What’s new with Staph: Durations, Bundles and Combination Treatment

Reviewed by: Sonali Advani MBBS, MPH, Duke University School of Medicine; Rupak Datta MD, PhD, Yale School of Medicine, and Cynthia T. Nguyen, PharmD, University of Chicago Medicine

Three articles published this month discuss various aspects of Staphylococcus aureus bacteremia (SAB) including redefining durations of persistent bacteremia, using combination therapy for initial treatment of SAB, and the impact of an automated electronic health record (EHR) intervention.

Standard definitions for persistent SAB have not been established. Kang and colleagues propose definitions based on methicillin resistance and primary foci of infection using a multicenter retrospective design. Definitions for persistent SAB were based on the top quartile for duration of bacteremia after stratification based on above criteria. Among 1917 cases of SAB across 14 hospitals in the Republic of Korea, the durations of SAB were longer in patients with methicillin-resistant versus methicillin-susceptible SAB as well as patients with endocarditis, bone/ joint, endovascular, and surgical site infections. New definitions proposed for persistent SAB included 4 days for methicillin-sensitive SAB endocarditis, bone/joint, and endovascular infections versus 10 days for methicillin-resistant SAB for these same foci.  Notably, these definitions were associated with higher inpatient mortality (aOR 1.41; CI 1.01, 1.97) on multivariate analysis.   

McCreary and colleagues performed a multicenter, retrospective, matched cohort study to compare outcomes for methicillin-resistant S. aureus (MRSA) bacteremia among 58 patients who received daptomycin with ceftaroline (DAP-CPT) during treatment versus 113 patients who received standard-of-care (SOC), including vancomycin or daptomycin and any subsequent combination of antibiotics except DAP-CPT.  In the SOC group, 96% received vancomycin, and 56% escalated therapy at least once during treatment. In the DAP-CPT group, 24 received treatment within 72 hours of an index culture. There were two deaths within 30 days in the DAP-CPT group versus 16 deaths in the SOC group (p > 0.05). Patients receiving DAP-CPT with a Charlson Comorbidity Index of 3 or more, an endovascular source and receipt of DAP-CPT therapy within 72 hours of index culture demonstrated numerically lower mortality, according to a subgroup analysis. While this is a retrospective study with some inherent survivor bias in the combination arm, this is the first matched cohort to assess DAP-CPT combination therapy used as both initial and salvage therapy for MRSA bacteremia.

To evaluate the impact of an EHR intervention on SAB, Brotherton and colleagues conducted a single-center retrospective quasi-experimental study of a best practice advisory alert that would prompt physicians to use an electronic order set with management recommendations including infectious disease consultation upon detection of SAB. The primary outcome was adherence to an institutional SAB bundle. When comparing 111 patients in pre-intervention versus 116 in post-intervention group, adherence improved (29.7% versus 56.9%, p<0.001).  Notably, in the post-intervention group, order set utilization occurred in only 57.8% despite best practice advisory alert activation in 95.7%.  There was no difference in a composite outcome of 30-day mortality or 90-day readmission for SAB between groups.   

The management of SAB remains challenging. Understanding the natural history of disease, including the typical duration of SAB, may help identify high-risk patients who may benefit the most from combination therapy and management bundles.


  1. Kang CK, Song KH, Kim SE, et al. A Prospective Cohort Study of Durations of Staphylococcus aureus Bacteremia According to Different Phenotypes and a New Concept of Persistent Bacteremia.Antimicrob Agents Chemother. 2019 Dec 20;64(1). pii: e01656-19. https://doi.org/10.1128/AAC.01656-19 
  2. McCreary EK, Kullar R, Geriak M, et al. Multicenter Cohort of Patients With Methicillin-Resistant Staphylococcus aureus Bacteremia Receiving Daptomycin Plus Ceftaroline Compared With Other MRSA Treatments. Open Forum Infect Dis. 2019 Dec 31;7(1):ofz538. https://doi.org/10.1093/ofid/ofz538 
  3. Brotherton AL, Rab S, Kandiah S, et al. The impact of an automated antibiotic stewardship intervention for the management of Staphylococcus aureus bacteraemia utilizing the electronic health record. J Antimicrob Chemother. 2020 Jan 13. pii: dkz518. https://doi.org/10.1093/jac/dkz518
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