Comparisons of clinical characteristics between adult patients with 2009 H1N1 influenza and those with seasonal influenza during the 2009 epidemic in Thailand.

Clinical presentations of patients with 2009 H1N1 influenza are generally similar to those of patients with seasonal influenza. A cross-sectional study was conducted among adults at an outpatient clinic in a university hospital setting during the 2009 epidemic. Infections in all patients were confirmed by real-time reverse transcription-polymerase chain reaction. There were 269 patients with 2009 H1N1 influenza and 128 patients with seasonal influenza. Compared with patients with seasonal influenza, patients with 2009 H1N1 influenza were more likely to be aged <20 years (25.7% vs. 8.6%, P < 0.001) and to be students (38.7% vs. 22.0%, P = 0.001), or healthcare workers (20.1% vs. 10.9%, P = 0.022); however, they were less likely to have an underlying disease (25.6% vs. 39.8%, P = 0.004) and influenza vaccination (4.2% vs. 12.2%, P = 0.021). There were no differences in the illness duration, vital signs, and symptoms between groups. Patients with seasonal influenza were more likely to be admitted to the intensive care unit (2.4% vs. 0%, P = 0.033) and exhibited a higher mortality rate (2.4% vs. 0%, P = 0.093). A history of contact with a confirmed 2009 H1N1 influenza case (odds ratio [OR] = 12.91, P < 0.001) and age (OR = 1.05 per 10 years younger, P = 0.015) were associated with 2009 H1N1 influenza infections. In conclusion, these results showed differences in characteristics between the patients with 2009 H1N1 influenza and those with seasonal influenza.

Simultaneous detection and subtyping of H274Y-positive influenza A (H1N1) using pyrosequencing.

INTRODUCTION: We investigated the frequency of H274Y-positive swine-origin 2009 A (H1N1) influenza virus outbreak in Thailand during May-August 2009.  METHODOLOGY: This study sought to find Oseltamivir resistance mutation H274Y by using pyrosequencing. RESULTS: From 8,710 real-time RT-PCR swine-origin 2009 A(H1N1) influenza virus-positive specimens, 100 randomly selected samples identified one such virus with H274Y mutation  using pyrosequencing. CONCLUSIONS: The patient probably acquired oseltamivir resistance from natural variation, since he had never received that form of treatment before and recovered from influenza-like symptoms without using anti-influenza drugs.

Invasive pneumococcal disease in Phramongkutklao Hospital 2004-2008: clinical data, serotype distribution and antimicrobial resistance patterns.

OBJECTIVE: To describe the clinical course, serotype distribution and antimicrobial resistance patterns of invasive pneumococcal disease (IPD) cases in a public hospital. MATERIAL AND METHOD: Retrospective review of IPD cases occurring from January 2004 through December 2008 was performed. Antibiotic susceptibility testing and serotyping were performed for available isolates. RESULTS: Fifty one IPD cases occurred during the study period, of which 47 had medical records available for review. The majority of cases occurred among children under 5 years of age (23.4%) and adults over 60 years of age (36.1%). Underlying diseases were identified in 72.3% of patients. Fifty-three percent of cases were associated with pneumonia, while 17% had meningitis, and 15% had isolated bacteremia. Serotype could be determined for 15 (31.9%) isolates, and 6B was most common. Based on current antibiotic susceptibility breakpoints for meningitis, 4 of the 7 available isolates from meningitis cases were penicillin resistant and one had reduced susceptibility to cefotaxime. Among non-meningitis isolates, 96.7% were penicillin susceptible and 3.3% had intermediate susceptibility to penicillin. Overall case fatality proportion was 19%. CONCLUSION: At this tertiary care hospital in Bangkok, IPD has disproportionately affected young children and the elderly. High rates of penicillin resistance among meningitis cases, the most severe form of IPD, underscore the need of appropriate treatment strategies and vaccine usage.

HIV-1 drug resistance mutations in children who failed non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy.

Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens have recently been used in HIV-1 infected children in resource-limited settings. Treatment failure with this regimen has become more common. A second regimen needs to be prepared for the Thai national program. Genotypic resistance testing was conducted among HIV-1 infected children who experienced virological failure with antiretroviral therapy (ART) using NNRTI-based regimens. Patterns of resistance mutations were studied and options for a second regimen were determined. There were 21 patients with a median (IQR) age of 4.1 (1.9-7.7) years. Sixteen patients were males. The median CD4 cell count and HIV-1 RNA at the time of virological failure were 647 cells/mm3 and 5.3 log copies/ml, respectively. The prevalences of patients with > or =1 major mutation conferring resistance to NRTIs and NNRTIs were 52% and 43%, respectively. Thymidine analoque mutations, M184V/I, and Q151M were observed in 38%, 33%, and 5%. The patterns of resistance mutations suggest that 48% of patients need a protease inhibitor-based regimen for the second regimen and didanosine+lamivudine is the most required nucleoside reverse transcriptase inhibitor backbone.

A patient with penicillin-resistant viridans group streptococcal endocarditis and unusual reactions to vancomycin.

There is a paucity of data regarding the treatment of endocarditis caused by penicillin-resistant viridans group streptococci (PR-VGS). We report a 16-year-old girl who had native-valve endocarditis due to PR-VGS which was identified as Streptococcus mitis. She also had unusual reactions to vancomycin. Eighteen hours after initiation of 50 mg/kg/day vancomycin, she developed a maculopapular rash, then at 48 hours she developed an intermittent high fever and a progressive decrease in peripheral leukocytes and platelets. She developed hypotension on Day 8. Her serum C-reactive protein and procalcitonin levels were high. All reactions improved after vancomycin was discontinued and oral prednisolone was started. This unusual combination of reactions to vancomycin was likely caused by immune and nonimmune mechanisms. Her endocarditis was successfully treated with cefotaxime 200 mg/kg/ day for 4 weeks.

Evidence-based medicine in clinical curriculum.

INTRODUCTION: The teaching of evidence-based medicine (EBM) has now been incorporated as an integral part of medical curriculum at the Faculty of Medicine, Ramathibodi Hospital but there is little research into the effectiveness of the course. The purpose of this report is to evaluate the EBM skills of medical students and competency of the faculty member. MATERIALS AND METHODS: The EBM course was created by the EBM Working Group at the Faculty of Medicine, Ramathibodi Hospital for 3rd- to 6th-year medical students. The principles of EBM, clinical epidemiology and biostatistics were gradually instilled during the 4 years of medical school. Information technology infrastructure was also provided to facilitate critical appraisal skills. At the end of the Community Medicine clerkship, students anonymously evaluated aspects of the course regarding their EBM skills and faculty member competency with Likert scale questions. RESULTS: Medical students generally gave high evaluations to all aspects of the EBM course taught in the Community Medicine Department. For each of the evaluation questions, the means were higher for faculty member competency. CONCLUSIONS: The teaching of EBM course at the Faculty of Medicine, Ramathibodi Hospital is useful for medical students to enhance their critical thinking skills, and they seem to value the sessions positively.

Four novel and three recurrent mutations of the BTK gene and pathogenic effects of putative splice mutations.

X-linked agammaglobulinemia is caused by mutations in the human BTK gene, leading to recurrent pyogenic infections. We describe four novel and three known BTK-mutations in seven patients from seven (six Thai and one Burmese) families. All but one were sporadic cases. Patients 1 and 2 had recurrent mutations in exon 10 (R288W) and exon 17 (R562W), respectively. Patient 3, a previously healthy individual who presented with pseudomonas sepsis with ecthyma gangrenosum had a known mutation in exon 17 (1749delT), leading to frameshift effect (F583fsX586). Patient 4 manifested with sepsis and concurrent acute appendicitis and pneumonia. He had a mutation, IVS8 + 1G > A, which led to an insertion of intron 8 into the transcripts. In Patient 5, a novel change in exon 7, c.588G > C, initially presumed Q196H, was found to cause a leaky splicing mutation, resulting in three distinct transcripts containing 17, 108, and 190 bp of the 5'-terminal of intron 7, which led to truncated peptides consisting of 203 and 211 amino acid residues (or Q196fsX204 and Q196fsX212, respectively). Patient 6 had a mutation in exon 14 (W421X), while patient 7 had a newly defined large deletion of exons 6-9. All of the mothers tested were mutation carriers. Transcript analysis in three mothers who were heterozygous for frameshift mutations revealed a minimal amount of aberrant transcripts, while their affected children had full expression of the mutant alleles, suggesting rapid degradation due to nonsense-mediated mRNA decay in the mothers. This is the first report of mutations of BTK from Thailand.

A bedside prediction-scoring model for late-onset neonatal sepsis.

OBJECTIVE: Insufficient tools for bedside prediction of late-onset neonatal sepsis (LNS) initiated this study. The objective was to develop and validate a simple prediction-scoring model for LNS defined as culture-proven sepsis occurring 72 hours after birth. METHODS: The study was performed at a university hospital in Bangkok. The derivation phase included medical records of 1870 neonates, randomly selected from 9347 records of neonates who had been hospitalized for >72 hours during 1998 to 2000, of which 1824 records were available. In all, 100 neonates were clinically suspected of sepsis and 17 had proven LNS. The validation phase included 73 neonates suspected of having sepsis during July 2002 to June 2003 and 25 who had LNS. Weighted coefficients from Cox's proportional hazards model and receiver-operating-characteristic (ROC) curve analysis were used. RESULTS: The incidence density of LNS was 17/11355 (1.5/1000) person-days. A scoring model was developed and consisted of the following: hypotension (score 4), abnormal body temperature (score 3), respiratory insufficiency (score 2), neutrophil band form fraction >1% (score 2), platelet count <150 x 10(3)/microl (score 2), and umbilical venous catheterization (1 to 7 or >7 days; score 2 or 4). The area under the ROC curves for prediction of LNS in a neonate suspected of sepsis in each of the two phases was 0.85 and 0.80, respectively (p=0.436). The mean probabilities of LNS were approximately 0.10 (low risk) for scores from 0 to 3; 0.50 (intermediate risk) for scores from 4 to 6; and 0.70 (high risk) for scores > or =7. CONCLUSION: A simple prediction-scoring model for LNS was developed. Validation of the scores suggested good diagnostic performance.

Invasive Chromobacterium violaceum infection in children: case report and review.

A 3.3-year-old boy developed Chromobacterium violaceum abscesses of lungs, liver and spleen and was successfully treated. He had chronic granulomatous disease (CGD). Twenty-five episodes of invasive C. violaceum infection in 24 children were reviewed. All 9 CGD and 10 nonbacteremic cases survived, but 12 of 16 (75%) non-CGD and 12 of 15 (80%) bacteremic patients died.

Vertical dengue infection: case reports and review.

Two vertical dengue infection cases are presented, and 15 others are reviewed. Twelve mothers had fever 0-9 (median, 2) days antepartum. The fevers of 17 neonates occurred at 1-11 (median, 4) days of life and lasted for 1-5 (median, 3) days. Neonatal thrombocytopenia was detected at 1-11 (median, 6) days of life and lasted for 3-18 (median, 6) days; the lowest platelet counts were 5-75 x 10(3) (median, 19 x 10 (3))/mm3. One neonate died.

Hemophagocytic syndrome and Burkholderia cepacia splenic microabscesses in a child with chronic granulomatous disease.

Hemophagocytic syndrome, splenic microabscesses and pulmonary cavitary lesions were presented in a 17-month-old boy with prolonged fever, hepatosplenomegaly and a history of tuberculous lymphadenitis. Clinical course mimicked tuberculosis. Blood cultures were negative. Ultrasound-guided, percutaneous aspiration from splenic microabscesses grew Burkholderia cepacia. He was treated successfully with trimethoprim-sulfamethoxazole. This child with chronic granulomatous disease had an unusual clinical manifestation of B. cepacia infection.

Detection of the impairment of CD80 expression on circulating monocytes in HIV-infected Thai children.

The mechanism of progressive anergic response in HIV-infected children has yet to be adequately described. One possibility is inappropriate delivery of an essential second signal for T-cell activation due to the inappropriate presentation of co-stimulatory molecules. To determine whether the ligand for the secondary signal is impaired in pediatric AIDS, we compared the level of CD80 expression by circulating monocytes in HIV-infected and-noninfected children (15 mild/asymptomatic, 13 symptomatic and 12 HIV seronegative children). By two-color flow cytometry analysis, there was no statistically significant difference in the percentage of monocytes expressing CD80 among the groups (i.e., 63.2 +/- 15.8, 60.9 +/- 12.7, 61.04 +/- 10.9 for uninfected children, mild-asymptomatic children and symptomatic children, respectively). However, both infected groups showed statistically significant lower levels of CD80 expression, with mean fluorescent intensities of 40.9 +/- 15.9 and 38.8 +/- 10.7 compared to 57.05 +/- 16.3 for the uninfected control group. Our data demonstrated a correlation between HIV infection and impairment of CD80 by circulating monocytes. Whether the impairment on CD80 expression contributes to destruction of the immunological network in HIV-infected children requires further investigation.

Antimicrobial resistance in countries with limited resources: unique challenges and limited alternatives.

The haphazard use of antimicrobial agents has caused these essential drugs to lose their effectiveness. In the resource-poor parts of the world, the problem is complex, involving inadequate access to antimicrobial agents in the poorest countries along with an excessive variety of drugs in middle-income countries that have inadequate capability to use them well or to control the unnecessary emergence of resistant microbes. Both circumstances may result in the rapid dissemination of antimicrobial resistance. Resistant organisms, which in wealthy countries would result in the increased expense or inconvenience of alternative agents, in poor countries may cause infections that for practical purposes are untreatable. The basic requirements for controlling drug-resistant problems in resource-poor and wealthy countries alike include first-line prevention of infectious diseases, laboratory support for etiologic diagnosis, adequate surveillance and epidemiological information, appropriate drug selection, locally appropriate guidelines for treatment, and proper education about infectious diseases in all levels. These requirements generally are lacking in resource-poor countries. The most important key to success in these countries is a strong central commitment and governmental support for minimizing drug-resistance problems while maintaining the highest effectiveness of health care within the limits of available resources.

Mother-to-child transmission of cryptococcus neoformans.

Cryptococcal meningitis was diagnosed in a 92-day-old boy who was not HIV-1-infected and who survived after treatment, although with hydrocephalus. The mother was HIV-1-infected, delivered prematurely, had peripartum cryptococcal meningitis and died 14 days postpartum. There was no other possible source for cryptococcal infection in this infant. This is believed to be a case of mother-to-child transmission of cryptococcosis.

Elective cesarean delivery plus short-course lamivudine and zidovudine for the prevention of mother-to-child transmission of human immunodeficiency virus type 1.

OBJECTIVE: The purpose of this study was to evaluate the effect of elective cesarean delivery plus a lamivudine-zidovudine prophylaxis regimen on non-breastfeeding mothers with human immunodeficiency virus type 1 and their infants. STUDY DESIGN: Forty-six antiretroviral-naïve, pregnant women with human immunodeficiency virus type 1 were included. The prophylactic regimen was a lamivudine-zidovudine tablet (150 mg/300 mg) twice daily from week 34 of pregnancy until cesarean delivery at week 38 of gestation, preoperative intravenous zidovudine, and neonatal zidovudine syrup for 4 weeks. RESULTS: At weeks 34 and 38 of gestation, the median maternal viral loads were, respectively, 3.65 log(10) copies/mL (range, 2.34-4.70 log(10) copies/mL) and 2.51 log(10) copies/mL (range, 2.04-3.66 log(10) copies/mL; P<.001), respectively; the viral reduction was 1.12 log(10) copies/mL (range, -0.16-2.60 log(10) copies/mL), and the CD4(+) cell counts increased from 335 cells/mm(3) (range, 57-974 cells/mm(3)) to 420 cells/mm(3) (range, 84-1,083 cells/mm(3); P=.002). No mother or infant had a serious adverse event. Two infants were infected (4.3%; 95% CI, 0.5%-15.7%); 1 infant had intrapartum infection. CONCLUSION: Elective cesarean delivery plus short-course lamivudine-zidovudine is safe but does not eliminate mother-to-child transmission of human immunodeficiency virus type 1.

Pediatric invasive pneumococcal disease in a teaching hospital in Bangkok.

BACKGROUND: Increased problems with drug-resistant Streptococcus pneumoniae (SP) and the dearth of epidemiologic and clinical information on invasive pneumococcal disease in children in Asia formed the basis for this study. METHODS: A periodic retrospective review of the records of 0-15-year-old patients was conducted at a teaching hospital in Bangkok, during 1971-2000. RESULTS: Infections with penicillin-non-susceptible SP (PNSSP) strains rapidly increased after they first appeared in 1988, and they accounted for 71% (29/41) of the total cases during 1996-2000. Of 137 patients, 74% were <60 months old, and 66% had an underlying condition. Infections included: bacteremia without focus 51; pneumonia 38; meningitis 35; peritonitis 13; and bone/joint infection 2. Two patients had two foci of infection. Eight of 10 episodes in patients with AIDS were bacteremic pneumonia. Median ages (range) in months for patients with and without an underlying condition were 24 (1-174) and 10 (0-160); and for the patients without an underlying condition they were: pneumonia 23 (4-156); bacteremia without focus 12 (0-160); and meningitis 7 (2-156). Case-fatality rates were 18% and 2% for patients with and without an underlying condition. The study also examined factors associated with PNSSP infection and death. During 1991-2000, 74% (43/58) of the total cases occurred from November to April, which are dry months. CONCLUSIONS: This study population contained a high proportion with both an underlying condition and infection with PNSSP, and a moderately low proportion with bacteremia without focus. The disease was two to three times more common in dry months than in rainy months.

Utilization of restricted antibiotics in a university hospital in Thailand.

Antibiotic resistance, a major negative consequence of antibiotic overuse, is an important problem worldwide. Various means have been used to control antibiotic usage including the use of an antibiotic order form (AOF), restricted antibiotic formularies and provision of educational information. The present study was designed to evaluate the use of antimicrobials in a 1,000-bed university hospital. Antimicrobial agents, likely to be abused namely ceftazidime, cefepime, cefoperazone/sulbactam, imipenem/cilastatin, meropenem, ciprofloxacin, netilmicin, vancomycin, azithromycin and clarithromycin, were selected for evaluation. A simple AOF with educational information was used as a mean to follow up the treatment. The investigator collected data from the filled AOF and the patient's charts of the Department of Internal Medicine from June to November 2000; all relevant data were assessed. The appropriateness of antibiotic use, assessed according to the criteria specified in the AOF, showed that 74% of these antibiotics were prescribed appropriately; this may prove the effectiveness of the system used in the present study. However, 348 of the 430 prescriptions (80.9%) were prescribed empirically at the initial stage for treatment of nosocomial infections in patients with serious conditions like pneumonia, sepsis and febrile neutropenia. Drugs that were frequently used empirically were ceftazidime (37.9%), imipenem/cilastatin or meropenem (19.3%), and cefoperazone/sulbactam (12.1%) respectively. Ceftazidime and imipenem/cilastatin or meropenem were also frequently used inappropriately among 111 prescriptions that were classified as an inappropriate prescribing. The most common misuses were prescriptions of the drug that did not follow the specified indications (70 prescriptions), no dosage adjustment in patients with renal impairment (39 prescriptions), improper dose (12 prescriptions) and improper dosing interval (9 prescriptions). The results suggested overuse of certain antibiotics remain to be an unsolved problem. Better monitoring and strict controlled use of the problematic antibiotics, ie ceftazidime, imipenem/cilastatin or meropenem and vancomycin are essential to promote rational drug use as well as to reduce the frequency of drug resistance.

Norfloxacin and azithromycin for treatment of nontyphoidal salmonella carriers.

There has been inadequate evaluation of an antibiotic for eradication of nontyphoidal salmonellae (NTS) in asymptomatic carriers. In a randomized, placebo-controlled trial, such efficacy was evaluated using 2 five-day regimens (norfloxacin, 400 mg twice per day, and azithromycin, 500 mg once per day) compared with placebo. The study included 265 food workers in an area of Thailand where NTS are endemic who were asymptomatic NTS carriers. The presence of NTS in stool samples was assessed on days 7, 30, 60, and 90 after start of treatment. At each assessment visit, <4% of participants in each of the 3 groups carried an initial Salmonella serotype; 16%-35% had new Salmonella serotypes detected, except on day 7 in the azithromycin group, when the rate was 4%. Sanitation was good at work but not at home. Selection of multidrug-resistant Salmonella enterica serotype Schwarzengrund was demonstrated. The study regimens were not better than placebo for treatment of asymptomatic food workers who carried NTS in an area where these organisms are endemic, and use of the regimens resulted in antimicrobial resistance.

Neonatal tuberculosis associated with shock, disseminated intravascular coagulation, hemophagocytic syndrome, and hypercalcemia: a case report.

We report on a female infant with disseminated tuberculosis who presented with clinical sepsis and disseminated intravascular coagulation starting at 14 days of age. Parenteral ofloxacin combined with streptomycin were used because the enteral route was not possible and intravenous isoniazid and rifampicin were not available. Rare complications including infection-associated hemophagocytic syndrome, hypercalcemia, and adrenal insufficiency were detected and successfully managed.