Identifying Effective Durations of Antibiotic Therapy for the Treatment of Carbapenem-resistant Enterobacterales Bloodstream Infections: A Multicenter Observational Study.

In a propensity-score-weighted cohort of 183 adults with carbapenem-resistant Enterobacterales bacteremia at 24 US hospitals, patients receiving short courses of active therapy (7-10 days, median 9 days) experienced similar odds of recurrent bacteremia or death within 30 days as those receiving prolonged courses of active therapy (14-21 days, median 14 days).

Antibiotic Stewardship Interventions Improve Choice of Antibiotic Prophylaxis in Total Joint Arthroplasty in Patients with Reported Penicillin Allergies.

BACKGROUND: Most patients who report a penicillin allergy can tolerate cefazolin, the preferred prophylaxis in a total joint arthroplasty (TJA). Regardless, patients with a reported penicillin allergy are less likely to receive first-line perioperative antibiotics as a result of inaccurate penicillin allergy documentation and misconceptions regarding cross-reactivity between penicillin and cephalosporins. The over-reporting of penicillin allergies and the safety of cephalosporins in patients with reported penicillin allergies have been well established throughout the evidence [13]. QUESTIONS/PURPOSES: The study sought to answer two questions: (1) Do antibiotic stewardship interventions improve adherence to appropriate prophylactic antibiotic usage in patients with a documented penicillin allergy undergoing primary TJA? (2) What is the risk of allergic or adverse reactions secondary to cefazolin use in patients with a documented penicillin allergy? METHODS: This was a single-center, retrospective study of orthopaedic patients older than 18 years who underwent a primary elective TJA at a 261-bed community hospital. The study had two periods: the preintervention period ran from March 1, 2017 to August 30, 2017 and the postintervention period was from March 1, 2019 to August 30, 2019. A total of 396 patients with a history of a documented penicillin allergy underwent a THA or TKA during the study periods. After reviewing every fourth patient with a history of a documented penicillin allergy who met study inclusion criteria and excluding those patients who had a codocumented cephalosporin allergy, a total of 180 patients with a documented penicillin allergy were evaluated (90 patients in the preintervention group and 90 patients in the postintervention group). To answer our first study question, regarding whether antibiotic stewardship interventions improve adherence to appropriate prophylactic antibiotic usage in patients with a documented penicillin allergy undergoing primary TJA, we evaluated appropriate antibiotic usage pre- and postintervention. To answer our second study question, concerning the risk of allergic or adverse reactions secondary to cefazolin use in patients with a documented penicillin allergy, we reviewed signs of allergic reactions in patients who received cefazolin for a primary TJA and had a documented penicillin allergy. RESULTS: Postintervention antibiotic use was more appropriate (91% [82 of 90] versus 54% [49 of 90], risk ratio 1.67 [95% confidence interval 1.37 to 2.04]; p < 0.01), particularly in patients with nonsevere allergy (preintervention: 47% [36 of 76] versus postintervention: 96% [76 of 79]; p < 0.01). No patients had signs of an allergic reaction related to cefazolin, including eight patients with severe penicillin allergy. CONCLUSION: A multifaceted antibiotic stewardship intervention increased the appropriateness of antibiotic prophylaxis in elective primary TJA. Patients with nonsevere penicillin allergies, even those reporting hives or local swelling, tolerated cefazolin. Antibiotic stewardship interventions can be implemented across institutions to expand cephalosporin use in patients with a reported penicillin allergy within orthopaedic TJA patients. LEVEL OF EVIDENCE: Level III, therapeutic study.

Extended-Infusion ß-Lactam Therapy, Mortality, and Subsequent Antibiotic Resistance Among Hospitalized Adults With Gram-Negative Bloodstream Infections.

Importance: Current evidence is conflicting for associations of extended-infusion ß-lactam (EI-BL) therapy with clinical outcomes. Objective: To investigate the association of EI-BL therapy with survival, adverse events, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections (GN-BSI). Design, Setting, and Participants: This cohort study of consecutive adults with GN-BSI admitted to 24 United States hospitals between January 1, 2019, and December 31, 2019, receiving EI-BL were compared with adults with GN-BSI receiving the same agents as intermittent infusion ß-lactam (II-BL; ≤1-hour infusions). Statistical analysis was performed from January to October 2023. Exposures: EI-BL (ie, ≥3-hour infusion). Main Outcomes and Measures: EI-BL and II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to investigate outcomes, all censored at day 90. The primary outcome was mortality; secondary outcomes included antibiotic adverse events and emergence of resistance (≥4-fold increase in the minimum inhibitory concentration of the ß-lactam used to treat the index GN-BSI). Results: Among the 4861 patients included, 2547 (52.4%) were male; and the median (IQR) age was 67 (55-77) years. There were 352 patients in the EI-BL 1:3 PSM group, and 1056 patients in the II-BL 1:3 PSM group. Among 1408 PSM patients, 373 (26.5%) died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (ie, in the intermediate range for the antibiotic administered). There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66 [95% CI, 1.68-7.95]). Emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% vs 7.2%, respectively (P = .35). Conclusions and Relevance: In this cohort study of patients with GN-BSI, EI-BL therapy was associated with reduced mortality for patients with severe illness or those infected with nonsusceptible organisms; potential advantages in other groups remain unclear and need to be balanced with potential adverse events. The subsequent emergence of resistance warrants investigation in a larger cohort.

Impact of antimicrobial stewardship interventions on peripartum antibiotic prescribing in patients with penicillin allergy.

BACKGROUND: Beta-lactam antibiotics (eg, penicillins, cephalosporins, and carbapenems) are preferred for group B streptococcus prophylaxis, intra-amniotic infection, and cesarean surgical site infection prophylaxis. Non-beta-lactam alternatives are associated with inferior efficacy and contribute to higher rates of surgical site infection and longer lengths of stay. Most patients who report a penicillin allergy can tolerate penicillins without any adverse reaction. There are low rates of cross-reactivity between penicillins and other beta-lactams, including cephalosporins and carbapenems. Efforts to evaluate penicillin allergy and promote the use of beta-lactams are needed. OBJECTIVE: This study aimed to evaluate whether an antimicrobial stewardship intervention improved the use of first-line antibiotics for peripartum indications in patients with a reported penicillin allergy, following updates to institutional guidelines. STUDY DESIGN: This was a retrospective study of adult patients presenting for vaginal or cesarean delivery at 2 hospitals within a healthcare system. Patients received at least 1 dose of antibiotics for a peripartum indication between May 1, 2018, and October 31, 2018 (preintervention group) and May 1, 2020, to October 31, 2020 (postintervention group). The stewardship intervention bundle, which was implemented between March 2019 and April 2020, included updates to institutional antibiotic guidelines, reclassification of severe penicillin allergy, development of obstetrical prophylaxis and treatment order sets, promotion of allergy referral services, and establishment of a physician champion. The primary outcome was the composite rates of patients with reported penicillin allergy who received a preferred antibiotic for a peripartum indication. The secondary measures included maternal and neonatal outcomes. RESULTS: A total of 192 patients with a history of documented penicillin allergy were evaluated (96 patients in the preintervention group and 96 patients in the postintervention group). Hives were the most commonly reported index symptom in both groups (40/96 [41.7%] vs 39/96 [40.6%]; P=.883). After stewardship interventions, there was a significant increase in the rate of preferred antibiotic use (33/96 [34.3%] vs 81/96 [84.3%]; P<.001). The effect was the greatest in patients with nonsevere allergy (14/76 [18.4%] vs 68/82 [82.9%]; P<.001). There was no difference in the rates of postpartum endometritis, 30-day readmission, 90-day surgical site infection, or neonatal early-onset sepsis between the pre- and postintervention groups. Of note, 1 patient in the postintervention group experienced itching, and another patient developed a rash, both of which resolved with medical management. CONCLUSION: A comprehensive antibiotic stewardship intervention was associated with a 50% increase in the use of preferred antibiotics for peripartum indications in patients with penicillin allergy. Allergic reactions with first-line beta-lactams were minimal and manageable.