Discrepant serological findings in SARS-CoV-2 PCR-negative hospitalized patients with fever and acute respiratory symptoms during the pandemic.

Coronavirus Disease 2019 (COVID-19) serology has an evolving role in the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, its use in hospitalized patients with acute respiratory symptoms remains unclear. Hospitalized patients with acute respiratory illness admitted to an isolation ward were recruited. All patients had negative nasopharyngeal swab polymerase chain reaction (PCR) for SARS-CoV-2. Serological studies using four separate assays (cPass: surrogate neutralizing enzyme-linked immunosorbent assay [ELISA]; Elecsys: N-antigen based chemiluminescent assay; SFB: S protein flow-based; epitope peptide-based ELISA) were performed on stored plasma collected from patients during the initial hospital stay, and a convalescent visit 4-12 weeks later. Of the 51 patients studied (aged 54, interquartile range 21-84; 62.7% male), no patients tested positive on the Elecsys or cPass assays. Out of 51 patients, 5 had antibodies detected on B-cell Epitope Assay and 3/51 had antibodies detected on SFB assay. These 8 patients with positive serological test to COVID-19 were more likely to have a high-risk occupation (p = 0.039), bacterial infection (p = 0.028), and neutrophilia (p = 0.013) during their initial hospital admission. Discrepant COVID-19 serological findings were observed among those with recent hospital admissions and bacterial infections. The positive serological findings within our cohort raise important questions about the interpretation of sero-epidemiology during the current pandemic.

Risk Communication and Community Engagement During the Migrant Worker COVID-19 Outbreak in Singapore.

In early phases of the COVID-19 pandemic in Singapore, Risk Communication and Community Engagement (RCCE) with large, diverse communities of migrant workers living in high-density accommodation was slow to develop. By August 2020, Singapore had reported 55,661 cases of COVID-19, with migrant workers comprising 94.6% of the cases. A system of RCCE among migrant worker communities in Singapore was developed to maximize synergy in RCCE. Proactive stakeholder engagement and participatory approaches with affected communities were key to effective dissemination of scientific information about COVID-19 and its prevention.

Establishing a New Normal for Hospital Care: A Whole of Hospital Approach to Coronavirus Disease 2019 (COVID-19).

Singapore's hospitals had prepared to receive patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), planning various scenarios and levels of surge with a policy of isolating all confirmed cases as inpatients. The National University Hospital adopted a whole of hospital approach to coronavirus disease 2019 (COVID-19) with 3 primary goals: zero hospital-acquired COVID-19, all patients receive timely necessary care, and maintenance of staff morale. These goals to date have been met. A large influx of COVID-19 cases required significant transformation of clinical and operational processes. Isolation room numbers almost tripled and dedicated COVID-19 cohort wards were established, elective care was postponed, and intensive care units were augmented with equipment and manpower. In the wake of the surge, establishing a new normal for hospital care requires maintaining vigilance to detect endemic COVID-19, establishing contingency plans to ramp up in case of another surge, while returning to business as usual.

Training for outbreak response through the Global Outbreak Alert and Response Network.

For 20 years, the Global Outbreak Response and Alert Network (GOARN) has been a leader in the coordination of international outbreak response. On the premise that no single institution can provide all capacities required to successfully respond to a complex public health emergency or fulfil all outbreak response training needs, GOARN embarked on a capacity building journey that draws on the unique strengths of more than 250 partner institutions. Through extensive engagement and collaboration, GOARN Partners have created a bespoke, multifaceted, 3-tiered training programme which has evolved over the last 15 years and enhanced the competencies of thousands of multidisciplinary outbreak responders around the world.

MDRO transmission in acute hospitals during the COVID-19 pandemic.

PURPOSE OF REVIEW: The coronavirus disease (COVID-19) pandemic has resulted in necessary modifications of infection control policies and practices in acute healthcare facilities globally. This is often accompanied by infrastructure modifications, ward redesignations, as well as healthcare staff redeployments and changes to infection prevention and control (IPC) practices. We review the potential for both negative and positive impacts these major changes can have on nosocomial transmission of multidrug-resistant organisms (MDROs). RECENT FINDINGS: Healthcare facilities around the world have reported outbreaks of MDROs during the COVID-19 pandemic. In contrast some centres have reported a decrease in baseline rates due to a number of possible factors. SUMMARY: While implementing crucial preventive measures for COVID-19, is it important to consider any collateral effects of changes in IPC and antimicrobial stewardship program (ASP) practices. The disruption caused to IPC and ASP practices during the pandemic are likely to see a counter intuitive increase in transmission of MDROs.

Disinfection capabilities of a 222 nm wavelength ultraviolet lighting device: a pilot study.

OBJECTIVE: To demonstrate the efficacy of the SafeZone UVC (Ushio Inc., Japan) 222 nm ultraviolet C (UVC) light to reduce bacterial burden in pressure ulcers (PUs) in human patients. This research is the first human clinical trial using 222 nm UVC in eradicating bacteria in human wounds. METHOD: Patients with Stage 2 or 3 (as defined by the revised National Pressure Ulcer Advisory Panel Pressure Injury Staging System) sacral or gluteal pressure ulcers (PUs) were subjected to four sessions of 222 nm UVC light therapy over two weeks. Pre- and post-UVC therapy, wound cultures were taken and quantitative analysis of bacterial colony forming units (CFU) were performed. RESULTS: A total of 68 UV light sessions across 16 different patients were conducted. Of these sessions, 59 (87.0%) sessions showed a reduction in CFU counts, with 20 (29.4%) showing complete eradication of bacteria. Bacteria identified included meticillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella Pneumoniae. The overall median reduction in CFU of the 68 sessions was 78.9%. No adverse events were reported in any of the UV sessions. CONCLUSION: In this study, 222 nm UVC light was safe and effective in reducing bacterial CFU counts in sacral and gluteal PUs across numerous different species of bacteria.

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.

Oral vs Intravenous Antibiotics for Patients With Klebsiella pneumoniae Liver Abscess: A Randomized, Controlled Noninferiority Study.

BACKGROUND: Klebsiella pneumoniae liver abscess (KLA) is emerging worldwide due to hypermucoviscous strains with a propensity for metastatic infection. Treatment includes drainage and prolonged intravenous antibiotics. We aimed to determine whether oral antibiotics were noninferior to continued intravenous antibiotics for KLA. METHODS: This noninferiority, parallel group, randomized, clinical trial recruited hospitalized adults with liver abscess and K. pneumoniae isolated from blood or abscess fluid who had received ≤7 days of effective antibiotics at 3 sites in Singapore. Patients were randomized 1:1 to oral (ciprofloxacin) or intravenous (ceftriaxone) antibiotics for 28 days. If day 28 clinical response criteria were not met, further oral antibiotics were prescribed until clinical response was met. The primary endpoint was clinical cure assessed at week 12 and included a composite of absence of fever in the preceding week, C-reactive protein <20 mg/L, and reduction in abscess size. A noninferiority margin of 12% was used. RESULTS: Between November 2013 and October 2017, 152 patients (mean age, 58.7 years; 25.7% women) were recruited, following a median 5 days of effective intravenous antibiotics. A total of 106 (69.7%) underwent abscess drainage; 71/74 (95.9%) randomized to oral antibiotics met the primary endpoint compared with 72/78 (92.3%) randomized to intravenous antibiotics (risk difference, 3.6%; 2-sided 95% confidence interval, -4.9% to 12.8%). Effects were consistent in the per-protocol population. Nonfatal serious adverse events occurred in 12/72 (16.7%) in the oral group and 13/77 (16.9%) in the intravenous group. CONCLUSIONS: Oral antibiotics were noninferior to intravenous antibiotics for the early treatment of KLA. CLINICAL TRIALS REGISTRATION: NCT01723150.

Responding to COVID-19: how an academic infectious diseases division mobilized in Singapore.

BACKGROUND: On January 30, COVID-19 was declared a Public Health Emergency of International Concern-a week after Singapore's first imported case and 5 days before local transmission. The National University Hospital (NUH) is Singapore's third largest hospital with 1200 beds, heavy clinical workloads, and major roles in research and teaching. MAIN BODY: With memories of SARS still vivid, there was an urgent requirement for the NUH Division of Infectious Diseases to adapt-undergoing major reorganization to face rapidly changing priorities while ensuring usual essential services and standards. Leveraging on individual strengths, our division mobilized to meet the demands of COVID-19 while engaging in high-level coordination, strategy, and advocacy. We present our experience of the 60 days since the nation's first case. During this time, our hospital has managed 3030 suspect cases, including 1300 inpatients, 37 confirmed cases, and overseen 4384 samples tested for COVID-19. CONCLUSION: Complex hospital adaptations were supported by an unprecedented number of workflows and coordination channels essential to safe and effective operations. The actions we describe, aligned with international recommendations and emerging evidence-based best practices, may serve as a framework for other divisions and institutions facing the spread of COVID-19 globally.

Melioidosis, Singapore, 2003-2014.

In contrast with northern Australia and Thailand, in Singapore the incidence of melioidosis and co-incidence of melioidosis and pneumonia have declined. Burkholderia pseudomallei deep abscesses increased 20.4% during 2003-2014. These trends could not be explained by the environmental and climatic factors conventionally ascribed to melioidosis.

Distinguishing Zika and Dengue Viruses through Simple Clinical Assessment, Singapore.

Dengue virus and Zika virus coexist in tropical regions in Asia where healthcare resources are limited; differentiating the 2 viruses is challenging. We showed in a case-control discovery cohort, and replicated in a validation cohort, that the diagnostic indices of conjunctivitis, platelet count, and monocyte count reliably distinguished between these viruses.

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.

Prevalence of Healthcare-Associated Infections and Antimicrobial Use Among Adult Inpatients in Singapore Acute-Care Hospitals: Results From the First National Point Prevalence Survey.

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.

Clinical and Molecular Epidemiology of Carbapenem-Resistant Enterobacteriaceae Among Adult Inpatients in Singapore.

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.

Outpatient parenteral antibiotic therapy (OPAT) in Asia: missing an opportunity.

Objectives: Healthcare facilities internationally have grown outpatient parenteral antibiotic administration services for the last few decades. The literature contains publications from dozens of countries describing systematized processes with specialist oversight and their levels of service provision and outcomes. Such descriptions are absent in the majority of Asian countries. We sought to elucidate the extent and nature of outpatient parenteral antibiotic therapy (OPAT) in Asia and to consider the ramifications and opportunities for improvement. Methods: Utilizing colleagues and their personal networks, we surveyed healthcare facilities across 17 countries in Asia to ascertain the current means (if any) of providing OPAT. In that survey we also sought to explore the capacity and interest of these facilities in developing systematized OPAT services. Results: Responses were received from 171 different healthcare facilities from 17 countries. Most (97/171, 57%) stated that they administer outpatient parenteral antibiotics, but only 5 of 162 facilities (3%) outside of Singapore described comprehensive services with specialist oversight. Conclusions: There is very likely a large unrecognized problem of unchecked outpatient parenteral antibiotic administration in Asia. Developing comprehensive and systematized OPAT in Asia is needed as a priority in an environment in which the infectious diseases community is demanding broad stewardship approaches. There are nonetheless challenges in establishing and sustaining OPAT programmes. Local champions and leverage off identified local incentives and needs are key to regional advancement.

Type I IFNs and IL-18 regulate the antiviral response of primary human γδ T cells against dendritic cells infected with Dengue virus.

Little is known about the cellular mechanisms of innate immunity against dengue virus (DV) infection. Specifically, the γδ T cell response to DV has not been characterized in detail. In this article, we demonstrate that markers of activation, proliferation, and degranulation are upregulated on γδ T cells in PBMC isolated from individuals with acute dengue fever. Primary γδ T cells responded rapidly in vitro to autologous DV-infected dendritic cells by secreting IFN-γ and upregulating CD107a. The anti-DV IFN-γ response is regulated by type I IFN and IL-18 in a TCR-independent manner, and IFN-γ secreting γδ T cells predominantly expressed IL-18Rα. Antagonizing the ATP-dependent P2X7 receptor pathway of inflammasome activation significantly inhibited the anti-DV IFN-γ response of γδ T cells. Overnight priming with IL-18 produced effector γδ T cells with significantly increased ability to lyse autologous DV-infected dendritic cells. Monocytes were identified as accessory cells that augmented the anti-DV IFN-γ response of γδ T cells. Lack of monocytes in culture is associated with lower IL-18 levels in culture supernatant and diminished production of IFN-γ by γδ T cells, whereas addition of exogenous IL-18 restored the IFN-γ response of γδ T cells in monocyte-depleted cocultures with DV-infected DC. Our results indicate that primary γδ T cells contribute to the immune response during DV infection by providing an early source of IFN-γ, as well as by killing DV-infected cells, and suggest that monocytes participate as accessory cells that sense DV infection and amplify the cellular immune response against this virus in an IL-18-dependent manner.

Impact of inpatient Care in Emergency Department on outcomes: a quasi-experimental cohort study.

BACKGROUND: Hospitals around the world are faced with the issue of boarders in emergency department (ED), patients marked for admission but with no available inpatient bed. Boarder status is known to be associated with delayed inpatient care and suboptimal outcomes. A new care delivery system was developed in our institution where boarders received full inpatient care from a designated medical team, acute medical team (AMT), while still residing at ED. The current study examines the impact of this AMT intervention on patient outcomes. METHODS: We conducted a retrospective quasi-experimental cohort study to analyze outcomes between the AMT intervention and conventional care in a 1250-bed acute care tertiary academic hospital in Singapore. Study participants included patients who received care from the AMT, a matched cohort of patients admitted directly to inpatient wards (non-AMT) and a sample of patients prior to the intervention (pre-AMT group). Primary outcomes were length of hospital stay (LOS), early discharges (within 24 h) and bed placement. Secondary outcomes included unplanned readmissions within 3 months, and patient's bill size. χ2- and Mann-Whitney U tests were used to test for differences between the cohorts on dichotomous and continuous variables respectively. RESULTS: The sample comprised of 2279 patients (1092 in AMT, 1027 in non-AMT, and 160 in pre-AMT groups). Higher rates of early discharge (without significant differences in the readmission rates) and shorter LOS were noted for the AMT patients. They were also more likely to be admitted into a ward allocated to their discipline and had lower bill size compared to non AMT patients. CONCLUSIONS: The AMT intervention improved patient outcomes and resource utilization. This model was noted to be sustainable and provides a potential solution for hospitals' ED boarders who face a gap in inpatient care during their crucial first few hours of admissions while waiting for an inpatient bed.

A qualitative study of sign-out processes between primary and on-call residents: relationships in information exchange, responsibility and accountability.

OBJECTIVE: To review a quality improvement event on the process of sign-outs between the primary and on-call residents. DESIGN: A retrospective qualitative study using semi-structured interviews. SETTING: A tertiary academic medical center in Singapore with 283 inpatient Medicine beds served by 28 consultants, 29 registrars, 45 residents and 30 interns during the day but 5 residents and 3 interns at night. PARTICIPANTS: Residents, registrars and consultants. INTERVENTION: Quality improvement event on sign-out. MAIN OUTCOME: Effectiveness of sign-out comprises exchange of patient information, professional responsibility and task accountability. RESULTS: The following process of sign-outs was noted. Primary teams were accountable to the on-call resident by selecting at-risk patients and preparing contingency plans for sign-out. Structured information exchanged included patient history, active problems and plans of care. On-call residents took ownership of at-risk patients by actively asking questions during sign-out and reporting back the agreed care plan. On-call residents were accountable to the primary team by reporting back at-risk patients the next day. CONCLUSION: A structured information exchange at sign-out increased the on-call resident's ability to care for at-risk patients when it was supported by two-way transfers of responsibility and accountability.