Nguyen Vu Trung

Oseltamivir Is Adequately Absorbed Following Nasogastric Administration to Adult Patients with Severe H5N1 Influenza

In the absence of a parenteral drug, oral oseltamivir is currently recommended by the WHO for treating H5N1 influenza. Whether oseltamivir absorption is adequate in severe influenza is unknown. We measured the steady state, plasma concentrations of nasogastrically administered oseltamivir 150 mg bid and its active metabolite, oseltamivir carboxylate (OC), in three, mechanically ventilated patients with severe H5N1 (male, 30 yrs; pregnant female, 22 yrs) and severe H3N2 (female, 76 yrs). Treatments were started 6, 7 and 8 days after illness onset, respectively. Both females were sampled while on continuous venovenous haemofiltration. Admission and follow up specimens (trachea, nose, throat, rectum, blood) were tested for RNA viral load by reverse transcriptase PCR. In vitro virus susceptibility to OC was measured by a neuraminidase inhibition assay. Admission creatinine clearances were 66 (male, H5N1), 82 (female, H5N1) and 6 (H3N2) ml/min. Corresponding AUC0–12 values (5932, 10,951 and 34,670 ng.h/ml) and trough OC concentrations (376, 575 and 2730 ng/ml) were higher than previously reported in healthy volunteers; the latter exceeded 545 to 3956 fold the H5N1 IC50 (0.69 ng/ml) isolated from the H5N1 infected female. Two patients with follow-up respiratory specimens cleared their viruses after 5 (H5N1 male) and 5 (H3N2 female) days of oseltamivir. Both female patients died of respiratory failure; the male survived. 150 mg bid of oseltamivir was well absorbed and converted extensively to OC. Virus was cleared in two patients but two patients died, suggesting viral efficacy but poor clinical efficacy.

Severe Pandemic H1N1 2009 Infection Is Associated with Transient NK and T Deficiency and Aberrant CD8 Responses

Background It is unclear why the severity of influenza varies in healthy adults or why the burden of severe influenza shifts to young adults when pandemic strains emerge. One possibility is that cross-protective T cell responses wane in this age group in the absence of recent infection. We therefore compared the acute cellular immune response in previously healthy adults with severe versus mild pandemic H1N1 infection. Methods and Principal Findings 49 previously healthy adults admitted to the National Hospital of Tropical Diseases, Viet Nam with RT-PCR-confirmed 2009 H1N1 infection were prospectively enrolled. 39 recovered quickly whereas 10 developed severe symptoms requiring supplemental oxygen and prolonged hospitalization. Peripheral blood lymphocyte subset counts and activation (HLADR, CD38) and differentiation (CD27, CD28) marker expression were determined on days 0, 2, 5, 10, 14 and 28 by flow cytometry. NK, CD4 and CD8 lymphopenia developed in 100%, 90% and 60% of severe cases versus 13% (p<0.001), 28%, (p = 0.001) and 18% (p = 0.014) of mild cases. CD4 and NK counts normalized following recovery. B cell counts were not significantly associated with severity. CD8 activation peaked 6–8 days after mild influenza onset, when 13% (6–22%) were HLADR+CD38+, and was accompanied by a significant loss of resting/CD27+CD28+ cells without accumulation of CD27+CD28− or CD27−CD28− cells. In severe influenza CD8 activation peaked more than 9 days post-onset, and/or was excessive (30–90% HLADR+CD38+) in association with accumulation of CD27+CD28− cells and maintenance of CD8 counts. Conclusion Severe influenza is associated with transient T and NK cell deficiency. CD8 phenotype changes during mild influenza are consistent with a rapidly resolving memory response whereas in severe influenza activation is either delayed or excessive, and partially differentiated cells accumulate within blood indicating that recruitment of effector cells to the lung could be impaired.

Profile of HIV Type 1 Infection and Genotypic Resistance Mutations to Antiretroviral Drugs in Treatment-Naive HIV Type 1-Infected Individuals in Hai Phong, Viet Nam

We evaluated the prevalence and profile of antiretroviral treatment (ART)-associated resistance mutations among HIV-1 strains in northern Vietnam by genotypically analyzing strains isolated from ART-naive individuals in Hai Phong, a city in which HIV-1 is highly prevalent. Plasma samples were collected from injecting drug users (IDU, n = 760), female sex workers (FSW, n = 91), seafarers (n = 94), pregnant women (n = 200), and blood donors (n = 210), and screened for HIV-1 antibodies. Plasma viral RNA was extracted from HIV-1-positive samples, amplified by reverse transcriptase (RT)-PCR of protease and RT genes, and analyzed for genotypes and ART-associated resistance mutations. HIV-1 prevalence among IDU, FSW, seafarers, pregnant women, and blood donors was 35.9%, 23.1%, 0%, 0.5%, and 2.9%, respectively. Phylogenetic analyses revealed that the most prevalent HIV-1 subtype was CRF01_AE (98.3%), similar to strains prevalent in southern China. Four (1.4%) subtype B strains and one (0.3%) unique recombinant between subtypes B and C were also identified. We found protease inhibitor-associated major resistance mutations in one of the 294 cases analyzed (0.3%; mutation M46I). We found RT inhibitor-associated major resistance mutations in 7/273 cases (2.6%; one occurrence each of L74I, M184I, and K219E; three cases of K103N; and two cases of G190E). One CRF01_AE strain harboring a protease codon 35 insertion was first identified in Vietnam. Thus, monitoring of drug-resistant HIV-1 and establishment of a database are required for the proper selection of ART in Vietnam.

Multi-drug resistant Vibrio cholerae O1 variant El Tor isolated in northern Vietnam between 2007 and 2010.

Since 2007, there has been a re-emergence of cholera outbreaks in northern Vietnam. To understand the molecular epidemiological relatedness and determine the antibiotic susceptibility profiles of responsible V. cholerae O1 outbreak strains, a representative collection of 100 V. cholerae O1 strains was characterized. V. cholerae O1 strains isolated from diarrhoeal patients in northern Vietnam between 2007 and 2010 were investigated for antibiotic susceptibility and characterized by using phenotypic and genotypic tests, including PFGE analysis. Ten clinical V. cholerae O1 isolates from Bangladesh and Zimbabwe were included for comparison. The results revealed that all isolates were resistant to co-trimoxazole and nalidixic acid, 29 % were resistant to tetracycline and 1 % were resistant to azithromycin. All strains were susceptible to ampicillin–sulbactam, doxycycline, chloramphenicol and ciprofloxacin and 95 % were susceptible to azithromycin. MIC values did show reduced susceptibility to fluoroquinolones and 63 % of the strains were intermediately resistant to tetracycline. The isolates expressed phenotypic traits of both serogroup O1 Ogawa and El Tor and harboured an rstR El Tor and ctxB classical biotype. Among the outbreak isolates, only a single PFGE pattern was observed throughout the study period. This study shows that multi-drug resistant V. cholerae altered El Tor producing classical CT strains are now predominant in northern Vietnam.

High prevalence of antibiotic resistance in commensal Escherichia coli among children in rural Vietnam

BackgroundCommensal bacteria represent an important reservoir of antibiotic resistance genes. Few community-based studies of antibiotic resistance in commensal bacteria have been conducted in Southeast Asia. We investigated the prevalence of resistance in commensal Escherichia coli in preschool children in rural Vietnam, and factors associated with carriage of resistant bacteria.MethodsWe tested isolates of E. coli from faecal samples of 818 children aged 6-60 months living in FilaBavi, a demographic surveillance site near Hanoi. Daily antibiotic use data was collected for participating children for three weeks prior to sampling and analysed with socioeconomic and demographic characteristics extracted from FilaBavis re-census survey 2007. Descriptive statistics were generated, and a logistic regression model was used to identify contributions of the examined factors.ResultsHigh prevalences of resistance were found to tetracycline (74%), co-trimoxazole (68%), ampicillin (65%), chloramphenicol (40%), and nalidixic acid (27%). Two isolates were resistant to ciprofloxacin. Sixty percent of isolates were resistant to three or more antibiotics. Recent sulphonamide use was associated with co-trimoxazole resistance [OR 3.2, 95% CI 1.8-5.7], and beta-lactam use with ampicillin resistance [OR 1.8, 95% CI 1.3-2.4]. Isolates from children aged 6-23 months were more likely to be resistant to ampicillin [OR 1.8, 95% CI 1.3-2.4] and co-trimoxazole [OR 1.5, 95% CI 1.1-2.0]. Associations were identified between geographical areas and tetracycline and ampicillin resistance.ConclusionsWe present high prevalence of carriage of commensal E. coli resistant to commonly used antibiotics. The identified associations with recent antibiotic use, age, and geographical location might contribute to our understanding of carriage of antibiotic resistant commensal bacteria.

Decreased Streptococcus pneumoniae susceptibility to oral antibiotics among children in rural Vietnam: a community study.

BackgroundStreptococcus pneumoniae is the most significant bacterial cause of community-acquired pneumonia among children under five years worldwide. Updated resistance information of S. pneumoniae among children is essential to adjust the recommendations for empirical treatment of community-acquired pneumonia, which will have immense implications for local and global health. This study investigated the prevalence of antibiotic resistance in isolated strains of S. pneumoniae and relationship with antibiotic use and demographic factors of children under five in rural Vietnam in 2007.MethodsIn Bavi district, 847 children 6 to 60 months were selected from 847 households. The main child-caregivers in the households were interviewed weekly using structured questionnaires to collect information of daily illness symptoms and drug use for the selected child over a four-week period (from March through June 2007). In the 3rd week, the children were invited for a clinical examination and to collect nasopharyngeal samples for S. pneumoniae identification. Etest and disk diffusion were used to test antibiotic susceptibility.ResultsOf 818 participating children, 258 (32%) had ongoing respiratory infections, 421 (52%) carried S. pneumoniae, and 477 (58%) had used antibiotics within the previous three weeks. Of the 421 isolates, 95% were resistant to at least one antibiotic (401/421). Resistance to co-trimoxazole, tetracycline, phenoxymethylpenicillin, erythromycin and ciprofloxacin was 78%, 75%, 75%, 70% and 28%, respectively. Low resistance was noted for amoxicillin (4%), benzylpenicillin (4%), and cefotaxime (2%). The intermediate resistance to amoxicillin was 32%. Multidrug-resistance was seen in 60%. The most common pattern was co-resistance to co-trimoxazole, tetracycline and erythromycin. The proportion of children carrying resistant bacteria was higher among the children who had used antibiotics in the previous three weeks.ConclusionsResistance to commonly used antibiotics and multidrug-resistance of S. pneumoniae in the area is remarkably high. High-dose amoxicillin is the only investigated oral antibiotic that can possibly be used for treatment of community-acquired pneumococcal infections. Strategies to promote appropriate prescribing and dispensing of effective antibiotics should be immediately implemented for the benefit of local and global health.

Antibiotics and paediatric acute respiratory infections in rural Vietnam: health-care providers’ knowledge, practical competence and reported practice

Objective  To assess knowledge, practical competence and reported practices among health‐care providers about antibiotics to treat acute respiratory infections in children under five in rural Vietnam.

Multiple routes of hepatitis C virus transmission among injection drug users in Hai Phong, Northern Vietnam.

To identify hepatitis C virus (HCV) transmission routes among injection drug users in Northern Vietnam, plasma samples were collected from 486 drug users in Hai Phong. Plasma viral RNA was extracted from 323 (66.5%) samples that were positive for anti‐HCV antibodies. Portions of the HCV 5′‐untranslated (5′UTR)‐Core and NS5B genes were amplified by reverse‐transcriptase polymerase chain reaction, sequenced directly, and genotyped in 194 and 195 specimens, respectively. Both regions were genotyped in 137 specimens. In the 5′UTR‐Core region, genotype 6a was predominant (32.5%), followed by genotype 1a (23.7%), genotype 1b (20.6%), and genotype 6e (14.4%). In the NS5B region, genotype 1a was predominant (42.6%), followed by genotype 1b (24.1%), genotype 6a (14.4%), genotype 3b (7.2%), and genotype 6e (5.1%). Of the 137 specimens with both regions genotyped, 23 (16.8%) showed discordant genotyping results between the two regions, suggesting possible recombination and/or dual infection. Phylogenetic analysis revealed close associations between Hai Phong strains and strains from Southern China: the Yunnan province for genotype 3b; the Guangxi province for genotype 6e; the USA for genotype 1a; and Southern Vietnam for genotypes 1a and 6e. The human immunodeficiency virus (HIV) infection rate among HCV‐infected injection drug users was 52.6–55.4% and did not differ significantly by HCV genotype. Most drug users infected with HIV‐1 [98.8% (171/173)] were co‐infected with HCV. These results suggest multiple routes of HCV transmission among injection drug users in Northern Vietnam that may also be HIV transmission routes. J. Med. Virol. 82:1355–1363, 2010.

Enterococcus faecalis Clones in Poultry and in Humans with Urinary Tract Infections, Vietnam

Transmission routes and reservoirs need to be elucidated.

Enterococcus and Streptococcus spp. associated with chronic and self-medicated urinary tract infections in Vietnam.

BackgroundUrinary tract infections (UTI) are one of the most common infections among women worldwide. E. coli often causes more than 75% of acute uncomplicated UTI, however, little is known about how recurrent UTIs and indiscriminate use of antimicrobials affect the aetiology of UTIs. This study aimed to establish the aetiology of UTI in a population of recurrent and self-medicated patients referred from pharmacies to a hospital in Hanoi, Vietnam and to describe genotypes and antimicrobial susceptibility of the associated bacterial pathogens. The aetiology of bacterial pathogens associated with UTI (defined as ≥ 104 CFU/ml urine) was established by phenotypic and molecular methods. Enterococcus faecalis isolates were typed by Multi Locus Sequence Typing (MLST), Pulsed-Field Gel Electrophoresis (PFGE) and antimicrobial susceptibility testing.MethodsUrine samples from 276 patients suffering symptoms of urinary tract infection were collected and cultured on Flexicult agar® allowing for detection of the most common urine pathogens. Patients were interviewed about underlying diseases, duration of symptoms, earlier episodes of UTI, number of episodes diagnosed by doctors and treatment in relation to UTI. All tentative E. faecalis and E. faecium isolates were identified to species level by PCR, 16S rRNA and partial sequencing of the groEL gene. E. faecalis isolates were further characterized by Multi Locus Sequence Typing and antimicrobial susceptibility testing.ResultsMean age of 49 patients was 48 yrs (range was 11–86 yrs) and included 94% women. On average, patients reported to have suffered from UTI for 348 days (range 3 days-10 years, and experienced 2.7 UTIs during the previous year). Cephalosporins were reported the second drug of choice in treatment of UTI at the hospital. E. faecalis (55.1%), E. coli (12.2%) and Streptococcus gallolyticus subsp. pasteurianus (8.2%) were main bacterial pathogens. MIC testing of E. faecalis showed susceptibility to ampicillin, penicillin and vancomycin, but high-level resistance against gentamicin (48.1%). MLST revealed 12 Sequence Types (ST) of which ST 16 made up 44.5% and showed closely related PFGE types.ConclusionThe different aetiology of UTI compared with reports elsewhere, where E. coli dominates, may be a result of chronic and recurrent UTIs together with indiscriminate use of antimicrobials. The similar genotypes shown by epidemiologically unrelated ST 16 isolates in Vietnam and elsewhere, suggest that E. faecalis ST 16 might represent a globally distributed clone. Treatment of UTI with cephalosporins may select for E. faecalis as it is intrinsic resistant and further studies are needed to establish the source(s) and role of E. faecalis ST 16 in acute UTI.