David W. Kubiak

Background: Antibiotic restriction policies are intended to curb resistance, but their effects on resistance, timely treatment, and patient outcomes remain uncertain. We evaluated linezolid restrictions and whether vancomycin-resistant Enterococcus (VRE) screening identifies patients most likely to benefit. Methods: We conducted a quasi-experimental difference-in-differences study using electronic health record data from 521 493 admissions at 2 academic medical centers from 2008 through 2019. Hospital 1 introduced a formal prior-authorization pager system in 2011 and stricter linezolid-specific criteria with enhanced post-prescription review in 2014; Hospital 2 served as a control. Outcomes included linezolid use, linezolid-resistant Enterococcus isolates, in-hospital mortality overall and by VRE status, and stewardship request behavior. Results: Linezolid was used in 2.3% of admissions; 1.2% of Enterococcus isolates were linezolid-resistant. Restriction policies were associated with a 27% reduction in linezolid use (−0.9 percentage points; 95% confidence interval, −1.1 to −0.7; P < .001) and a 41% reduction in resistance (−1.0 percentage points; 95% confidence interval, −1.6 to −0.4; P = .003). Overall mortality did not increase, but mortality among VRE-screen-positive patients increased by 4.7 percentage points (95% confidence interval, 1.9 to 7.5; P < .001), with larger increases among those with bacteremia or sepsis. Approval rates declined first, followed by fewer linezolid requests. Conclusions: Restriction policies can reduce antibiotic use and resistance but may benefit from screening-informed safeguards to preserve timely treatment for high-risk patients.

Accelerated venovenous hemofiltration (AVVH) is a hybrid renal replacement therapy (RRT) offering higher hemofiltration rates and improved hemodynamic stability, but can alter pharmacokinetics and pharmacodynamics of numerous antibiotics, creating uncertainty in efficacy and toxicity. The purpose of this study was to describe vancomycin dosing practices in patients receiving AVVH, with the potential to model vancomycin dosing and monitoring strategies. This was a single‐center retrospective analysis of vancomycin dosing strategies utilized in critically ill adult patients receiving AVVH. Patients were included if they received vancomycin while undergoing AVVH and had a vancomycin concentration measured within the first 24 h of initiating concomitant vancomycin and AVVH. Major endpoint of this study was the incidence of in‐range vancomycin concentrations (10–20 mcg/mL) in patients undergoing AVVH. There were 52 patients included in the analysis, with 79 unique AVVH sessions with an associated vancomycin concentration assessed. Median dose of vancomycin was 1250 mg (1000–1500), or 14.5 mg/kg (12.7–16.6), per AVVH session. Incidence of in‐range vancomycin concentrations was 68.4%, with a median vancomycin concentration of 17.1 mcg/mL (14.0–21.5). Median duration of vancomycin therapy with concomitant AVVH was 2 days (1–7) and the median time from AVVH completion to vancomycin concentration obtainment was 2.8 h (0.3–5.7). The majority of vancomycin concentrations collected were in range, using a median vancomycin dose of 14.5 mg/kg and achieving a median vancomycin concentration of 17.6 mcg/mL. This suggests most patients achieved in‐range concentrations, but additional prospective pharmacokinetic studies are needed to understand vancomycin exposure and dosing requirements in patients undergoing AVVH.

In outpatient parenteral antimicrobial therapy, weekly lab monitoring is often standard practice, even for antimicrobials with low complication rates. We reviewed 420 patients treated with cefazolin: lab abnormalities associated with readmission or treatment changes occurred in 2% of patients. Reduced-frequency monitoring may be reasonable for patients treated with cefazolin outpatient.

Background: Current vancomycin monitoring guidelines recommend monitoring 24-hour area under the concentration-time curve (AUC) to minimum inhibitory concentration ratios for patients with serious methicillin-resistant Staphylococcus aureus infections. However, there are sparse data on the safety, feasibility, and efficacy of vancomycin AUC monitoring for outpatients. Traditional AUC pharmacokinetic calculations require 2 concentrations, while bayesian software allows for single-concentration AUC estimations. Methods: We conducted a single-center, quasi-experimental, interrupted time series study of patients enrolled in the outpatient parenteral antimicrobial therapy program at our institution for vancomycin management. Our institution implemented a pharmacist-driven vancomycin AUC monitoring program from September 2019 to February 2020, and again from September 2022 to March 2023. Patients enrolled underwent vancomycin monitoring using an AUC goal of 400–600 mg⋅h/L, estimated through bayesian modeling. Patients enrolled in the outpatient parenteral antimicrobial therapy program from July 2021 through August 2022 for trough-based monitoring were used for comparison. The primary outcome was nephrotoxicity incidence, defined as a serum creatinine increase by ≥0.5 mg/dL or ≥50% during outpatient vancomycin therapy. Results: We enrolled 63 patients in the AUC group and 60 patients in the trough-based group. Nephrotoxicity was significantly lower in the AUC cohort (6.3% vs 23.3%; P = .01). The number of unusable vancomycin concentrations was also significantly lower in the AUC cohort (0% vs 6%; P < .01). There was no difference in composite 90-day all-cause mortality or readmission (33.3% vs 38.3%; P = .56). Conclusions: Following implementation of a pharmacist-driven AUC monitoring program, patients were less likely to develop nephrotoxicity during outpatient vancomycin therapy.

Streptococcus mitis commonly causes bloodstream infections (BSIs) in neutropenic patients but infrequently results in infective endocarditis (IE) in this population. Among 210 patients with neutropenia and S. mitis BSI, 55% underwent cardiac imaging. None were diagnosed with S. mitis IE; 3 had recurrent S. mitis BSI within 12 weeks.

Current vancomycin guidelines recommend early and frequent area-under-the-curve monitoring in patients with obesity. Vancomycin's volume of distribution is likely altered in patients with obesity, which may result in lower serum concentrations initially but lead to accumulation with continued use. The objective of this study was to evaluate the incidence of vancomycin accumulation in patients with obesity and identify potential factors associated with accumulation. This was a single-center, retrospective, observational study at a tertiary academic medical center. Adult patients with a body mass index (BMI) ≥ 30 kg/m² and ≥ 2 vancomycin serum trough concentrations drawn in 2019 were screened for inclusion. The major endpoint was the incidence of vancomycin accumulation defined as ≥ 20% increase in trough concentration within the first 10 days of therapy. Key minor endpoints included incidence of acute kidney injury (AKI) and factors associated with accumulation. Of the 443 patients screened, 162 were included. The median age was 56.5 years (interquartile range [IQR], 43–65.3), and 62.3% were male. The median weight was 112.7 kg (IQR, 99.8–122.6) and the median BMI was 36.8 kg/m² (IQR, 33.1–41). The total daily dose median at initiation was 28.7 mg/kg per day (IQR, 25.4–31.2). Accumulation occurred in 99 of 162 patients (61.1%) and AKI occurred in 20 of 140 patients (14.3%). No specific factors were found to be associated with accumulation. Patients with obesity are likely to experience vancomycin accumulation within the first 10 days of therapy. Clinicians should use frequent monitoring of vancomycin and use caution when interpreting early concentrations in patients with obesity.

Chronic granulomatous disease (CGD) is a primary immunodeficiency syndrome that results in increased risk for bacterial and fungal infections, as well as inflammatory/autoimmune complications. While CGD historically has been associated with early death in childhood, the life expectancy and morbidity of patients with CGD have greatly improved. Many patients with CGD now survive well into adulthood, and data on adult cohorts of patients with CGD have been published. However, reports of pregnancy management, complications, and outcomes for patients with CGD are sparse. In addition, management of invasive fungal infections, including use of newer triazole antifungals, during pregnancy has not been well described. We report a case of fungal lung infection in a pregnant woman with CGD, diagnosed during her second trimester, which was treated with multiple antifungal agents, including more than 12 weeks of isavuconazole therapy, resulting in resolution of infection and delivery of a healthy newborn at term.

Objective: To determine whether oral vancomycin prophylaxis accompanying systemic antibiotics reduces the risk of relapse in patients with history ofClostridioides difficileinfection (CDI).Design: Retrospective cohort study.Patients: Adult inpatients with a history of CDI who received systemic antibiotics in either of 2 hospitals between January 2009 and June 2015.Methods: We compared relapse rates in patients who started oral vancomycin concurrently with systemic antibiotics (exposed group) versus those who did not. We assessed for CDI relapse by toxin or nucleic acid testing at 90 days. We used inverse probability weighting and machine learning to adjust for confounders, to estimate propensity for treatment, and to calculate odds ratios for CDI relapse. We performed secondary analyses limited to toxin-positive relapses, patients with 1 versus >1 prior CDI episodes, and patients who received oral vancomycin on each antibiotic day.Results: CDI relapse occurred within 90 days in 19 of 193 exposed patients (9.8%) versus 53 of 567 unexposed patients (9.4%; unadjusted odds ratio [OR], 1.06; 95% confidence interval [CI], 0.60–1.81; adjusted OR, 0.63; 95% CI, 0.35–1.14). CDI relapses at 90 days were less frequent in exposed patients with only 1 prior episode of CDI (OR, 0.42; 95% CI, 0.19–0.93) but not in those with >1 prior episode (OR, 1.19; 95% CI, 0.42–3.33). Our findings were consistent with a lack of benefit of oral vancomycin when restricting results to toxin-positive relapses and to patients who received vancomycin each antibiotic day.Conclusions: Prophylactic oral vancomycin was not consistently associated with reduced risk of CDI relapse among hospitalized patients receiving systemic antibiotics. However, patients with only 1 prior CDI episode may benefit.