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Experimental and observational studies have suggested that empirical treatment for bacterial sepsis with antianaerobic antibiotics (eg, piperacillin-tazobactam) is associated with adverse outcomes compared with anaerobe-sparing antibiotics (eg, cefepime). However, a recent pragmatic clinical trial of piperacillin-tazobactam and cefepime showed no difference in short-term outcomes at 14 days. Further studies are needed to help clarify the empirical use of these agents.

To examine the use of piperacillin-tazobactam compared with cefepime in 90-day mortality in patients treated empirically for sepsis, using instrumental variable analysis of a 15-month piperacillin-tazobactam shortage.

In a retrospective cohort study, hospital admissions at the University of Michigan from July 1, 2014, to December 31, 2018, including a piperacillin-tazobactam shortage period from June 12, 2015, to September 18, 2016, were examined. Adult patients with suspected sepsis treated with vancomycin and either piperacillin-tazobactam or cefepime for conditions with presumed equipoise between piperacillin-tazobactam and cefepime were included in the study. Data analysis was conducted from December 17, 2022, to April 11, 2023.

The primary outcome was 90-day mortality. Secondary outcomes included organ failure-free, ventilator-free, and vasopressor-free days. The 15-month piperacillin-tazobactam shortage period was used as an instrumental variable for unmeasured confounding in antibiotic selection.

Among 7569 patients (4174 men [55%]; median age, 63 [IQR 52-73] years) with sepsis meeting study eligibility, 4523 were treated with vancomycin and piperacillin-tazobactam and 3046 were treated with vancomycin and cefepime. Of patients who received piperacillin-tazobactam, only 152 (3%) received it during the shortage. Treatment groups did not differ significantly in age, Charlson Comorbidity Index score, Sequential Organ Failure Assessment score, or time to antibiotic administration. In an instrumental variable analysis, piperacillin-tazobactam was associated with an absolute mortality increase of 5.0% at 90 days (95% CI, 1.9%-8.1%) and 2.1 (95% CI, 1.4-2.7) fewer organ failure-free days, 1.1 (95% CI, 0.57-1.62) fewer ventilator-free days, and 1.5 (95% CI, 1.01-2.01) fewer vasopressor-free days.

Among patients with suspected sepsis and no clear indication for antianaerobic coverage, administration of piperacillin-tazobactam was associated with higher mortality and increased duration of organ dysfunction compared with cefepime. These findings suggest that the widespread use of empirical antianaerobic antibiotics in sepsis may be harmful.

ClinicalTrials.gov, NCT05968794.

We designed two multicentre randomised trials involving eight hospitals in the Netherlands (sites in other countries may be added at a later date). Women older than 16 years with a twin pregnancy at <24 weeks of gestation and an asymptomatic short cervix of ≤25 mm or cervical dilatation will be randomly allocated (1:1) to both trials on vaginal cerclage and standard treatment according to the current Dutch Society of Obstetrics and Gynaecology guideline (no cerclage). Permuted blocks sized 2 and 4 will be used to minimise the risk of disbalance. The primary outcome measure is PTB of <28 weeks. Analyses will be by intention to treat. The first trial is to demonstrate a risk reduction from 25% to 10% in the short cervix group, for which 194 patients need to be recruited. The second trial is to demonstrate a risk reduction from 80% to 35% in the dilatation group and will recruit 44 women. A cost-effectiveness analysis will be performed from a societal perspective.

To compare living wages and salaries at US residency programs.

It is unknown how resident salary compares to living wages across the United States (US).

Cross-sectional analysis of publicly available resident salary affordability from training centers with post-graduate-year (PGY)-1 through PGY-7 resident compensation for 2022-2023 was compared with the Massachusetts Institute of Technology (MIT) Living-Wage Calculator. Resident salary to living wage ratios were calculated using PGY-4 salary for each family composition. Univariate and multivariable analysis of PGY-4 salary affordability was performed, accounting for proportion of expected living wages to taxes, transportation, housing, healthcare, childcare, and food, as well as unionization and state income-tax.

118 residency programs, representing over 60% of US trainees, were included, 20 (17%) of which were unionized. Single-parent families were unable to earn a living wage until PGY-7. Residents with 1 child in 2-adult (single-income) and 2-adult (dual-income) families earn below living wages until PGY-5 and PGY-3, respectively. Residents with more than 1 child never earn a living wage. Multivariable regression analysis using PGY-4 salary: living wage ratios in single-child, 2-parent homes showed food expense and unionization status were consistent predictors of affordability. Unionization was associated with lower affordability pre-stipend, almost equivalent affordability post-stipend, and lower affordability post-stipend and union dues.

Resident salaries often preclude residents with children from earning a living wage. Unionization is not associated with increased resident affordability in this cross-sectional analysis. All annual reimbursement data should be centrally compiled, and additional stipends should be considered for residents with children.