Comparison of Ashdown's medium, Burkholderia cepacia medium, and Burkholderia pseudomallei selective agar for clinical isolation of Burkholderia pseudomallei

Ashdown's medium, Burkholderia pseudomallei selective agar (BPSA), and a commercial Burkholderia cepacia medium were compared for their abilities to grow B. pseudomallei from 155 clinical specimens that proved positive for this organism. The sensitivity of each was equivalent; the selectivity of BPSA was lower than that of Ashdown's or B. cepacia medium.     

Three-year durability of dual-nucleoside versus triple-nucleoside therapy in a Thai population with HIV infection

We compared the long-term immunologic and virologic efficacy of the dual- and triple-nucleoside therapy for HIV infection. This was a retrospective analysis of 2 randomized clinical trials in antiretroviral-naive patients. In the dual-nucleoside group, 15 started with didanosine (ddI) monotherapy and then added stavudine (d4T) after 24 weeks, 63 started with various doses of d4T and ddI, and 53 started with zidovudine (ZDV) and lamivudine (3TC). In the triple-nucleoside group, 53 started with ZDV, 3TC, and ddI. After 48 weeks, patients who were not failing were randomized to immediate (before treatment failure) versus delayed (at the time of virologic failure) switching from ddI and d4T to ZDV and 3TC or vice versa and from ZDV, 3TC, and ddI to d4T, 3TC, and abacavir (ABC). Failure was defined as a plasma HIV-1 RNA level>or=1 log10 above nadir or >or=10,000 copies/mL when nadir was <500 copies/mL. Patients failing therapy before week 48 received the new treatment as in the immediate switching group. Hydroxyurea was added to the last treatment regimen if patients failed after week 96. CD4 count and plasma HIV-1 RNA level (branched DNA assay with a cutoff point of 50 copies/mL) at week 144 were analyzed by intention to treat. Compared with the dual-nucleoside group, the triple-nucleoside group had a higher proportion of patients with <50 copies/mL at 144 weeks (60% vs. 18%; P<0.001), higher median CD4 count (388 cells/microL vs. 346 cells/microL; P=0.018), and longer duration of response, defined as the time from onset of viral suppression (<500 copies/mL) to the time of treatment failure (the first of 2 consecutive HIV-1 RNA measurements >500 copies/mL never followed by 2 consecutive visits showing suppressible viremia to <500 copies/mL) or discontinuation from the study (144 weeks vs. 104 weeks; P=0.002). Multivariate regression analyses showed that significant predictors for treatment success, defined as a plasma viral load <50 copies/mL at week 144, were asymptomatic clinical status at enrollment, a baseline plasma viral load 相似文献   

Anogenital HIV RNA in Thai men who have sex with men in Bangkok during acute HIV infection and after randomization to standard vs. intensified antiretroviral regimens

Introduction

HIV transmission risk is highest during acute HIV infection (AHI). We evaluated HIV RNA in the anogenital compartment in men who have sex with men (MSM) during AHI and compared time to undetectable HIV RNA after three-drug versus five-drug antiretroviral therapy (ART) to understand risk for onward HIV transmission.

Methods

MSM with AHI (n=54) had blood, seminal plasma and anal lavage collected for HIV RNA at baseline, days 3 and 7, and weeks 2, 4, 12 and 24. Data were compared between AHI stages: 1 (fourth-generation antigen-antibody combo immunoassay [IA]–, third-generation IA–, n=15), 2 (fourth-generation IA+, third-generation IA–, n=9) and 3 (fourth-generation IA+, third-generation IA+, western blot–/indeterminate, n=30) by randomization to five-drug (tenofovir+emtricitabine+efavirenz+raltegravir+maraviroc, n=18) versus three-drug (tenofovir+emtricitabine+efavirenz, n=18) regimens.

Results

Mean age was 29 years and mean duration since HIV exposure was 15.4 days. Mean baseline HIV RNA was 5.5 in blood, 3.9 in seminal plasma and 2.6 log₁₀ copies/ml in anal lavage (p<0.001). Blood and seminal plasma HIV RNA were higher in AHI Stage 3 compared to Stage 1 (p<0.01). Median time from ART initiation to HIV RNA <50 copies/ml was 60 days in blood, 15 days in seminal plasma and three days in anal lavage. Compared with the three-drug ART, the five-drug ART had a shorter time to HIV RNA <1500 copies/ml in blood (15 vs. 29 days, p=0.005) and <50 copies/ml in seminal plasma (13 vs. 24 days, p=0.048).

Conclusions

Among MSM with AHI, HIV RNA was highest in blood, followed by seminal plasma and anal lavage. ART rapidly reduced HIV RNA in all compartments, with regimen intensified by raltegravir and maraviroc showing faster HIV RNA reductions in blood and seminal plasma.     

Failure of Burkholderia pseudomallei to Grow in an Automated Blood Culture System

We compared the organisms isolated from 30,210 pairs of blood culture bottles by using BacT/Alert system and the conventional system. Overall, 2,575 (8.5%) specimens were culture positive for pathogenic organisms. The sensitivity for detection of pathogenic organisms with the BACT/Alert system (85.6%, 2,203 of 2,575) was significantly higher than that with the conventional method (74.1%, 1,908 of 2,575; P < 0.0001). However, Burkholderia pseudomallei was isolated less often with the BacT/ALERT system (73.5%, 328 of 446) than with the conventional system (90.3%, 403 of 446; P < 0.0001). This finding suggests that use of the conventional culture method in conjunction with the BacT/Alert system may improve the isolation rate for B. pseudomallei in melioidosis-endemic areas.The Gram-negative bacillus Burkholderia pseudomallei is a Tier 1 select agent and the cause of melioidosis.¹ The disease accounts for 20% of all community-acquired septicemias in northeastern Thailand,² where melioidosis is the third most frequent cause of death from infectious diseases.³ Melioidosis is notoriously difficult to cure despite appropriate antimicrobial therapy and has a case-fatality rate of up to 43%.³ More than half of all melioidosis patients are bacteremic, and positive blood cultures for B. pseudomallei obtained at hospital admission and/or during hospitalization are strong prognostic markers for death.⁴Although the automated blood culture system (BacT/Alert) is convenient and currently used in many laboratories in provincial hospitals in Thailand, it is unclear whether its sensitivity for the detection of pathogens is similar to that obtained using a conventional low tech system still commonly used in small hospitals in resource-limited settings.In a retrospective study conducted during January 1, 2009–July 31, 2011 as part of routine patient care at Sappasithiprasong Hospital, a 1,000-bed tertiary-care hospital in northeastern Thailand, we compared the organisms isolated from more than 30,000 pairs of blood culture bottles by using the BacT/Alert system and the conventional system.In conventional system, the culture medium is made in-house, blood culture bottles are incubated in a conventional incubator, and bacterial detection is made by direct visualization with or without regular sub-culture. During the study period, two 5-mL blood samples were regularly obtained from each patient 10–15 minutes apart. The first 5 mL of blood was inoculated into a 40 mL culture media BacT/Alert SA bottle (catalog no. 259789; bioMérieux, Durham, NC). The second 5 mL of blood was inoculated into an in-house bottle containing 40 mL of broth, which consisted of 37 g of brain heart infusion medium broth (catalogue no, 211059; Becton Dickinson, Franklin Lakes, NJ) and 0.25 g of sodium polyanatholesulfonate (catalog no.1000907362; Sigma, St. Louis, MO), in 1 liter of purified water. BacT/Alert bottles were incubated in the BacT/Alert automated blood culture system (bioMérieux) at 35°C for 7 days, and in-house bottles were incubated aerobically in a normal incubator at 35°C for 7 days. Examination of BacT/Alert bottles was done according to the directions provided by the manufacturer, and positive cultures were indicated on the computer screen accompanied by a beeping sound. Positive cultures in the in-house bottles were detected by direct visualization of cloudy broth.Positive bottles from both systems were sub-cultured by using airway needles (bioMérieux) to place approximately 15–20 μL of the culture on chocolate agar, blood agar, and eosin-methylene blue agar. In addition, all in-house bottles were routinely sub-cultured onto blood agar on day 2 of incubation, and all in-house and BacT/Alert bottles were routinely sub-cultured onto blood agar on day 7 of incubation. Blood agar and eosin-methylene blue agar plates were incubated aerobically at 35°C and inspected at 24 hours. Chocolate agar plates were incubated in an atmosphere of 5% CO₂ at 35°C and were inspected at 48 hours. Bacterial or fungal colonies that grew on culture plates were identified by using standard biochemical tests and colonies of presumptive B. pseudomallei were identified by typical colony morphology on Ashdown agar, resistance to gentamicin and colistin, and a positive result for a highly specific latex agglutination test, as described.^5,6A total of 30,210 pairs of blood culture bottles were collected during the study period (10,208, 12,574 and 7,428 in 2009, 2010 and 2011, respectively). Overall, 2,575 (8.5%) specimens were culture positive for pathogenic organisms. A total of 1,536 (59.7%) grew with both methods, 667 (25.9%) grew only with the BacT/Alert system, and 372 (14.4%) grew only with the conventional method.The pathogenic organisms isolated were gram-negative bacteria (68.1%), gram-positive bacteria (20.0%), fungi (9.7%) and polymicrobial organisms (2.2%). The most common pathogens were Escherichia coli (18.9%, 486 of 2,575), B. pseudomallei (17.3%, 446 of 2,575), Klebsiella species (10.3%, 266 of 2,575), Staphylococcus aureus (8.5%, 219 of 2,575), and Pseudomonas spp. (8.0%, 207 of 2,575) (

The association between 10-year fracture risk by FRAX and osteoporotic fractures with disease activity in patients with rheumatoid arthritis

As rheumatoid arthritis (RA) is an independent risk factor for osteoporotic fractures, the severity of disease activity may correlate with fracture risk. Our objectives were to determine the prevalence of major osteoporotic and hip fractures in patients with RA and to identify the factors related to their 10-year probabilities. This study enrolled 232 patients with RA, aged 40–90 years, who participated in the Siriraj RA Cohort in 2016 and 2017. Demographic data, disease activity scores 28 (DAS28), and health assessment questionnaires (HAQ) were collected. All participants were evaluated for asymptomatic vertebral fractures by thoracolumbar spine radiography. The osteoporotic fracture risks were determined using the fracture risk assessment tool (FRAX). Most subjects were postmenopausal women in their sixth decade; the median disease duration was 12.95 years. Forty-six percent of patients had osteoporotic fractures, and most (87%) were vertebral fractures. Eighty-one patients had asymptomatic vertebral compression fractures. Of those, 57%, 25%, and 18% had low, moderate, and high 10-year probabilities of major osteoporotic fractures, respectively, while 51%, 34%, and 15% had low, moderate, and high 10-year probabilities of hip fractures, respectively. Factors significantly associated with the 10-year probabilities of major osteoporotic and hip fractures were disease duration (p 0.017, 0.009), menopause duration (p?<?0.001 both), cumulative disease activity (DAS28; p 0.004, 0.029), and cumulative functional disability (HAQ; p?<?0.001 both). Moderate to high 10-year probabilities of major osteoporotic and hip fractures are common in RA. Cumulative disease severity is a high risk for osteoporotic fractures.     

The question of the question: impactful implementation science to address the HIV epidemic

IntroductionQuestions about the implementation of evidence‐based intervention to treat and prevent HIV have risen to the top of the field''s scientific priorities. Despite the availability of highly efficacious treatment and prevention interventions, impact has fallen short of targets because these interventions are used with insufficient reach, consistency, sustainability and equity in diverse real‐world settings. At present, substantial excitement for implementation science — defined as research methods and strategies to improve use of evidence‐based interventions — has focused on developing and disseminating methods to conduct rigorous research. Yet, impactful answers depend on a sometimes less visible, but even more important, step: asking good questions about implementation.DiscussionIn this commentary, we offer several considerations for researchers formulating implementation research questions based on several distinctive features of the field. First, as findings are used not only by other researchers but by implementers, scientific questions must incorporate a range of stakeholder and community perspectives to be most relevant. Second, real‐world settings are contextually diverse, and the most relevant scientific questions must position answers to make sense within these contexts (whether geographical, organizational and sociological), rather than apart from them. Third, implementation is complex and dynamic; consequently, research questions must make use of emerging standards in describing implementation strategies and their effects whenever possible. Finally, the field of implementation science continues to evolve, so framing problems with a diverse disciplinary lens will enable researchers to pose insightful and impactful questions.ConclusionsWe are now at a juncture marked by both rich evidence‐based interventions and a persistent global pandemic. To achieve continued scientific progress against the HIV epidemic, asking the right questions might be part of the answer itself.     

Increasing Incidence of Human Melioidosis in Northeast Thailand

Melioidosis is a serious community-acquired infectious disease caused by the Gram-negative environmental bacterium Burkholderia pseudomallei. A prospective cohort study identified 2,243 patients admitted to Sappasithiprasong Hospital in northeast Thailand with culture-confirmed melioidosis between 1997 and 2006. These data were used to calculate an average incidence rate for the province of 12.7 cases of melioidosis per 100,000 people per year. Incidence increased incrementally from 8.0 (95% confidence interval [CI] = 7.2–10.0) in 2000 to 21.3 (95% CI = 19.2–23.6) in 2006 (P < 0.001; χ² test for trend). Male sex, age ≥ 45 years, and either known or undiagnosed diabetes were independent risk factors for melioidosis. The average mortality rate from melioidosis over the study period was 42.6%. The minimum estimated population mortality rate from melioidosis in 2006 was 8.63 per 100,000 people (95% CI = 7.33–10.11), the third most common cause of death from infectious diseases in northeast Thailand after human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and tuberculosis.     

Low uptake of HIV testing and no HIV positivity in stable serodiscordant heterosexual partners of long-term treated HIV-infected Thais

The objective of this study was to characterize HIV-serodiscordant heterosexual couples and to evaluate acceptance for HIV testing and HIV prevalence in nonindex partners. We conducted a cross-sectional study with quantitative and qualitative components. Two cohorts of 1767 HIV-positive people were screened to identify heterosexual HIV-serodiscordant couples. HIV-positive partners (index) were administered a questionnaire; CD4, viral load (VL), and antiretroviral therapy (ART) history were gathered from clinical records. HIV-negative/unknown status partners (nonindex) were invited for a similar questionnaire and HIV testing. In-depth interviews with three HIV-serodiscordant couples were conducted. Two hundred and ninety-seven index partners agreed to enroll in this study. The median duration of the relationship was 10 years, and 81% were sexually active. All but two index partners were on ART, and 98% had VL < 1000 copies/mL. Only 111 (37%) nonindex partners came for HIV testing, and all of them tested HIV-negative. In addition, only 41% of nonindex partners had HIV testing in the last one year. The main reasons for the nonindex partners not to come for HIV testing were “no interest” (n = 117, 63%) and “nondisclosure of HIV status” (n = 46, 25%). The latter was substantiated and explained by the qualitative outcome of this study, suggesting relation to stigma against HIV-positive people. Our results support the WHO recommendation for starting ART for treatment and prevention in HIV-serodiscordant couples at any CD4 count. Furthermore, we recommend the dissemination of data showing that no HIV transmission in heterosexual couples through sex practice has been observed provided VL is suppressed. This could be a powerful tool for effective fight against stigma and self-stigma in people living with HIV.