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.

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.

Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients.

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

Efficacy of ß-lactam/ß-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project).

BACKGROUND: Whether active therapy with ß-lactam/ß-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. METHODS: We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. RESULTS: Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/µL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. CONCLUSIONS: Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).

Déjà Vu or Jamais Vu? How the Severe Acute Respiratory Syndrome Experience Influenced a Singapore Radiology Department's Response to the Coronavirus Disease (COVID-19) Epidemic.

OBJECTIVE. This article shares the ground operational perspective of how a tertiary hospital radiology department in Singapore is responding to the coronavirus disease (COVID-19) epidemic. This same department was also deeply impacted by the severe acute respiratory syndrome (SARS) outbreak in 2003. CONCLUSION. Though similar to SARS, the COVID-19 outbreak has several differences. We share how lessons from 2003 are applied and modified in our ongoing operational response to this evolving novel pathogen.

Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales: The impact of cytomegalovirus disease and lymphopenia.

Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score ≥8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score ≥8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.

The epidemiology of non-Candida yeast isolated from blood: The Asia Surveillance Study.

BACKGROUND: Current guidelines recommend echinocandins as first-line therapy for candidemia. However, several non-Candida yeast are non-susceptible to echinocandins (echinocandin non-susceptible yeast, ENSY), including Cryptococcus, Geotrichum, Malassezia, Pseudozyma, Rhodotorula, Saprochaete, Sporobolomyces and Trichosporon. In laboratories that are not equipped with rapid diagnostic tools, it often takes several days to identify yeast, and this may lead to inappropriate presumptive use of echinocandins in patients with ENSY fungemia. The aim of this study was to determine the distribution of ENSY species during a 1-year, laboratory surveillance programme in Asia. METHODS: Non-duplicate yeast isolated from blood or bone marrow cultures at 25 hospitals in China, Hong Kong, India, Singapore, Taiwan and Thailand were analysed. Isolates were considered to be duplicative if they were obtained within 7 days from the same patient. RESULTS: Of 2155 yeast isolates evaluated, 175 (8.1%) were non-Candida yeast. The majority of non-Candida yeast were ENSY (146/175, 83.4%). These included Cryptococcus (109 isolates), Trichosporon (23), Rhodotorula (10) and Malassezia (4). The proportion of ENSY isolates (146/2155, 6.7%) differed between tropical (India, Thailand and Singapore; 51/593, 8.6%) and non-tropical countries/regions (China, Hong Kong and Taiwan; 95/1562, 6.1%, P = 0.038). ENSY was common in outpatient clinics (25.0%) and emergency departments (17.8%) but rare in intensive care units (4.7%) and in haematology-oncology units (2.9%). Cryptococcus accounted for the majority of the non-Candida species in emergency departments (21/24, 87.5%) and outpatient clinics (4/5, 80.0%). CONCLUSIONS: Isolation of non-Candida yeast from blood cultures was not rare, and the frequency varied among medical units and countries.

Survey of laboratory practices for diagnosis of fungal infection in seven Asian countries: An Asia Fungal Working Group (AFWG) initiative.

An online survey of mycology laboratories in seven Asian countries was conducted to assess the status, competence, and services available. Country representatives from the Asia Fungal Working Group (AFWG) contacted as many laboratories performing mycology diagnosis as possible in their respective countries, requesting that the laboratory heads complete the online survey. In total, 241 laboratories responded, including 71 in China, 104 in India, 11 in Indonesia, 26 in the Philippines, four in Singapore, 18 in Taiwan, and seven in Thailand. Overall, 129/241 (53.5%) surveyed mycology laboratories operate as separate designated mycology laboratories, 75/241 (31.1%) conduct regular formal staff training, 103/241 (42.7%) are accredited, and 88/157 (56.1%) participate in external quality assurance scheme (EQAS) programs. Microscopy and culture methods are available in nearly all laboratories, although few perform DNA sequencing (37/219; 16.9%) or use matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS) (27/219; 12.3%) for isolate identification. Antifungal susceptibility testing is performed in 142/241 (58.9%) laboratories, mainly for yeasts. The most commonly performed nonculture diagnostic is cryptococcal antigen testing (66 laboratories), followed by galactomannan testing (55), polymerase chain reaction (PCR) diagnosis (37), and beta-D-glucan testing (24). Therapeutic drug monitoring is conducted in 21 laboratories. There is almost no access to advanced diagnostic tests, like galactomannan, ß-D-glucan, and PCR, in the surveyed laboratories in Indonesia, the Philippines, and Thailand. These results highlight the need for development of quality laboratories, accreditation and training of manpower in existing laboratories, and access to advanced non-culture-based diagnostic tests to facilitate the diagnosis of fungal infections in Asia.

Epidemiology and risk factors for cytomegalovirus infection in glomerular diseases treated with immunosuppressive therapy.

AIM: Cytomegalovirus (CMV) infections are associated with morbidity and mortality. We aimed to describe the epidemiology, risk factors and outcomes of CMV infection among patients with glomerulonephritis (GN) who received potent immunosuppressants (IS). METHODS: Single-centre retrospective study of adults with biopsy-proven GN prescribed methylprednisolone (MP), cyclophosphamide (CYC) or rituximab (RTX). Primary endpoint was CMV infection defined by significant CMV antigenaemia (>10 positive cells in 106 cells) or viraemia (>2000 copies/mL). Death was related to CMV if CMV infection occurred within the same hospitalization as death. RESULTS: Ninety-four patients were studied. CYC was prescribed in 65% and MP in 71% of the cohort. Only two patients received RTX and 15 patients received plasma exchanges (PEX). Median follow up was 31.9 (IQR: 13.7, 53.6) months. CMV infection occurred in 13 patients (13.8%) at 1.3 (0.6, 3.0) months from biopsy. Patients with CMV infection had higher serum creatinine [404 (272, 619) vs. 159 (93, 317) µmol/L, P < 0.001] and greater proteinuria [UPCR 7.5, (4.8, 11.8) vs. 4.2 (2.3, 8.4) g/g, P = 0.02] than those who did not have CMV infection. Also, more patients received CYC (92% vs. 60%, P = 0.03), RTX (15% vs. 0, P = 0.02) and PEX (38% vs. 12%, P = 0.01) than those who did not have CMV infection. Two patients had CMV-related deaths. CONCLUSION: Cytomegalovirus infection is common in GN patients receiving potent IS. Surveillance and possibly anti-viral prophylaxis should be considered for high-risk patients.

Respiratory virus infection after allogeneic hematopoietic stem cell transplant in a tropical center: Predictive value of the immunodeficiency scoring index.

BACKGROUND: Respiratory virus infection (RVI) is a prevalent infection in patients after allogeneic hematopoietic stem cell transplant (allo-HSCT) and can result in significant morbidity and mortality. Ability to assess the potential severity of RVI is important in the management of such patients. METHODS: We reviewed the cases of RVI in allo-HSCT recipients and explored the predictive value of the immunodeficiency scoring index (ISI) established for respiratory syncytial virus (RSV) and its applicability for RVI caused by other respiratory viruses. RESULTS: RVI occurred year-round in our tropical transplant center, with peaks in the middle and end of the year. Ninety-five of the 195 recipients developed a total of 191 episodes of RVI, giving a cumulative incidence of 28% by 6 months and 52% by 24 months for the first episode of RVI. RSV, influenza, rhinovirus, and parainfluenza were the most common viruses. Pneumonia occurred in 63.64%, 42.31%, and 32.42% of adenovirus, influenza, and RSV RVI episodes, respectively, but was also non-negligible in the more benign viruses, such as coronavirus (31.58%) and rhinovirus (23.68%). Nineteen of the 63 episodes of viral pneumonia required mechanical ventilation and 14 deaths occurred within 6 weeks of the RVI. Receiver operating characteristic analysis showed that an ISI of ≥8 predicted pneumonia with a positive predictive value of >80% for RVI caused by RSV, influenza, adenovirus, and parainfluenza, while it was not predictive for coronavirus and rhinovirus. CONCLUSIONS: The ISI is a useful aid for decision-making during clinic consultation for patients presenting with symptoms suggestive of an RVI.

The risk of tuberculosis in SLE patients from an Asian tertiary hospital.

Systemic lupus erythematosus (SLE) has been associated with increased risk of tuberculosis (TB). However, little is known about the extent and risk factors for TB among Asian patient with SLE. We aimed to assess the rate of TB in patients with SLE, and investigate the risk of SLE on TB development using hospital administrative database. This is an historical cohort study of hospital discharge database from 2004 to 2011 to identify cases with SLE and TB using International Statistical Classification of Diseases and Related Health Problems, 9th Revision, Australian Modification (ICD-9-AM) codes. Of 301568 hospitalized patients, 841 (0.3%) patients had SLE, 1843 (0.6%) patients had TB, including 17 SLE patients (2.0%). SLE patients had a significantly higher rate of TB (2.0 vs. 0.6%, p < 0.001) compared to that of patients without SLE. The differences in the higher rate after breaking down was in the pulmonary TB group (1.7 vs. 0.5%, p < 0.00) but not in extrapulmonary TB group (0.4 vs. 0.1%, p = 0.060). Logistic regression analyses showed that SLE was a significant and independent predictor of TB (odds ratio 4.6, 95% CI 2.8-7.5, p < 0.001) after adjustment for factors such as age group, gender, ethnicity, admission class, nutritional deficiency, organ transplantation, and Charlson comorbidity index. SLE patients were found to experience higher rates of tuberculosis in this group of Asian patient population. Patients with SLE should be considered as a high-risk group for TB, active screening for latent patients and treatment for positive TB patients is needed.

Network Meta-analysis and Pharmacoeconomic Evaluation of Fluconazole, Itraconazole, Posaconazole, and Voriconazole in Invasive Fungal Infection Prophylaxis.

Invasive fungal infections (IFIs) are associated with high mortality rates and large economic burdens. Triazole prophylaxis is used for at-risk patients with hematological malignancies or stem cell transplants. We evaluated both the efficacy and the cost-effectiveness of triazole prophylaxis. A network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating fluconazole, itraconazole capsule and solution, posaconazole, and voriconazole was conducted. The outcomes of interest included the incidences of IFIs and deaths. This was coupled with a cost-effectiveness analysis from patient perspective over a lifetime horizon. Probabilities of transitions between health states were derived from the NMA. Resource use and costs were obtained from the Singapore health care institution. Data on 5,505 participants in 21 RCTs were included. Other than itraconazole capsule, all triazole antifungals were effective in reducing IFIs. Posaconazole was better than fluconazole (odds ratio [OR], 0.35 [95% confidence interval [CI], 0.16 to 0.73]) and itraconazole capsule (OR, 0.25 [95% CI, 0.06 to 0.97]), but not voriconazole (OR, 1.31 [95% CI, 0.43 to 4.01]), in preventing IFIs. Posaconazole significantly reduced all-cause deaths, compared to placebo, fluconazole, and itraconazole solution (OR, 0.49 to 0.54 [95% CI, 0.28 to 0.88]). The incremental cost-effectiveness ratio for itraconazole solution was lower than that for posaconazole (Singapore dollars [SGD] 12,546 versus SGD 26,817 per IFI avoided and SGD 5,844 versus SGD 12,423 per LY saved) for transplant patients. For leukemia patients, itraconazole solution was the dominant strategy. Voriconazole was dominated by posaconazole. All triazole antifungals except itraconazole capsule were effective in preventing IFIs. Posaconazole was more efficacious in reducing IFIs and all-cause deaths than were fluconazole and itraconazole. Both itraconazole solution and posaconazole were cost-effective in the Singapore health care setting.

A retrospective review of a tertiary Hospital's isolation and de-isolation policy for suspected pulmonary tuberculosis.

BACKGROUND: Effective protocols for the isolation and de-isolation of patients with suspected pulmonary tuberculosis (PTB) are essential determinants of health-care costs. Early de-isolation needs to be balanced with the need to prevent nosocomial transmission of PTB. The aim of our study was to evaluate the efficiency of our hospital's current protocol for isolating and de-isolating patients with suspected PTB, in particular assessing the timeliness to de-isolation of patients with AFB smear negative respiratory samples. METHODS: We retrospectively reviewed 121 patients with suspected PTB who were admitted to our hospital's isolation ward. We analyzed the time spent in isolation, the total number of respiratory samples that were collected for each patient and the time taken from collection of the first respiratory sample to release of the result of third respiratory sample for acid-fast bacilli (AFB) smear. We also calculated the direct cost of isolation for each patient. RESULTS: The mean and median number of AFB smears for each patient was three. Thirty percent of patients had four or more AFB smears taken and 20% were de-isolated before the results of three negative AFB smears were obtained. The mean duration of isolation was significantly shorter in patients who had fewer than three negative AFB smears compared to those who had three or more negative AFB smears (three days vs. five days, p <0.01). The mean cost in patients who were de-isolated before three negative smears were obtained was USD 947 compared to USD 1,636 in those were only de-isolated after three negative AFB smears (p <0.01). CONCLUSIONS: Our study suggests that our institution's current infection control policy for the isolation of patients with suspected PTB is fairly satisfactory, but may need to be tightened further to prevent true cases of PTB being de-isolated prematurely. However, there may be instances when patients could potentially be de-isolated more quickly without risk to others, thus saving on the use of limited resources and costs to patients.

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.

Detection and characterisation of a sixth Candida auris clade in Singapore: a genomic and phenotypic study.

BACKGROUND: The emerging fungal pathogen Candida auris poses a serious threat to global public health due to its worldwide distribution, multidrug resistance, high transmissibility, propensity to cause outbreaks, and high mortality. We aimed to characterise three unusual C auris isolates detected in Singapore, and to determine whether they constitute a novel clade distinct from all previously known C auris clades (I-V). METHODS: In this genotypic and phenotypic study, we characterised three C auris clinical isolates, which were cultured from epidemiologically unlinked inpatients at a large tertiary hospital in Singapore. The index isolate was detected in April, 2023. We performed whole-genome sequencing (WGS) and obtained hybrid assemblies of these C auris isolates. The complete genomes were compared with representative genomes of all known C auris clades. To provide a global context, 3651 international WGS data from the National Center for Biotechnology Information (NCBI) database were included in a high-resolution single nucleotide polymorphism (SNP) analysis. Antifungal susceptibility testing was done and antifungal resistance genes, mating-type locus, and chromosomal rearrangements were characterised from the WGS data of the three investigated isolates. We further implemented Bayesian logistic regression models to classify isolates into known clades and simulate the automatic detection of isolates belonging to novel clades as their WGS data became available. FINDINGS: The three investigated isolates were separated by at least 37 000 SNPs (range 37 000-236 900) from all existing C auris clades. These isolates had opposite mating-type allele and different chromosomal rearrangements when compared with their closest clade IV relatives. The isolates were susceptible to all tested antifungals. Therefore, we propose that these isolates represent a new clade of C auris, clade VI. Furthermore, an independent WGS dataset from Bangladesh, accessed via the NCBI Sequence Read Archive, was found to belong to this new clade. As a proof-of-concept, our Bayesian logistic regression model was able to flag these outlier genomes as a potential new clade. INTERPRETATION: The discovery of a new C auris clade in Singapore and Bangladesh in the Indomalayan zone, showing a close relationship to clade IV members most commonly found in South America, highlights the unknown genetic diversity and origin of C auris, particularly in under-resourced regions. Active surveillance in clinical settings, along with effective sequencing strategies and downstream analysis, will be essential in the identification of novel strains, tracking of transmission, and containment of adverse clinical effects of C auris infections. FUNDING: Duke-NUS Academic Medical Center Nurturing Clinician Researcher Scheme, and the Genedant-GIS Innovation Program.

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.