Assessing feasibility of establishing antimicrobial stewardship programmes in two provincial-level hospitals in Vietnam: an implementation research study.

OBJECTIVES: To investigate the feasibility of establishing hospital-based antimicrobial stewardship (AMS) programmes comprising action-planning, educational interventions and data feedback in two provincial-level hospitals in Viet Nam. DESIGN AND SETTING: This was an implementation research using participatory action process and existing resources from the Duke Antimicrobial Stewardship Outreach Network with local adjustments. A national stakeholder meeting and Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis were conducted to identify gaps and potential interventions. PARTICIPANTS: Hospital AMS staff implemented activities throughout the study phases. Routinely collected patient data were analysed to support planning, implementation and evaluation. INTERVENTIONS: Hospitals were considered as a complex adaptive system and leveraged their unique characteristics and interconnections to develop 1-year plans containing core interventions (data use, educational training, prospective audit with feedback (PAF) and evaluations). OUTCOME MEASURES: We assessed feasibility using outputs from stakeholder meeting, SWOT analysis, baseline data, planning process and implementation. RESULTS: The stakeholder meeting identified three gaps for AMS at national level: supportive policies, AMS training and core competencies and collaboration. At the hospitals, AMS programmes took 1 year for planning due to lack of hospital-specific procedures and relevant staff competencies. Baseline data (January-December 2019) showed variations in antibiotic consumption: 951 days of therapy (DOT) per 1000 days present in the control and 496 in the intervention wards in hospital 1, and 737 and 714 in hospital 2, respectively. During 1-year implementation, clinical pharmacists audited 1890 antibiotic prescriptions in hospital 1 (June 2020-May 2021) and 1628 in hospital 2 (July 2020-July 2021), and will continue PAF in their daily work. CONCLUSION: Our data confirmed the need to contextualise AMS programmes in low-income and middle-income countries (LMICs) and demonstrated the usefulness of implementation research design in assessing programme feasibility. Developing staff competencies, using local data to stimulate actions and integrating programme activities in routine hospital work are key to success in LMICs.

The emergence of rotavirus G12 and the prevalence of enteric viruses in hospitalized pediatric diarrheal patients in southern Vietnam.

Diarrhea is a major cause of childhood morbidity and mortality in developing countries, and the majority of infections are of viral etiology. We aimed to compare the etiological prevalence of the major enteric viruses in an urban and a rural setting in southern Vietnam. We simultaneously screened fecal specimens from 362 children in Ho Chi Minh City and Dong Thap province that were hospitalized with acute diarrhea over a 1-month-long period for four viral gastrointestinal pathogens. Rotavirus was the most common pathogen identified, but there was a differential prevalence of rotavirus and norovirus between the urban and rural locations. Furthermore, rotavirus genotyping and phylogenetic analysis again differentiated the genotypes by the sampling location. Our data show a disproportional distribution of enteric viral pathogens in urban and rural locations, and we provide evidence of continual importation of new rotavirus strains into southern Vietnam and report the emergence of rotavirus genotype G12.

A multi-center randomized trial to assess the efficacy of gatifloxacin versus ciprofloxacin for the treatment of shigellosis in Vietnamese children.

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.

A changing picture of shigellosis in southern Vietnam: shifting species dominance, antimicrobial susceptibility and clinical presentation.

BACKGROUND: Shigellosis remains considerable public health problem in some developing countries. The nature of Shigellae suggests that they are highly adaptable when placed under selective pressure in a human population. This is demonstrated by variation and fluctuations in serotypes and antimicrobial resistance profile of organisms circulating in differing setting in endemic locations. Antimicrobial resistance in the genus Shigella is a constant threat, with reports of organisms in Asia being resistant to multiple antimicrobials and new generation therapies. METHODS: Here we compare microbiological, clinical and epidemiological data from patients with shigellosis over three different periods in southern Vietnam spanning 14 years. RESULTS: Our data demonstrates a shift in dominant infecting species (S. flexneri to S. sonnei) and resistance profile of the organisms circulating in southern Vietnam. We find that there was no significant variation in the syndromes associated with either S. sonnei or S. flexneri, yet the clinical features of the disease are more severe in later observations. CONCLUSIONS: Our findings show a change in clinical presentation of shigellosis in this setting, as the disease may be now more pronounced, this is concurrent with a change in antimicrobial resistance profile. These data highlight the socio-economic development of southern Vietnam and should guide future vaccine development and deployment strategies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN55945881.

Specimens and culture media for the laboratory diagnosis of typhoid fever.

BACKGROUND: Culture of S. Typhi is necessary for the definitive diagnosis of typhoid fever and provides isolates for antibiotic susceptibility testing and epidemiological studies. However, current methods are not fully optimised and sourcing culture media and bottles for culture media may be problematic. METHODOLOGY: In two hospital laboratories in Viet Nam, comparisons of media for blood and stool culture were conducted. The effect of the volume of blood or stool on culture positivity rate was examined and direct plating of the blood buffy coat was trialed. RESULTS: For 148 suspected typhoid fever cases, ox bile broth (58 positive) and brain-heart infusion broth containing saponin (63 positive), performed equally well. For 69 confirmed adult typhoid fever cases, large-volume (15 ml) blood culture gave the same sensitivity as 1 ml of bone marrow culture. For 44 confirmed typhoid fever cases, the direct plating of the buffy coat was positive in 28 cases. For 263 positive stool cultures, selenite F and selenite mannitol performed equally well and culturing 2 g rather than 1g increased the isolation rate by 10.5%. CONCLUSIONS: For the diagnosis of typhoid fever by blood culture the medium should be a rich nutrient broth containing a lysing agent. In adults 1 ml bone marrow or 15 ml blood culture gave similar results. Where isolates are needed for susceptibility testing or epidemiological studies, but resources for culture are scarce, direct plating of the blood buffy coat can be used with a 50% fall in sensitivity compared to standard blood culture.

Randomized controlled comparison of ofloxacin, azithromycin, and an ofloxacin-azithromycin combination for treatment of multidrug-resistant and nalidixic acid-resistant typhoid fever.

Isolates of Salmonella enterica serovar Typhi that are multidrug resistant (MDR, resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) and have reduced susceptibility to fluoroquinolones (nalidixic acid resistant, Na(r)) are common in Asia. The optimum treatment for infections caused by such isolates is not established. This study compared different antimicrobial regimens for the treatment of MDR/Na(r) typhoid fever. Vietnamese children and adults with uncomplicated typhoid fever were entered into an open randomized controlled trial. Ofloxacin (20 mg/kg of body weight/day for 7 days), azithromycin (10 mg/kg/day for 7 days), and ofloxacin (15 mg/kg/day for 7 days) combined with azithromycin (10 mg/kg/day for the first 3 days) were compared. Of the 241 enrolled patients, 187 were eligible for analysis (186 S. enterica serovar Typhi, 1 Salmonella enterica serovar Paratyphi A). Eighty-seven percent (163/187) of the patients were children; of the S. enterica serovar Typhi isolates, 88% (165/187) were MDR and 93% (173/187) were Na(r). The clinical cure rate was 64% (40/63) with ofloxacin, 76% (47/62) with ofloxacin-azithromycin, and 82% (51/62) with azithromycin (P = 0.053). The mean (95% confidence interval [CI]) fever clearance time for patients treated with azithromycin (5.8 days [5.1 to 6.5 days]) was shorter than that for patients treated with ofloxacin-azithromycin (7.1 days [6.2 to 8.1 days]) and ofloxacin (8.2 days [7.2 to 9.2 days]) (P < 0.001). Positive fecal carriage immediately posttreatment was detected in 19.4% (12/62) of patients treated with ofloxacin, 6.5% (4/62) of those treated with the combination, and 1.6% (1/62) of those treated with azithromycin (P = 0.006). Both antibiotics were well tolerated. Uncomplicated typhoid fever due to isolates of MDR S. enterica serovar Typhi with reduced susceptibility to fluoroquinolones (Na(r)) can be successfully treated with a 7-day course of azithromycin.

Comparative trial of short-course ofloxacin for uncomplicated typhoid fever in Vietnamese children.

An open, randomised comparison of 2 or 3 days of oral ofloxacin (10 mg/kg/day) for uncomplicated typhoid fever was conducted in 235 Vietnamese children. Multi-drug-resistant Salmonella typhi was isolated from 182/202 (90%) children and 5/166 (3%) tested isolates were nalidixic acid-resistant (Na(R)). Eighty-nine of 116 children randomised to 2 days and 107/119 randomised to 3 days were blood culture-positive and eligible for analysis. There were 12 (13.5%) failures in the 2-day group (six clinical failures, four blood culture-positive post treatment, two relapses) compared with eight (7.5%) failures in the 3-day group (four clinical failures, one blood culture-positive post treatment, three relapses) (OR 1.9, 95% CI 0.7-5.5,p = 0.17). There were no significant differences in the mean (95% confidence interval) fever clearance times (h) [92 (82-102) vs 101 (93-110), p = 0.18] or duration of hospitalisation (d) [7.6 (7.2-8.1) vs 8.0 (7.6-8.4), p = 0.19] between the two groups. There was one failure in the four eligible children infected with an Na(R) isolate of S. typhi. No adverse events were attributable to the ofloxacin. These results extend previous observations on the efficacy of short courses of ofloxacin for children with uncomplicated multi-drug-resistant typhoid fever.