Sarah C J Jorgensen1, Evan J Zasowski1,2, Trang D Trinh1,3, Abdalhamid M Lagnf1, Sahil Bhatia1, Noor Sabagha1, Jacinda C Abdul-Mutakabbir1, Sara Alosaimy1, Ryan P Mynatt4, Susan L Davis1,5, Michael J Rybak1,4,6. 1. Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA. 2. Department of Clinical Pharmacy, Touro University California College of Pharmacy, Vallejo, California, USA. 3. Department of Clinical Pharmacy, University of California San Francisco School of Pharmacy, San Francisco, California, USA. 4. Department of Pharmacy, Detroit Medical Center, Detroit, Michigan, USA. 5. Department of Pharmacy, Henry Ford Hospital, Detroit; and. 6. School of Medicine, Wayne State University, Detroit, Michigan, USA.
Abstract
BACKGROUND: Mounting evidence suggests the addition of a β-lactam (BL) to daptomycin (DAP) results in synergistic in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) and bolsters the innate immune response to infection. This study's objective was to provide clinical translation to these experimental data and determine if DAP+BL combination therapy results in improved clinical outcomes compared with treatment with DAP alone in patients with MRSA bloodstream infections (BSIs). METHODS: This was a retrospective, comparative cohort study conducted at 2 academic medical centers between 2008 and 2018. Adults with MRSA BSI treated with DAP for ≥72 hours and initiated ≤5 days of culture collection were included. Patients who received a BL for ≥24 hours and initiated ≤24 hours of DAP comprised the DAP+BL group. The primary outcome was composite clinical failure (60-day all-cause mortality and/or 60-day recurrence). Analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). RESULTS: A total of 229 patients were included (72 DAP+BL and 157 DAP). In unadjusted and IPTW-adjusted analyses, DAP+BL was associated with significantly reduced odds of clinical failure (odds ratio [OR], 0.362; 95% confidence interval [CI], .164-.801; adjusted OR, 0.386; 95% CI, .175-.853). Adjusted analyses restricted to prespecified subgroups based on infection complexity and baseline health status were consistent with the main analysis. CONCLUSIONS: The addition of a BL to DAP was associated with improved clinical outcomes in patients with MRSA BSI. This study provides support to ongoing and future studies evaluating the impact of combination therapy for invasive MRSA infections.Patients treated with daptomycin plus a β-lactam for MRSA bloodstream infection had lower odds of composite clinical failure defined as 60-day all-cause mortality and/or 60-day recurrence compared with patients treated with daptomycin monotherapy after adjusting for confounding variables using inverse probability of treatment weighting.
BACKGROUND: Mounting evidence suggests the addition of a β-lactam (BL) to daptomycin (DAP) results in synergistic in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) and bolsters the innate immune response to infection. This study's objective was to provide clinical translation to these experimental data and determine if DAP+BL combination therapy results in improved clinical outcomes compared with treatment with DAP alone in patients with MRSA bloodstream infections (BSIs). METHODS: This was a retrospective, comparative cohort study conducted at 2 academic medical centers between 2008 and 2018. Adults with MRSA BSI treated with DAP for ≥72 hours and initiated ≤5 days of culture collection were included. Patients who received a BL for ≥24 hours and initiated ≤24 hours of DAP comprised the DAP+BL group. The primary outcome was composite clinical failure (60-day all-cause mortality and/or 60-day recurrence). Analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). RESULTS: A total of 229 patients were included (72 DAP+BL and 157 DAP). In unadjusted and IPTW-adjusted analyses, DAP+BL was associated with significantly reduced odds of clinical failure (odds ratio [OR], 0.362; 95% confidence interval [CI], .164-.801; adjusted OR, 0.386; 95% CI, .175-.853). Adjusted analyses restricted to prespecified subgroups based on infection complexity and baseline health status were consistent with the main analysis. CONCLUSIONS: The addition of a BL to DAP was associated with improved clinical outcomes in patients with MRSA BSI. This study provides support to ongoing and future studies evaluating the impact of combination therapy for invasive MRSA infections.Patients treated with daptomycin plus a β-lactam for MRSA bloodstream infection had lower odds of composite clinical failure defined as 60-day all-cause mortality and/or 60-day recurrence compared with patients treated with daptomycin monotherapy after adjusting for confounding variables using inverse probability of treatment weighting.
Authors: Arnold S Bayer; Selvi C Ersoy; Warren E Rose; Ana M Bienvenida; Yan Q Xiong; Henry F Chambers Journal: Antimicrob Agents Chemother Date: 2020-02-21 Impact factor: 5.191
Authors: Sarah C J Jorgensen; Trang D Trinh; Evan J Zasowski; Abdalhamid M Lagnf; Samuel P Simon; Sahil Bhatia; Sarah M Melvin; Molly E Steed; Natalie A Finch; Taylor Morrisette; Sandy J Estrada; Joshua R Rosenberg; Susan L Davis; Michael J Rybak Journal: Antimicrob Agents Chemother Date: 2020-03-24 Impact factor: 5.191
Authors: Kyle C Molina; Taylor Morrisette; Matthew A Miller; Vanthida Huang; Douglas N Fish Journal: Antimicrob Agents Chemother Date: 2020-06-23 Impact factor: 5.191
Authors: Sara Alosaimy; Noor L Sabagha; Abdalhamid M Lagnf; Evan J Zasowski; Taylor Morrisette; Sarah C J Jorgensen; Trang D Trinh; Ryan P Mynatt; Michael J Rybak Journal: Infect Dis Ther Date: 2020-04-04
Authors: Courtney N Nichols; Lynn C Wardlow; Kelci E Coe; Mohammad Mahdee E Sobhanie Journal: Open Forum Infect Dis Date: 2021-06-22 Impact factor: 3.835