Alyssa R. Letourneau

Disseminated nontuberculous mycobacterial disease is a severe complication of NEMO (IKBKG) and IκBα (NFKBIA) defects. It may present in adulthood, and diagnosis was often delayed. Despite intensive multidrug therapy and adjunctive IFN-γ, treatment responses were frequently inadequate. Hematopoietic cell transplantation may offer immune reconstitution but carries risks.

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.

Objective: To compare clinical outcomes in adults with uncomplicated enterococcal bacteremia treated with intravenous (IV) therapy alone versus an early oral (PO) transition and evaluate treatment characteristics and safety outcomes. Design: Retrospective cohort study between January 1, 2021, and August 1, 2024. The primary outcome was clinical cure at 90 days after antibiotic completion. Secondary outcomes included treatment failure, infection-related readmission, hospital length of stay (HLOS), and 90-day mortality. Setting: Massachusetts General Hospital and Brigham and Women’s Hospital, two tertiary care centers in Boston, MA. Patients: Adult patients with at least one positive blood culture with Enterococcus spp. Patients were excluded if they had polymicrobial or persistent bacteremia, invasive infection, incomplete source control, died before completing therapy, or received fewer than 7 days of antibiotics. Results: 209 patients were included, of which 119 received IV therapy alone and 90 underwent early PO transition. Gastrointestinal (41.6%) and genitourinary (32.1%) sources were most common, and 86 patients (41.1%) had immunocompromising conditions. Clinical cure was similar between the IV and early PO transition groups (73.9% vs 82.2%; P = .156), with no significant differences in secondary and safety outcomes. HLOS was significantly shorter in the early PO transition group (9 days vs 20 days; P < .001). Conclusion: Early PO transition appears to be a safe and effective strategy for uncomplicated enterococcal bacteremia and was associated with reduced HLOS.

Cefepime, a cornerstone antibiotic in critical care, is associated with underrecognized cefepime-induced neurotoxicity (CIN), particularly in patients 65 years old and older. The true incidence is unknown due to inconsistent monitoring and a lack of diagnostic criteria. The recent Antibiotic Choice on Renal Outcomes (ACORN) trial underscored CIN’s clinical significance, finding that cefepime recipients experienced 21% fewer delirium- and coma-free days than those on piperacillin-tazobactam. Current guidelines lack active surveillance recommendations, leading to delayed diagnosis and intervention. We propose three informatics-based strategies to address these challenges: 1) electronic health record (EHR)-integrated datasets utilizing machine learning and natural language processing to identify CIN at scale, 2) automated electroencephalogram tools to provide real-time alerts to clinicians, and 3) dynamic risk scores that continuously update from EHR data to guide prescribing. Implementing these safeguards to optimize CIN prevention, which may be relevant for other antibiotics with neurotoxicity risk, can improve neurologic outcomes and patient safety in critically ill populations.

Background: Remdesivir (RDV) was approved for treatment of coronavirus disease 2019 (COVID-19), in May 2020 under US Food and Drug Administration emergency use authorization (EUA). Clinical outcomes related to RDV use in hospitalized patients during the EUA period are not well described. Methods: We conducted a retrospective study of patients who received RDV under EUA. The primary outcome was clinical recovery by day 14 as determined by an eight-category ordinal scale. Secondary outcomes included recovery and survival to day 28, and adverse events. Recovery and survival were calculated using a stratified log-rank Kaplan–Meier estimator and a Cox proportional hazards model. Results: Overall, 164 patients received RDV between May and October 2020, and 153 (93.3%) had evaluable data. Most (77.1%) were hospitalized within 10 days of symptom onset, and 79.7% started RDV within 48 hours. By days 14 and 28, 96 (62.7%) and 117 patients (76.5%) met the definition of clinical recovery, respectively. Median time to recovery was 6 days [interquartile range (IQR) 4–12]. Mortality rates were 6.5% and 11.8% by days 14 and 28, respectively. Age and time to start of RDV after hospital admission were predictive of recovery and 28-day mortality. Conclusions: In this real-world experience, outcomes after 5 days of RDV therapy were comparable to those of clinical trials. Disease severity, age, and dexamethasone use influenced clinical outcomes. Time to RDV initiation appeared to affect recovery and 28-day mortality, a finding that should be explored further. Mortality rate decreased over the analysis period, which could be related to dexamethasone use and improved management of COVID-19.