Daily fosfomycin versus levofloxacin for complicated urinary tract infections.

IMPORTANCE: Concerns over resistance and safety have been identified in the current treatment regimen for complicated urinary tract infections. Fosfomycin is a drug that is routinely used for the treatment of uncomplicated cystitis. This study shows that fosfomycin could be an oral alternative as step-down therapy for the treatment of complicated urinary tract infections, with a clinical cure rate comparable to levofloxacin but a lower microbiological success rate 3 weeks from start of antibiotics.

Determinates of Clostridioides difficile infection (CDI) testing practices among inpatients with diarrhea at selected acute-care hospitals in Rochester, New York, and Atlanta, Georgia, 2020-2021.

OBJECTIVE: We evaluated the impact of test-order frequency per diarrheal episodes on Clostridioides difficile infection (CDI) incidence estimates in a sample of hospitals at 2 CDC Emerging Infections Program (EIP) sites. DESIGN: Observational survey. SETTING: Inpatients at 5 acute-care hospitals in Rochester, New York, and Atlanta, Georgia, during two 10-workday periods in 2020 and 2021. OUTCOMES: We calculated diarrhea incidence, testing frequency, and CDI positivity (defined as any positive NAAT test) across strata. Predictors of CDI testing and positivity were assessed using modified Poisson regression. Population estimates of incidence using modified Emerging Infections Program methodology were compared between sites using the Mantel-Hanzel summary rate ratio. RESULTS: Surveillance of 38,365 patient days identified 860 diarrhea cases from 107 patient-care units mapped to 26 unique NHSN defined location types. Incidence of diarrhea was 22.4 of 1,000 patient days (medians, 25.8 for Rochester and 16.2 for Atlanta; P < .01). Similar proportions of diarrhea cases were hospital onset (66%) at both sites. Overall, 35% of patients with diarrhea were tested for CDI, but this differed by site: 21% in Rochester and 49% in Atlanta (P < .01). Regression models identified location type (ie, oncology or critical care) and laxative use predictive of CDI test ordering. Adjusting for these factors, CDI testing was 49% less likely in Rochester than Atlanta (adjusted rate ratio, 0.51; 95% confidence interval [CI], 0.40-0.63). Population estimates in Rochester had a 38% lower incidence of CDI than Atlanta (summary rate ratio, 0.62; 95% CI, 0.54-0.71). CONCLUSION: Accounting for patient-specific factors that influence CDI test ordering, differences in testing practices between sites remain and likely contribute to regional differences in surveillance estimates.

Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. METHODS: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 µg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475. FINDINGS: Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87-1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3-7%) in the interferon beta-1a plus remdesivir group and 3% (2-6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69-2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group. INTERPRETATION: Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo. FUNDING: The National Institute of Allergy and Infectious Diseases (USA).

Staphylococcus simulans: A rare uropathogen.

Urinary tract infections (UTIs) are clinically and economically burdensome. Gram positive causative uropathogens are rare, and Staphylococcus simulans has infrequently been isolated as a causative agent for UTIs. Here, we present two cases of S. simulans causing complicated urinary tract infections.