Empirical antimicrobial prescribing for pyelonephritis in patients discharged from 15 US Emergency Departments: an opportunity for improvement.

BACKGROUND: Urinary tract infections (UTIs) are commonly treated in the emergency department (ED), and unfortunately, resistance to first-line agents is increasing. OBJECTIVES: To characterize treatment of pyelonephritis in a nationally representative sample of ED patients and to identify patient- and treatment-specific factors associated with receiving initial inactive antibiotics. METHODS: We conducted a multicentre, observational cohort study utilizing the Emergency Medicine PHARMacotherapy Research NETwork (EMPHARM-NET), comprising 15 geographically diverse US EDs. All patients ≥18 years of age with a diagnosis of pyelonephritis between 2018 and 2020 were included. The primary endpoint was the proportion of patients who received initial inactive empirical antibiotic therapy and to identify predictive factors of inactive antibiotic therapy. RESULTS: Of the 3714 patients evaluated, 223 had culture-positive pyelonephritis. Median patient age was 50.1 years and patients were mostly female (78.3%). Overall, 40.4% of patients received an IV antibiotic, most commonly ceftriaxone (86.7%). The most frequently prescribed antibiotics were cefalexin (31.8%), ciprofloxacin (14.3%), cefdinir (13.5%) and trimethoprim/sulfamethoxazole (12.6%). Overall, 10.3% of patients received initial inactive therapy. After adjustment in a multivariable analysis, long-acting IV antibiotic was predictive of inactive therapy (OR 0.23, 95% CI 0.07-0.83). CONCLUSIONS: In our prospective, multicentre observational study, we found that only 40.4% of patients with pyelonephritis received empirical IV antibiotics in the ED, contributing to inactive therapy. Receipt of long-acting IV antibiotics was independently associated with a decreased rate of initial inactive therapy. This reinforces guideline recommendations to administer long-acting IV antibiotics empirically in the ED upon suspicion of pyelonephritis.

High prevalence of fluoroquinolone-resistant UTI among US emergency department patients diagnosed with urinary tract infection, 2018-2020.

BACKGROUND: Uropathogen resistance, fluoroquinolone-resistance (FQR), and extended spectrum beta-lactamase (ESBL), has been observed to be emerging worldwide with prevalences above recommended thresholds for routine empirical treatment. The primary aim of our study was to determine the prevalence of FQR from a geographically diverse sample of United States emergency departments (EDs). METHODS: We conducted a multi-center, observational cohort study using a network of 15 geographically diverse US EDs. All patients ≥18 years of age with the primary or secondary diagnosis of urinary tract infection (UTI) in the ED identified using International Classification of Diseases (ICD-10) diagnosis code of cystitis, pyelonephritis, or UTI from 2018 to 2020 were included. We calculated descriptive statistics for uropathogens and susceptibilities. Logistic regression analysis was used to identify antimicrobial resistance risk factors associated with FQR Escherichia coli. RESULTS: Among 3779 patients who met inclusion criteria, median age was 62.9 years (interquartile range [IQR]: 41-77.6) and 76.3% were female. The most common diagnoses were complicated (41.2%) and uncomplicated cystitis (40.3%). E. coli was the most common pathogen (63.2%), followed by Klebsiella pneumoniae (13.2%) and Enterococcus species (5.8%). Across all sites, overall E. coli FQ-resistance prevalence was 22.1%, ranging from 10.5 to 29.7% by site. The prevalence of ESBL-producing uropathogen was 7.4%, ranging from 3.6% to 11.6% by site. Previous IV or oral antimicrobial use in the past 90-days and history of a multi-drug resistant pathogen were associated with FQ-resistant E. coli (odds ratio [OR] 2.68, 95% confidence interval [CI]: 2.04-3.51, and OR 6.93, 95% CI: 4.95-9.70, respectively). Of the patients who had FQ-resistant E. coli or an ESBL-producing uropathogen isolated, 116 (37.1%) and 61 (36.7%) did not have any documented risk factors for resistance. CONCLUSION: FQ-resistant E. coli is widely prevalent across US sites highlighting the need for ongoing monitoring of antimicrobial resistance and, at some locations, modification of empirical treatments.

Daptomycin dosing in obese patients: analysis of the use of adjusted body weight versus actual body weight.

BACKGROUND: Food and Drug Administration-approved daptomycin dosing uses actual body weight, despite limited dosing information for obese patients. Studies report alterations in daptomycin pharmacokinetics and creatine phosphokinase elevations associated with higher weight-based doses required for obese patients. Limited information regarding clinical outcomes with alternative daptomycin dosing strategies in obesity exists. OBJECTIVE: This study evaluates equivalency of clinical and safety outcomes in obese patients with daptomycin dosed on adjusted body weight versus a historical cohort using actual body weight. METHODS: This retrospective, single center study compared equivalency of outcomes with two one-sided tests in patients with body mass index ⩾30 kg/m2 who received daptomycin dosed on actual body weight versus adjusted body weight. The primary outcome was clinical failure. Secondary outcomes included 90-day readmission and 90-day mortality. A combined safety endpoint included creatine phosphokinase elevation, patient-reported myopathy, and rhabdomyolysis. RESULTS: A total of 667 patients were screened for inclusion; 101 patients were analyzed with 50 in the actual body weight cohort and 51 in the adjusted body weight cohort. The two regimens were statistically equivalent for clinical failure (2% actual body weight versus 4% adjusted body weight; p < 0.001 for equivalency). The two regimens were also statistically equivalent for 90-day mortality (6% actual body weight versus 4% adjusted body weight; p = 0.0014 for equivalency). Limitations include single center, retrospective design, and sample size. Daptomycin dosing intensified throughout the study period. CONCLUSION: The two daptomycin dosing cohorts were statistically equivalent for both clinical failure and 90-day mortality. More data are needed to assess outcomes with higher (⩾8 mg/kg/day) daptomycin doses in this patient population.