Table 1.
Characteristics of Included Studies.
| Study | Methods | Surgery Type | Interventions | Outcomes | Results | Notes |
|---|---|---|---|---|---|---|
| Berry 1982 [17] |
Cluster randomised controlled trial Clustered by given day of surgery Single centre study |
Operations on biliary tract, large bowel, laparotomy, operations on hernia, genitalia, varicose veins and other ‘clean’ non-abdominal operations | Group A Povidone-iodine 10%in alcohol (n total = 413; included in trial analysis n = 413) Group B Chlorhexidine (‘Hibitane’) 0.5% in spirit (n total = 453; included in trial analysis n = 453) |
Wound infection defined as any wound abnormality at time of participant’s discharge as agreed by two observers. Wounds were judged at each inspection as fitting one or more of the following categories: normal, erythematous, oedematous, discharging or purulent. |
SSI Iodophor-alcohol 61/413 (14.8%) Chlorhexidine-alcohol 44/453 (9.7%) |
No sample size estimate provided Follow up: until discharge Data extracted from wound abnormalities at discharge (Table III in the publication by Berry et al.) based on participants with “any abnormality” No data provided on whether wound abnormalities were superficial, deep or organ/space |
| Broach 2017 [18] |
Randomised controlled trial Blinded Non-inferiority trial design Setting of study is not stated |
Elective clean-contaminated colorectal surgery | Group A 26 mL single use applicator containing iodine povacrylex [0.7% available iodine]/74% isopropyl alcohol (w/w) [“Duraprep”] (n total = 402; included in trial analysis n = 396) Group B 26 mL single-use applicator containing 2% chlorhexidine gluconate (w/v) and 70% isopropyl alcohol (v/v) [“ChloraPrep”]. (n total = 400; included in trial analysis n = 392) |
Surgical site infection at 30 days post discharge (±5 days) applying the CDC definition of superficial or deep surgical site infection. Cellulitis and organ/space SSI included as a secondary outcome measure |
SSI All SSI Iodophor-alcohol 90/396 (22.7%) Chlorhexidine-alcohol 82/392 (20.9%) Superficial SSI Iodophor-alcohol 46/396 (11.6%) Chlorhexidine-alcohol 40/392 (10.2%) Deep SSI Iodophor-alcohol 28/396 (7.1%) Chlorhexidine-alcohol 22/392 (5.6%) Organ space SSI Iodophor-alcohol 16/396 (4.0%) Chlorhexidine-alcohol 20/392 (5.1%) Cellulitis Iodophor-alcohol 19/396 (4.8%) Chlorhexidine-alcohol 14/392 (3.6%) Adverse reactions No adverse reactions (skin irritation/allergy) reported in either arm |
Sample size estimate provided For the analysis, organ space SSI included with data from primary outcome (superficial and deep SSI) Follow-up: 30 days ± 5 days |
| Cheng 2009 [19] |
Randomised controlled trial Single centre study |
Foot surgery including: metatarsal osteotomies for correction of hallux valgus deformity, removal of osteophytes from the first metatarsal and correction of lesser toe deformities | Group A alcoholic betadine (Ecolab Videne Alcoholic tincture, povidine-iodine 10% w/w (1% w/w available iodine)) (n total = 25; included in trial analysis n = 25) Group B alcoholic chlorhexidine (Ecolab Hydrex, clear Chlorhexidine gluconate 0.5% w/v in 70% v/v) (n total = 25; included in trial analysis n = 25) |
Number of bacterial colony forming units pre- and post-treatment with surgical site skin preparation taken from three sites (medial hallucal nail fold, interdigital web-spaces and the dorsal aspect of the first metatarsal phalangeal joint). Postoperative infection rate was reported as a secondary outcome. No definition for infection provided |
Positive cultures Iodine-alcohol: positive cultures prior to preparation 62, after 9 from 3 sites in 25 participants Chlorhexidine-alcohol: positive cultures prior to preparation 55, after 4 from 3 sites in 25 participants Postoperative infection No participant allocated to either iodine-alcohol or chlorhexidine developed a post-operative infection |
In addition to the skin preparation on the surgical site (the foot), the participant’s opposite foot (i.e., the foot not being operated upon) was scrubbed with a bristle brush for 3-min before the same preparation was applied. For the purposes of analysis, only data from the surgical site included. Sample size estimate provided Follow-up: not defined |
| Kesani 2019 [20] |
Randomised controlled trial Single centre study |
Caesarean section | Group A povidone iodine-alcohol (10% povidone-iodine and then with surgical spirit) (n total = 287; included in trial analysis n = 287) Group B chlorhexidine alcohol (2% chlorhexidine gluconate and 70% isopropyl alcohol) (n total = 273; included in trial analysis n = 273) |
SSI defined as per the CDC definitions. Superficial and deep SSI reported. | SSI All SSI Iodophor-alcohol 41/287 (14.3%) Chlorhexidine-alcohol 19/273 (7.0%) Superficial SSI Iodophor-alcohol 29/287 (10.1%) Chlorhexidine-alcohol 15/273 (5.5%) Deep SSI Iodophor-alcohol 12/287 (4.2%) Chlorhexidine-alcohol 4/273 (1.5%) No difference in microorganisms from cultured reported. |
Sample size estimate not provided Follow-up: 30 days postoperatively |
| Ngai 2015 [21] |
Randomised controlled trial Three-arm study Two centres |
Caesarean section | Group A povidone iodine-alcohol (concentrations not stated) (n total = 463; included in trial analysis n = 463) Group B chlorhexidine alcohol (concentrations not stated) (n total = 474; included in trial analysis n = 474) Group C combination of povidone iodine-alcohol (concentrations not stated) applied first followed by chlorhexidine alcohol (concentrations not stated) (n total = 467; included in trial analysis n = 467) |
Surgical site infection defined according to the CDC definition assessed at 2- and 6-weeks post-cesarean | SSI All SSI Iodophor-alcohol 21/463 (4.5%) Chlorhexidine-alcohol 21/474 (4.4%) Combination 18/467 (3.9%) Superficial SSI Iodophor-alcohol 16/463 (3.5%) Chlorhexidine-alcohol 15/474 (3.2%) Combination 15/467 (3.2%) Deep SSI Iodophor-alcohol 3/463 (0.6%) Chlorhexidine-alcohol 3/474 (0.4%) Combination 1/467 (0.2%) Organ space Iodophor-alcohol 2/463 (0.4%) Chlorhexidine-alcohol 3/474 (0.6%) Combination 2/467 (0.4%) |
Analysis included data for participants administered povidone iodine-alcohol or chlorhexidine alcohol arms. Data from the combination arm with povidone iodine-alcohol followed by chlorhexidine alcohol excluded from analysis Sample size estimate provided Follow-up: 30 days postoperatively |
| Ostrander 2005 [22] |
Randomised controlled trial Three-arm study Single centre study |
Foot and ankle surgery | Group A “DuraPrep” [0.7% available iodine/74% isopropyl alcohol (w/w)] (n total = 40; included in trial analysis n = 40) Group B “Techni-Care” [3.0% chloroxylenol] (n total = 40; included in trial analysis n = 40) Group C “ChloraPrep” [2% chlorhexidine gluconate (w/v) and 70% isopropyl alcohol (v/v)]. (n total = 40; included in trial analysis n = 40) |
Number of bacterial colonies forming units pre- and post-treatment with surgical site skin preparation: specimens collected from three sites: tibia, 12 cm proximal to the ankle Joint (labelled as control), hallucal nail fold (labelled as hallux), web spaces between the second and third and between the fourth and fifth digits (labelled as toe site). Postoperative infection rate was reported as a secondary outcome. No definition for infection provided |
Positive cultures Iodophor-alcohol: 65% of hallux cultures positive, 45% of toe cultures and 23% of control cultures positive in 40 participants Chlorhexidine-alcohol: 30% of hallux cultures positive, 23% of toe cultures and 10% of control cultures positive in 40 participants Chloroxylenol: 95% of hallux cultures positive, 98% of toe cultures and 35% of control cultures positive in 40 participants Postoperative infections Iodophor-alcohol 0/40 (0%) Chlorhexidine-alcohol 1/40 (2.5%) Chloroxylenol: 2/40 (5.0%) |
All procedures performed by one surgeon Analysis included data for participants administered DuraPrep [0.7% available iodine/74% isopropyl alcohol] or ChloraPrep [2% chlorhexidine gluconate/70% isopropyl alcohol] arms. Data from the Techni-Care (3.0% chloroxylenol) arm excluded from analysis. Sample size not met Follow-up: not defined |
| Peel 2019 [23] |
Cluster randomised controlled trial Clustered by given day of surgery Single centre study |
Elective hip or knee arthroplasty | Group A 1% iodine (w/v) in 70% ethanol (v/v) (n total = 390; included in trial analysis n = 390) Group B 0.5% chlorhexidine gluconate (w/v) in 70% ethanol (v/v) (n total = 390; included in trial analysis n = 390) |
Primary outcome: superficial wound complication (composite of superficial incisional SSI and/or clinically significant wound ooze) Secondary outcome: SSI (superficial incisional SSI and/or prosthetic joint infection (PJI) based on the CDC definition |
SSI Superficial and prosthetic joint infection (PJI) Iodophor-alcohol 4/390 (1.0%) Chlorhexidine-alcohol 12/390 (3.1%) Superficial SSI Iodophor-alcohol 3/390 (0.9%) Chlorhexidine-alcohol 4/390 (1.1%) Prosthetic joint infection Iodophor-alcohol 2/390 (0.6%) Chlorhexidine-alcohol 7/390 (2.0%) Superficial wound complication (composite of wound ooze and superficial SSI) Iodophor-alcohol 15/390 (3.8%) Chlorhexidine-alcohol 19/390 (4.9%) Wound Ooze Iodophor-alcohol 13/390 (3.3%) Chlorhexidine-alcohol 15/390 (3.8%) Adverse reactions No adverse reactions (skin irritation/allergy) reported in either arm |
Sample size provided Follow-up: 30 days for primary outcome and 365 days for secondary outcome 90 Protocol violations observed. Sensitivity analysis with per-protocol and as-treated analysis |
| Rodrigues 2013 [24] |
Randomised controlled trial Single centre study |
Abdominal and thoracic surgery with subcostal abdominal, vertical abdominal and thoracic incision. | Group A 10% hydroalcoholic povidone-iodine (n total = 102; included in trial analysis n = 102) Group B 0.5% alcoholic chlorhexidine (n total = 103; included in trial analysis n = 103) |
Diagnosis for SSI based on clinical, microbiological and radiological findings. Definition maps to the CDC definition for SSI. Diagnosis of SSI required at least one of the following signs: fever, without other apparent cause, pain, heat, swelling, or confluent erythema around the incision and extrapolating the boundaries of the wound, pus in the incision site or in the deep soft tissue, or in organ/cavity handled during operation; presence of abscesses or, in the case of deep tissues, histological or radiological evidence suggestive of infection; isolated microorganism from theoretically sterile source or harvested with aseptic technique from a previously closed site, and spontaneous dehiscence of deep tissues. |
SSI All SSI Iodophor-alcohol 7/102 (6.7%) Chlorhexidine-alcohol 11/103 (10/7%) Superficial SSI Iodophor-alcohol 5/102 (4.9%) Chlorhexidine-alcohol 9/103 (8.7%) Deep SSI Iodophor-alcohol 1/102 (1.0%) Chlorhexidine-alcohol 2/103 (1.9%) Organ space Iodophor-alcohol 1/102 (1.0%) Chlorhexidine-alcohol 0/103 (0%) |
Sample size not provided Follow-up: 30 days |
| Saltzman 2009 [25] |
Randomised controlled trial Three-arm study Single centre study |
Shoulder surgery including shoulder arthroplasty (n = 4) | Group A “DuraPrep” [0.7% iodophor and 74% isopropyl alcohol] (n total = 50; included in trial analysis n = 50) Group B “ChloraPrep” [2% chlorhexidine gluconate and 70% isopropyl alcohol]. (n total = 50; included in trial analysis n = 50) Group C povidone-iodine scrub and paint [0.75% iodine scrub and 1.0% iodine paint] (n total = 50; included in trial analysis n = 50) |
Rate of positive microbiological cultures pre- and post-treatment with surgical site skin preparation. Postoperative infection rate was reported as a secondary outcome. No definition for infection provided |
Positive cultures Iodophor-alcohol: 19% of cultures were positive in 50 participants Chlorhexidine-alcohol: 7% of cultures were positive in 50 participants Aqueous-based iodophor: 31% of cultures were positive in 50 participants Postoperative infections No postoperative infections developed in any intervention arm |
All surgery performed by three surgeons Analysis included data for participants administered DuraPrep or ChloraPrep arms. Data from the povidone-iodine scrub and paint arm excluded from analysis. Sample size provided Follow-up: 10 months minimum |
| Savage 2012 [26] |
Randomised controlled trial Single centre study |
Lumbar spine surgery, including: microdisectomy, posterior spinal fusion with or without an associated interbody fusion decompression, kyphoplasty | Group A “DuraPrep” [0.7% iodophor and 74% isopropyl alcohol] (n total = 50; included in trial analysis n = 50) Group B “ChloraPrep” [2% chlorhexidine gluconate and 70% isopropyl alcohol]. (n total = 50; included in trial analysis n = 50) |
Rate of positive microbiological cultures pre- and post-treatment with surgical site skin preparation. Postoperative infection rate was reported as a secondary outcome. No definition for infection provided |
Positive cultures Iodophor-alcohol: 80% of cultures positive pre-preparation, 6% positive post-preparation, 32% positive post-closure in 50 participants Chlorhexidine-alcohol: 84% of cultures positive pre-preparation, 0% positive post-preparation, 34% positive post-closure in 50 participants Postoperative infection Iodophor-alcohol 0/50 (0%) Chlorhexidine-alcohol 1/50 (2.0%): All classed as superficial |
All surgery performed by four surgeons Sample size provided Follow-up: 6 months minimum |
| Tuuli 2016 [27] |
Randomised controlled trial Single centre study |
Caesarean section | Group A chlorhexidine–alcohol combination [2% chlorhexidine gluconate with 70% isopropyl alcohol] (n total = 575; included in trial analysis n = 575) Group B iodine–alcohol combination [8.3% povidone–iodine with 72.5% isopropyl alcohol] (n total = 572; included in trial analysis n = 572) |
Superficial or deep SSI based on the CDC/National Healthcare Safety Network definitions | SSI All SSI Iodophor-alcohol 42/575 (7.3%) Chlorhexidine-alcohol 23/572 (4.0%) Superficial SSI Iodophor-alcohol 28/575 (4.9%) Chlorhexidine-alcohol 17/572 (3.0%) Deep SSI Iodophor-alcohol 14/575 (2.4%) Chlorhexidine-alcohol 6/572 (1.0%) Adverse reactions Iodophor-alcohol 4/575 (0.7%) Chlorhexidine-alcohol 2/572 (0.3%) In a post hoc analysis, the use of healthcare resources did not differ intervention arms |
Sample size provided Follow-up: 30 days |
| Veiga 2008 [29] |
Randomised controlled trial Single centre study |
Elective and clean plastic surgery procedures including: breast surgery, abdominoplasty, scar revision, zetaplasty, lipoma excision | Group A alcohol solution of povidone- iodine 10% (n total = 125; included in trial analysis n = 125) Group B alcohol solution of chlorhexidine 0.5% (n total = 125; included in trial analysis n = 125) |
Primary outcome was quantitative skin cultures before and after surgical site skin preparation. Surgical site infection was a secondary outcome, defined according to the CDC definition |
Colony-forming units (standard deviation) Iodophor-alcohol: 75.4 (115.9) colony-forming units pre-preparation, 1.3 (5.7) colony-forming units 2-min after preparation, 17.6 (64.7) colony-forming units at end of surgery in 125 participants Chlorhexidine-alcohol: 93.8 (127.3) colony-forming units pre-preparation, 0.3 (1.3) colony-forming units 2-min after preparation, 7.8 (46.1) colony-forming units at end of surgery in 125 participants SSI Postoperative infection Iodophor-alcohol 4/125 (03.2%) Chlorhexidine-alcohol 0/125 (0%) All classed as superficial |
Study authors reported four infections (in 125 participants) in the iodophor-alcohol intervention arm calculated as 3.2%. The study authors however reported this proportion as “1.6%” (equating to 2 infections in 125 participants). Given this discrepancy, for the analysis, the number of events was transcribed as 4 infections. Sample size not provided Follow-up: 30 days |
| Xu 2017 [28] |
Randomised controlled trial Three arm trial Single centre study |
Elective clean soft tissue hand surgery (e.g., carpal tunnel release, trigger finger, de Quervain release, mass excision or excision ganglion cyst) | Group A “DuraPrep” [0.7% iodophor and 74% isopropyl alcohol] (n total = 81; included in trial analysis n = 81) Group B “ChloraPrep” [2% chlorhexidine gluconate and 70% isopropyl alcohol]. (n total = 79; included in trial analysis n = 79) Group C “Betadine solution” [10% povidone-iodine] (n total = 80; included in trial analysis n = 80) |
Rate of positive microbiological cultures pre- and post-treatment with surgical site skin preparation. Postoperative infection rate was reported as a secondary outcome. Postoperative infection defined as defined as need for antibiotics or surgical intervention. |
Positive cultures Iodophor-alcohol: cultures positive in 24 of 81 participants (29.6%) pre-preparation and 3 of 81 participants (3.7%) post-preparation Chlorhexidine-alcohol: cultures positive in 32 of 79 participants (40.5%) pre-preparation and 21 of 79 participants (26.6%) post-preparation Aqueous-iodophor: cultures positive in 35 of 80 participants (43.8%) pre-preparation and 1 of 80 participants (1.3%) post-preparation SSI Postoperative infections Iodophor-alcohol 1/81 (1.2%) Chlorhexidine-alcohol 2/79 (2.5%) Aqueous-iodophor 1/80 (1.3%) All classed as superficial |
Number of participants allocated to intervention arms differs across Figure 1, Table 2 and in text. For the purposes of the analysis, the number of participants has been transcribed keeping with Figure 1 (Consort flow diagram). Analysis included data for participants administered DuraPrep or ChloraPrep arms. Data from the Betadine solution arm excluded from analysis. Sample size provided Follow-up: 42 days |