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The efficacy of very low-density sodium hypochloride washes in preventing healthcare-associated infections in pediatric intensive care units

Yıl 2019, Cilt: 3 Sayı: 9, 648 - 651, 01.09.2019
https://doi.org/10.28982/josam.613450

Öz

Aim: Healthcare-associated infections (HAIs) have increased in pediatric intensive care units (ICUs) within the last decade. Maintaining hand hygiene, performing invasive interventions in accordance with aseptic techniques, contact precautions and chlorhexidine gluconate showers are the usual prevention methods against HAIs. However, despite all prevention methods, HAI incidence has globally increased in pediatric ICUs. The purpose of this study is to investigate the preventive effects of 0.005% sodium hypochlorite (NaOCl) showers against HAIs in pediatric ICUs. 

Methods: This case control study was conducted in a 17-bed pediatric intensive care unit. Patients were washed with water and soap during the first six months and water and 0.005% sodium hypochlorite during the following six months, after which the incidence of HAIs was compared. The diagnosis of HAIs was made according to Centers for Disease Control and Prevention National Healthcare Safety Network guidelines.

Results: Two hundred thirty patients (118 patients in control group, 112 patients in NaOCl group) who met the inclusion criteria were included in the study. 26 patients among the control group and 20 patients among the NaOCl group were diagnosed with HAIs. In the NaOCl group, we detected 100% and 66% reductions in P. aeruginosa and S. aureus infections, respectively. There was no statistically significant difference between the groups in terms of overall HAI incidences (P=0.510). Most frequently encountered HAIs in both groups were ventilator-associated pneumonia and bloodstream infections. The rates of multidrug resistant gram-negative bacterial isolation were 77.8% (14/18) in the control group and 66.7% (5/15) in the sodium hypochlorite group. The rates of extensive drug resistant gram-negative bacterial isolation were 38.9% (7/18) in the control group and 26.7% (4/15) in the NaOCl group. There was no statistically significant difference between the two groups (P=0.458). We did not encounter any local or systemic side effects in any of our patients.

Conclusion: We found that weekly 0.005% NaOCl showers reduced P. aeruginosa and S. aureus infections, although it did not change length of hospital stay, incidence of total HAIs and the sensitivity of gram-negative bacteria to antibiotics.

Destekleyen Kurum

yok

Proje Numarası

yok

Teşekkür

-

Kaynakça

  • 1. Vincent JL. Nosocomial infections in adult intensive-care units. Lancet. 2003;361(9374):2068-77.
  • 2. Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370(13):1198-208.
  • 3. O'Grady NP, Alexander M, Dellinger EP, Gerberding JL, Heard SO, Maki DG, et al. Guidelines for the prevention of intravascular catheter-related infections. The Hospital Infection Control Practices Advisory Committee, Center for Disease Control and Prevention, U.S. Pediatrics. 2002;110(5):e51.
  • 4. Heggers JP, Sazy JA, Stenberg BD, Strock LL, McCauley RL, Herndon DN, et al. Bactericidal and wound-healing properties of sodium hypochlorite solutions: the 1991 Lindberg Award. J Burn Care Rehabil. 1991;12(5):420-4.
  • 5. Sassone LM, Fidel RA, Murad CF, Fidel SR, Hirata R. Antimicrobial activity of sodium hypochlorite and chlorhexidine by two different tests. Aust Endod J. 2008;34(1):19-24.
  • 6. Barnes TM, Greive KA. Use of bleach baths for the treatment of infected atopic eczema. Australas J Dermatol. 2013;54(4):251-8.
  • 7. Wong SM, Ng TG, Baba R. Efficacy and safety of sodium hypochlorite (bleach) baths in patients with moderate to severe atopic dermatitis in Malaysia. J Dermatol. 2013;40(11):874-80.
  • 8. Hon KL, Tsang YC, Lee VW, Pong NH, Ha G, Lee ST, et al. Efficacy of sodium hypochlorite (bleach) baths to reduce Staphylococcus aureus colonization in childhood onset moderate-to-severe eczema: A randomized, placebo-controlled cross-over trial. J Dermatolog Treat. 2016;27(2):156-62.
  • 9. Kaplan SL, Forbes A, Hammerman WA, Lamberth L, Hulten KG, Minard CG, et al. Randomized trial of "bleach baths" plus routine hygienic measures vs. routine hygienic measures alone for prevention of recurrent infections. Clin Infect Dis. 2014;58(5):679-82.
  • 10. Lee M, Van Bever H. The role of antiseptic agents in atopic dermatitis. Asia Pac Allergy. 2014;4(4):230-40.
  • 11. Milstone AM, Passaretti CL, Perl TM. Chlorhexidine: expanding the armamentarium for infection control and prevention. Clin Infect Dis. 2008;46(2):274-81.
  • 12. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36(5):309-32.
  • 13. Vernon MO, Hayden MK, Trick WE, Hayes RA, Blom DW, Weinstein RA. Chlorhexidine gluconate to cleanse patients in a medical intensive care unit: the effectiveness of source control to reduce the bioburden of vancomycin-resistant enterococci. Arch Intern Med. 2006;166(3):306-12.
  • 14. Lin MY, Lyles-Banks RD, Lolans K, Hines DW, Spear JB, Petrak R, et al. The importance of long-term acute care hospitals in the regional epidemiology of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. Clin Infect Dis. 2013;57(9):1246-52.
  • 15. Coello R, Glynn JR, Gaspar C, Picazo JJ, Fereres J. Risk factors for developing clinical infection with methicillin-resistant Staphylococcus aureus (MRSA) amongst hospital patients initially only colonized with MRSA. J Hosp Infect. 1997;37(1):39-46.
  • 16. Bonten MJ, Slaughter S, Ambergen AW, Hayden MK, van Voorhis J, Nathan C, et al. The role of "colonization pressure" in the spread of vancomycin-resistant enterococci: an important infection control variable. Arch Intern Med. 1998;158(10):1127-32.
  • 17. Playford EG, Craig JC, Iredell JR. Carbapenem-resistant Acinetobacter baumannii in intensive care unit patients: risk factors for acquisition, infection and their consequences. J Hosp Infect. 2007;65(3):204-11.
  • 18. Hugonnet S, Pittet D. Hand hygiene-beliefs or science? Clin Microbiol Infect. 2000;6(7):350-6.
  • 19. Saint S, Higgins LA, Nallamothu BK, Chenoweth C. Do physicians examine patients in contact isolation less frequently? A brief report. Am J Infect Control. 2003;31(6):354-6.
  • 20. Evans HL, Dellit TH, Chan J, Nathens AB, Maier RV, Cuschieri J. Effect of chlorhexidine whole-body bathing on hospital-acquired infections among trauma patients. Arch Surg. 2010;145(3):240-6.
  • 21. Bleasdale SC, Trick WE, Gonzalez IM, Lyles RD, Hayden MK, Weinstein RA. Effectiveness of chlorhexidine bathing to reduce catheter-associated bloodstream infections in medical intensive care unit patients. Arch Intern Med. 2007;167(19):2073-9.
  • 22. Borer A, Gilad J, Porat N, Megrelesvilli R, Saidel-Odes L, Peled N, et al. Impact of 4% chlorhexidine whole-body washing on multidrug-resistant Acinetobacter baumannii skin colonisation among patients in a medical intensive care unit. J Hosp Infect. 2007;67(2):149-55.
  • 23. Derde LP, Dautzenberg MJ, Bonten MJ. Chlorhexidine body washing to control antimicrobial-resistant bacteria in intensive care units: a systematic review. Intensive Care Med. 2012;38(6):931-9.
  • 24. O'Horo JC, Silva GL, Munoz-Price LS, Safdar N. The efficacy of daily bathing with chlorhexidine for reducing healthcare-associated bloodstream infections: a meta-analysis. Infect Control Hosp Epidemiol. 2012;33(3):257-67.
  • 25. Racioppi F, Daskaleros PA, Besbelli N, Borges A, Deraemaeker C, Magalini SI, et al. Household bleaches based on sodium hypochlorite: review of acute toxicology and poison control center experience. Food Chem Toxicol. 1994;32(9):845-61.
  • 26. Bloomfield SF. A review. The use of disinfectants in the home. Bacteriol. 1978;45(1):1-38.
  • 27. Smith RF, Blasi D, Dayton SL, Chipps DD. Effects of sodium hypochlorite on the microbial flora of burns and normal skin. J Trauma. 1974;14(11):938-44.
  • 28. Cotter JL, Fader RC, Lilley C, Herndon DN. Chemical parameters, antimicrobial activities, and tissue toxicity of 0.1 and 0.5% sodium hypochlorite solutions. Antimicrob Agents Chemother. 1985;28(1):118-22.
  • 29. McDonnell KJ, Sculco TP. Dakin's solution revisited. Am. J. Orthop (Belle Mead, NJ). 1997;26(7):471-3.
  • 30. Bloomfield SF ST. Eusol BPC and other hypochlorite formulations used in hospitals. Pharm J. 1985;235:153-5.
  • 31. Slahetka F. Dakin's solution for deep ulcers. Geriatr. Nurs. 1984;5(3):168-9.
  • 32. Ridenour G, Lampen R, Federspiel J, Kritchevsky S, Wong E, Climo M. Selective use of intranasal mupirocin and chlorhexidine bathing and the incidence of methicillin-resistant Staphylococcus aureus colonization and infection among intensive care unit patients. Infect Control Hosp Epidemiol. 2007;28(10):1155-61.
  • 33. Sandri AM, Dalarosa MG, Ruschel de Alcantara L, da Silva Elias L, Zavascki AP. Reduction in incidence of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection in an intensive care unit: role of treatment with mupirocin ointment and chlorhexidine baths for nasal carriers of MRSA. Infect Control Hosp Epidemiol. 2006;27(2):185-7.
  • 34. Gaynes R, Edwards JR. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis. 2005;41(6):848-54.
  • 35. Parajuli NP, Acharya SP, Mishra SK, Parajuli K, Rijal BP, Pokhrel BM. High burden of antimicrobial resistance among gram negative bacteria causing healthcare associated infections in a critical care unit of Nepal. Antimicrob Resist Infect Control. 2017;6:67.

Çocuk yoğun bakım ünitelerinde sağlık hizmeti ilişkili enfeksiyonları önlemede düşük konsantrasyonlu sodyum hipokloritli banyo uygulamalarının etkinliği

Yıl 2019, Cilt: 3 Sayı: 9, 648 - 651, 01.09.2019
https://doi.org/10.28982/josam.613450

Öz

Amaç: Sağlık hizmeti ile ilişkili enfeksiyonlar (SHİE) son on yılda çocuk yoğun bakım ünitelerinde (YBÜ) artış göstermiştir. El hijyeni sağlamak, girişimsel uygulamalarda asepsi şartlarına uymak, temas önlemleri ve klorheksidin glukonat banyoları, SHİE’leri önlemenin en temel yollarıdır. Ancak, tüm önlemlere rağmen, SHİE insidansının global olarak pediatrik yoğun bakımlarda artış gösterdiği görülmektedir. Bu çalışmanın amacı çocuk YBÜ’de %0,005 sodyum hipokloritli (NaOCl) banyo uygulamalarının dirençli bakteriler ile ortaya çıkan SHİE önleyip önlemeyeceğini değerlendirmektir.

Yöntemler: Bu vaka kontrol çalışması, 17 yataklı çocuk BYÜ’de prospektif olarak yapıldı. Çalışmanın ilk altı ayında hastalar sadece su ve sabun ile yıkanırken ikinci altı aylık dönemde NaOCl ile yıkandılar. SHİE tanıları hastalık kontrol ve önleme merkezinin rehberine göre konuldu.

Bulgular: Çalışma kriterlerini karşılayan 230 hasta (118 kontrol grubu, 112 NaOCl grubu) çalışmaya dahil edildi. Kontrol grubundan 26 hasta ve NaOCl grubundan 20 hastada sağlık hizmeti ile ilişkili enfeksiyon saptandı. NaOCl grubunda kontrol grubuna göre P. aeruginosa ve S. aureus enfeksiyonlarında sırasıysa %100 ve %66 oranında azalma tespit edildi. SHİE sayısı açısından gruplar arasında istatiksel olarak anlamlı fark saptanmadı. Her iki grupta da en sık görülen SHİE ventilator ile ilişkili pnömoni ve kan dolaşım yolu enfeksiyonlarıydı. Çoklu ilaç dirençli gram negatif bakteri oranı kontrol grubunda %77,8 (17/18) iken, NaOCl grubunda %66,7 (5/15) olarak saptandı. Yaygın ilaç dirençli bakteri oranı kontrol grubunda %38,9 (7/18), NaOCl grubunda %26,7 (4/15) idi. Gruplar arasında anlamlı fark yoktu (P=0,458). NaOCl uygulanan hastalarda herhangi bir lokal veya sistemik yan etki gözlenmedi.

Sonuç: Haftalık %0,005’lik NaOCl banyo uygulamalarının P. aeruginosa ve S. aureus enfeksiyonlarında azalma sağladığı, ancak hastane kalma süresi, total SHİE sayısı ve gram negatif bakterilerin antibiyotik duyarlılıklarında ise bir değişikliğe sebep olmadığı gösterilmiştir.

Proje Numarası

yok

Kaynakça

  • 1. Vincent JL. Nosocomial infections in adult intensive-care units. Lancet. 2003;361(9374):2068-77.
  • 2. Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370(13):1198-208.
  • 3. O'Grady NP, Alexander M, Dellinger EP, Gerberding JL, Heard SO, Maki DG, et al. Guidelines for the prevention of intravascular catheter-related infections. The Hospital Infection Control Practices Advisory Committee, Center for Disease Control and Prevention, U.S. Pediatrics. 2002;110(5):e51.
  • 4. Heggers JP, Sazy JA, Stenberg BD, Strock LL, McCauley RL, Herndon DN, et al. Bactericidal and wound-healing properties of sodium hypochlorite solutions: the 1991 Lindberg Award. J Burn Care Rehabil. 1991;12(5):420-4.
  • 5. Sassone LM, Fidel RA, Murad CF, Fidel SR, Hirata R. Antimicrobial activity of sodium hypochlorite and chlorhexidine by two different tests. Aust Endod J. 2008;34(1):19-24.
  • 6. Barnes TM, Greive KA. Use of bleach baths for the treatment of infected atopic eczema. Australas J Dermatol. 2013;54(4):251-8.
  • 7. Wong SM, Ng TG, Baba R. Efficacy and safety of sodium hypochlorite (bleach) baths in patients with moderate to severe atopic dermatitis in Malaysia. J Dermatol. 2013;40(11):874-80.
  • 8. Hon KL, Tsang YC, Lee VW, Pong NH, Ha G, Lee ST, et al. Efficacy of sodium hypochlorite (bleach) baths to reduce Staphylococcus aureus colonization in childhood onset moderate-to-severe eczema: A randomized, placebo-controlled cross-over trial. J Dermatolog Treat. 2016;27(2):156-62.
  • 9. Kaplan SL, Forbes A, Hammerman WA, Lamberth L, Hulten KG, Minard CG, et al. Randomized trial of "bleach baths" plus routine hygienic measures vs. routine hygienic measures alone for prevention of recurrent infections. Clin Infect Dis. 2014;58(5):679-82.
  • 10. Lee M, Van Bever H. The role of antiseptic agents in atopic dermatitis. Asia Pac Allergy. 2014;4(4):230-40.
  • 11. Milstone AM, Passaretti CL, Perl TM. Chlorhexidine: expanding the armamentarium for infection control and prevention. Clin Infect Dis. 2008;46(2):274-81.
  • 12. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36(5):309-32.
  • 13. Vernon MO, Hayden MK, Trick WE, Hayes RA, Blom DW, Weinstein RA. Chlorhexidine gluconate to cleanse patients in a medical intensive care unit: the effectiveness of source control to reduce the bioburden of vancomycin-resistant enterococci. Arch Intern Med. 2006;166(3):306-12.
  • 14. Lin MY, Lyles-Banks RD, Lolans K, Hines DW, Spear JB, Petrak R, et al. The importance of long-term acute care hospitals in the regional epidemiology of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. Clin Infect Dis. 2013;57(9):1246-52.
  • 15. Coello R, Glynn JR, Gaspar C, Picazo JJ, Fereres J. Risk factors for developing clinical infection with methicillin-resistant Staphylococcus aureus (MRSA) amongst hospital patients initially only colonized with MRSA. J Hosp Infect. 1997;37(1):39-46.
  • 16. Bonten MJ, Slaughter S, Ambergen AW, Hayden MK, van Voorhis J, Nathan C, et al. The role of "colonization pressure" in the spread of vancomycin-resistant enterococci: an important infection control variable. Arch Intern Med. 1998;158(10):1127-32.
  • 17. Playford EG, Craig JC, Iredell JR. Carbapenem-resistant Acinetobacter baumannii in intensive care unit patients: risk factors for acquisition, infection and their consequences. J Hosp Infect. 2007;65(3):204-11.
  • 18. Hugonnet S, Pittet D. Hand hygiene-beliefs or science? Clin Microbiol Infect. 2000;6(7):350-6.
  • 19. Saint S, Higgins LA, Nallamothu BK, Chenoweth C. Do physicians examine patients in contact isolation less frequently? A brief report. Am J Infect Control. 2003;31(6):354-6.
  • 20. Evans HL, Dellit TH, Chan J, Nathens AB, Maier RV, Cuschieri J. Effect of chlorhexidine whole-body bathing on hospital-acquired infections among trauma patients. Arch Surg. 2010;145(3):240-6.
  • 21. Bleasdale SC, Trick WE, Gonzalez IM, Lyles RD, Hayden MK, Weinstein RA. Effectiveness of chlorhexidine bathing to reduce catheter-associated bloodstream infections in medical intensive care unit patients. Arch Intern Med. 2007;167(19):2073-9.
  • 22. Borer A, Gilad J, Porat N, Megrelesvilli R, Saidel-Odes L, Peled N, et al. Impact of 4% chlorhexidine whole-body washing on multidrug-resistant Acinetobacter baumannii skin colonisation among patients in a medical intensive care unit. J Hosp Infect. 2007;67(2):149-55.
  • 23. Derde LP, Dautzenberg MJ, Bonten MJ. Chlorhexidine body washing to control antimicrobial-resistant bacteria in intensive care units: a systematic review. Intensive Care Med. 2012;38(6):931-9.
  • 24. O'Horo JC, Silva GL, Munoz-Price LS, Safdar N. The efficacy of daily bathing with chlorhexidine for reducing healthcare-associated bloodstream infections: a meta-analysis. Infect Control Hosp Epidemiol. 2012;33(3):257-67.
  • 25. Racioppi F, Daskaleros PA, Besbelli N, Borges A, Deraemaeker C, Magalini SI, et al. Household bleaches based on sodium hypochlorite: review of acute toxicology and poison control center experience. Food Chem Toxicol. 1994;32(9):845-61.
  • 26. Bloomfield SF. A review. The use of disinfectants in the home. Bacteriol. 1978;45(1):1-38.
  • 27. Smith RF, Blasi D, Dayton SL, Chipps DD. Effects of sodium hypochlorite on the microbial flora of burns and normal skin. J Trauma. 1974;14(11):938-44.
  • 28. Cotter JL, Fader RC, Lilley C, Herndon DN. Chemical parameters, antimicrobial activities, and tissue toxicity of 0.1 and 0.5% sodium hypochlorite solutions. Antimicrob Agents Chemother. 1985;28(1):118-22.
  • 29. McDonnell KJ, Sculco TP. Dakin's solution revisited. Am. J. Orthop (Belle Mead, NJ). 1997;26(7):471-3.
  • 30. Bloomfield SF ST. Eusol BPC and other hypochlorite formulations used in hospitals. Pharm J. 1985;235:153-5.
  • 31. Slahetka F. Dakin's solution for deep ulcers. Geriatr. Nurs. 1984;5(3):168-9.
  • 32. Ridenour G, Lampen R, Federspiel J, Kritchevsky S, Wong E, Climo M. Selective use of intranasal mupirocin and chlorhexidine bathing and the incidence of methicillin-resistant Staphylococcus aureus colonization and infection among intensive care unit patients. Infect Control Hosp Epidemiol. 2007;28(10):1155-61.
  • 33. Sandri AM, Dalarosa MG, Ruschel de Alcantara L, da Silva Elias L, Zavascki AP. Reduction in incidence of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection in an intensive care unit: role of treatment with mupirocin ointment and chlorhexidine baths for nasal carriers of MRSA. Infect Control Hosp Epidemiol. 2006;27(2):185-7.
  • 34. Gaynes R, Edwards JR. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis. 2005;41(6):848-54.
  • 35. Parajuli NP, Acharya SP, Mishra SK, Parajuli K, Rijal BP, Pokhrel BM. High burden of antimicrobial resistance among gram negative bacteria causing healthcare associated infections in a critical care unit of Nepal. Antimicrob Resist Infect Control. 2017;6:67.
Toplam 35 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Çocuk Sağlığı ve Hastalıkları
Bölüm Araştırma makalesi
Yazarlar

Eren Çağan 0000-0001-5640-9196

Nevin Kılıç Bu kişi benim 0000-0002-5803-5850

Proje Numarası yok
Yayımlanma Tarihi 1 Eylül 2019
Yayımlandığı Sayı Yıl 2019 Cilt: 3 Sayı: 9

Kaynak Göster

APA Çağan, E., & Kılıç, N. (2019). The efficacy of very low-density sodium hypochloride washes in preventing healthcare-associated infections in pediatric intensive care units. Journal of Surgery and Medicine, 3(9), 648-651. https://doi.org/10.28982/josam.613450
AMA Çağan E, Kılıç N. The efficacy of very low-density sodium hypochloride washes in preventing healthcare-associated infections in pediatric intensive care units. J Surg Med. Eylül 2019;3(9):648-651. doi:10.28982/josam.613450
Chicago Çağan, Eren, ve Nevin Kılıç. “The Efficacy of Very Low-Density Sodium Hypochloride Washes in Preventing Healthcare-Associated Infections in Pediatric Intensive Care Units”. Journal of Surgery and Medicine 3, sy. 9 (Eylül 2019): 648-51. https://doi.org/10.28982/josam.613450.
EndNote Çağan E, Kılıç N (01 Eylül 2019) The efficacy of very low-density sodium hypochloride washes in preventing healthcare-associated infections in pediatric intensive care units. Journal of Surgery and Medicine 3 9 648–651.
IEEE E. Çağan ve N. Kılıç, “The efficacy of very low-density sodium hypochloride washes in preventing healthcare-associated infections in pediatric intensive care units”, J Surg Med, c. 3, sy. 9, ss. 648–651, 2019, doi: 10.28982/josam.613450.
ISNAD Çağan, Eren - Kılıç, Nevin. “The Efficacy of Very Low-Density Sodium Hypochloride Washes in Preventing Healthcare-Associated Infections in Pediatric Intensive Care Units”. Journal of Surgery and Medicine 3/9 (Eylül 2019), 648-651. https://doi.org/10.28982/josam.613450.
JAMA Çağan E, Kılıç N. The efficacy of very low-density sodium hypochloride washes in preventing healthcare-associated infections in pediatric intensive care units. J Surg Med. 2019;3:648–651.
MLA Çağan, Eren ve Nevin Kılıç. “The Efficacy of Very Low-Density Sodium Hypochloride Washes in Preventing Healthcare-Associated Infections in Pediatric Intensive Care Units”. Journal of Surgery and Medicine, c. 3, sy. 9, 2019, ss. 648-51, doi:10.28982/josam.613450.
Vancouver Çağan E, Kılıç N. The efficacy of very low-density sodium hypochloride washes in preventing healthcare-associated infections in pediatric intensive care units. J Surg Med. 2019;3(9):648-51.