Oral Antibiotics and Risk of Serious Cutaneous Adverse Drug Reactions.

Importance: Serious cutaneous adverse drug reactions (cADRs) are potentially life-threatening drug hypersensitivity reactions involving the skin and internal organs. Antibiotics are a recognized cause of these reactions, but no studies have compared relative risks across antibiotic classes. Objectives: To explore the risk of serious cADRs associated with commonly prescribed oral antibiotics, and to characterize outcomes of patients hospitalized for them. Design, Setting, and Participants: Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not. Exposure: Various classes of oral antibiotics. Main Outcomes and Measures: Conditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group. Results: During the 20-year study period, we identified 21 758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87 025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital. Conclusion and Relevance: Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate.

Variation in antibiotic use across intensive care units (ICU): A population-based cohort study in Ontario, Canada.

OBJECTIVES: Antibiotics are commonly used in intensive care units (ICUs), yet differences in antibiotic use across ICUs are unknown. Herein, we studied antibiotic use across ICUs and examined factors that contributed to variation. METHODS: We conducted a retrospective cohort study using data from Ontario's Critical Care Information System (CCIS), which included 201 adult ICUs and 2,013,397 patient days from January 2012 to June 2016. Antibiotic use was measured in days of therapy (DOT) per 1,000 patient days. ICU factors included ability to provide ventilator support (level 3) or not (level 2), ICU type (medical-surgical or other), and academic status. Patient factors included severity of illness using multiple-organ dysfunction score (MODS), ventilatory support, and central venous catheter (CVC) use. We analyzed the effect of these factors on variation in antibiotic use. RESULTS: Overall, 269,351 patients (56%) received antibiotics during their ICU stay. The mean antibiotic use was 624 (range 3-1460) DOT per 1,000 patient days. Antibiotic use was significantly higher in medical-surgical ICUs compared to other ICUs (697 vs 410 DOT per 1,000 patient days; P < .0001) and in level 3 ICUs compared to level 2 ICUs (751 vs 513 DOT per 1,000 patient days; P < .0001). Higher antibiotic use was associated with higher severity of illness and intensity of treatment. ICU and patient factors explained 47% of the variation in antibiotic use across ICUs. CONCLUSIONS: Antibiotic use varies widely across ICUs, which is partially associated with ICUs and patient characteristics. These differences highlight the importance of antimicrobial stewardship to ensure appropriate use of antibiotics in ICU patients.

The impact of CCL3L1 copy number in an HIV-1-infected white population.

We examined the effect of CCL3L1 gene copy number on disease progression in a North American white cohort of HIV-1-infected individuals. Although CCL3L1 copy number is enriched in uninfected Caucasians, in HIV-1-infected individuals CCL3L1 copy number did not correlate either with long-term nonprogression or with CD4 cell count or viral load in chronic progressors. These findings underscore the heterogeneity of factors involved with long-term nonprogression when comparing cohorts of varying ethnic backgrounds.