Administering antimicrobial agents before obtaining blood cultures could potentially decrease time to treatment and improve outcomes, but it is unclear how this strategy affects diagnostic sensitivity. To determine the sensitivity of blood cultures obtained shortly after initiation of antimicrobial therapy in patients with severe manifestations of sepsis. Patient-level, single-group, diagnostic study. (ClinicalTrials.gov: NCT01867905) 7 emergency departments in North America. Adults with severe manifestations of sepsis, including systolic blood pressure less than 90 mm Hg or a serum lactate level of 4 mmol/L or more. Blood cultures were obtained before and within 120 minutes after initiation of antimicrobial treatment. Sensitivity of blood cultures obtained after initiation of antimicrobial therapy. Of 3164 participants screened, 325 were included in the study (mean age, 65.6 years; 62.8% men) and had repeated blood cultures drawn after initiation of antimicrobial therapy (median time, 70 minutes [interquartile range, 50 to 110 minutes]). Preantimicrobial blood cultures were positive for 1 or more microbial pathogens in 102 of 325 (31.4%) patients. Postantimicrobial blood cultures were positive for 1 or more microbial pathogens in 63 of 325 (19.4%) patients. The absolute difference in the proportion of positive blood cultures between pre- and postantimicrobial testing was 12.0% (95% CI, 5.4% to 18.6%; P < 0.001). Sensitivity of postantimicrobial culture was 52.9% (CI, 42.8% to 62.9%). When the results of other microbiological cultures were included, microbial pathogens were found in 69 of 102 (67.6% [CI, 57.7% to 76.6%]) patients. Only a proportion of screened patients were recruited. Among patients with severe manifestations of sepsis, initiation of empirical antimicrobial therapy significantly reduces the sensitivity of blood cultures drawn shortly after treatment initiation. Vancouver Coastal Health, St. Paul's Hospital Foundation Emergency Department Support Fund, the Fonds de recherche Santé–Québec, and the Maricopa Medical Foundation.

The effect of surges in COVID-19 caseload on COVID-19 survival rates is unclear, especially independent of temporal changes in survival. This retrospective cohort study used data from a large U.S. ... Visual Association Between Caseload Surge and COVID-19 Survival in U.S. Hospitals. The effect of surges in COVID-19 caseload on COVID-19 survival rates is unclear, especially independent o... Background: Several U.S. hospitals had surges in COVID-19 caseload, but their effect on COVID-19 survival rates remains unclear, especially independent of temporal changes in survival. Objective: T...

Bloodstream infections (BSI) with methicillin-susceptible Staphylococcus aureus (MSSA) are associated with significant morbidity and mortality. The objective of our study was to determine the efficacy of synergistic treatment of daptomycin when given with either cefazolin or cloxacillin for the treatment of MSSA BSI. A randomized, double blind, placebo-controlled trial was performed at two academic hospitals in Montreal, Canada. Patients ≥ 18 years of age with MSSA BSI receiving either cefazolin or cloxacillin monotherapy were considered for inclusion. In addition to the standard of care treatment, participants received a 5-day course of adjunctive daptomycin or placebo. The primary outcome was the duration of MSSA BSI in days. Of 318 participants screened, 115 were enrolled and 104 were included in the intention to treat analysis (median age 67 years; 34.5% female). The median duration of bacteremia was 2.04 days among patients who received daptomycin versus 1.65 days in those who received placebo (absolute difference 0.39 days, p=0.40). A modified intention to treat analysis involving participants who remained bacteremic at the time of enrollment found a median duration of bacteremia of 3.06 days among patients who received daptomycin versus 3.0 days in those who received placebo (absolute difference 0.06 days, p=0.77). Ninety-day mortality in the daptomycin arm was 18.9% vs. 17.7% in the placebo arm (p=1.0). Among patients with MSSA bloodstream infections, the administration of adjunctive daptomycin therapy to standard of care treatment did not shorten the duration of bacteremia and should not be routinely considered.

Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection causing more than 400000 cases annually worldwide. Although antiretroviral therapy has reduced the burden of PCP in persons with human immunodeficiency virus (HIV), an increasing proportion of cases occur in other immunocompromised populations. In this review, we synthesize the available randomized controlled trial (RCT) evidence base for PCP treatment. We identified 14 RCTs that were conducted 25–35 years ago, principally in 40-year-old men with HIV. Trimethoprim-sulfamethoxazole, at a dose of 15–20 mg/kg per day, is the treatment of choice based on historical practice rather than on quality comparative, dose-finding studies. Treatment duration is similarly based on historical practice and is not evidence based. Corticosteroids have a demonstrated role in hypoxemic patients with HIV but have yet to be studied in RCTs as an adjunctive therapy in non-HIV populations. The echinocandins are potential synergistic treatments in need of further investigation.

Background: Little is known about the frequency, hospital-level variation, predictors, and outcomes of antibiotic de-escalation in suspected sepsis. Methods: We retrospectively analyzed adults admitted to 236 US hospitals from 2017–2021 with suspected sepsis (defined by blood culture draw, lactate measurement, and intravenous antibiotic administration) who were initially treated with ≥2 days of anti–methicillin-resistant Staphylococcus aureus (MRSA) and anti-pseudomonal antibiotics but had no resistant organisms that required these agents identified through hospital day 4. De-escalation was defined as stopping anti-MRSA and anti-pseudomonal antibiotics or switching to narrower antibiotics by day 4. We created a propensity score for de-escalation using 82 hospital and clinical variables; matched de-escalated to non–de-escalated patients; and assessed associations between de-escalation and outcomes. Results: Among 124 577 patients, antibiotics were de-escalated in 36 806 (29.5%): narrowing in 27 177 (21.8%), cessation in 9629 (7.7%). De-escalation rates varied between hospitals (median, 29.4%; interquartile range, 21.3%–38.0%). Predictors of de-escalation included less severe disease on day 3–4, positive cultures for nonresistant organisms, and negative/absent MRSA nasal swabs. De-escalation was more common in medium, large, and teaching hospitals in the Northeast and Midwest. De-escalation was associated with lower adjusted risks for acute kidney injury (AKI) (odds ratio [OR], 0.80; 95% confidence interval [CI], .76–.84), intensive-care unit (ICU) admission after day 4 (OR, 0.59; 95% CI, .52–.66), and in-hospital mortality (OR, 0.92; 95% CI, .86–.996). Conclusions: Antibiotic de-escalation in suspected sepsis is infrequent, variable across hospitals, linked with clinical and microbiologic factors, and associated with lower risk for AKI, ICU admission, and in-hospital mortality.

OBJECTIVES: Serum procalcitonin is often ordered at admission for patients with suspected sepsis and bloodstream infections (BSIs), although its performance characteristics in this setting remain contested. This study aimed to evaluate use patterns and performance characteristics of procalcitonin-on-admission in patients with suspected BSI, with or without sepsis. DESIGN: Retrospective cohort study. SETTING: Cerner HealthFacts Database (2008–2017). PATIENTS: Adult inpatients (≥ 18 yr) who had blood cultures and procalcitonin drawn within 24 hours of admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Testing frequency of procalcitonin was determined. Sensitivity of procalcitonin-on-admission for detecting BSI due to different pathogens was calculated. Area under the receiver operating characteristic curve (AUC) was calculated to assess discrimination by procalcitonin-on-admission for BSI in patients with and without fever/hypothermia, ICU admission and sepsis defined by Centers for Disease Control and Prevention Adult Sepsis Event criteria. AUCs were compared using Wald test and p values were adjusted for multiple comparisons. At 65 procalcitonin-reporting hospitals, 74,958 of 739,130 patients (10.1%) who had admission blood cultures also had admission procalcitonin testing. Most patients (83%) who had admission day procalcitonin testing did not have a repeat procalcitonin test. Median procalcitonin varied considerably by pathogen, BSI source, and acute illness severity. At a greater than or equal to 0.5 ng/mL cutoff, sensitivity for BSI detection was 68.2% overall, ranging between 58.0% for enterococcal BSI without sepsis and 96.4% for pneumococcal sepsis. Procalcitonin-on-admission displayed moderate discrimination at best for overall BSI (AUC, 0.73; 95% CI, 0.72–0.73) and showed no additional utility in key subgroups. Empiric antibiotic use proportions were not different between blood culture sampled patients with a positive procalcitonin (39.7%) and negative procalcitonin (38.4%) at admission. CONCLUSIONS: At 65 study hospitals, procalcitonin-on-admission demonstrated poor sensitivity in ruling out BSI, moderate-to-poor discrimination for both bacteremic sepsis and occult BSI and did not appear to meaningfully alter empiric antibiotic usage. Diagnostic stewardship of procalcitonin-on-admission and risk assessment of admission procalcitonin-guided clinical decisions is warranted.