Correspondence
enhanced antimicrobial stewardship, or mupirocin use) were not introduced throughout their study.3 The World Medical Association’s Declaration of Helsinki4 states that “the benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best proven intervention(s) except for cases in which due to convincing and scientifically acceptable methodological reasons, the use of any intervention less effective than the best proven one, the use of placebo, or no intervention is necessary provided that the patients who receive any intervention less effective than the best proven one, placebo, or no intervention will not be subject to additional risks of serious or irreversible harm as a result of not receiving the best proven intervention.”4 Because in this study 60% of patients had endotracheal tubes and almost 70% had central venous catheters, the probable risks for patients of not receiving bundles for central-lineassociated bloodstream infection or ventilator-associated pneumonia seem to have been overlooked. Rights and interests of individual research participants should never be superseded by the prime purpose of medical research—ie, to yield new knowledge.4 We declare that we have no competing interests.
Samad E J Golzari, *Ata Mahmoodpoor [email protected]
Liver and Gastrointestinal Disease Research Center (SEJG) and Cardiovascular Research Center (AM), Tabriz University of Medical Sciences, Tabriz, Iran 1
2
3
4
372
Vincent JL, Rello J, Marshall J, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009; 302: 2323–29. Zilberberg MD, Shorr AF, Kollef MH. Implementing quality improvements in the intensive care unit: ventilator bundle as an example. Crit Care Med 2009; 37: 305–09. Derde LPG, Cooper BS, Goossens H, et al. Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial. Lancet Infect Dis 2014; 14: 31–39. World Medical Association Declaration of Helsinki—ethical principles for medical research involving human subjects. http:// www.wma.net/en/30publications/10policies/ b3/ (accessed April 4, 2014).
Authors’ reply
We thank Samad Golzari and Ata Mahmoodpoor for their interest and critical reading of our study about reducing antibiotic resistance in intensive care units. Our study was focused on reduction of the overall risk of transmission of antimicrobial-resistant bacteria, thereby aiming to reduce all infections acquired in intensive care units associated with these bacteria, including pneumonia and catheter-related infections. The point we made about care bundles and other interventions was that preventive practices other than the interventions assessed did not change during the study period. It does not imply that best practices, such as using care bundles, were not applied in participating centres. All participating units actually used best care according to national guidelines. Furthermore, ethics committees of all participating hospitals, undoubtedly familiar with the Declaration of Helsinki, approved the study after critically reviewing all aspects of the study protocol. We feel that patients received optimum care with our interventions, which substantially reduced acquisition of antimicrobial-resistiant bacteria (especially meticillinresistance Staphylococcus aureus), probably because of the high level of compliance achieved for hand hygiene and chlorhexidine bodywashing, both major components of patient safety and quality of care. Indeed, the overall quality of care achieved in the intensive care units participating in our study is supported by the fact that rates of meticillin-resistance S aureus and vancomycin-resistant enterococci bacteraemia were too low to allow meaningful statistical analyses. We declare that we have no competing interests.
Marc J M Bonten, Christian Brun-Buisson, Ben S Cooper, *Lennie P G Derde, on behalf of all authors [email protected]
Department of Medical Microbiology and Julius Center for Health Sciences and Primary Care (MB) and Department of Intensive Care Medicine (LD), University Medical Center Utrecht, Utrecht, Netherlands; Service de réanimation médicale and INSERM U657, Institut Pasteur, APHP GH Henri Mondor, Université Paris Est-Créteil, Creteil, France (CB-B); and Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK (BSC) 1
Derde LPG, Cooper BS, Goossens H, et al. Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial. Lancet Infect Dis 2014; 14: 31–39.
Imiquimod is not an effective drug for molluscum contagiosum In a Review of treatment options for molluscum contagiosum infection, Xiaoying Chen and colleagues 1 include imiquimod, citing three small randomised controlled trials and observational data as evidence of its effectiveness. They do not note that findings from two large, well designed, randomised trials (1494-IMIQ and 1495-IMIQ), completed in 2006 but to date unpublished, definitively showed that imiquimod does not effectively treat molluscum contagiosum in children. The two trials together enrolled 702 participants aged 2–12 years, of whom 470 were randomly assigned to imiquimod 5% cream. At week 18, imiquimod was no more effective than was vehicle-containing cream in clearing molluscum contagiosum (24% vs 26% in one study, 24% vs 28% in the other).2 In 2007, the prescribing information approved by the US Food and Drug Administration (FDA) for imiquimod was updated to incorporate results from these two trials as well as a companion pharmacokinetic study (1490-IMIQ), including a statement that the studies “failed to demonstrate efficacy”, and new safety concerns.2 www.thelancet.com/infection Vol 14 May 2014
enhanced antimicrobial stewardship, or mupirocin use) were not introduced throughout their study.3 The World Medical Association’s Declaration of Helsinki4 states that “the benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best proven intervention(s) except for cases in which due to convincing and scientifically acceptable methodological reasons, the use of any intervention less effective than the best proven one, the use of placebo, or no intervention is necessary provided that the patients who receive any intervention less effective than the best proven one, placebo, or no intervention will not be subject to additional risks of serious or irreversible harm as a result of not receiving the best proven intervention.”4 Because in this study 60% of patients had endotracheal tubes and almost 70% had central venous catheters, the probable risks for patients of not receiving bundles for central-lineassociated bloodstream infection or ventilator-associated pneumonia seem to have been overlooked. Rights and interests of individual research participants should never be superseded by the prime purpose of medical research—ie, to yield new knowledge.4 We declare that we have no competing interests.
Samad E J Golzari, *Ata Mahmoodpoor [email protected]
Liver and Gastrointestinal Disease Research Center (SEJG) and Cardiovascular Research Center (AM), Tabriz University of Medical Sciences, Tabriz, Iran 1
2
3
4
372
Vincent JL, Rello J, Marshall J, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009; 302: 2323–29. Zilberberg MD, Shorr AF, Kollef MH. Implementing quality improvements in the intensive care unit: ventilator bundle as an example. Crit Care Med 2009; 37: 305–09. Derde LPG, Cooper BS, Goossens H, et al. Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial. Lancet Infect Dis 2014; 14: 31–39. World Medical Association Declaration of Helsinki—ethical principles for medical research involving human subjects. http:// www.wma.net/en/30publications/10policies/ b3/ (accessed April 4, 2014).
Authors’ reply
We thank Samad Golzari and Ata Mahmoodpoor for their interest and critical reading of our study about reducing antibiotic resistance in intensive care units. Our study was focused on reduction of the overall risk of transmission of antimicrobial-resistant bacteria, thereby aiming to reduce all infections acquired in intensive care units associated with these bacteria, including pneumonia and catheter-related infections. The point we made about care bundles and other interventions was that preventive practices other than the interventions assessed did not change during the study period. It does not imply that best practices, such as using care bundles, were not applied in participating centres. All participating units actually used best care according to national guidelines. Furthermore, ethics committees of all participating hospitals, undoubtedly familiar with the Declaration of Helsinki, approved the study after critically reviewing all aspects of the study protocol. We feel that patients received optimum care with our interventions, which substantially reduced acquisition of antimicrobial-resistiant bacteria (especially meticillinresistance Staphylococcus aureus), probably because of the high level of compliance achieved for hand hygiene and chlorhexidine bodywashing, both major components of patient safety and quality of care. Indeed, the overall quality of care achieved in the intensive care units participating in our study is supported by the fact that rates of meticillin-resistance S aureus and vancomycin-resistant enterococci bacteraemia were too low to allow meaningful statistical analyses. We declare that we have no competing interests.
Marc J M Bonten, Christian Brun-Buisson, Ben S Cooper, *Lennie P G Derde, on behalf of all authors [email protected]
Department of Medical Microbiology and Julius Center for Health Sciences and Primary Care (MB) and Department of Intensive Care Medicine (LD), University Medical Center Utrecht, Utrecht, Netherlands; Service de réanimation médicale and INSERM U657, Institut Pasteur, APHP GH Henri Mondor, Université Paris Est-Créteil, Creteil, France (CB-B); and Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK (BSC) 1
Derde LPG, Cooper BS, Goossens H, et al. Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial. Lancet Infect Dis 2014; 14: 31–39.
Imiquimod is not an effective drug for molluscum contagiosum In a Review of treatment options for molluscum contagiosum infection, Xiaoying Chen and colleagues 1 include imiquimod, citing three small randomised controlled trials and observational data as evidence of its effectiveness. They do not note that findings from two large, well designed, randomised trials (1494-IMIQ and 1495-IMIQ), completed in 2006 but to date unpublished, definitively showed that imiquimod does not effectively treat molluscum contagiosum in children. The two trials together enrolled 702 participants aged 2–12 years, of whom 470 were randomly assigned to imiquimod 5% cream. At week 18, imiquimod was no more effective than was vehicle-containing cream in clearing molluscum contagiosum (24% vs 26% in one study, 24% vs 28% in the other).2 In 2007, the prescribing information approved by the US Food and Drug Administration (FDA) for imiquimod was updated to incorporate results from these two trials as well as a companion pharmacokinetic study (1490-IMIQ), including a statement that the studies “failed to demonstrate efficacy”, and new safety concerns.2 www.thelancet.com/infection Vol 14 May 2014
