A retrospective study of intravenous pentamidine for Pneumocystis jirovecii pneumonia prophylaxis in adult patients with hematologic malignancies-its utility during respiratory virus pandemics.

OBJECTIVES: In hematology, prophylaxis for Pneumocystis jirovecii pneumonia (PCP) is recommended for patients undergoing hematopoietic stem cell transplantation and in selected categories of intensive chemotherapy for hematologic malignancies. Trimethoprim-sulfamethoxazole (TMP-SMX) is the recommended first-line agent; however, its use is not straightforward. Inhaled pentamidine is the recommended second-line agent; however, aerosolized medications were discouraged during respiratory virus outbreaks, especially during the COVID-19 pandemic, in view of potential contamination risks. Intravenous (IV) pentamidine is a potential alternative agent. We evaluated the effectiveness and tolerability of IV pentamidine use for PCP prophylaxis in adult allogeneic hematopoietic stem cell transplantation recipients and patients with hematologic malignancies during COVID-19. RESULTS: A total of 202 unique patients who received 239 courses of IV pentamidine, with a median of three doses received (1-29). The largest group of the patients (49.5%) who received IV pentamidine were undergoing or had received a hematopoietic stem cell transplant. The most common reason for not using TMP-SMX prophylaxis was cytopenia (34.7%). We have no patients who had breakthrough PCP infection while on IV pentamidine. None of the patients developed an infusion reaction or experienced adverse effects from IV pentamidine. CONCLUSIONS: Pentamidine administered IV monthly is safe and effective.

Consensus position statement on advancing the standardised reporting of infection events in immunocompromised patients.

Patients can be immunocompromised from a diverse range of disease and treatment factors, including malignancies, autoimmune disorders and their treatments, and organ and stem-cell transplantation. Infections are a leading cause of morbidity and mortality in immunocompromised patients, and the disease treatment landscape is continually evolving. Despite being a critical but preventable and curable adverse event, the reporting of infection events in randomised trials lacks sufficient detail while inconsistency of categorisation and definition of infections in observational and registry studies limits comparability and future pooling of data. A core reporting dataset consisting of category, site, severity, organism, and endpoints was developed as a minimum standard for reporting of infection events in immunocompromised patients across study types. Further additional information is recommended depending on study type. The standardised reporting of infectious events and attributable complications in immunocompromised patients will improve diagnostic, treatment, and prevention approaches and facilitate future research in this patient group.

Moist heat as a promising method to decontaminate N95 masks: A large scale clinical study comparing four decontamination modalities-moist heat, steam, ultraviolet-C irradiation, and hydrogen peroxide plasma.

BACKGROUND: Early in the COVID-19 pandemic, there was a global shortage of masks. Although mask reprocessing was practiced, no clinical study has assessed systematically the impact of repeated cycles of wear and decontamination on the integrity of N95 filtering facepiece respirators (FFRs). METHODS: We evaluated mask fit assessed by qualitative respirator fit test (QRFT) after each cycle of wear and decontamination, as well as four measures of mask integrity-bacterial filtration efficacy, particle filtration efficacy, differential pressure, and splash resistance through five cycles of wear and decontamination using one of the four modalities (moist heat, steam, ultraviolet-C irradiation, and hydrogen peroxide plasma). RESULTS: A total of 60.6% (hydrogen peroxide plasma) to 77.5% (moist heat) of the FFRs passed five cycles of wear and decontamination, as assessed by the wearers passing QRFT all five times. Moist heat-decontaminated FFRs retained all technical measures of integrity through all five cycles. CONCLUSIONS: This is the first large-scale study to assess systematically the impact (clinically and quantitatively) on N95 FFR integrity of repeated cycles of wearing followed by decontamination. Our results suggest that moist heat is a promising method for decontaminating N95 FFRs. Performing QRFT after every cycle of wear and decontamination ensures wearer safety. Although there is currently no mask shortage, reprocessing may reduce medical waste and improve sustainability.

Clinical features, management and outcomes of peritoneal dialysis patients during Delta and Omicron waves of COVID-19 infections.

INTRODUCTION: There were discrete outbreaks of SARS-CoV-2 infection in 2021 (Delta wave) and 2022 (Omicron wave) in Singapore, which affected patients receiving peritoneal dialysis (PD). METHODS: This study included all PD patients with COVID-19 infection from a single center between October 2021 and March 2022. The clinical presentation, management and outcomes of patients during the Delta and Omicron outbreaks were compared. RESULTS: A total of 44 PD patients developed SARS-CoV-2 infection (23 during the Delta wave and 21 during the Omicron wave): median age 66 (60.5-68.5) years, male (63.6%), Chinese ethnic (77.3%), diabetes mellitus (56.8%), and cardiovascular disease (45.5%). Approximately, 93.2% received two doses of the mRNA COVID-19 vaccine. Cough (81.8%) and fever (54.5%) were common presenting symptoms. Chest radiography showed ground glass opacity in 23.5% of patients, consolidation in 55.6%, and bilateral lung involvement in 33.3%. Eleven patients (25.6%) received antiviral therapy (Remdesivir), 7 (16.3%) received steroid, and 4 (9.3%) received monoclonal antibodies. Patients infected during the Delta wave were more likely to be hospitalized (73.9 vs 14.3%; p < 0.001) and receive antiviral therapy (39.1 vs 10.0%; p = 0.03) than those during the Omicron wave. The overall mortality rate was 11.4%, with significantly higher mortality during the Delta wave than during the Omicron wave (21.7 vs 0%; p = 0.03). CONCLUSIONS: The mortality rate was high among infected PD patients during Delta wave of COVID-19 infection. However, during the Omicron wave, most infected patients were treated in the community with favorable outcomes.

Trends in Pseudomonas aeruginosa (P. aeruginosa) Bacteremia during the COVID-19 Pandemic: A Systematic Review.

Pseudomonas aeruginosa (P. aeruginosa) is among the most common pathogens associated with healthcare-acquired infections, and is often antibiotic resistant, causing significant morbidity and mortality in cases of P. aeruginosa bacteremia. It remains unclear how the incidence of P. aeruginosa bacteremia changed during the Coronavirus Disease 2019 (COVID-19) pandemic, with studies showing almost contradictory conclusions despite enhanced infection control practices during the pandemic. This systematic review sought to examine published reports with incidence rates for P. aeruginosa bacteremia during (defined as from March 2020 onwards) and prior to the COVID-19 pandemic. A systematic literature search was conducted in accordance with PRISMA guidelines and performed in Cochrane, Embase, and Medline with combinations of the key words (pseudomonas aeruginosa OR PAE) AND (incidence OR surveillance), from database inception until 1 December 2022. Based on the pre-defined inclusion criteria, a total of eight studies were eligible for review. Prior to the pandemic, the prevalence of P. aeruginosa was on an uptrend. Several international reports found a slight increase in the incidence of P. aeruginosa bacteremia during the COVID-19 pandemic. These findings collectively highlight the continued importance of good infection prevention and control and antimicrobial stewardship during both pandemic and non-pandemic periods. It is important to implement effective infection prevention and control measures, including ensuring hand hygiene, stepping up environmental cleaning and disinfection efforts, and developing timely guidelines on the appropriate prescription of antibiotics.

The current state of laboratory mycology in Asia/Pacific: A survey from the European Confederation of Medical Mycology (ECMM) and International Society for Human and Animal Mycology (ISHAM).

INTRODUCTION: Invasive fungal infections (IFIs) in Asia/Pacific are a particular threat to patients with malignancies, uncontrolled diabetes mellitus or undiagnosed/untreated human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS). Adequate and early access to diagnostic tools and antifungals is essential for IFI clinical management and patient survival. METHODS: Details on institution profile, self-perception on IFI, and access to microscopy, culture, serology, antigen detection, molecular testing, and therapeutic drug monitoring for IFI were collected in a survey. RESULTS: As of June 2022, 235 centres from 40 countries/territories in Asia/Pacific answered the questionnaire. More than half the centres were from six countries: India (25%), China (17%), Thailand (5%), Indonesia, Iran, and Japan (4% each). Candida spp. (93%) and Aspergillus spp. (75%) were considered the most relevant pathogens. Most institutions had access to microscopy (98%) or culture-based approaches (97%). Furthermore, 79% of centres had access to antigen detection, 66% to molecular assays, and 63% to antibody tests. Access to antifungals varied between countries/territories. At least one triazole was available in 93% of the reporting sites (voriconazole [89%] was the most common mould-active azole), whereas 80% had at least one amphotericin B formulation, and 72% had at least one echinocandin. CONCLUSION: According to the replies provided, the resources available for IFI diagnosis and management vary among Asia/Pacific countries/territories. Economical or geographical factors may play a key role in the incidence and clinical handling of this disease burden. Regional cooperation may be a good strategy to overcome shortcomings.

Favorable outcomes of COVID-19 in vaccinated hematopoietic stem cell transplant recipients: A single-center experience.

INTRODUCTION: A high incidence of mortality and severe COVID-19 infection was reported in hematopoietic stem cell transplant (HSCT) recipients during the early phases of the COVID-19 pandemic; however, outcomes with subsequent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, such as the omicron variant, have yet to be reported. Additionally, rollout of COVID-19 vaccinations in subsequent pandemic waves may modify COVID-19 disease severity and mortality in this immunocompromised population. We describe COVID-19 outcomes among a highly vaccinated population of HSCT recipients at a single center during successive waves of community transmission arising from the SARS-CoV-2 delta and omicron variants. METHODS: We retrospectively reviewed medical records of all HSCT recipients at our institution who tested positive for SARS-CoV-2 from May 2021 to May 2022. Descriptive statistics were reported; the chi-square test was utilized to identify factors associated with 90-day all-cause mortality and severity of COVID-19 infection. RESULTS: Over the 1-year study period, 77 HSCT recipients at our center contracted COVID-19 (43 allogenic; 34 autologous). Twenty-six (33.8%) patients were infected with the SARS-CoV-2 delta variant, while 51 (66.2%) had the SARS-CoV-2 omicron variant. Thirty-nine (50.6%) patients required hospitalization. More than 80% had received prior COVID-19 vaccination (57.1% with two doses, 27.3% with three doses). The majority (90.9%) had mild disease; only one (1.3%) patient required mechanical ventilation. Active hematological disease at time of COVID-19 infection was associated with increased odds of mortality [odds ratio (OR) = 6.90, 95% confidence interval (CI) = 1.20-40]. The 90-day all-cause mortality was 7.8% (six patients). Infection with the omicron variant (vs. delta) was associated with less severe illness (OR = 0.05, 95% CI = 0.01-0.47) and decreased odds of mortality (OR = 0.08, 95% CI = 0.01-0.76). Being on immunosuppression (OR = 5.10, 95% CI = 1.10-23.60) and being unvaccinated at disease onset (OR = 14.76, 95% CI = 2.89-75.4) were associated with greater severity of COVID-19 infection. CONCLUSION: We observed favorable outcomes with COVID-19 infection in a cohort of vaccinated HSCT patients. The SARS-CoV-2 omicron variant was associated with both less severe illness and decreased odds of mortality. As COVID-19 moves toward endemicity, early access to treatment and encouraging vaccination uptake is crucial in mitigating the challenge of COVID-19 management among HSCT recipients. Surveillance and assessment of clinical outcomes with new SARS-CoV-2 variants also remains important in this immunocompromised population.

The Performance of Lateral Flow Tests in the Age of the Omicron: A Rapid Systematic Review.

Prompt detection and isolation of COVID-19 cases is vital for preventing further viral transmission, and lateral flow or rapid antigen tests have been an important diagnostic tool in this pandemic. However, concerns have emerged regarding the sensitivity of these devices for the new BA.1, BA.2, and BA.4/5 omicron variants, which have greater transmissibility and extensive mutations in its spike (S) and nucleocapsid (N) proteins. N protein is an important target protein for existing lateral flow devices. This paper therefore aimed to provide a rapid review of available literature on the performance of the lateral flow tests for detecting the omicron coronavirus variant. A systematic literature search of PubMed, EMBASE, OVID Medline, and Google Scholar found six published studies and four preprints investigating the performance of existing lateral flow devices for the omicron variant, as compared to the B.1.617.2 (Delta) variant. Overall, it appears that the devices have poorer performance for the omicron variant and when testing samples with cycle threshold (Ct) values greater than 25 and in asymptomatic individuals. As most available data were preliminary and had small sample sizes, it is recommended that these data be further studied to better inform and adapt our public health responses.

Unmet needs and practical solutions in the management of invasive mould infections in Asia.

Management of invasive mould infections (IMIs) is challenging in Asia, as awareness among medical practitioners can be low and resources are limited. Timely diagnosis and appropriate treatment of IMIs can mitigate the impact on morbidity and mortality, but diagnostic methods, as well as access to preferred antifungal medications, may vary throughout the region. Knowledge of local epidemiology and accurate diagnosis and identification of causal pathogens would facilitate optimal treatment but data in Asia are lacking. To address these unmet needs in the management of IMIs, this paper is a call for urgent action in the following areas: improving awareness of the threat of IMIs; providing education to frontline clinicians across a broad range of specialties on 'red flags' for suspicion of IMIs; prioritizing cost-effective rapid diagnostic testing; improving access to preferred antifungal medications; and closing the gaps in local epidemiological data on IMIs to inform local treatment guidelines.

Current state of antimicrobial stewardship in organ transplantation in Singapore.

BACKGROUND: Antibiotic stewardship programs (ASPs) are well established in the public hospitals in Singapore, but they are not mandatory for transplant programs. Given the positive impact of ASPs in non-organ transplant patients (improved use of broad-spectrum antibiotics, reduced length of stay, and lower healthcare costs), stewardship principles are likely to benefit transplant recipients. METHODS: We reviewed the progress made in ASPs in the Asia Pacific region as well as the progress of our ASP over the last decade since it was established. We also described how stewardship strategies have evolved for the purposes of our transplant program. RESULTS: Currently, pressing stewardship issues for our transplant program include high antibiotic consumption, as well as the burden, morbidity, and mortality associated with drug-resistant bacterial infections. Transplanting the model of stewardship onto a transplant program ignores the intricacies of transplant patients; the bespoke form of stewardship, "handshake stewardship", is more appropriate. CONCLUSION: To advance the cause of ASP in the transplant unit in Singapore, stakeholder buy-in is key; empowering transplant physicians to be stewardship-focused would be more sustainable in the long run. In addition, expanding our diagnostic armamentarium, optimizing existing therapeutics and multi-disciplinary team involvement (including stakeholders from microbiology, and infection prevention teams) are vital.

Factors Associated With Prolonged Psychological Distress Among Nurses and Physicians Engaged in COVID-19 Patient Care in Singapore and Japan.

This study explores the factors contributing to the prolonged psychological distress of frontline nurses and physicians caring for COVID-19 patients in hospitals in Singapore and Japan. A cross-sectional survey between September and December 2020 yielded 1,644 responses (23.8%), from 62 nurses and 64 physicians in Singapore and 1,280 nurses and 238 physicians in Japan. Multivariate logistic regression analysis revealed that significant risk factors for prolonged psychological distress included being a frontline nurse [adjusted odds ratio (aOR) = 2.40, 95% confidence interval (CI): 1.24-4.66], having an underlying medical condition (aOR = 1.74, 95% CI: 1.22-2.46), experiencing prejudice because they undertook COVID-19 patient care (aOR = 3.05, 95% CI: 2.23-4.18), having trouble dealing with panicked or uncooperative patients (aOR = 2.36, 95% CI: 1.71-3.25), and experiencing an outbreak of COVID-19 in the hospital (aOR = 2.05, 95% CI: 1.38-3.04). Factors inversely associated with psychological distress included age (OR = 0.98, 95% CI: 0.97-1.00), number of beds in the hospital (aOR = 0.73, 95% CI: 0.57-0.94), clinical practice of carefully putting on and taking off personal protective equipment in daily COVID-19 patient care (aOR = 0.52, 95% CI: 0.37-0.73), and knowledge on COVID-19 (aOR = 0.82, 95% CI: 0.72-0.94). These results could help us identify vulnerable healthcare providers who need urgent mental care during the COVID-19 pandemic. Measures that may reduce psychological strain include adequate supply of medical resources, education on precautionary measures, and communication strategies to combat discrimination against frontline healthcare providers.

Healthcare workers as a sentinel surveillance population in the early phase of the COVID-19 pandemic.

Introduction: Healthcare workers (HCWs) are a critical resource in the effort to control the COVID-19 pandemic. They are also a sentinel surveillance population whose clinical status reflects the effectiveness of the hospital's infection prevention measures in the pandemic. Methods: This was a retrospective cohort study conducted in Singapore General Hospital (SGH), a 1,822-bed tertiary hospital. Participants were all HCWs working in SGH during the study period. HCW protection measures included clinical workflows and personal protective equipment developed and adapted to minimise the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. HCW monitoring comprised staff contact logs in high-risk locations, twice-daily temperature monitoring, assessment of HCWs with acute respiratory illnesses (ARIs) in the staff clinic and, in the event of an exposure, extensive contact tracing, detailed risk assessment and risk-based interventions. HCW surveillance utilised monitoring data and ARI presentations and outcomes. Results: In the ten-week period between 6 January 2020 and 16 March 2020, 333 (17.1%) of 1,946 HCWs at risk of occupational COVID-19 presented with ARI. 32 (9.6%) screened negative for SARS-CoV-2 from throat swabs. Five other HCWs developed COVID-19 attributed to non-clinical exposures. From the nine COVID-19 exposure episodes investigated, 189 HCW contacts were identified, of whom 68 (36.2%) were placed on quarantine and remained well. Conclusion: Early in an emerging infectious disease outbreak, close monitoring of frontline HCWs is essential in ascertaining the effectiveness of infection prevention measures. HCWs are at risk of community disease acquisition and should be monitored and managed to prevent onward transmission.

Estimating the economic cost of carbapenem resistant Enterobacterales healthcare associated infections in Singapore acute-care hospitals.

Quantifying the costs of hospital associated infections (HAIs) caused by carbapenem-resistant Enterobacterales (CRE) can aid hospital decision makers in infection prevention and control decisions. We estimate the costs of a CRE HAI by infection type and the annual costs of CRE HAIs to acute-care hospitals in Singapore. We used tree diagrams to estimate the costs (in Singapore dollar) of different CRE HAI types from the health service perspective and compared them to the costs of carbapenem-susceptible HAIs. We used two approaches to estimate costs-direct costs of consumables for infection prevention and treatment; and costs associated with lost bed days. Cost of a HAI were extrapolated to annual CRE HAI incidence in Singapore acute-care hospitals to estimate the annual cost to the hospitals. We found that the cost of a CRE HAI based on direct cost and lost bed days are SGD$9,913 (95% CI, SGD$9,431-10,395) and SGD$10,044 (95% CI, SGD$9,789-10,300) respectively. CRE HAIs are markedly higher than the carbapenem-susceptible HAIs for all infection types. In both approaches, CRE pneumonia was the costliest infection. Based on a CRE HAI incidence of 233 per 100,000 inpatient admissions, CRE HAIs costed SGD$12.16M (95% CI, SGD$11.84-12.48M) annually based on direct costs, and SGD$12.33M (95% CI, SGD$12.01-12.64M) annually based on lost bed days. In conclusion, we described the cost of CRE HAIs in Singapore hospitals and identified infections with the highest costs. The findings may be useful in informing future economic evaluations of competing CRE HAI prevention and treatment programmes.

Candida Endophthalmitis Treated Successfully With Isavuconazole: A Case Report.

Candida endophthalmitis is a serious complication of candidemia. Diagnosis requires identification of ocular lesions on dilated fundoscopy, aided by isolation of the organism from blood and/or vitreous humor. However, the initial ophthalmological examination may be negative in some cases. Experience with isavuconazole for the treatment of Candida endophthalmitis is limited. We present a case of a 65-year-old woman with metastatic breast cancer on chemotherapy who developed Candida dubliniensis endophthalmitis with initial negative ophthalmological examination. She was treated with vitrectomy and 6 weeks of oral fluconazole. Despite vitrectomy and culture-directed antifungal treatment, management was complicated by lack of response to fluconazole and intolerance to other antifungals, necessitating the use of isavuconazole, which proved efficacious.

Exploring Reusability of Disposable Face Masks: Effects of Disinfection Methods on Filtration Efficiency, Breathability, and Fluid Resistance.

To curb the spread of the COVID-19 virus, the use of face masks such as disposable surgical masks and N95 respirators is being encouraged and even enforced in some countries. The widespread use of masks has resulted in global shortages and individuals are reusing them. This calls for proper disinfection of the masks while retaining their protective capability. In this study, the killing efficiency of ultraviolet-C (UV-C) irradiation, dry heat, and steam sterilization against bacteria (Staphylococcus aureus), fungi (Candida albicans), and nonpathogenic virus (Salmonella virus P22) is investigated. UV-C irradiation for 10 min in a commercial UV sterilizer effectively disinfects surgical masks. N95 respirators require dry heat at 100 °C for hours while steam treatment works within 5 min. To address the question on safe reuse of the disinfected masks, their bacteria filtration efficiency, particle filtration efficiency, breathability, and fluid resistance are assessed. These performance factors are unaffected after 5 cycles of steam (10 min per cycle) and 10 cycles of dry heat at 100 °C (40 min per cycle) for N95 respirators, and 10 cycles of UV-C irradiation for surgical masks (10 min per side per cycle). These findings provide insights into formulating the standard procedures for reusing masks without compromising their protective ability.