Mueang Nonthaburi, Thailand
Mueang Nonthaburi, Thailand

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Aramwit P.,Chulalongkorn University | Palapinyo S.,Chulalongkorn University | Srichana T.,Prince of Songkla University | Chottanapund S.,Bamrasnaradura Infectious Diseases Institute | Muangman P.,Mahidol University
Archives of Dermatological Research | Year: 2013

The aim of this study was to evaluate the effect of silk sericin, a protein from silkworm cocoon, on scratch wound healing in vitro. For applicable result in clinical use, we also study the efficacy of sericin added to a standard antimicrobial cream, silver zinc sulfadiazine, for open wound care in the treatment of second-degree burn wounds. In vitro scratch assays show that sericin at concentration 100 μg/mL can promote the migration of fibroblast L929 cells similar to epidermal growth factor (positive control) at 100 μg/mL. After 1 day of treatment, the length of scratch in wounds treated with sericin was significantly shorter than the length of negative control wounds (culture medium without sericin). For clinical study, a total of 29 patients with 65 burn wounds which covered no less than 15 % of total body surface area were randomly assigned to either control (wounds treated with silver zinc sulfadiazine cream) or treatment (wounds treated with silver zinc sulfadiazine with added sericin cream) group in this randomized, double-blind, standard-controlled study. The results showed that the average time to reach 70 % re-epithelialization of the burned surface and complete healing in the treatment group was significantly shorter, approximately 5-7 days, than in the control group. Regarding time for complete healing, control wounds took approximately 29.28 ± 9.27 days, while wounds treated with silver zinc sulfadiazine with added sericin cream took approximately 22.42 ± 6.33 days, (p = 0.001). No infection or severe reaction was found in any wounds. This is the first clinical study to show that silk sericin is safe and beneficial for burn wound treatment when it is added to silver sulfadiazine cream. © 2013 Springer-Verlag Berlin Heidelberg.


Wattanakul T.,Chulalongkorn University | Avihingsanon A.,Red Cross | Avihingsanon A.,Chulalongkorn University | Manosuthi W.,Bamrasnaradura Infectious Diseases Institute | Punyawudho B.,Chulalongkorn University
Antiviral Therapy | Year: 2014

Background: Nevirapine-based antiretroviral therapy is widely used as a first-line treatment for HIV-infected patients in resource-limited settings. Nevirapine plasma concentration has been shown to be associated with virological response and treatment failure. Therefore, identifying sources of the variability of nevirapine pharmacokinetics is important for dose optimization. The purpose of the current study was to determine the population mean pharmacokinetic parameters and identify factors that influence pharmacokinetic parameters of nevirapine in Thai HIV-infected patients.Methods: The model was developed by a non-linear mixed-effects modelling approach using NONMEM. Model validation was performed using bootstrap analysis and external validation. Additionally, nevirapine plasma concentrations of 200 mg twice daily (NVPBID) and 400 mg once daily (NVPOD) were simulated using the final model to investigate the impact of the covariates and different dosage regimens on nevirapine steady state concentrations.Results: The apparent clearance (CL/F) of nevirapine estimated from this population was 2.51 l/h which is lower than the values previously reported in other populations. The concomitant use of rifampicin increased CL/F by 20%. Simulated nevirapine plasma concentrations from NVPBID were superior to the NVPOD regimen.Conclusions: This population-based pharmacokinetic model can be used for optimizing nevirapine dosage regimens for individual patients to improve efficacy and safety of nevirapine therapy in this population. © 2014 International Medical Press.


Khawcharoenporn T.,Thammasat University | Apisarnthanarak A.,Thammasat University | Manosuthi W.,Bamrasnaradura Infectious Diseases Institute | Sungkanuparph S.,Mahidol University | Mundy L.M.,L M Mundy LLC
International Journal of Tuberculosis and Lung Disease | Year: 2012

SETTING: Human immunodeficiency virus (HIV) clinics at two Thai tertiary care medical centres. OBJECTIVES: To evaluate the efficacy of tuberculin skin test (TST) guided isoniazid preventive therapy (IPT) in combination with antiretroviral therapy (ART) in the prevention of tuberculosis (TB). DESIGN: A 4-year prospective comparative study of patients at two HIV clinics: one performed TST at enrolment and, if positive, prescribed IPT (IPT group), while the other did not perform TST (non-IPT group). RESULTS: There were 200 patients included in each group. Baseline characteristics and drop-out rates were similar in both groups. The incidence of pulmonary TB over 4 years was not significantly different between the IPT and non-IPT groups (0.80 cases vs. 1.76 per 100 person-years [py], P = 0.13). However, the incidence of pulmonary TB in the non-IPT group was significantly higher during the first 6 months (8.60 vs. 0 cases/100 py, P = 0.01) and among patients with initial CD4 < 200 cells/μl (9.41 vs. 0 cases/100 py, P = 0.02). The survival analyses demonstrated a protective effect of IPT (χ2 = 3.66, P = 0.04) for early TB. CONCLUSIONS: Benefit of IPT plus ART was evident only in the first 6 months of care. These findings suggest that TST-guided IPT should be routinely provided for HIV-infected patients after initial entry into medical care. © 2012 The Union.


Siripongpreeda N.,Bamrasnaradura Infectious Diseases Institute
Journal of the Medical Association of Thailand = Chotmaihet thangphaet | Year: 2010

This study assessed clinical differences between invasive pneumococcal disease (IPD) caused by penicillin-resistant and penicillin-sensitive Streptococcus pneumoniae. Patients with IPD confirmed during January 1996-December 2007 at three hospitals were included. Clinical characteristics and outcomes were compared between patients infected with penicillin-resistant Streptococcus pneumoniae (PRSP) and penicillin-sensitive Streptococcus pneumoniae (PSSP). Sixty-nine patients with IPD were identified during the study period, 20 (29%) of whom were infected with PRSP and 49 (71%) with PSSP. Sex, mean age, underlying diseases and seasonal variation did not differ statistically between the two groups. No significant differences were identified in clinical course as measured by time until defervescence, duration of hospitalization and clinical outcome. Minimum inhibitory concentrations (MIC) for other antibiotics were determined; 20% and 10% of PRSP isolates were nonsusceptible to cephalosporins and meropenem, respectively, but all isolates were sensitive to vancomycin. There were no significant differences identified in the clinical epidemiology of lPD cases caused by PRSP and PSSP.


Mankhatitham W.,Bamrasnaradura Infectious Diseases Institute | Lueangniyomkul A.,Bamrasnaradura Infectious Diseases Institute | Manosuthi W.,Bamrasnaradura Infectious Diseases Institute
Southeast Asian Journal of Tropical Medicine and Public Health | Year: 2011

To evaluate the rate of and risk factors for hepatotoxicity in tuberculosis (TB) and human immunodeficiency virus type 1 (HIV-1) co-infected patients while receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) and a rifampicin (RMP)-containing anti-TB regimen. We analyzed data from the N2R study which was an open label, randomized, comparative trial comparing treatment outcomes between 71 TB/HIV-1 co-infected patients receiving efavirenz (EFV)-based and nevirapine (NVP)-based ART; all of whom were receiving RMP-containing anti-TB treatment. Demographic data, liver function test, CD4 cell count, plasma HIV-1 RNA, hepatitis B surface antigen and anti-hepatitis C virus antibody were collected before initiating ART (week 0). Liver enzymes and total bilirubin levels were monitored at 6 weeks, 12 weeks and 24 weeks after ART initiation. All patients were followed until TB therapy was completed. Of 142 patients, 8 patients were excluded. Among the remaining 134 patients, the mean ± SD age was 36.8 ± 8.6 years and 67.2% were male. Severe hepatotoxicity (grade 3 or 4) developed in 4 patients (2.9%); 3 patients (4.6%) in the NVP group and 1 patient (1.4%) in the EFV group. Severe hyperbilirubinemia (grade 3or 4) occurred in 7 patients (5.2%); 5 patients (7.7%) in the NVP group and 2 patients (2.9%) in the EFV group. Grade 1 or 2 hepatotoxicity occurred in 34 patients (31.4%). Hepatitis C virus co-infection (adjusted OR 3.03; 95%CI 1.26-7.29) was an independent risk factor associated with grade 1-4 hepatotoxicity (p=0.013). Monitoring of hepatotoxicity should be considered in TB/HIV-1 co-infected patients who are infected with HCV and receiving NVP.


Manosuthi W.,Bamrasnaradura Infectious Diseases Institute | Sukasem C.,Mahidol University | Lueangniyomkul A.,Bamrasnaradura Infectious Diseases Institute | Mankatitham W.,Bamrasnaradura Infectious Diseases Institute | And 4 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2013

Comprehensive information on the effects of cytochrome P450 2B6 (CYP2B6) polymorphisms, clinical factors, and drug-drug interactions on efavirenz concentrations in HIV/tuberculosis-coinfected (HIV/TB) patients is unavailable.A total of 139 HIV/TB adults, 101 of whom received a rifampin-containing anti-TB regimen, were prospectively enrolled to receive efavirenz (600 mg)/ tenofovir/lamivudine.Nine single nucleotide polymorphisms (SNPs) within CYP2B6 were genotyped.Plasma efavirenz concentrations were measured at 12 weeks.The median (interquartile range [IQR]) efavirenz concentration was 2.3 (1.4 to 3.9) mg/liter.The SNPs (frequencies of heterozygous and homozygous mutants) were 64C>T (10% and 1%), 499C>G (0% and 0%), 516G>T (47% and 8%), 785A>G (54% and 10%), 1375A>G (0% and 0%), 1459C>T (3% and 0%), 3003C>T (44% and 27%), 18492T>C (39% and 6%), and 21563C>T (57% and 5%).The four most frequent CYP2B6 haplotypes identified were *1/*6 (41%), *1/*1 (35%), *1/*2 (7%), and *6/*6 (7%).The heterozygous/homozygous mutation associated with low efavirenz concentrations was 18492T>C (P<0.001), and those associated with high efavirenz concentrations were 516G>T, 785A>G, and 21563C>T (all P<0.05).Haplotype *1/*1 was associated with low efavirenz concentrations, and *6/*6, *1/*6, and *5/6 were associated with high efavirenz concentrations.As shown by multivariate analysis, low efavirenz concentrations were significantly associated with the *1/*1 haplotype (beta=-1.084, P=.027) and high body weight (beta=-0.076, P=.002).In conclusion, pharmacogenetic markers of CYP2B6 have the greatest impact with respect to inducing low plasma efavirenz concentrations in HIV/TB Thai patients.Copyright © 2013, American Society for Microbiology.All Rights Reserved.


Wongsawat J.,Bamrasnaradura Infectious Diseases Institute
Journal of the Medical Association of Thailand = Chotmaihet thangphaet | Year: 2010

The pneumococcal conjugate vaccines (PCVs) have demonstrated good safety profile and efficacy against invasive pneumococcal diseases (IPD) caused by the serotypes included in the vaccines. The PCV also benefit to the unvaccinated children and adults from herd immunity. With the widespread use of the vaccine, emerging of non vaccine serotypes has been documented. The IPD burden in Thailand was found to be lower than that found in the western countries but the data in high risk population has been lacking. The PCV has been available in Thailand since 2006 as an optional vaccine, out of National Vaccine Program, with the uptake of less than 5% in children under 5 years of age. The serotypes distribution in Thailand has not changed significantly. In the year 2000-2005, compared with year 2006-2009, the most common serotypes in children < 5 years have been similar; comprising of 6B, 23F, 14, and 19F, however 19A has become more prevalence (6.2%) in the years 2006-2009. With the new breakpoint of penicillin susceptibility for non-meningeal strains, most penumococcal isolates in Thailand were susceptible to penicillin. To project the benefit for widespread use of PCV in Thailand the cost benefit analyses including the different types of PCV, the various dosing schedule, the benefit from herd immunity and the disadvantage of serotype replacement are needed.


Manosuthi W.,Bamrasnaradura Infectious Diseases Institute | Sukasem C.,Mahidol University | Thongyen S.,Bamrasnaradura Infectious Diseases Institute | Nilkamhang S.,Bamrasnaradura Infectious Diseases Institute | Sungkanuparph S.,Mahidol University
Journal of Antimicrobial Chemotherapy | Year: 2014

Objectives: To study the correlations of genetic variants of tenofovir tubular transporters, plasma tenofovir concentrations and clinical factors with decreased glomerular filtration rate in HIV-infected patients who received tenofovir. Methods: A total of 117 HIV-1-infected patients were administered antiretroviral therapy with tenofovir/ lamivudine/efavirenz. Two single nucleotide polymorphisms (SNPs), ABCC2*1C c.-24C>T and ABCB1*6 c.3435C>T, were genotyped. At week 24, plasma tenofovir concentration at 12 h after drug intake was measured. Serum creatinine and estimated glomerular filtration rate (eGFR) calculated by the Modification of Diet in Renal Disease study formula were measured every 24 weeks until 96 weeks. Results: Overall, mean±SD age was 37±9 years. Mean±SD baseline eGFR was 130.3±35.0 mL/min/1.73 m2. The frequencies of wild-type/heterozygous/homozygous mutants of ABCC2*1C were 57%/39%/4% and those of ABCB1*6 were 28%/51%/21%. Mean±SD plasma tenofovir concentration at 24 weeks was 105±46 ng/mL. At week 48, mean±SD eGFR of ABCC2*1C CC versus CT/TT was 96 versus 108 mL/min (P=0.005) and mean±SD eGFR of ABCB1*6 CC versus CT/TT was 106 versus 99 mL/min (P=0.157). Mean±SD tenofovir concentration in ABCC2*1C genotype CC versus CT/TT was 113±47 versus 93±44 ng/mL, respectively (P=0.018). By multivariate analysis I, decreased eGFR at week 48 was correlated to ABCC2*1C genotype CC (P=0.001), low eGFR at baseline (P=0.006) and older age (P=0.048). By multivariate analysis II, decreased eGFR at week 48 was correlated to high plasma tenofovir concentration (P=0.001) and low eGFR at baseline (P=0.019). Conclusions: HIV-infected patients who carry ABCC2*1C genotype CC at position -24 or have high plasma tenofovir concentration are at risk of decreased glomerular filtration rate. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Manosuthi W.,Bamrasnaradura Infectious Diseases Institute | Mankatitham W.,Bamrasnaradura Infectious Diseases Institute | Lueangniyomkul A.,Bamrasnaradura Infectious Diseases Institute | Thongyen S.,Bamrasnaradura Infectious Diseases Institute | And 6 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2012

Background: Optimal timing for initiation of antiretroviral therapy (ART) among HIV-infected patients with tuberculosis (TB) is not well established. Methods: HIV/TB-coinfected patients were randomized to initiate tenofovir/lamivudine/efavirenz at 4 weeks (4-week group) or 12 weeks (12-week group) of TB treatment. The primary outcome was 1-year all-cause mortality. Results: Of 156 patients, 79 were in 4-week group and 77 in 12-week group. Overall, median (interquartile range) CD4 was 43 (47-106) cells per cubic millimeter and median (interquartile range) HIV-1 RNA was 5.8 (5.4-6.3) log copies per milliliter. Eleven (7%) mortalities occurred in a total follow-up period of 137 patient-years. Seven percent (6/79, 8.76 per 100 patient-years) mortalities were in 4-week group, and 6% (5/77, 7.25 per 100 person-years) mortalities were in 12-week group [relative risk (RR) = 0.845, 95% confidence interval (CI) = 0.247 to 2.893]. Twenty-eight (35%) patients in 4-week group and 25 (32%) patients in 12-week group were hospitalized (RR = 1.142, 95% CI = 0.588 to 2.217). Grade 2-4 adverse events were 39% (31/79) in 4-week group and 34% (26/77) in 12-week group (RR = 1.267, 95% CI = 0.659 to 2.435). In multivariate analysis, "low albumin" (RR = 2.695, 95% CI = 1.353 to 5.475) and "low baseline CD4 count" (RR = 4.878, 95% CI = 1.019 to 23.256) were the independent predictors of mortality. Immune reconstitution inflammatory syndrome was more frequent in 4-week group with an incidence of 8.86 versus 5.02 per 100 person-months in 12-week group over the first 6 months of ART (P = 0.069). Conclusions: In middle-income countries where ART is initiated at CD4 count of <350 cells per cubic millimeter, immediate initiation of ART in HIV-infected patients with active TB was not associated with survival advantage when compared to initiation of ART at 12 weeks. © 2012 by Lippincott Williams & Wilkins.


Mankhatitham W.,Bamrasnaradura Infectious Diseases Institute | Luaengniyomkul A.,Bamrasnaradura Infectious Diseases Institute | Manosuthi W.,Bamrasnaradura Infectious Diseases Institute
Journal of the Medical Association of Thailand | Year: 2012

Objective: To study and compare the pattern of lipid profile changes in Thai HIV and tuberculosis (TB) co-infected patients after receiving two non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based antiretroviral therapy (ART). Material and Method: From an open label, randomized, comparative trial comparing treatment outcome between HIV and TB co-infected patients receiving nevirapine (NVP) or efavirenz (EFV) combined with stavudine and lamivudine, patient's body mass index (BMI), CD4 cell count, plasma HIV-1 RNA, fasting blood glucose, plasma total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglyceride (TG) were collected at baseline, 24, and 48 weeks of ART. Results: Of the 121 patients included in the present study, mean (SD) age was 36.9 (8.4) years and 66% were male. After 48 weeks of ART, the median (IQR) percentage of TC, LDL-C, HDL-C and TG values were 21.1% (5.4-40.7), 23.5% (-0.8-49.8), 22.7% (0-50) and -1.0% (-34.6-32.2) respectively. The median (IQR) percentage change of the HDL-C value was significantly higher in NVP-based than EFV-based ART (31.9 [9.6-50.0] vs. 12.2 [-8.8-51.2]; p = 0.03). The proportions of patients with high TC (21.5%) and high LDL-C (29.2%) increased and low HDL-C (11.6%) decreased significantly at 48 weeks of ART, compared to baseline (all, p < 0.01). The proportions of patients with high TC, high TG and low HDL-C were significantly higher in the EFV group than in the NVP group (p = 0.03 for high TC, p = 0.01 for high TG and p < 0.01 for low HDL-C). Conclusion: NNRTI-based ART is associated with increases of TC, LDL-C and HDL-C values in Thai HIV and TB co-infected patients. More favorable lipid profile is observed in NVP-based than EFV-based ART.

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