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Background: An endotracheal tube cuff pressure between 20 and 30 cmH2O is recommended to prevent ventilator-associated respiratory infection (VARI). We aimed to evaluate whether continuous cuff pressure control (CPC) was associated with reduced VARI incidence compared with intermittent CPC., Methods: We conducted a multicenter open-label randomized controlled trial in intensive care unit (ICU) patients within 24 hours of intubation in Vietnam. Patients were randomly assigned 1:1 to receive either continuous CPC using an automated electronic device or intermittent CPC using a manually hand-held manometer. The primary endpoint was the occurrence of VARI, evaluated by an independent reviewer blinded to the CPC allocation., Results: We randomized 600 patients; 597 received the intervention or control and were included in the intention to treat analysis. Compared with intermittent CPC, continuous CPC did not reduce the proportion of patients with at least one episode of VARI (74/296 [25%] vs 69/301 [23%]; odds ratio [OR] 1.13; 95% confidence interval [CI] .77-1.67]. There were no significant differences between continuous and intermittent CPC concerning the proportion of microbiologically confirmed VARI (OR 1.40; 95% CI .94-2.10), the proportion of intubated days without antimicrobials (relative proportion [RP] 0.99; 95% CI .87-1.12), rate of ICU discharge (cause-specific hazard ratio [HR] 0.95; 95% CI .78-1.16), cost of ICU stay (difference in transformed mean [DTM] 0.02; 95% CI -.05 to .08], cost of ICU antimicrobials (DTM 0.02; 95% CI -.25 to .28), cost of hospital stay (DTM 0.02; 95% CI -.04 to .08), and ICU mortality risk (OR 0.96; 95% CI .67-1.38)., Conclusions: Maintaining CPC through an automated electronic device did not reduce VARI incidence., Clinical Trial Registration: NCT02966392., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: The Project Extension for Community Healthcare Outcomes (ECHO) model is considered a platform for academic medical centers to expand their healthcare workforce capacity to medically underserved populations. It has been known as an effective solution of continuing medical education (CME) for healthcare workers that used a hub-and-spoke model to leverage knowledge from specialists to primary healthcare providers in different regions. In this study, we aim to explore the views of healthcare providers and hospital leaders regarding the feasibility, acceptability, and sustainability of Project ECHO for pediatricians., Methods: This qualitative study was conducted at the Vietnam National Children's Hospital and its satellite hospitals from July to December 2020. We conducted 39 in-depth interviews with hospital managers and healthcare providers who participated in online Project ECHO courses. A thematic analysis approach was performed to extract the qualitative data from in-depth interviews., Results: Project ECHO shows high feasibility when healthcare providers find motivated to improve their professional knowledge. Besides, they realized the advantages of saving time and money with online training. Although the courses had been covered fully by the Ministry of Health's fund, the participants said they could pay fees or be supported by the hospital's fund. In particular, the expectation of attaining the CME-credited certificates after completing the course also contributes to the sustainability of the program. Project ECHO's online courses should be improved if the session was better monitored with suitable time arrangements., Conclusions: Project ECHO model is highly feasible, acceptable, and sustainable as it brings great benefits to the healthcare providers, and is appropriate with the policy theme of continuing medical education of the Ministry of Health. We recommend that further studies should be conducted to assess the impact of the ECHO program, especially for patient and community outcomes., (© 2021. The Author(s).)

The ECHO (Extension for Community Health Outcomes) model has been introduced and implemented in several hospitals and health programs in Vietnam since 2015. In 2018, Vietnam National Children's Hospital (VNCH) officially implemented the ECHO model to provide continuing medical education (CME) credits on pediatrics topics for medical staff in its satellite hospitals and health centers in the Northern region of Vietnam. This paper presents preliminary results of the ECHO program at VNCH. Methods included pre- and post-program assessments of pediatricians' clinical knowledge, self-efficacy, and professional satisfaction. The analysis compared the differences between pre/post scores descriptively. Knowledge of participants increased by 22.5% points on average. More than 90% of Project ECHO-Pediatrics participants experienced increased confidence. Overall, there was an improvement in participants' self-efficacy in the post-training compared to the pre-training (range 14.7%-22.6% difference from pre-training). All participants improved on their results in the clinical test immediately after the training and maintained it after 3 months. The study demonstrated the ability Project ECHO to improve healthcare worker knowledge and satisfaction., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Human serum IgG contains multiple glycoforms which exhibit a range of binding properties to effector molecules such as cellular Fc receptors. Emerging knowledge of how the Fc glycans contribute to the antibody structure and effector functions has opened new avenues for the exploitation of defined antibody glycoforms in the treatment of diseases. Here, we review the structure and activity of antibody glycoforms and highlight developments in antibody glycoengineering by both the manipulation of the cellular glycosylation machinery and by chemoenzymatic synthesis. We discuss wide ranging applications of antibody glycoengineering in the treatment of cancer, autoimmunity and inflammation. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Acinetobacter baumannii is a significant cause of opportunistic hospital acquired infection and has been identified as an important emerging infection due to its high levels of antimicrobial resistance. Multidrug resistant A. baumannii has risen rapidly in Vietnam, where colistin is becoming the drug of last resort for many infections. In this study we generated spontaneous colistin resistant progeny (up to >256 μg/μl) from four colistin susceptible Vietnamese isolates and one susceptible reference strain (MIC <1.5 μg/μl). Whole genome sequencing was used to identify single nucleotide mutations that could be attributed to the reduced colistin susceptibility. We identified six lpxACD and three pmrB mutations, the majority of which were novel. In addition, we identified further mutations in six A. baumannii genes (vacJ, pldA, ttg2C, pheS and conserved hypothetical protein) that we hypothesise have a role in reduced colistin susceptibility. This study has identified additional mutations that may be associated with colistin resistance through novel resistance mechanisms. Our work further demonstrates how rapidly A. baumannii can generate resistance to a last resort antimicrobial and highlights the need for improved surveillance to identified A. baumannii with an extensive drug resistance profile.

Objectives: We aimed to quantify the impact of fluoroquinolone resistance on the clinical outcome of paediatric shigellosis patients treated with fluoroquinolones in southern Vietnam. Such information is important to inform therapeutic management for infections caused by this increasingly drug-resistant pathogen, responsible for high morbidity and mortality in young children globally., Methods: Clinical information and bacterial isolates were derived from a randomized controlled trial comparing gatifloxacin with ciprofloxacin for the treatment of paediatric shigellosis. Time-kill experiments were performed to evaluate the impact of MIC on the in vitro growth of Shigella and Cox regression modelling was used to compare clinical outcome between treatments and Shigella species., Results: Shigella flexneri patients treated with gatifloxacin had significantly worse outcomes than those treated with ciprofloxacin. However, the MICs of fluoroquinolones were not significantly associated with poorer outcome. The presence of S83L and A87T mutations in the gyrA gene significantly increased MICs of fluoroquinolones. Finally, elevated MICs and the presence of the qnrS gene allowed Shigella to replicate efficiently in vitro in high concentrations of ciprofloxacin., Conclusions: We found that below the CLSI breakpoint, there was no association between MIC and clinical outcome in paediatric shigellosis infections. However, S. flexneri patients had worse clinical outcomes when treated with gatifloxacin in this study regardless of MIC. Additionally, Shigella harbouring the qnrS gene are able to replicate efficiently in high concentrations of ciprofloxacin and we hypothesize that such strains possess a competitive advantage against fluoroquinolone-susceptible strains due to enhanced shedding and transmission., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Acinetobacter baumannii has become one of the major infection threats in intensive care units (ICUs) globally. Since 2008, A. baumannii has been the leading cause of ventilator-associated pneumonia (VAP) in our ICU at an infectious disease hospital in southern Vietnam. The emergence of this pathogen in our setting is consistent with the persistence of a specific clone exhibiting resistance to carbapenems. Antimicrobial combinations may be a strategy to treat infections caused by these carbapenem-resistant A. baumannii. Therefore, we assessed potential antimicrobial combinations against local carbapenem-resistant A. baumannii by measuring in vitro interactions of colistin with four antimicrobials that are locally certified for treating VAP. We first performed antimicrobial susceptibility testing and multilocus variable number tandem repeat analysis (MLVA) genotyping on 74 A. baumannii isolated from quantitative tracheal aspirates from patients with VAP over an 18-month period. These 74 isolates could be subdivided into 21 main clusters by MLVA and >80 % were resistant to carbapenems. We selected 56 representative isolates for in vitro combination synergy testing. Synergy was observed in four (7 %), seven (13 %), 20 (36 %) and 38 (68 %) isolates with combinations of colistin with ceftazidime, ceftriaxone, imipenem and meropenem, respectively. Notably, more carbapenem-resistant A. baumannii isolates (36/43; 84 %) exhibited synergistic activity with a combination of colistin and meropenem than carbapenem-susceptible A. baumannii isolates (2/13; 15 %) (P = 0.023; Fisher's exact test). Our findings suggest that combinations of colistin and meropenem should be considered when treating carbapenem-resistant A. baumannii infections in Vietnam, and we advocate clinical trials investigating combination therapy for VAP.

Rhodococcus equi infection is increasing in regions with high HIV prevalence worldwide. The microbiological features and clinical mimicry of tuberculosis infection pose diagnostic challenges in high-tuberculosis-incidence settings. We present two HIV-associated cases of R. equi infection from Vietnam and discuss the unique diagnostic challenges in such settings., (Copyright © 2015, Le et al.)

Background: Iatrogenic skin and soft tissue infections by rapidly growing mycobacteria are described with increasing frequency, especially among immunocompromised patients., Case Presentation: Here, we present an immunocompetent patient with extensive Mycobacterium fortuitum skin and soft tissue infections after subcutaneous injections to relieve joint pains by a Vietnamese traditional medicine practitioner. Moreover, we present dilemmas faced in less resourceful settings, influencing patient management., Conclusion: This case illustrates the pathogenic potential of rapid growing mycobacteria in medical or non-medical skin penetrating procedures, their world-wide distribution and demonstrates the dilemmas faced in settings with fewer resources.

The toxigenic bacterium Vibrio cholerae belonging to the O1 and O139 serogroups is commonly associated with epidemic diarrhea in tropical settings; other diseases caused by this environmental pathogen are seldom identified. Here we report two unassociated cases of nonfatal, nontoxigenic V. cholerae non-O1, non-O139 bacteremia in patients with comorbidities in Ho Chi Minh City, Vietnam, that occurred within a 4-week period., (Copyright © 2014 Lan et al.)

Background: Chromobacterium violaceum is a proteobacterium found in soil and water in tropical regions. The organism rarely causes infection in humans, yet can cause a severe systemic infection by entering the bloodstream via an open wound., Case Presentation: We recently identified a case of severe bacteremia caused by Chromobacterium violaceum at the Hospital for Tropical Diseases (HTD) in Ho Chi Minh City, Vietnam. Here, we describe how rapid microbiological identification and a combination of antimicrobials was used to successfully treat this life threatening infection in a four-year-old child., Conclusions: This case shows the need for rapid diagnosis when there is the suspicion of a puncture wound contaminated with water and soil in tropical regions. We suggest that the aggressive antimicrobial combination used here is considered when this infection is suspected.

Point-of-care (POC) diagnostic tests for influenza can considerably shorten the time to clinical decision making. An investigational POC test based on a multiplexed immunoassay was developed by Meso Scale Diagnostics, LLC (MSD), with the objective to make a more sensitive rapid test that can also subtype influenza A viruses (1977 H1, H3, and H5). Between February and November 2010, we conducted a prospective multicenter study at four hospitals in Vietnam and compared the performance of this test to that of the WHO/CDC real-time reverse transcriptase PCR (RT-PCR) on nasal and throat swab specimens from patients presenting with influenza-like illness. Five hundred sixty-three adults and children with a median age of 25 months were enrolled. Sensitivity and specificity of the test with combined results from nasal and throat swab samples were 74.0% (131/177) and 99.7% (351/352), respectively, compared to RT-PCR. The POC test was as sensitive for influenza virus B as for influenza virus A (74.4% [64/86] versus 73.6% [67/91]). The positivity rate was associated with lower cycle threshold values (a marker for higher viral loads), sample type (73.6% for nasal swab versus 52.4% for throat swab), and younger age. A total of 210 (18.7%) out of 1,126 MSD tests failed, and for 34 (6%) of patients, both test samples failed (these were excluded from the performance analysis). Subtyping could be assessed only for influenza virus A/H3N2, as 1977 H1N1 was not circulating at the time and no H5N1-infected patients were enrolled, and was successful only in 9/54 patients infected with H3 influenza virus who had a positive POC test result for influenza virus A. This novel POC test provided highly sensitive detection of influenza viruses A and B compared to the reported sensitivities of other rapid tests. However, 18.7% of tests failed for technical reasons and subtyping for H3 was poor. Drawbacks to the technology include the requirement for a dedicated reader instrument and the need for continual updating of subtyping antibodies within the test array.

The etiological spectrum of bloodstream infections is variable between industrialized and developing countries and even within a defined location over time. We investigated trends in bloodstream infections at an infectious disease hospital in Ho Chi Minh City, Vietnam, from 1994-2008. Amongst 66,111 blood cultures performed, a clinically relevant pathogen was isolated in 7645 episodes (positivity rate; 116/1000 cultures). Salmonella Typhi was the predominant pathogen until 2002; however, a considerable annual decline in the proportion of S. Typhi was observed (OR 0.6993, 95% CI [0.6885, 0.7103], p<0.0001). Conversely, there was a significant increase in the proportions of non-typhoidal Salmonella (NTS), Cryptococcus neoformans and Penicillium marneffei, concurrent with increasing HIV prevalence. These data document a substantial longitudinal shift in bloodstream infection etiology in southern Vietnam. We propose such changes are related to increasing economic prosperity and HIV prevalence, and this pattern marks a substantial change in the epidemiology of invasive salmonellosis in Southeast Asia., (Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.)

Background: The bacterial genus Shigella is the leading cause of dysentery. There have been significant increases in the proportion of Shigella isolated that demonstrate resistance to nalidixic acid. While nalidixic acid is no longer considered as a therapeutic agent for shigellosis, the fluoroquinolone ciprofloxacin is the current recommendation of the World Health Organization. Resistance to nalidixic acid is a marker of reduced susceptibility to older generation fluoroquinolones, such as ciprofloxacin. We aimed to assess the efficacy of gatifloxacin versus ciprofloxacin in the treatment of uncomplicated shigellosis in children., Methodology/principal Findings: We conducted a randomized, open-label, controlled trial with two parallel arms at two hospitals in southern Vietnam. The study was designed as a superiority trial and children with dysentery meeting the inclusion criteria were invited to participate. Participants received either gatifloxacin (10 mg/kg/day) in a single daily dose for 3 days or ciprofloxacin (30 mg/kg/day) in two divided doses for 3 days. The primary outcome measure was treatment failure; secondary outcome measures were time to the cessation of individual symptoms. Four hundred and ninety four patients were randomized to receive either gatifloxacin (n=249) or ciprofloxacin (n=245), of which 107 had a positive Shigella stool culture. We could not demonstrate superiority of gatifloxacin and observed similar clinical failure rate in both groups (gatifloxacin; 12.0% and ciprofloxacin; 11.0%, p=0.72). The median (inter-quartile range) time from illness onset to cessation of all symptoms was 95 (66-126) hours for gatifloxacin recipients and 93 (68-120) hours for the ciprofloxacin recipients (Hazard Ratio [95%CI]=0.98 [0.82-1.17], p=0.83)., Conclusions: We conclude that in Vietnam, where nalidixic acid resistant Shigellae are highly prevalent, ciprofloxacin and gatifloxacin are similarly effective for the treatment of acute shigellosis.

Background: Penicillium marneffei is an important human immunodeficiency virus (HIV)-associated opportunistic pathogen in Southeast Asia. The epidemiology and the predictors of penicilliosis outcome are poorly understood., Methods: We performed a retrospective study of culture-confirmed incident penicilliosis admissions during 1996-2009 at the Hospital for Tropical Diseases in Ho Chi Minh City, Viet Nam. Seasonality of penicilliosis was assessed using cosinor models. Logistic regression was used to assess predictors of death or worsening disease based on 10 predefined covariates, and Cox regression was performed to model time-to-antifungal initiation., Results: A total of 795 patients were identified; hospital charts were obtainable for 513 patients (65%). Cases increased exponentially and peaked in 2007 (156 cases), mirroring the trends in AIDS admissions during the study period. A highly significant seasonality for penicilliosis (P<.001) but not for cryptococcosis (P=.63) or AIDS admissions (P=.83) was observed, with a 27% (95% confidence interval, 14%-41%) increase in incidence during rainy months. All patients were HIV infected; the median CD4 cell count (62 patients) was 7 cells/μL (interquartile range, 4-24 cells/μL). Hospital outcome was an improvement in 347 (68%), death in 101 (20%), worsening in 42 (8%), and nonassessable in 23 (5%) cases. Injection drug use, shorter history, absence of fever or skin lesions, elevated respiratory rates, higher lymphocyte count, and lower platelet count independently predicted poor outcome in both complete-case and multiple-imputation analyses. Time-to-treatment initiation was shorter for patients with skin lesions (hazard ratio, 3.78; 95% confidence interval, 2.96-4.84; P<.001)., Conclusions: Penicilliosis incidence correlates with the HIV/AIDS epidemic in Viet nam. The number of cases increases during rainy months. Injection drug use, shorter history, absence of fever or skin lesions, respiratory difficulty, higher lymphocyte count, and lower platelet count predict poor in-hospital outcome., (© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.)

Cytochrome P450 (CYP) enzymes are important in the metabolism of some endogenous compounds, environmental and dietary xenobiotics and many drugs. Many of these enzymes have genetic polymorphisms that produce significant changes in metabolic activity, however the function of other polymorphisms is unknown. Genetic polymorphisms have important influences on variability in human pharmacokinetics, including intra-individual differences in drug toxicity, drug interactions and response to chemotherapy. Other factors that influence drug metabolism include differences in enzyme expression due to differences in age, gender, smoking status, exposure to dietary or environmental xenobiotics or co-administration of other drugs. In addition, some xenobiotics and drugs can directly inhibit or induce the activity of CYPs. All of these factors can produce differences in metabolic capacities among individuals which can produce toxicity in some patients and sub-effective dosing in others. Maximum clinical benefit will require a more complete understanding of the influence of these polymorphisms on allele function and their interaction with inducers and inhibitors of enzyme expression or activity. This effort will permit the pharmacogenetic screening of patients before the administration of drugs and result in the identification of individuals who are prone to adverse reactions or poor response, resulting in more effective individualized therapy.