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BACKGROUND: S. pneumoniae (SPN) is the most common cause of pneumonia. The disease can be effectively prevented through immunisation. Since December 2020, the Malaysian Government has included the 10-valent pneumococcal conjugate vaccine (PCV10) for all infants born on or after 1 January 2020 as part of the National Immunisation Programme (NIP). However, the epidemiology of pneumonia remains poorly understood. To fill the knowledge gap, we established a multicentre surveillance study to understand the burden of pneumococcal pneumonia among young children in Peninsular Malaysia. METHODS: MY-Pneumo is a multicentre prospective case-control study conducted in three sentinel sites located in three different states of Peninsular Malaysia - Kuala Lumpur, Pahang, and Kelantan. A cohort of at least 500 incident cases and 500 controls is enrolled beginning in October 2021 and matched for age. Cases are hospitalised children < 5 years with radiologically confirmed pneumonia, and the controls are children without any features suggestive of pneumonia. Clinical samples, including nasopharyngeal swabs (NPS) and urine, are collected according to the study protocol. Biological fluids such as blood, cerebrospinal fluid (CSF) and pleural fluid are obtained from invasive pneumonia disease (IPD) patients, if available. All children are tested for SPN using polymerase chain reaction (PCR) and pneumococcal urine antigen test (PUAT) using BinaxNow. DISCUSSION: Surveillance data, including carriage rate, serotype variations and the phylogeny data structure of SPN among young children in Malaysia during PCV implementation, will be generated from this study. Trends and patterns of pneumococcal serotypes by different regions are important for targeted public health strategies. Our data will provide baseline information for estimating the impact of PCV10 implementation and will influence policymakers' decisions regarding the upgrade from PCV10 to a higher-valency conjugate vaccine in Malaysia. TRIAL REGISTRATION: This project was registered at ClinicalTrials.gov (NCT04923035) on 2021, June 11. The study protocol was approved by the International Medical University Joint-Committee on Research & Ethics (4.15/JCM-216/2021) and the Institutional Review Board at sentinel sites (USM/JEPeM/21020190, IREC 2021-114, MREC ID No: 2021128-9769) and University of Southampton's Ethics and Research Governance (ERGo II 64844).
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Pneumonia Pneumocócica , Humanos , Malásia/epidemiologia , Estudos de Casos e Controles , Lactente , Pré-Escolar , Estudos Prospectivos , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Masculino , Streptococcus pneumoniae/isolamento & purificação , FemininoRESUMO
Weedy rice is a major problem in paddy fields around the world. It is well known that weedy rice appears to grow faster and mature earlier than cultivated rice. It is possible that differences in the root microbial genetics are correlated with this characteristic. This study incorporated 16S rRNA amplicon sequencing to study the microbial composition in the rhizosphere and endosphere of rice root. No significant difference was found between the microbiota associated with weedy and cultivated rice lines grown in the same field. It was found that the endosphere had less microbial diversity compared to the rhizosphere. The major groups of bacteria found in the endosphere are from the phylum Proteobacteria, Myxococcota, Chloroflexota, and Actinobacteria. In addition, by analyzing the microbiome of japonica rice grown in the field in a temperate climate, we found that despite differences in genotype and location, some bacterial taxa were found to be common and these members of the putative rice core microbiome can also be detected by in situ hybridization. The delineation of a core microbiome in the endosphere of rice suggests that these bacterial taxa might be important in the life cycle of a wide range of rice types.
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Microbiota , Oryza , Raízes de Plantas , RNA Ribossômico 16S , Rizosfera , Microbiologia do Solo , Oryza/microbiologia , Oryza/crescimento & desenvolvimento , Raízes de Plantas/microbiologia , RNA Ribossômico 16S/genética , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Filogenia , Clima Tropical , Plantas Daninhas/microbiologiaRESUMO
Background: The high burden of extended-spectrum beta-lactamase-producing (ESBL)-producing Enterobacterales worldwide, especially in the densely populated South East Asia poses a significant threat to the global transmission of antibiotic resistance. Molecular surveillance of ESBL-producing pathogens in this region is vital for understanding the local epidemiology, informing treatment choices, and addressing the regional and global implications of antibiotic resistance. Methods: Therefore, an inventory surveillance of the ESBL-Escherichia coli (ESBL-EC) isolates responsible for infections in Malaysian hospitals was conducted. Additionally, the in vitro efficacy of flomoxef and other established antibiotics against ESBL-EC was evaluated. Results: A total of 127 non-repetitive ESBL-EC strains isolated from clinical samples were collected during a multicentre study performed in five representative Malaysian hospitals. Of all the isolates, 33.9% were isolated from surgical site infections and 85.8% were hospital-acquired infections. High rates of resistance to cefotaxime (100%), cefepime (100%), aztreonam (100%) and trimethoprim-sulfamethoxazole (100%) were observed based on the broth microdilution test. Carbapenems remained the most effective antibiotics against the ESBL-EC, followed by flomoxef. Antibiotic resistance genes were identified by PCR. The blaCTX-M-1 was the most prevalent ESBL gene, with 28 isolates (22%) harbouring blaCTX-M-1 only, 27 isolates (21.3%) co-harbouring blaCTX-M-1 and blaTEM, and ten isolates (7.9%) co-harbouring blaCTX-M-1, blaTEM and blaSHV. A generalised linear model showed significant antibacterial activity of imipenem against different types of infection. Besides carbapenems, this study also demonstrated a satisfactory antibacterial activity of flomoxef (81.9%) on ESBL-EC, regardless of the types of ESBL genes.
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Infecções por Escherichia coli , Humanos , Antibacterianos/farmacologia , beta-Lactamases/genética , Carbapenêmicos/farmacologia , Escherichia coli/genética , Infecções por Escherichia coli/tratamento farmacológico , Malásia/epidemiologiaRESUMO
Background: While oral mirobial dysbiosis due to tobacco smoking has been studied thoroughly, there is limited data on the effect of waterpipe smoking on the oral microbiome. This study aims to compare the salivary microbiome between waterpipe smokers and non-smokers. Materials and methods: Unstimulated saliva samples were collected from 60 participants, 30 smokers and 30 non-smokers in Kuala Lumpur and Klang Valley, Malaysia. DNA extraction was performed using the Qiagen DNA mini kit, and the 16S rRNA bacterial gene was amplified and sequenced using the Illumina MiSeq platform. Sequencing reads were processed using DADA2, and the alpha and beta diversity of the bacterial community was assessed. Significantly differentiated taxa were identified using LEfSe analysis, while differentially expressed pathways were identified using MaAsLin2. Results: A significant compositional change (beta diversity) was detected between the two groups (PERMANOVA P < 0.05). Specifically, the levels of phylum Firmicutes and genus Streptococcus were elevated in smokers, whereas phylum Proteobacteria and genus Haemophilus were depleted compared to non-smokers. At the species level, Streptococcus oralis, Streptococcus salivarius, and Streptococcus gingivalis were enriched in smokers. We observed significant differences in the abundance of thirty-seven microbial metabolic pathways between waterpipe smokers and non-smokers. The microbial pathways enriched in smokers were those implicated in polymer degradation and amino acid metabolism. Conclusion: The taxonomic and metabolic profile of the salivary microbiome in waterpipe smokers compared to healthy controls exhibited a paradigm shift, thus, implying an alteration in the homeostatic balance of the oral cavity posing unique challenges for oral health.
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Background: Adequate calcium intake at an early age is crucial to achieving peak bone mass. Nevertheless, low calcium intake is common in Malaysian children. Aim: This study examined the calcium food sources and factors associated with low calcium intake among 243 children aged 9-11 years in Kuala Lumpur. Methods: Diet histories and bone density were measured. Results: The mean calcium intake was 370 ± 187 mg/day. The main contributors to calcium intake were beverages (19.2%), cereal (18.6%), milk and dairy (13.0%), meat and poultry (12.9%), and fish and seafood (10.1%). Within each food group, calcium-contributing foods tend to be from low bioavailability sources such as rice, cocoa-based and malted drinks, and chicken rather than milk. Children who practised regular meals, ate breakfast and snacks and consumed milk more than one serving daily have a higher calcium intake. Conclusion: In conclusion, public health strategies to improve the status of low calcium intake and poor choices of calcium-rich foods are needed to optimise bone health in this population.
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(1) Background: Antibiotic resistance is a serious health issue, and raising public awareness of it is crucial to combating it. This study aimed to assess the socio-demographic factors associated with knowledge of antibiotics and antibiotic resistance in Malaysia. (2) Methods: A cross-sectional study was carried out between April 2022 and March 2023. Malaysian adults aged ≥18 years old and able to understand English or Malay were recruited. During data collection, the WHO questionnaire "Antibiotic Resistance, Multi-Country Public Awareness Survey" was used. Data were collected across 14 states in Malaysia. (3) Results: A total of 517 participants completed the questionnaire. Most participants were females (67.9%), aged 30-49 (46%), and from central Malaysia (69.8%). Most participants (98.5%) reported taking antibiotics. A misconception presented was that sore throats, fevers, colds, and flu can be treated with antibiotics. A total of 58.8% of participants had high knowledge of antibiotic usage (scores 12-15), while 64% had high knowledge of antibiotic resistance (scores 9-14). Findings indicate that increasing age, income, and education were associated with higher knowledge. (4) Conclusions: This study highlights the knowledge deficiency of antibiotic resistance among Malaysians. Educational programs should engage a younger and lower socio-economic population to increase awareness.
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Medication adherence profoundly affects blood glucose management in patients with type 2 diabetes. Measures to contain the COVID-19 pandemic have affected disease management and medication adherence, owing to limited access to healthcare facilities. This study aimed to examine the impact of the COVID-19 lockdown on adherence to glucose-lowering and lipid-lowering therapies (statins), and glycemic, weight, and systolic blood pressure control measures. A retrospective chart review was conducted one year pre- and post- March 18, 2020, for patients receiving glucose-lowering medications and lipid-lowering therapies (statins) in two major public hospitals in Malaysia. We compared the proportion of days covered by medication, HbA1c level, weight, and systolic blood pressure (SBP) values pre- and after the index date. A total of 1985 patients were included in this study. The adherence rate significantly increased for metformin, sulfonylureas dipeptidyl peptidase 4 inhibitors (DPP4i) and statin after the index date (metformin (PDC: 0.985 vs 0.978, p < 0.001), sulfonylureas (PDC: 0.988 vs 0.979, p < 0.01), DPP4i (PDC: 0.987 vs 0.98, p < 0.001), and statins (PDC: 0.983 vs 0.978, p < 0.05)). HbA1c levels were significantly reduced after the index follow-up (Mean difference: -0.43%, p < 0.001), while there was a 2.5 mmHg (p = 0.03) significant increase in SBP post-index follow-up. No significant changes in weight were observed during the post-index follow-up period. In this study, we observed better medication adherence and glycemic control among patients during the lockdown, but not for weight and systolic blood pressure control.
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OBJECTIVES: This study aims to evaluate the cost-effectiveness of various glucose-lowering therapies as add-on to standard care for people with type 2 diabetes (T2D) in Malaysia. METHODS: A state-transition microsimulation model was developed to compare the clinical and economic outcomes of 4 treatments: standard care, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors (SGLT2is), and glucagon-like peptide-1 receptor agonists. Cost-effectiveness was assessed from a healthcare provider's perspective over a lifetime horizon with 3% discount rate in a hypothetical cohort of people with T2D. Data input were informed from literature and local data when available. Outcome measures include costs, quality-adjusted life-years, incremental cost-effectiveness ratios, and net monetary benefits. Univariate and probabilistic sensitivity analyses were performed to assess uncertainties. RESULTS: Over a lifetime horizon, the costs to treat a person with T2D ranged from RM 12 494 to RM 41 250, whereas the QALYs gains ranged from 6.155 to 6.731, depending on the treatment. Based upon a willingness-to-pay threshold of RM 29 080 per QALY, we identified SGLT2i as the most cost-effective glucose-lowering treatment, as add-on to standard care over patient's lifetime, with the net monetary benefit of RM 176 173 and incremental cost-effectiveness ratios of RM 12 279 per QALY gained. The intervention also added 0.577 QALYs and 0.809 LYs compared with standard care. Cost-effectiveness acceptability curve showed that SGLT2i had the highest probability of being cost-effective in Malaysia across varying willingness-to-pay threshold. The results were robust to various sensitivity analyses. CONCLUSIONS: SGLT2i was found to be the most cost-effective intervention to mitigate diabetes-related complications.
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Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Análise Custo-Benefício , Glucose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , MalásiaRESUMO
Phages, which are often used therapeutically, have begun to receive interest as alternatives to antibiotic growth promoters (AGPs) for enhancing chicken growth. Another option that has been extensively studied as a growth promoter in chickens is probiotics. To the best of our knowledge, there is currently no study available on the use of phages and probiotics in combination as potential feed additives for broiler chickens. Therefore, this study demonstrated the effects of a phage cocktail, probiotics, and their combination on the growth performance and gut microbiota of broiler chickens. A total of 288 one-day-old male Cobb 500 broilers were randomly allotted to one of six treatments in a completely randomised design. The treatments were (i) C (basal diet (BD) only), (ii) 1Ï (BD + 0.1% phage cocktail), (iii) 2Ï (BD + 0.2% phage cocktail), (iv) P (BD + 0.1% probiotic), (v) 1ÏP (BD + 0.1% phage cocktail + 0.1% probiotic), and (vi) 2ÏP (BD + 0.2% phage cocktail + 0.1% probiotic). The 1ÏP treatment had significantly (p < 0.05) better BW (35 days), BWG (22-35 days, 1-35 days), and FCR (1-21 days, 22-35 days, 1-35 days) compared to C. Unique gut microbiota diversity was also found between the ÏP (1ÏP and 2ÏP) and non-ÏP groups (C, 1Ï, 2Ï, and P) in ilea, particularly in the 35-day-old chickens. Microorganisms associated with short-chain fatty acid (SCFA) producers were significantly (p < 0.05) more present in the ÏP group than in the non-ÏP group. The predicted genes related to carbohydrate and amino acid metabolism were significantly upregulated in ÏP groups compared to non-ÏP groups. These genes were involved in the digestion and absorption of nutrients, as well as the production of energy. Our findings showed that the 1ÏP treatment could be a potential alternative to AGPs for poultry, as growth performance was enhanced, and gut microbiota was positively modulated.
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Background: Diabetes is one of the leading causes of chronic kidney disease (CKD) and end-stage renal disease. This study aims to develop and validate different risk predictive models for incident CKD and CKD progression in people with type 2 diabetes (T2D). Methods: We reviewed a cohort of people with T2D seeking care from two tertiary hospitals in the metropolitan cities of the state of Selangor and Negeri Sembilan from January 2012 to May 2021. To identify the 3-year predictor of developing CKD (primary outcome) and CKD progression (secondary outcome), the dataset was randomly split into a training and test set. A Cox proportional hazards (CoxPH) model was developed to identify predictors of developing CKD. The resultant CoxPH model was compared with other machine learning models on their performance using C-statistic. Results: The cohorts included 1992 participants, of which 295 had developed CKD and 442 reported worsening of kidney function. Equation for the 3-year risk of developing CKD included gender, haemoglobin A1c, triglyceride and serum creatinine levels, estimated glomerular filtration rate, history of cardiovascular disease and diabetes duration. For risk of CKD progression, the model included systolic blood pressure, retinopathy and proteinuria. The CoxPH model was better at prediction compared with other machine learning models examined for incident CKD (C-statistic: training 0.826; test 0.874) and CKD progression (C-statistic: training 0.611; test 0.655). The risk calculator can be found at https://rs59.shinyapps.io/071221/. Conclusions: The Cox regression model was the best performing model to predict people with T2D who will develop a 3-year risk of incident CKD and CKD progression in a Malaysian cohort.
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BACKGROUND AND AIM: The gut microbiota in irritable bowel syndrome (IBS) is known to vary with diet. We aim to (i) analyze the gut microbiota composition of IBS patients from a multi-ethnic population and (ii) explore the impact of a low FODMAP diet on gastrointestinal symptoms and gut microbiota composition among IBS patients. METHODS: A multi-center study of multi-ethnic Asian patients with IBS was conducted in two phases: (i) an initial cross-sectional gut microbiota composition study of IBS patients and healthy controls, followed by (ii) a single-arm 6-week dietary interventional study of the IBS patients alone, exploring clinical and gut microbiota changes. RESULTS: A total of 34 adult IBS patients (IBS sub-types of IBS-D 44.1%, IBS-C 32.4%, and IBS-M 23.5%) and 15 healthy controls were recruited. A greater abundance of Parabacteroides species with lower levels of bacterial fermenters and short-chain fatty acids producers were found among IBS patients compared with healthy controls. Age and ethnicity were found to be associated with gut microbiota composition. Following a low FODMAP dietary intervention, symptom and quality of life improvement were observed in 24 (70.6%) IBS patients. Symptom improvement was associated with adherence to the low FODMAP diet (46.7% poor adherence vs 92.9% good adherence, P = 0.014), and gut microbiota patterns, particularly with a greater abundance of Bifidobacterium longum, Anaerotignum propionicum, and Blautia species post-intervention. CONCLUSION: Gut microbiota variation in multi-ethnic IBS patients may be related to dietary intake and may be helpful to identify patients who are likely to respond to a low FODMAP diet.
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Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Adulto , Humanos , Síndrome do Intestino Irritável/diagnóstico , Qualidade de Vida , Estudos Transversais , Etnicidade , Dieta/efeitos adversos , FermentaçãoRESUMO
The prevalence of pre-diabetes is increasing globally, affecting an estimated 552 million people by 2030. While lifestyle interventions are the first line of defense against progression toward diabetes, information on barriers toward pre-diabetes management and how to overcome these barriers are scarce. This systematic review describes the publics' and healthcare professionals' knowledge, attitude and practice (KAP) toward pre-diabetes and determines the barriers toward pre-diabetes management. A systematic search for studies examining KAP towards pre-diabetes was conducted in six databases from inception to September 2022. Studies that quantitatively assessed at least two KAP elements using questionnaires were included. The quality of studies was assessed using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Barriers and enablers were identified and mapped onto the Capability, Motivation, and Behaviour model to identify factors that influence behavior change. Twenty-one articles that surveyed 8876 participants were included in this review. Most of the reviews (n=13) were directed to healthcare professionals. Overall, positive attitudes toward diabetes prevention efforts were observed, although there were still knowledge deficits and poor behavior toward pre-diabetes management. Barriers and enablers were detected at patients (eg, goals and intention), healthcare professionals (eg, clinical judgement) and system (eg, access and resources) levels. The use of different survey instruments to assess KAP prevented a head-to-head comparison between studies. Most studies conducted among patients were from middle-income countries, while among healthcare professionals (HCPs) were from high-income countries, which may produce some biasness. Nevertheless, the development of pre-diabetes intervention should focus on: (1) increasing knowledge on pre-diabetes and its management; (2) imparting practical skills to manage pre-diabetes; (3) providing resources for lifestyle management; (4) improving the accessibility of lifestyle management programs; and (5) other HCPs and human support to pre-diabetes management.
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Diabetes Mellitus , Estado Pré-Diabético , Humanos , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/terapia , Conhecimentos, Atitudes e Prática em Saúde , Estudos Transversais , Pessoal de Saúde , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/prevenção & controleRESUMO
Non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae (NC-CRKP) confers carbapenem resistance through a combination of chromosomal mutations and acquired non-carbapenemase resistance mechanisms. In this study, we aimed to evaluate the clinical and molecular profiles of NC-CRKP isolated from patients in a tertiary teaching hospital in Malaysia from January 2013 to October 2019. During the study period, 54 NC-CRKP-infected/colonised patients' isolates were obtained. Clinical parameters were assessed in 52 patients. The all-cause in-hospital mortality rate among NC-CRKP patients was 46.2% (24/52). Twenty-three (44.2%) patients were infected, while others were colonised. Based on the Charlson Comorbidity Index (CCI) score, 92.3% (48/52) of the infected/colonised patients had a score of ≥ 1. Resistance genes found among the 54 NC-CRKP isolates were blaTEM, blaSHV, blaCTX-M, blaOXA, and blaDHA. Porin loss was detected in 25/54 (46.3%) strains. None of the isolated strains conferred carbapenem resistance through the efflux pumps system. In conclusion, only 25/54 (46.3%) NC-CRKP conferred carbapenem resistance through a combination of porin loss and the acquisition of non-carbapenemase resistance mechanisms. The carbapenem resistance mechanisms for the remaining strains (53.7%) should be further investigated as rapid identification and distinction of the NC-CRKP mechanisms enable optimal treatment and infection control efforts.
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Altered gut microbiota composition has been observed in individuals with hidradenitis suppurutiva (HS) and many other inflammatory diseases, including obesity, type 1 and type 2 diabetes. Here, we addressed whether adalimumab, a systemic anti-inflammatory therapy, may impact the microbiota biochemical profile, particularly on beneficial metabolites such as short-chain fatty acids (SCFAs). We conducted an observational single-arm pilot trial to assess gut microbiota composition by 16S rRNA gene sequence analysis and to detect metabolite signatures by gas chromatography in stool samples from participants with HS prior to and 12 weeks after commencing adalimumab therapy. HS individuals that better responded to adalimumab treatment showed a shift in the composition and function of the gut microbiota with significantly increased SCFA acetate and propionate compared to age, gender and BMI-matched healthy controls. A positive correlation was observed between propionate with Prevotella sp and Faecalibacterium prausnitsii. Increased SCFAs, changes in gut microbiota composition, function and metabolic profile following 12 weeks of adalimumab suggest that targeting SCFAs may be considered a potential biomarker to be evaluated as a complementary protective factor or as a diagnostically relevant signal in HS.
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Diabetes Mellitus Tipo 2 , Hidradenite Supurativa , Humanos , Hidradenite Supurativa/tratamento farmacológico , Adalimumab/uso terapêutico , RNA Ribossômico 16S/genética , Propionatos/uso terapêutico , Ácidos Graxos Voláteis/metabolismoRESUMO
Staphylococcus aureus expresses diverse proteins at different stages of growth. The immunodominant staphylococcal antigen A (IsaA) is one of the proteins that is constitutively produced by S. aureus during colonisation and infection. SACOL2584 (or isaA) is the gene that encodes this protein. It has been suggested that IsaA can hydrolyse cell walls, and there is still need to study isaA gene disruption to analyse its impact on staphylococcal phenotypes and on alteration to its transcription and protein profiles. In the present study, the growth curve in RPMI medium (which mimics human plasma), autolytic activity, cell wall morphology, fibronectin and fibrinogen adhesion and biofilm formation of S. aureus SH1000 (wildtype) was compared to that of S. aureus MS001 (isaA mutant). RNA sequencing and liquid chromatography-tandem mass spectrometry were carried out on samples of both S. aureus strains taken during the exponential growth phase, followed by bioinformatics analysis. Disruption of isaA had no obvious effect on the growth curve and autolysis ability or thickness of cell walls, but this study revealed significant strength of fibronectin adherence in S. aureus MS001. In particular, the isaA mutant formed less biofilm than S. aureus SH1000. In addition, proteomics and transcriptomics showed that the adhesin/biofilm-related genes and hemolysin genes, such as sasF, sarX and hlgC, were consistently downregulated with isaA gene disruption. The majority of the upregulated genes or proteins in S. aureus MS001 were pur genes. Taken together, this study provides insight into how isaA disruption changes the expression of other genes and has implications regarding biofilm formation and biological processes.
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OBJECTIVES: This study profiled the prevalence of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) in the community and compared their resistome and genomic profiles with isolates from clinical patients through whole-genome sequencing. METHODS: Fecal samples from 233 community dwellers from Segamat, a town in southern Malaysia, were obtained between May through August 2018. Putative ESBL strains were screened and tested using antibiotic susceptibility tests. Additionally, eight clinical ESBL-EC were obtained from a hospital in the same district between June through October 2020. Whole-genome sequencing was then conducted on selected ESBL-EC from both settings (n = 40) for pan-genome comparison, cluster analysis, and resistome profiling. RESULTS: A mean ESBL-EC carriage rate of 17.82% (95% CI: 10.48%- 24.11%) was observed in the community and was consistent across demographic factors. Whole-genome sequences of the ESBL-EC (n = 40) enabled the detection of multiple plasmid replicon groups (n = 28), resistance genes (n = 34) and virulence factors (n = 335), with no significant difference in the number of genes carried between the community and clinical isolates (plasmid replicon groups, p = 0.13; resistance genes, p = 0.47; virulence factors, p = 0.94). Virulence gene marker analysis detected the presence of extraintestinal pathogenic E. coli (ExPEC), uropathogenic E. coli (UPEC), and enteroaggregative E. coli (EAEC) in both the community and clinical isolates. Multiple blaCTX-M variants were observed, dominated by blaCTX-M-27 (n = 12), blaCTX-M-65 (n = 10), and blaCTX-M-15 (n = 9). The clinical and community isolates did not cluster together based on the pan-genome comparison, suggesting isolates from the two settings were clonally unrelated. However, cluster analysis based on carried plasmids, resistance genes and phenotypic susceptibility profiles identified four distinct clusters, with similar patterns between the community and clinical isolates. CONCLUSION: ESBL-EC from the clinical and community settings shared similar resistome profiles, suggesting the frequent exchange of genetic materials through horizontal gene transfer.
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Infecções por Escherichia coli , Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Escherichia coli/genética , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Humanos , Malásia/epidemiologia , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Fatores de Virulência , beta-Lactamases/genéticaRESUMO
BACKGROUND: Carbapenem resistant Enterobacteriaceae (CRE) has rapidly disseminated worldwide and has become a global threat to the healthcare system due to its resistance towards "last line" antibiotics. This study aimed to investigate the prevalence of CRE and the resistance mechanism as well as the risk factors associated with in-hospital mortality. METHODS: A total of 168 CRE strains isolated from a tertiary teaching hospital from 2014-2015 were included in this study. The presence of carbapenemase genes and minimum inhibitory concentration of imipenem, meropenem and colistin were investigated. All carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) strains were characterised by PFGE. The risk factors of patients infected by CRE associated with in-hospital mortality were determined statistically. RESULTS: The predominant CRE species isolated was K. pneumoniae. The carbapenemases detected were blaOXA-48, blaOXA-232, blaVIM and blaNDM of which blaOXA-48 was the predominant carbapenemase detected among 168 CRE strains. A total of 40 CRE strains harboured two different carbapenemase genes. A total of seven clusters and 48 pulsotypes were identified among 140 CRKp strains. A predominant pulsotype responsible for the transmission from 2014 to 2015 was identified. Univariate statistical analysis identified that the period between CRE isolation and start of appropriate therapy of more than 3 days was statistically associated with in-hospital mortality.
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Enterobacteriáceas Resistentes a Carbapenêmicos , Humanos , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Estudos Retrospectivos , Epidemiologia Molecular , Malásia , Carbapenêmicos/farmacologia , Klebsiella pneumoniae , Hospitais de EnsinoRESUMO
Inappropriate use of antibiotics has been shown to contribute to the occurrence of multidrug-resistant organisms (MROs). A surveillance study was performed in the largest tertiary care hospital in Kuala Lumpur, Malaysia, from 2018 to 2020 to observe the trends of broad-spectrum antibiotics (beta-lactam/beta-lactamases inhibitors (BL/BLI), extended-spectrum cephalosporins (ESC), and fluoroquinolones (FQ)) and antibiotics against MRO (carbapenems, polymyxins, and glycopeptides) usage and the correlation between antibiotic consumption and MROs. The correlation between 3-year trends of antibiotic consumption (defined daily dose (DDD)/100 admissions) with MRO infection cases (per 100 admissions) was determined using a Jonckheere-Terpstra test and a Pearson's Correlation coefficient. The antimicrobial resistance trend demonstrated a positive correlation between ESC and FQ towards the development of methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Klebsiella spp, ESBL-producing Escherichia coli (E. coli), and MRO Acinetobacter baumannii (A. baumannii). Increasing carbapenem consumption was positively correlated with the occurrence of ESBL-producing Klebsiella spp and E. coli. Polymyxin use was positively correlated with ESBL-producing Klebsiella spp, MRO A. baumannii, and carbapenem-resistant Enterobacteriaceae. The findings reinforced concerns regarding the association between MRO development, especially with a surge in ESC and FQ consumption. Stricter use of antimicrobials is thus crucial to minimise the risk of emerging resistant organisms.
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Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Prescrição Inadequada/tendências , Carbapenêmicos/farmacologia , Cefalosporinas/farmacologia , Infecção Hospitalar/epidemiologia , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Fluoroquinolonas/farmacologia , Humanos , Klebsiella/efeitos dos fármacos , Infecções por Klebsiella/tratamento farmacológico , Malásia/epidemiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Centros de Atenção Terciária , Inibidores de beta-Lactamases/farmacologia , beta-LactamasesRESUMO
Burkholderia pseudomallei, a Gram-negative bacterial pathogen that causes melioidosis, is of public health importance in endemic areas including Malaysia. An investigation of the molecular epidemiology links of B. pseudomallei would contribute to better understanding of the clonal relationships, transmission dynamics and evolutionary change. Multilocus sequence typing (MLST) of 45 clinical B. pseudomallei isolates collected from sporadic melioidosis cases in Malaysia was performed. In addition, a total of 449 B. pseudomallei Malaysian strains submitted to the MLST database from 1964 until 2019 were included in the temporal analysis to determine the endemic sequence types (STs), emergence and re-emergence of ST(s). In addition, strain-specific distribution was evaluated using BURST tool. Genotyping of 45 clinical strains was resolved into 12 STs, and the majority were affiliated with ST46 (n = 11) and ST1342 (n = 7). Concomitantly, ST46 was the most prevalent ST in Malaysia, which was first reported in 1964. All the Malaysian B. pseudomallei strains were resolved into 76 different STs with 36 of them uniquely present only in Malaysia. ST1342 was most closely related to ST1034, in which both STs were unique to Malaysia and first isolated from soil samples in Pahang, a state in Malaysia. The present study revealed a high diversity of B. pseudomallei in Malaysia. Localized evolution giving rise to the emergence of new STs was observed, suggesting that host and environmental factors play a crucial role in the evolutionary changes in B. pseudomallei.