Publications by authors named "Thuan-Tong Tan"

Article Synopsis
  • Solid organ transplantation (SOT) in Asia has grown significantly, but donor-derived infections (DDIs) are a major concern as they can negatively affect transplant outcomes.
  • A study was conducted by reaching out to transplant infectious diseases experts in Asia to gather standardized data on SOT numbers, DDI incidence, and screening protocols in countries like Singapore, Japan, and Thailand.
  • The findings reveal that while mandatory screening for common infections like HIV and hepatitis is in place across the region, there is a notable lack of surveillance for DDIs, indicating an urgent need for a DDI registry and coordinated efforts to improve safety in organ transplantation.
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Background: Donor-derived dengue infections present significant challenges to organ transplantation, particularly in endemic regions like Singapore. Although primarily transmitted by Aedes mosquitoes, dengue can also be transmitted through organ transplantation, occasionally with fatal outcomes. This study aims to evaluate the outcomes and evolution of dengue screening protocols for potential deceased donors in Singapore from 2006 to 2022.

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Background: Post-transplant or hematological cancer patients have a higher risk of mortality after infection with ancestral and early variants of severe acute respiratory syndrome (SARS)-CoV-2. Adoptive cell therapy (ACT) with virus-specific T cells (VSTs) could augment endogenous T cell immunity to avoid disease deterioration before viral clearance.

Methods: We established a third-party SARS-CoV-2-specific T cell (COVID-T) bank in 2020 (NCT04351659) using convalescent and/or vaccinated donors.

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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.

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The emergence of carbapenem-resistant Enterobacterales (CRE) has been recognized as a significant concern globally. Ceftazidime/avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor that has demonstrated activity against isolates producing class A, C, and D β-lactamases. Here-in, we evaluated the in vitro activity of CZA and comparator antimicrobial agents against 858 CRE isolates, arising from the Southeast Asian region, collected from a large tertiary hospital in Singapore.

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Importance: Despite patients with cancer being at risk of poor outcomes from COVID-19, there are few published studies for vaccine efficacy in this group, with suboptimal immunogenicity and waning vaccine efficacy described in small studies being a concern.

Objective: To assess the incidence rate of severe COVID-19 disease outcomes associated with the number of vaccine doses received and the waning of protection over time.

Design, Setting, And Participants: A prospective multicenter observational cohort study was carried out over 2 time periods (September 15, 2021, to December 20, 2021 [delta wave], and January 20, 2022, to November 11, 2022 [omicron wave]) predominated by SARS-CoV-2 delta and omicron variants, respectively.

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Limited treatment options exist for the treatment of carbapenem-resistant (CRE) bacteria. Fortunately, there are several recently approved antibiotics indicated for CRE infections. Here, we examine the activity of various novel agents (eravacycline, plazomicin, ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam) and comparators (tigecycline, amikacin, levofloxacin, fosfomycin, polymyxin B) against 365 well-characterized CRE clinical isolates with various genotypes.

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Introduction: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including administration of booster doses, continues to be the most effective method for controlling COVID-19-related complications including progression to severe illness and death. However, there is mounting evidence that more needs to be done to protect individuals with compromised immune function.

Areas Covered: Here, we review the effectiveness of COVID-19 vaccination in immunocompromised patients, including those with primary immunodeficiencies, HIV, cancer (including hematological malignancies), solid organ transplant recipients, and chronic kidney disease, as reported in systematic reviews/meta-analyses published over a 12-month period in PubMed.

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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.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected half a billion people, including vulnerable populations such as cancer patients. While increasing evidence supports the persistence of SARS-CoV-2 months after a negative nasopharyngeal swab test, the effects on long-term immune memory and cancer treatment are unclear. In this report, we examined post-COVID-19 tissue-localized immune responses in a hepatocellular carcinoma (HCC) patient and a colorectal cancer (CRC) patient.

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Introduction: Intravesical Bacillus Calmette-Guerin (BCG) therapy is the standard adjuvant treatment for non-muscle-invasive bladder carcinoma (NMIBC) with carcinoma in situ, in addition to tumour resection. We aimed to study BCG complications that preclude adequate treatment of NMIBC in an Asian population.

Methods: This retrospective study was conducted using a large, prospectively maintained bladder cancer database.

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Article Synopsis
  • Prolonged shedding of COVID-19 is notable in patients treated with anti-CD20 agents like rituximab, with cases of occult infection, where the virus persists in the lungs despite negative nasal tests, being rare.
  • Two immunocompromised patients, previously treated with rituximab, showed ground-glass infiltrates in lung scans, and despite negative SARS-CoV-2 results in nasal swabs, they were diagnosed with ongoing infection after testing lung fluid.
  • The findings suggest that negative nasal tests don’t rule out lung infections, indicating the need for invasive tests like bronchoalveolar lavage; this also emphasizes the importance of strict infection control during procedures that might spread the virus.
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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.

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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.

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Immunocompromised hosts with prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been implicated in the emergence of highly mutated SARS-CoV-2 variants. Spike mutations are of particular concern because the spike protein is a key target for vaccines and therapeutics for SARS-CoV-2. Here, we report the emergence of spike mutations in two immunocompromised patients with persistent SARS-CoV-2 reverse transcription (RT)-PCR positivity (>90 days).

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Sporadic clusters of healthcare-associated coronavirus disease 2019 (COVID-19) occurred despite intense rostered routine surveillance and a highly vaccinated healthcare worker (HCW) population, during a community surge of the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) B.1.617.

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Fosfomycin-based combination therapy has emerged as an attractive option in our armamentarium due to its synergistic activity against carbapenem-resistant Gram-negative bacteria (CRGNB). The ability to simultaneously measure fosfomycin and other antibiotic drug levels will support in vitro and clinical investigations to develop rational antibiotic combination dosing regimens against CRGNB infections. We developed an analytical assay to measure fosfomycin with nine important antibiotics in human plasma and cation-adjusted Mueller-Hinton II broth (CAMHB).

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Carbapenem-resistant (CRKP) is becoming increasingly problematic due to the limited effectiveness of new antimicrobials or other factors such as treatment cost. Thus, combination therapy remains a suitable treatment option. We aimed to evaluate the bactericidal activity of various antibiotic combinations against CRKP with different carbapenemase genotypes and sequence types (STs).

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Introduction: Dengue is a mosquito-borne viral infection endemic in Singapore. Its impact on renal transplantation is limited to small case series. We aimed to characterise the clinical presentation and outcomes of dengue infection among renal transplant recipients in Singapore.

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Article Synopsis
  • A clinically significant pathogen is causing many hospital-acquired infections and is a public health threat due to its growing antibiotic resistance.
  • Researchers sequenced genomes from 222 carbapenem-non-susceptible isolates in Singapore over 14 years to assess their antimicrobial resistance and genetic diversity.
  • The study revealed high levels of multi-drug resistance, identified prevalent clones like ST235 and NDM-1-producing ST308, and examined the mechanisms behind carbapenem resistance to inform future surveillance.
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