophylactic antibiotics were inappropriate timing 20 (36.4%) and inappropriate duration of prophylaxis 19 (34.5%). In cases of inappropriate timing, 9 (45%) were administered too late while 6 (30%) were too early. In contrast, inappropriate choice of antibiotics (42.1%) and inappropriate indication (40.7%) were the most common reasons encountered for inappropriate therapeutic antibiotics.
CONCLUSION: Our study suggests considerable inappropriate use of both prophylactic and therapeutic antibiotics in the surgical wards; highlighting an urgent need for antibiotic stewardship initiatives in this setting.
Fulltext Elucidating the survival and response of carbapenem resistant Klebsiella pneumoniae after exposure to imipenem at sub-lethal concentrations

Low YM, Chong CW, Yap IKS, Chai LC, Clarke SC, Ponnampalavanar S, et al.

Pathog Glob Health, 2018 10;112(7):378-386.
PMID: 30380366 DOI: 10.1080/20477724.2018.1538281

The increasing prevalence of antibiotic resistant pathogens poses a serious threat to global health. However, less emphasis has been placed to co-relate the gene expression and metabolism of antibiotic resistant pathogens. This study aims to elucidate gene expression and variations in metabolism of multidrug resistant Klebsiella pneumoniae after exposure to antibiotics. Phenotypic responses of three genotypically distinct carbapenem resistant Klebsiella pneumoniae (CRKP) strains untreated and treated with sub-lethal concentrations of imipenem were investigated via phenotype microarrays (PM). The gene expression and metabolism of the strain harboring blaNDM-1 before and after exposure to sub-lethal concentration of imipenem were further investigated by RNA-sequencing (RNA-Seq) and 1H NMR spectroscopy respectively. Most genes related to cell division, central carbon metabolism and nucleotide metabolism were downregulated after imipenem treatment. Similarly, 1H NMR spectra obtained from treated CRKP showed decrease in levels of bacterial end products (acetate, pyruvate, succinate, formate) and metabolites involved in nucleotide metabolism (uracil, xanthine, hypoxanthine) but elevated levels of glycerophosphocholine. The presence of anserine was also observed for the treated CRKP while FAPγ-adenine and methyladenine were only present in untreated bacterial cells. As a conclusion, the studied CRKP strain exhibited decrease in central carbon metabolism, cell division and nucleotide metabolism after exposure to sub-lethal concentrations of imipenem. The understanding of the complex biological system of this multidrug resistant bacterium may help in the development of novel strategies and potential targets for the management of the infections.
Fulltext Serotypes & penicillin susceptibility of Streptococcus pneumoniae isolated from children admitted to a tertiary teaching hospital in Malaysia

Subramaniam P, Jabar KA, Kee BP, Chong CW, Nathan AM, de Bruyne J, et al.

Indian J Med Res, 2018 Aug;148(2):225-231.
PMID: 30381546 DOI: 10.4103/ijmr.IJMR_1987_16

Background & objectives: Streptococcus pneumoniae: (pneumococcus) is a highly invasive extracellular pathogen that causes diseases such as pneumonia, otitis media and meningitis. This study was undertaken to determine the serotype diversity and penicillin susceptibility of S. pneumoniae isolated from paediatric patients in a tertiary teaching hospital in Malaysia.
Methods: A total of 125 clinical isolates collected from January 2013 to May 2015 were serotyped using seven sequential multiplex polymerase chain reactions. The susceptibility of these isolates to penicillin was also investigated.
Results: Serotypes detected among the isolates were serotypes 3, 6A/B, 6C, 11/A/D/F, 15A/F, 19A, 19F, 23A, 23F, 34. Serotypes 19F and 6A/B were the most prevalent serotypes detected. Most of the S. pneumoniae were isolated from nasopharyngeal samples of children below five years of age. Majority of the isolates were penicillin susceptible. Only 5.6 per cent of the isolates were non-susceptible to penicillin, mostly of serotype 19F.
Interpretation & conclusions: Our study revealed the distribution of various serotypes in S. pneumoniae isolates obtained from children in a teaching hospital at Kuala Lumpur, Malaysia and decreasing rates of penicillin resistance among them. The shifts in serotypes and susceptibility to penicillin from time to time have been observed. Continuous monitoring and surveillance are pivotal for better infection control and management of pneumococcal infections among children.