Development and validation of multiplex real-time PCR for simultaneous detection of six bacterial pathogens causing lower respiratory tract infections and antimicrobial resistance genes.

Background: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Streptococcus pneumoniae and Staphylococcus aureus are major bacterial causes of lower respiratory tract infections (LRTIs) globally, leading to substantial morbidity and mortality. The rapid increase of antimicrobial resistance (AMR) in these pathogens poses significant challenges for their effective antibiotic therapy. In low-resourced settings, patients with LRTIs are prescribed antibiotics empirically while awaiting several days for culture results.

An open label randomized controlled trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis.

Background: Cryptococcal meningitis has high mortality. Flucytosine is a key treatment but is expensive and rarely available. The anticancer agent tamoxifen has synergistic anti-cryptococcal activity with amphotericin in vitro.

Colonization with and causes infections in a Vietnamese intensive care unit.

Pre-existing colonization with or has been found to increase the risk of infection in intensive care patients. We previously conducted a longitudinal study to characterize colonization of these two organisms in patients admitted to intensive care in a hospital in southern Vietnam. Here, using genomic and phylogenetic analyses, we aimed to assess the contribution these colonizing organisms made to infections.

Antifungal Susceptibility Does Not Correlate With Fungal Clearance or Survival in AIDS-Associated Cryptococcal Meningitis.

We investigated the value of susceptibility testing in predicting response in AIDS-associated cryptococcal meningitis using clinical isolates from a randomized controlled trial of antifungal treatment (amphotericin monotherapy, amphotericin with flucytosine, or amphotericin with fluconazole). We found no correlation between antifungal susceptibility and either early or late survival, or fungal clearance.

Automating the Generation of Antimicrobial Resistance Surveillance Reports: Proof-of-Concept Study Involving Seven Hospitals in Seven Countries.

Background: Reporting cumulative antimicrobial susceptibility testing data on a regular basis is crucial to inform antimicrobial resistance (AMR) action plans at local, national, and global levels. However, analyzing data and generating a report are time consuming and often require trained personnel.

Objective: This study aimed to develop and test an application that can support a local hospital to analyze routinely collected electronic data independently and generate AMR surveillance reports rapidly.

The role of animals as a source of antimicrobial resistant nontyphoidal Salmonella causing invasive and non-invasive human disease in Vietnam.

Background: Nontyphoidal Salmonella (NTS) are associated with both diarrhea and bacteremia. Antimicrobial resistance (AMR) is common in NTS in low-middle income countries, but the major source(s) of AMR NTS in humans are not known. Here, we aimed to assess the role of animals as a source of AMR in human NTS infections in Vietnam.

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia.

Background: Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. South and Southeast Asia are major hubs for antimicrobial-resistant (AMR) K.

One hypervirulent clone, sequence type 283, accounts for a large proportion of invasive Streptococcus agalactiae isolated from humans and diseased tilapia in Southeast Asia.

Background: In 2015, Singapore had the first and only reported foodborne outbreak of invasive disease caused by the group B Streptococcus (GBS; Streptococcus agalactiae). Disease, predominantly septic arthritis and meningitis, was associated with sequence type (ST)283, acquired from eating raw farmed freshwater fish. Although GBS sepsis is well-described in neonates and older adults with co-morbidities, this outbreak affected non-pregnant and younger adults with fewer co-morbidities, suggesting greater virulence.

The combination of tamoxifen with amphotericin B, but not with fluconazole, has synergistic activity against the majority of clinical isolates of Cryptococcus neoformans.

Background: Cryptococcal meningitis has fatality rates of 40%-70%, resulting in 200 000 deaths each year. The best outcomes are achieved with amphotericin combined with flucytosine but flucytosine is expensive and unavailable where most disease occurs. More effective and affordable treatments are needed.

A randomised controlled trial of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDITOF-MS) versus conventional microbiological methods for identifying pathogens: Impact on optimal antimicrobial therapy of invasive bacterial and fungal infections in Vietnam.

Objectives: We assessed the impact of MALDITOF-MS on the timeliness of optimal antimicrobial therapy through a parallel-arm randomised controlled trial in two hospitals in Vietnam.

Methods: We recruited patients with a pathogen (bacterial or fungal) cultured from a normally sterile sample. Samples were randomly assigned (1:1) to identification by MALDITOF-MS or conventional diagnostics.

A randomized open label trial of tamoxifen combined with amphotericin B and fluconazole for cryptococcal meningitis.

: Cryptococcal meningitis is a leading cause of death in HIV-infected patients. International treatment guidelines recommend induction therapy with amphotericin B and flucytosine. This antifungal combination is most effective, but unfortunately flucytosine is expensive and unavailable where the burden of disease is greatest.

Clinical and laboratory-induced colistin-resistance mechanisms in Acinetobacter baumannii.

The increasing incidence and emergence of multi-drug resistant (MDR) Acinetobacter baumannii has become a major global health concern. Colistin is a historic antimicrobial that has become commonly used as a treatment for MDR A. baumannii infections.

New Variant of Multidrug-Resistant Serovar Typhimurium Associated with Invasive Disease in Immunocompromised Patients in Vietnam.

Nontyphoidal (NTS), particularly serovar Typhimurium, is among the leading etiologic agents of bacterial enterocolitis globally and a well-characterized cause of invasive disease (iNTS) in sub-Saharan Africa. In contrast,  Typhimurium is poorly defined in Southeast Asia, a known hot spot for zoonotic disease with a recently described burden of iNTS disease. Here, we aimed to add insight into the epidemiology and potential impact of zoonotic transfer and antimicrobial resistance (AMR) in  Typhimurium associated with iNTS and enterocolitis in Vietnam.

The Control of Typhoid Fever in Vietnam.

Typhoid fever, caused by serovar Typhi (. Typhi), is a diminishing public health problem in Vietnam, and this process may represent a prototype for typhoid elimination in Asia. Here, we review typhoid epidemiology in Vietnam over 20 years and assess the potential drivers associated with typhoid reduction.

Continuous versus intermittent endotracheal cuff pressure control for the prevention of ventilator-associated respiratory infections in Vietnam: study protocol for a randomised controlled trial.

Background: Ventilator-associated respiratory infection (VARI) comprises ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT). Although their diagnostic criteria vary, together these are the most common hospital-acquired infections in intensive care units (ICUs) worldwide, responsible for a large proportion of antibiotic use within ICUs. Evidence-based strategies for the prevention of VARI in resource-limited settings are lacking.

Phenotypic and genotypic characteristics of ESBL and AmpC producing organisms associated with bacteraemia in Ho Chi Minh City, Vietnam.

Background: Broad-spectrum antimicrobials are commonly used as empirical therapy for infections of presumed bacterial origin. Increasing resistance to these antimicrobial agents has prompted the need for alternative therapies and more effective surveillance. Better surveillance leads to more informed and improved delivery of therapeutic interventions, potentially leading to better treatment outcomes.

Development and evaluation of a real-time polymerase chain reaction assay for the rapid detection of Talaromyces marneffei MP1 gene in human plasma.

Penicilliosis caused by Talaromyces marneffei is a common AIDS-defining illness in South and Southeast Asia. Diagnosis is based on culture which can take up to 14 days for identification, leading to treatment delay and increased mortality. We developed a TaqMan real-time PCR assay targeting the MP1 gene encoding an abundant cell wall protein specific to T.

Clinical implications of reduced susceptibility to fluoroquinolones in paediatric Shigella sonnei and Shigella flexneri infections.

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.

Diagnosing Rhodococcus equi infections in a setting where tuberculosis is highly endemic: a double challenge.

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.

Mycobacterium fortuitum skin infections after subcutaneous injections with Vietnamese traditional medicine: a case report.

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.

Variation at HLA-DRB1 is associated with resistance to enteric fever.

Enteric fever affects more than 25 million people annually and results from systemic infection with Salmonella enterica serovar Typhi or Paratyphi pathovars A, B or C(1). We conducted a genome-wide association study of 432 individuals with blood culture-confirmed enteric fever and 2,011 controls from Vietnam. We observed strong association at rs7765379 (odds ratio (OR) for the minor allele = 0.

Two cases of bacteriemia caused by nontoxigenic, non-O1, non-O139 Vibrio cholerae isolates in Ho Chi Minh City, Vietnam.

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.