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$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)

Rosuvastatin adjunctive therapy for rifampicin-susceptible pulmonary tuberculosis: a phase 2b, randomised, open-label, multicentre trial

Background: Shorter treatments are needed for drug-susceptible tuberculosis. Adjunctive statins increase bactericidal activity in preclinical tuberculosis models. We investigated the safety and efficacy of adjunctive rosuvastatin in people with tuberculosis. We tested the hypothesis that adjunctive rosuvastatin accelerates sputum culture conversion within the first 8 weeks of treatment of rifampicin-susceptible tuberculosis. Methods: This phase 2b, randomised, open-label, multicentre trial conducted in five hospitals or clinics in three countries with high tuberculosis burden (ie, the Philippines, Viet Nam, and Uganda) enrolled adult participants aged 18–75 years with sputum smear or Xpert MTB/RIF positive, rifampicin-susceptible tuberculosis who had received less than 7 days of previous tuberculosis treatment. Participants were randomly assigned via a web-based system to receive either 10 mg rosuvastatin once per day for 8 weeks plus standard tuberculosis therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol; rosuvastatin group) or standard tuberculosis therapy alone (control group). Randomisation was stratified by trial site, history of diabetes, and HIV co-infection. Laboratory staff and central investigators involved in data cleaning and analysis were masked to treatment allocation, but study participants and site investigators were not. Both groups continued standard treatment to week 24. Sputum samples were collected once per week for the first 8 weeks after randomisation, and then at weeks 10, 12, and 24. The primary efficacy outcome was time to culture conversion (TTCC; days) in liquid culture by week 8, assessed in randomised participants who had microbiological confirmation of tuberculosis, took at least one dose of rosuvastatin, and who did not show resistance to rifampicin (modified intention-to-treat population), for which groups were compared with the Cox proportional hazards model. The main safety outcome was grade 3–5 adverse events by week 24, assessed in the intention-to-treat population, for which groups were compared with Fisher\u27s exact test. All participants completed 24 weeks of follow-up. This trial is registered with ClinicalTrials.gov (NCT04504851). Findings: Between Sept 2, 2020, and Jan 14, 2021, 174 participants were screened and 137 were randomly assigned to the rosuvastatin group (70 participants) or control group (67 participants). In the modified intention-to-treat population of 135 participants, 102 (76%) were men and 33 (24%) were women. Median TTCC in liquid media was 42 days (95% CI 35–49) in the rosuvastatin group (68 participants) and 42 days (36–53) in the control group (67 participants; hazard ratio 1·30 [0·88–1·91], p=0·19). Grade 3–5 adverse events occurred in six (9%) of 70 in the rosuvastatin group (none were considered related to rosuvastatin) and four (6%) of 67 in the control group (p=0·75). There were no serious adverse events that were considered to be related to rosuvastatin. Interpretation: Adjunctive rosuvastatin at 10 mg once per day was safe but did not produce substantive benefits on culture conversion in the overall study population. Future trials could explore the safety and efficacy of higher doses of adjunctive rosuvastatin. Funding: National Medical Research Council, Singapore

Oral vs intravenous antibiotics for patients with klebsiella pneumoniae liver abscess: A randomized, controlled noninferiority study

Background Klebsiella pneumoniae liver abscess (KLA) is emerging worldwide due to hypermucoviscous strains with a propensity for metastatic infection. Treatment includes drainage and prolonged intravenous antibiotics. We aimed to determine whether oral antibiotics were noninferior to continued intravenous antibiotics for KLA. Methods This noninferiority, parallel group, randomized, clinical trial recruited hospitalized adults with liver abscess and K. pneumoniae isolated from blood or abscess fluid who had received ≤7 days of effective antibiotics at 3 sites in Singapore. Patients were randomized 1:1 to oral (ciprofloxacin) or intravenous (ceftriaxone) antibiotics for 28 days. If day 28 clinical response criteria were not met, further oral antibiotics were prescribed until clinical response was met. The primary endpoint was clinical cure assessed at week 12 and included a composite of absence of fever in the preceding week, C-reactive protein <20 mg/L, and reduction in abscess size. A noninferiority margin of 12% was used. Results Between November 2013 and October 2017, 152 patients (mean age, 58.7 years; 25.7% women) were recruited, following a median 5 days of effective intravenous antibiotics. A total of 106 (69.7%) underwent abscess drainage; 71/74 (95.9%) randomized to oral antibiotics met the primary endpoint compared with 72/78 (92.3%) randomized to intravenous antibiotics (risk difference, 3.6%; 2-sided 95% confidence interval, −4.9% to 12.8%). Effects were consistent in the per-protocol population. Nonfatal serious adverse events occurred in 12/72 (16.7%) in the oral group and 13/77 (16.9%) in the intravenous group. Conclusions Oral antibiotics were noninferior to intravenous antibiotics for the early treatment of KLA

Art therapy is associated with sustained improvement in cognitive function in the elderly with mild neurocognitive disorder: findings from a pilot randomized controlled trial for art therapy and music reminiscence activity versus usual care

BACKGROUND: Mild cognitive impairment (MCI) is a phase in cognitive decline when it is still possible to intervene to reverse the decline. Cognitive stimulation delivered through psychosocial interventions provides both psychological intervention and social stimulation to improve cognition. A pilot open-label parallel-arms randomized controlled trial was undertaken to examine the effects of art therapy (AT) and music reminiscence activity (MRA) compared to the control, on the primary outcome of neurocognitive domain assessments in elderly people with MCI. METHODS: Community-living elderly people with MCI (Petersen's criteria), assessed for study eligibility, were randomized using a web-based system with equal allocation to two intervention arms: AT (guided viewing of art pieces and production of visual arts) and MRA (listening, and recalling memories related to music) and a control arm (standard care without any intervention). Interventions were led by trained therapists weekly for 3 months, then fortnightly for 6 months. Neurocognitive domains (mean of memory, attention, and visuo-spatial abilities standardized scores), psychological wellbeing (subsyndromal depression and anxiety) and telomere length as a biological marker of cellular ageing, were assessed by intervention-blinded assessors at baseline, 3 months and 9 months. RESULTS: In total, 250 people were screened and 68 were randomized and included in the analysis. In the AT arm, neurocognitive domains improved compared to the control arm at 3 months (mean difference (d)?=?0.40; 90% CI 0.126, 0.679) and were sustained at 9 months (d?=?0.31; 90% CI 0.068, 0.548). There was some improvement in depression and anxiety at 3 and 9 months and in telomere length at 9 months, but this was not significant. Similar improvements were observed in the MRA arm over the control arm, but they were not significant. There were no intervention-related adverse effects. CONCLUSIONS: Art therapy delivered by trained staff as "art as therapy" and "art psychotherapy" may have been the significant contributor to cognitive improvements. The findings support cognitive stimulation for elderly people with cognitive decline and signal the need for larger studies and further investigation of carefully designed psycho-social interventions for this group. TRIAL REGISTRATION: Clinical Trials.gov, NCT02854085 . Registered on 7 July 2016