b Piperacillin-tazobactam (PTZ) is frequently used as empirical and targeted therapy for Gram-negative sepsis. Time-dependent killing properties of PTZ support the use of extended-infusion (EI) dosing; however, studies have shown inconsistent benefits of EI PTZ treatment on clinical outcomes. We performed a retrospective cohort study of adult patients who received EI PTZ treatment and historical controls who received standard-infusion (SI) PTZ treatment for presumed sepsis syndromes. Data on mortality rates, clinical outcomes, length of stay (LOS), and disease severity were obtained. A total of 843 patients (662 with EI treatment and 181 with SI treatment) were available for analysis. Baseline characteristics of the two groups were similar, except for fewer female patients receiving EI treatment. No significant differences between the EI and SI groups in inpatient mortality rates (10.9% versus 13.8%; P ‫؍‬ 0.282), overall LOS (10 versus 12 days; P ‫؍‬ 0.171), intensive care unit (ICU) LOS (7 versus 6 days; P ‫؍‬ 0.061), or clinical failure rates (18.4% versus 19.9%; P ‫؍‬ 0.756) were observed. However, the duration of PTZ therapy was shorter in the EI group (5 versus 6 days; P < 0.001). Among ICU patients, no significant differences in outcomes between the EI and SI groups were observed. Patients with urinary or intra-abdominal infections had lower mortality and clinical failure rates when receiving EI PTZ treatment. We did not observe significant differences in inpatient mortality rates, overall LOS, ICU LOS, or clinical failure rates between patients receiving EI PTZ treatment and patients receiving SI PTZ treatment. Patients receiving EI PTZ treatment had a shorter duration of PTZ therapy than did patients receiving SI treatment, and EI dosing may provide cost savings to hospitals.T he current prevalence of multidrug-resistant (MDR) Gramnegative infections challenges clinicians to ensure appropriate and pharmacokinetically optimized antimicrobial therapy for patients with presumed Gram-negative infections (1-5). Piperacillin-tazobactam (PTZ) is frequently administered as empirical or targeted therapy for hospitalized patients who have risk factors for Pseudomonas aeruginosa or other MDR Gram-negative organisms.␤-Lactam antimicrobials, including PTZ, exhibit time-dependent killing properties, in which fractional time above the MIC is a critical factor determining pharmacological outcomes (6, 7). Monte Carlo simulations have been used to identify a higher probability of target attainment when PTZ is administered using extended infusion (EI) or continuous infusion (CI) for Gram-negative infections, including P. aeruginosa (8-12).EI and CI PTZ protocols have been adopted in many hospitals in an effort to optimize the effectiveness of PTZ treatment. However, clinical studies have shown inconsistent benefits of EI versus standard-infusion (SI) PTZ protocols, in terms of mortality rates, length of stay (LOS), and clinical outcomes. Many of those studies were limited by small sample sizes, exclusion of patients who d...

Background: Parameters within reconstitution, storage, stability, and administration may be optimized according to the unique pharmacokinetics of each antibiotic to ensure a successful desensitization. Objective: The study aims to evaluate the successfulness and safety of antibiotic desensitization protocols developed by the pharmacy department at our institution. Methods: A retrospective study was conducted at an 800-bed, urban, tertiary care, academic medical center. A total of 36 patients 18 years of age or older, admitted to our intensive care units between March 2013 and July 2017, who underwent antibiotic desensitization utilizing our pharmacy developed protocols were included. Results: In 36 patients, 61 desensitization cases were identified and included; 17 (47%) were male, 27 (75%) were Caucasian, and the median age was 55 years (range 19-94). In all, 15 different antibiotics were administered for desensitization, with meropenem (n = 12, 20%), ampicillin (n = 7, 11%), piperacillin/tazobactam (n = 7, 11%), and penicillin (n = 7, 11%) being the most common; 59 (97%) of 61 desensitizations were completed successfully with or without experiencing reactions, and 53 (89%) of the successful desensitization cases were completed without reactions. Two cases were categorized as anaphylaxis, which was severe enough to terminate the desensitization process. Of the 59 cases successfully completed, the 6 (10%) cases that experienced reactions were managed successfully during desensitization with completion of the process. Conclusion and Relevance: The findings suggest that our pharmacy-developed antibiotic desensitization protocols are successful and safe and may be adapted by other institutions.

Background: Midline catheters (MCs) have arisen as alternatives to peripherally inserted central catheters (PICCs) for both general intravenous therapy and extended outpatient parenteral therapy. However, there is a lack of data concerning the safety of medication therapy through midline for extended durations. Objective: The purpose of this study is to evaluate the safety of MCs for extended intravenous use. Methods: This was a retrospective cohort study evaluating patients who received intravenous therapy through an MC at a tertiary care academic medical center. The primary end point was the incidence of composite catheter-related adverse events that included local events, catheter dislodgment, infiltration, catheter occlusion, catheter-related venous thromboembolism, extravasation, and line-associated infection. Results: A total of 82 MC placements and 50 PICC placements were included; 50 MCs were for outpatient parenteral antimicrobial therapy, and 32 were for inpatient intravenous use. There were 21 complications per 1000 catheter-days in the outpatient group and 7 complications per 1000 catheter-days in the PICC group ( P = 0.91). The median time to complication in both groups was 8 days. The antimicrobial classes commonly associated with complications were cephalosporins, carbapenems, and penicillins. Conclusion and Relevance: Our results suggest that intravenous therapy with MCs is generally safe for prolonged courses that do not exceed 14 days as compared with PICC lines, which can be placed for months. There is still limited evidence for the use of MCs between 14 and 28 days of therapy. This study can help guide our selection of intravenous catheters for the purpose of outpatient antimicrobial therapy.

In one of the largest retrospective reviews of hospitalized patients who received full dose therapy with cefepime, ceftriaxone, and meropenem, the incidence of allergic reactions was low and reactions were mild. Cefepime, ceftriaxone, and meropenem can be considered for use in patients with a self-reported nontype I penicillin allergy.

Background Severe hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven. Objectives The primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure. Methods A multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit. Results The steroid-only, tocilizumab-only, and combination groups showed hazard reduction in mortality at 28 days when compared with supportive therapy. In a propensity-matched analysis, the combination group (daily equivalent dexamethasone 10 mg and tocilizumab 400 mg) had an improved 28-day mortality compared with the steroid-only group (daily equivalent dexamethasone 10 mg; hazard ratio (95% CI) = 0.56 (0.38-0.84), P = 0.005] without increasing the risk of infection. Conclusion and Relevance Combination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.