Kumthorn Malathum

Population Pharmacokinetics of Vancomycin in Thai Patients

Population pharmacokinetics of vancomycin in Thai adult patients was determined by non-linear mixed-effects approach using 319 vancomycin serum concentrations from 212 patients. The data were best fitted by a two-compartment model and it was used to examine the effect of patient characteristics on the vancomycin pharmacokinetics. In the final model, there was a linear relationship between vancomycin clearance, CL (L/h), and creatinine clearance calculated by Cockcroft-Gault equation, CLCr (mL/min): CL  =0.044  ×  CLCr. Meanwhile, volume of central compartment, V 1 (L), was linearly related with the age (years old): V 1 = 0.542  × Age. Intercompartment clearance (Q) and volume of peripheral compartment (V 2) was 6.95 L/h and 44.2 L, respectively. The interindividual variability for CL, V 1, Q, and V 2 was 35.78, 20.93, 39.50, and 57.27%, respectively. Whereas, the intraindividual variability was 4.51 mg/L. Final model then was applied to predict serum vancomycin concentrations on validation group. Predictive performance revealed a bias of −1.43 mg/L (95% CI: −5.82–2.99) and a precision of 12.2 mg/L (95% CI: −1.60–26.16). In conclusion, population pharmacokinetic of vancomycin in Thai adult patients was developed. The model could be used to create vancomycin dosage regimen in the type of patient similar with the present study.

Concomitant tuberculous and cryptococcal thyroid abscess in a human immunodeficiency virus-infected patient

Suppurative thyroiditis is a rare condition caused mostly by Staphylococcus aureus and streptococci. Both tuberculous and cryptococcal thyroid abscess are even rarer. The incidence of extrapulmonary forms of tuberculosis and cryptococcosis has increased in areas with a high prevalence of human immunodeficiency virus (HIV) infection. A case is reported of dual infection by M. tuberculosis and Cryptococcus neoformans presenting as a thyroid abscess in a 32-y-old woman with symptomatic HIV infection. Atypical presentations of both tuberculosis and cryptococcosis should be considered in areas with a high incidence of these diseases.

High coverage and safety of influenza A (H1N1) 2009 monovalent vaccination among health care personnel in Thailand

We aimed to report the coverage and safety of the influenza A (H1N1) 2009 monovalent vaccination (Panenza; Sanofi Pasteur, Val de Reuil Cedex, France) among health care personnel (HCP) in a university hospital setting in Thailand. The hospital set up a system to vaccinate HCP and did surveillance of the adverse effects (AEs). During a 4-week period, 6,210 (78.7%) HCP were vaccinated. There were 82 reported nonserious AEs among 32 HCP. The most common AE was fatigue/uncomfortable feeling (24%).

Pandemic (H1N1) 2009 virus infection: Persistent viral shedding after Oseltamivir treatment

OBJECTIVES To study pandemic (H1N1) 2009 virological outcomes after Oseltamivir treatment in confirmed cases of pandemic (H1N1) 2009 virus infections. A hospital-based cohort study was conducted in south Thailand, between June and September 2009. METHODS Throat/swab specimens were tested by real-time reverse transcriptase polymerase chain reaction (rRT-PCR) for pandemic (H1N1) 2009. All 357 confirmed cases (122 inpatients, 235 outpatients), whose received a 5-day Oseltamivir treatment. Post-treatment virological follow-up was performed in 91 eligible cases. The NA gene was screened for the H275Y mutation responsible for Oseltamivir resistance. RESULTS Thirty-three of 91 patients (36%) had underlying diseases. The duration from the onset of illness to the detection of virus ranged 1-14 days (median 3 days). The rRT-PCR was positive on day 5 of treatment in 24 of 91 patients (26%). Patients with underlying diseases had a higher proportion of post-treatment positive test than those without underlying diseases (15/33 vs 9/58). The rRT-PCR-confirmed viruses detected in all 125 throat swab specimens did not show evidence suggesting Oseltamivir resistance. CONCLUSIONS Prolonged presence of pandemic (H1N1) 2009 detected by rRT-PCR was found. An extended course of antiviral treatment should be considered in patients with underlying diseases and severe clinical symptoms.

H1N1 2009 influenza among healthcare workers in a tertiary care hospital in Thailand

resources besides causing inconvenience to patients (staying indoors in an isolation room, visitor restriction, and potential breach of personal confidential clinical information). In view of the above limitations of clinical algorithms and the consequences its implementation may generate, it is imperative that a rational approach is adopted with regard to resource utilisation and infection control needs. Infection control teams of most hospitals are under significant pressure to prevent nosocomial infections to patients, visitors and staff. Understandably under these circumstances it is not uncommon for a safety-first attitude to be adopted, leading to over-utilisation of available resources. Novel swine influenza should not blind us to the fact that there are many other old infections which are equally important and worthy of prevention. The latest data from the World Health Organization show that the basic reproduction rate (R0: mean number of secondary cases a single case will cause) of the novel H1N1 influenza virus is <2 in most European countries and in the USA, which is significantly less than for many common diseases such as measles (R0: 12e18) and mumps (R0: 4e7). 5 Although the preventive measures to contain swine flu are justified (e.g. use of FFP3 mask for aerosol-generating procedures such as endotracheal intubation or suctioning), it is unreasonable not to take such measures for other diseases with potentially serious consequences (e.g. intubation of a patient suspected to have chickenpox or measles). Case definitions are like diagnostic tests. Since case definitions act as a screening tool they are designed to have a high level of sensitivity at the expense of specificity. However, like other diagnostic tests the test for swine flu is likely to have a number of false-negative and false-positive results. It is important that users are aware of its limitations so that when one or more of certain symptoms are absent or additional symptoms/signs are present, the context within which the case definition is being applied is considered. If the consequence of spread of H1N1 virus is higher (inpatient, pregnancy, intubation), a higher level of caution is reasonable, and testing patients or using PPE or other infection control measures can be justified. Clinical algorithms are not tablets of stone. They are rather guide maps akin to the global positioning system. Keeping eyes and ears open is as important as the ability to read these maps.

Predicting factors for unsuccessful switching from nevirapine to efavirenz in HIV-infected patients who developed nevirapine-associated skin rash.

Summary Skin rash associated with nevirapine (NVP) is common and efavirenz (EFV) is often used as a substitute. We aimed to determine the predicting factors for unsuccessful switching from NVP to EFV. A retrospective cohort study was conducted in HIV-infected patients who developed rash after taking NVP. There were 109 patients with a mean standard deviation (SD) age of 36.6 (7.4) years and 45% were males. Median (interquartile range) CD4 cell count and HIV RNA at the time of NVP initiation were 163 (50–273) cells/mm3 and 4.6 (1.7–5.4) log copies/mL, respectively. Twenty (18.3%) patients subsequently developed EFV-associated rash. By logistic regression, history of drug allergy apart from NVP (odds ratio [OR] 11.42) and CD4 cell count <100 cells/mm3 (OR 6.14) were significant predicting factors for EFV-associated rash. Two predicting factors for unsuccessful switching from NVP to EFV were found. Patients who have these factors need to have a close follow-up if EFV is substituted.

HIV-1 genotype after interruption of non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy and virological response after resumption of the same regimen

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have a longer half-life than nucleoside reverse transcriptase inhibitor (NRTIs). Simultaneous interruption of all drugs exposes the patients to NNRTI monotherapy. This study evaluated HIV-1 genotype after treatment interruption (TI) of NNRTI-based antiretroviral therapy (ART) and virological response after resumption of the same ART regimen. A prospective study was conducted in HIV-1-infected patients who enrolled into a CD4-guided TI study. All patients continued dual NRTIs for a further 7–10 days at NNRTI TI. HIV-1 genotypic assay was performed prior to resumption of the same ART regimen. Forty-three patients required ART resumption after TI from NNRTI-based regimens. Mean age was 42.7 years; 44% were men. Median CD4 and HIV-1 RNA at the time of ART resumption were 178 cell/mm3 and 5.78 log copies/mL, respectively. HIV-1 genotype revealed no mutations contributed to NRTI or NNRTI resistance. Of all, 56% and 100% patients achieved undetectable HIV-1 RNA at three and six months, respectively. Median CD4 were 386 and 419 cells/mm3 at the corresponding periods. In conclusion, continuation of dual NRTIs for 7–10 days after TI of NNRTI-based regimens can minimize the risk of acquired NNRTI resistance. With this strategy, the same regimen can be used for resumption and also yield good virological and immunological outcomes.

Clinical Specimen-Direct LAMP: A Useful Tool for the Surveillance of blaOXA-23-Positive Carbapenem-Resistant Acinetobacter baumannii

Healthcare-associated infections are a leading cause of morbidity and mortality worldwide. Treatment is increasingly complicated by the escalating incidence of antimicrobial resistance. Among drug-resistant pathogens, carbapenem-resistant Acinetobacter baumannii (CRAb) is of increasing concern because of the limited applicable therapies and its expanding global distribution in developed countries and newly industrialized countries. Therefore, a rapid detection method that can be used even in resource-poor countries is urgently required to control this global public health threat. Conventional techniques, such as bacterial culture and polymerase chain reaction (PCR), are insufficient to combat this threat because they are time-consuming and laborious. In this study, we developed a loop-mediated isothermal amplification (LAMP) method for detecting bla OXA-23-positive CRAb, the most prevalent form of CRAb in Asia, especially in Thailand, and confirmed its efficacy as a surveillance tool in a clinical setting. Clinical samples of sputum and rectal swabs were collected from patients in a hospital in Bangkok and used for LAMP assays. After boiling and centrifugation, the supernatants were used directly in the assay. In parallel, a culture method was used for comparison purposes to evaluate the specificity and sensitivity of LAMP. As a first step, a total of 120 sputum samples were collected. The sensitivity of LAMP was 88.6% (39/44), and its specificity was 92.1% (70/76) using the culture method as the “gold standard”. When surveillance samples including sputum and rectal swabs were analyzed with the LAMP assay, its sensitivity was 100.0%. This method enables the direct analysis of clinical specimens and provides results within 40 minutes of sample collection, making it a useful tool for surveillance even in resource-poor countries.

Five-year prospective study of tuberculin skin testing among new healthcare personnel at a university hospital in Thailand

We determined the prevalence of a positive tuberculin skin test (TST) and the incidence of TST conversion among new healthcare personnel (HCP) in a hospital in Thailand. During 2005-2008, TST was performed on 1438 HCP and the prevalence of positive TST was 66.3%. Age, male gender, and the presence of Bacille Calmette-Guérin (BCG) scar were associated with odds of positive TST (all P < 0.05). The incidence of TST conversion was 4.8 per 100 HCP-years. Nine (0.6%) HCP were diagnosed with active tuberculosis. The annual surveillance programme is important for the early diagnosis and prevention of tuberculosis among HCP in Thailand.

A Model and Risk Score for Predicting Nevirapine-Associated Rash among HIV-infected Patients: In Settings of Low CD4 Cell Counts and Resource Limitation

Background: Rash is the most common adverse effect associated with nevirapine (NVP). We aimed to develop a model and risk score for predicting NVP-associated rash among HIV-infected patients with low CD4 cell counts. Methods: Cross-sectional study was conducted and 383 HIV-infected patients consecutively enrolled in the study. Results: Of 222 patients in the training set, 116 (52.2%) were males and median (IQR) age was 35.2 (31.1-42.0) years. Median (IQR) CD4 cell count was 104 (35-225) cells/mm3. Of these, 72 and 150 patients were in “rash” and “no rash” group, respectively. Four factors were independently associated with rash: a history of drug allergy (odds ratio (OR) 4.01, 95% confidence interval (CI), 1.75-9.20, P = 0.001), body weight <55 kg. (OR 2.02, 95% CI, 1.09-3.76, p = 0.026), not receiving slow dose escalation (OR 2.00, 95% CI, 1.06-3.77, p = 0.032), and no concomitant drug(s) (OR 2.48, 95% CI, 1.32-4.64, p = 0.005). Receiver-operator characteristic analysis yielded area under the curve of 71% and the goodness-offit statistics was 6.48 (p = 0.840). The variables were given scores of 14, 7, 7 and 9, respectively. A cutoff >21 points defined the high risk individuals which yielded specificity and positive predictive value of 99% and 69%, respectively, with OR of 3.96 (95% CI, 1.79-8.86, p = 0.001). Conclusions: A model and risk score for predicting NVP-associated rash performed well in this study population. It might be useful for predicting the risk of rash before NVP initiation among HIV-infected patients with low CD4 cell counts.