Importance: Adherence to quality-of-care indictors (QCIs) is associated with better Staphylococcus aureus bacteremia (SAB) outcomes. It is unknown whether clinical trial participation adventitiously improves QCI adherence and clinical outcomes compared with nontrial routine care for SAB.

Objective: To evaluate whether health care practitioners of trial participants with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia have better QCI adherence compared with practitioners of contemporaneous nontrial patients with MRSA bacteremia and whether QCI adherence or trial participation is associated with lower mortality.

Design, setting, and participants: This ad hoc, post hoc analysis of the Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Trial included 17 CAMERA2 hospital sites from 4 countries. The present study involved data collection mirroring the CAMERA2 case report forms from nontrial patients selected from sites' CAMERA2 screening logs. The newly collected data were analyzed with existing data from trial participants. Both groups of patients were diagnosed with MRSA bacteremia between August 2015 and July 2018. Statistical analyses were performed from September 2024 to February 2025.

Exposures: Nontrial vs trial participation, including health care practitioner adherence to 7 evidence-based QCIs (individually and collectively) for SAB management.

Main outcome and measures: All-cause 90-day mortality; the association of the exposures with this outcome was assessed using Cox proportional hazards regressions. Multiple sensitivity analyses were performed, including propensity score matching and exclusion of early deaths.

Results: This study included 722 participants (467 nontrial [64.7%] and 255 trial [35.3%]; mean [SD] age, 63.2 [18.4] years; 482 [66.8%] male). Demographics were comparable in the 2 study groups. Nontrial patients had a higher range of Charlson Comorbidity Index (median, 2.0 [range, 0-16.0] vs 2.0 [range, 0-13.0]; P < .001) and Pitt bacteremia score (median, 1.0 [range, 1.0-12.0] vs 1.0 [range, 1.0-7.0]; P < .001) compared with trial participants. Ninety-day mortality was not significantly different in the nontrial and trial groups (106 of 457 [23.2%] vs 48 of 251 [19.1%]; P = .25). Health care practitioners of nontrial patients had a lower mean (SD) number of adherent QCIs compared with practitioners of trial participants (3.90 [1.38] vs 4.28 [1.17]; P = .003). While increasing number of adherent QCIs was associated with lower 90-day mortality (adjusted hazard ratio [AHR], 0.73; 95% CI, 0.59-0.91; P = .005), adherence to QCIs individually was not associated with lower mortality. Study group (nontrial vs trial) was not associated with mortality (AHR, 1.08; 95% CI, 0.73-1.61; P = .68).

Conclusions and relevance: In this post hoc analysis of a randomized clinical trial, health care practitioners of trial participants had greater adherence to QCIs for MRSA bacteremia management compared with practitioners of nontrial patients. Trial participation was not associated with lower mortality.