Population Decolonized and Decolonization Regimen

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1 Appendix Table 1a Characteristics Studies Evaluating a Bundle Including Decolonization and Glycopeptide Prophylaxis as a Means of Preventing Gram-Positive Surgical Site Infections First Author, Year, Location Study Design, Sample Size (n), Reviewed Publication? Study Dates Patient Screened For Number of Nasal S. aureus Carriers Decolonized and Decolonization Regimen Antimicrobial Agents Compared Outcome Definition and Assessment Mupirocin Resistance Gram-positive SSI RR (95% CI) a Jog 2008, Plymouth, UK Walsh 2011, Rochester, NY, Kim 2010, Boston, MA, Sporer 2011, Wheaton, IL, Acebedo 2009, (n=1,462), (n=5,262) (n=12,312) (n=4,873), t (n=1,981), 2004-Sept 2005; 2005-Sept Jan 2007; Period: Feb Jan 2010 Period: July 2006-Sept 2007; 2005-July 2006 Period: July Dec 2008; July 2009 Period: Aug Cardiothoracic PCR PCR group, 19/765 were group, 56/2,496 were group, 1,588/7,019 were and 309/7,019 were group 4.3% were 18% were t stated began 2% nasal until PCR results were known; if PCR was negative, was stopped; if PCR was positive, was continuee; topical triclosan for all received nasal c 1 day, 4 days postoperatively ; 2% nasal BID for 5 days; 2% CHG shower qd for 5 days ; 2% nasal for 5 days ; CHG bathing for all Only Teicoplanin and gentamicin carriers vs. flucloxacillin and gentamicin negative Vancomycin and carriers vs. negative Vancomycin carriers Vancomycin to carriers vs. for negative Vancomycin and Definition established by the English Health Protection Agency; infection control staff assessed SSI CDC definition; assessed by an infection prevention practitioner in consultation with an infectious disease specialist and with a cardiothoracic surgeon CDC definition; assessed by surgeons and infection control staff Purulent drainage from wound, note in medical record from surgeon stated that patient had an SSI SSI within 1 year; definition was not t stated 0.56 (0.23, 1.34) 10/12 randomly selected isolates from control period were susceptible to ; 10/10 randomly selected isolates from intervention period were susceptible to t stated 0.26 (0.13, 0.52) 0.41 b (0.21, 0.80) t stated 0.56 (0.29, 1.09) t stated 0.48 (0.21, 1.07)

2 Cincinnati, OH, Rao 2011, Pittsburgh, PA, t (n=2,181) 2004-Aug 2005; Period: Dec 2005-Dec Oct 2005; 2005-Oct 2007 on CHROM agar group 278/1440 were and 43/1440 were ; nasal c BID for 5 days; CHG qd for 5 days if positive or CHG qd 3 days if negative Only ; nasal c BID 5 days ; CHG qd for 5 days for carriers carriers vs. for negative Vancomycin for carriers or those with history of vs. for negative specified; assessed by infection control staff SSI within 1 year; definition was not specified; did not t stated 0.23 b (0.08, 0.67) Hadley 2010, New York, NY, (n=2,058) v June 2009 group, 351/1,644 were and 58/1,644 were ; 2% nasal for 5 days; CHG shower 1 day before the operation Vancomycin for carriers vs. or clindamycin for negative did not specify who made the assessment t stated 0.76 b (0.08, 7.24) a Some studies provided data on only S. aureus SSIs, not all Gram-positive SSIs; b These studies provided data on only S. aureus SSIs not all Gram-positive SSIs; c Percent not defined te:, quasi-experimental;, methicillin-resistant S. aureus;, methicillin-susceptible S. aureus; qd, daily; BID, two times a day; CHG, chlorhexidine; RR, relative risk; CI, confidence interval; BID, two times a day; PCR, polymerase chain reaction; CDC, Centers for Disease and Prevention; SSI, surgical site infection

3 Appendix Table 1b Characteristics of Studies Evaluating Nasal Decolonization as a Means of Preventing Gram-Positive Surgical Site Infections First Author, Year, Location Study Dates Patient Screened For Number of Nasal S. aureus Carriers Bundled? Study Design, Sample Size (n), Reviewed Publication? Randomized led Trials (RCT) Konvalinka 2006, Toronto, ON, Canada Perl 2002, Iowa City, IA, Segers 2006, Amsterdam, The Bode 2010, Rotterdam, The Double blinded RCT (n=257) Double blinded RCT (n=699) Double blinded RCT (n=954) Doubleblinded RCT (n=505) Mar Mar 2003 Apr Dec 1998 Aug Sept 2005 Oct June 2007 CABG or Valve and PCR 130 in group, 127 in placebo group 430 in group, 439 in placebo group; 6/1021 S. aureus isolates were resistant; 3/6 were from treated with placebo 321/954 were, 2/954 were. difference in colonization in the CHG and placebo groups 505 in - CHG group, 413 in placebo group Decolonized and Decolonization Regimen carriers; 2% nasal BID for 7 days All regardless of colonization; 2% nasal BID for up to 5 days All regardless of CHG QID then QID until nasogastric tube removed carriers; 2% nasal administration varied Yes, oral CHG Yes, CHG soap for S. aureus carriers randomized to Outcome Definition and Assessment Occurrence of 1 of the following within 8 weeks of the operation: the presence of exudate from the wound, the edges of the wound were erythematous beyond a 2 cm margin, the wound culture yielded a pathogen with signs of inflammation, or a physician stated in the medical record that the surgical site was infected as corroborated by one or more of the listed criteria; assessed by surgeon and researcher assessed by infection control staff and a researcher assessed by a researcher assessed by a researcher Mupirocin Resistance Short-term use did not select for resistant S. aureus 6/1021 S. aureus isolates were resistant, 3 of these were from treated with placebo Gram-positive SSI RR (95% CI) a 1.22 (0.34, 4.44) 0.80 b (0.34, 1.91) t stated 0.82 (0.53, 1.28) All strains were susceptible 0.14 b (0.04, 0.49)

4 decolonization to Kalmeijer 2002, Rotterdam, The Doubleblinded RCT (n=614) Observational studies Cimochowski 2001, Wilkes- (n=1,846) Barre, PA, Coskun 2005, Istanbul, Turkey Graf 2009, Hannover, Germany Kluytmans 1996, Dijkzigt, The Martorell 2004, Springfield, MA, Nicholson 2006, Cincinnati, OH, (n= 12,066) (n=308) (n=868) (n=935) (n=2,031) Jan July Oct 1996; Period: Dec 1997-Mar Dec v Sept 2007; 2007-Mar 2008 Period: Aug 1989-Feb 1991; Period: Mar 1991-Aug 1992 Period: ; Period: 9 months of Apr 2003; Period: Apr 2003-Sept 2004 Open Heart Cardiovascular Cardiothoracic CABG Cardiovascular t t (nasal, oral) t 95 in group, 86 in placebo group 126/472 in control group, 26/100 in t stated t stated 16.0% of ; 15.1% of control group t stated 222/1077 in the All regardless of colonization; 2.15% nasal BID; administration varied c 2 preoperative doses, BID for 5 days postoperatively c TID for 3 days Nasal ; did not specify who was decolonized or the dose of c c 1 dose, BID for 5 days postoperatively c for 3 days received 2% nasal 1 dose and BID until culture results were known, if culture was negative, was Yes, and decolonized healthcare workers Yes, CHG throat rinse and antiseptic body scrub, plus 14 item prevention bundle Yes, 1 day CHG bathing researcher utilized a standardized questionnaire to determine whether the wound met the SSI definition Modified CDC criteria; assessed by surgeons and/or infection control staff Did not Did not assessed by a researcher NNIS definitions; assessed by the surgeon and infection control staff CDC HICPAC definition; assessed by infection control staff All strains were susceptible to 1 strain from the intervention group was resistant t stated t stated Mupirocin resistant S. aureus not observed t stated t stated 0.59 b (0.20, 1.79) 0.31 (0.11, 0.82) 0.60 b (0.35, 1.02) 0.41 b (0.19, 0.86) 0.28 (0.11, 0.75) 0.27 b (0.08, 0.97) 0.22 b (0.07, 0.66)

5 Coskun 2004, Istanbul, Turkey Gernaat-van der Sluis 1998, Nijmegen, The Price 2008, Denver, CO, Hacek 2008, Evanston, IL, Sankar 2005, Worcestershire, UK Wilcox 2003, Leeds UK (n=3,249) (n=2,304) Cross sectional analysis (n=88) (n=1,495) (n=396) (n=4,120) 1999-Dec 2000, 2001-Dec 2003 Period: July 1992-July 1994; Period: Aug Jan 1996 Sept Sept 2005 Period: Feb 2003-July 2003; Period: Aug 2003-Feb Oct 2001; Period: Apr 2001-Oct Mar 1999; Period: Apr t t PCR t stated t stated 81/284 were and 5/284 were 223/912 in stopped, if culture was positive, was continued for a total of 14 doses c TID for 3 days c 3 doses carriers; 2% nasal for at least 6 doses ; nasal c BID for 5 days t stated Only carriers in the intervention group; nasal c t 28/74 were in the control period; 49/361 in the intervention period c 1 dose, 4 Yes, axilla and groin for, if positive provided povidone iodine or triclosan; if any site +, admission was delayed until 3 consecutive swabs were negative Yes, triclosan did not did not CDC definition; did not specify who made the assessment assessed by infection control staff and a researcher t defined; did not CDC NNIS criteria; microbiology lab ward liaison surveillance and surgeons t stated t stated Did not assess Tested for high-level resistance but results not stated 0.25 b (0.11, 0.58) 0.60 b (0.24, 1.49) 0.19 b (0.01, 3.86) 0.43 (0.19, 0.94) t stated 0.24 (0.01, 5.78) Low-level resistance was found in 2.3% (2/88) of S. aureus 0.17 b (0.08, 0.33)

6 1999-Mar 2001 times postoperatively isolates during control period, and in 4.2% (6/143) in intervention period (not significant) a Some studies provided data only on S. aureus SSIs, not all Gram-positive SSIs; b These studies provided data on only S. aureus SSIs not all Gram-positive SSIs; c Percent not defined te: RCT, randomized controlled trial;, quasi-experimental; RR, relative risk; CI, confidence interval; CABG, coronary artery bypass surgery, BID, two times a day; TID, three times a day; QID, four times a day;, methicillin-resistant S. aureus;, methicillin-susceptible S. aureus; PCR, polymerase chain reaction; CDC, Centers for Disease and Prevention; NNIS, National socomial Infection Surveillance System; NHSN, National Health Safety Network; HICPAC, Healthcare Infection Practices Advisory Committee; SSI, surgical site infection

7 Appendix Table 1c Characteristics of Studies Evaluating Glycopeptide Prophylaxis as a Means of Preventing Gram-Positive Surgical Site Infections First Author, Year, Study Location Study Design and Sample Size (n), Reviewed Publication? Study Dates Patient Bundle? Antimicrobial Agents Compared Outcome Definition and Assessment Randomized led Trials (RCT) Dhadwal 2007, Middlesex, UK Finkelstein 2002, Haifa, Israel Niederhäuser 1997, Zurich, Switzerland Saginur 2000, Canada Salminen 1999, Helsinki, Finland Vuorisalo 1998, Oulu, Finland Periti 1999, Italy Tyllianakis 2010, Rio-Patras, Greece (Hellas) Double-blinded RCT (n=186), RCT, t blinded (n=886), RCT, t blinded (n=55), Double-blinded RCT (n=3,027), RCT, t blinded (n=200), RCT, t blinded (n=884), Reviewed RCT, Outcome assessment blinded (n=826), RCT, t blinded (n=317), Observational Studies Pear 1998, (n=242), Tucson, AZ, Spelman 2002, Prahran, VIC, AUS Bull 2010, rth Melbourne, VIC, AUS (n=1,114), Retrospective cohort study (n=22,777), t June 2003-May 2004 Jan 1997-Dec 1999 Jan 1991-Jan 1994 t stated After May 1994 CABG CABG or Valve CABG or Valve CABG Oct 1989-July Hip and Knee Standard Care Period: Jan 1995-Dec 1995; Limited Vancomycin 1996-June 1996 Period: Feb 1999-Jan 2000; Period: Feb 2000-Jan 2001 t stated CABG CABG Surgery and Yes, CHG bathing Vancomycin and rifampin and gentamicin vs. cefuroxime Group 1: prolonged ticarcillin/ clavulante and vancomycin and vs. Group 2: Teicoplanin vs. ceftriaxone cefuroxime Teicoplanin vs cefuroxime Vancomycin +/- cefalosporin vs. cephalosporins Vancomycin and rifampin vs. beta-lactams CDC definition evaluated within 90 days; assessed by surgeons, infection control staff CDC definition; assessed by surgeons, infection control staff, and researchers CDC definition, did not the assessment Cellulitis with systemic signs of infection and/or purulent wound discharge within 30 days or 6 months; Deep SSI: drainage required; did not Gram-positive SSI RR (95% CI) a 0.46 (0.15, 1.40) 1.07 (0.69, 1.66) 0.30 (0.01, 7.02) 1.38 (0.99, 1.90) Purulent secretion; assessed by researcher 1.26 (0.29, 5.47) CDC definition; assessed by surgeons and infection control staff Hematoma with bacteriological evidence of infection on aspirate, inflammation or pain with purulent exudate, fever, leukocytosis, severe pain, increased erythrocyte sedimentation rate with leukocytes; did not specify who made Erythema, local pain, tenderness, drainage, possibly radiographic changes, fever/night sweats, dehiscence; did not 0.79 (0.36, 1.73) 1.01 (0.30, 3.48) 0.87 (0.21, 3.59) CDC definition; did not 0.62 (0.14, 2.71) CDC definition; assessed by infection control staff 0.05 b (0.01, 0.20) Definition and assessment not stated 1.29 (0.91, 1.82) Gupta 2011, Retrospective Jan Dec 2009 Surgery Yes, VA Vancomycin +/- CDC NHSN definition; assessed by infection control staff 0.92

8 Boston, MA, Merrer 2006, Paris, France Sewick 2012, Philadelphia, PA, Soriano 2006, Barcelona, Spain cohort study (n=990), Reviewed (n=258), Retrospective cohort study (n=1,828), (n=763), Mar 2004-Feb 2005 Sept 2008-Dec 2010 Cefuroxime 2002-May 2002; Cefuroxime+teicoplanin Period: Jun 2002-May 2003 and Femoral Neck Fracture Surgery prevention initiative other antimicrobial agent vs. a betalactam without vancomycin Cefazolin and vancomycin vs. vancomycin Hip Teicoplanin and cefuroxime vs cefuroxime CDC definition evaluated for 60 days; did not specify who made CDC definition; assessed by infection control staff CDC definition; did not (0.05, 15.93) 0.48 b (0.05, 4.53) 0.38 b (0.13, 1.07) 0.07 b (0.01, 0.58) a Some studies provided data on only S. aureus SSIs, not all Gram-positive SSIs; b These studies provided data on only S. aureus SSIs not all Gram-positive SSIs te:, methicillin-resistant S. aureus; RCT, randomized controlled trial;, quasi-experimental; RR, relative risk; CI, confidence interval; CDC, Centers for Disease and Prevention; NHSN, National Health Safety Network; VA, Veterans Administration; SSI, surgical site infection

Responders as percent of overall members in each category: Practice: Adult 490 (49% of 1009 members) 57 (54% of 106 members)

Responders as percent of overall members in each category: Practice: Adult 490 (49% of 1009 members) 57 (54% of 106 members) Infectious Diseases Society of America Emerging Infections Network 6/2/10 Report for Query: Perioperative Staphylococcus aureus Screening and Decolonization Overall response rate: 674/1339 (50.3%) physicians