Cost-minimization analysis of oral versus intravenous antibiotic treatment for Klebsiella pneumoniae liver abscess.

A cost-minimization analysis was conducted for Klebsiella pneumoniae liver abscess (KLA) patients enrolled in a randomized controlled trial which found oral ciprofloxacin to be non-inferior to intravenous (IV) ceftriaxone in terms of clinical outcomes. Healthcare service utilization and cost data were obtained from medical records and estimated from self-reported patient surveys in a non-inferiority trial of oral ciprofloxacin versus IV ceftriaxone administered to 152 hospitalized adults with KLA in Singapore between November 2013 and October 2017. Total costs were evaluated by category and payer, and compared between oral and IV antibiotic groups over the trial period of 12 weeks. Among the subset of 139 patients for whom cost data were collected, average total cost over 12 weeks was $16,378 (95% CI, $14,620-$18,136) for the oral ciprofloxacin group and $20,569 (95% CI, $18,296-$22,842) for the IV ceftriaxone group, largely driven by lower average outpatient costs, as the average number of outpatient visits was halved for the oral ciprofloxacin group. There were no other statistically significant differences, either in inpatient costs or in other informal healthcare costs. Oral ciprofloxacin is less costly than IV ceftriaxone in the treatment of Klebsiella liver abscess, largely driven by reduced outpatient service costs.Trial registration: ClinicalTrials.gov Identifier NCT01723150 (7/11/2012).

Early oral stepdown antibiotic therapy versus continuing intravenous therapy for uncomplicated Gram-negative bacteraemia (the INVEST trial): study protocol for a multicentre, randomised controlled, open-label, phase III, non-inferiority trial.

BACKGROUND: The incidence of Gram-negative bacteraemia is rising globally and remains a major cause of morbidity and mortality. The majority of patients with Gram-negative bacteraemia initially receive intravenous (IV) antibiotic therapy. However, it remains unclear whether patients can step down to oral antibiotics after appropriate clinical response has been observed without compromising outcomes. Compared with IV therapy, oral therapy eliminates the risk of catheter-associated adverse events, enhances patient quality of life and reduces healthcare costs. As current management of Gram-negative bacteraemia entails a duration of IV therapy with limited evidence to guide oral conversion, we aim to evaluate the clinical efficacy and economic impact of early stepdown to oral antibiotics. METHODS: This is an international, multicentre, randomised controlled, open-label, phase III, non-inferiority trial. To be eligible, adult participants must be clinically stable / non-critically ill inpatients with uncomplicated Gram-negative bacteraemia. Randomisation to the intervention or standard arms will be performed with 1:1 allocation ratio. Participants randomised to the intervention arm (within 72 h from index blood culture collection) will be immediately switched to an oral fluoroquinolone or trimethoprim-sulfamethoxazole. Participants randomised to the standard arm will continue to receive IV therapy for at least 24 h post-randomisation before clinical re-assessment and decision-making by the treating doctor. The recommended treatment duration is 7 days of active antibiotics (including empiric therapy), although treatment regimen may be longer than 7 days if clinically indicated. Primary outcome is 30-day all-cause mortality, and the key secondary outcome is health economic evaluation, including estimation of total healthcare cost as well as assessment of patient quality of life and number of quality-adjusted life years saved. Assuming a 30-day mortality of 8% in the standard and intervention arms, with 6% non-inferiority margin, the target sample size is 720 participants which provides 80% power with a one-sided 0.025 α-level after adjustment for 5% drop-out. DISCUSSION: A finding of non-inferiority in efficacy of oral fluoroquinolones or trimethoprim-sulfamethoxazole versus IV standard of care antibiotics may hypothetically translate to wider adoption of a more cost-effective treatment strategy with better quality of life outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05199324 . Registered 20 January 2022.

Responding to COVID-19: how an academic infectious diseases division mobilized in Singapore.

BACKGROUND: On January 30, COVID-19 was declared a Public Health Emergency of International Concern-a week after Singapore's first imported case and 5 days before local transmission. The National University Hospital (NUH) is Singapore's third largest hospital with 1200 beds, heavy clinical workloads, and major roles in research and teaching. MAIN BODY: With memories of SARS still vivid, there was an urgent requirement for the NUH Division of Infectious Diseases to adapt-undergoing major reorganization to face rapidly changing priorities while ensuring usual essential services and standards. Leveraging on individual strengths, our division mobilized to meet the demands of COVID-19 while engaging in high-level coordination, strategy, and advocacy. We present our experience of the 60 days since the nation's first case. During this time, our hospital has managed 3030 suspect cases, including 1300 inpatients, 37 confirmed cases, and overseen 4384 samples tested for COVID-19. CONCLUSION: Complex hospital adaptations were supported by an unprecedented number of workflows and coordination channels essential to safe and effective operations. The actions we describe, aligned with international recommendations and emerging evidence-based best practices, may serve as a framework for other divisions and institutions facing the spread of COVID-19 globally.

Twelve tips for developing and running a successful women's group in international academic medicine.

Gender inequity in academic medicine remains an important issue worldwide. While institutional programs and policies can help promote equity in recruitment, retention, scholarship, promotion, and leadership, they often do not address the physical and social isolation that many women in international academic medicine face. Creating networking opportunities through building women's groups can provide a personal and professional support structure that decreases isolation and promotes the advancement of women. Based on a multidisciplinary literature review on change processes, group formation, and women's empowerment, as well as lessons learned from personal experience, we offer 12 tips to successfully create, maintain, and support physician women's groups, employing Kotter's change-management framework. We believe that these groups can provide a structured platform for networking opportunities to advance women physicians in academic medicine worldwide.

Twelve tips to promote gender equity in international academic medicine.

Gender inequity in academic medicine remains an important issue worldwide, with more female faculty entering academic medicine internationally. Some academic institutions have initiated programs and created policies to promote gender equity, but disparities remain in faculty numbers, promotions rates, research productivity and access to funding and resources. We offer 12 tips for best practices in the broad domains of faculty recruitment, retention and scholarship, promotion and leadership that institutions and individual faculty can adopt to promote gender equity. While the 12 tips form a comprehensive approach, each tip can be implemented individually depending on institutional needs and culture. Each tip includes practical advice for implementation supported by a successful example from the literature.

Clinician-educators in emerging graduate medical education systems: description, roles and perceptions.

OBJECTIVES: To describe clinician-educators (CEs) in new graduate medical education (GME) systems and characterize perception of preparedness, roles and rewards, and factors affecting job satisfaction and retention. METHODS: A cross-sectional survey of all CEs of institutions using competency-based GME and accredited by the Accreditation Council for Graduate Medical Education-International (ACGME-I). RESULTS: 274 of 359 eligible participants (76.3%) responded, representing 47 residency programs across 17 specialties. CEs were predominantly married men aged in their 40s, employed at their current institution 9.3 years (±6.4 years). CEs judged themselves competent or expert in teaching skills (91.5%), trainee assessment (82%) and mentoring (75%); less so in curriculum development (44%) and educational research skills (32%). Clinical productivity was perceived by the majority (62%) as the item most valued by their institutions, with little or no perceived value for teaching or educational efforts. Overall, 58.3% were satisfied or very satisfied with their roles, and 77% expected to remain in academic medicine for 5 years. A strong negative correlation was found between being a program or associate program director and likelihood of staying in academic medicine (aOR 0.42; 0.22 to 0.80). CONCLUSIONS: In the GME systems studied, CEs, regardless of country or programme, report working in environments that value clinical productivity over educational efforts. CEs feel competent and prepared for many aspects of their roles, have positive attitudes towards teaching, and report overall job satisfaction, with most likely to remain in academic medicine. As medical training advances internationally, the impact on and by CEs requires ongoing attention.

Reducing hypersensitivity reactions with HLA-B*5701 genotyping before abacavir prescription: clinically useful but is it cost-effective in Singapore?

AIM: Abacavir (ABC) is one of the more affordable antiretroviral drugs used for controlling HIV. Although with similar efficacy to current first-line drugs, its limited usage in Singapore can be attributed to its possible side effect of adverse hypersensitivity reactions (HSRs). HLA-B*5701 genotyping is a clinically relevant procedure for avoiding abacavir-induced HSRs. As patients who do not carry the risk allele are unlikely to develop HSRs, a simple rule can be developed to allow abacavir prescription for patients who are B*5701 negative. Here, we carry out a cost-effectiveness analysis of HLA-B*5701 genotyping before abacavir prescription in the context of the Singapore healthcare system, which caters predominantly to Han Chinese, Southeast-asian Malays, and South-asian Indians. In addition, we aim to identify the most cost-effective treatment regimen for HIV patients. METHODS: A decision tree model was developed in TreeAge. The model considers medical treatment and genotyping costs, genotyping test characteristics, the prevalence of the risk allele, reduction in the quality of life, and increased expenditure due to side effects and other factors, evaluating independently over early-stage and late-stage HIV patients segmented by drug contraindications. RESULTS: The study indicates that genotyping is not cost-effective for any ethnicity irrespective of the disease stage, except for Indian patients with early-stage HIV who are contraindicated to tenofovir. CONCLUSION: Abacavir (as first-line) without genotyping is the cheapest and most cost-effective treatment for all ethnicities except for early-stage Indian HIV patients contraindicated to tenofovir. The HLA-B*5701 frequency, the mortality rate from abacavir-induced HSRs, and genotyping costs are among the major factors influencing the cost-effectiveness.

Oral versus intravenous antibiotics for patients with Klebsiella pneumoniae liver abscess: study protocol for a randomized controlled trial.

BACKGROUND: Klebsiella pneumoniae liver abscess is the most common etiology of liver abscess in Singapore and much of Asia, and its incidence is increasing. Current management includes prolonged intravenous antibiotic therapy, but there is limited evidence to guide oral conversion. The implicated K1/K2 capsule strain of Klebsiella pneumoniae is almost universally susceptible to ciprofloxacin, an antibiotic with high oral bioavailability. Our primary aim is to compare the efficacy of early (< one week) step-down to oral antibiotics, to continuing four weeks of intravenous antibiotics, in patients with Klebsiella liver abscess. METHODS/DESIGN: The study is designed as a multi-center randomized open-label active comparator-controlled non-inferiority trial, with a non-inferiority margin of 12%. Eligible participants will be inpatients over the age of 21 with a CT or ultrasound scan suggestive of a liver abscess, and Klebsiella pneumoniae isolated from abscess fluid or blood. Randomization into intervention or active control arms will be performed with a 1:1 allocation ratio. Participants randomized to active control will receive IV ceftriaxone 2 grams daily to complete a total of four weeks of IV antibiotics. Participants randomized to intervention will be immediately converted to oral ciprofloxacin 750 mg twice daily. At Week four, all participants will undergo abdominal imaging and be assessed for clinical response (CRP < 20 mg/l, absence of fever, plus scan showing that the maximal diameter of the abscess has reduced). If criteria are met, antibiotics are stopped; if not, oral antibiotics are continued, with reassessment for clinical response fortnightly. If criteria for clinical response are met by Week 12, the primary endpoint of clinical cure is met. A cost analysis will be performed to assess the cost saving of early conversion to oral antibiotics, and a quality of life analysis will be performed to assess whether treatment with oral antibiotics is less burdensome than prolonged IV antibiotics. DISCUSSION: Our results would help inform local and international practice guidelines regarding the optimal antibiotic management of Klebsiella liver abscess. A finding of non-inferiority may translate to the wider adoption of a more cost-effective strategy that reduces hospital length of stay and improves patient-centered outcomes and satisfaction. TRIAL REGISTRATION: Clinical trials gov NCT01723150.

An outcomes analysis of outpatient parenteral antibiotic therapy (OPAT) in a large Asian cohort.

Outpatient parenteral antibiotic therapy (OPAT) facilitates early discharge, easing demands on inpatient resources and allowing patients the opportunity to restore home life. In Singapore, two large hospitals established a common prospective database in 2006. This study presents an analysis of all enrolled cases over 6 years to consider factors potentially causing adverse outcomes. In this prospective observational study, patients' first OPAT episodes, from initiation to completion, re-admission or early cessation, were recorded and analysed using Cox regression to identify factors associated with clinical deterioration leading to unplanned hospital re-admission. Of 2229 first episodes, 1874 (84.1%) completed treatment in OPAT as planned; 201 episodes (9.0%) were complicated by clinical deterioration and re-admitted. Other patients who failed to complete treatment were either re-admitted for elective procedures, experienced adverse drug reactions or peripherally inserted central catheter-related complications, or had other reasons for not completing treatment. Increased risk of clinical deterioration was associated with homecare OPAT (aHR=2.5, 95% CI 1.7-3.8; P<0.001), age >70 years (aHR=1.6, 95% CI 1.1-2.2; P=0.008) and non-private care (aHR=1.8, 95% CI 1.0-3.0; P=0.033). Diagnosis and type of antibiotic treatment were not significant risk factors for re-admission. OPAT provides intravenous antibiotics to those who would otherwise remain as hospital inpatients. In this large Asian cohort, clinical factors did not relate to the ability of patients to complete their treatment in OPAT. Criteria identified as significant warrant ongoing consideration as patients are assessed for acceptance into OPAT programmes.