Effects of Lianhuaqingwen Capsules in adults with mild-to-moderate coronavirus disease 2019: an international, multicenter, double-blind, randomized controlled trial.

BACKGROUND: In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence. OBJECTIVES: To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19. METHODS: We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms. RESULTS: The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported. INTERPRETATION: LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 .

A Comparison Between 12 Versus 20 Weeks of Trimethoprim-sulfamethoxazole as Oral Eradication Treatment for Melioidosis: An Open-label, Pragmatic, Multicenter, Non-inferiority, Randomized Controlled Trial.

BACKGROUND: Treatment of melioidosis comprises intravenous drugs for at least 10 days, followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) for 12 to 20 weeks. Oral TMP-SMX is recommended for 12 weeks in Australia and 20 weeks in Thailand. METHODS: For this open-label, pragmatic, multicenter, noninferiority, randomized controlled trial, we enrolled patients with culture-confirmed melioidosis who had received oral eradication treatment for 12 weeks and had no clinical evidence of active melioidosis. We randomly assigned patients to stop treatment (12-week regimen) or continue treatment for another 8 weeks (20-week regimen). The primary end point was culture-confirmed recurrent melioidosis within 1 year after enrollment. The noninferiority margin was a hazard ratio (HR) of 2.0. The secondary composite end point, combining overall recurrent melioidosis and mortality, was assessed post hoc. RESULTS: We enrolled 658 patients: 322 to the 12-week regimen and 336 to the 20-week regimen. There were 5 patients (2%) in the 12-week regimen and 2 patients (1%) in the 20-week regimen who developed culture-confirmed recurrent melioidosis (HR, 2.66; 95% confidence interval [CI], .52-13.69). The criterion for noninferiority of the primary event was not met (1-sided P = .37). However, all-cause mortality was significantly lower in the 12-week regimen group than in the 20-week regimen group (1 [.3%] vs 11 [3%], respectively; HR, 0.10; 95% CI, .01-.74). The criterion for noninferiority of the secondary composite end point, combining overall recurrent melioidosis and mortality, was met (1-sided P = .022). CONCLUSIONS: Based on the lower total mortality and noninferiority of the secondary composite end point observed, we recommend the 12-week regimen of TMP-SMX for oral eradication treatment of melioidosis. CLINICAL TRIALS REGISTRATION: NCT01420341.

Natural History and Evolution of Anti-Interferon-γ Autoantibody-Associated Immunodeficiency Syndrome in Thailand and the United States.

BACKGROUND: The natural history of anti-interferon-γ (IFN-γ) autoantibody-associated immunodeficiency syndrome is not well understood. METHODS: Data of 74 patients with anti-IFN-γ autoantibodies at Srinagarind Hospital, Thailand, were collected annually (median follow-up duration, 7.5 years). Annual data for 19 patients and initial data for 4 patients with anti-IFN-γ autoantibodies at the US National Institutes of Health were collected (median follow-up duration, 4.5 years). Anti-IFN-γ autoantibody levels were measured in plasma samples. RESULTS: Ninety-one percent of US patients were of Southeast Asian descent; there was a stronger female predominance (91%) in US than Thai (64%) patients. Mycobacterium abscessus (34%) and Mycobacterium avium complex (83%) were the most common nontuberculous mycobacteria in Thailand and the United States, respectively. Skin infections were more common in Thailand (P = .001), whereas bone (P < .0001), lung (P = .002), and central nervous system (P = .03) infections were more common in the United States. Twenty-four percent of Thai patients died, most from infections. None of the 19 US patients with follow-up data died. Anti-IFN-γ autoantibody levels decreased over time in Thailand (P < .001) and the United States (P = .017), with either cyclophosphamide (P = .01) or rituximab therapy (P = .001). CONCLUSIONS: Patients with anti-IFN-γ autoantibodies in Thailand and the United States had distinct demographic and clinical features. While titers generally decreased with time, anti-IFN-γ autoantibody disease had a chronic clinical course with persistent infections and death. Close long-term surveillance for new infections is recommended.

Efficacy of anidulafungin in 539 patients with invasive candidiasis: a patient-level pooled analysis of six clinical trials.

Objectives: To evaluate the efficacy of anidulafungin for the treatment of candidaemia and invasive candidiasis in a large dataset, including patients with deep-seated tissue candidiasis, neutropenia and infection due to non- albicans Candida species. Methods: Data were pooled from six prospective, multicentre, multinational studies: four open-label, non-comparative studies of anidulafungin and two double-blind, double-dummy, randomized studies of anidulafungin versus caspofungin (clinical trial registrations: NCT00496197, NCT00548262, NCT00537329, NCT00689338, NCT00806351 and NCT00805740; ClinicalTrials.gov). In all studies, patients with culture-confirmed invasive candidiasis received a single intravenous (iv) loading dose of anidulafungin 200 mg on day 1, followed by 100 mg once-daily. Switch to oral fluconazole or voriconazole was permitted after 5-10 days of iv treatment in all studies except one. Antifungal treatment (iv plus oral therapy if applicable) was maintained for ≥14 days after the last positive Candida culture. The primary endpoint was successful global response at end of iv therapy (EOivT) in the modified ITT (mITT) population. Results: In total, 539 patients were included (mITT population). The most common baseline Candida species were Candida albicans (47.9%), Candida glabrata (21.0%), Candida tropicalis (13.7%), Candida parapsilosis (13.2%) and Candida krusei (3.5%). Median duration of anidulafungin iv treatment was 10.0 days. The global response success rate at EOivT was 76.4% (95% CI 72.9%-80.0%). All-cause mortality was 13.0% on day 14 and 19.1% on day 28. Adverse events (AEs) were consistent with the known AE profile for anidulafungin. Conclusions: These data demonstrate that anidulafungin is effective for treatment of candidaemia and invasive candidiasis in a broad patient population.

Improvement of lipid profiles when switching from efavirenz to rilpivirine in HIV-infected patients with dyslipidemia.

Rilpivirine (RPV) is a non-nucleoside reverse transcriptase inhibitor, which has better lipid profiles than efavirenz (EFV) in treatment naïve patients. However, the data on treatment experience are limited especially in dyslipidemic HIV patients; thus, we aimed to assess the change of lipid profiles after switching from EFV to RPV in these patients. In this prospective, open-label, cohort study, we enrolled HIV-1 infected adults who had received at least 6 months of EFV-based regimen, with HIV RNA <50 copies/mL for ≥6 months prior to switching. The objectives of this study were to analyze lipid changes and to evaluate the efficacy, safety, tolerability at 24 weeks after switching therapy. Fifty-three patients were enrolled and completed the study. At week 24, a significant decrease in the mean (95% confident interval, CI) total cholesterol (-28.06 mg/dL, 95%CI -35.20 to -20.91, p < 0.0001), LDL-cholesterol (-20.96 mg/dL, 95%CI -28.12 to -13.80, p < 0.0001), high-density lipoprotein (HDL)-cholesterol (-5.11 mg/dL, 95%CI -7.79 to -2.44, p < 0.0001), and triglyceride (-29.79 mg/dL. 95%CI -52.39 to -7.19, p = 0.011) levels were observed. One patient had virologic rebound with HIV RNA of 114 copies/mL at week 24. Three (5.7%) patients had grade 2 elevations of liver enzymes. None of the patients discontinued RPV during the study. Switching from EFV-based therapy to RPV-based regimen improved lipid profiles in fully suppressed HIV patients with dyslipidemia. This treatment should be considered in these patients.

Candidate HLA genes for prediction of co-trimoxazole-induced severe cutaneous reactions.

BACKGROUND: Co-trimoxazole is a sulfonamide-containing antibiotic that is effective in the treatment of several infections and for prophylaxis of Pneumocystis jiroveci pneumonia. This drug has been reported as a common culprit drug for the Stevens-Johnson syndrome (SJS) and for toxic epidermal necrolysis (TEN). Human leukocyte antigens (HLAs) play a key role in the immunopathogenesis of severe cutaneous reactions induced by several drugs. This study investigated the association between the HLA class I and HLA-DRB1 polymorphisms and co-trimoxazole-induced SJS/TEN in a Thai population. METHODS: Forty-three patients with co-trimoxazole-induced SJS/TEN and 91 co-trimoxazole-tolerant patients were enrolled in the study. HLA class I and HLA-DRB1 were genotyped using the reverse sequence-specific oligonucleotide probe method. RESULTS: The frequencies of three alleles of HLA, namely HLA-B*15:02, HLA-C*06:02, and HLA-C*08:01, were significantly higher in the co-trimoxazole-induced SJS/TEN group compared with controls. The risks for co-trimoxazole-induced SJS/TEN in patients with the HLA-B*15:02, HLA-C*06:02, or HLA-C*08:01 allele were about 3-11-fold higher when compared with those who did not carry one of these alleles. Individuals who carried the HLA-B*15:02-C*08:01 haplotype had a 14-fold higher risk for co-trimoxazole-induced SJS/TEN. CONCLUSION: Evidence of associations between co-trimoxazole-induced SJS/TEN and HLA alleles including HLA-B*15:02, HLA-C*06:02, and HLA-C*08:01 were found in the study population. These findings may suggest that apart from the HLA molecules, other molecules involved in the molecular pathogenesis of these severe cutaneous adverse drug reactions may play an important role in the susceptibility of individuals to SJS/TEN caused by co-trimoxazole.

Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre, double-blind, non-inferiority, randomised controlled trial.

BACKGROUND: Melioidosis, an infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei, is difficult to cure. Antimicrobial treatment comprises intravenous drugs for at least 10 days, followed by oral drugs for at least 12 weeks. The standard oral regimen based on trial evidence is trimethoprim-sulfamethoxaxole (TMP-SMX) plus doxycycline. This regimen is used in Thailand but is associated with side-effects and poor adherence by patients, and TMP-SMX alone is recommended in Australia. We compared the efficacy and side-effects of TMP-SMX with TMP-SMX plus doxycycline for the oral phase of melioidosis treatment. METHODS: For this multi-centre, double-blind, non-inferiority, randomised placebo-controlled trial, we enrolled patients (aged ≥15 years) from five centres in northeast Thailand with culture-confirmed melioidosis who had received a course of parenteral antimicrobial drugs. Using a computer-generated sequence, we randomly assigned patients to receive TMP-SMX plus placebo or TMP-SMX plus doxycycline for 20 weeks (1:1; block size of ten, stratified by study site). We followed patients up every 4 months for 1 year and annually thereafter to the end of the study. The primary endpoint was culture-confirmed recurrent melioidosis, and the non-inferiority margin was a hazard ratio (HR) of 1.7. This study is registered with www.controlled-trials.com, number ISRCTN86140460. FINDINGS: We enrolled and randomly assigned 626 patients: 311 to TMP-SMX plus placebo and 315 to TMP-SMX plus doxycycline. 16 patients (5%) in the TMP-SMX plus placebo group and 21 patients (7%) in the TMP-SMX plus doxycycline group developed culture-confirmed recurrent melioidosis (HR 0.81; 95% CI 0.42-1.55). The criterion for non-inferiority was met (p=0.01). Adverse drug reactions were less common in the TMP-SMX plus placebo group than in the TMP-SMX plus doxycycline group (122 [39%] vs 167 [53%]). INTERPRETATION: Our findings suggest that TMP-SMX is not inferior to TMP-SMX plus doxycycline for the oral phase of melioidosis treatment, and is preferable on the basis of safety and tolerance by patients. FUNDING: Thailand Research Fund, the Melioidosis Research Center, the Center of Excellence in Specific Health Problems in Greater Mekong Sub-region cluster, and the Wellcome Trust.

Adult-onset immunodeficiency in Thailand and Taiwan.

BACKGROUND: Autoantibodies against interferon-γ are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown. METHODS: We enrolled 203 persons from sites in Thailand and Taiwan in five groups: 52 patients with disseminated, rapidly or slowly growing, nontuberculous mycobacterial infection (group 1); 45 patients with another opportunistic infection, with or without nontuberculous mycobacterial infection (group 2); 9 patients with disseminated tuberculosis (group 3); 49 patients with pulmonary tuberculosis (group 4); and 48 healthy controls (group 5). Clinical histories were recorded, and blood specimens were obtained. RESULTS: Patients in groups 1 and 2 had CD4+ T-lymphocyte counts that were similar to those in patients in groups 4 and 5, and they were not infected with the human immunodeficiency virus (HIV). Washed cells obtained from patients in groups 1 and 2 had intact cytokine production and a response to cytokine stimulation. In contrast, plasma obtained from these patients inhibited the activity of interferon-γ in normal cells. High-titer anti-interferon-γ autoantibodies were detected in 81% of patients in group 1, 96% of patients in group 2, 11% of patients in group 3, 2% of patients in group 4, and 2% of controls (group 5). Forty other anticytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte-macrophage colony-stimulating factor. No other anticytokine autoantibodies or genetic defects correlated with infections. There was no familial clustering. CONCLUSIONS: Neutralizing anti-interferon-γ autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research; ClinicalTrials.gov number, NCT00814827.).

INTRAOSSEOUS PROLIFERATIVE SPARGANOSIS PRESENTING AS A PATHOLOGICAL FRACTURE: A CASE REPORT AND REVIEW OF THE LITERATURE.

We report a case of 63-year-old male, who presented with pathological fracture of left distal humerus 3 weeks previously. The radiographic findings showed an ill-defined permeative osteolytic lesion of the left distal humerus. Incisional biopsy and debridement was done; pathological examination revealed a folded cestode larva with calcareous corpuscles in the bone and soft tissue, and increased eosinophils. IgG antibody tests for sparganosis were positive. The patient refused to have surgery for internal fixation and placement of an endoprosthesis.

Comparison of Standard and Prone-Position Electrocardiograms in COVID-19 Patients With Pulmonary Complications: Correlations and Implications.

BACKGROUND: Previous research highlighted variability in electrocardiogram (ECG) readings across patient positions, particularly in the context of COVID-19 patients with pulmonary complications requiring prone positioning as part of the treatment. OBJECTIVE: This study aimed to elucidate the effects of prone positioning on ECG parameters and explore its association with the severity of COVID-19. METHODS: A prospective cohort study involved 60 patients diagnosed with COVID-19 and presenting pulmonary complications. ECGs were recorded in both supine and prone positions, and analyzed for various parameters including heart rate, QRS axis, and QTc interval. Clinical severity was assessed using APACHE II scores and SpO2/FiO2 ratios. RESULTS: Prone positioning led to an increase in heart rate (mean difference: 2.100, 95% CI: 0.471-3.729, p = 0.012), with minor shifts in the QRS axis. Heart rate and QRS axis demonstrated strong positive correlations between positions, with Pearson's correlation coefficients of 0.927 and 0.894, respectively. The study also found a significant association between prolonged QTc intervals in the prone position and elevated APACHE II scores, with a relative risk of 10.75 (95% CI: 1.82-63.64, p = 0.008). CONCLUSIONS: The prone positioning caused minor yet significant changes in heart rate and QRS axis. The correlation of prolonged QTc intervals in the prone position with higher APACHE II scores suggests the prognostic relevance of prone ECG in COVID-19 patients. However, further research is needed to fully understand the clinical implications and mechanisms of these findings.

Intravenous anidulafungin followed optionally by oral voriconazole for the treatment of candidemia in Asian patients: results from an open-label Phase III trial.

BACKGROUND: Candidemia is a significant cause of morbidity and mortality in hospitalized patients, particularly in Asia. Anidulafungin has been reported to be an effective treatment for candidemia in Western populations, but little is known about its efficacy in Asian patients, where the clinical presentation and epidemiology may be different. METHODS: An open-label study of anidulafungin for the treatment of candidemia was recently conducted in several Asian countries. Treatment was initiated with intravenous anidulafungin, given for at least 5 days, with the option to complete treatment with oral voriconazole. The primary endpoint was global (clinical and microbiological) response, and the primary analysis was the proportion of patients in the modified intent-to-treat population with successful global response at the end of therapy. Secondary analyses included proportion with successful global response in clinically relevant patient subgroups. The safety and tolerability profile of anidulafungin and voriconazole in this population was also investigated. RESULTS: Forty-three patients were studied, including 42 in the modified intent-to-treat population. Eighteen patients were > 65 years, the largest age subgroup, and 21 had central venous catheters. The most common Candida species causing infection were C. tropicalis (n = 18) and C. albicans (n = 10). In the primary analysis, 73.8% had a successful global response at end of therapy. Success rates in subgroups were: 72.2% for C. tropicalis and 71.4% for C. albicans infection, 58.8% for patients > 65 years, and 81.0% for patients with central venous catheters. Safety and tolerability were comparable with the known profiles for anidulafungin (and voriconazole). CONCLUSIONS: Although the epidemiology of Candida infections was different in this open-label study, the efficacy of anidulafungin in Asian patients with documented candidemia was consistent with previous studies in Western populations. No new safety concerns were identified. TRIAL REGISTRATION: http://www.clinicaltrials.gov identifier NCT00537329.

A two-arm analysis of the immune response to heterologous boosting of inactivated SARS-CoV-2 vaccines.

Several vaccine programs were introduced during the COVID-19 pandemic, which included inactivated virus, DNA viral vectors and mRNA vaccines. Booster programs are recommended, especially for those in high-risk groups. However, many of these booster programs involve heterologous vaccines. This study enrolled volunteers who first received two full-dose CoronaVac vaccinations before receiving heterologous boosters with DNA- and/or mRNA-vaccines for an additional 2 doses (n = 40) or an additional 3 doses (n = 16). Our results showed no difference in side effects, neutralizing antibodies, or T-cell responses for any of the heterologous vaccination programs. However, the neutralizing capacity and IFN-γ responses against the Omicron variant in volunteers who received 4 or 5 doses were improved. Polarization of peripheral memory T cells after stimulation in all booster groups with Omicron peptide showed an increased trend of naïve and central memory phenotypes of both CD4+ and CD8+ T cells, suggesting that exposure to Omicron antigens will drive T cells into a lymphoid resident T cell phenotype. Our data support a continuous vaccination program to maximize the effectiveness of immunity, especially in people at high risk. Furthermore, the number of boosting doses is important for maintaining immunity.

Efficacy and safety of Lianhua Qingwen capsules combined with standard of care in the treatment of adult patients with mild to moderate COVID-19 (FLOSAN): protocol for a randomized, double-blind, international multicenter clinical trial.

Background: Effective anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs are not only the next defense after vaccines but also the key part of establishing a multi-tiered coronavirus disease 2019 (COVID-19) prevention and control system. Previous studies had indicated that Lianhua Qingwen (LHQW) capsules could be an efficacious Chinese patent drug for treating mild to moderate COVID-19. However, pharmacoeconomic evaluations are lacking, and few trials have been conducted in other countries or regions to evaluate the efficacy and safety of LHQW treatment. So, this study aims to explore the clinical efficacy, safety, and economy of LHQW for treating adult patients with mild to moderate COVID-19. Methods: This is a randomized, double-blind, placebo-controlled, international multicenter clinical trial protocol. A total of 860 eligible subjects are randomized at a 1:1 ratio into the LHQW or placebo group to receive two-week treatment and follow-up visits on days 0, 3, 7, 10, and 14. Clinical symptoms, patient compliance, adverse effects, cost scale, and other indicators are recorded. The primary outcomes will be the measured median time to sustained improvement or resolution of the nine major symptoms during the 14-day observation period. Secondary outcomes regarding clinical efficacy will be evaluated in detail on the basis of clinical symptoms (especially body temperature, gastrointestinal symptoms, smell loss, and taste loss), viral nucleic acid, imaging (CT/chest X-ray), the incidence of severe/critical illness, mortality, and inflammatory factors. Moreover, we will assess health care cost, health utility, and incremental cost-effectiveness ratio (ICER) for economic evaluation. Discussion: This is the first international multicenter randomized controlled trial (RCT) of Chinese patent medicine for the treatment of early COVID-19 in accordance with WHO guidelines on COVID-19 management. This study will help clarify the potential efficacy and cost-effectiveness of LHQW in the treatment of mild to moderate COVID-19, facilitating decision-making by healthcare workers. Registration: This study is registered at the Chinese Clinical Trial Registry, with registration number: ChiCTR2200056727 (date of first registration: 11/02/2022).

Prevalence and genotypic relatedness of carbapenem resistance among multidrug-resistant P. aeruginosa in tertiary hospitals across Thailand.

BACKGROUND: Increased infection caused by multidrug resistant (MDR) Pseudomonas aeruginosa has raised awareness of the resistance situation worldwide. Carbapenem resistance among MDR (CR-MDR) P. aeruginosa has become a serious life-threatening problem due to the limited therapeutic options. Therefore, the objectives of this study were to determine the prevalence, the antibiotic susceptibility patterns and the relatedness of CR-MDR P. aeruginosa in tertiary hospitals across Thailand. METHODS: MDR P. aeruginosa from eight tertiary hospitals across Thailand were collected from 2007-2009. Susceptibility of P. aeruginosa clinical isolates was determined according to the Clinical and Laboratory Standards Institute guideline. Selected CR-MDR P. aeruginosa isolates were genetically analyzed by pulsed-field gel electrophoresis. RESULTS: About 261 clinical isolates were identified as MDR P. aeruginosa and approximately 71.65% were found to be CR-MDR P. aeruginosa. The result showed that the meropenem resistance rate was the highest reaching over 50% in every hospitals. Additionally, the type of hospitals was a major factor affecting the resistance rate, as demonstrated by significantly higher CR-MDR rates among university and regional hospitals. The fingerprinting map identified 107 clones with at least 95% similarity. Only 4 clones were detected in more than one hospital. CONCLUSIONS: Although the antibiotic resistance rate was high, the spreading of CR-MDR was found locally. Specific strains of CR-MDR did not commonly spread from one hospital to another. Importantly, clonal dissemination ratio indicated limited intra-hospital transmission in Thailand.

Acinetobacter baumannii nosocomial pneumonia in tertiary care hospitals in Thailand.

BACKGROUND: Nosocomial pneumonia (NP) is an important cause of morbidity and mortality in hospitalized patients. Acinetobacter baumannii is one of the common causative pathogens in NP. The prevalence of multi-drug resistance in A. baumannii has been increasing. The information on clinical features and clinical courses of A. baumannii NP in Thai patients are limited. OBJECTIVE: To determine the clinical features, risk factors and clinical courses of A. baumannii NP in Thai patients hospitalized in tertiary care hospitals in Thailand. MATERIAL AND METHOD: This was a prospective, hospital-based, active surveillance study on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) in adults hospitalized in 12 tertiary care hospitals in Thailand between 2008 and 2009. RESULTS: There were 651 NP patients. A. baumannii was the most common cause of NP in 198 patients (30.4%). Most of NP patients were males with median age of 71 years. About 80% had late onset NP with the median duration of 10 days after admission in both A. baumannii and non-A. baumannii NP. Most of NP occurred in patients hospitalized in general medical wards. Most of the features of NP in A. baumannii NP and non-A. baumannii NP were not significantly different. The initial antibiotics prescribed were concordant in about 50% of the patients in both groups. Colistin was usually prescribed to the patients who received antibiotic modifications. The initial clinical responses in A. baumannii NP were less favorable than those in non-A. baumannii NP. The mortality rate in A. baumannii NP seemed to be more than that in non-A. baumannii NP. There was a trend of more persistence of pathogen in A. baumannii NP. Most isolates of A. baumannii were resistant to antibiotics including carbapenems. The patients with extensive drug resistant A. baumannii NP had less favorable responses than NP due to other bacteria, including non-extensive drug resistant A. baumannii. VAP, NP developed in medical ICU and NP with bilateral lung involvements on chest X-ray were associated with A. baumannii as the isolated pathogen. CONCLUSION: A. baumannii is the most common causative pathogen for NP in tertiary care hospitals in Thailand and most of A. baumannii isolates were resistant to many antibiotics including carbapenems. The hospitalized patient in tertiary care hospitals with VAP, or NP that was developed in medical ICU, or NP with bilateral lung involvements on chest x-ray was likely to be due to A. baumannii. Many NP patients received inappropriate initial antibiotic regimens leading to a high mortality.

Varicella zoster meningitis following COVID-19 vaccination: a report of two cases.

Most of the adverse effects reported in patients who have received COVID-19 vaccines have been mild. However, possible serious adverse effects are being monitored cautiously. There have also been a number of case reports of reactivation of varicella zoster infection within 28 days after immunization with mRNA COVID-19 vaccines. A few cases have also been reported after viral vector and inactivated COVID-19 vaccination. The incidence of meningitis following varicella zoster virus infection is rare. In the current study, we report two cases of male patients who received two different types of COVID-19 vaccine (inactivated and viral vector) and developed varicella zoster meningitis within 10 days after vaccination.

Evaluation of an in-house immunoperoxidase staining assay for histodiagnosis of human pythiosis.

Pythiosis, a life-threatening infectious disease of humans and animals in tropical and subtropical countries, is caused by the fungus-like organism Pythium insidiosum. As diagnosis of pythiosis is difficult, delayed diagnosis of pythiosis leads to poor prognosis. We developed an immunoperoxidase staining assay using rabbit anti-P. insidiosum antibodies to detect P. insidiosum directly in infected tissues of 19 patients with vascular (n = 11), ocular (n = 7) or cutaneous (n = 1) pythiosis. Tissue sections from 31 patients with various fungal infections were included as controls. Tissue sections from all pythiosis patients and 2 patients with Fusarium infections were stained positive, whereas the other 29 control sections were stained negative. Sensitivity and specificity of the assay was 100% and 94%, respectively. Based on the prevalence of human pythiosis (2%), calculated positive predictive value and negative predictive value was 24% and 100%, respectively. Thus, the diagnostic value of this assay is for ruling out pythiosis. The assay requires routine laboratory equipments and can easily be performed by pathologists in rural hospitals where the disease is more prevalent.

Antimicrobial resistance surveillance of Vibrio cholerae in Thailand from 2000 to 2004.

OBJECTIVE: To study the trends of antimicrobial resistance pattern of Vibrio cholerae in Thailand between 2000 and 2004. MATERIAL AND METHOD: All isolates of Vibrio cholerae from 28 hospitals across Thailand between 2000 and 2004 were tested for their susceptibility to ampicillin, chloramphenicol, norfloxacin, tetracycline and trimethoprim/sulfamethoxazole by the disk diffusion method (Kirby Bauer). The relevant data were collected and analyzed by the WHONET software program supported by the World Health Organization (WHO). RESULTS: V. cholerae O1, serotype Inaba was much more common than serotype Ogawa. The most frequent type of clinical specimens that V. cholerae isolated was the stool. There was no trend of increasing resistance of all V. cholerae both O1 and non O1. Over all average rates of tetracycline resistance of V. cholerae O1, Inaba and Ogawa were 0.9% and 16.3% respectively and trimethoprim/sulfamethoxazole resistance were 0.4% and 60.5% respectively. The strains were not resistant to norfloxacin. CONCLUSION: In Thailand, V. cholerae O1 were still susceptible to tetracycline and norfloxacin which were the most frequently antimicrobial used for the treatment of cholera. The trend of increasing resistance during the study period was not detected.

An overview of antimicrobial susceptibility patterns of gram-positive bacteria from National Antimicrobial Resistance Surveillance Thailand (NARST) program from 2000 to 2005.

In this overview, the authors summarize the antimicrobial susceptibility patterns of important Gram-positive bacteria from the National Antimicrobial Resistance Surveillance Thailand (NARST) program between 2000 and 2005 as well as the clinical implications. This collaborative network program was funded by the World Health Organization, and involved 33 hospitals throughout Thailand. There are rising trends of drug-resistant S. pneumoniae (DRSP), ampicillin-resistant enterococci, but a constant occurrence of methicillin-resistant S. aureus (MRSA) was noted during this period. The rates of penicillin and erythromycin resistances of S. pneumoniae were constantly high, ranging from 42.5% to 47.7% and 24.6% to 31.1%, respectively, whereas the rates of cefotaxime resistance were quite low, ranging from 2.1% to 8.4%. The rates of multidrug-resistant (MDR) S. pneumoniae ranged from 14.8% to 34.3%. Of all S. aureus isolates, MRSA comprised 24% to 27%, and vancomycin resistance rates of these MRSA isolates ranged from 0.1% to 0.8%. The antimicrobial resistance rates of methicillin-susceptible S. aureus isolates were very low. The rates of ampicillin and high-level gentamicin resistances of E. faecium from 2000 to 2005 have been significantly increasing from 52% to 84.1%, and from 46.9% to 75%, respectively, but vancomycin resistance was stable at the rates between 0.4% and 1.9%. In conclusions, antimicrobial resistance rates of important Gram-positive bacteria have been increasing in Thailand. All local, national, and international surveillance data will help to set the strategic plan for control and treatment of these resistant organisms. Appropriate and accurate microbiological procedures regarding the collection and transportation of clinical specimens as well as the identification of these emerging resistant organisms are urgently needed, in collaboration with other concerned sectors.

Antimicrobial resistance of Escherichia coli isolated from urine in Thailand from 2000 to 2005.

OBJECTIVE: To study the trends of antimicrobial resistance of Escherichia coli in Thailand during 2000 and 2005. MATERIAL AND METHOD: All isolates of E. coli from 28 hospitals across Thailand from 2000 to 2005 were tested for their susceptibility to aminoglycosides, beta-lactams, fluoroquinolones, and trimethoprim-sulfamethoxazole by the disk diffusion method (Kirby Bauer). The relevant data were collected and analyzed by the WHONET software program supported by the World Health Organization. RESULTS: The rate of resistance to ampicillin, ceftriaxone, ceftazidime gentamicin, and ciprofloxacin increased from 79.3% to 85.3%, 12.7% to 28.5%, 10.7% to 15.2%, 25% to 32.9%, and 45.1% to 51% during the 6-year period from 2000 to 2005 among isolates from catheterized urine, respectively. The rate of resistance to gentamicin and ceftriaxone increased from 23.2% to 28.9% and 6.8% to 24.2%, from 2000 to 2005 respectively among isolates in non-intensive care units (non-ICUs). The rate of resistance to gentamicin increased from 18% to 26.1%, and 24.2% to 29.6% among isolates in out-patient department (OPD) and non-OPD, respectively. The rate of resistance to ceftriaxone increased from 2.5% to 15.4%, and 7.9% to 25.9% among isolates in OPD and non-OPD, respectively. The rate of resistance to gentamicin and ceftriaxone increased from 23.2% to 28.9%, and 6.8% to 24.2% among isolates in non-ICU, respectively. The rate of resistance to trimethoprim-sulfamethoxazole decreased from 71.2% to 62.6% among isolates in non-ICUs. Isolates from catheterized urine were significantly associated with imipenem resistance (p > 0.05). CONCLUSION: The present study shows a significant correlation between ciprofloxacin resistance and fluoroquinolone use, and indicates that prior fluoroquinolone use seems to be the most important risk factor for ciprofloxacin-resistant E. coli bacteremia. Isolates from catheterized urine were significantly associated with resistance to imipenem, and the ICU hospitalization and OPD attention during the previous year were significantly associated with ofloxacin resistant E. coli.