Appendix 1. Search terms

Medline / 1."antibiotic prophylaxis"[MeSH] OR antibiotic prophylaxis [tiab] OR antimicrobial agent*[tiab] OR antimicrobial [tiab] OR antibiotic therapy [tiab] OR antibiotic*[tiab]
2."surgical wound Infection"[MeSH] OR surgical site infection*[tiab] OR SSI [tiab]OR SSIs [tiab]OR surgical wound infection*[tiab]OR surgical infection*[tiab]OR post-operative wound infection*[tiab]OR postoperative wound infection*[tiab]
3."time factors"[MeSH] OR timing [tiab]
Embase: / 4.surgical infection/ or (surgical site infection* or SSI or SSIs or surgical wound infection* or surgical infection* or post-operative wound infection* or postoperative wound infection*).ti,ab,kw.
5.exp prophylaxis/ or exp antibiotic prophylaxis/ or exp antibiotic agent/ or antibiotic*.mp. or antiinfective agent/ct, ad, iv, su
6.exp time/ or timing.ti,ab,kw.
7.1 and 2 and 3
Cochrane: / 1.wound infection:ti,ab,kw
2.surgical wound infection:ti,ab,kw
3.Time:ti,ab,kw
4.Timing:ti,ab,kw
5.Prophylaxis:ti,ab,kw
6.Antibiotic:ti,ab,kw
7.1 or 2
8.3 or 4
9.5 and 6 and 7 and 8
WHO regional medical databases: / 1.(ssi)
2.(surgical site infection)
3.(surgical site infections)
4.(Wound infection)
5.(Wound infections)
6.(postoperative wound infection)
7.(prophylaxis)(prohpylactic)
8.(antibiotic)
9.(antimicrobial)
10.(antiinfective)
11.(time)
12.(timing)
African Index Medicus / 1.infection [Key Word]
2.surgical [Key Word]
3.surgery [Key Word]
4.2 or 3
5.1 and 4

Appendix 2. Excluded studies

Reference: / Reason for exclusion:
Hollenbeak 20001 / No different timing groups compared / timing groups unclear*
Hawn 20132 / No different timing groups compared / timing groups unclear*
Hawn 20083 / No different timing groups compared / timing groups unclear*
Oh 20144 / Article did not asses an association between timing of pre-operative antibiotic prophylaxis and SSI
Junker 20125 / Irrelevant study type (i.e. conference abstract/narrative review/ survey)
Miliani 20096 / No different timing groups compared / timing groups unclear*
Lallemand 20027 / No different timing groups compared / timing groups unclear*
Walz 20068 / No different timing groups compared / timing groups unclear*
Butts 19979 / Irrelevant study type (i.e. conference abstract/narrative review/ survey)
Nishant 201310 / Study provided insufficient data for comparison
Misteli 201211 / Article did not asses an association between timing of pre-operative antibiotic prophylaxis and SSI
Montes 201412 / No different timing groups compared / timing groups unclear*
Norman 201313 / Irrelevant study type (i.e. conference abstract/narrative review/ survey)
Lee 201314 / No different timing groups compared / timing groups unclear*
Wang 201215 / Article did not asses an association between timing of pre-operative antibiotic prophylaxis and SSI
Akinyoola 201116 / Article did not asses an association between timing of pre-operative antibiotic prophylaxis and SSI
Soriano 200817 / Article did not asses an association between timing of pre-operative antibiotic prophylaxis and SSI
Matuschka 199618 / Irrelevant study type (i.e. conference abstract/narrative review/ survey)
Silver 199619 / Article did not asses an association between timing of pre-operative antibiotic prophylaxis and SSI
Keller 199620 / Article did not asses an association between timing of pre-operative antibiotic prophylaxis and SSI
Peterson 199021 / Article did not asses an association between timing of pre-operative antibiotic prophylaxis and SSI
Willemsen 200722 / Article did not asses an association between timing of pre-operative antibiotic prophylaxis and SSI
Sorenson 199223 / Irrelevant study type (i.e. conference abstract/narrative review/ survey)
Goede 201324 / Article did not asses an association between timing of pre-operative antibiotic prophylaxis and SSI
Turner Vosseler 201625 / Irrelevant study type (i.e. conference abstract/narrative review/ survey)
Wu 201426 / No different timing groups compared / timing groups unclear*

References

1.Hollenbeak CS, Murphy DM, Koenig S, Woodward RS, Dunagan WC, Fraser VJ. The clinical and economic impact of deep chest surgical site infections following coronary artery bypass graft surgery. Chest. 2000;118(2):397-402.

2.Hawn MT, Richman JS, Vick CC, et al. Timing of surgical antibiotic prophylaxis and the risk of surgical site infection. JAMA Surg. 2013;148(7):649-657.

3.Hawn MT, Itani KM, Gray SH, Vick CC, Henderson W, Houston TK. Association of timely administration of prophylactic antibiotics for major surgical procedures and surgical site infection. JAmCollSurg. 2008;206(5):814-819.

4.Oh AL, Goh LM, Nik Azim NA, Tee CS, Shehab Phung CW. Antibiotic usage in surgical prophylaxis: a prospective surveillance of surgical wards at a tertiary hospital in Malaysia. JInfectDevCtries. 2014;8(2):193-201.

5.Junker T, Mujagic E, Hoffmann H, et al. Prevention and control of surgical site infections: review of the Basel Cohort Study. SwissMedWkly. 2012;142:w13616.

6.Miliani K, L'Heriteau F, Astagneau P. Non-compliance with recommendations for the practice of antibiotic prophylaxis and risk of surgical site infection: results of a multilevel analysis from the INCISO Surveillance Network. JAntimicrobChemother. 2009;64(6):1307-1315.

7.Lallemand S, Thouverez M, Bailly P, Bertrand X, Talon D. Non-observance of guidelines for surgical antimicrobial prophylaxis and surgical-site infections. PharmWorld Sci. 2002;24(3):95-99.

8.Walz JM, Paterson CA, Seligowski JM, Heard SO. Surgical site infection following bowel surgery: a retrospective analysis of 1446 patients. Arch Surg. 2002;141(10):1014-1018.

9.Butts JD, Wolford ET. Timing of perioperative antibiotic administration. AORN J. 1997;65(1):109-115.

10.Nishant, Kailash KK, Vijayraghavan PV. Prospective randomized study for antibiotic prophylaxis in spine surgery: choice of drug, dosage, and timing. Asian Spine J. 2013;7(3):196-203.

11.Misteli H, Widmer AF, Weber WP, et al. Successful implementation of a window for routine antimicrobial prophylaxis shorter than that of the World Health Organization standard. InfectControl HospEpidemiol. 2012;33(9):912-916.

12.Montes CV, Vilar-Compte D, Velazquez C, Golzarri MF, Cornejo-Juarez P, Larson EL. Risk Factors for Extended Spectrum beta-Lactamase-Producing Escherichia coli versus Susceptible E. coli in Surgical Site Infections among Cancer Patients in Mexico. Surg Infect(Larchmt). 2014.

13.Norman BA, Bartsch SM, Duggan AP, et al. The economics and timing of preoperative antibiotics for orthopaedic procedures. JHospInfect. 2013;85(4):297-302.

14.Lee FM, Trevino S, Kent-Street E, Sreeramoju P. Antimicrobial prophylaxis may not be the answer: Surgical site infections among patients receiving care per recommended guidelines. AmJInfectControl. 2013;41(9):799-802.

15.Wang F, Chen XZ, Liu J, et al. Short-term versus long-term administration of single prophylactic antibiotic in elective gastric tumor surgery. Hepatogastroenterology. 2012;59(118):1784-1788.

16.Akinyoola AL, Adegbehingbe OO, Odunsi A. Timing of antibiotic prophylaxis in tourniquet surgery. JFoot Ankle Surg. 2011;50(4):374-376.

17.Soriano A, Bori G, Garcia-Ramiro S, et al. Timing of antibiotic prophylaxis for primary total knee arthroplasty performed during ischemia. ClinInfectDis. 2008;46(7):1009-1014.

18.Matuschka PR. Improving the timing of antimicrobial prophylaxis. AmJHealth SystPharm. 1996;53(15):1846, 1849.

19.Silver A, Eichorn A, Kral J, et al. Timeliness and use of antibiotic prophylaxis in selected inpatient surgical procedures. The Antibiotic Prophylaxis Study Group. AmJSurg. 1996;171(6):548-552.

20.Keller CE, Cobb AB, Moseley B. Timing of prophylactic antibiotics in selected surgical procedures. JMissState MedAssoc. 1995;36(6):166-167.

21.Peterson CD, Schultz NJ, Goldberg DE. Pharmacist monitoring of the timing of preoperative antibiotic administration. AmJHospPharm. 1990;47(2):384-386.

22.Willemsen I, van den Broek R, Bijsterveldt T, et al. A standardized protocol for perioperative antibiotic prophylaxis is associated with improvement of timing and reduction of costs. Journal of Hospital Infection.67(2):October.

23.Sorensen R. Preoperative antibiotics and time of administration. P and T.18(3):1993.

24.Goede WJ, Lovely JK, Thompson RL, Cima RR. Assessment of prophylactic antibiotic use in patients with surgical site infections. HospPharm. 2013;48(7):560-567.

25.Turner Vosseller J, Tantigate D, Jang E, et al. Timing of antibiotic prophylaxis for preventing surgical site infections in foot and ankle surgery. Foot and Ankle Surgery. 2016;1):57-58.

26.Wu W-T, Tai F-C, Wang P-C, Tsai M-L. Surgical site infection and timing of prophylactic antibiotics for appendectomy. Surgical Infections. 2014;15(6):781-785.

Appendix 3. Crude Data Meta-Analysis

A) Comparison 1: Administration of surgical antibiotic prophylaxis post- vs. pre- incision

B) Comparison 2: Administration of surgical antibiotic prophylaxis more than 120 minutes prior to incision vs. within 120 minutes prior to incision.

C) Comparison 3a: Administration of surgical antibiotic prophylaxis 120-60 minutes prior to incision vs. 60-0 minutes prior to incision.

D) Comparison 3b: Administration of surgical antibiotic prophylaxis 60-30 minutes prior to incision vs. 30-0 minutes prior to incision.

Appendix 4. Funnel plots

A) Comparison 1: Administration of surgical antibiotic prophylaxis post- vs. pre- incision

C) Comparison 3a: Administration of surgical antibiotic prophylaxis 120-60 minutes prior to incision vs. 60-0 minutes prior to incision.

*Crude unadjusted data were used in the meta analyses

B) Comparison 2: Administration of surgical antibiotic prophylaxis more than 120 minutes prior to incision vs. within 120 minutes prior to incision

D) Comparison 3b: Administration of surgical antibiotic prophylaxis 60-30 minutes prior to incision vs. 30-0 minutes prior to incision.