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Biomedical subjects

Piroon Mootsikapun

Publications and source records attributed to Piroon Mootsikapun.

At least 19 recordsLinked to original sources

Clinical and epidemiological analyses of human pythiosis in Thailand.

BACKGROUND: Pythiosis is an emerging and life-threatening infectious disease in humans and animals that is caused by the pathogenic oomycete Pythium insidiosum. Human pythiosis is found mostly in Thailand, although disease in animals has been increasingly reported worldwide. Clinical information on human pythiosis is limited, and health care professionals are unfamiliar with the disease, leading to underdiagnosis, delayed treatment, and poor prognosis. METHODS: To retrospectively study the clinical and epidemiological features of human pythiosis, we analyzed clinical data from patients with pythiosis diagnosed during the period of January 1985 through June 2003 at 9 tertiary care hospitals throughout Thailand. RESULTS: A total of 102 cases of human pythiosis were documented nationwide. A substantial proportion (40%) of cases occurred in the last 4 years of the 18-year study interval. Clinical presentations fell into 4 groups: cutaneous/subcutaneous cases (5% of cases), vascular cases (59%), ocular cases (33%), and disseminated cases (3%). Almost all patients with cutaneous/subcutaneous, vascular, and disseminated pythiosis (85%) had underlying thalassemia-hemoglobinopathy syndrome. Most ocular cases (84%) were associated with no underlying disease. A majority of the patients were male (71%), were aged 20-60 years (86%), and reported an agricultural occupation (75%). Regarding treatment outcomes, all patients with disseminated infection died; 78% of patients with vascular disease required limb amputation, and 40% of these patients died; and 79% of patients with ocular pythiosis required enucleation/evisceration. CONCLUSIONS: Here, we report, to our knowledge, the largest case study of human pythiosis. The disease has high rates of morbidity and mortality. Early diagnosis and effective treatment are urgently needed to improve clinical outcomes. Because P. insidiosum is distributed worldwide and can infect healthy individuals, an awareness of human pythiosis should be promoted in Thailand and in other countries.

Adolescent↗

Bacteremia in adult patients with acquired immunodeficiency syndrome in the northeast of Thailand.

BACKGROUND: Bacteremia is a frequent complication found in HIV-infected patients and is usually associated with a poor prognosis. This study was undertaken to describe the bacterial pathogens causing bacteremia in adult Thai HIV-infected patients, and hence to give guidance in the choice of empirical antimicrobials. METHODS: Blood culture results at Srinagarind Hospital, Khon Kaen during the period January 1996 to December 2001 were retrospectively reviewed. RESULTS: In HIV-infected and HIV-uninfected patients, 172 and 4082 episodes of bacteremia occurred, respectively. In HIV-infected patients, community-acquired and nosocomial bacteremia were found in 78.5% and 21.5%, respectively and most were monomicrobial. Gram-negative bacteria were the main pathogens isolated in both groups of bacteremia. Escherichia coli and methicillin-resistant Staphylococcus aureus were more common pathogens causing nosocomial bacteremia in HIV-infected patients, whereas Acinetobacter spp were more common in HIV-uninfected patients. Salmonella spp, especially Salmonella groups D and B, were the most common (62.2%) pathogen in community-acquired bacteremia in HIV-infected patients whereas Escherichia coli was the most common in HIV-uninfected patients. Only a few episodes of community-acquired bacteremia in HIV-infected patients had identified sources. Co-trimoxazole resistance was common in community-acquired bacteremia caused by Gram-negative bacilli in HIV-infected patients, with Salmonella group B being more resistant to co-trimoxazole than Salmonella group D (statistically significant, p<0.001). However, resistance rates to ceftriaxone and ofloxacin were low. CONCLUSIONS: Bacteremia in adult HIV-infected patients was usually caused by Gram-negative bacilli in both community-acquired and nosocomial settings. Salmonella spp was the most common organism identified, especially Salmonella group B and D. Ceftriaxone or fluoroquinolones such as ofloxacin or ciprofloxacin should be used as the initial empiric therapy for HIV-infected patients with suspected bacteremia.

Acquired Immunodeficiency Syndrome↗

Identification of a novel 74-kiloDalton immunodominant antigen of Pythium insidiosum recognized by sera from human patients with pythiosis.

The oomycetous, fungus-like, aquatic organism Pythium insidiosum is the etiologic agent of pythiosis, a life-threatening infectious disease of humans and animals that has been increasingly reported from tropical, subtropical, and temperate countries. Human pythiosis is endemic in Thailand, and most patients present with arteritis, leading to limb amputation and/or death, or cornea ulcer, leading to enucleation. Diagnosis of pythiosis is time-consuming and difficult. Radical surgery is the main treatment for pythiosis because conventional antifungal drugs are ineffective. The aims of this study were to evaluate the use of Western blotting for diagnosis of human pythiosis, to identify specific immunodominant antigens of P. insidiosum, and to increase understanding of humoral immune responses against the pathogen. We performed Western blot analysis on 16 P. insidiosum isolates using 12 pythiosis serum samples. These specimens were derived from human patients with pythiosis who had different forms of infection and lived in different geographic areas throughout Thailand. We have identified a 74-kDa immunodominant antigen in all P. insidiosum isolates tested. The 74-kDa antigen was also recognized by sera from all patients with pythiosis but not by control sera from healthy individuals, patients with thalassemia, and patients with various infectious diseases, indicating that Western blot analysis could facilitate diagnosis of pythiosis. Therefore, the 74-kDa antigen is a potential target for developing rapid serodiagnostic tests as well as a therapeutic vaccine for pythiosis. These advances could lead to early diagnosis and effective treatment, crucial factors for better prognosis for patients with pythiosis.

Antibodies↗

Histoplasmosis and penicilliosis: comparison of clinical features, laboratory findings and outcome.

INTRODUCTION: Histoplasmosis and penicilliosis are infections caused by the dimorphic fungi, Histoplasma capsulatum and Penicillium marneffei, respectively. The aim of this study was to compare the clinical presentation, laboratory and radiologic findings and outcome of these infections at Srinagarind Hospital, Khon Kaen, Thailand. METHODS: The medical records of patients who had positive cultures for Histoplasma capsulatum and Penicillium marneffei during 1996-2002 were reviewed. The data were compared and analyzed by the Chi-square and Fisher's exact tests. RESULTS: There were 32 and 36 medical records of patients with H. capsulatum and P. marneffei infection, respectively, available for review. The most common underlying disease of patients with histoplasmosis and penicilliosis was acquired immunodeficiency syndrome (AIDS), which accounted for 90.6% and 91.7%, respectively. The most common clinical findings in both infections were fever, weight loss, cough, anemia, lymphadenopathy, hepatomegaly and splenomegaly. Frequencies of skin lesions were not statistically different between either group (P=0.20). Laboratory findings were similar between the two infections, except hyperbilirubinemia, which was more common in the penicilliosis group (P=0.02). There were similar abnormal X-ray findings in both groups with interstitial infiltration the most common abnormality. CONCLUSIONS: Histoplasmosis and penicilliosis had similar clinical presentations, laboratory findings and chest X-ray abnormalities. Itraconazole is recommended as secondary prophylaxis in HIV-infected patients who have histoplasmosis or penicilliosis.

AIDS-Related Opportunistic Infections↗

Time-kill curves as a tool for targeting ceftazidime serum concentration during continuous infusion for treatment of septicaemic melioidosis.

Melioidosis is a fatal community-acquired infection endemic in tropical areas. Ten isolates of the causative microorganism were subjected to time-kill study using a range of ceftazidime concentrations. This study demonstrated that a ceftazidime concentration of eight times the minimum inhibitory concentration yielded an optimal bactericidal effect and should be the target concentration administered by continuous infusion.

Anti-Bacterial Agents↗

Two randomized controlled trials of ceftazidime alone versus ceftazidime in combination with trimethoprim-sulfamethoxazole for the treatment of severe melioidosis.

BACKGROUND: Two antibiotic regimens are used commonly in Thailand for the initial treatment of severe melioidosis: ceftazidime in combination with trimethoprim-sulfamethoxazole (TMP-SMX) and ceftazidime monotherapy. It is not known whether TMP-SMX provides an additional benefit. METHODS: Two prospective, randomized trials that compared these regimens for patients presenting with acute severe melioidosis were started independently at tertiary care hospitals in Ubon Ratchathani and Khon Kaen (in northeastern Thailand), and the results were analyzed together as a prospective, individual-patient data meta-analysis. The primary end point was in-hospital mortality rate. RESULTS: The in-hospital mortality rate among all enrolled patients (n=449) was not significantly different between those randomized to ceftazidime alone (25.1%; 56 of 223 subjects) and those randomized to ceftazidime with TMP-SMX (26.6%; 60 of 226 subjects; odds ratio [OR], 1.08; 95% confidence interval [CI], 0.7-1.7; stratified P=.73). Of the 241 patients with culture-confirmed melioidosis, 51 (21.2%) died. Of these 241 patients, 31 (12.9%) died > or =48 h after the time of study entry. Among patients with melioidosis, there was no difference in death rate between the 2 treatment groups for either all deaths (OR, 0.88; 95% CI, 0.48-1.6; stratified P=.70) or for deaths that occurred > or =48 h after hospital admission (OR, 0.88; 95% CI, 0.41-1.9; stratified P=.73). Conditional logistic regression analysis revealed that bacteremia, respiratory failure, and renal failure were independently associated with death and treatment failure. Drug regimens were not associated with death or treatment failure in this model. CONCLUSION: We conclude that the addition of TMP-SMX to ceftazidime therapy during initial treatment of severe melioidosis does not reduce the acute mortality rate.

Adult↗

Nocardiosis in Srinagarind Hospital, Thailand: review of 70 cases from 1996-2001.

OBJECTIVE: Nocardiosis is a common opportunistic infection found in both immunocompromised and immunocompetent patients. The clinical manifestations, underlying diseases, radiologic findings, antimicrobial susceptibility and treatment of nocardial infection are presented here. METHOD: A retrospective study at Srinagarind Hospital, Khon Kaen in Thailand was performed. Medical records from 1996-2001 were reviewed. RESULTS: There were 81 cases of nocardiosis during the study period but data of only 70 cases were available. 80% of cases were male. The mean age was 39.7+/-14.9 years. Underlying diseases were found in 80%, of which HIV infection was the most common (34.3%). The common clinical findings were fever, cough, and cutaneous abscess. The most common clinical syndrome was pleuropulmonary infection (44.3%), followed by skin and soft tissue infection (22.8%). Multiorgan dissemination was found in 11.4% of cases. The chest X-rays were abnormal in 46 cases (65.7%); alveolar and reticulonodular infiltration was common. Only 70% had positive cultures for Nocardia spp. The resistance rate of Nocardia isolates to trimethoprim-sulfamethoxazole (TMP-SMX) was very high (57.9%) in this study. Most of the patients (85.7%) were treated with antimicrobials, of which TMP-SMX was commonly used. In-hospital mortality was 20%. Most of the cases who died had dissemination, brain abscesses or infection with TMP-SMX-resistant strains. The long-term prognosis was good, with a treatment success rate of 93.75%. CONCLUSION: Nocardiosis is a common opportunistic infection in many immunocompromised conditions. It can present with various clinical syndromes, especially pleuropulmonary infection. Culture may not yield the organism but modified acid-fast staining is very helpful in diagnosis. Drug susceptibility testing should be performed due to increasing resistance to TMP-SMX.

Adult↗

Pharmacokinetics of reduced-dose indinavir/ritonavir 400/100 mg twice daily in HIV-1-infected Thai patients.

OBJECTIVE: To study the pharmacokinetics of indinavir/ ritonavir 400/100 mg twice daily in antiretroviral-naive patients at Srinagarind Hospital in Khon Kaen, Thailand. METHODS: This was a steady-state, open-label pharmacokinetic study of 19 patients. A 12 h pharmacokinetic curve was recorded after an overnight fast. Plasma levels of indinavir and ritonavir were determined by a validated HPLC method. Virological failure was defined according to the most recent US Department of Health and Human Services guidelines as a viral load above 400 copies/ml at week 24. RESULTS: Median baseline values for CD4 and viral load were 13cells/mm3 and 167000 copies/ml, respectively. The median (interquartile ranges) for indinavir AUC, Cmax and Cmin were 18.1 (15.3-23.8) mg/l x h, 4.1 (3.6-4.8) mg/l and 0.17 (0.12-0.30) mg/l, respectively. These values represent 37%, 39% and 24% of the AUC, Cmax and Cmin values found, respectively, for the indinavir/ritonavir 800/100 mg dose in HIV-1-infected Thai patients. Short-term virological response was satisfactory. There were three subjects with an indinavir Cmin. below the target value of 0.10 mg/l, of whom one had virological failure (33%). Among the other 16 subjects with an indinavir Cmin above 0.10 mg/l, there was also one virological failure (6%) (P=0.30). CONCLUSIONS: Indinavir exposure in this reduced-dose regimen of 400 mg with 100 mg ritonavir twice daily was more than dose-proportionally lower than previously observed with the indinavir/ritonavir 800/100 mg twice daily regimen. Therapeutic Cmin levels of indinavir were achieved in >80% of the subjects and short-term virological response was satisfactory in this cohort of patients starting highly active antiretroviral therapy at an advanced disease stage with high baseline viral loads.

Administration, Oral↗

Body composition in adults infected with human immunodeficiency virus in Khon Kaen, Thailand.

A cross-sectional study of 77 patients infected with human immunodeficiency virus (HIV) in Khon Kaen, Thailand examined association of nutritional status with active opportunistic infections (AOIs)/HIV status and assessed degree of correlation between bioelectrical impedance analysis (BIA) and anthropometry. Many patients (41.3%) were malnourished using World Health Organization criteria for underweight, and malnutrition was associated with AOI status. Unconditional odds ratios (P < 0.05) for AOI as opposed to no AOI were 4.57 for underweight, 9.87 for severe underweight, 2.55 for triceps < 10th percentile, and 5.22 for mid-arm circumference < 10th percentile. Body fat composition from BIA, anthropometry, and body mass index were moderate to highly correlated (P < 0.001), with the highest correlation between BIA and subscapular skinfold (r = 0.86) and the lowest between BIA and triceps skinfold (r = 0.54). Insights were gained about relative value of using various measurements to assess nutritional status of HIV-infected populations.

AIDS-Related Opportunistic Infections↗

HIV-associated primary pulmonary hypertension: a first case report in Thailand and literature review.

A 32-year-old woman had asymptomatic HIV infection diagnosed with primary pulmonary hypertension simultaneously. She presented after a three-month rapid progression of symptoms and hemodynamic change. Physical examination and laboratory findings were compatible with pulmonary hypertension. No sensible cause could be found for the pulmonary hypertension except the HIV seropositivity; therefore, HIV-associated primary pulmonary hypertension was diagnosed. She was treated with diltiazem and oral anti-coagulation. After four months, her functional status improved from a NYHA functional class of II to I and improved in right venticular function. Since HIV is epidemic, the authors recommend HIV testing in cases of primary pulmonary hypertension.

Adult↗

Detection of opportunistic and non-opportunistic intestinal parasites and liver flukes in HIV-positive and HIV-negative subjects.

We assessed the frequency and distribution of infection with opportunistic and non-opportunistic intestinal parasites and the liver fluke, Opisthorchis viverrini, in HIV-seropositive and HIV-seronegative subjects. Age- and sex-matched HIV-seropositive (n = 78) and HIV-seronegative patients (n = 78) from two hospitals in Khon Kaen Province, Thailand, participated in this study from November 1998 to August 2000. These subjects were divided according to the presence of diarrhea and CD4 counts. A single stool sample was obtained and analyzed by using specific techniques. Opisthorchis viverrini, was the most common parasite (19.2%) in each group. The prevalence rates of Cryptosporidium spp (11.5%) and Strongyloides stercoralis (17.9%) in the HIV-seropositive group were significantly (p < 0.05) higher than those in the HIV-seronegative group (1.0% for Cryptosporidium spp and 7.7% for S. stercoralis infections). The prevalences of these two parasites were 28% for Cryptosporidium spp and 20% for S. stercoralis in HIV-seropositives with diarrhea and CD4 counts lower than 100 cells/mm3, and were higher compared with patients without diarrhea or with high CD4 counts. These results suggest that infection with these parasites increases during HIV infection. The epidemiological distribution of Cryptosporidium and S. stercoralis may have implications for AIDS-related diseases.

AIDS-Related Opportunistic Infections↗

Efficacy and safety of indinavir/ritonavir 400/100 mg twice daily plus two nucleoside analogues in treatment-naive HIV-1-infected patients with CD4+ T-cell counts <200 cells/mm3: 96-week outcomes.

OBJECTIVE: To evaluate the efficacy and safety of indinavir/ritonavir 400/100 mg plus stavudine and lamivudine twice daily in antiretroviral-therapy-naive Thai HIV-1-infected patients. METHODS: This was an open-label, non-randomized single arm study. Antiretroviral-naive patients (n=80) with CD4+ cell count < 200 x 10(6)/l were started on stavudine and lamivudine plus indinavir/ritonavir 400/100 mg twice daily. CD4+ cell count and HIV RNA were determined at week 0, 12, 24, 48 and 96. HIV RNA was measured to a level of 50 copies/ml by RT-PCR assay. Primary analysis was statistically performed as intent to treat. The primary endpoint was the percentage of patients with plasma HIV RNA below 50 copies/ml at week 96. RESULT: Eighty antiretroviral-therapy-naive patients with median CD4+ cell count 19 x 10(6)/l (range: 2 - 197 x 10(6)/l) and median baseline plasma HIV RNA of 174,000 copies/ml (range 16,800-750,000 copies/ml) were enrolled. In the intent-to-treat analysis at week 96, the proportion of patients with HIV RNA of <50 copies/ml was 68.8% (95% confidence interval [CI]: 68.3-69.3), whereas it was 88.7% (95% CI: 88.1-89.3) in the on-treatment analysis at week 96. The regimen was well tolerated. Hyperglycaemia, hypercholesterolaemia and hypertriglyceridaemia were found in 8.3, 33.3 and 37.0% of the patients, respectively. Treatment was stopped in 18 patients; two from intolerance, two switched therapy, four as a result of serious adverse event-related death, and ten were lost to follow-up. CONCLUSION: Our study demonstrates that indinavir/ritonavir 400/100 mg plus stavudine and lamivudine twice daily, the least expensive boosted protease inhibitor, appears to be effective and safe up to 96 weeks despite high baseline viraemia and low CD4+ cell count in antiretroviral-naive patients.

Administration, Oral↗

Nevirapine plasma concentrations and concomitant use of rifampin in patients coinfected with HIV-1 and tuberculosis.

OBJECTIVES: In countries with high numbers of HIV/tuberculosis coinfection nevirapine and rifampin are used extensively. However, limited data are available about whether or not nevirapine and rifampin can be safely coadministered without the plasma concentration of nevirapine falling below therapeutic levels. METHODS: Blood samples for determination of nevirapine plasma concentrations were collected from patients using nevirapine 200 mg twice daily with or without concomitant rifampin. Bivariate and multivariate linear regression models were used to investigate factors possibly related to nevirapine concentrations. RESULTS: We received 74 blood samples from patients using nevirapine plus rifampin, and collected blood samples from an equal number of controls using nevirapine only. Groups were similar for age, gender, weight, height and body mass index (BMI). In the rifampin group the mean nevirapine concentration was 5.47 +/- 2.66 mg/l, whereas in the control group the mean nevirapine concentration was 8.72 +/- 3.98 mg/l. In the rifampin group seven nevirapine trough concentrations were low (< 3.1 mg/l), while in the control group two patients had low nevirapine trough concentrations (P = 0.164). In the multivariate linear regression analysis, corrected for time after drug intake, the use of rifampin was significantly (P < 0.001) associated with lower nevirapine plasma concentrations, whereas higher BMI reached borderline significance (P = 0.065). CONCLUSION: Although nevirapine plasma concentrations were 3.3 mg/l lower when co-administered with rifampin, still more than 86% of these patients had nevirapine plasma concentrations > 3.1 mg/l. Our results suggest that from a pharmacological point of view the majority of Thai coinfected patients, who have low BMIs, reach nevirapine plasma concentrations that are adequate for treatment of HIV. However this can only be undertaken if nevirapine plasma concentration monitoring is available and can be closely followed.

Anti-Infective Agents↗

PCR diagnosis of Pneumocystis carinii on sputum and bronchoalveolar lavage samples in immuno-compromised patients.

The polymerase chain reaction (PCR) technique was compared with Wright-Giemsa (WG), Gomori methenamine silver (GMS) stains and an immunofluorescence assay (IFA) for detection of Pneumocystis carinii in immuno-compromised patients. Specimens of 21 bronchoalveolar lavages (BAL) and 139 sputum samples, were obtained from 157 patients (38 with AIDS and 119 with HIV) from four hospitals in Khon Kaen, Thailand. A true positive required at least two positives by techniques considered gold standard tests. Eleven (52.38%) BAL and 13 (9.35%) sputum specimens were positive. PCR produced the highest sensitivity and negative predictive values for the BAL (100% for each) vs. sputum samples at 84.62 and 98.41 percent, respectively. The specificity of PCR was 90% and 98.41% for BAL and sputum samples, respectively. We suggest PCR is an important tool for the epidemiological study of P. carinii in high-risk individuals.

AIDS-Related Opportunistic Infections↗

Acute lupus hemophagocytic syndrome: report of a case and review of the literature.

The authors reported a case of systemic lupus erythematosus (SLE) with an unusual presentation. The patient presented with acute febrile illness along with progressive pancytopenia related to increasing hemophagocytic activity of histiocytes in the bone marrow. Concomitant polyarthritis, myositis, nephritis, high titer of antinuclear factor (1:2,560) and positive test for anti-DNA antibody made him fit the diagnostic criteria of SLE. No definite evidence of associated infections was confirmed by bacteriologic, serologic and viral studies. He did not respond to empiric antibiotic therapy but dramatically responded to corticosteroid treatment. Therefore, diagnosis of acute lupus hemophagocytic syndrome was made. The clinical presentation, laboratory diagnosis, and management of the patient are discussed and the literature was reviewed and presented.

Acute Disease↗

Discontinuation of secondary prophylaxis for cryptococcal meningitis in human immunodeficiency virus-infected patients treated with highly active antiretroviral therapy: a prospective, multicenter, randomized study.

A prospective, multicenter, randomized study was conducted with human immunodeficiency virus (HIV)-infected patients who were successfully treated for acute cryptococcal meningitis, were receiving secondary prophylaxis, and were naive for antiretroviral therapy. Patients were randomized to continue or discontinue secondary prophylaxis when the CD4 cell count had increased to >100 cells/microL and an undetectable HIV RNA level had been sustained for 3 months. At a median of 48 weeks after randomization, there were no episodes of cryptococcal meningitis in either group.

AIDS-Related Opportunistic Infections↗