Supplementary appendix

Transcription

1 Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Mimoz O, Lucet J-C, Kerforne T, et al. Skin antisepsis with chlorhexidine alcohol versus povidone iodine alcohol, with and without skin scrubbing, for prevention of intravascular-catheter-related infection (CLEAN): an open-label, multicentre, randomised, controlled, two-by-two factorial trial. Lancet 2015; published online Sept 18.

2 Appendix This appendix is provided by the authors to give readers additional information about their work. The authors of the manuscript Skin antisepsis with chlorhexidine-alcohol versus povidone iodine-alcohol, with or without skin scrubbing, for prevention of catheter-related infection: an open-label, multicentre, randomised, controlled, two-by-two factorial trial (Prof Olivier Mimoz, Prof Jean-Christophe Lucet, Thomas Kerforne, Julien Pascal, Prof Bertrand Souweine, Lila Bouadma, Véronique Goudet, Prof Alain Mercat, Prof Sigismond Lasocki, Arnaud Friggeri, Serge Alfandari, Florent Wallet, Nicolas Allou, Stéphane Ruckly, Dorothée Balayn, Alain Lepape, and Prof Jean-François Timsit, on behalf of the Clean Study Group) assume responsibility for the integrity of the article and its supplementary appendix. 1

3 CLEAN collaborators Participating centres (all in France) and investigators (in alphabetical order) Poitiers, Centre Hospitalier et Universitaire la Milétrie (Dorothée Balayn, Séverin Cabasson, Bertrand Debaene, Céline Deletage, Véronique Goudet, Thomas Kerforne, Olivier Mimoz, René Robert, and Sabrina Seguin); Paris, Assistance Publique Hôpitaux de Paris (Nicolas Allou, Lila Bouadma, Lynda Lagha, Jean-Christophe Lucet, Philippe Montravers, Jean-François Timsit, and Michel Wolff); Clermont Ferrand, Centre Hospitalier et Universitaire (Mireille Adda, Jean-Michel Constantin, Julien Pascal, Bertrand Souweine, and Sandrine Thibault); Angers, Centre Hospitalier et Universitaire (Caroline François, Soizic Gergaud, Sigismond Lasocki, Alain Mercat, and Gwenaelle Soulard); Lyon, Hospices Civils (Severine Fournel, Arnaud Friggeri, Alain Lepape, Nathalie Panel, and Florent Wallet); Tourcoing, Centre Hospitalier (Serge Alfandari, Pierre-Yves Delannoy, Virginie Suffys, and Damien Thellier); OutcomeRea organisation, Paris, France (Stéphane Ruckly). 2

4 Table S1. Main outcome results when only cultured catheter cases were included in the analysis (n=4442 catheters) Antiseptic groups Chlorhexidine-alcohol group (n=2198) Povidone iodinealcohol group (n=2244) One-step or two-step groups Non-scrubbing group (n=2219) Scrubbing group (n=2223) Catheter-related infection 0 16 ( ), p= ( ), p= CR-BSI 0 21 ( ), p= ( ), p= Catheter colonisation 0 17 ( ), p< ( ), p= Values are hazard ratio (95% CI) for chlorhexidine-alcool vs povidone iodine-alcohol groups and non-scrubbing vs scrubbing groups. CR-BSI: Catheter-related bloodstream infection. 3

5 Table S2. Main microbiological outcomes per numbers of catheters Entire population (n=5159) Antiseptic groups Chlorhexidinealcohol group (n=2547) Povidone iodinealcohol group (n=2612) One-step or two-step groups Non-scrubbing group (n=2603) Scrubbing group (n=2556) Catheter-related infections* 45 (0 9%) 6 (0 2%) 39 (1 5%) 24 (0 9%) 21 (0 8%) Staphylococcus aureus 18/45 (40%) 3/6 (50%) 15/39 (38%) 12/24 (50%) 6/21 (29%) Coagulase-neg. staphylococci 11/45 (24%) 0/6 (0%) 11/39 (28%) 6/24 (25%) 5/21 (24%) Other Gram-positive cocci 4/45 (9%) 0/6 (0%) 4/39 (10%) 4/24 (17%) 0/21 (0%) Enterobacteriaceae 14/45 (31%) 1/6 (17%) 13/39 (33%) 6/24 (25%) 8/21 (38%) Pseudomonas spp. 3/45 (7%) 1/6 (17%) 2/39 (5%) 1/24 (4%) 2/21 (9%) Acinetobacter baumannii 2/45 (4%) 0/6 (0%) 2/39 (5%) 0/24 (0%) 2/21 (9%) Other Gram-negative bacilli 1/45 (2%) 0/6 (0%) 1/39 (3%) 0/24 (0%) 1/21 (5%) Candida sp. 1/45 (2%) 1/6 (17%) 0/39 (0%) 0/24 (0%) 1/21 (5%) Hazard ratio (95% CI) 0 15 ( ), p= ( ), p= Catheter-related bloodstream infection* 35 (0 7%) 6 (0 2%) 29 (1 1%) 17 (0 7%) 18 (0 7%) Staphylococcus aureus 17/35 (49%) 3/6 (50%) 14/29 (48%) 11/17 (65%) 6/18 (33%) Coagulase-neg. staphylococci 5/35 (14%) 0/6 (0%) 5/29 (17%) 2/17 (12%) 3/18 (17%) Other Gram-positive cocci 3/35 (9%) 0/6 (0%) 3/29 (10%) 3/17 (18%) 0/18 (%) Enterobactericeae 10/35 (29%) 1/6 (17%) 9/29 (31%) 3/17 (18%) 7/18 (39%) Pseudomonas spp. 3/35 (9%) 1/6 (17%) 2/29 (7%) 1/17 (6%) 2/18 (11%) Acinetobacter baumannii 1/35 (3%) 0/6 (0%) 1/29 (3%) 0/17 (0%) 1/18 (6%) Other Gram-negative bacilli 1/35 (3%) 0/6 (0%) 1/29 (3%) 0/17 (0%) 1/18 (6%) Candida sp. 1/35 (3%) 1/6 (17%) 0/29 (0%) 0/17 (0%) 1/18 (6%) Hazard ratio (95% CI) 0 21 ( ), p= ( ), p= Colonisation* 483 (9%) 71 (3%) 412 (15 8%) 255 (9 8%) 228 (8 9%) Staphylococcus aureus 32/483 (7%) 3/71 (4%) 29/412 (7%) 16/255 (6%) 16/228 (7%) Coagulase-neg. staphylococci 268/483 (55%) 22/71 (31%) 246/412 (60%) 148/255 (58%) 120/228 (53%) Other Gram-positive cocci 71/483 (15%) 13/71 (18%) 58/412 (14%) 44/255 (17%) 27/228 (12%) Enterobactericeae 107/483 (22%) 18/71 (25%) 89/412 (22%) 52/255 (20%) 55/228 (24%) Pseudomonas spp. 48/483 (10%) 14/71 (20%) 34/412 (8%) 23/255 (9%) 25/228 (11%) Acinetobacter baumannii 6/483 (1%) 1/71 (1%) 5/412 (1%) 1/255 (0%) 5/228 (2%) Other Gram-negative bacilli 13/483 (3%) 4/71 (6%) 9/412 (2%) 5/255 (2%) 8/228 (4%) Anaerobes 4/483 (1%) 1/71 (1%) 3/412 (1%) 4/255 (2%) 0/228 (0%) Candida sp. 16/483 (3%) 6/71 (8%) 10/412 (2%) 12/255 (5%) 4/228 (2%) Hazard ratio (95% CI) 0 18 ( ), p< ( ), p= Data are n (%) or n/n (%) *More than one micro-organism was recorded in some cases. Cox model was adjusted on patient-based and catheter-based parameters imbalanced between groups and (1) performance of scrubbing or not for comparison between antiseptic groups or (2) kind of antiseptic used for comparison between non-scrubbing and scrubbing groups. 4

6 Table S3. Results of semi-quantitative skin cultures at catheter removal by treatment group Entire population (n=3657) Antiseptic groups Chlorhexidine-alcohol group (n=1793) Povidone iodinealcohol group (n=1864) One-step or two-step groups Non-scrubbing group (n=1875) Scrubbing group (n=1782) Sterile 1125 (31%) 666 (37%) 459 (25%) 583 (31%) 542 (30%) 1 to 9 cfu 600 (16%) 363 (20%) 237 (13%) 298 (16%) 302 (17%) 10 to 49 cfu 544 (15%) 293 (16%) 251 (13%) 278 (15%) 266 (15%) 50 to 99 cfu 256 (7%) 119 (7%) 137 (7%) 131 (7%) 125 (7%) 100 cfu 1132 (31%) 352 (20%) 780 (42%) 585 (31%) 547 (31%) Values are n (%) ANOVA was used to test the effects of chlorhexidine-alcohol vs povidone iodine-alcohol, non-scrubbing vs scrubbing, and the interaction between the two study interventions. Results were significantly different for chlorhexidine-alcohol vs povidone iodine-alcohol groups (p<0 0001), and not significantly different for non-scrubbing vs scrubbing groups (p=0 8978). No significant interaction between the two study interventions was noted (p=0 0930). Cfu=colony-forming units 5

7 Table S4. Skin reactions classified using the International Contact Dermatitis Research Group scale, 1 by treatment group Entire population (n=2055) Antiseptic groups Chlorhexidinealcohol group (n=1044) Povidone iodinealcohol group (n=1011) One- vs two-step groups Non-scrubbing group (n=1033) Scrubbing group (n=1022) None 1726 (84%) 861 (82%) 865 (86%) 868 (84%) 858 (84%) Mild (Grade 1) 232 (11%) 127 (12%) 105 (10%) 116 (11%) 116 (11%) Moderate (Grade 2) 63 (3%) 29 (3%) 34 (3%) 31 (3%) 32 (3%) Severe (Grade 3) 34 (2%) 27 (3%) 7 (1%) 18 (2%) 16 (2%) Data are n (%) Data are per patient, among the 2055 patients with at least one dressing change. The worst grade per patient is reported. ANOVA was used to test the effects of chlorhexidine-alcohol vs povidone iodine-alcohol, non-scrubbing vs scrubbing, and the interaction between the two study interventions. Results were significantly different for chlorhexidine-alcohol vs povidone iodine-alcohol groups (p=0 0110), and not significantly different for non-scrubbing vs scrubbing groups (p=0 9554). No significant interaction between the two study interventions was noted (p=0 6211). Reference 1. Fowler J Jr, Taylor J, Storrs F, et al. Gold allergy in North America. Am J Contact Dermat 2001; 12: 3-5 6

8 Figure S1. Efficacy of skin antisepsis with chlorhexidine-alcohol vs povidone iodine-alcohol for prevention of catheter-related infection, catheter-related bloodstream infection, and catheter colonisation, in various subgroups. 7

9 P values <0 05 indicate a significant decrease in the outcome measure by the use of chlorhexidine-alcohol instead of povidone iodine-alcohol in the corresponding subgroup. SAPSII score=simplified Acute Physiology Score II 1 Site of venous catheters excludes haemodialysis catheters Reference 1. Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993; 270: