Evaluating outcomes associated with revised fluoroquinolone breakpoints for Enterobacterales urinary tract infections: A retrospective cohort study.

PURPOSE: In 2019, minimum inhibitory concentration (MIC) breakpoints of ciprofloxacin and levofloxacin for Enterobacterales were lowered. This study sought to determine whether there is a correlation between MIC and outcomes in those receiving fluoroquinolones (FQs) for urinary tract infections (UTIs) caused by Enterobacterales pathogens. METHODS: This was a retrospective study of adult patients treated with ciprofloxacin or levofloxacin for a UTI caused by an Enterobacterales pathogen. Patients were placed into low MIC (ciprofloxacin: ≤ 0.25 mcg/mL; levofloxacin ≤ 0.5 mcg/mL), intermediate MIC (ciprofloxacin: 0.5-2 mcg/mL; levofloxacin: 1-4 mcg/mL), or high MIC groups (ciprofloxacin: > 2 mcg/mL; levofloxacin: > 4 mcg/mL). The primary outcome was UTI recurrence, defined as hospital admission, emergency department or clinic visit due to UTI, or antibiotic prescription within 28 days of FQ initiation. RESULTS: A total of 1022 patients were included: 887, 75, and 60 with a low, intermediate, and high MIC, respectively. UTI recurrence within 28 days occurred most frequently in the high MIC group (20.5% vs. 25.3% vs. 60%; P < 0.01). Risk factors for UTI recurrence identified by multivariable analysis were those with a high MIC (high vs. low MIC: OR 5.20, 95% CI 2.99-9.05, P < 0.01; high vs. intermediate MIC: OR 4.72, 95%CI 2.22-10.03, P < 0.01), a complicated UTI (OR 1.85, 95% CI 1.35-2.54; P < 0.01), a history of recurrent UTIs (OR 1.84, 95% CI 1.29-2.62; P < 0.01), or a respiratory disorder (OR 1.58, 95% CI 1.04-2.42; P = 0.03). CONCLUSION: This study supports separate, less stringent FQ MIC breakpoint interpretive criteria for UTIs caused by Enterobacterales pathogens.

High frequency of potential phosphodiesterase type 5 inhibitor drug interactions in males with HIV infection and erectile dysfunction.

OBJECTIVES: We sought to determine the prevalence of phosphodiesterase type 5 inhibitor (PDE-5) mediated drug-drug interactions (DDIs) in males with HIV infection receiving antiretroviral therapy (ART) and identify factors associated with PDE-5-mediated DDIs. METHODS: Male US Military HIV Natural History Study participants diagnosed with erectile dysfunction (ED) and having a PDE-5 inhibitor and potentially-interacting ART co-dispensed within 30 days were included. DDIs were defined according to criteria found in published guidelines and drug information resources. The primary outcome of interest was overall PDE-5 inhibitor-mediated DDI prevalence and episode duration. A secondary logistic regression analysis was performed on those with and without DDIs to identify factors associated with initial DDI episode. RESULTS: A total of 235 male participants with ED met inclusion criteria. The majority were White (50.6%) or African American (40.4%). Median age at medication co-dispensing (45 years), duration of HIV infection (14 years), and duration of ED (1 year) did not differ between the two groups (p>0.05 for all). PDE-5 inhibitors included sildenafil (n = 124), vardenafil (n = 99), and tadalafil (n = 14). ART regimens included RTV-boosted protease inhibitors (PIs) atazanavir (n = 83) or darunavir (n = 34), and COBI-boosted elvitegravir (n = 43). Potential DDIs occurred in 181 (77.0%) participants, of whom 122 (67.4%) had multiple DDI episodes. The median DDI duration was 8 (IQR 1-12) months. In multivariate analyses, non-statistically significant higher odds of DDIs were observed with RTV-boosted PIs or PI-based ART (OR 2.13, 95% CI 0.85-5.37) and in those with a diagnosis of major depressive disorder (OR 1.74, 95% CI 0.83-3.64). CONCLUSIONS: PDE-5-mediated DDIs were observed in the majority of males with HIV infection on RTV- or COBI-boosted ART in our cohort. This study highlights the importance of assessing for DDIs among individuals on ART, especially those on boosted regimens.

Stratifying Therapeutic Enoxaparin Dose in Morbidly Obese Patients by BMI Class: A Retrospective Cohort Study.

BACKGROUND: Enoxaparin is a low-molecular weight heparin (LMWH) commonly used for treatment of venous thromboembolism and acute coronary syndromes. The recommended dose for these conditions is weight-based (1 mg/kg) and doesn't require dose-capping. However, previous studies have shown that in those with a body mass index (BMI) > 40 kg/m2, this dose results in supratherapeutic levels. OBJECTIVE: This study investigated enoxaparin dosing in morbidly obese patients with a goal of identifying a dose with the greatest chance of producing favorable anti-factor Xa (anti-Xa) levels. METHODS: This retrospective cohort study by electronic chart review was used to record data of patients who received enoxaparin with anti-Xa level monitoring between 2012 and 2017. The primary outcome was the enoxaparin dose that results in a therapeutic anti-Xa level (0.5-1.0 IU/mL) among three BMI groups. Secondary outcomes were bleeding and thromboembolic events. RESULTS: Two hundred forty-one patients were included in the study, and 132 achieved a therapeutic dose. For those with a BMI of 40-50 kg/m2, the median therapeutic dose was 0.97 mg/kg every 12 h. In subjects with a BMI of 50-60 kg/m2, the median therapeutic dose was 0.70 mg/kg. Finally, the median therapeutic dose for subjects with a BMI over 60 kg/m2 was 0.71 mg/kg. In all three groups, 53-65% of patients had a supratherapeutic anti-Xa level while less than 10% had a subtherapeutic level. Relatively few patients (4.1%) experienced major bleeding and only one thromboembolic event was reported. CONCLUSION: Standard dosing of enoxaparin in morbidly obese patients will most likely lead to supratherapeutic anti-Xa levels and thus further investigation is warranted to better determine appropriate dosing.