A pilot program of HIV pre-exposure prophylaxis in Thai youth.

INTRODUCTION: There are gaps in knowledge and experience of antiretroviral pre-exposure prophylaxis (PrEP) delivery in adolescents. METHODS: This pilot study enrolled Thai adolescents 14-20 year-old without HIV who reported risk behaviour. All participants were offered daily tenofovir/emtricitabine (TDF-FTC) and followed for 24 weeks. HIV testing, renal function, bone density scan, and sexually transmitted infection (STI) testing including syphilis serology and urine molecular testing for gonorrhoea and C. trachomatis were performed at baseline and weeks 12 and 24. Adherence was evaluated through intracellular tenofovir diphosphate (TFV-DP) levels in dried blood spots. RESULTS: Of the 61 enrolled adolescents, median age 18.1 (IQR: 14.8-20.9) years, 46 (75.4%) were males and 36 (59%) were MSM. Retention to week 24 was 80.3%. One third (36%) had TFV-DP levels consistent with taking ≥6 pills/week at week 12 and 29% at week 24. The factors associated with taking ≥6 pills/week were being MSM (adjusted odds ratio [aOR]: 53.2, 95% CI: 1.6-1811; p = 0.027), presence of STI at baseline (aOR: 9.4, 95% CI: 1.5-58.5; p = 0.016), and self-report of decreased condom use while taking PrEP (aOR: 8.7, 95% CI: 1.4-56.6; p = 0.023). 31% had an STI at baseline and this declined to 18% at week 24. No renal or bone toxicity was observed and there were no HIV seroconversions. CONCLUSIONS: Daily oral PrEP with FTC-TDF in high-risk Thai adolescents is feasible, accepted, well-tolerated, and had no increased risk compensation; however, low adherence was a major challenge. Adolescent-specific PrEP strategies including long-acting modalities are needed for successful HIV prevention.

A Risk Prediction Model and Risk Score of SARS-CoV-2 Infection Following Healthcare-Related Exposure.

Hospital workers are at high risk of contact with COVID-19 patients. Currently, there is no evidence-based, comprehensive risk assessment tool for healthcare-related exposure; so, we aimed to identify independent factors related to COVID-19 infection in hospital workers following workplace exposure(s) and construct a risk prediction model. We analyzed the COVID-19 contact tracing dataset from 15 July to 31 December 2021 using multiple logistic regression analysis, considering exposure details, demographics, and vaccination history. Of 7146 included exposures to confirmed COVID-19 patients, 229 (4.2%) had subsequently tested positive via RT-PCR. Independent risk factors for a positive test were having symptoms (adjusted odds ratio 4.94, 95%CI 3.83−6.39), participating in an unprotected aerosol-generating procedure (aOR 2.87, 1.66−4.96), duration of exposure >15 min (aOR 2.52, 1.82−3.49), personnel who did not wear a mask (aOR 2.49, 1.75−3.54), exposure to aerodigestive secretion (aOR 1.5, 1.03−2.17), index patient not wearing a mask (aOR 1.44, 1.01−2.07), and exposure distance <1 m without eye protection (aOR 1.39, 1.02−1.89). High-potency vaccines and high levels of education protected against infection. A risk model and scoring system with good discrimination power were built. Having symptoms, unprotected exposure, lower education level, and receiving low potency vaccines increased the risk of laboratory-confirmed COVID-19 following healthcare-related exposure events.

Depression and Anxiety in Youth and Young Adults Living with HIV: Frequency and Associated Factors in Thai Setting.

Integrative mental health care in HIV patients is an important contributor to successful therapy. This is a cross-sectional study in youth and young adults who attend routine HIV clinic at a tertiary care centre in Bangkok. We recruited 100 youth and 130 young adults living with HIV to evaluate the frequency of depression and anxiety and associated sociodemographic including sexual orientation and health-related behaviours. Overall, about a fifth of the participants had significant depression or anxiety. Interestingly, we found different factors associated with depression in youth and young adults living with HIV. Loss of their father, loss of close relatives or friends, and being unemployed or school exclusion were the factors associate with depression in youth; while dangerous alcohol use, feeling discriminated against and having lipodystrophy were factors in young adults. The understanding of the frequency and different associated factors can inform more effective prevention and treatment strategies.

Attitudes towards, knowledge about, and confidence to prescribe antiretroviral pre-exposure prophylaxis among healthcare providers in Thailand.

ABSTRACT: HIV pre-exposure prophylaxis (HIV-PrEP) is an effective method for preventing HIV transmission, and it is recommended in several international guidelines. Perceptions and knowledge about HIV-PrEP prescription among healthcare providers have not been investigated in Thailand where HIV-PrEP is a novel healthcare topic. The objective of study was to determine healthcare providers' attitudes towards, knowledge about, and confidence to prescribe HIV-PrEP in Thailand.A questionnaire was administered to Thai healthcare providers during May 1, 2017 to September 5, 2018.Of the 500 questionnaires that were distributed, 460 were returned (92%). Respondents included 336 physicians (48 infectious disease [ID] physicians, 288 non-ID physicians) and 124 non-physicians (70 nurses, 35 pharmacists, and 19 others). Eighty one percent of respondents had a positive attitude towards HIV-PrEP. Multivariate analysis revealed being a non-ID physician, having prior knowledge about HIV-PrEP, believing that HIV-PrEP can reduce the number of new patients, and believing that HIV-PrEP is not associated with a higher incidence of other sexually transmitted infections were all factors significantly associated with having a positive attitude towards HIV-PrEP. The issue of most concern to respondents who had a negative attitude toward HIV-PrEP was poor patient adherence to antiviral medications. Only 57% of respondents had confidence to prescribe HIV-PrEP. Factors associated with confidence to prescribe HIV-PrEP included being an ID physician, believing that HIV-PrEP can reduce the number of new patients, believing in the safety of antiviral medications, and believing that HIV-PrEP is not associated with increased development of HIV drug resistance. The results of HIV-PrEP knowledge testing (8 questions) were categorized into good score (≥7/8) and fair score (≤6/8). Fifty five percent of participants had a good score result. Using multivariate analysis, the factors associated with a good score result were ID physician, having HIV-PrEP prescription experience, and believing that HIV-PrEP can reduce the number of new patients.Most Thai healthcare providers (81%) reported having a positive attitude towards HIV-PrEP. Successful HIV-PrEP implementation in Thailand will require steps to mitigate the described barriers, and training for healthcare providers, which will strengthen knowledge and improve both experience with and confidence to prescribe HIV-PrEP.

Raltegravir versus efavirenz in antiretroviral-naive pregnant women living with HIV (NICHD P1081): an open-label, randomised, controlled, phase 4 trial.

BACKGROUND: Although antiretroviral regimens containing integrase inhibitors rapidly suppress HIV viral load in non-pregnant adults, few published data from randomised controlled trials have compared the safety and efficacy of any integrase inhibitor to efavirenz when initiated during pregnancy. We compared safety and efficacy of antiretroviral therapy with either raltegravir or efavirenz in late pregnancy. METHODS: An open-label, randomised controlled trial was done at 19 hospitals and clinics in Argentina, Brazil, South Africa, Tanzania, Thailand, and the USA. Antiretroviral-naive pregnant women (20-<37 weeks gestation) living with HIV were assigned to antiretroviral regimens containing either raltegravir (400 mg twice daily) or efavirenz (600 mg each night) plus lamivudine 150 mg and zidovudine 300 mg twice daily (or approved alternative backbone regimen), using a web-based, permuted-block randomisation stratified by gestational age and backbone regimen. The primary efficacy outcome was plasma HIV viral load below 200 copies per mL at (or near) delivery. The primary efficacy analysis included all women with a viral load measurement at (or near) delivery who had viral load of at least 200 copies per mL before treatment and no genotypic resistance to any study drugs; secondary analyses eliminated these exclusion criteria. The primary safety analyses included all women who received study drug, and their infants. This trial is registered with Clinicaltrials.gov, number NCT01618305. FINDINGS: From Sep 5, 2013, to Dec 11, 2018, 408 women were enrolled (206 raltegravir, 202 efavirenz) and 394 delivered on-study (200 raltegravir, 194 efavirenz); 307 were included in the primary efficacy analysis (153 raltegravir, 154 efavirenz). 144 (94%) women in the raltegravir group and 129 (84%) in the efavirenz group met the primary efficacy outcome (absolute difference 10%, 95% CI 3-18; p=0·0015); the difference primarily occurred among women enrolling later in pregnancy (interaction p=0·040). Frequencies of severe or life-threatening adverse events were similar among mothers (30% in each group; 61 raltegravir, 59 efavirenz) and infants (25% in each group; 50 raltegravir, 48 efavirenz), with no treatment-related deaths. INTERPRETATION: Our findings support major guidelines. The integrase inhibitor dolutegravir is currently a preferred regimen for the prevention of perinatal HIV transmission with raltegravir recommended as a preferred or alternative integrase inhibitor for pregnant women living with HIV. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Institute of Allergy and Infectious Diseases.

Efficacy and safety of de-escalation therapy to ertapenem for treatment of infections caused by extended-spectrum-ß-lactamase-producing Enterobacteriaceae: an open-label randomized controlled trial.

BACKGROUND: Carbapenem antibiotics are considered the treatment of choice for serious extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria (GNB) infections. The study objectives were to evaluate efficacy and safety of de-escalation therapy to ertapenem for treatment of infections caused by extended-spectrum-ß-lactamase-producing Enterobacteriaceae. METHODS: We conducted a randomized controlled trial of adult patients with documented ESBL-producing Enterobacteriaceae infections who had received any group 2 carbapenem for less than 96 h. In the intervention group, the previously-prescribed group 2 carbapenem was de-escalated to ertapenem. In the control group, the group 2 carbapenem was continued. RESULTS: During June 2011-December 2014, 32 patients were randomized to the de-escalation group and 34 to the control group. Most common sites of infection were urinary tract infection (42%). Characteristics of both groups were comparable. By using a 15% predefined margin, ertapenem was non-inferior to control group regarding the clinical cure rate (%Δ = 14.0 [95% confidence interval: -2.4 to 31.1]), the microbiological eradication rate (%Δ = 4.1 [-5.0 to 13.4]), and the superimposed infection rate (%Δ = -16.5 [-38.4 to 5.3]). Patients in the de-escalation group had a significantly lower 28-day mortality rate (9.4% vs. 29.4%; P = .05), a significantly shorter median length of stay (16.5 days [4.0-73.25] vs. 20.0 days [1.0-112.25]; P = .04), and a significantly lower defined daily dose of carbapenem use (12.9 ± 8.9 vs. 18.4 ± 12.6; P = .05). CONCLUSIONS: Ertapenem could be safely used as de-escalation therapy for ESBL-producing Enterobacteriaceae infections, once the susceptibility profiles are known. Future studies are needed to investigate ertapenem efficacy against ESBL-producing Enterobacteriaceae pneumonia to determine its applicability in life-threatening conditions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01297842 . Registered on 14 February 2011. First patient enrolled on 27 June 2011.

Serological response of patients with influenza A (H1N1) pdm09-associated pneumonia: an observational study.

BACKGROUND: Little is known about the dynamics or magnitude of antibody response in patients with influenza A (H1N1) pdm09-associated pneumonia. We described and compared the antibody response to influenza A (H1N1) pdm09 in patients with and without pneumonia. METHODS: We collected serum samples and determined antibody titers by the hemagglutination inhibition (HI) and microneutralization (mNT) assays from patients with RT-PCR confirmed influenza A (H1N1) pdm09 virus at baseline, 1, 2 and 6 months after onset of illness. RESULTS: Fifty-nine patients were enrolled, 45 (76.3%) were between 15 and 60 years of age, 49 (83.1%) were hospitalized and 25 (42.4%) had complications with pneumonia. Ninety-four percent of patients had HI titers ≥ 1: 40 and 90% had mNT titers ≥ 1: 160 at 2 months after illness. Geometric mean titers (GMT) of HI and mNT increased significantly (p<0.001) between baseline and months 1 or 2, then declined significantly (p<0.001) at month 6 by the HI assay, but dropped to an insignificant level (p=0.24) by the mNT assay. The mNT-GMT was at least twice as high as corresponding HI antibodies over a 6 month period. The GMT of HI and mNT in those with pneumonia (1 mo) peaked earlier than that of those without pneumonia (2 mo). When adjusted by age and gender, those with pneumonia had a higher HI-GMT than those without pneumonia at 1 month (264 vs. 117, p=0.007), 2 months (212 vs. 159, p=0.013), and 6 months (160 vs. 82, p=0.018). CONCLUSIONS: The patients recovered from influenza A (H1N1) pdm09-associated pneumonia, clearly developed an earlier and more robust antibody response until 6 months after onset of illness. The results in our study are useful to determine an appropriate donor and timing to obtain convalescent plasma for adjunctive treatment of seriously ill patients with pandemic H1N1 influenza.

Effectiveness and safety of generic formulation of meropenem (Penem) for treatment of infections at Siriraj Hospital.

OBJECTIVE: Generic meropenem (Penem) has been available and was substituted for original meropenem in Siriraj Hospital, but its effectiveness and safety for treatment of infection in clinical setting are the main concern. MATERIAL AND METHOD: From July 2007 to July 2010, hospitalized patients aged 18 or older who received meropenem for at least 48 hours were identified retrospectively from the pharmacy database of Siriraj Hospital. 260 patients per group were required to demonstrate non-inferiority of generic meropenem (Penem) versus original meropenem in term of overall favorable outcome. RESULTS: 275 and 273 patients receiving original and generic meropenem were enrolled and analyzed. Overall favorable outcome and overall mortality were comparable between generic and original group (72.5% vs. 65.8%, p = 0.108; 38.6% vs. 39.3%, p = 0.918, respectively). No significant difference of adverse effect was found between two groups. The non-inferiority test indicated that the clinical outcome and overall mortality of the generic meropenem were non-inferior to the original meropenem (p < 0.001, p = 0.005, respectively). The independent factors associated with unfavorable outcome were previous use of an antibiotic, having respiratory tract infection, receiving lower dose and shorter duration of antibiotic. The independent factors associated with the overall mortality were underlying pulmonary disease, previous use of antibiotic, having respiratory tract or catheter related blood stream infection. Treatment with either generic or original meropenem did not relate to unfavorable outcome (p = 0.320) or overall mortality (p = 0.640). CONCLUSION: Generic meropenem (Penem) was not inferior to original meropenem for therapy of infections in the hospitalized patients at Siriraj Hospital.

Acinetobacter baumannii nosocomial pneumonia in tertiary care hospitals in Thailand.

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

Monitoring of effectiveness and safety of generic formulation of meropenem for treatment of infections at Siriraj Hospital.

OBJECTIVE: In Siriraj Hospital, generic meropenem (Monem) has been available and was substituted for original meropenem, but the effectiveness and safety of using generic meropenem in a clinical setting are the main concern. MATERIAL AND METHOD: From July 2007 to June 2009, hospitalized patients aged 18 or older who received meropenem for 48 hours were identified from the pharmacy database of Siriraj hospital. A retrospective study was conducted. Three hundred patients in each of original and generic meropenem groups were required to demonstrate non-inferiority of generic to original meropenem. RESULTS: The mean age of all patients was 63 years. Most of the patients had co-morbidities. Approximately 90% of the infections were health-care associated. Drug-resistant gram-negative bacteria including ESBL producing E. coli and K. pneumoniae, P. aeruginosa and A. baumannii account for nearly 50% of all organisms. No significant difference was found regarding characteristics, type or site of infection and pathogen between generic and original groups but for more patients in the original group having cardiovascular disease and more patients in the generic group receiving immunosuppressive agents. Eighty-two to 85% received meropenem with one of appropriate indications. No statistically significant difference occurred either in an overall favorable outcome (63% vs.70.4%, p = 0.07) or in overall mortality (38% vs. 32%, p = 0.17), as well as adverse effects between the original and the generic groups. CONCLUSION: Generic meropenem (Monem) was not inferior to original meropenem for therapy of infections in the hospitalized patients at Siriraj Hospital.

Hospital-acquired pneumonia and ventilator-associated pneumonia in adults at Siriraj Hospital: etiology, clinical outcomes, and impact of antimicrobial resistance.

BACKGROUND: Nosocomial pneumonia (NP), hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), is an important cause of morbidity and mortality in hospitalized patients. One of the factors contributing to a high mortality rate of HAP and VAP could be antibiotic resistance among the causative agents. OBJECTIVE: To determine prevalence of bacterial pathogens clinical features, risk factors of HAP and VAP, antimicrobial resistance among major respiratory pathogens, clinical implication of antimicrobial resistance, antimicrobial regimens used, and treatment outcomes of adult patients with HAP and VAP at Siriraj Hospital. MATERIAL AND METHOD: This was a prospective, hospital-based, active surveillance study on HAP and VAP in hospitalized adults at Siriraj Hospital from December 2007 to March 2009. The patients with HAP and VAP were followed prospectively until they expired or were discharged from the hospital. RESULTS: One hundred and forty-six adult patients were included. Seventy percent of the patients were males with the mean age of 70.8 years. HAP was accounted for 24.7% and VAP 75.3%. Most of the patients (82.9%) had late-onset HAP or VAP with the median day of onset of pneumonia of 11 days. Two third of the patients were hospitalized in general medical wards. Bronchopneumonia was observed in 53.4% and multilobar pneumonia in 24.7%. A. baumanni was the most common isolated pathogen and 92.3% of them were multidrug-resistant (MDR) or pandrug-resistant (PDR). The other common isolated pathogens were K. pneumoniae, P. aeruginosa and methicillin-resistant S. aureus (MRSA). Carbapenem was the most commonly used initial antibiotic (45.9%) followed by colistin (21.9%) and cephalosporins (21.1%). The concordance of initial antibiotics was 58.9%. Antibiotics were modified 43.8% of the patients. Colistin was the most commonly used modified antibiotic followed by carbapenem. The modified antibiotics were concordant with isolated bacteria in 98.4%. The patients received mechanical ventilators in 81.5% with the median ventilator day of 10 days. At the initial response (72 hours after antibiotic therapy), an improvement was 56.8% and a mortality rate due to pneumonia was 14.4%. Death due to pneumonia at the end of treatment was 42.5%. The 30-day mortality from pneumonia was 45.9%. There were no significant differences in the outcomes of pneumonia between HAP and VAP. The factors associated with PDR-organisms were late-onset hospital-acquired pneumonia and previous carbapenem usage within 72 hours. Septic shock and bilateral lung involvement were significantly associated with unfavorable outcomes at 72 hours. Septic shock, severe sepsis, and previous carbapenem usage within 72 hours were significantly associated with mortality at the end of treatment and at 30 days after developing pneumonia. CONCLUSION: HAP and VAP remain to be very important hospital-acquired infections at Siriraj Hospital. The isolated pathogens are usually multidrug-resistant and the mortality rate remains high. The local data on prevalence of the isolated pathogens and their antibiotic susceptibility may help clinicians choose more appropriate initial antibiotics in order to improve the outcome and to decrease the emergence of resistant organisms.