The prevalence of gram-negative bacteria with difficult-to-treat resistance and utilization of novel ß-lactam antibiotics in the southeastern United States.

Objective: To evaluate temporal trends in the prevalence of gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) in the southeastern United States. Secondary objective was to examine the use of novel ß-lactams for GNB with DTR by both antimicrobial use (AU) and a novel metric of adjusted AU by microbiological burden (am-AU). Design: Retrospective, multicenter, cohort. Setting: Ten hospitals in the southeastern United States. Methods: GNB with DTR including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp. from 2015 to 2020 were tracked at each institution. Cumulative AU of novel ß-lactams including ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, and cefiderocol in days of therapy (DOT) per 1,000 patient-days was calculated. Linear regression was utilized to examine temporal trends in the prevalence of GNB with DTR and cumulative AU of novel ß-lactams. Results: The overall prevalence of GNB with DTR was 0.85% (1,223/143,638) with numerical increase from 0.77% to 1.00% between 2015 and 2020 (P = .06). There was a statistically significant increase in DTR Enterobacterales (0.11% to 0.28%, P = .023) and DTR Acinetobacter spp. (4.2% to 18.8%, P = .002). Cumulative AU of novel ß-lactams was 1.91 ± 1.95 DOT per 1,000 patient-days. When comparing cumulative mean AU and am-AU, there was an increase from 1.91 to 2.36 DOT/1,000 patient-days, with more than half of the hospitals shifting in ranking after adjustment for microbiological burden. Conclusions: The overall prevalence of GNB with DTR and the use of novel ß-lactams remain low. However, the uptrend in the use of novel ß-lactams after adjusting for microbiological burden suggests a higher utilization relative to the prevalence of GNB with DTR.

Novel method of calculating adjusted antibiotic use by microbiological burden.

OBJECTIVE: To determine the usefulness of adjusting antibiotic use (AU) by prevalence of bacterial isolates as an alternative method for risk adjustment beyond hospital characteristics. DESIGN: Retrospective, observational, cross-sectional study. SETTING: Hospitals in the southeastern United States. METHODS: AU in days of therapy per 1,000 patient days and microbiologic data from 2015 and 2016 were collected from 26 hospitals. The prevalences of Pseudomonas aeruginosa, extended-spectrum ß-lactamase (ESBL)-producing bacteria, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) were calculated and compared to the average prevalence of all hospitals in the network. This proportion was used to calculate the adjusted AU (a-AU) for various categories of antimicrobials. For example, a-AU of antipseudomonal ß-lactams (APBL) was the AU of APBL divided by (prevalence of P. aeruginosa at that hospital divided by the average prevalence of P. aeruginosa). Hospitals were categorized by bed size and ranked by AU and a-AU, and the rankings were compared. RESULTS: Most hospitals in 2015 and 2016, respectively, moved ≥2 positions in the ranking using a-AU of APBL (15 of 24, 63%; 22 of 26, 85%), carbapenems (14 of 23, 61%; 22 of 25; 88%), anti-MRSA agents (13 of 23, 57%; 18 of 26, 69%), and anti-VRE agents (18 of 24, 75%; 15 of 26, 58%). Use of a-AU resulted in a shift in quartile of hospital ranking for 50% of APBL agents, 57% of carbapenems, 35% of anti-MRSA agents, and 75% of anti-VRE agents in 2015 and 50% of APBL agents, 28% of carbapenems, 50% of anti-MRSA agents, and 58% of anti-VRE agents in 2016. CONCLUSIONS: The a-AU considerably changes how hospitals compare among each other within a network. Adjusting AU by microbiological burden allows for a more balanced comparison among hospitals with variable baseline rates of resistant bacteria.

Role of Early De-escalation of Antimicrobial Therapy on Risk of Clostridioides difficile Infection Following Enterobacteriaceae Bloodstream Infections.

BACKGROUND: There is a paucity of data on the effect of early de-escalation of antimicrobial therapy on rates of Clostridioides difficile infection (CDI). This retrospective cohort study evaluated impact of de-escalation from antipseudomonal ß-lactam (APBL) therapy within 48 hours of Enterobacteriaceae bloodstream infections (BSIs) on 90-day risk of CDI. METHODS: Adult patients hospitalized for >48 hours for treatment of Enterobacteriaceae BSI at Palmetto Health hospitals in Columbia, South Carolina, from 1 January 2011 through 30 June 2015 were identified. Multivariable Cox proportional hazards regression was used to examine time to CDI in patients who received >48 hours or ≤48 hours of APBL for empirical therapy of Enterobacteriaceae BSI after adjustment for the propensity to receive >48 hours of APBL. RESULTS: Among 808 patients with Enterobacteriaceae BSI, 414 and 394 received >48 and ≤48 hours of APBL, respectively. Incidence of CDI was higher in patients who received >48 hours than those who received ≤48 hours of APBL (7.0% vs 1.8%; log-rank P = .002). After adjustment for propensity to receive >48 hours of APBL and other variables in the multivariable model, receipt of >48 hours of APBL (hazard ratio [HR], 3.56 [95% confidence interval {CI}, 1.48-9.92]; P = .004) and end-stage renal disease (HR, 4.27 [95% CI, 1.89-9.11]; P = .001) were independently associated with higher risk of CDI. CONCLUSIONS: The empirical use of APBL for >48 hours was an independent risk factor for CDI. Early de-escalation of APBL using clinical risk assessment tools or rapid diagnostic testing may reduce the incidence of CDI in hospitalized adults with Enterobacteriaceae BSIs.