Editorial Opinion

lected environmental surfaces and S aureus contamination of that surface; however, self-reported cleaning may poorly reflect actual cleaning practices in the household. Their study10 did identify some important potential reservoirs of contamination, including bed sheets, television remote controls, and hand towels. To our knowledge, there are no controlled studies that have explored the independent effect of household cleaning on reducing recurrent MRSA colonization or infection. Many studies have recommended environmental cleaning in combination with decolonization, yet recurrent infection rates remain high in these studies.6,8 Anecdotally, most clinicians encourage families to clean their household environment while undergoing decolonization therapy. Considerations for decoloARTICLE INFORMATION Author Affiliations: Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Hospital Epidemiology and Infection Control, Johns Hopkins Hospital, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland. Corresponding Author: Aaron M. Milstone, MD, MHS, Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, 200 N Wolfe St, Rubenstein 3141, Baltimore, MD 21287 ([email protected]). Published Online: September 8, 2014. doi:10.1001/jamapediatrics.2014.1260. Conflict of Interest Disclosures: None reported. REFERENCES 1. Moran GJ, Krishnadasan A, Gorwitz RJ, et al; EMERGEncy ID Net Study Group. Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med. 2006;355(7):666-674. 2. Milstone AM, Goldner BW, Ross T, Shepard JW, Carroll KC, Perl TM. Methicillin-resistant Staphylococcus aureus colonization and risk of subsequent infection in critically ill children: importance of preventing nosocomial

nization of pets have been described elsewhere,9 but no data support routine treatment or removal of pets from households of children with recurrent SSTIs. A prospective controlled study is needed to determine whether a contaminated environment increases the risk of recurrent infections or whether infected children simply contaminate their environment. In the meantime, health care workers should inform families with recurrent MRSA infections that the household environment might be contaminated with MRSA and that thoroughly cleaning the house should not make matters worse. Health care workers should be sure to inform families that up to 50% of children may develop a recurrent infection despite the use of best prevention measures.

methicillin-resistant Staphylococcus aureus transmission. Clin Infect Dis. 2011;53(9):853-859.

alone for prevention of recurrent infections. Clin Infect Dis. 2014;58(5):679-682.

3. Iwamoto M, Mu Y, Lynfield R, et al. Trends in invasive methicillin-resistant Staphylococcus aureus infections. Pediatrics. 2013;132(4):e817-e824.

9. Davis MF, Iverson SA, Baron P, et al. Household transmission of meticillin-resistant Staphylococcus aureus and other staphylococci. Lancet Infect Dis. 2012;12(9):703-716.

4. Singer AJ, Talan DA. Management of skin abscesses in the era of methicillin-resistant Staphylococcus aureus. N Engl J Med. 2014;370(11): 1039-1047. 5. Creech CB, Beekmann SE, Chen Y, Polgreen PM. Variability among pediatric infectious diseases specialists in the treatment and prevention of methicillin-resistant Staphylococcus aureus skin and soft tissue infections. Pediatr Infect Dis J. 2008;27 (3):270-272. 6. Fritz SA, Hogan PG, Hayek G, et al. Household versus individual approaches to eradication of community-associated Staphylococcus aureus in children: a randomized trial. Clin Infect Dis. 2012;54 (6):743-751. 7. Fritz SA, Camins BC, Eisenstein KA, et al. Effectiveness of measures to eradicate Staphylococcus aureus carriage in patients with community-associated skin and soft-tissue infections: a randomized trial. Infect Control Hosp Epidemiol. 2011;32(9):872-880.

10. Fritz SA, Hogan PG, Singh LN, et al. Contamination of environmental surfaces with Staphylococcus aureus in households with children infected with methicillin-resistant S aureus [published online September 8, 2014]. JAMA Pediatr. doi:10.1001/jamapediatrics.2014.1218. 11. Uhlemann AC, Knox J, Miller M, et al. The environment as an unrecognized reservoir for community-associated methicillin resistant Staphylococcus aureus USA300: a case-control study. PLoS One. 2011;6(7):e22407. 12. Weber DJ, Rutala WA. Understanding and preventing transmission of healthcare-associated pathogens due to the contaminated hospital environment. Infect Control Hosp Epidemiol. 2013; 34(5):449-452. 13. Huang SS, Datta R, Platt R. Risk of acquiring antibiotic-resistant bacteria from prior room occupants. Arch Intern Med. 2006;166(18):1945-1951.

8. Kaplan SL, Forbes A, Hammerman WA, et al. Randomized trial of “bleach baths” plus routine hygienic measures vs. routine hygienic measures

Vitamin A Shortage and Risk of Bronchopulmonary Dysplasia Matthew M. Laughon, MD, MPH

Bronchopulmonary dysplasia is the most common serious pulmonary morbidity in premature infants.1 Premature infants with bronchopulmonary dysplasia are at increased risk of death, and survivors have life-long morbidities.1-3 DeRelated article page 1039 spite the increased survival of extremely premature infants, bronchopulmonary dysplasia remains a major morbidity.1,2,4 Approximately 40% of infants born between 22 and 28 weeks’ gestation are diagnosed with

bronchopulmonary dysplasia, defined as requiring oxygen supplementation at 36 weeks’ postmenstrual age, although this varies greatly depending on the site of care.1,3,5 The neonatal community has conducted many trials evaluating treatments to reduce the incidence of bronchopulmonary dysplasia, with little success. The only treatments that have reduced the incidence of bronchopulmonary dysplasia in randomized trials without serious adverse events in premature infants are caffeine and vitamin A.

jamapediatrics.com

JAMA Pediatrics November 2014 Volume 168, Number 11

Copyright 2014 American Medical Association. All rights reserved.

Downloaded From: http://archpedi.jamanetwork.com/ by a University of Georgia User on 05/25/2015

995

Opinion Editorial

In an adequately powered, scientifically rigorous randomized clinical trial, vitamin A reduced the incidence of death or bronchopulmonary dysplasia at 36 weeks’ postmenstrual age in premature infants.6 The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network trial was the largest trial in the Cochrane review and drives the main effect of the reduction of bronchopulmonary dysplasia observed with vitamin A.7 The NICHD Neonatal Research Network uses trained research coordinators to abstract data from the medical record and uses a physiologic-based definition of bronchopulmonary dysplasia to reduce the variability of the definition of bronchopulmonary dysplasia between centers. As such, the data are of high quality. However, only 20% of neonatal programs adopted routine vitamin A supplementation after the trial was completed.8 Drug shortages harm patients and are frustrating for health care professionals. Since 2005, there have been multiple drug shortages that affect premature infants, including shortages of ibuprofen, metronidazole, and vitamin A (a full and current list can be found on the US Food and Drug Administration [FDA] website9). The reasons for these shortages include manufacturing problems, discontinuation of older drugs, and lack of FDA labeling. Lack of FDA labeling means that pharmaceutical companies cannot market the product and are subject to severe penalties should they encourage off-label use. Vitamin A is FDA labeled for the treatment of vitamin A deficiency but not for the reduction or prevention of bronchopulmonary dysplasia in premature infants, which may have contributed to the national shortage. Thus, neonatologists are forced to use vitamin A off label to prevent bronchopulmonary dysplasia. The article by Tolia et al10 reviews the effect of the shortage of vitamin A on the incidence of bronchopulmonary dysplasia among infants admitted to a center managed by the Pediatrix Medical Group whose data are included in the Pediatrix Data Warehouse. Tolia et al attempted to replicate the inclu-

ARTICLE INFORMATION Author Affiliation: Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of North Carolina, Chapel Hill. Corresponding Author: Matthew M. Laughon, MD, MPH, Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of North Carolina at Chapel Hill, 101 Manning Dr, Campus Box 7596, Fourth Floor, Chapel Hill, NC 27599 (matt [email protected]). Published Online: September 15, 2014. doi:10.1001/jamapediatrics.2014.1416. Conflict of Interest Disclosures: Dr Laughon reports receiving support from Astellas Pharma, Pfizer, AbbVie, and Discovery Laboratories for consulting and work on data safety and monitoring boards. Funding/Support: Dr Laughon’s work in pediatric and neonatal clinical pharmacology is supported by grant 1K23 HD068497-01 from the National Institute of Child Health and Human Development. Role of the Funder/Sponsor: The National Institute of Child Health and Human Development had no role in the design and conduct of the study; collection, management, analysis, and 996

sion criteria of the NICHD vitamin A trial, which included infants who weigh less than 1000 g and receive oxygen within 24 hours of birth. The authors found that, despite a large decrease in the use of vitamin A, there was no increase in the incidence of death or bronchopulmonary dysplasia. Even the centers with high use (75%-100% of infants) before the shortage did not have an increase in death or chronic lung disease once vitamin A became unavailable. One would have expected the vitamin A shortage to increase the incidence of bronchopulmonary dysplasia or death. Why not? The authors note that perhaps there were some other interventions or practices that were put into place, such as a change in noninvasive ventilation or oxygen saturation targets, that might have replaced the beneficial effect of vitamin A. The risk of death or bronchopulmonary dysplasia in the NICHD vitamin A trial was 62% in the placebo group, while the risk was approximately 48% in the study by Tolia et al.10 It is possible that vitamin A is optimally effective among infants with a higher risk of death or bronchopulmonary dysplasia and becomes less effective with lower risks. Bronchopulmonary dysplasia remains a prevalent morbidity among infants who are born premature, and prevention would greatly benefit public health. Bronchopulmonary dysplasia is the end result of a variety of risk factors and varies widely among neonatal units. Few drugs prevent or reduce bronchopulmonary dysplasia, and none of those that do, including vitamin A, are FDA labeled for the indication of reducing bronchopulmonary dysplasia. Although vitamin A clearly reduces bronchopulmonary dysplasia in rigorous clinical trials (showing efficacy), translating the effect into the “real world” is challenging (to show effectiveness). More effort is needed from the neonatal community to (1) conduct trials using the principles of good drug development to identify drugs to prevent bronchopulmonary dysplasia and (2) find strategies that optimally translate evidence from high-quality trials into clinical practice.

interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. REFERENCES 1. Stoll BJ, Hansen NI, Bell EF, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics. 2010;126(3):443-456. 2. Baraldi E, Filippone M. Chronic lung disease after premature birth. N Engl J Med. 2007;357(19):19461955. 3. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163(7): 1723-1729. 4. Anderson PJ, Doyle LW. Neurodevelopmental outcome of bronchopulmonary dysplasia. Semin Perinatol. 2006;30(4):227-232. 5. Ambalavanan N, Walsh M, Bobashev G, et al; NICHD Neonatal Research Network. Intercenter differences in bronchopulmonary dysplasia or death among very low birth weight infants. Pediatrics. 2011;127(1):e106-e116.

6. Darlow BA, Graham PJ. Vitamin A supplementation to prevent mortality and shortand long-term morbidity in very low birthweight infants. Cochrane Database Syst Rev. 2011;(10): CD000501. 7. Tyson JE, Wright LL, Oh W, et al; National Institute of Child Health and Human Development Neonatal Research Network. Vitamin A supplementation for extremely-low-birth-weight infants. N Engl J Med. 1999;340(25):1962-1968. 8. Ambalavanan N, Kennedy K, Tyson J, Carlo WA. Survey of vitamin A supplementation for extremely-low-birth-weight infants: is clinical practice consistent with the evidence? J Pediatr. 2004;145(3):304-307. 9. FDA drug shortages. Food and Drug Administration website. http://www.accessdata.fda .gov/scripts/drugshortages/default.cfm. Accessed June 1, 2014. 10. Tolia VN, Murthy K, McKinley PS, Bennett MM, Clark RH. The effect of the national shortage of vitamin A on death or chronic lung disease in extremely low-birth-weight infants [published online September 15, 2014]. JAMA Pediatr. doi:10.1001/jamapediatrics.2014.1353.

JAMA Pediatrics November 2014 Volume 168, Number 11

Copyright 2014 American Medical Association. All rights reserved.

Downloaded From: http://archpedi.jamanetwork.com/ by a University of Georgia User on 05/25/2015

jamapediatrics.com

Vitamin A shortage and risk of bronchopulmonary dysplasia.

Vitamin A shortage and risk of bronchopulmonary dysplasia. - PDF Download Free
119KB Sizes 0 Downloads 5 Views