Evaluation of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia: Epidemiology, clinical characteristics, and outcomes in the older patients in a tertiary teaching hospital in Malaysia.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a major concern in the global healthcare system. However, data from Asian regions dealing with the singularity of this infection in older persons is lacking. We aimed to identify the differences in the clinical characteristics and outcomes of MRSA bacteremia between adults aged 18-64 and ≥ 65 years. METHODS: A retrospective study cohort was conducted at the University Malaya Medical Centre (UMMC) on cases of MRSA bacteremia from 2012 to 2016. Patient demographic and clinical data were collected for risk factors analyses. RESULTS: New cases of MRSA bacteremia showed a trend of increase from 0.12 to 100 admissions in 2012 to 0.17 per 100 admissions in 2016 but a drop was observed in 2014 (0.07 per 100 admissions). Out of the 275 patients with MRSA bacteremia, 139 (50.5%) patients were aged ≥ 65 years old. Co-morbidities and severity at presentation were significantly higher among older adults, including diabetes mellitus (p = 0.035), hypertension (p = 0.001), and ischemic heart disease (p < 0.001), as well as higher Charlson Comorbidity Index (p < 0.001) and Pitt bacteremia scores (p = 0.016). Central line-associated bloodstream infections were more common among younger patients (37.5% vs. 17.3% in older patients, p < 0.001), while skin and soft tissue infections are more frequent among older adults (20.9% vs. 10.3% in younger patients, p = 0.016). All-cause mortality and in-hospital mortality were significantly higher in older patients (82.7% and 56.1% vs. 63.2% and 28.7% in younger patients, p < 0.001). Multivariate analysis revealed age ≥ 65 years (adjusted odds ratio: 3.36; 95% confidence interval: 1.24-9.13), Pitt score ≥ 3 (2.15; 1.54-3.01), hospital (6.12; 1.81-20.72) and healthcare (3.19; 1.30-7.81) acquisition of MRSA, indwelling urinary catheters (5.43; 1.39-21.23), inappropriate targeted treatment (8.08; 1.15-56.86), lack of infectious disease team consultation (2.90; 1.04-8.11) and hypoalbuminemia (3.31; 1.25-8.79), were significant risk factors for 30-day mortality. CONCLUSION: Older patients' risk of mortality from MRSA bacteremia was three times higher than younger patients. Our data will contribute to developing and validating a robust scoring system for risk-stratifying patients to achieve better management and improved clinical outcomes.

Utility and Applicability of Rapid Diagnostic Testing in Antimicrobial Stewardship in the Asia-Pacific Region: A Delphi Consensus.

Rapid diagnostic tests (RDTs) facilitate fast and accurate identification of infectious disease microorganisms and are a valuable component of multimodal antimicrobial stewardship (AMS) programs but are currently underutilized in the Asia-Pacific region. An experienced group of infectious diseases clinicians, clinical microbiologists, and a clinical pharmacist used a modified Delphi consensus approach to construct 10 statements, aiming to optimize the utility and applicability of infection-related RDTs for AMS in the Asia-Pacific region. They provide guidance on definition, types, optimal deployment, measuring effectiveness, and overcoming key challenges. The Grading of Recommendations Assessment, Development, and Evaluation system was applied to indicate the strength of the recommendation and the quality of the underlying evidence. Given the diversity of the Asia-Pacific region, the trajectory of RDT development will vary widely; the collection of local data should be prioritized to allow realization and optimization of the full benefits of RDTs in AMS.

Changing predominant SARS-CoV-2 lineages drives successive COVID-19 waves in Malaysia, February 2020 to March 2021.

Malaysia has experienced three waves of coronavirus disease 2019 (COVID-19) as of March 31, 2021. We studied the associated molecular epidemiology and SARS-CoV-2 seroprevalence during the third wave. We obtained 60 whole-genome SARS-CoV-2 sequences between October 2020 and January 2021 in Kuala Lumpur/Selangor and analyzed 989 available Malaysian sequences. We tested 653 residual serum samples collected between December 2020 to April 2021 for anti-SARS-CoV-2 total antibodies, as a proxy for population immunity. The first wave (January 2020) comprised sporadic imported cases from China of early Pango lineages A and B. The second wave (March-June 2020) was associated with lineage B.6. The ongoing third wave (from September 2020) was propagated by a state election in Sabah. It is due to lineage B.1.524 viruses containing spike mutations D614G and A701V. Lineages B.1.459, B.1.470, and B.1.466.2 were likely imported from the region and confined to Sarawak state. Direct age-standardized seroprevalence in Kuala Lumpur/Selangor was 3.0%. The second and third waves were driven by super-spreading events and different circulating lineages. Malaysia is highly susceptible to further waves, especially as alpha (B.1.1.7) and beta (B.1.351) variants of concern were first detected in December 2020/January 2021. Increased genomic surveillance is critical.

Quality Improvement Report: Safety Program for Prevention of Central Line-associated Bloodstream Infections.

The increasing usage of peripherally inserted central catheters (PICCs) in medical imaging departments has led to a corresponding increase in cases of central line-associated bloodstream infection (CLABSI). However, this condition is preventable with proper monitoring and use of aseptic techniques. A Comprehensive Unit-based Safety Program (CUSP) is a quality improvement (QI) measure implemented by health care institutions to reduce the incidence of CLABSI. However, effective strategies have yet to be established. The authors describe a QI project that evaluated the implementation of CUSP at a teaching hospital to reduce PICC-associated bloodstream infection (BSI). The framework consists of a five-step process: understand and train staff on the science of safety, assemble a team, engage senior executives, identify defects through sensemaking, and implement teamwork and communication strategies in a series of related and sequential steps that use QI tools. Targets were identified for improvement from existing processes, and the workflow was reengineered. Nine months after the start of the CUSP intervention, PICC-associated BSI incidence in the hospital had been reduced from 3.4 to 2.7 per 1000 central lines days after intervention. The incidence of BSI was also reduced correspondingly from 8.8% to 5.9%. The QI processes in this study may be adopted by other hospitals, as they involve minimal cost with significant impact on patient safety and well-being. The QI sequential steps described capture the implementation processes that can be modified for use in other department settings where patient safety could be compromised. Online supplemental material is available for this article. ©RSNA, 2022.

Knowledge, attitude and practice in relation to catheter-associated urinary tract infection (CAUTI) prevention: A cross-sectional study.

BACKGROUND: Healthcare-associated infection (HAI) is one of the major threats to patients' safety besides being among the principal causes of patient morbidity and mortality. Catheter-associated urinary tract infection (CAUTI) is reported to be the most common HAI worldwide. CAUTI can be prevented with appropriate practice and care by healthcare personnel, especially nurses, who play the main role in urinary catheter care. Nurses' knowledge and attitude are considered to be important factors that influence their practice. OBJECTIVES: To assess nurses' level of knowledge, attitude and perceived practice regarding CAUTI and its preventive measures. METHODS: A cross-sectional design was adopted, and a self-administered questionnaire was used to collect data. Nurses from the medical and surgical inpatient wards of a tertiary teaching hospital in Malaysia were recruited in two stages using the stratified and simple random sampling methods. A total of 301 nurses participated. Descriptive analysis, an independent t test, ANOVA and hierarchical multiple regression were employed to analyse the data using SPSS software version 25. In addition, a STROBE checklist was used to report the results of this study. RESULTS: Nurses were found to have good knowledge, a positive attitude and good perceived practice regarding CAUTI prevention. Nurses aged above 30 and who had more than ten years of experience reported higher knowledge levels. Knowledge was found to be positively correlated with attitude and perceived practice; however, attitude explained a higher variance in perceived practice of CAUTI prevention compared with knowledge. CONCLUSION: Attitude was found to have a higher significant influence on perceived practice in this study. Educators need to emphasise the inculcation of a positive attitude among nurses rather than just knowledge for CAUTI prevention. Since this study assessed perceived practice, examining nurses' actual practice and its impact on patient outcomes is recommended in future studies.

Propagation of a hospital-associated cluster of COVID-19 in Malaysia.

BACKGROUND: Hospitals are vulnerable to COVID-19 outbreaks. Intrahospital transmission of the disease is a threat to the healthcare systems as it increases morbidity and mortality among patients. It is imperative to deepen our understanding of transmission events in hospital-associated cases of COVID-19 for timely implementation of infection prevention and control measures in the hospital in avoiding future outbreaks. We examined the use of epidemiological case investigation combined with whole genome sequencing of cases to investigate and manage a hospital-associated cluster of COVID-19 cases. METHODS: An epidemiological investigation was conducted in a University Hospital in Malaysia from 23 March to 22 April 2020. Contact tracing, risk assessment, testing, symptom surveillance, and outbreak management were conducted following the diagnosis of a healthcare worker with SARS-CoV-2 by real-time PCR. These findings were complemented by whole genome sequencing analysis of a subset of positive cases. RESULTS: The index case was symptomatic but did not fulfill the initial epidemiological criteria for routine screening. Contact tracing suggested epidemiological linkages of 38 cases with COVID-19. Phylogenetic analysis excluded four of these cases. This cluster included 34 cases comprising ten healthcare worker-cases, nine patient-cases, and 15 community-cases. The epidemic curve demonstrated initial intrahospital transmission that propagated into the community. The estimated median incubation period was 4.7 days (95% CI: 3.5-6.4), and the serial interval was 5.3 days (95% CI: 4.3-6.5). CONCLUSION: The study demonstrated the contribution of integrating epidemiological investigation and whole genome sequencing in understanding disease transmission in the hospital setting. Contact tracing, risk assessment, testing, and symptom surveillance remain imperative in resource-limited settings to identify and isolate cases, thereby controlling COVID-19 outbreaks. The use of whole genome sequencing complements field investigation findings in clarifying transmission networks. The safety of a hospital population during this COVID-19 pandemic may be secured with a multidisciplinary approach, good infection control measures, effective preparedness and response plan, and individual-level compliance among the hospital population.

Predictors and Clinical Outcomes of Poor Platelet Recovery in Adult Dengue With Thrombocytopenia: A Multicenter, Prospective Study.

BACKGROUND: Platelet transfusion is common in dengue patients with thrombocytopenia. We previously showed in a randomized clinical trial that prophylactic platelet transfusion did not reduce clinical bleeding. In this study, we aimed to characterize the predictors and clinical outcomes of poor platelet recovery in transfused and nontransfused participants. METHODS: We analyzed patients from the Adult Dengue Platelet Study with laboratory-confirmed dengue with ≤20 000 platelets/µL and without persistent mild bleeding or any severe bleeding in a post hoc analysis. Poor platelet recovery was defined as a platelet count of ≤20 000/µL on Day 2. We recruited 372 participants from 5 acute care hospitals located in Singapore and Malaysia between 29 April 2010 and 9 December 2014. Of these, 188 were randomly assigned to the transfusion group and 184 to the control group. RESULTS: Of 360 patients, 158 had poor platelet recovery. Age, white cell count, and day of illness at study enrollment were significant predictors of poor platelet recovery after adjustment for baseline characteristics and platelet transfusion. Patients with poor platelet recovery had longer hospitalizations but no significant difference in other clinical outcomes, regardless of transfusion. We found a significant interaction between platelet recovery and transfusion; patients with poor platelet recovery were more likely to bleed if given a prophylactic platelet transfusion (odds ratio 2.34, 95% confidence interval 1.18-4.63). CONCLUSIONS: Dengue patients with thrombocytopenia who were older or presented earlier and with lower white cell counts were more likely to have poor platelet recovery. In patients with poor platelet recovery, platelet transfusion does not improve outcomes and may actually increase the risk of bleeding. The mechanisms of poor platelet recovery need to be determined. CLINICAL TRIALS REGISTRATION: NCT01030211.

First detection of Klebsiella quasipneumoniae producing OXA-181 carbapenemase in Malaysia.

The emergence of carbapenemase-producing Enterobacteriaceae has become a major global concern. OXA-48-like carbapenemase gene and its variants have been increasingly reported worldwide. This study reported the first OXA-181-producing Klebsiella quasipneumoniae isolate in Malaysia. This bacterium was isolated from blood specimen of a three-year-old boy with Alagille syndrome who had liver biopsy on October 2016. He had undergone liver transplant in India ten months previously. The genotypic and phenotypic characteristics of the strain were elucidated in this study. To our best knowledge, this is the first report of OXA-181-producing K. quasipneumoniae in Malaysia.

Evolving trends in infective endocarditis in a developing country: a consequence of medical progress?

BACKGROUND: Staphylococcus has replaced streptococcus as the most common cause of infective endocarditis (IE) in developed health care systems. The trend in developing countries is less clear. AIM: To examine the epidemiological trends of infective endocarditis in a developing nation. METHODS: Single-centre, retrospective study of patients admitted with IE to a tertiary hospital in Malaysia over a 12-year period. RESULTS: The analysis included 182 patients (n = 153 Duke's definite IE, n = 29 possible IE). The mean age was 51 years. Rheumatic heart disease was present in 42%, while 7.6% were immunocompromised. IE affected native valves in 171 (94%) cases. Health-care associated IE (HCAIE) was recorded in 68 (37.4%). IE admission rates increased from 25/100,000 admissions (2012) to 59/100,000 admissions (2017). At least one major complication on admission was detected in 59 (32.4%) patients. Left-sided IE was more common than right-sided IE [n = 159 (87.4%) vs. n = 18 (9.9%)]. Pathogens identified by blood culture were staphylococcus group [n = 58 (40.8%)], streptococcus group [n = 51 (35.9%)] and Enterococcus species [n = 13 (9.2%)]. staphylococcus infection was highest in the HCAIE group. In-hospital death occurred in 65 (35.7%) patients. In-hospital surgery was performed for 36 (19.8%) patients. At least one complication was documented in 163 (85.7%). CONCLUSION: Staphylococcus is the new etiologic champion, reflecting the transition of the healthcare system. Streptococcus is still an important culprit organism. The incidence rate of IE appears to be increasing. The rate of patients with underlying rheumatic heart disease is still high.

Prophylactic platelet transfusion plus supportive care versus supportive care alone in adults with dengue and thrombocytopenia: a multicentre, open-label, randomised, superiority trial.

BACKGROUND: Dengue is the commonest vector-borne infection worldwide. It is often associated with thrombocytopenia, and prophylactic platelet transfusion is widely used despite the dearth of robust evidence. We aimed to assess the efficacy and safety of prophylactic platelet transfusion in the prevention of bleeding in adults with dengue and thrombocytopenia. METHODS: We did an open-label, randomised, superiority trial in five hospitals in Singapore and Malaysia. We recruited patients aged at least 21 years who had laboratory-confirmed dengue (confirmed or probable) and thrombocytopenia (≤20 000 platelets per µL), without persistent mild bleeding or any severe bleeding. Patients were assigned (1:1), with randomly permuted block sizes of four or six and stratified by centre, to receive prophylactic platelet transfusion in addition to supportive care (transfusion group) or supportive care alone (control group). In the transfusion group, 4 units of pooled platelets were given each day when platelet count was 20 000 per µL or lower; supportive care consisted of bed rest, fluid therapy, and fever and pain medications. The primary endpoint was clinical bleeding (excluding petechiae) by study day 7 or hospital discharge (whichever was earlier), analysed by intention to treat. Safety outcomes were analysed according to the actual treatment received. This study was registered with ClinicalTrials.gov, number NCT01030211, and is completed. FINDINGS: Between April 29, 2010, and Dec 9, 2014, we randomly assigned 372 patients to the transfusion group (n=188) or the control group (n=184). The intention-to-treat analysis included 187 patients in the transfusion group (one patient was withdrawn immediately) and 182 in the control group (one was withdrawn immediately and one did not have confirmed or probable dengue). Clinical bleeding by day 7 or hospital discharge occurred in 40 (21%) patients in the transfusion group and 48 (26%) patients in the control group (risk difference -4·98% [95% CI -15·08 to 5·34]; relative risk 0·81 [95% CI 0·56 to 1·17]; p=0·16). 13 adverse events occurred in the transfusion group and two occurred in the control group (5·81% [-4·42 to 16·01]; 6·26 [1·43 to 27·34]; p=0·0064). Adverse events that were possibly, probably, or definitely related to transfusion included three cases of urticaria, one maculopapular rash, one pruritus, and one chest pain, as well as one case each of anaphylaxis, transfusion-related acute lung injury, and fluid overload that resulted in serious adverse events. No death was reported. INTERPRETATION: In adult patients with dengue and thrombocytopenia, prophylactic platelet transfusion was not superior to supportive care in preventing bleeding, and might be associated with adverse events. FUNDING: National Medical Research Council, Singapore.

Relapse of chronic melioidosis in a paediatric cystic fibrosis patient: first case report from Malaysia.

BACKGROUND: Burkholderia pseudomallei is the causative agent of melioidosis, which is a potentially life threatening disease endemic in Southeast Asian countries. In Malaysia, cystic fibrosis (CF) is an uncommon condition. The association between CF and B.pseudomallei infections has been reported previously. However, this is the first case report of a pediatric melioidosis relapse and co-infection with other Gram-negative bacteria in Malaysia. CASE PRESENTATION: A 14-year-old Chinese Malaysian boy presented with a history of recurrent pneumonia, poor growth and steatorrhoea since childhood, and was diagnosed with CF. B. pseudomallei was cultured from his sputum during three different admissions between 2013 and 2016. However, the patient succumbed to end stage of respiratory failure in 2017 despite antibiotics treatment against B.pseudomallei. The isolates were compared using multilocus-sequence typing and repetitive-element polymerase chain reaction (PCR), and confirmed that two of the isolates were of same sequence type, which may indicate relapse. CONCLUSIONS: CF patients should be aware of melioidosis in endemic regions, as it is an emerging infectious disease, especially when persistent or recurrent respiratory symptoms and signs of infection occur. The high prevalence rates of melioidosis in Malaysia warrants better management options to improve quality of life, and life expectancy in patients with CF. Travel activities to endemic regions should also be given more consideration, as this would be crucial to identify and initiate appropriate empiric treatment.

Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection and the molecular characteristics of MRSA bacteraemia over a two-year period in a tertiary teaching hospital in Malaysia.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an established pathogen that causes hospital- and community-acquired infections worldwide. The prevalence rate of MRSA infections were reported to be the highest in Asia. As there is limited epidemiological study being done in Malaysia, this study aimed to determine the prevalence of MRSA infection and the molecular characteristics of MRSA bacteraemia. METHODS: Two hundred and nine MRSA strains from year 2011 to 2012 were collected from a tertiary teaching hospital in Malaysia. The strains were characterized by antimicrobial susceptibility testing, staphylococcal cassette chromosome mec (SCCmec) typing, detection of Panton-Valentine leukocidin (PVL) gene, multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Patient's demographic and clinical data were collected and correlated with molecular data by statistical analysis. RESULTS: Male gender and patient >50 years of age (p < 0.0001) were significantly associated with the increased risk of MRSA acquisition. Fifty-nine percent of MRSA strains were HA-MRSA that carried SCCmec type II, III, IV and V while 31% were CA-MRSA strains with SCCmec III, IV and V. The prevalence of PVL gene among 2011 MRSA strains was 5.3% and no PVL gene was detected in 2012 MRSA strains. All of the strains were sensitive to vancomycin. However, vancomycin MIC creep phenomenon was demonstrated by the increased number of MRSA strains with MIC ≥1.5 µg/mL (p = 0.008) between 2011 and 2012. Skin disease (p = 0.034) and SCCmec type III (p = 0.0001) were found to be significantly associated with high vancomycin MIC. Forty-four percent of MRSA strains from blood, were further subtyped by MLST and PFGE. Most of the bacteraemia cases were primary bacteraemia and the common comorbidities were diabetes, hypertension and chronic kidney disease. The predominant pulsotype was pulsotype C exhibited by SCCmec III-ST239. This is a first study in Malaysia that reported the occurrence of MRSA clones such as SCCmec V-ST5, untypeable-ST508, SCCmec IV-ST1 and SCCmec IV-ST1137. CONCLUSIONS: SCCmec type III remained predominant among the MRSA strains in this hospital. The occurrence of SCCmec IV and V among hospital strains and the presence of SCCmec III in CA-MRSA strains are increasing. MRSA strains causing bacteraemia over the two-year study period were found to be genetically diverse.

Concurrent loss of co-stimulatory molecules and functional cytokine secretion attributes leads to proliferative senescence of CD8(+) T cells in HIV/TB co-infection.

The role of T-cell immunosenescence and functional CD8(+) T-cell responses in HIV/TB co-infection is unclear. We examined and correlated surrogate markers of HIV disease progression with immune activation, immunosenescence and differentiation using T-cell pools of HIV/TB co-infected, HIV-infected and healthy controls. Our investigations showed increased plasma viremia and reduced CD4/CD8 T-cell ratio in HIV/TB co-infected subjects relative to HIV-infected, and also a closer association with changes in the expression of CD38, a cyclic ADP ribose hydrolase and CD57, which were consistently expressed on late-senescent CD8(+) T cells. Up-regulation of CD57 and CD38 were directly proportional to lack of co-stimulatory markers on CD8(+) T cells, besides diminished expression of CD127 (IL-7Rα) on CD57(+)CD4(+) T cells. Notably, intracellular IFN-γ, perforin and granzyme B levels in HIV-specific CD8(+) T cells of HIV/TB co-infected subjects were diminished. Intracellular CD57 levels in HIV gag p24-specific CD8(+) T cells were significantly increased in HIV/TB co-infection. We suggest that HIV-TB co-infection contributes to senescence associated with chronic immune activation, which could be due to functional insufficiency of CD8(+) T cells.

Molecular diversity of HIV-1 and surveillance of transmitted drug resistance variants among treatment Naïve patients, 5 years after active introduction of HAART in Kuala Lumpur, Malaysia.

Expansion of antiretroviral treatment programs have led to the growing concern for the development of antiretroviral drug resistance. The aims were to assess the prevalence of drug resistant HIV-1 variants and to identify circulating subtypes among HAART-naïve patients. Plasma specimens from N = 100 HIV+ HAART-naïve adult were collected between March 2008 and August 2010 and viral RNA were extracted for nested PCR and sequenced. PR-RT sequences were protein aligned and checked for transmitted drug resistance mutations. Phylogenetic reconstruction and recombination analysis were performed to determine the genotypes. Based on the WHO consensus guidelines, none of the recruited patients had any transmitted drug resistance mutations. When analyzed against the Stanford guidelines, 35% of patients had at least one reported mutation that may reduce drug susceptibility to PI (24%), NRTI (5%), and NNRTI (14%). The commonly detected mutation that may affect current first line therapy was V179D (3%), which may lead to reduced susceptibility to NNRTI. The predominant circulating HIV-1 genotypes were CRF01_AE (51%) and CRF33_01B (17%). The prevalence of unique recombinant forms (URF) was 7%; five distinct recombinant structures involving CRF01_AE and subtype B' were observed, among them a cluster of three isolates that could form a novel circulating recombinant form (CRF) candidate. Transmitted drug resistance prevalence among HAART-naïve patients was low in this cohort of patients in Kuala Lumpur despite introduction of HAART 5 years ago. Owing to the high genetic diversity, continued molecular surveillance can identify the persistent emergence of HIV-1 URF and novel CRF with significant epidemiological impact.

Severe Plasmodium falciparum infection mimicking acute myocardial infarction.

This case report describes a case of presumed acute myocardial infarction in a returned traveler who was later diagnosed to have severe malaria. Emergency coronary angiography was normal and subsequent peripheral blood film was positive for Plasmodium falciparum.

Occurrence and characterization of Candida nivariensis from a culture collection of Candida glabrata clinical isolates in Malaysia.

BACKGROUND: Candida nivariensis and C. bracarensis have been recently identified as emerging yeast pathogens which are phenotypically indistinguishable from C. glabrata. However, there is little data on the prevalence and antifungal susceptibilities of these species. OBJECTIVE: This study investigated the occurrence of C. nivariensis and C. bracarensis in a culture collection of 185 C. glabrata isolates at a Malaysian teaching hospital. METHODS: C. nivariensis was discriminated from C. glabrata using a PCR assay as described by Enache-Angoulvant et al. (J Clin Microbiol 49:3375-9, 2011). The identity of the isolates was confirmed by sequence analysis of the D1D2 domain and internal transcribed spacer region of the yeasts. The isolates were cultured on Chromogenic CHROMagar Candida (®) agar (Difco, USA), and their biochemical and enzymic profiles were determined. Antifungal susceptibilities of the isolates against amphotericin B, fluconazole, voriconazole and caspofungin were determined using E tests. Clotrimazole MICs were determined using a microbroth dilution method. RESULTS: There was a low prevalence (1.1 %) of C. nivariensis in our culture collection of C. glabrata. C. nivariensis was isolated from a blood culture and vaginal swab of two patients. C. nivariensis grew as white colonies on Chromogenic agar and demonstrated few positive reactions using biochemical tests. Enzymatic profiles of the C. nivariensis isolates were similar to that of C. glabrata. The isolates were susceptible to amphotericin B, fluconazole, voriconazole and caspofungin. Clotrimazole resistance is suspected in one isolate. CONCLUSION: This study reports for the first time the emergence of C. nivariensis in our clinical setting.

Study of the Practice of Surgical Antibiotic Prophylaxis Use for Elective Neurosurgical Cases in a Tertiary Hospital and Understanding the Rationale.

BACKGROUND: This study aims to evaluate the adherence to surgical antibiotic prophylaxis (SAP) guidelines in elective neurosurgery and assess the impact on surgical site infection (SSI) rates in a tertiary teaching hospital in Malaysia. METHOD: A retrospective review was conducted on patients who underwent elective neurosurgical procedures from January 1, 2021, to December 31, 2021, in a 1600-bed tertiary teaching hospital. The study assessed adherence to national and hospital SAP guidelines, focusing on the choice of antibiotic, dosage, timing, and duration. Additionally, a survey was conducted among neurosurgeons to evaluate their knowledge, attitudes, and practices regarding SAP. RESULT: Out of 202 patients included, there was a 99% compliance rate with antibiotic choice and 69.8% with the antibiotic duration. The SSI rate was identified at 6.4%. The knowledge, attitudes, and practices survey highlighted a strong awareness of SAP guidelines among surgeons, albeit with variations in practice, particularly in antibiotic duration and choice of antibiotics. CONCLUSIONS: While there is high adherence to the correct choice of antibiotic for SAP in elective neurosurgery, there are gaps in compliance with the recommended duration of antibiotic use. The study highlights the need for targeted interventions to improve adherence to SAP guidelines, which could potentially reduce the incidence of SSI in neurosurgery. Ongoing education and auditing are essential to optimize SAP practices and enhance patient outcomes in neurosurgery.

A visualized hybrid PCR-LAMP assay for the detection of human Plasmodium species.

Combining the advantages of PCR and LAMP, we described a new technique, namely PCR-LAMP, for malaria diagnosis. The whole process of DNA amplification can be completed in 35 min. This hybrid amplification technique markedly improved the sensitivity of detection compared to the classic single PCR or LAMP assay alone. PCR-LAMP assay had a detection limit of 1 copy/µL for P. knowlesi and P. ovale, 0.1 copy/µL for P. vivax, P. falciparum and P. malariae, respectively. To facilitate the endpoint detection, xylenol orange was added. Positive samples were indicated in orange while negative reactions were violet. The inclusion of xylenol orange into the LAMP reaction mix significantly reduces the post-amplification workload. Without relying on the use of specific instruments, the color changes of the amplicons could be visualized directly through the naked eye. In conclusion, PCR-LAMP poses the potential to be developed as a new malaria molecular diagnosis tool.

Investigation on the mechanisms of carbapenem resistance among the non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae.

Background: In Malaysia, an increase in non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae (NC-CRKP) has been observed over the years. Previously, four NC-CRKP with increased susceptibility to ciprofloxacin in the presence of phenylalanine-arginine ß-naphthylamide (PAßN) were identified. However, no contribution of the PAßN-inhibited efflux pump to carbapenem resistance was observed. All four NC-CRKP harboured non-carbapenemase ß-lactamase, with two also exhibiting porin loss. In this study, we further investigated the genomic features and resistance mechanisms of these four isolates. Methods: All four NC-CRKP were subjected to whole-genome sequencing, followed by comparative genomic and phylogenetic analyses. Results: Multi-locus sequence typing (MLST) analysis divided the four NC-CRKP into different sequence types: ST392, ST45, ST14, and ST5947. Neither major nor rare carbapenemase genes were detected. Given the presence of non-carbapenemase ß-lactamase in all isolates, we further investigated the potential mechanisms of resistance by identifying related chromosomal mutations. Deletion mutation was detected in the cation efflux system protein CusF. Insertion mutation was identified in the nickel/cobalt efflux protein RcnA. Missense mutation of ompK36 porin was detected in two isolates, while the loss of ompK36 porin was observed in another two isolates. Conclusions: This study revealed that NC-CRKP may confer carbapenem resistance through a combination of non-carbapenemase ß-lactamase and potential chromosomal mutations including missense mutation or loss of ompK36 porin and/or a frameshift missense mutation in efflux pump systems, such as cation efflux system protein CusF and nickel/cobalt efflux protein RcnA. Our findings highlighted the significance of implementing whole-genome sequencing into clinical practice to promote the surveillance of carbapenem resistance mechanisms among NC-CRKP.