Clinical and microbiological evaluation of ventilator-associated pneumonia in an intensive care unit in Vietnam.

Background: The increasing incidence of multidrug-resistant Gram-negative bacteria causing ventilator-associated pneumonia (VAP) is a global concern. A better understanding of the epidemiology of VAP in Southeast Asia is essential to optimise treatments and patient outcomes. Methods: VAP epidemiology in an intensive care unit in Vietnam was investigated. A prospective cohort study was conducted. Patients who were ventilated for >48 hours, diagnosed with VAP, and had a positive respiratory culture between October 2015 and March 2017 were included. Whole-genome sequencing (WGS) was performed on Acinetobacter baumannii isolates. Results: We identified 125 patients (137 episodes) with VAP from 1,699 admissions. Twelve patients had 2 VAP episodes. The median age was 60 years (interquartile range: 48-70), and 68.8% of patients were male. Diabetes mellitus was the most frequent comorbidity (N=35, 28%). Acinetobacter baumannii was most frequently isolated in the first VAP episode (N=84, 67.2%) and was multiply resistant to meropenem, levofloxacin, and amikacin. The 30-day mortality rate was 55.2% (N=69) and higher in patients infected with A. baumannii (N=52, 65%). WGS results suggested a complex spread of multiple clones. Conclusions: In an intensive care unit in Vietnam, VAP due to A. baumannii had a high mortality rate, and A. baumannii and K. pneumoniae were multidrug resistant, with carbapenem resistance of 97% and 70%, respectively.

Evidence of widespread endemic populations of highly multidrug resistant Klebsiella pneumoniae in hospital settings in Hanoi, Vietnam: a prospective cohort study.

BACKGROUND: Patients with prolonged hospitalisation have a significant risk of carriage of and subsequent infection with extended spectrum ß-lactamase (ESBL)-producing and carbapenemase-producing Klebsiella pneumoniae. However, the distinctive roles of the community and hospital environments in the transmission of ESBL-producing or carbapenemase-producing K pneumoniae remain elusive. We aimed to investigate the prevalence and transmission of K pneumoniae within and between the two tertiary hospitals in Hanoi, Viet Nam, using whole-genome sequencing. METHODS: We did a prospective cohort study of 69 patients in intensive care units (ICUs) from two hospitals in Hanoi, Viet Nam. Patients were included if they were aged 18 years or older, admitted for longer than the mean length of stay in their ICU, and cultured K pneumoniae from their clinical samples. Longitudinally collected samples from patients (collected weekly) and the ICU environment (collected monthly) were cultured on selective media, and whole-genome sequences from K pneumoniae colonies analysed. We did phylogenetic analyses and correlated phenotypic antimicrobial susceptibility testing with genotypic features of K pneumoniae isolates. We constructed transmission networks of patient samples, relating ICU admission times and locations with genetic similarity of infecting K pneumoniae. FINDINGS: Between June 1, 2017, and Jan 31, 2018, 69 patients were in the ICUs and eligible for inclusion, and a total of 357 K pneumoniae isolates were cultured and successfully sequenced. 228 (64%) of K pneumoniae isolates carried between two and four different ESBL-encoding and carbapenemase-encoding genes, with 164 (46%) isolates carrying genes encoding both, with high minimum inhibitory concentrations. We found a novel co-occurrence of blaKPC-2 and blaNDM-1 in 46·6% of samples from the globally successful ST15 lineage. Despite being physically and clinically separated, the two hospitals shared closely related strains carrying the same array of antimicrobial resistance genes. INTERPRETATION: These results highlight the high prevalence of ESBL-positive carbapenem-resistant K pneumoniae in ICUs in Viet Nam. Through studying K pneumoniae ST15 in detail, we showed how important resistance genes are contained within these strains that are carried broadly by patients entering the two hospitals directly or through referral. FUNDING: Medical Research Council Newton Fund, Ministry of Science and Technology, Wellcome Trust, Academy of Medical Sciences, Health Foundation, and National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Genomic characterisation of multidrug-resistant Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii in two intensive care units in Hanoi, Viet Nam: a prospective observational cohort study.

BACKGROUND: Viet Nam has high rates of antimicrobial resistance (AMR) but little capacity for genomic surveillance. This study used whole genome sequencing to examine the prevalence and transmission of three key AMR pathogens in two intensive care units (ICUs) in Hanoi, Viet Nam. METHODS: A prospective surveillance study of all adults admitted to ICUs at the National Hospital for Tropical Diseases and Bach Mai Hospital was done between June 19, 2017, and Jan 16, 2018. Clinical and environmental samples were cultured on selective media, characterised with MALDI TOF mass spectrometry, and sequenced with Illumina. Phylogenies based on the de-novo assemblies (SPAdes) were constructed with MAFFT (PARsnp), Gubbins, and RAxML. Resistance genes were detected with Abricate against the US National Center for Biotechnology Information database. FINDINGS: 3153 Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii isolates from 369 patients were analysed. Phylogenetic analysis revealed predominant lineages within A baumannii (global clone 2, sequence types ST2 and ST571) and K pneumoniae (ST15, ST16, ST656, ST11, and ST147) isolates. Isolation from stool was most common with E coli (87·0%) followed by K pneumoniae (62·5%). Of the E coli, 85·0% carried a blaCTX-M variant, while 81·8% of K pneumoniae isolates carried blaNDM (54·4%), or blaKPC (45·1%), or both. Transmission analysis with single nucleotide polymorphisms identified 167 clusters involving 251 (68%) of 369 patients, in some cases involving patients from both ICUs. There were no clear differences between the lineages or AMR genes recovered between the two ICUs. INTERPRETATION: This study represents the largest prospective surveillance study of key AMR pathogens in Vietnamese ICUs. Clusters of closely related isolates in patients across both ICUs suggests recent transmission before ICU admission in other health-care settings or in the community. FUNDING: UK Medical Research Council Newton Fund, Viet Nam Ministry of Science and Technology, Wellcome Trust, Academy of Medical Sciences, Health Foundation, and UK National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Clinical epidemiology and mortality on patients with acute respiratory distress syndrome (ARDS) in Vietnam.

BACKGROUND: The clinical epidemiology and disease prognosis in patients with acute respiratory distress syndrome (ARDS) have not yet been fully elucidated in Vietnam. METHODS: We conducted a retrospective observational study at a national tertiary hospital in Hanoi, Vietnam. Participants were adult patients (age ≥18 years) who were admitted and diagnosed with ARDS during 2015-2017. Data on patients' general and clinical conditions, radiographic findings, ventilator settings, gas exchange, and treatment methods were collected and compared between survivors and non-survivors. Risk factors for mortality were assessed using logistic regression analysis. RESULTS: Among 126 eligible patients with ARDS admitted to the central tertiary hospital in Vietnam, we observed high mortality (57.1%). Of the total patients, 91.3% were transferred from local hospitals with a diagnosis of severe pneumonia and then diagnosed with ARDS at the central hospital. At the time of admission, 53.2% of patients had severe ARDS, 37.3% had moderate ARDS, and 9.5% had mild ARDS. The mean (standard deviation) sequential organ failure assessment (SOFA) score was 9.5 (3.4) in non-survivors and 7.4 (3.4) in survivors (p = 0.002). Although there was no significant difference in PaO2/FiO2 on admission between non-survivors and survivors, that on day 3 after admission was significantly different (p = 0.002). Logistic regression revealed that PaO2/FiO2 on day 3 [odds ratio (OR), 1.010; 95% confidence interval (CI), 1.003-1.017], length of stay in a local hospital before admission to the central hospital (OR, 1.122; 95% CI, 1.042-1.210) due to stable condition, and SOFA score on Day 1 (OR, 0.842; 95% CI, 0.708-1.002) were independent factors in patient survival. CONCLUSIONS: Patients with ARDS admitted the central tertiary hospital had severe illness and high mortality. Most patients were transferred from local hospitals. Improvements in human, medical, and sociological resources in local will contribute to reducing the mortality of ARDS in Vietnam.

Tuberculosis-induced acute respiratory distress syndrome treated with veno-venous extracorporeal membrane oxygenation.

Tuberculosis (TB) is a rare but known cause of acute respiratory distress syndrome (ARDS) with a high mortality. Veno-venous extracorporeal membrane oxygenation (VV-ECMO) may be an alternative option for treating TB-induced ARDS. However, the literature on TB-induced ARDS treated with VV-ECMO is limited and the most of them were prolonged therapy. We report on a-48-year-old man with TB-induced ARDS who was successfully treated by short-term use of VV-ECMO (5 days). He was developed symptoms and hospitalized with severe dyspnea in a local hospital for 3 days before admission to our hospital. At the time when he was transferred to our hospital, his chest computed tomography showed bilateral, diffuse and consolidative shadows all over the lungs, the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) was 50 mmHg, and respiratory system compliance was 12.5 mL/cmH2O. Two days after admission, Mycobacterium tuberculosis was detected by a sputum smear examination and he was diagnosed with TB-induced ARDS. VV-ECMO support was then initiated with administration of anti-TB drugs and systemic corticosteroid treatment. On the 4thday of ECMO support, his PaO2/FiO2 increased to 400 mmHg and lung compliance increased to 45 mL/cmH2O. He was weaned from ECMO on the 5th day of ECMO support and was extubated at the 8th day. He was discharged from hospital on the 47th hospitalized day and continued anti-TB medication at home. VV-ECMO is effective for TB-induced ARDS even in short-term administration if progression of ARDS is rapid.

Professional burnout among physicians and nurses in Asian intensive care units: a multinational survey.

PURPOSE: Professional burnout is a multidimensional syndrome comprising emotional exhaustion, depersonalization, and diminished sense of personal accomplishment, and is associated with poor staff health and decreased quality of medical care. We investigated burnout prevalence and its associated risk factors among Asian intensive care unit (ICU) physicians and nurses. METHODS: We conducted a cross-sectional survey of 159 ICUs in 16 Asian countries and regions. The main outcome measure was burnout as assessed by the Maslach Burnout Inventory-Human Services Survey. Multivariate random effects logistic regression analyses of predictors for physician and nurse burnout were performed. RESULTS: A total of 992 ICU physicians (response rate 76.5%) and 3100 ICU nurses (response rate 63.3%) were studied. Both physicians and nurses had high levels of burnout (50.3% versus 52.0%, P = 0.362). Among countries or regions, burnout rates ranged from 34.6 to 61.5%. Among physicians, religiosity (i.e. having a religious background or belief), years of working in the current department, shift work (versus no shift work) and number of stay-home night calls had a protective effect (negative association) against burnout, while work days per month had a harmful effect (positive association). Among nurses, religiosity and better work-life balance had a protective effect against burnout, while having a bachelor's degree (compared to having a non-degree qualification) had a harmful effect. CONCLUSIONS: A large proportion of Asian ICU physicians and nurses experience professional burnout. Our study results suggest that individual-level interventions could include religious/spiritual practice, and organizational-level interventions could include employing shift-based coverage, stay-home night calls, and regulating the number of work days per month.

Ventilator-associated respiratory infection in a resource-restricted setting: impact and etiology.

BACKGROUND: Ventilator-associated respiratory infection (VARI) is a significant problem in resource-restricted intensive care units (ICUs), but differences in casemix and etiology means VARI in resource-restricted ICUs may be different from that found in resource-rich units. Data from these settings are vital to plan preventative interventions and assess their cost-effectiveness, but few are available. METHODS: We conducted a prospective observational study in four Vietnamese ICUs to assess the incidence and impact of VARI. Patients ≥ 16 years old and expected to be mechanically ventilated > 48 h were enrolled in the study and followed daily for 28 days following ICU admission. RESULTS: Four hundred fifty eligible patients were enrolled over 24 months, and after exclusions, 374 patients' data were analyzed. A total of 92/374 cases of VARI (21.7/1000 ventilator days) were diagnosed; 37 (9.9%) of these met ventilator-associated pneumonia (VAP) criteria (8.7/1000 ventilator days). Patients with any VARI, VAP, or VARI without VAP experienced increased hospital and ICU stay, ICU cost, and antibiotic use (p < 0.01 for all). This was also true for all VARI (p < 0.01 for all) with/without tetanus. There was no increased risk of in-hospital death in patients with VARI compared to those without (VAP HR 1.58, 95% CI 0.75-3.33, p = 0.23; VARI without VAP HR 0.40, 95% CI 0.14-1.17, p = 0.09). In patients with positive endotracheal aspirate cultures, most VARI was caused by Gram-negative organisms; the most frequent were Acinetobacter baumannii (32/73, 43.8%) Klebsiella pneumoniae (26/73, 35.6%), and Pseudomonas aeruginosa (24/73, 32.9%). 40/68 (58.8%) patients with positive cultures for these had carbapenem-resistant isolates. Patients with carbapenem-resistant VARI had significantly greater ICU costs than patients with carbapenem-susceptible isolates (6053 USD (IQR 3806-7824) vs 3131 USD (IQR 2108-7551), p = 0.04) and after correction for adequacy of initial antibiotics and APACHE II score, showed a trend towards increased risk of in-hospital death (HR 2.82, 95% CI 0.75-6.75, p = 0.15). CONCLUSIONS: VARI in a resource-restricted setting has limited impact on mortality, but shows significant association with increased patient costs, length of stay, and antibiotic use, particularly when caused by carbapenem-resistant bacteria. Evidence-based interventions to reduce VARI in these settings are urgently needed.

Withholding and withdrawal of life-sustaining treatments in low-middle-income versus high-income Asian countries and regions.

PURPOSE: To compare the attitudes of physicians towards withholding and withdrawing life-sustaining treatments in intensive care units (ICUs) in low-middle-income Asian countries and regions with those in high-income ones, and to explore differences in the role of families and surrogates, legal risks, and financial considerations between these countries and regions. METHODS: Questionnaire study conducted in May-December 2012 on 847 physicians from 255 ICUs in 10 low-middle-income countries and regions according to the World Bank's classification, and 618 physicians from 211 ICUs in six high-income countries and regions. RESULTS: After we accounted for personal, ICU, and hospital characteristics on multivariable analyses using generalised linear mixed models, physicians from low-middle-income countries and regions were less likely to limit cardiopulmonary resuscitation, mechanical ventilation, vasopressors and inotropes, tracheostomy and haemodialysis than those from high-income countries and regions. They were more likely to involve families in end-of-life care discussions and to perceive legal risks with limitation of life-sustaining treatments and do-not-resuscitate orders. Nonetheless, they were also more likely to accede to families' requests to withdraw life-sustaining treatments in a patient with an otherwise reasonable chance of survival on financial grounds in a case scenario (adjusted odds ratio 5.05, 95 % confidence interval 2.69-9.51, P < 0.001). CONCLUSIONS: Significant differences in ICU physicians' self-reported practice of limiting life-sustaining treatments, the role of families and surrogates, perception of legal risks and financial considerations exist between low-middle-income and high-income Asian countries and regions.

Chronological, geographical, and seasonal trends of human cases of avian influenza A (H5N1) in Vietnam, 2003-2014: a spatial analysis.

BACKGROUND: Human cases of highly pathogenic avian influenza A (H5N1) virus infection continue to occur in Southeast Asia. The objective of this study was to identify when and where human H5N1 cases have occurred in Vietnam and how the situation has changed from the beginning of the H5N1 outbreaks in 2003 through 2014, to assist with implementing methods of targeted disease management. METHODS: We assessed the disease clustering and seasonal variation of human H5N1 cases in Vietnam to evaluate the geographical and monthly timing trends. The clustering of H5N1 cases and associated mortality were examined over three time periods: the outbreak period (2003-2005), the post-outbreak (2006-2009), and the recent period (2010-2014) using the flexibly shaped space-time scan statistic. The most likely cases to co-cluster and the elevated risks for incidence and mortality were assessed via calculation of the relative risk (RR). The H5N1 case seasonal variation was analysed as the cyclic trend in incidence data using Roger's statistical test. RESULTS: Between 2003 and 2005, H5N1 cases (RR: 2.15, p = 0.001) and mortality (RR: 2.49, p = 0.021) were significantly clustered in northern Vietnam. After 2010, H5N1 cases tended to occur on the border with Cambodia in the south, while H5N1 mortality clustered significantly in the Mekong delta area (RR: 6.62, p = 0.002). A significant seasonal variation was observed (p < 0.001), with a higher incidence of morbidity in December through April. CONCLUSIONS: These findings indicate that clinical preparedness for H5N1 in Vietnam needs to be strengthened in southern Vietnam in December-April.

Polymyxin-B-immobilized-fiber column hemoperfusion with oseltamivir treatment for ARDS due to influenza H1N1/09.

Acute respiratory distress syndrome (ARDS) is one of the severe complications of influenza H1N1/09 infection, resulting in high mortality. Effective treatment strategies for ARDS are needed. This report presents two cases of ARDS due to influenza in Vietnam. Both cases were similar in terms of starting symptoms, the rapid progression to ARDS, and the treatment strategy, direct hemoperfusion with a polymyxin-B-immobilized fiber column (PMX-DHP) and oseltamivir. However, the clinical course of disease and the outcomes were different. For case 1, treatment was initiated on day 4 following the onset of hypoxemia due to ARDS. Symptoms improved rapidly after treatment and the patient was discharged on day 12. For case 2, treatment was initiated on day 9 after the onset of symptoms. Despite intensive therapy, the patient died on day 18. In conclusion, treatment with PMX-DHP and oseltamivir is effective on ARDS due to influenza but only if initiated early.

Evaluation of the Etest method for detecting colistin susceptibility of multidrug-resistant Gram-negative isolates in Vietnam.

The minimum inhibitory concentrations (MICs) of colistin for 241 multidrug-resistant (MDR) Gram-negative pathogens were determined by the Etest and by the broth microdilution method (BMD). The two methods showed essential agreements of 76% (77/102) for Acinetobacter baumannii, 90% (36/40) for Pseudomonas aeruginosa and 84% (83/99) for Enterobacteriaceae isolates, with categorical agreements of 100%, 98%, and 100%, respectively. Of the 241 isolates, none showed a very major error and one (0.4%) showed a major error. MICs ranged from 0.125 to 0.5 µg/ml for all A. baumannii and most Enterobacteriaceae isolates, and from 1 to 2 µg/ml for most P. aeruginosa isolates. Of the 40 P. aeruginosa isolates, 27 (68%) showed higher colistin MICs by the Etest than by the BMD. In contrast, 77% (78/102) of the A. baumannii and 57% (56/99) of the Enterobacteriaceae isolates showed lower colistin MICs by the Etest than by the BMD. The Etest is a reliable and easy-to-use method to measure colistin MICs of MDR Gram-negative pathogens in clinical laboratories and can be used following validation by microdilution methods.

The efficacy and nephrotoxicity associated with colistin use in an intensive care unit in Vietnam: Use of colistin in a population of lower body weight.

BACKGROUND: There has been a growing need for colistin as a key drug for the treatment of MDR-GNB infection. Information on colistin use in Asian population is limited. METHODS: A retrospective observational study was conducted to assess the efficacy and nephrotoxicity in critically ill adult patients who received intravenous colistin for MDR-GNB infection in the intensive care unit (ICU) at Bach Mai Hospital in Hanoi, Vietnam. Colistin was administered according to the dosing guideline that was based on pharmacokinetic, pharmacodynamic and toxicodynamic principles, adjusted by body weight and creatinine clearance. RESULTS: Twenty-eight eligible patients were included. The mean patient age was 60±20.4 years. The mean body weight was 53±8.6kg. The mean daily dose of colistin was 4.1±1.6 MIU, and the mean cumulative dose of colistin was 48.2±22.8 MIU. Colistin therapies were classified as clinically effective in 19 (67.9%) cases. Six (21.4%) patients developed nephrotoxicity during the study period according to RIFLE criteria. CONCLUSION: A personalized dosing protocol of colistin was effective, with low nephrotoxicity, among critically ill Vietnamese patients with low body weight. Further studies are warranted for assessing the efficacy and toxicity in a larger cohort.

Withholding and withdrawal of life-sustaining treatments in intensive care units in Asia.

IMPORTANCE: Little data exist on end-of-life care practices in intensive care units (ICUs) in Asia. OBJECTIVE: To describe physicians' attitudes toward withholding and withdrawal of life-sustaining treatments in end-of-life care and to evaluate factors associated with observed attitudes. DESIGN, SETTING, AND PARTICIPANTS: Self-administered structured and scenario-based survey conducted among 1465 physicians (response rate, 59.6%) who manage patients in ICUs (May-December 2012) at 466 ICUs (response rate, 59.4%) in 16 Asian countries and regions. RESULTS: For patients with no real chance of recovering a meaningful life, 1029 respondents (70.2%) reported almost always or often withholding whereas 303 (20.7%) reported almost always or often withdrawing life-sustaining treatments; 1092 respondents (74.5%) deemed withholding and withdrawal ethically different. The majority of respondents reported that vasopressors, hemodialysis, and antibiotics could usually be withheld or withdrawn in end-of-life care, but not enteral feeding, intravenous fluids, and oral suctioning. For severe hypoxic-ischemic encephalopathy after cardiac arrest, 1201 respondents (82.0% [range between countries, 48.4%-100%]) would implement do-not-resuscitate orders, but 788 (53.8% [range, 6.1%-87.2%]) would maintain mechanical ventilation and start antibiotics and vasopressors if indicated. On multivariable analysis, refusal to implement do-not-resuscitate orders was more likely with physicians who did not value families' or surrogates' requests (adjusted odds ratio [AOR], 1.67 [95% CI, 1.16-2.40]; P = .006), who were uncomfortable discussing end-of-life care (AOR, 2.38 [95% CI, 1.62-3.51]; P < .001), who perceived greater legal risk (AOR, 1.92 [95% CI, 1.26-2.94]; P = .002), and in low- to middle-income economies (AOR, 2.73 [95% CI, 1.56-4.76]; P < .001). Nonimplementation was less likely with physicians of Protestant (AOR, 0.36 [95% CI, 0.16-0.80]; P = .01) and Catholic (AOR, 0.22 [95% CI, 0.09-0.58]; P = .002) faiths, and when out-of-pocket health care expenditure increased (AOR, 0.98 per percentage of total health care expenditure [95% CI, 0.97-0.99]; P = .02). CONCLUSIONS AND RELEVANCE: Whereas physicians in ICUs in Asia reported that they often withheld but seldom withdrew life-sustaining treatments at the end of life, attitudes and practice varied widely across countries and regions. Multiple factors related to country or region, including economic, cultural, religious, and legal differences, as well as personal attitudes, were associated with these variations. Initiatives to improve end-of-life care in Asia must begin with a thorough understanding of these factors.

Emergence of 16S rRNA methylase-producing Acinetobacter baumannii and Pseudomonas aeruginosa isolates in hospitals in Vietnam.

BACKGROUND: 16S rRNA methylase-producing Gram-negative bacteria are highly resistant to all clinically important aminoglycosides. We analyzed clinical strains of 16S rRNA methylase-producing Acinetobactor baumannii and Pseudomonas aeruginosa obtained from clinical isolates in medical settings in Vietnam. METHODS: From 2008 to 2011, 101 clinical strains of A. baumannii and 15 of P. aeruginosa were isolated from patients in intensive care units (ICUs) in two medical settings in Vietnam. Antimicrobial susceptibilities were determined using the microdilution method and epidemiological analysis was performed by pulsed-field gel electrophoresis and MLST. Genes encoding the 16S rRNA methylases, OXAs and CTX-Ms were analyzed by PCR and sequence analysis. RESULTS: 16S rRNA methylase-producing Gram-negative pathogens were detected in two hospitals in Vietnam. Of the 101 clinical isolates of A. baumannii and the 15 of P. aeruginosa isolated from two ICUs in these hospitals, 72 (71.3%) were highly resistant to amikacin, arbekacin and gentamicin, with MICs greater than 1,024 mg/L. The 16S rRNA methylases ArmA and RmtB were produced by 61 and 9 isolates of A. baumannii, respectively, and RmtB was produced by 2 isolates of P. aeruginosa. Moreover, 52 of the A. baumannii isolates producing 16S rRNA methylases harbored both blaOXA-23-like and blaOXA-51-like genes. Most A. baumannii isolates producing 16S rRNA methylase obtained in hospital A in Hanoi were ST91 and ST231, whereas most from hospital B in Ho Chi Minh City were ST136, ST195, and ST254. CONCLUSIONS: Gram-negative bacteria producing the 16S rRNA methylases ArmA and RmtB are emerging in medical settings in Vietnam. A. baumannii isolates in northern and southern regions of Vietnam may be of different lineages.

Clinical preparedness for severe pneumonia with highly pathogenic avian influenza A (H5N1): experiences with cases in Vietnam.

BACKGROUND: Avian influenza A (H5N1) in human presents a global pandemic threat, and preparedness is urgently required in high-risk countries. METHODS: A retrospective chart review was conducted on 8 patients with H5N1 infection (aged 2-30 years; 3 fatal) who were hospitalized in Bach Mai Hospital (BMH), Vietnam, or in affiliated hospitals with consultation by physicians in BMH between 2007 and 2010. Demographic background, chest radiographs, and clinical and laboratory data were evaluated to determine the critical issues in relation to clinical outcomes. Treatment of 4 patients with acute respiratory distress syndrome (ARDS) (2 fatal) was assessed for renal replacement therapy using continuous hemodiafiltration (CHDF), polymyxin B-immobilized (PMX) hemoperfusion, or their combination. RESULTS: Patients had direct contact with dead/sick poultry infected with H5N1 virus or lived in areas where H5N1 poultry outbreaks had been reported at the same time as their illness. Time to initiation of oseltamivir from symptom onset was 2-6 days for survivors and 7-9 days for non-survivors. All patients except one had infiltrative shadows on chest radiographs on admission. Patients with delayed treatment developed ARDS. Renal replacement therapy contributed to patient survival, with improvement of oxygenation and a dramatic decrease in serum cytokine levels if initiated earlier. CONCLUSIONS: Understanding local H5N1 poultry outbreaks and chest radiography assist early diagnosis and initiation of antiviral treatment. Developing a network among local and tertiary care hospitals can reduce the time to initiation of treatment. CHDF and PMX hemoperfusion are possible candidates for effective treatment of ARDS with H5N1 if applied earlier.

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 AUC(0-12) 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 IC(50) (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.