- Email: [email protected]
Antibiotic sutures against surgical site infections
Correspondence
diseases. It will also enable quick follow-up trials of combinations of antivirals and new treatments that have already shown evidence of activity. A different type of RCT might also become an option once more than one drug has shown efficacy— even efficacy in animal models. Then, patients could ethically be randomised to one investigational drug or another. No-one would get only standard care. We accept that RCTs can generate strong evidence in ordinary circumstances; not, however, in the midst of the worst Ebola epidemic in history. The urgent need is to establish whether new investigational drugs offer survival benefits, and thus which, if any, should be recommended by WHO to save lives. We have innovative but proven trial designs for doing exactly that. We should be using them, rather than doggedly insisting on gold standards that were developed for different settings and purposes. We declare no competing interests.
Clement Adebamowo, Oumou Bah-Sow, Fred Binka, Roberto Bruzzone, Arthur Caplan, Jean-François Delfraissy, David Heymann, Peter Horby, Pontiano Kaleebu, Jean-Jacques Muyembe Tamfum, *Piero Olliaro, Peter Piot, Abdul Tejan-Cole, Oyewale Tomori, Aissatou Toure, Els Torreele, John Whitehead [email protected] National Health Research Ethics Committee, Abuja, Nigeria (CA); Hôpital National Ignace Deen, Conakry, Guinea (OB-S); University of Health and Allied Sciences, Ho, Ghana (FB); Hong Kong University-Pasteur Research Pole, School of Public Health, University of Hong Kong, Hong Kong, China (RB); New York University Langone Medical Center, New York, NY, USA (AC); Institut de Microbiologie et Maladies Infectieuses and INSERM, Paris, France (J-FD); Centre on Global Health Security, Chatham House, London, UK (DH); University of Oxford, Oxford, UK (PH); Medical Research Council, Uganda Virus Research Institute, Entebbe, Uganda (PK); Institut National de Recherche Biomedicale, Kinshasa, DR Congo (J-JMT); WHO, Geneva, Switzerland, and University of Oxford, Oxford, UK (PO); London School of Hygiene & Tropical Medicine, London, UK (PP); Open Society Initiative for West Africa, Dakar, Senegal (AT-C); Nigerian
1424
Academy of Science, Lagos, Nigeria (OT); Institut Pasteur Dakar, Dakar, Senegal (AT); Open Society Foundations, New York, NY, USA (ET); and Lancaster University, Lancaster, UK (JW)
*Claire Bayntun, Catherine Houlihan, John Edmunds
1
London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK
2
Wellcome Trust. Ebola treatment trials to be fast-tracked in West Africa. Sept 23, 2014. http://www.wellcome.ac.uk/News/Mediaoffice/Press-releases/2014/WTP057419.htm (accessed Oct 9, 2014). Joffe S. Evaluating novel therapies during the Ebola epidemic. JAMA 2014; 312: 1299–300.
Ebola crisis: beliefs and behaviours warrant urgent attention Why is this 25th outbreak of Ebola in Africa presenting an impending geopolitical crisis?1 This is the first recognised outbreak in the west Africa region; the communities are not familiar with Ebola virus. Health beliefs, cultural practices, and human behaviour have combined to fan the dispersal of the disease. The concerns of the west African people, the myths, and conspiracies need to be heard and understood before communities will sufficiently engage to reduce further spread. Civil unrest is a feature of this humanitarian disaster; suspicion and aggression towards health workers is widespread. 2 The US and British military are indeed best resourced to build field hospitals; but their arrival is being seen on the ground, by some, as an invasion. These fears need to be addressed. The socioeconomic collapse of the worst affected countries, already causing food insecurity, 3 could exacerbate the destructive effects of Ebola, and create violence. The delivery of effective infection control measures and health care will be challenging under the threat of regional conflict.4 This humanitarian disaster will deepen in spite of committed efforts of governments, unless we can understand and address the human beliefs and behaviours fuelling this crisis. We declare no competing interests.
[email protected]
1
2
3
4
Martin-Moreno JM, Ricciardi W, Bjegovic-Mikanovic V, Maguire P, McKee M. Ebola: an open letter to European governments. Lancet 2014; 384: 1259. BBC. Ebola: Guineans riot in Nzerekore over disinfectant. Aug 29, 2014. http://www.bbc. co.uk/news/world-africa-28984259 (accessed Oct 8, 2014). World Food Programme. Guinea: Assistance to Food insecure Ebola Victims, Households and Communities in Forest Guinea. http://www. wfp.org/content/guinea-assistance-foodinsecure-ebola-victims-households-andcommunities-forest-guinea (accessed Oct 7, 2014). International Crisis Group. Statement on Ebola and Conflict in West Africa. http://www. crisisgroup.org/en/publication-type/mediareleases/2014/africa/statement-on-ebola-andconflict-in-west-africa.aspx (accessed Sept 26, 2014).
Antibiotic sutures against surgical site infections Markus Diener and colleagues (July 12, p 142)1 might believe that the study protocol and sample size account for the conflicting findings in the PROUD trial 1 (not showing a prophylactic effect of triclosancoated sutures against surgical site infection [SSI]) and for findings from smaller randomised controlled trials 2–4 that show benefits for use in antibiotic sutures in prevention of SSI. However, the discrepancy might be more because of differences in baseline characteristics of participants. Antimicrobial effects of triclosancoated sutures seem to depend on the length of skin incision, extent of wound contamination at operation, and concurrent diseases amenable to infections, such as diabetes. In a single-centre randomised trial, 2 investigators reported triclosancoated sutures to be of slight benefit because they decreased the rate of SSIs after open colorectal surgery, but did not change infection www.thelancet.com Vol 384 October 18, 2014
rates after laparoscopic colorectal surgery. In another random ised trial, 3 856 patients were recruited and underwent several types of abdominal surgery. Triclosan-coated sutures had reduced the SSI rate after hepatopancreatobiliary surgery and colorectal surgery, whereas the incidence of SSIs after upper-gastrointestinal surgery and vascular surgery was not reduced. In a prospective study 5 that assessed the benefits for use of antibacterial sutures in many surgical steps, as wound contamination progressed and the number of established risk factors for nosocomial infections increased, additional benefits of antibacterial sutures were noted, including further reductions in SSI rates.5 To define a subset of patients who could benefit from antibiotic-coated sutures a subgroup analysis of the PROUD trial targeting high-risk groups is needed, but a selection bias might arise. I declare no competing interests.
Tetsuji Fujita [email protected] Department of Surgery, Jikei University School of Medicine, Tokyo 105-8461, Japan 1
2
3
4
5
Diener MK, Knebel P, Kieser M, et al. Effectiveness of triclosan-coated PDS Plus versus uncoated PDS II sutures for prevention of surgical site infection after abdominal wall closure: the randomised controlled PROUD trial. Lancet 2014; 384: 142–52. Nakamura T, Kashimura N, Niji T, et al. Triclosan-coated sutures reduce the incidence of wound infections and the costs after colorectal surgery: a randomized controlled trial. Surgery 2013; 153: 576–83. Justinger C, Slotta JE, Ningel S, Graber S, Kollmar O, Schilling MK. Surgical-site infection after abdominal wall closure with triclosan-impregnated polydioxanone sutures: results of a randomized clinical pathway facilitated trial (NCT00998907). Surgery 2013; 154: 589–95. Rasic Z, Schwarz D, Adam VN, et al. Efficacy of antimicrobial triclosan-coated polyglactin 910 (Vicryl* Plus) suture for closure of the abdominal wall after colorectal surgery. Coll Antropol 2011; 35: 439–43. Galal I, El-Hindawy K. Impact of using triclosan-antibacterial sutures on incidence of surgical site infection. Am J Surg 2011; 202: 133–38.
Authors’ reply We thank Tetsuji Fujita for his very insightful comments about our PROUD trial. 1 We followed his suggestion to look further into subgroups of all the patients in our trial, which then were comparable with the trial groups of the single-centre studies by Nakamura and colleagues, 2 Justinger and colleagues, 3 and the multicentre trial by Galal and El-Hindawy. 4 Results from these trials showed, in contrast with our PROUD trial, 1 a significantly reduced rate of surgical site infections (SSI) using triclosan-coated sutures. Nakamura and colleagues2 investigated 410 patients undergoing open and laparoscopic colorectal surgery and showed a non-significant benefit for coated sutures, although a slightly greater reduction in SSI was reported for patients who had open surgery. This non-significant benefit supports Fujita’s underlying hypothesis that triclosan-coated are better than uncoated sutures in special high-risk groups, such as in potential wound contamination after open colorectal surgery. Additionally, another monocentre trial by Justinger and colleagues 3 included 856 patients undergoing transverse and midline incisions for different indications, and identified a significant reduction of SSIs in the triclosan-coated group and colorectal surgery as an independent risk factor for SSI. As suggested by Fujita, we did additional analyses of the 1185 patients in PROUD 1 in the modified intention-to-treat set of the primary analysis. We have also
Colorectal Hepatopancreatobiliary Upper-gastrointestinal tract
analysed data for different organ related subgroups, but did not note any significant differences in the SSI rates in the colorectal or the hepatopancreatobiliary subgroup (table). However, we did note a significant reduction of SSI in the upper-gastrointestinal subgroup, a result which needs to be interpreted with caution because of the exploratory nature of these analyses for which no adjustment for multiplicity was done. We reassessed the effect of triclosan on SSIs in high-risk patients in an additional analysis of patients according to presence of risk factors for SSI, as defined by the US Centers for Disease Control and Prevention (CDC).5 There seems to be a trend towards an effect of triclosan in patients with accumulating risk factors, which, however, was in contrast with Galal and El-Hindawy4 non-significant result (appendix). As mentioned by Fujita, many potential baseline risk factors exist for SSI and these were all assessed prospectively in the PROUD trial as recommended by the CDC. 5 As a result, all baseline variables in our initial publication1 were entered into a logistic regression model, which identified extended multivisceral resections, malignant disease, missing antibiotic prophylaxis, chronic renal insufficiency, anaemia, and obesity as surgical and patient-related risk factors.1 In summary, we think that the conflicting (PROUD vs above-mentioned trials) results cannot be attributed to differences in baseline characteristics and still emphasise the need for large multicentre trials
Number Triclosan-coated sutures
Uncoated sutures
690
Science Photo Library
Correspondence
See Online for appendix
p value
62 of 344 (18·0%)
60 of 346 (17·3%)
0·814
74
4 of 34 (11·8%)
3 of40 (7·5%)
0·532
140
5 of 67 (7·5%)
15 of 73 (20·5%)
0·027
Table: Organ-related subgroup analysis for surgical site infection
www.thelancet.com Vol 384 October 18, 2014
1425
diseases. It will also enable quick follow-up trials of combinations of antivirals and new treatments that have already shown evidence of activity. A different type of RCT might also become an option once more than one drug has shown efficacy— even efficacy in animal models. Then, patients could ethically be randomised to one investigational drug or another. No-one would get only standard care. We accept that RCTs can generate strong evidence in ordinary circumstances; not, however, in the midst of the worst Ebola epidemic in history. The urgent need is to establish whether new investigational drugs offer survival benefits, and thus which, if any, should be recommended by WHO to save lives. We have innovative but proven trial designs for doing exactly that. We should be using them, rather than doggedly insisting on gold standards that were developed for different settings and purposes. We declare no competing interests.
Clement Adebamowo, Oumou Bah-Sow, Fred Binka, Roberto Bruzzone, Arthur Caplan, Jean-François Delfraissy, David Heymann, Peter Horby, Pontiano Kaleebu, Jean-Jacques Muyembe Tamfum, *Piero Olliaro, Peter Piot, Abdul Tejan-Cole, Oyewale Tomori, Aissatou Toure, Els Torreele, John Whitehead [email protected] National Health Research Ethics Committee, Abuja, Nigeria (CA); Hôpital National Ignace Deen, Conakry, Guinea (OB-S); University of Health and Allied Sciences, Ho, Ghana (FB); Hong Kong University-Pasteur Research Pole, School of Public Health, University of Hong Kong, Hong Kong, China (RB); New York University Langone Medical Center, New York, NY, USA (AC); Institut de Microbiologie et Maladies Infectieuses and INSERM, Paris, France (J-FD); Centre on Global Health Security, Chatham House, London, UK (DH); University of Oxford, Oxford, UK (PH); Medical Research Council, Uganda Virus Research Institute, Entebbe, Uganda (PK); Institut National de Recherche Biomedicale, Kinshasa, DR Congo (J-JMT); WHO, Geneva, Switzerland, and University of Oxford, Oxford, UK (PO); London School of Hygiene & Tropical Medicine, London, UK (PP); Open Society Initiative for West Africa, Dakar, Senegal (AT-C); Nigerian
1424
Academy of Science, Lagos, Nigeria (OT); Institut Pasteur Dakar, Dakar, Senegal (AT); Open Society Foundations, New York, NY, USA (ET); and Lancaster University, Lancaster, UK (JW)
*Claire Bayntun, Catherine Houlihan, John Edmunds
1
London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK
2
Wellcome Trust. Ebola treatment trials to be fast-tracked in West Africa. Sept 23, 2014. http://www.wellcome.ac.uk/News/Mediaoffice/Press-releases/2014/WTP057419.htm (accessed Oct 9, 2014). Joffe S. Evaluating novel therapies during the Ebola epidemic. JAMA 2014; 312: 1299–300.
Ebola crisis: beliefs and behaviours warrant urgent attention Why is this 25th outbreak of Ebola in Africa presenting an impending geopolitical crisis?1 This is the first recognised outbreak in the west Africa region; the communities are not familiar with Ebola virus. Health beliefs, cultural practices, and human behaviour have combined to fan the dispersal of the disease. The concerns of the west African people, the myths, and conspiracies need to be heard and understood before communities will sufficiently engage to reduce further spread. Civil unrest is a feature of this humanitarian disaster; suspicion and aggression towards health workers is widespread. 2 The US and British military are indeed best resourced to build field hospitals; but their arrival is being seen on the ground, by some, as an invasion. These fears need to be addressed. The socioeconomic collapse of the worst affected countries, already causing food insecurity, 3 could exacerbate the destructive effects of Ebola, and create violence. The delivery of effective infection control measures and health care will be challenging under the threat of regional conflict.4 This humanitarian disaster will deepen in spite of committed efforts of governments, unless we can understand and address the human beliefs and behaviours fuelling this crisis. We declare no competing interests.
[email protected]
1
2
3
4
Martin-Moreno JM, Ricciardi W, Bjegovic-Mikanovic V, Maguire P, McKee M. Ebola: an open letter to European governments. Lancet 2014; 384: 1259. BBC. Ebola: Guineans riot in Nzerekore over disinfectant. Aug 29, 2014. http://www.bbc. co.uk/news/world-africa-28984259 (accessed Oct 8, 2014). World Food Programme. Guinea: Assistance to Food insecure Ebola Victims, Households and Communities in Forest Guinea. http://www. wfp.org/content/guinea-assistance-foodinsecure-ebola-victims-households-andcommunities-forest-guinea (accessed Oct 7, 2014). International Crisis Group. Statement on Ebola and Conflict in West Africa. http://www. crisisgroup.org/en/publication-type/mediareleases/2014/africa/statement-on-ebola-andconflict-in-west-africa.aspx (accessed Sept 26, 2014).
Antibiotic sutures against surgical site infections Markus Diener and colleagues (July 12, p 142)1 might believe that the study protocol and sample size account for the conflicting findings in the PROUD trial 1 (not showing a prophylactic effect of triclosancoated sutures against surgical site infection [SSI]) and for findings from smaller randomised controlled trials 2–4 that show benefits for use in antibiotic sutures in prevention of SSI. However, the discrepancy might be more because of differences in baseline characteristics of participants. Antimicrobial effects of triclosancoated sutures seem to depend on the length of skin incision, extent of wound contamination at operation, and concurrent diseases amenable to infections, such as diabetes. In a single-centre randomised trial, 2 investigators reported triclosancoated sutures to be of slight benefit because they decreased the rate of SSIs after open colorectal surgery, but did not change infection www.thelancet.com Vol 384 October 18, 2014
rates after laparoscopic colorectal surgery. In another random ised trial, 3 856 patients were recruited and underwent several types of abdominal surgery. Triclosan-coated sutures had reduced the SSI rate after hepatopancreatobiliary surgery and colorectal surgery, whereas the incidence of SSIs after upper-gastrointestinal surgery and vascular surgery was not reduced. In a prospective study 5 that assessed the benefits for use of antibacterial sutures in many surgical steps, as wound contamination progressed and the number of established risk factors for nosocomial infections increased, additional benefits of antibacterial sutures were noted, including further reductions in SSI rates.5 To define a subset of patients who could benefit from antibiotic-coated sutures a subgroup analysis of the PROUD trial targeting high-risk groups is needed, but a selection bias might arise. I declare no competing interests.
Tetsuji Fujita [email protected] Department of Surgery, Jikei University School of Medicine, Tokyo 105-8461, Japan 1
2
3
4
5
Diener MK, Knebel P, Kieser M, et al. Effectiveness of triclosan-coated PDS Plus versus uncoated PDS II sutures for prevention of surgical site infection after abdominal wall closure: the randomised controlled PROUD trial. Lancet 2014; 384: 142–52. Nakamura T, Kashimura N, Niji T, et al. Triclosan-coated sutures reduce the incidence of wound infections and the costs after colorectal surgery: a randomized controlled trial. Surgery 2013; 153: 576–83. Justinger C, Slotta JE, Ningel S, Graber S, Kollmar O, Schilling MK. Surgical-site infection after abdominal wall closure with triclosan-impregnated polydioxanone sutures: results of a randomized clinical pathway facilitated trial (NCT00998907). Surgery 2013; 154: 589–95. Rasic Z, Schwarz D, Adam VN, et al. Efficacy of antimicrobial triclosan-coated polyglactin 910 (Vicryl* Plus) suture for closure of the abdominal wall after colorectal surgery. Coll Antropol 2011; 35: 439–43. Galal I, El-Hindawy K. Impact of using triclosan-antibacterial sutures on incidence of surgical site infection. Am J Surg 2011; 202: 133–38.
Authors’ reply We thank Tetsuji Fujita for his very insightful comments about our PROUD trial. 1 We followed his suggestion to look further into subgroups of all the patients in our trial, which then were comparable with the trial groups of the single-centre studies by Nakamura and colleagues, 2 Justinger and colleagues, 3 and the multicentre trial by Galal and El-Hindawy. 4 Results from these trials showed, in contrast with our PROUD trial, 1 a significantly reduced rate of surgical site infections (SSI) using triclosan-coated sutures. Nakamura and colleagues2 investigated 410 patients undergoing open and laparoscopic colorectal surgery and showed a non-significant benefit for coated sutures, although a slightly greater reduction in SSI was reported for patients who had open surgery. This non-significant benefit supports Fujita’s underlying hypothesis that triclosan-coated are better than uncoated sutures in special high-risk groups, such as in potential wound contamination after open colorectal surgery. Additionally, another monocentre trial by Justinger and colleagues 3 included 856 patients undergoing transverse and midline incisions for different indications, and identified a significant reduction of SSIs in the triclosan-coated group and colorectal surgery as an independent risk factor for SSI. As suggested by Fujita, we did additional analyses of the 1185 patients in PROUD 1 in the modified intention-to-treat set of the primary analysis. We have also
Colorectal Hepatopancreatobiliary Upper-gastrointestinal tract
analysed data for different organ related subgroups, but did not note any significant differences in the SSI rates in the colorectal or the hepatopancreatobiliary subgroup (table). However, we did note a significant reduction of SSI in the upper-gastrointestinal subgroup, a result which needs to be interpreted with caution because of the exploratory nature of these analyses for which no adjustment for multiplicity was done. We reassessed the effect of triclosan on SSIs in high-risk patients in an additional analysis of patients according to presence of risk factors for SSI, as defined by the US Centers for Disease Control and Prevention (CDC).5 There seems to be a trend towards an effect of triclosan in patients with accumulating risk factors, which, however, was in contrast with Galal and El-Hindawy4 non-significant result (appendix). As mentioned by Fujita, many potential baseline risk factors exist for SSI and these were all assessed prospectively in the PROUD trial as recommended by the CDC. 5 As a result, all baseline variables in our initial publication1 were entered into a logistic regression model, which identified extended multivisceral resections, malignant disease, missing antibiotic prophylaxis, chronic renal insufficiency, anaemia, and obesity as surgical and patient-related risk factors.1 In summary, we think that the conflicting (PROUD vs above-mentioned trials) results cannot be attributed to differences in baseline characteristics and still emphasise the need for large multicentre trials
Number Triclosan-coated sutures
Uncoated sutures
690
Science Photo Library
Correspondence
See Online for appendix
p value
62 of 344 (18·0%)
60 of 346 (17·3%)
0·814
74
4 of 34 (11·8%)
3 of40 (7·5%)
0·532
140
5 of 67 (7·5%)
15 of 73 (20·5%)
0·027
Table: Organ-related subgroup analysis for surgical site infection
www.thelancet.com Vol 384 October 18, 2014
1425