Bookstaver, P. Brandon

Cephalosporins have traditionally been administered as an intermittent infusion. With the knowledge that cephalosporins demonstrate a time-dependent pharmacodynamic profile, administration via continuous infusion may provide more effective antibiotic exposure for successful therapy. Proposed benefits of administration via continuous infusion include less IV manipulation, decreased potential for antibiotic resistance, and potential cost savings. The objective of this review was to provide a detailed assessment of available evidence for the use of continuous infusion cephalosporins and practical dosing and administration recommendations. Studies were gathered and assessed for inclusion via a literature search of PubMed and Ovid MEDLINE using mesh terms [“continuous infusion” and “cephalosporin”], “intermittent infusion”, [“intermittent versus continuous” and “cephalosporin”], “continuous infusion cephalosporin”, as well as specific drug names. References from included studies were also evaluated for inclusion. Data which compared the two administration methods (continuous infusion vs. intermittent infusion) were evaluated. Thirty-five studies were analyzed among several cephalosporins with variable delivery. Dosing regimens utilized in the selected studies were assessed with known compatibility and stability data and further summarized.

AbstractIntroductionLetters of recommendation (LORs) are important in pharmacy residency applications. Applicant gender, among other variables, may result in implicit biases that could impact LORs and/or residency attainment. This study hypothesized that LORs have linguistic gender differences in pharmacy residency applications.ObjectivesThe primary objective was to determine if gender‐linguistic differences exist in applicants' LORs. Gender was assessed via the pronouns utilized within the applications. The secondary outcome was to assess LOR linguistic and demographic differences between candidates who did and did not receive interviews.MethodsThis was a multiyear, multicenter study involving postgraduate year one (PGY1) applicants to participating pharmacy residency programs. Demographic data were extracted using the PhORCAS (Pharmacy Online Residency Centralized Application Service) WebADMIT (Admissions Management System) portal, and LORs were analyzed by validated linguistics processing software.ResultsA total of 7529 LORs and 2383 applicants (28.5% men, 71.5% women) were included. Women candidates had higher mean number of awards (4.71 vs. 4.1, p = 0.001) and leadership positions (4.87 vs. 4.48, p = 0.019). Compared with men candidates, women had statistically significantly higher levels of clout (p < 0.001), positive emotion (p = 0.01), social processes (p < 0.001), prosocial behavior (p = 0.002), and social referents (p < 0.001). Women also had lower authenticity compared with men candidates (p < 0.001). Two thousand and one hundred twenty applicants included in the secondary analysis found no difference in offer to interview between women and men candidates (odds ratio [OR] 1.173 [95% confidence interval (CI) 0.895–1.57], p = 0.247).ConclusionsMen and women applicants' LORS differed in specific linguistic variables, although offer to interview was not significantly different based on gender. LOR writers and programs should consider implicit biases that could affect residency offers to interview.

Abstract Background Multi-drug resistant (MDR) pathogens are a continuously evolving threat for which there are limited effective treatment modalities. Omadacycline (OMC) is a novel oral and intravenously administered aminomethylcycline with potent in-vitro activity against MDR gram-negative and gram-positive pathogens. Post-marketing data investigating its potential place in the antibiotic armamentarium is limited. This study aimed at describing the clinical success and tolerability of patients receiving OMC for various infections. Methods This was a multicenter, retrospective, observational study conducted from January 2020 to March 30, 2022. We included all patients ≥ 18 years of age that received OMC for any infection not related to Mycobacterium spp. for ≥72 hours. The primary outcome was clinical success at 30 days, defined as survival, the absence of persistence or re-emergence of infection during or after therapy, and the absence of escalation or alteration of OMC. Incidence of adverse effects while on OMC and reasons for OMC utilization were also analyzed. Results This analysis included 19 patients from 10 distinct academic centers. The median age was 50 years (IQR, 37-63), 58% were male, 63% were Caucasian, and the median APACHE II, Charlson and SOFA scores were 10 (IQR 5-12.5), 4 (IQR 2-6.3), and 1 (IQR 0 – 2.25), respectively. Most patients had a bone and joint (8/19, 42.1%) or intra-abdominal infections (4/19, 21.1%), all with positive cultures. Eight patients (44.1%) had a polymicrobial infection and 4 (22.2%) had bacteremia. The most common pathogens encountered were Carbapenem-resistant A. baumannii (5/19, 27.8%), E. coli (5/19, 27.8%), Vancomycin-resistant Enterococcus spp. (4/19, 22.2%), and K. pneumoniae (3/19, 16.7%). Clinical success was observed in 14 patients (74%) and 7 (36.8%) received combination therapy. Adverse drug reactions were reported in 3 patients (15.8%) and of those patients, none discontinued therapy. Reasons for prescribing OMC were mostly attributed to oral availability (12/14, 85.7%) and resistance to other agents (7/14, 50%). Conclusion OMC demonstrated clinical effectiveness and safety against a large number of MDR pathogens. More robust, prospective, comparative studies are needed to confirm our preliminary findings. Disclosures P. Brandon Bookstaver, PharmD, Spero Therapeutics: Advisor/Consultant.

Abstract Background Omadacycline (OMC) is an aminomethylcycline antibiotic in the tetracycline class that has been Food and Drug Administration-approved for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. OMC has been shown to have potent in vitro activity against a broad-spectrum of Gram-positive and Gram-negative organisms, as well as Nontuberculous Mycobacteria (NTM). Due to it’s unique activity and availability as an oral agent, off-label use of OMC has been increasing. We evaluated the real-world effectiveness and safety of OMC for a variety of infections. Methods This was a multicenter, retrospective, observational study that was conducted from January 2020 to June 2020. We included all patients ≥ 18 years of age that received OMC for ≥ 72 hours for any indication and/or pathogen. The primary outcome was clinical success, defined as a lack of 30-day (non-NTM) or 90-day (NTM) mortality or microbiologic recurrence and absence of therapy escalation or alteration. Reasons for OMC utilization and incidence of potential adverse effects attributable to OMC were also analyzed. Results A total of 18 patients were included from six geographically distinct academic health systems (median age: 56 (IQR, 49-60.5) years; 61% male; 72% Caucasian). The majority of OMC use was in NTM (61%; 100% Mycobacterium abscessus) and in Acinetobacter baumannii (22%) for bone/joint (39%) and respiratory tract (33%) infections. OMC was used primarily in the outpatient setting alone (83%) and most isolates did not have OMC susceptibility conducted (89%). Clinical success was reported in 83% of the total population (71% non-NTM and 91% NTM). The majority of patients were prescribed OMC due to antimicrobial resistance to previous antibiotic(s) (61%) and/or due to OMC’s availability as an oral agent (44%). Three patients experienced side effects while on therapy (serum creatinine elevation, AST/ALT increase, and gastrointestinal distress). Conclusion OMC appears to be effective and well-tolerated for a variety of infections caused by various pathogens, including M. abscessus and A. baumannii. Disclosures Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support)