Antibiotics for Preventing Recurrent Urinary Tract Infection: Systematic Review and Meta-analysis.

Recurrent urinary tract infections are a common health problem. The only comprehensive synthesis on antibiotic prophylaxis in the last 15 years has been a guideline-embedded meta-analysis. We conducted a systematic review and meta-analysis of randomized controlled trials published up to October 13, 2020, evaluating patients age ≥12 years with either ≥2 episodes of lower urinary tract infection (UTI) within 6 months or ≥3 in the past year. Placebo or antibiotics were allowed as comparators. Study quality was low. In the 11 placebo-controlled trials, the risk for developing UTI was 85% lower with prophylaxis in comparison with placebo (risk ratio [RR], 0.15; 95% CI, 0.08-0.29). In the 9 head-to-head trials, the efficacy of the antibiotic agents appeared similar: The pooled RR indicated no difference between nitrofurantoin and comparators (RR, 1.01; 95% CI, 0.74-1.37), nor trimethoprim (+/- sulfamethoxazole; RR, 1.34; 95% CI, 0.89-2.03) or norfloxacin and comparators (RR, 1.17; 95% CI, 0.43-1.70). Studies comparing intermittent (postcoital) with continuous strategies revealed intermittent application to be equally effective

Antibiotics for preventing recurrent urinary tract infection: Systematic review and meta-analysis

Recurrent urinary tract infections are a common health problem. The only comprehensive synthesis on antibiotic prophylaxis in the last 15 years has been a guideline-embedded meta-analysis. We conducted a systematic review and meta-analysis of randomized controlled trials published up to October 13, 2020, evaluating patients age ≥12 years with either ≥2 episodes of lower urinary tract infection (UTI) within 6 months or ≥3 in the past year. Placebo or antibiotics were allowed as comparators. Study quality was low. In the 11 placebo-controlled trials, the risk for developing UTI was 85% lower with prophylaxis in comparison with placebo (risk ratio [RR], 0.15; 95% CI, 0.08-0.29). In the 9 head-to-head trials, the efficacy of the antibiotic agents appeared similar: The pooled RR indicated no difference between nitrofurantoin and comparators (RR, 1.01; 95% CI, 0.74-1.37), nor trimethoprim (+/- sulfamethoxazole; RR, 1.34; 95% CI, 0.89-2.03) or norfloxacin and comparators (RR, 1.17; 95% CI, 0.43-1.70). Studies comparing intermittent (postcoital) with continuous strategies revealed intermittent application to be equally effective

Optimizing Antibiotic Stewardship in Nursing Homes: A Narrative Review and Recommendations for Improvement

The emerging crisis in antibiotic resistance and concern that we now sit on the precipice of a post-antibiotic era have given rise to advocacy at the highest levels for widespread adoption of programmes that promote judicious use of antibiotics. These antibiotic stewardship programmes, which seek to optimize antibiotic choice when clinically indicated and discourage antibiotic use when clinically unnecessary, are being implemented in an increasing number of acute care facilities, but their adoption has been slower in nursing homes. The antibiotic prescribing process in nursing homes is fundamentally different from that observed in hospital and clinic settings, with formidable challenges to implementation of effective antibiotic stewardship. Nevertheless, an emerging body of research points towards ways to improve antibiotic prescribing practices in nursing homes. This review summarizes the findings of this research and presents ways in which antibiotic stewardship can be implemented and optimized in the nursing home setting

Identifying nonprescription antibiotic users with screening questions in a primary care setting

Background: Antibiotic use without a prescription (nonprescription use) leads to antibiotic overuse, with negative consequences for patient and public health. We studied whether screening patients for prior nonprescription antibiotic use in the past 12 months predicted their intentions to use them in the future. Methods: A survey asking respondents about prior and intended nonprescription antibiotic use was performed between January 2020 and June 2021 among patients in waiting rooms of 6 public clinics and 2 private emergency departments in economically and socially diverse urban and suburban areas. Respondents were classified as prior nonprescription users if they reported previously taking oral antibiotics without contacting a doctor, dentist, or nurse. Intended use was defined as answering “yes” or “maybe” to the question, “Would you use antibiotics without contacting a doctor, nurse, or dentist?” We calculated the sensitivity, specificity, and positive and negative predictive value (PPV and NPV) of prior nonprescription antibiotic use in the past 12 months for future intended nonprescription use. Bayes PPV and NPV were also calculated, considering the prevalence of nonprescription antibiotic use (24.8%) in our study. Results: Of the 564 patients surveyed, the median age was 51 years (SD, 19–92), with 72% of patients identifying as female. Most were from the public healthcare system (72.5%). Most respondents identified as Hispanic or Latino(a) (47%) or African American (33%), and 57% received Medicaid or the county financial assistance program. Prior nonprescription use was reported by 246 (43%) of 564 individuals, with 91 (16%) reporting nonprescription use within the previous 12 months. Intention to use nonprescription antibiotics was reported by 140 participants (25%). The sensitivity and specificity of prior nonprescription use in the past 12 months to predict the intention to use nonprescription antibiotics in the future were 75.9% (95% CI, 65.3–84.6) and 91.4% (95% CI, 87.8–94.2), respectively. After the Bayes’ adjustment, the PPV and NPV of prior use to predict future intention were 74.5% (95% CI, 66.7–80.9) and 92.0% (95% CI, 88.7–94.4) (Table 1). Conclusions: These results show that prior nonprescription antibiotic use in the past 12 months predicted the intention to use nonprescription antibiotics in the future (PPV of 75%). As a stewardship effort, we suggest clinicians use a simple question about prior nonprescription antibiotic use in primary-care settings as a screening question for patients at high risk for future nonprescription antibiotic use

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

BACKGROUND: We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. METHODS: In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. FINDINGS: Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50-72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74-1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67-1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74-1·58]; BRII-196 plus BRII-198 1·00 [0·68-1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91-1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88-1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. INTERPRETATION: Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. FUNDING: US National Institutes of Health and Operation Warp Speed