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1.
Artigo em Inglês | MEDLINE | ID: mdl-38156208

RESUMO

The COVID-19 pandemic led to an initial increase in the incidence of carbapenem-resistant Enterobacterales (CRE) from clinical cultures in South-East Asia hospitals, which was unsustained as the pandemic progressed. Conversely, there was a decrease in CRE incidence from surveillance cultures and overall combined incidence. Further studies are needed for future pandemic preparedness.

2.
J Med Virol ; 95(11): e29204, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37937705

RESUMO

The Omicron variant has been reported to present with milder disease compared with Delta, although this may be due to immunity from vaccination and prior exposure. Predictors of severity with recent strains have not been well characterized. We retrospectively examined consecutive cases of moderate-to-severe COVID-19 (defined as requiring supplemental oxygenation, intensive care or mortality) admitted to seven tertiary hospitals across Singapore in April 2023. Whole genome sequencing was performed on each isolate to determine the sublineage, while baseline clinical, laboratory data and outcomes were tabulated. We reviewed 182 patients with moderate-to-severe illness and 466 controls hospitalized at the same time. Advanced age and presence of chronic kidney disease predicted adverse outcome. Previously reported markers such as radiographic evidence of pneumonia, elevated C-reactive protein and serum creatinine levels at presentation also correlated with adverse outcomes. There were no observable differences in outcomes with any specific Omicron XBB sublineage. We did not find any specific Omicron XBB sublineage that was associated with worse outcomes. Larger multinational studies would be important to track the clinical evolution of the virus in its current endemic state.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , Gravidade do Paciente , Estudos Retrospectivos , SARS-CoV-2/genética
3.
BMC Infect Dis ; 23(1): 93, 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36788516

RESUMO

OBJECTIVES: The objectives of this study were to describe the coronavirus disease caused by SARS-CoV-2 (COVID-19) reinfection evaluation algorithm used in the early phase of the pandemic in Singapore and analyze the clinical and laboratory characteristics of the cases evaluated. METHODS: We performed a retrospective case-control analysis including all COVID-19 cases evaluated for possible reinfection under the local COVID-19 reinfection evaluation programme between 1 June 2020-30 June 2021. Whole genome sequencing (WGS) was used as confirmatory testing. We compared all reinfection ("RI") cases against those who were evaluated but eventually assessed not to be reinfection ("non-RI"). RESULTS: There were 74 possible reinfection cases evaluated through the programme, of which 32 were subsequently classified as RI. There was strong statistical evidence that RI cases had a longer interval between 1st and 2nd episode (mean 297 days; 95%-confidence interval (CI) 267-327) compared to non-RI cases (mean 186 days; 95%-CI 144-228). The cycle threshold (Ct) value of initial polymerase chain rection (PCR) at 2nd episode was also found to be significantly lower in RI cases (mean 23; 95%-CI 20-26) compared to non-RI cases (mean 34; 95%-CI 32-36). There was no significant difference in the proportion of individuals who had fever, acute respiratory symptoms or asymptomatic in both groups. Delta and beta variants were most commonly identified from WGS and provide indication of re-infection as these were not 'wild-type' and were not circulating during the time period of the index infection. CONCLUSIONS: Using a combination of serologic, microbiologic and genomic criteria to evaluate possible reinfection cases is useful and can provide a framework for evaluation that may be modified for future similar situations.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2/genética , Pandemias , Reinfecção/diagnóstico , Reinfecção/epidemiologia , Estudos Retrospectivos , Singapura/epidemiologia
4.
Nat Commun ; 13(1): 3052, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35650193

RESUMO

Carbapenemase-producing Enterobacterales (CPE) infection control practices are based on the paradigm that detected carriers in the hospital transmit to other patients who stay in the same ward. The role of plasmid-mediated transmission at population level remains largely unknown. In this retrospective cohort study over 4.7 years involving all multi-disciplinary public hospitals in Singapore, we analysed 779 patients who acquired CPE (1215 CPE isolates) detected by clinical or surveillance cultures. 42.0% met putative clonal transmission criteria, 44.8% met putative plasmid-mediated transmission criteria and 13.2% were unlinked. Only putative clonal transmissions associated with direct ward contact decreased in the second half of the study. Both putative clonal and plasmid-mediated transmission associated with indirect (no temporal overlap in patients' admission period) ward and hospital contact did not decrease during the study period. Indirect ward and hospital contact were identified as independent risk factors associated with clonal transmission. In conclusion, undetected CPE reservoirs continue to evade hospital infection prevention measures. New measures are needed to address plasmid-mediated transmission, which accounted for 50% of CPE dissemination.


Assuntos
Infecções por Enterobacteriaceae , Gammaproteobacteria , Proteínas de Bactérias , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/transmissão , Gammaproteobacteria/genética , Humanos , Estudos Retrospectivos , Sequenciamento Completo do Genoma , beta-Lactamases/genética
5.
Singapore Med J ; 63(12): 715-722, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34157808

RESUMO

Introduction: The majority of patients with COVID-19 infection do not progress to pneumonia. We report emergency department (ED)-specific variables and evaluate their predictive performance on diagnosis of pneumonia, intensive care unit (ICU) admission and death. Methods: This was a retrospective, single-centre cohort study of confirmed COVID-19 patients admitted to a Singapore tertiary hospital. Primary outcome was diagnosis of COVID-19 pneumonia. Secondary outcomes were ICU admission and/or death. Multivariate logistic regression was used to analyse the predictive performance of ED-specific variables. Accuracy of continuous variables was measured by area under receiver operating characteristic (ROC) curve. Results: 294 patients were included. Patients with pneumonia were older (52.0 years, P < 0.001) and had higher C-reactive protein (CRP; 33.8 mg/L, P < 0.001). Patients with indeterminate chest radiograph (CRX) findings were at risk of pneumonia vs. patients with normal CRX (37.5% vs. 4.3%, P < 0.001). Patients admitted to ICU were older (60.0 years, P < 0.001) and had higher CRP (40.0 mg/L, P < 0.001). Diagnosis of COVID-19 pneumonia was associated with ICU admission and death (30.0% vs 0.39%, P < 0.001). Multivariate logistic regression analysis showed that age (aOR 1.07, P = 0.049), CRP (aOR 1.05, P = 0.006) and CRX findings (aOR 50.00, P < 0.001) had increased odds of pneumonia. ROC curve analysis showed that CRP of 23.3 mg/L was the optimal cut-off for predicting pneumonia. Conclusion: Older age, higher CRP and CRX findings are associated with COVID-19 pneumonia, ICU admission and death. Prospective studies should be undertaken to validate these findings.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Estudos de Coortes , Estudos Retrospectivos , Estudos Prospectivos , Unidades de Terapia Intensiva , Curva ROC , Serviço Hospitalar de Emergência
7.
J Med Virol ; 93(5): 3023-3032, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33527464

RESUMO

Diabetes is a risk factor for developing severe COVID-19, but the pathogenesis remains unclear. We investigated if the association of diabetes and COVID-19 severity may be mediated by inflammation. We also hypothesized that this increased risk may extend to prediabetes. Hospitalized patients in Singapore with COVID-19 were subdivided into three groups in a retrospective cohort: normoglycemia (HbA1c: ≤5.6%), prediabetes (HbA1c: 5.7%-6.4%) and diabetes (HbA1c: ≥6.5%). The primary outcome of severe COVID-19 was defined by respiratory rate ≥30, SpO2 ≤93% or intensive care unit admission. The association between clinical factors on severe COVID-19 outcome was analyzed by cox regression. Adjusted mediation analysis of C-reactive protein (CRP) on the relationship between diabetes and severe COVID-19 was performed. Of 1042 hospitalized patients, mean age 39 ± 11 years, 13% had diabetes, 9% prediabetes and 78% normoglycemia. Severe COVID-19 occurred in 4.9% of subjects. Compared to normoglycemia, diabetes was significantly associated with severe COVID-19 on both univariate (hazard ratio [HR]: 9.94; 95% confidence interval [CI]: 5.54-17.84; p < .001) and multivariate analysis (HR: 3.99; 95% CI: 1.92-8.31; p < .001), while prediabetes was not a risk factor (HR: 0.94; 95% CI: 0.22-4.03; p = .929). CRP, a biomarker of inflammation, mediated 32.7% of the total association between diabetes and severe COVID-19 outcome. In conclusion, CRP is a partial mediator of the association between diabetes and severe COVID-19 infection, confirming that inflammation is important in the pathogenesis of severe COVID-19 in diabetes.


Assuntos
Proteína C-Reativa/metabolismo , COVID-19/diagnóstico , COVID-19/epidemiologia , Diabetes Mellitus/epidemiologia , Adulto , Biomarcadores/sangue , COVID-19/sangue , Diabetes Mellitus/sangue , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Singapura/epidemiologia
8.
Open Forum Infect Dis ; 7(11): ofaa486, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33235888

RESUMO

This is a retrospective cohort study of hospitalized adults with coronavirus disease 2019 (COVID-19). Fifty-seven patients received treatment alone, and 35 patients received treatment with adjunctive prednisolone. A combination of corticosteroids and antivirals was associated with lower risk of clinical progression and invasive mechanical ventilation or death in early COVID-19 pneumonia.

9.
Sci Rep ; 10(1): 18219, 2020 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106525

RESUMO

Central nervous system (CNS) infections cause substantial morbidity and mortality worldwide, with mounting concern about new and emerging neurologic infections. Stratifying etiologies based on initial clinical and laboratory data would facilitate etiology-based treatment rather than relying on empirical treatment. Here, we report the epidemiology and clinical outcomes of patients with CNS infections from a prospective surveillance study that took place between 2013 and 2016 in Singapore. Using multiple correspondence analysis and random forest, we analyzed the link between clinical presentation, laboratory results, outcome and etiology. Of 199 patients, etiology was identified as infectious in 110 (55.3%, 95%-CI 48.3-62.0), immune-mediated in 10 (5.0%, 95%-CI 2.8-9.0), and unknown in 79 patients (39.7%, 95%-CI 33.2-46.6). The initial presenting clinical features were associated with the prognosis at 2 weeks, while laboratory-related parameters were related to the etiology of CNS disease. The parameters measured were helpful to stratify etiologies in broad categories, but were not able to discriminate completely between all the etiologies. Our results suggest that while prognosis of CNS is clearly related to the initial clinical presentation, pinpointing etiology remains challenging. Bio-computational methods which identify patterns in complex datasets may help to supplement CNS infection diagnostic and prognostic decisions.


Assuntos
Antígenos de Bactérias/análise , Antígenos de Fungos/análise , Antígenos Virais/análise , Infecções do Sistema Nervoso Central/complicações , Doenças Transmissíveis/diagnóstico , Idoso , Infecções do Sistema Nervoso Central/microbiologia , Doenças Transmissíveis/classificação , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/etiologia , Interpretação Estatística de Dados , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Singapura/epidemiologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-31383670

RESUMO

Carbapenem-resistant Enterobacteriaceae (CRE) can be mechanistically classified into carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing carbapenem nonsusceptible Enterobacteriaceae (NCPCRE). We sought to investigate the effect of antecedent carbapenem exposure as a risk factor for NCPCRE versus CPE. Among all patients with CRE colonization and infection, we conducted a case-control study comparing patients with NCPCRE (cases) and patients with CPE (controls). The presence of carbapenemases was investigated with phenotypic tests followed by PCR for predominant carbapenemase genes. We included 843 unique patients with first-episode CRE, including 387 (45.9%) NCPCRE and 456 (54.1%) CPE. The resistance genes detected in CPEs were blaNDM (42.8%), blaKPC (38.4%), and blaOXA-48-like (12.1%). After adjusting for confounders and clustering at the institutional level, the odds of prior 30-day carbapenem exposure was three times higher among NCPCRE than CPE patients (adjusted odds ratio [aOR], 3.48; 95% confidence interval [CI], 2.39 to 5.09; P < 0.001). The odds of prior carbapenem exposure and NCPCRE detection persisted in stratified analyses by Enterobacteriaceae species (Klebsiella pneumoniae and Escherichia coli) and carbapenemase gene (blaNDM and blaKPC). CPE was associated with male gender (aOR, 1.45; 95% CI, 1.07 to 1.97; P = 0.02), intensive care unit stay (aOR, 1.84; 95% CI, 1.24 to 2.74; P = 0.003), and hospitalization in the preceding 1 year (aOR, 1.42; 95% CI, 1.01 to 2.02; P = 0.05). In a large nationwide study, antecedent carbapenem exposure was a significant risk factor for NCPCRE versus CPE, suggesting a differential effect of antibiotic selection pressure.


Assuntos
Antibacterianos/efeitos adversos , Proteínas de Bactérias/metabolismo , Carbapenêmicos/efeitos adversos , Enterobacteriaceae/efeitos dos fármacos , beta-Lactamases/metabolismo , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/metabolismo , Estudos de Casos e Controles , Enterobacteriaceae/metabolismo , Infecções por Enterobacteriaceae/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Feminino , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana/métodos , Fatores de Risco
11.
Front Pharmacol ; 10: 641, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244657

RESUMO

Background: Chronic kidney disease (CKD) patients requiring intravenous vancomycin bear considerable risks of adverse outcomes both from the infection and vancomycin therapy itself, necessitating especially precise dosing to avoid sub- and supratherapeutic vancomycin exposure. Methods: In this retrospective study, we performed a population pharmacokinetic analysis to construct a vancomycin dose prediction model for CKD patients who do not require renal replacement therapy. The model was externally validated on an independent cohort of patients to assess its prediction accuracy. The pharmacokinetic parameter estimates and the equations were productized into a Web application (VancApp) subsequently implemented in routine care. The association between VancApp-based dosing and time-to-target concentration attainment, 30-day mortality, and nephrotoxicity were assessed postimplementation. Results: The model constructed from an initial cohort (n = 80) revealed a population clearance and volume of distribution of 1.30 L/h and 1.23 L/kg, respectively. External model validation (n = 112) demonstrated a mean absolute prediction error of 1.25 mg/L. Following 4 months of clinical implementation of VancApp as an optional alternative to usual care [VancApp (n = 22) vs. usual care (n = 21)], patients who had received VancApp-based dosing took a shorter time to reach target concentrations (median: 66 vs. 102 h, p = 0.187) and had fewer 30-day mortalities (14% vs. 24%, p = 0.457) compared to usual care. While statistical significance was not achieved, the clinical significance of these findings appear promising. Conclusion: Clinical implementation of a population pharmacokinetic model for vancomycin in CKD can potentially improve dosing precision in CKD and could serve as a practical means to improve vital clinical outcomes.

12.
Clin Infect Dis ; 64(suppl_2): S61-S67, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28475790

RESUMO

BACKGROUND: We conducted a national point prevalence survey (PPS) to determine the prevalence of healthcare-associated infections (HAIs) and antimicrobial use (AMU) in Singapore acute-care hospitals. METHODS: Trained personnel collected HAI, AMU, and baseline hospital- and patient-level data of adult inpatients from 13 private and public acute-care hospitals between July 2015 and February 2016, using the PPS methodology developed by the European Centre for Disease Prevention and Control. Factors independently associated with HAIs were determined using multivariable regression. RESULTS: Of the 5415 patients surveyed, there were 646 patients (11.9%; 95% confidence interval [CI], 11.1%-12.8%) with 727 distinct HAIs, of which 331 (45.5%) were culture positive. The most common HAIs were unspecified clinical sepsis (25.5%) and pneumonia (24.8%). Staphylococcus aureus (12.9%) and Pseudomonas aeruginosa (11.5%) were the most common pathogens implicated in HAIs. Carbapenem nonsusceptibility rates were highest in Acinetobacter species (71.9%) and P. aeruginosa (23.6%). Male sex, increasing age, surgery during current hospitalization, and presence of central venous or urinary catheters were independently associated with HAIs. A total of 2762 (51.0%; 95% CI, 49.7%-52.3%) patients were on 3611 systemic antimicrobial agents; 462 (12.8%) were prescribed for surgical prophylaxis and 2997 (83.0%) were prescribed for treatment. Amoxicillin/clavulanate was the most frequently prescribed (24.6%) antimicrobial agent. CONCLUSIONS: This survey suggested a high prevalence of HAIs and AMU in Singapore's acute-care hospitals. While further research is necessary to understand the causes and costs of HAIs and AMU in Singapore, repeated PPSs over the next decade will be useful to gauge progress at controlling HAIs and AMU.


Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Fatores Etários , Idoso , Combinação Amoxicilina e Clavulanato de Potássio/administração & dosagem , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Carbapenêmicos/farmacologia , Infecção Hospitalar/tratamento farmacológico , Feminino , Cirurgia Geral , Inquéritos Epidemiológicos , Hospitais , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/estatística & dados numéricos , Prevalência , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Fatores Sexuais , Singapura/epidemiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação
13.
Clin Infect Dis ; 64(suppl_2): S68-S75, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28475792

RESUMO

BACKGROUND: Since 2010, the incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing in Singapore. We analyzed the clinical and molecular epidemiology of CRE among adult inpatients in Singapore. METHODS: Quarterly incidence of unique subjects (per 100000 patient-days) with positive clinical and surveillance cultures for CRE were estimated based on mandatory data submitted to the National Public Health Laboratory by public hospitals between 2010 and 2015. CRE-positive adult inpatients were prospectively recruited from 6 public sector hospitals between December 2013 and April 2015. Subjects answered a standardized epidemiologic questionnaire and provided samples for this study. Further clinical information was extracted from subjects' electronic medical records. Whole-genome sequencing was performed on study isolates to determine transmission clusters. RESULTS: Incidence of CRE clinical cultures among adult inpatients plateaued from 2013 (range: 7.73 to 10.32 per 100000 patient-days) following an initial increase between 2010 and end-2012. We prospectively recruited 249 subjects. Their median age was 65 years, 108 (43%) were female, and 161 (64.7%) had carbapenemase-producing Enterobacteriaceae (CPE). On multivariate analysis, prior carbapenem exposure (OR: 3.23; 95% CI: 1.67-6.25) and hematological malignancies (OR: 2.85; 95% CI: 1.10-7.41) were associated with non-carbapenemase-producing CRE (NCPE) (n = 88) compared with CPE (n = 161) subjects. Among 430 CRE isolates from the 249 subjects, 307(71.3%) were CPE, of which 154(50.2%) were blaKPC-positive, 97(31.6%) blaNDM-positive, and 42 (13.7%) blaOXA-positive. Klebsiella pneumoniae (n = 180, 41.9%), Escherichia coli (n = 129, 30.0%) and Enterobacter cloacae (n = 62, 14.4%) were the main Enterobacteriaceae species. WGS (n = 206) revealed diverse bacterial strain type (STs). The predominant blaKPC-positive plasmid was pHS102707 (n = 62, 55.4%) and the predominant blaNDM-positive plasmid was pNDM-ECS01 (n = 46, 48.9%). Five transmission clusters involving 13 subjects were detected. CONCLUSIONS: Clinical CRE trend among adult inpatients showed stabilization following a rapid rise since introduction in 2010 potentially due to infection prevention measures and antimicrobial stewardship. More work is needed on understanding CPE transmission dynamics.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Infecção Hospitalar/epidemiologia , Infecções por Enterobacteriaceae/epidemiologia , Pacientes Internados , Adulto , Idoso , Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , DNA Bacteriano/genética , Registros Eletrônicos de Saúde , Enterobacter cloacae/genética , Enterobacter cloacae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/transmissão , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/epidemiologia , Feminino , Genoma Bacteriano , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Incidência , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Masculino , Inquéritos e Questionários , Adulto Jovem , Resistência beta-Lactâmica , beta-Lactamases/biossíntese , beta-Lactamases/genética
14.
J Antimicrob Chemother ; 71(11): 3081-3089, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27494913

RESUMO

OBJECTIVES: Owing to gene transposition and plasmid conjugation, New Delhi metallo-ß-lactamase (NDM) is typically identified among varied Enterobacteriaceae species and STs. We used WGS to characterize the chromosomal and plasmid molecular epidemiology of NDM transmission involving four institutions in Singapore. METHODS: Thirty-three Enterobacteriaceae isolates (collection years 2010-14) were sequenced using short-read sequencing-by-synthesis and analysed. Long-read single molecule, real-time sequencing (SMRTS) was used to characterize genetically a novel plasmid pSg1-NDM carried on Klebsiella pneumoniae ST147. RESULTS: In 20 (61%) isolates, blaNDM was located on the pNDM-ECS01 plasmid in the background of multiple bacterial STs, including eight K. pneumoniae STs and five Escherichia coli STs. In six (18%) isolates, a novel blaNDM-positive plasmid, pSg1-NDM, was found only in K. pneumoniae ST147. The pSg1-NDM-K. pneumoniae ST147 clone (Sg1-NDM) was fully sequenced using SMRTS. pSg1-NDM, a 90 103 bp IncR plasmid, carried genes responsible for resistance to six classes of antimicrobials. A large portion of pSg1-NDM had no significant homology to any known plasmids in GenBank. pSg1-NDM had no conjugative transfer region. Combined chromosomal-plasmid phylogenetic analysis revealed five clusters of clonal bacterial NDM-positive plasmid transmission, of which two were inter-institution clusters. The largest inter-institution cluster involved six K. pneumoniae ST147-pSg1-NDM isolates. Fifteen patients were involved in transmission clusters, of which four had ward contact, six had hospital contact and five had an unknown transmission link. CONCLUSIONS: A combined sequencing-by-synthesis and SMRTS approach can determine effectively the transmission clusters of blaNDM and genetically characterize novel plasmids. Plasmid molecular epidemiology is important to understanding NDM spread as blaNDM-positive plasmids can conjugate extensively across species and STs.


Assuntos
Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/enzimologia , Enterobacteriaceae/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Plasmídeos/isolamento & purificação , Análise de Sequência de DNA , beta-Lactamases/genética , Enterobacteriaceae/classificação , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/transmissão , Transferência Genética Horizontal , Instalações de Saúde , Humanos , Epidemiologia Molecular , Plasmídeos/classificação , Singapura/epidemiologia
15.
Hemodial Int ; 20(2): 253-60, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26486806

RESUMO

Ceftazidime is a cost-effective antimicrobial against Gram-negative pathogens associated with sepsis in end-stage renal disease (ESRD) hemodialysis patients with potential for wider use with the advent of ceftazidime-avibactam. Dosing ceftazidime post-hemodialysis appears attractive and convenient, but limited in vivo data on pharmacodynamic efficacy (PE) attainment, defined as >70% of the interdialytic period drug concentrations exceed susceptible pathogens minimal inhibitory concentrations (MICs) (%TMIC), warrants further assessment. We therefore evaluated PE and tolerability of 1 against 2 g regime in anuric ESRD patients on low-flux hemodialysis. Two doses of 1 or 2 g ceftazidime were administered post-hemodialysis prior to 48- and 72-hour interdialytic intervals in ESRD inpatients without active infections. Peak and trough concentrations (mg/L) were assayed using a validated liquid chromatography-tandem mass spectrometry method. Proportion of patients achieving PE for known pathogens with MICs ≤ 8 mg/L and adverse effects were assessed. Six (43%) and eight (57%) adult patients received 1 and 2 g dose, respectively. Median (25th-75th percentile), peak, 48- and 72-hour trough ceftazidime concentrations were 78 (60-98) vs. 158 (128-196), 37 (23-37) vs. 49 (39-71), and 13 (12-20) vs. 26 (21-41) mg/L, respectively, resulting in 100% TMIC for both doses. One patient on the 1-g dose experienced mild pruritus. Reliable and safe PE attainment over both 48- and 72-hour interdialytic interval was achievable with 1 g of ceftazidime dosed post-hemodialysis. The 2 g dose was equally effective and well tolerated but may not be necessary. These findings need validation in non-anuric patients, high-flux hemodialysis, and during avibactam co-administration.


Assuntos
Antibacterianos/uso terapêutico , Ceftazidima/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Diálise Renal/métodos , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Ceftazidima/administração & dosagem , Ceftazidima/farmacologia , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
16.
PLoS One ; 10(3): e0119485, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25790305

RESUMO

BACKGROUND: Southeast Asia is a potential locus for the emergence of novel influenza strains. However, information on influenza within the region is limited. OBJECTIVES: This study was to determine the proportion of influenza-like illness (ILI) caused by influenza A and B viruses in a university cohort in Singapore, identify important distinctive clinical features of influenza infection and potential factors associated with influenza infection compared with other causes of ILI. METHODOLOGY: A surveillance study was conducted from 2007 to 2009, at the University Health and Wellness Centre, National University of Singapore (NUS). Basic demographic information and nasopharyngeal swabs were collected from consenting students and staff with ILI, with Influenza A and B identified by both culture and molecular methods. RESULTS: Proportions of influenza A and B virus infections in subjects with ILI were 153/500 (30.6%) and 11/500 (2.2%) respectively. The predominant subtype was A/H1N1, including both the seasonal strain (20/153) and the pandemic strain (72/153). The clinical symptom of fever was more common in subjects with laboratory confirmed influenza than other ILIs. On-campus hostel residence and being a student (compared with staff) were associated with increased risk of laboratory confirmed influenza A/H1N1 2009 infection. CONCLUSIONS: This study provides a baseline prevalence of influenza infection within young adults in Singapore in a university setting. Potential risk factors, such as hostel residence, were identified, allowing for more targeted infection control measures in the event of a future influenza pandemic.


Assuntos
Influenza Humana/epidemiologia , Adulto , Estudos de Coortes , Demografia , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza B/genética , Vírus da Influenza B/isolamento & purificação , Influenza Humana/virologia , Masculino , Nasofaringe/virologia , Razão de Chances , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Singapura/epidemiologia , Universidades , Adulto Jovem
17.
Am J Trop Med Hyg ; 92(3): 620-4, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25548377

RESUMO

Patients with rickettsial infection may present with encephalitis or meningitis but neurologic involvement is rare in murine typhus. Here, we report two patients with Rickettsia typhi meningitis who presented with cranial neuropathy, presumably caused by two distinct disease processes. Recognition of the disease manifestations is important because rickettsial infections are potentially associated with significant morbidity. Simple effective treatments are available.


Assuntos
Doenças do Nervo Abducente/microbiologia , Meningites Bacterianas/microbiologia , Rickettsia typhi , Tifo Endêmico Transmitido por Pulgas/complicações , Adulto , Humanos , Masculino , Tifo Endêmico Transmitido por Pulgas/diagnóstico , Tifo Endêmico Transmitido por Pulgas/patologia
18.
Hemodial Int ; 18(1): 142-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23763574

RESUMO

There has been a paucity of literature on methicillin-resistant Staphylococcus aureus (MRSA) colonization in chronic hemodialysis patients who required admission. The purpose of this study is to determine the MRSA carriage rate in hospitalized chronic hemodialysis patients, to identify the risk factors, and assess the consequences of MRSA colonization. This was a retrospective study of hospitalized chronic hemodialysis patients at Khoo Teck Puat Hospital from July 1, 2010 to June 30, 2011. MRSA screening was done on the day of admission using culture method with MRSA select (Bio-Rad)™. The patients were divided into two groups: MRSA carriers and noncarriers. Demographic data, medical, and laboratory information was obtained via electronic medical record system. Outcome measures were infection rates during current hospitalization episode, frequency of hospitalization, and cumulative hospitalization days per year. Prevalence rate of MRSA colonization in hospitalized chronic hemodialysis patients was 15.1%, compared to all admitted patients (5.8%). Diabetes mellitus, Malay ethnicity, shorter hemodialysis duration and use of tunneled hemodialysis catheters were associated with MRSA colonization (P < 0.05). Relative risk of infection during the episode of admission among MRSA carriers was 3.2-fold compared to noncarriers. MRSA colonization rates tend to be higher in patients on hemodialysis for less than 3 years and it correlates with longer hospitalization after adjustment for other variables (P < 0.05). Patients on chronic hemodialysis requiring admission have higher rates of MRSA colonization. The risk factors of MRSA carriers and the correlation of MRSA rates to longer hospitalization suggest its nosocomial origin in this group of patients.


Assuntos
Registros Eletrônicos de Saúde , Doença Iatrogênica/epidemiologia , Staphylococcus aureus Resistente à Meticilina , Diálise Renal , Infecções Estafilocócicas/epidemiologia , Idoso , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Tempo
20.
Diagn Microbiol Infect Dis ; 55(1): 69-73, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16490338

RESUMO

We tracked cultures submitted to a laboratory in 2004 in which mycobacteria other than Mycobacterium tuberculosis or Mycobacterium avium complex were grown (n = 11). We reviewed clinical information, other mycobacterial cultures, and radiologic findings. We measured the time from specimen submission to first growth and to final species identification. We assessed the response to this information based on notes, laboratory tests, consultations, and radiology studies. The median time to identification was 68 days (47-292 days). In 5 cases, the clinician failed to retrieve the data, and in 3 of these cases, there was a resultant loss of opportunity to treat. In 3 cases, the laboratory never reported a definitive species, and in 3 cases, the culture results were clinically unimportant. We show that the results of positive cultures of these mycobacteria are effectively lost because they are not available in a timely fashion, and even when available, the results are overlooked.


Assuntos
Técnicas de Tipagem Bacteriana , Infecções por Mycobacterium/diagnóstico , Infecções por Mycobacterium/microbiologia , Mycobacterium/classificação , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Adolescente , Adulto , Idoso , Líquido da Lavagem Broncoalveolar/microbiologia , Sondas de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium/isolamento & purificação , Complexo Mycobacterium avium/isolamento & purificação , Mycobacterium tuberculosis/isolamento & purificação , Padrões de Prática Médica , Estudos Retrospectivos , Escarro/microbiologia , Fatores de Tempo
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