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1 Supplementary Online Content Schweizer ML, Chiang H-Y, Septimus E, Moody J, Braun B, Hafner J, et al. Association of a bundled intervention with surgical site infections among patients undergoing cardiac, hip, or knee surgery. JAMA. doi: /jama etable 1. Definition of Bundle Adherence eappendix 1. Details of Bundle Implementation and Measurement of Outcomes eappendix 2. Teaching status definition, American Hospital Association etable 2. International Classification of Diseases, Ninth Edition (ICD-9) Procedure Codes for Included etable 3. Monthly Rate of Complex S. aureus Surgical Site Infections efigure1. Number of Patients Receiving Each Bundle Component during the Intervention Period (Intention-to-Treat) This supplementary material has been provided by the authors to give readers additional information about their work.

2 etable 1: Definition of Bundle Adherence Scheduled MRSA Positive or MRSA Unknown MRSA Negative MRSA Negative Any MSSA status MSSA Positive MSSA ---- or Unknown Negative Full Received any CHG Received any Received any Adherence bathing, mupirocin CHG bathing, CHG bathing for 3 days, and mupirocin for 3 and vancomycin plus days, and Partial Received any CHG Received any Received any Adherence bathing, or any CHG bathing, or CHG bathing or mupirocin, or any mupirocin, or vancomycin or vancomycin plus No Did not receive Did not receive Received Adherence CHG bathing, CHG bathing, neither CHG mupirocin, or mupirocin, or bathing nor vancomycin or vancomycin plus a If the patient had confirmed beta-lactam allergy, use vancomycin in place of (cefuroxime). Note: CHG, chlorhexidine-gluconate Urgent or Emergent ---- Received any CHG bathing, mupirocin for 1 days, and vancomycin plus Received any CHG bathing, or any mupirocin, or vancomycin or vancomycin plus Did not receive CHG bathing, mupirocin, or vancomycin or vancomycin plus

3 eappendix 1: Details of Bundle Implementation and Measurement of Outcomes Participating hospital staff at each site filled out a survey regarding current use of bundle components at the site. During the pre-intervention period, all (20/20) requested that patients having elective procedures bathe with CHG for at least 1 day before their operations; 65% (13/20) bathed patients having emergent procedures with CHG for at least 1 day. All (20/20) of the hospitals screened patients for MRSA carriage; only 3 (15%) indicated PCR testing was used. Nine (45%) prescribed intranasal mupirocin for elective operations and 30% (6/20) treated patients having emergent operations with mupirocin. All sites used vancomycin prophylaxis for some patients. Nine (45%) used vancomycin only for patients with a known history of MRSA or allergy to penicillin or cephalosporin; the remainder stated vancomycin use varied by surgeon within the hospital. None of the hospitals used all components of the bundle in the preintervention period. Nine hospitals reported that they prescribed mupirocin to some surgical patients during the preintervention period. In the subgroup analysis of these 9 hospitals, the rates of complex S. aureus surgical site infections decreased significantly (rate ratio: 0.51; 95% confidence interval: 0.34, 0.78) during the intervention period. Eleven hospitals reported that they did not prescribe mupirocin for surgical patients during the pre-intervention period. In the subgroup analysis of these 11 hospitals, the rates of complex S. aureus surgical site infections decreased, but the decrease did not attain statistical significance (rate ratio: 0.65; 95% confidence interval: 0.29, 1.43). During the intervention period, CHG bathing was performed using one of the following products 2% CHG cloths (Sage products, Cary, IL, USA) or 4% CHG liquid (Hibiclens, Mölnlycke Health Care, Norcross, GA, USA) or 4% CHG sponge (Exidine, CareFusion, San Diego, CA). Patients were provided with instructions for CHG product application (Supplement 4). Mupirocin was provided as either generic mupirocin topical polyethylene glycol base or Bactroban ointment (Bactroban, GlaxoSmithKline). Hospital staff gave patients a compliance form on which to record their use of mupirocin and CHG and staff were instructed to enter this information into the electronic patient record. We retrospectively applied the 2013 NHSN definition to SSIs that occurred between 2009 and All hospitals performed in-hospital surveillance for SSI. Nineteen hospitals surveyed readmitted patients for SSIs, 19 included patients treated for SSIs at other hospitals, 18 contacted physicians offices to identify patients with SSIs, 15 received reports about patients who were treated as outpatients for SSIs, 14 received reports about patients with SSIs from long-term care facilities, and 1 hospital surveyed patients directly. We instructed sites to use the same surveillance and reporting practices during the pre-intervention and intervention periods to maintain consistency in reporting. Record-keeping processes, staff turnover among infection preventionists, and information management systems for the retrospective data varied across facilities. However, this was a pragmatic trial and these elements could not be controlled. Monthly coaching calls were used to educate sites and remind the staff about study-related adverse event forms and patient compliance forms. The study investigators validated sites NHSN SSI report forms and information shared by sites during monthly coaching calls to identify sites requiring additional support, education, and site visits.

4 eappendix 2: Teaching status definition, American Hospital Association Major Teaching Hospitals those with Council of Teaching (COTH) hospitals designation. Minor Teaching Hospitals those either Approved to participate in residency and/or internship training by the Accreditation Council for Graduate Medical Education (ACGME) or those with medical school affiliation reported to the American Medical Association. Non-Teaching Hospitals those without COTH, ACGME, or American Medical School (AMA) affiliation. (

5 etable 2: International Classification of Diseases, Ninth Edition (ICD-9) Procedure Codes for Included ICD-9 CM code Procedure description Cardiac Open heart valvuloplasty without replacement, unspecified valve Open heart valvuloplasty of aortic valve without replacement Open heart valvuloplasty of mitral valve without replacement Open heart valvuloplasty of pulmonary valve without replacement Open heart valvuloplasty of tricuspid valve without replacement Replacement of unspecified heart valve Replacement of aortic valve with tissue graft Other replacement of aortic valve, NOS Replacement of mitral valve with tissue graft Other replacement of mitral valve, NOS Replacement of pulmonary valve with tissue graft Other replacement of pulmonary valve, NOS Replacement of tricuspid valve with tissue graft Other replacement of tricuspid valve, NOS on papillary muscle on chordae tendineae Annuloplasty on other structures adjacent to valves of heart Repair of unspecified septal defect of heart with prosthesis Repair of atrial septal defect with prosthesis, open technique Repair of ventricular septal defect with prosthesis, open technique Repair of unspecified septal defect of heart with tissue graft Repair of atrial septal defect with tissue graft Repair of ventricular septal defect with tissue graft Other and unspecified repair of unspecified septal defect of heart, NOS Other and unspecified repair of ventricular septal defect Other operations on valves of heart (Aorto)coronary bypass of one coronary artery (Aorto)coronary bypass of two coronary arteries (Aorto)coronary bypass of three coronary arteries (Aorto)coronary bypass of four or more coronary arteries Single internal mammary-coronary artery bypass Double internal mammary-coronary artery bypass Abdominal - coronary artery bypass Other bypass anastomosis for heart revascularization Arthroplasty Resurfacing hip, total, acetabulum and femoral head

6 00.86 Resurfacing hip, partial, femoral head Resurfacing hip, partial, acetabulum Total hip replacement Partial hip replacement Total knee replacement

7 etable 3. Monthly Rate of Complex S. aureus Surgical Site Infections Admission Month Number of Hospitals Number of Number of Complex S. aureus SSI Pooled Rate, per 10,000 Mean Rate ± SD, per 10,000 Median Rate (Range), per 10,000 03/ a ± (0 909) 04/ a ± 23 0 (0 103) 05/ ± 58 0 (0 213) 06/ ± 0 0 (0 0) 07/ a ± 0 0 (0 0) 08/ a ± 42 0 (0 167) 09/ ± (0 1111) 10/ ± 86 0 (0 377) 11/ ± 97 0 (0 435) 12/ a ± (0 385) 01/ b ± (0 571) 02/ b ± (0 1000) 03/ b ± (0 1667) 04/ ± 33 0 (0 147) 05/ ± (0 377) 06/ b ± (0 1429) 07/ a ± 49 0 (0 217) 08/ ± 95 0 (0 357) 09/ ± (0 833) 10/ ± (0 303) 11/ b ± (0 556) 12/ ± 42 0 (0 189) 01/ b ± 36 0 (0 161) 02/ b ± (0 500) 03/ b ± 75 0 (0 299) 04/ ± (0 588) 05/ ± (0 1000) 06/ ± 22 0 (0 100) 07/ a ± 68 0 (0 270) 08/ ± 48 0 (0 159) 09/ a ± (0 417) 10/ ± (0 909) 11/ ± (0 1364) 12/ ± 31 0 (0 141) 01/ b ± (0 476) 02/ ± 92 0 (0 323) 03/ ± 39 0 (0 141) 04/ ± 25 0 (0 111) 05/ ± (0 909) Hospitals began implementing interventions in 6/ / ± (0 476) 07/ a ± 92 0 (0 370) 08/ a ± 50 0 (0 222) 09/ a ± (0 556) 10/ ± 0 0 (0 0) 11/ ± 27 0 (0 122) 12/ a ± 0 0 (0 0)

8 01/ b ± 0 0 (0 0) 02/ ± (0 870) 03/ a ± (0 333) 04/ b ± (0 435) 05/ a ± 0 0 (0 0) 06/ ± 0 0 (0 0) 07/ ± (0 526) 08/ a ± 50 0 (0 179) 09/ ± (0 588) 10/ b ± 24 0 (0 103) 11/ ± 0 0 (0 0) 12/ b ± 0 0 (0 0) 01/ b ± (0 1111) 02/ b ± 33 0 (0 145) 03/ ± 0 0 (0 0) a. Number of operations is less than the 25 th percentile. b. Number of operations is more than the 75 th percentile.

9 efigure1. Number of Receiving Each Bundle Component during the Intervention Period (Intention-to- Treat) a Includes patients whose surgeons did not implement the bundle. b Cefazolin or cefuroxime.

10 c Fully adherent among urgent/emergent operations defined as patient received both mupirocin ( 1 day) and prophylaxis with vancomycin and. d Among MRSA unknown, 1,924 (79.8%) were MSSA unknown, 376 (15.6%) were MSSA negative, and 111 (4.6%) were MSSA carriers. e Fully adherent among MRSA carriers or MRSA unknown defined as patient received CHG bathing, mupirocin for 3 days, and prophylaxis with vancomycin and. f Fully adherent among MSSA carriers or MSSA unknown (MRSA negative) defined as patient received CHG bathing, mupirocin for 3 days, and prophylaxis. g Fully adherent among S. aureus negative defined as patient received both CHG bathing and prophylaxis. Note: CHG, chlorhexidine gluconate; MSSA, methicillin-susceptible S. aureus; MRSA, methicillin-resistant S. aureus.