A case of naganishial pleuritis in a kidney transplant recipient.

The Naganishia species is a mycosis, previously classified as a non-neoformans Cryptococcus species. The increased number of naganishial infections occurs predominantly in immunocompromised conditions, especially in people living with HIV with low CD4 cell count, primary immunodeficiencies, and iatrogenic immunosuppression. The lungs can serve as the primary site of infection, leading to various pulmonary manifestations. However, naganishial pleural effusions are unrecognized and challenged in diagnosis because of their presentation, which can mimic tuberculous pleural effusion. Herein, we report the case of a 53-year-old man who had undergone kidney transplantation for more than 2 years and presented with chest tightness and dyspnea. Computed chest tomography demonstrated left pleural nodules and pleural effusion, later confirmed as exudative pleural effusion with a lymphocyte predominance. Pleuroscopy revealed multiple small pleural nodules, and biopsies of these nodules were performed. Naganishia spp. was identified by the 18S rRNA sequencing technique.

Immunogenicity and safety of heterologous versus homologous prime-boost schedules with inactivated and adenoviral vectored SARS-CoV-2 vaccines - A prospective multi-center study.

Background: During the peak of Coronavirus disease (COVID-19) pandemic in Thailand when the emergence of delta variant reduced the efficacy of inactivated vaccine, Thailand had abundance of inactivated vaccine but mRNA vaccine was not available and the supply of adenoviral-vectored vaccine was limited. The heterologous vaccination using CoronaVac and ChAdOx1-nCoV-19 vaccines was applied. We aim to compare the immunogenicity of immune response of primary vaccination with homologous ChAdOx1 nCoV-19 and heterologous vaccination with CoronaVac and ChAdOx1 nCoV-19. Methods: A total of 430 adults, scheduled to receive ChAdOx1-nCoV-19 as their second dose of primary COVID-19 vaccination, were enrolled. Participants were classified into two groups based on the first dose vaccine as CoronaVac (heterologous group) or ChAdOx1 nCoV-19 (homologous group). The primary outcome was antibodies to the SARS-CoV-2 spike protein receptor binding domain (anti-RBD) titres at 28 days after the second dose of vaccination. Secondary outcomes were anti-RBD titres at 90 days, surrogate viral neutralizing test (sVNT) at 28 and 90 days, and adverse events. Findings: In 358 participants with correct vaccine interval, the anti-RBD geometric mean titre ratio for the heterologous versus homologous group was 0.55 (95%CI; 0.44-0.067); p < 0.001 at day 28, and 0.80 (95%CI; 0.65-1.00); P = 0.05 at day 90. Median sVNT neutralizing activity was not significantly different in the heterologous versus homologous group at 28 days (93.5 vs 92.7 %); p = 0.13, but significantly higher in the heterologous group at day 90 (82.9 vs 76.4 %); p = 0.01. Interpretation: The homologous vaccination resulted in higher anti-RBD titres at 28 days after vaccination, but titres in the homologous group showed more rapid decline at 90 days. In the sVNT assay, median neutralization was similar at 28 days, but was longer-lasting and higher in the heterologous group at 90 days. Funding: This research received funding from the Royal College of Physicians of Thailand special grant 2021 for research initiative during COVID-19 pandemic.

Longitudinal study of disease severity and external factors in cognitive failure after COVID-19 among Indonesian population.

The COVID-19 infection is assumed to induce cognitive failure. Identifying the relationship between COVID-19, the effect of vaccination and medication, and accommodating non-COVID-19 factors to cognitive failure is essential. This study was conducted in Indonesia from September 2021 to January 2023. Demographic information, clinical data, comorbidities, vaccination, and medication during COVID-19 were obtained, as well as a 6-month cognitive assessment with Cognitive Failures Questionnaire/CFQ, Fatigue Severity Score, and Generalized Anxiety Disorder (GAD-7). A Structural Equation Model explains the relationship between potential predictors and cognitive failure. The average score of CFQ after 6 months was 45.6 ± 23.1 out of 100. The severity of the disease, which was associated with vaccination status, age, previous infection, and unit of treatment (p < 0.05), was not related to cognitive failure (p = 0.519), although there is a significant direct impact of worst vaccination status to cognitive failure(p < 0.001). However, age, fatigue, and current anxiety were associated with higher cognitive failure (p < 0.001), although comorbidities and recent headaches were not significant in other models (p > 0.05). This study concludes that cognitive failure after COVID-19 is a multifactorial event and does not solely depend on COVID-19 severity. It is crucial to re-address the factors related to the long-term efficacy of vaccination and medication and focus on non-health factors affecting cognitive failure.Trial Registration: NCT05060562.

Health related quality of life in anti interferon γ autoantibody associated immunodeficiency syndrome measured with EQ5D5L and SF36.

The anti-IFN-γ disease is a rare condition characterized by recurrent and persistent infections, potentially impacting the quality of life (QoL). However, comprehensive data on QoL in this population are lacking. This study aims to evaluate the QoL of Anti-IFN-γ patients compared to healthy control and explore potential differences in QoL between patients in the active and remission stages. A cross-sectional study design was conducted, recruiting 38 Anti-IFN-γ patients and 38 sex- and age-matched healthy controls. QoL assessment utilized the 5-level EuroQol-5 Dimension (EQ-5D-5L) and the 36-Item Short Form Health Survey (SF-36). The Anti-IFN-γ group had a mean age of 57.37 (± 10.32) years, with females comprising 60.53%. Among the Anti-IFN-γ patients, 55.26% were classified as having active disease. 63% of Anti-IFN-γ patients received Immunosuppressive treatments. Anti-IFN-γ disease exhibited a significant negative impact on HRQoL, as evidenced by lower utility scores in EQ-5D-5L and lower physical and mental component scores in SF-36 across various domains, including physical function, role physical, general health, bodily pain, social functioning, role emotion and mental health, compared to healthy controls. Additionally, patients in the active disease displayed lower scores in multiple domains, including bodily pain, general health, role emotion and mental health, and a lower utility score in EQ-5D-5L compared to patients in remission. The anti-IFN-γ disease significantly impairs the HRQoL of affected individuals compared to healthy controls. However, effective treatment leading to remission holds promise for improving the HRQoL of patients with Anti-IFN-γ disease.

Adverse Drug Reactions of Acetylcholinesterase Inhibitors in Older People Living with Dementia: A Comprehensive Literature Review.

The rising of global geriatric population has contributed to increased prevalence of dementia. Dementia is a neurodegenerative disease, which is characterized by progressive deterioration of cognitive functions, such as judgment, language, memory, attention and visuospatial ability. Dementia not only has profoundly devastating physical and psychological health outcomes, but it also poses a considerable healthcare expenditure and burdens. Acetylcholinesterase inhibitors (AChEIs), or so-called anti-dementia medications, have been developed to delay the progression of neurocognitive disorders and to decrease healthcare needs. AChEIs have been widely prescribed in clinical practice for the treatment of Alzheimer's disease, which account for 70% of dementia. The rising use of AChEIs results in increased adverse drug reactions (ADRs) such as cardiovascular and gastrointestinal adverse effects, resulting from overstimulation of peripheral cholinergic activity and muscarinic receptor activation. Changes in pharmacokinetics (PK), pharmacodynamics (PD) and pharmacogenetics (PGx), and occurrence of drug interactions are said to be major risk factors of ADRs of AChEIs in this population. To date, comprehensive reviews in ADRs of AChEIs have so far been scarcely studied. Therefore, we aimed to recapitulate and update the diverse aspects of AChEIs, including the mechanisms of action, characteristics and risk factors of ADRs, and preventive strategies of their ADRs. The collation of this knowledge is essential to facilitate efforts to reduce ADRs of AChEIs.

CONVALESCENT plasma for COVID-19: A meta-analysis of clinical trials and real-world evidence.

BACKGROUND: There is still a lack of consensus on the efficacy of convalescent plasma (CP) treatment in COVID-19 patients. We performed a systematic review and meta-analysis to investigate the efficacy of CP vs standard treatment/non-CP on clinical outcomes in COVID-19 patients. METHODS: Cochrane Library, PubMed, EMBASE and ClinicalTrials.gov were searched from December 2019 to 16 July 2021, for data from clinical trials and observational studies. The primary outcome was all-cause mortality. Risk estimates were pooled using a random-effect model. Risk of bias was assessed by Cochrane Risk of Bias tool for clinical trials and Newcastle-Ottawa Scale for observational studies. RESULTS: In total, 18 peer-reviewed clinical trials, 3 preprints and 26 observational studies met the inclusion criteria. In the meta-analysis of 18 peer-reviewed trials, CP use had a 31% reduced risk of all-cause mortality compared with standard treatment use (pooled risk ratio [RR] = 0.69, 95% confidence interval [CI]: 0.56-0.86, P = .001, I2  = 50.1%). Based on severity and region, CP treatment significantly reduced risk of all-cause mortality in patients with severe and critical disease and studies conducted in Asia, pooled RR = 0.61, 95% CI: 0.47-0.81, P = .001, I2  = 0.0%; pooled RR = 0.67, 95% CI: 0.49-0.92, P = .013, I2  = 0.0%; and pooled RR = 0.62, 95% CI: 0.48-0.80, P < .001, I2  = 20.3%, respectively. The meta-analysis of observational studies showed the similar results to the clinical trials. CONCLUSIONS: Convalescent plasma use was associated with reduced risk of all-cause mortality in severe or critical COVID-19 patients. However, the findings were limited with a moderate degree of heterogeneity. Further studies with well-designed and larger sample size are needed.

Nationwide Surveillance and Molecular Characterization of Critically Drug-Resistant Gram-Negative Bacteria: Results of the Research University Network Thailand Study.

A large-scale surveillance is an important measure to monitor the regional spread of antimicrobial resistance. We prospectively studied the prevalence and molecular characteristics of clinically important Gram-negative bacilli, including Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii complex (ABC), and Pseudomonas aeruginosa, from blood, respiratory tract, urine, and sterile sites at 47 hospitals across Thailand. Among 187,619 isolates, 93,810 isolates (50.0%) were critically drug resistant, of which 12,915 isolates (13.8%) were randomly selected for molecular characterization. E. coli was most commonly isolated from all specimens, except the respiratory tract, in which ABC was predominant. Prevalence of extended-spectrum cephalosporin resistance (ESCR) was higher in E. coli (42.5%) than K. pneumoniae (32.0%), but carbapenem-resistant (CR)-K. pneumoniae (17.2%) was 4.5-fold higher than CR-E. coli (3.8%). The majority of ESCR/CR-E. coli and K. pneumoniae isolates carried blaCTX-M (64.6% to 82.1%). blaNDM and blaOXA-48-like were the most prevalent carbapenemase genes in CR-E. coli/CR-K. pneumoniae (74.9%/52.9% and 22.4%/54.1%, respectively). In addition, 12.9%/23.0% of CR-E. coli/CR-K. pneumoniae cocarried blaNDM and blaOXA-48-like. Among ABC isolates, 41.9% were extensively drug resistant (XDR) and 35.7% were multidrug resistant (MDR), while P. aeruginosa showed XDR/MDR at 6.3%/16.5%. A. baumannii was the most common species among ABC isolates. The major carbapenemase gene in MDR-A. baumannii/XDR-A. baumannii was blaOXA-23-like (85.8%/93.0%), which had much higher rates than other ABC species. blaIMP, blaVIM, blaOXA-40-like, and blaOXA-58-like were also detected in ABC at lower rates. The most common carbapenemase gene in MDR/XDR-P. aeruginosa was blaIMP (29.0%/30.6%), followed by blaVIM (9.5%/25.3%). The findings reiterate an alarming situation of drug resistance that requires serious control measures.

Dose recommendations for intravenous colistin in pediatric patients from a prospective, multicenter, population pharmacokinetic study.

OBJECTIVES: The aim of this study was to describe the population pharmacokinetics of intravenous colistin use in children and to propose optimal dosage regimens. METHODS: A prospective, multicenter, population pharmacokinetic (PPK) study was conducted. Phoenix 64 version 8.3 was used for the PPK analysis. Simulations were performed to estimate the probability of target attainment for patients achieving target plasma colistin average steady-state concentrations (Css,avg). RESULTS: A total of 334 plasma colistin concentrations were obtained from 79 pediatric patients with a median age (interquartile range) of 2.6 years (0.8-6.8 years); 73 (92.4%) were admitted to intensive care units. Colistin pharmacokinetics were adequately described by a one-compartment model with first-order elimination along with serum creatinine (SCr) as a significant covariate in colistin clearance. The simulation demonstrated that the recommended dose of 5 mg of colistin base activity (CBA)/kg/day resulted in 18.2-63.0% probability of achieving a target Css,avg of 2 mg/l. With a lower targeted Css,avg of 1 mg/l, colistin dosing with 7.5 mg and 5 mg of CBA/kg/day were adequate for children with SCr levels of 0.1-0.3 mg/dl and >0.3 mg/dl, respectively. CONCLUSIONS: SCr is a significant covariate in colistin clearance in children. Colistin dosing should be selected according to the patient's SCr level and the desired target Css,avg.

A case of acute suppurative thyroiditis caused by Streptococcus suis infection.

INTRODUCTION: Acute suppurative thyroiditis (AST) is an uncommon but potentially life-threatening condition. The majority of AST cases are caused by bacterial infection. Streptococcus suis is a swine pathogen that mostly causes meningitis and septicemia. To date, AST caused by Streptococcus suis has not yet been reported. CASE REPORT: A 64-year-old Thai female presented with rapid enlargement of a preexisting large left thyroid nodule without compressive symptoms for one week. She had a fever and purulent discharge spontaneously drained from her fluctuated mass. Her thyroid function workup revealed elevated serum thyroid hormone levels with suppressed thyrotropin levels. Thyroid scan and uptake showed functioning thyroid tissue in the left lobe of the thyroid. Prompt antibiotic therapy and drainage were performed, and this led to significant improvement. However, thyroid cancer was suspected, and the patient underwent lobectomy. Pus cultures grew Streptococcus suis. She had a history of raw pork product consumption. CONCLUSIONS: This case highlights the importance of correct identification of pathogens for proper antibiotic therapy. AST caused by Streptococcus suis should be included in the differential diagnosis, especially in areas with a high prevalence of Streptococcus suis diseases.

Population Pharmacokinetics of Voriconazole in Patients With Invasive Aspergillosis: Serum Albumin Level as a Novel Marker for Clearance and Dosage Optimization.

BACKGROUND: Voriconazole (VRCZ) is an antifungal triazole recommended as an effective first-line agent for treating invasive aspergillosis. OBJECTIVES: To develop a population pharmacokinetic model of VRCZ and trough concentration-based dosing simulation for dynamic patient conditions. METHODS: The authors combined plasma VRCZ data from intensive sampling, and retrospective trough concentration monitoring for analysis. Nonlinear mixed-effects modeling with subsequent model validation was performed. The recommended dosage regimens were simulated based on the developed model. RESULTS: The study participants included 106 patients taking oral VRCZ. A linear one-compartment model with first-order elimination and absorption best described the observed data. The CYP2C19 phenotypes did not influence the pharmacokinetic parameters. Serum albumin (SA) levels and gamma-glutamyl transferase significantly correlated with the VRCZ clearance rate, whereas the actual body weight influenced the volume. A visual predictive check showed good consistency with the observed data, whereas SA levels across the treatment course correlated with linear clearance, irrespective of the CYP2C19 phenotype. Patients with SA levels ≤30 g/L had lower linear clearance than that in patients with SA levels >30 g/L. Dosing simulation based on the developed model indicated that patients with SA levels of ≤30 g/L required a lower daily maintenance dose to attain the therapeutic trough level. CONCLUSIONS: SA level was identified as a novel marker associated with VRCZ clearance. This marker may be a practical choice for physicians to perform therapeutic drug monitoring and optimize VRCZ dosage.

EPIDEMIOLOGY AND CONTROL OF THE FIRST REPORTED VANCOMYCIN-RESISTANT ENTEROCOCCUS OUTBREAK AT A TERTIARY-CARE HOSPITAL IN BANGKOK, THAILAND.

This retrospective study described the first reported vancomycin-resistant enterococci (VRE) outbreak from June 2013 through January 2014 at a tertiary-care hospital in Bangkok, Thailand. After the index case was detected in an 18-bed medical intermediate care unit, a number of interventions was implemented, including targeted active surveillance for VRE, strict contact precautions, enhanced standard precautions, dedicated units for VRE cases, extensive cleaning of the environment and the restricted use of antibiotics. VRE isolates were evaluated by polymerase chain reaction and random amplified polymorphic DNA (RAPD) testing. A prevalence case-control study was conducted. Among 3,699 culture samples from 2,671 patients screened, 74 patients (2.8%) had VRE. The positivity rate declined from 15.1% during week 1 to 8.2% during week 2 and then 1.4% during week 3. By weeks 4-9, the prevalences were 0-2.7%. However, the prevalence rose to 9.4% during week 10 and then subsequently declined. All VRE isolates were Enterococcus faecium and had the vanA gene. RAPD analysis revealed a single predominant clone. Multivariate analysis showed mechanical ventilation for ≥ 7 days was a predictive factor for VRE colonization [odds ratio (OR) 11.47; 95% confidence interval (CI): 1.75-75.35; p = 0.011]. This experience demonstrates VRE can easily spread and result in an outbreak in multiple-bed units. Active surveillance, early infection control interventions and rapid patient cohorting were important tools for control of this outbreak. Patients requiring mechanical ventilator for ≥ 7 days were at higher risk for VRE acquisition.