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.

Invariant Natural Killer T (iNKT) cells response in human melioidosis.

BACKGROUND: Melioidosis is an infectious disease caused by Burkholderia pseudomallei. In infected mice, IFN-γ can provide protection against B. pseudomallei infection. Invariant Natural Killer T (iNKT) cells are a subpopulation of T lymphocytes, activated by recognition of glycolipid ligands such as α-Galactosylceramide presented by CD1d, produce and secrete several cytokines, including IFN-γ and IL-4. The response of iNKT cells in human melioidosis was then investigated. OBJECTIVE: To determine the iNKT cells response in human melioidosis. METHODS: The number of human iNKT cells and its activation states were investigated in sepsis melioidosis patients compared with healthy controls using flow cytometry. The iNKT cells activation was confirmed in vitro using heatkilled B. pseudomallei with normal peripheral blood mononuclear cells. The components induced iNKT cell were also determined using different concentration of B. pseudomallei lipopolysaccharide (LPS), heat-killed B. pseudomallei treated with or without DNase, RNase, or proteinase. RESULTS: The number of human iNKT cells was significantly lower while the percentage of activated iNKT cells was higher in sepsis melioidosis when compared to control. In addition, B. pseudomallei can stimulate human iNKT cells in vitro. Heat-killed B. pseudomallei could activate iNKT cells but not relate to nucleic acid, proteins, or LPS. CONCLUSIONS: We found for the first time that the iNKT cells were activated during B. pseudomallei infection in human. However, the roles and the mechanism of iNKT cells during early state of infection needed to be further investigated.

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.

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.

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.).

Linezolid in the treatment of disseminated nontuberculous mycobacterial infection in anti-interferon-gamma autoantibody-positive patients.

Disseminated nontuberculous mycobacterial (NTM) infection is the most common feature in patients positive for anti-interferon-gamma autoantibody (IFN-gamma Ab). The condition is a form of anticytokine autoantibody syndrome. It is difficult to treat because of multiple drug resistance in mycobacteria. Linezolid is active against NTM in vitro; however clinical experience using this drug against NTM is limited. We report our experience using linezolid as part of an antimycobacterial regimen for treatment of 16 refractory cases of disseminated NTM at Srinagarind University Hospital, Khon Kaen, between September 2008 and December 2012. Complete resolution of signs and symptoms was seen in eight patients (50%) on linezolid therapy. Partial or no improvement was seen in a further four (25%) and three (19%) cases, respectively. Five (31%) patients developed an adverse reaction to linezolid; three of whom received 600 mg of linezolid twice daily. The study demonstrated the modest efficacy of linezolid for treating patients with a protracted course of disseminated-NTM; however, adverse effects were significant, especially for those on the high-dosage regimen.

ACORN (A Clinically-Oriented Antimicrobial Resistance Surveillance Network) II: protocol for case based antimicrobial resistance surveillance.

Background: Antimicrobial resistance surveillance is essential for empiric antibiotic prescribing, infection prevention and control policies and to drive novel antibiotic discovery. However, most existing surveillance systems are isolate-based without supporting patient-based clinical data, and not widely implemented especially in low- and middle-income countries (LMICs). Methods: A Clinically-Oriented Antimicrobial Resistance Surveillance Network (ACORN) II is a large-scale multicentre protocol which builds on the WHO Global Antimicrobial Resistance and Use Surveillance System to estimate syndromic and pathogen outcomes along with associated health economic costs. ACORN-healthcare associated infection (ACORN-HAI) is an extension study which focuses on healthcare-associated bloodstream infections and ventilator-associated pneumonia. Our main aim is to implement an efficient clinically-oriented antimicrobial resistance surveillance system, which can be incorporated as part of routine workflow in hospitals in LMICs. These surveillance systems include hospitalised patients of any age with clinically compatible acute community-acquired or healthcare-associated bacterial infection syndromes, and who were prescribed parenteral antibiotics. Diagnostic stewardship activities will be implemented to optimise microbiology culture specimen collection practices. Basic patient characteristics, clinician diagnosis, empiric treatment, infection severity and risk factors for HAI are recorded on enrolment and during 28-day follow-up. An R Shiny application can be used offline and online for merging clinical and microbiology data, and generating collated reports to inform local antibiotic stewardship and infection control policies. Discussion: ACORN II is a comprehensive antimicrobial resistance surveillance activity which advocates pragmatic implementation and prioritises improving local diagnostic and antibiotic prescribing practices through patient-centred data collection. These data can be rapidly communicated to local physicians and infection prevention and control teams. Relative ease of data collection promotes sustainability and maximises participation and scalability. With ACORN-HAI as an example, ACORN II has the capacity to accommodate extensions to investigate further specific questions of interest.

Risk factors and clinical outcomes of extended spectrum beta-lactamase (ESBL)-producing Escherichia coli septicemia at Srinagarind University Hospital, Thailand.

Escherichia coli producing extended spectrum beta-lactamase (ESBL) has emerged as a worldwide, public health problem. The aims of this study were to determine the incidence of ESBL-producing E. coli septicemia and evaluate the factors associated with the infection and the clinical outcomes. We reviewed 145 cases of E. coli septicemia among adult patients admitted to Srinagarind University Hospital in northeastern Thailand between 2005 and 2006. The incidence of ESBL-producing E. coli septicemia was 9.9 cases per 10,000 hospital admissions. The factors significantly associated with ESBL-producing E. coli septicemia were: 1) hospital acquisition [odds ratio (OR) 6.46; 95% confidence interval (CI) 2.01-20.79], 2) previous use of a fluoroquinolone, (OR 19.14; 95% CI 5.82-62.96), and 3) use of a central venous catheter (OR, 8.59; 95% CI, 1.11-66.27). Seventy-two hours after receiving empiric treatment, a significantly greater proportion of patients with ESBL-producing E. coli septicemia had a worse clinical outcome than those with non-ESBL producing E. coli septicemia (p = 0.01). The overall mortality rate was significantly higher among the ESBL-producing E. coli septicemia group than the non-ESBL producing E. coli septicemia group (29% vs 11.5%, respectively, p = 0.02). A high APACHE II score, ESBL-producing E. coli septicemia, primary septicemia, and having a non-urinary tract infecting as a source of septicemia were significantly independent factors related to mortality among patients with E. coli septicemia. ESBL-producing E. coli septicemia is an important cause of nosocomial infection and is related to higher mortality risk, especially among those with primary septicemia and secondary septicemia due to a non-urinary tract infection.

Disease patterns among Thai adult population: an analysis of data from the hospitalization National Health Insurance System 2010.

BACKGROUND: Disease pattern is an important informational tool used by policymakers in setting priorities, strategies and allocating budgets to address the precursors or causes of health problems. OBJECTIVE: To analyze the common diseases in the adult population using in-patient information from the three health insurance coverage schemes in the fiscal year 2010. MATERIAL AND METHOD: The authors analyzed the data on in-patients with 23 major disease groups as per ICD-10 coding. The data were analyzed to obtain the number of patients, number of admissions, number of hospital mortalities, mortality rates and length of hospital stays. RESULTS: The total number of adult in-patients was 3,876,792 presenting for admission 4,863,935 times. Infectious and parasitic diseases were the most common causes of admission. Diseases of the circulatory system resulted in the highest number of mortality rate (8.72%). Intracerebral hemorrhage, neoplasm, septicemia, liver failure, coronary heart disease, HIV/AIDS, status epilepticus, pneumonia, accidents and acute renal failure were the top ten diseases with a high mortality rate. CONCLUSION: The review indicated communicable diseases are the most common disease group although non-communicable diseases were also important because of their high mortality rate.

Health insurance system and healthcare provision: nationwide hospital admission data 2010.

BACKGROUND: The three major health insurance systems are different in their medical service coverage, reimbursement process and choice of providers; leading to the question of how great are the variations in the healthcare offered and disease outcomes. OBJECTIVE: To assess whether differences exist and to analyze the effects of on healthcare provision and disease outcomes in the adult population across the three health insurance systems. MATERIAL AND METHOD: The authors analyzed the disease outcomes of the 23 major ICD-10 disease groups among the three major health insurance systems to obtain the death rates, levels of healthcare provision and the hospital charges. Factors influencing mortality rates were evaluated by multiple logistic regression analysis. RESULTS: The community, general, tertiary care and private hospitals provided hospitalization for 41.4%, 22%, 27.3% and 9.3% of hospitalized adult patients, respectively. Infectious & parasitic diseases were the most common causes of admissions. Disease of the digestive system was the most common cause of admission in general hospitals while malignancy was the most common in the tertiary care hospitals. Patients with congenital malformation, neoplasm, mental and behavioral disorder and diseases of the eye were commonly treated at tertiary care hospitals. The mean and median of hospital charges were highest in the Civil Servant Medical Benefit System (CSMBS) (26,668; 10,209 Baht), followed by the Social Security System (SSS) (21,455; 9,713 Baht) and the Universal Coverage System (UC) (13,086; 5,246 Baht). The respective overall mortality rates for the CSMBS, SSS and UC were 4.40%, 1.38% and 3.32%. After adjustment, however a significant association between UC and mortality was found with an odds ratio of 1.43 (1.40-1.45) as compared to CSMBS. In addition, other factors most influencing mortality rates were male sex, elderly age, and the levels of healthcare. CONCLUSION: The differences in charges for some groups of diseases and significantly different clinical outcomes across schemes existed. The differences in disease outcomes were not adjusted for socioeconomic status and disease severity, requiring a cautious interpretation; nevertheless, an association with a higher mortality rate under the UC scheme for inpatient services need prompt further study

Risk factors and clinical outcomes of multidrug-resistant Acinetobacter baumannii bacteremia at a university hospital in Thailand.

Multidrug-resistant (MDR) Acinetobacter baumannii has become a major cause of hospital-acquired infection worldwide. There are few papers regarding this particular subject. Our aim was to assess the incidence of bacteremia due to MDR Acinetobacter baumannii, factors associated with the infection, and clinical outcomes. We studied 49 cases of A. baumannii bacteremia in adult patients admitted to a university hospital in Northeast Thailand between 2005 and 2007. The incidence of MDR A. baumannii bacteremia was 3.6 episodes per 10,000 hospital admissions. Significantly independent factors associated with MDR A. baumannii bacteremia were previous: 1) ICU admission [odds ratio (OR) 10.01; 95% confidence interval (CI) 1.39-72.20]; 2) use of beta-lactam/beta-lactamase inhibitor antibiotics (OR 8.06; 95%CI 1.39-46.64); and 3) use of a carbapenem antibiotics (OR 11.40; 95%CI 1.44-89.98). The overall mortality rate was significantly higher in the MDR group than in the susceptible group (91.7% vs 48%, respectively) (p=0.001). The significantly independent factors related to mortality were: 1) APACHE II score (OR 1.25; 95%CI 1.03-1.52) and 2) secondary bacteremia (OR 14.86; 95%CI 1.37-161.90). This study revealed the significantly independent factors associated with MDR A. baumannii bacteremia were prior ICU admission and prior use of broad spectrum antibiotics. This infection has a high mortality rate. Emphasis needs to be on prevention, strict application of infection control and appropriate use of antibiotics.

Colistin-Induced Acute Kidney Injury and the Effect on Survival in Patients with Multidrug-Resistant Gram-Negative Infections: Significance of Drug Doses Adjusted to Ideal Body Weight.

BACKGROUND: Colistin is a lifesaving treatment for multidrug-resistant Gram-negative bacterial (MDR-GNB) infections along with its well-known nephrotoxicity. The controversy of colistin-induced acute kidney injury (AKI) on mortality is noted. This study aimed to determine the risk factors and impact of AKI on the survival and significance of colistin dosage. METHODS: A retrospective cohort study was performed in adult patients who received intravenous colistin for MDR-GNB treatment between June 2015 and June 2017. Factors influencing colistin-induced AKI and survival were evaluated by Cox regression analysis. Cut-off levels of the colistin dose per ideal body weight (IBW) that significantly affected clinical outcomes were assessed with linearity trends and receiver operating characteristic analyses. RESULTS: AKI occurred in 68.5% of 412 enrolled patients with an incidence rate of 10.6 per 100 patients-days and a median time was 6 (3-13) days. Stages I-III of AKI were 38.3, 24.5, and 37.2%. Factors associated with colistin-induced AKI were advanced age, high serum bilirubin, AKI presented before colistin administration, increased daily colistin doses per IBW, and concomitant use of nephrotoxic drugs. Colistin-induced AKI was related to mortality (HR 1.74, 95% CI 1.06-2.86, p=0.028). In the non-AKI before colistin usage subgroup, the total dose and total dose/IBW were >1,500-2,000 mg and 30-35 mg/kg to benefit mortality reduction but were <2,500-3,000 mg and 45-50 mg/kg for risk reduction of AKI. A daily colistin dose/IBW >4.5 mg/kg/day also increased the risk of AKI. In the AKI developed before colistin subgroup, the cut-off values of total colistin dose >1250-1350 mg and total dose/IBW >23.5-24 mg/kg demonstrated significant risks of AKI. CONCLUSION: The incidence of AKI after colistin administration was high and impacted mortality. Prevention and early correction of these related factors are mandatory. Careful use of colistin was also both beneficial in mortality and AKI reductions.

Melioidosis pericarditis mimicking tuberculous pericarditis.

Cases of melioidosis (N = 2) and tuberculous pericarditis (N = 33) during 1996-2006 were reviewed. Clinical presentations were similar, but pericardial pathological findings were not. Nine of 12 patients with melioidosis required pericardectomy. In areas where these diseases are endemic, pericardial fluid culture and pericardial biopsy can differentiate between melioidosis and tuberculosis.

Mycotic aneurysm in Northeast Thailand: the importance of Burkholderia pseudomallei as a causative pathogen.

Forty cases of mycotic aneurysm that occurred during the period 1993-2007 were reviewed. The most common causative pathogen was Burkholderia pseudomallei (17 cases; 42.5%). Postoperative complications and bacteremia were significantly more common among patients with mycotic aneurysm due to B. pseudomallei than they were among patients with mycotic aneurysm that was not attributable to B. pseudomallei. In a region in which melioidosis is endemic, empirical antimicrobial therapy for suspected mycotic aneurysm should cover B. pseudomallei.

Intravenous Cyclophosphamide Therapy for Anti-IFN-Gamma Autoantibody-Associated Mycobacterium abscessus Infection.

INTRODUCTION: Anti-interferon-gamma (IFN-γ) autoantibodies are increasingly recognized as a cause of adult-onset immunodeficiency (AOID) worldwide. These patients are susceptible to various intracellular pathogens especially nontuberculous mycobacteria. Most of the patients have a refractory clinical course. Herein, we report the use of immunotherapy with pulse intravenous cyclophosphamide (IVCY) in patients who had progressive, refractory Mycobacterium abscessus infection. METHOD: We included patients, seen at Srinagarind Hospital, Thailand, infected with M. abscessus, who had received ≥3 courses of parenteral antibiotics within the last 12 months and who received pulse IVCY with a tapering dose of prednisolone. RESULTS: There were 8 AOID patients who met the criteria and received pulse IVCY between January 2011 and December 2015. One patient was lost to follow-up after 5 courses of IVCY: he had died at home 3 months later. Five patients had favorable outcomes: 2 were able to discontinue NTM therapy, and 3 had stable disease and were on NTM treatment without hospitalization for parenteral antibiotics. Two patients relapsed and needed hospitalization. The IFN-γ Ab titers among the 7 patients were significantly decreased during treatment, and the median initial antibody titer started at 200,000 and then decreased to 5,000 after 2 years of treatment (P < 0.0001). The antibody titer reduction among responsive vs. nonresponsive patient was significantly different after 6 months of treatment: the median antibody titer was 5,000 and 100,000, respectively (P = 0.0467). CONCLUSION: IVCY therapy might be an alternative treatment for AOID patients infected with M. abscessus and refractory to antimycobacterial therapy.

Melioidosis in Thailand: Present and Future.

A recent modelling study estimated that there are 2800 deaths due to melioidosis in Thailand yearly. The Thailand Melioidosis Network (formed in 2012) has been working closely with the Ministry of Public Health (MoPH) to investigate and reduce the burden of this disease. Based on updated data, the incidence of melioidosis is still high in Northeast Thailand. More than 2000 culture-confirmed cases of melioidosis are diagnosed in general hospitals with microbiology laboratories in this region each year. The mortality rate is around 35%. Melioidosis is endemic throughout Thailand, but it is still not uncommon that microbiological facilities misidentify Burkholderia pseudomallei as a contaminant or another organism. Disease awareness is low, and people in rural areas neither wear boots nor boil water before drinking to protect themselves from acquiring B. pseudomallei. Previously, about 10 melioidosis deaths were formally reported to the National Notifiable Disease Surveillance System (Report 506) each year, thus limiting priority setting by the MoPH. In 2015, the formally reported number of melioidosis deaths rose to 112, solely because Sunpasithiprasong Hospital, Ubon Ratchathani province, reported its own data (n = 107). Melioidosis is truly an important cause of death in Thailand, and currently reported cases (Report 506) and cases diagnosed at research centers reflect the tip of the iceberg. Laboratory training and communication between clinicians and laboratory personnel are required to improve diagnosis and treatment of melioidosis countrywide. Implementation of rapid diagnostic tests, such as a lateral flow antigen detection assay, with high accuracy even in melioidosis-endemic countries such as Thailand, is critically needed. Reporting of all culture-confirmed melioidosis cases from every hospital with a microbiology laboratory, together with final outcome data, is mandated under the Communicable Diseases Act B.E.2558. By enforcing this legislation, the MoPH could raise the priority of this disease, and should consider implementing a campaign to raise awareness and melioidosis prevention countrywide.

Disseminated nontuberculous mycobacterial infection in patients who are not infected with HIV in Thailand.

BACKGROUND: Disseminated nontuberculous mycobacterial (NTM) infection is an emerging infectious disease worldwide that occurs mostly in immunocompromised hosts. Disseminated NTM infection is uncommon in persons who are not infected with human immunodeficiency virus (HIV). Recently, we described a group of non-HIV-infected Thai patients whose disease manifestation was a previously unrecognized clinical entity characterized by chronic bilateral lymphadenopathy due to rapidly growing mycobacteria. Most of the patients had coinfection with other opportunistic pathogens and reactive skin diseases. Therefore, in recognition of the increasing significance of this unique disease due to NTM in our country, we initiated a study to assess the prevalence, clinical characteristics, and geographic variations of this disease. METHODS: There were 129 cases of disseminated NTM infection identified from 4 university hospitals located in major areas throughout Thailand. All patients but 1 were adults. Only 12% of patients had underlying diseases. The majority of the patients (81%) lived in the northeast of Thailand. RESULTS: The most common organ involved was the lymph node (89%), followed by skin and soft tissue (26%), lung (19%), and others. Fifty-nine patients (46%) had 81 episodes of coinfection with other opportunistic infections (e.g., salmonellosis, 32 cases; cryptococcosis, 8 cases; penicilliosis, 8 cases; histoplasmosis, 5 cases). Seventy-seven patients had 86 episodes of reactive skin diseases (e.g., Sweet syndrome, 60 cases; pustular psoriasis, 6 cases; erythematous pustulosis, 5 cases). CONCLUSIONS: These findings suggest a cell-mediated immune defect in these patients that needs to be further investigated. This study strongly suggests that the prevalence of NTM infection in Thailand is increasing. To our knowledge, this is the largest study of disseminated NTM infection among non-HIV-infected patients.

A rapidly fatal case of Panton-valentine leukocidin positive Staphylococcus aureus necrotizing pneumonia in an HIV-infected patient.

This article reports a rare case of necrotizing pneumonia caused by Panton-Valentine leukocidin (PVL) positive Staphylococcus aureus in an HIV-infected patient presenting with severe back pain and rash. The back pain progressed to excruciating abdominal pain which was misleading, resulting in an investigation on intraabdominal conditions. He developed massive hemoptysis and died within 2 days of the first clinical symptoms. Recognizing the emergence of PVL-producing S. aureus is important in both immunocompetent and immunocompromised patients. This organism was transmitted from his wife.

Predictive Model for Permanent Shunting in Cryptococcal meningitis.

Cryptococcal meningitis may have long-term morbidity and requires a permanent cerebrospinal fluid shunt. This study aimed to evaluate the risk factors and create a predictive model for permanent shunt treatment in cryptococcal meningitis patients. This was a retrospective analytical study conducted at Khon Kaen University. The study period was from January 2005 to December 2015. We enrolled all adult patients diagnosed with cryptococcal meningitis. Risk factors predictive for permanent shunting treatment were analyzed by multivariate logistic regression analysis. There were 341 patients diagnosed with cryptococcal meningitis. Of those, 64 patients (18.7%) were treated with permanent shunts. There were three independent factors associated with permanent shunt treatment. The presence of hydrocephalus had the highest adjusted odds ratio at 56.77. The resulting predictive model for permanent shunt treatment (y) is (-3.85) + (4.04 × hydrocephalus) + (2.13 × initial cerebrospinal fluid (CSF) opening pressure (OP) > 25 cm H2O) + (1.87 × non-human immune deficiency vrus (HIV)). In conclusion, non-HIV status, initial CSF OP greater than or equal to 25 cm H2O, and the presence of hydrocephalus are indicators of the future necessity for permanent shunt therapy.