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Türkiye'nin güneyinde üçüncü basamak bir hastanede çocuklarda Staphylococcus aureus enfeksiyonlarının klinik özellikleri ve direnç paternleri

Yıl 2022, Cilt: 47 Sayı: 2, 580 - 588, 30.06.2022

Öz

Amaç: Bu çalışmda çocuklarda invaziv enfeksiyonların önde gelen bir nedeni olan Staphylococcus aureus (S. aureus) izolatlarının klinik ve demografik özelliklerinin, antistafilokokal antibiyotiklere direnç durumlarının değerlendirilmesi amaçlanmıştır.
Gereç ve Yöntem: Temmuz 2018-Temmuz 2020 tarihleri arasında Çocuk Sağlığı ve Hastalıkları Kliniği'nde takip edilen, apse, yara, kan, beyin omurilik sıvısı, eklem sıvısı ve diğer steril vücut sıvısı kültürlerinde S. aureus üremesi olan 18 yaş altı hastaların dosya kayıtları retrospektif olarak incelendi.
Bulgular: 135 hasta çalışmaya alındı. Hastaların 105’inde (77.7%) toplum kökenli, 30’unda (22.3%) ise hastane kökenli S. aureus (HA-SA, Hospital Acquired S. aureus) enfeksiyonu mevcuttu. S. aureus en yaygın olarak cilt ve yumuşak doku enfeksiyonlarında saptandı. Toplum kökenlilerde cilt ve yumuşak doku enfeksiyonları, nozokomiyallerde ise bakteriyemi sık gözlendi. Tüm hastaların %53.3’ünde metisilin dirençli S. aureus (MRSA); %20’sinde klindamisin, %14.4’ünde mupirosin direnci saptandı. Toplum Kökenli S. aureus’ların (CS-SA, Community-acquired SA) %55,8’i, HA-SA’ların %46,7’si MRSA idi. MRSA olanlarda penisilin, mupirosin, eritromisin ve tetrasiklin direnci anlamlı derecede daha fazlaydı. CA-SA’larda mupirosin direnci anlamlı derecede daha fazlaydı. Yatış süresi median 12 gündü. Yatış süresi, IV antibiyotik alma süresi, mortalite, klindamisin direnci HA-MRSA enfeksiyonlarında anlamlı derecede daha yüksekti. S. aureus enfeksiyonlarında mortalite %2.2 iken, HA-SA enfeksiyonlarında mortalite %10 olarak saptandı.
Sonuç: Toplum kökenli MRSA oranlarımız oldukça yüksek olup; klindamisin ve mupirosin direnci bölgemizde önemli bir sorun olarak görünmektedir. Doğru zamanda, uygun kültür örneğinin alınması; direnç paternlerinin ve ampirik tedavi rejimlerinin belirlenmesinde önemlidir.

Kaynakça

  • 1. Kaplan SL HK, Mason EO. Staphylococcus aureus Infections (Coagulase-Positive Staphylococci). In: Cherry JD KS, Steinbach WJ, Hotez PJ, editor. Feiginand Cherry's Textbook of Pediatric InfectiousDiseases. 8th ed. Philadelphia, PA: Elsevier; 2018. p. 794-806.
  • 2. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clinical infectious diseases. 2011;52(3):e18-e55.
  • 3. Rybak MJ, LaPlante KL. Community‐associated methicillin‐resistant Staphylococcus aureus: a review. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2005;25(1):74-85.
  • 4. SL K. Methicillin-resistant Staphylococcus aureus infections in children: Epidemiology and clinical spectrum [15 July 2021]. Available from: http://www.uptodate.com/contents/Methicillin-resistant-Staphylococcus-aureus-infections-in-children:-Epidemiology-and-clinical-spectrum.
  • 5. Khamash DF, Voskertchian A, Tamma PD, Akinboyo IC, Carroll KC, Milstone AM. Increasing clindamycin and trimethoprim-sulfamethoxazole resistance in pediatric Staphylococcus aureus infections. Journal of the Pediatric Infectious Diseases Society. 2019;8(4):351-3.
  • 6. Dadashi M, Hajikhani B, Darban-Sarokhalil D, van Belkum A, Goudarzi M. Mupirocin resistance in Staphylococcus aureus: A systematic review and meta-analysis. Journal of global antimicrobial resistance. 2020;20:238-47.
  • 7. EUCAST. European Committee on Antimicrobial Susceptibility Testing, Clinical breakpoints [cited 2017]. Available from: http:// www.eucast.org/clinical_breakpoints/
  • 8. Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, et al. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. Jama. 2007;298(15):1763-71.
  • 9. Kaplan SL, Hulten KG, Gonzalez BE, Hammerman WA, Lamberth L, Versalovic J, et al. Three-year surveillance of community-acquired Staphylococcus aureus infections in children. Clinical Infectious Diseases. 2005;40(12):1785-91.
  • 10. Arikan K, Karadag-Oncel E, Aycan AE, Yuksekkaya S, Sancak B, Ceyhan M. Epidemiologic and Molecular Characteristics of Staphylococcus aureus Strains Isolated From Hospitalized Pediatric Patients. The Pediatric Infectious Disease Journal. 2020;39(11):1002-6.
  • 11. Crandall H, Kapusta A, Killpack J, Heyrend C, Nilsson K, Dickey M, et al. Clinical and molecular epidemiology of invasive Staphylococcus aureus infection in Utah children; continued dominance of MSSA over MRSA. Plos one. 2020;15(9):e0238991.
  • 12. Tong SY, Davis JS, Eichenberger E, Holland TL, Fowler Jr VG. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clinical microbiology reviews. 2015;28(3):603-61.
  • 13. Karbuz A, Karahan ZC, Aldemir-Kocabaş B, Tekeli A, Özdemir H, Güriz H, et al. Evaluation of antimicrobial susceptibilities and virulence factors of Staphylococcus aureus strains isolated from community-acquired and health-care associated pediatric infections. The Turkish journal of pediatrics. 2017;59(4):395-403.
  • 14. Yeşil E, Çelebi S, Arife Ö, HACIMUSTAFAOĞLU M. Evaluation of Methicillin Resistant Staphylococcus aureus Infection in Children. Güncel Pediatri. 2019;17(1):121-7.
  • 15. Gomes RT, Lyra TG, Alves NN, Caldas RM, Barberino M-G, Nascimento-Carvalho CM. Methicillin-resistant and methicillin-susceptible community-acquired Staphylococcus aureus infection among children. Brazilian Journal of Infectious Diseases. 2013;17:573-8.
  • 16. Ganesan SL, Mehta A, Lakshmikantha K, Jayashree M, Gautam V, Ray P. Community-acquired methicillin-resistant staphylococcus aureus infections in acutely ill children: a retrospective case-control study. The Indian Journal of Pediatrics. 2021;88(2):141-6.
  • 17. Sola C, Paganini H, Egea AL, Moyano AJ, Garnero A, Kevric I, et al. Spread of epidemic MRSA-ST5-IV clone encoding PVL as a major cause of community onset staphylococcal infections in Argentinean children. PLoS One. 2012;7(1):e30487.
  • 18. Galper E, Bdolah‐Abram T, Megged O. Assessment of infections rate due to community‐acquired Methicillin‐resistant Staphylococcus aureus and evaluation of risk factors in the paediatric population. Acta Paediatrica. 2021;110(5):1579-84.
  • 19. Kirby WM. Extraction of a highly potent penicillin inactivator from penicillin resistant staphylococci. Science. 1944;99(2579):452-3.
  • 20. Jevons MP. “Celbenin”-resistant staphylococci. British medical journal. 1961;1(5219):124.
  • 21. ŞANLI K. Hastane Kökenli ve Toplum Kaynaklı ID Staphylococcus aureus Suşlarının Çeşitli Antimikrobiyallere Duyarlılıkları. İstanbul Kanuni Sultan Süleyman Tıp Dergisi. 2020;12(2):188-93.
  • 22. Rağbetli C, Parlak M, Bayram Y, Guducuoglu H, Ceylan N. Evaluation of antimicrobial resistance in Staphylococcus aureus isolates by years. Interdisciplinary perspectives on infectious diseases. 2016;2016.
  • 23. Kumar SK KA. Antibiotic resistance pattern of Staphylococcus aureus infections in children. Int J Contemp Pediatr. 2019;6:727-31.
  • 24. Gurung RR, Maharjan P, Chhetri GG. Antibiotic resistance pattern of Staphylococcus aureus with reference to MRSA isolates from pediatric patients. Future science OA. 2020;6(4):FSO464.
  • 25. Staphylococcus aureus. 31st ed. Kimberlin DW BM, Jackson MA, Long SS, editor. Itasca, IL: American Academy of Pediatrics; 2018-2021.
  • 26. SL K. Staphylococcus aureus in children: Overview of treatment of invasive infections [July 2021]. Available from: http://www.uptodate.com/contents/Staphylococcus-aureus-in-children: Overview -of –treatment- of- invasive- infections.
  • 27. Stein M, Komerska J, Prizade M, Sheinberg B, Tasher D, Somekh E. Clindamycin resistance among Staphylococcus aureus strains in Israel: implications for empirical treatment of skin and soft tissue infections. International Journal of Infectious Diseases. 2016;46:18-21.
  • 28. Pérez G, Martiren S, Reijtman V, Romero R, Mastroianni A, Casimir L, et al. Community-acquired Staphylococcus aureus bacteremia in children: a cohort study for 2010-2014. Archivos argentinos de pediatria. 2016;114(6):508-13.
  • 29. Liu Y, Kong F, Zhang X, Brown M, Ma L, Yang Y. Antimicrobial susceptibility of Staphylococcus aureus isolated from children with impetigo in China from 2003 to 2007 shows community-associated methicillin-resistant Staphylococcus aureus to be uncommon and heterogeneous. The British journal of dermatology. 2009;161(6):1347-50.
  • 30. Arianpoor A, Estaji F, Naderinasab M, Askari E. Antimicrobial susceptibility pattern of Staphylococcus aureus isolates against newly marketed antibiotics: a report from Imam Reza Hospital of Mashhad, Iran. Razavi Int J Med. 2015;3(4):e31568.
  • 31. Rudresh MS, Ravi GS, Motagi A, Alex AM, Sandhya P, Navaneeth BV. Prevalence of mupirocin resistance among staphylococci, its clinical significance and relationship to clinical use. Journal of laboratory physicians. 2015;7(02):103-7.
  • 32. Sareyyüpoğlu B, Ozyurt M, Haznedaroğlu T, Ardiç N. Detection of methicillin and mupirocin resistance in staphylococcal hospital isolates with a touchdown multiplex polymerase chain reaction. Folia microbiologica. 2008;53(4):363-7.
  • 33. Hiramatsu K, Hanaki H, Ino T, Yabuta K, Oguri T, Tenover F. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. The Journal of antimicrobial chemotherapy. 1997;40(1):135-6.
  • 34. Krishnamurthy V, Saha A, Renushri BV, Nagaraj ER. Methicillin Resistant Staphylococcus aureus Carriage, Antibiotic Resistance and Molecular Pathogenicity among Healthy Individuals Exposed and Not Exposed to Hospital Environment. Journal of clinical and diagnostic research : JCDR. 2014;8(7):Dc04-8.
  • 35. Fomda BA, Thokar MA, Khan A, Bhat JA, Zahoor D, Bashir G, et al. Nasal carriage of Methicillin-resistant Staphylococcus aureus among healthy population of Kashmir, India. Indian journal of medical microbiology. 2014;32(1):39-43.
  • 36. Cosgrove SE, Qi Y, Kaye KS, Harbarth S, Karchmer AW, Carmeli Y. The impact of methicillin resistance in Staphylococcus aureus bacteremia on patient outcomes: mortality, length of stay, and hospital charges. Infection control and hospital epidemiology. 2005;26(2):166-74.

Clinical characteristics and resistance patterns of Staphylococcus aureus infections in children at a tertiary care hospital in southern Turkey

Yıl 2022, Cilt: 47 Sayı: 2, 580 - 588, 30.06.2022

Öz

Purpose: The aim of this study was to evaluate the clinical and demographic characteristics and resistance patterns to antistaphylococcal antibiotics of Staphylococcus aureus (S. aureus) isolates, which is a leading cause of invasive infections in children.
Materials and Methods: Patients who were under 18 years of age and who had S. aureus growth in abscess, wound, blood, cerebrospinal fluid, joint fluid and any other sterile body fluid cultures, who were followed up at Children’s Health and Diseases Clinic in between July 2018 and July 2020 were included in the study.
Results: A total of 135 patients and cultures were included in the study. Community-acquired S. aureus (CA-SA) infection was present in 105 (77.7%) patients and hospital-acquired S. aureus (HA-SA) infections in 30 (22.3%). S. aureus was most commonly detected in skin and soft tissue infections. Skin and soft tissue infections were more common in patients with community-acquired disease, whereas bacteremia was more common in patients with nosocomial infection. Methicillin-resistant S. aureus (MRSA) isolates was encountered in 53.3% of all patients; Clindamycin resistance was found in 20% of all staphylococcal isolates and the ratio of mupirocin resistance was 14.4%.55.8% of all CA-SA and 46.7% of all HA-SA isolates were MRSA. Penicillin, mupirocin, erythromycin, and tetracycline resistance were significantly higher in MRSA isolates as compares to non-MRSA isolates. Mupirocin resistance was significantly higher in CA-SA isolates. The median length of hospital stay was 12 days. Length of hospital stay, duration of intravenous antibiotics use, mortality, and clindamycin resistance were significantly higher in patients with HA-MRSA infections. While overall mortality was 2.2% in patients with S. aureus infections, when evaluated separately, it was 10% in patients with HA-SA infections.
Conclusion: Our CA-MRSA rates are quite high as compared to other reports, and clindamycin and mupirocin resistance seems to be an important problem in our region. Taking appropriate cultures at the right time is important in determining resistance patterns and guiding empirical treatment regimens.

Kaynakça

  • 1. Kaplan SL HK, Mason EO. Staphylococcus aureus Infections (Coagulase-Positive Staphylococci). In: Cherry JD KS, Steinbach WJ, Hotez PJ, editor. Feiginand Cherry's Textbook of Pediatric InfectiousDiseases. 8th ed. Philadelphia, PA: Elsevier; 2018. p. 794-806.
  • 2. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clinical infectious diseases. 2011;52(3):e18-e55.
  • 3. Rybak MJ, LaPlante KL. Community‐associated methicillin‐resistant Staphylococcus aureus: a review. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2005;25(1):74-85.
  • 4. SL K. Methicillin-resistant Staphylococcus aureus infections in children: Epidemiology and clinical spectrum [15 July 2021]. Available from: http://www.uptodate.com/contents/Methicillin-resistant-Staphylococcus-aureus-infections-in-children:-Epidemiology-and-clinical-spectrum.
  • 5. Khamash DF, Voskertchian A, Tamma PD, Akinboyo IC, Carroll KC, Milstone AM. Increasing clindamycin and trimethoprim-sulfamethoxazole resistance in pediatric Staphylococcus aureus infections. Journal of the Pediatric Infectious Diseases Society. 2019;8(4):351-3.
  • 6. Dadashi M, Hajikhani B, Darban-Sarokhalil D, van Belkum A, Goudarzi M. Mupirocin resistance in Staphylococcus aureus: A systematic review and meta-analysis. Journal of global antimicrobial resistance. 2020;20:238-47.
  • 7. EUCAST. European Committee on Antimicrobial Susceptibility Testing, Clinical breakpoints [cited 2017]. Available from: http:// www.eucast.org/clinical_breakpoints/
  • 8. Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, et al. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. Jama. 2007;298(15):1763-71.
  • 9. Kaplan SL, Hulten KG, Gonzalez BE, Hammerman WA, Lamberth L, Versalovic J, et al. Three-year surveillance of community-acquired Staphylococcus aureus infections in children. Clinical Infectious Diseases. 2005;40(12):1785-91.
  • 10. Arikan K, Karadag-Oncel E, Aycan AE, Yuksekkaya S, Sancak B, Ceyhan M. Epidemiologic and Molecular Characteristics of Staphylococcus aureus Strains Isolated From Hospitalized Pediatric Patients. The Pediatric Infectious Disease Journal. 2020;39(11):1002-6.
  • 11. Crandall H, Kapusta A, Killpack J, Heyrend C, Nilsson K, Dickey M, et al. Clinical and molecular epidemiology of invasive Staphylococcus aureus infection in Utah children; continued dominance of MSSA over MRSA. Plos one. 2020;15(9):e0238991.
  • 12. Tong SY, Davis JS, Eichenberger E, Holland TL, Fowler Jr VG. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clinical microbiology reviews. 2015;28(3):603-61.
  • 13. Karbuz A, Karahan ZC, Aldemir-Kocabaş B, Tekeli A, Özdemir H, Güriz H, et al. Evaluation of antimicrobial susceptibilities and virulence factors of Staphylococcus aureus strains isolated from community-acquired and health-care associated pediatric infections. The Turkish journal of pediatrics. 2017;59(4):395-403.
  • 14. Yeşil E, Çelebi S, Arife Ö, HACIMUSTAFAOĞLU M. Evaluation of Methicillin Resistant Staphylococcus aureus Infection in Children. Güncel Pediatri. 2019;17(1):121-7.
  • 15. Gomes RT, Lyra TG, Alves NN, Caldas RM, Barberino M-G, Nascimento-Carvalho CM. Methicillin-resistant and methicillin-susceptible community-acquired Staphylococcus aureus infection among children. Brazilian Journal of Infectious Diseases. 2013;17:573-8.
  • 16. Ganesan SL, Mehta A, Lakshmikantha K, Jayashree M, Gautam V, Ray P. Community-acquired methicillin-resistant staphylococcus aureus infections in acutely ill children: a retrospective case-control study. The Indian Journal of Pediatrics. 2021;88(2):141-6.
  • 17. Sola C, Paganini H, Egea AL, Moyano AJ, Garnero A, Kevric I, et al. Spread of epidemic MRSA-ST5-IV clone encoding PVL as a major cause of community onset staphylococcal infections in Argentinean children. PLoS One. 2012;7(1):e30487.
  • 18. Galper E, Bdolah‐Abram T, Megged O. Assessment of infections rate due to community‐acquired Methicillin‐resistant Staphylococcus aureus and evaluation of risk factors in the paediatric population. Acta Paediatrica. 2021;110(5):1579-84.
  • 19. Kirby WM. Extraction of a highly potent penicillin inactivator from penicillin resistant staphylococci. Science. 1944;99(2579):452-3.
  • 20. Jevons MP. “Celbenin”-resistant staphylococci. British medical journal. 1961;1(5219):124.
  • 21. ŞANLI K. Hastane Kökenli ve Toplum Kaynaklı ID Staphylococcus aureus Suşlarının Çeşitli Antimikrobiyallere Duyarlılıkları. İstanbul Kanuni Sultan Süleyman Tıp Dergisi. 2020;12(2):188-93.
  • 22. Rağbetli C, Parlak M, Bayram Y, Guducuoglu H, Ceylan N. Evaluation of antimicrobial resistance in Staphylococcus aureus isolates by years. Interdisciplinary perspectives on infectious diseases. 2016;2016.
  • 23. Kumar SK KA. Antibiotic resistance pattern of Staphylococcus aureus infections in children. Int J Contemp Pediatr. 2019;6:727-31.
  • 24. Gurung RR, Maharjan P, Chhetri GG. Antibiotic resistance pattern of Staphylococcus aureus with reference to MRSA isolates from pediatric patients. Future science OA. 2020;6(4):FSO464.
  • 25. Staphylococcus aureus. 31st ed. Kimberlin DW BM, Jackson MA, Long SS, editor. Itasca, IL: American Academy of Pediatrics; 2018-2021.
  • 26. SL K. Staphylococcus aureus in children: Overview of treatment of invasive infections [July 2021]. Available from: http://www.uptodate.com/contents/Staphylococcus-aureus-in-children: Overview -of –treatment- of- invasive- infections.
  • 27. Stein M, Komerska J, Prizade M, Sheinberg B, Tasher D, Somekh E. Clindamycin resistance among Staphylococcus aureus strains in Israel: implications for empirical treatment of skin and soft tissue infections. International Journal of Infectious Diseases. 2016;46:18-21.
  • 28. Pérez G, Martiren S, Reijtman V, Romero R, Mastroianni A, Casimir L, et al. Community-acquired Staphylococcus aureus bacteremia in children: a cohort study for 2010-2014. Archivos argentinos de pediatria. 2016;114(6):508-13.
  • 29. Liu Y, Kong F, Zhang X, Brown M, Ma L, Yang Y. Antimicrobial susceptibility of Staphylococcus aureus isolated from children with impetigo in China from 2003 to 2007 shows community-associated methicillin-resistant Staphylococcus aureus to be uncommon and heterogeneous. The British journal of dermatology. 2009;161(6):1347-50.
  • 30. Arianpoor A, Estaji F, Naderinasab M, Askari E. Antimicrobial susceptibility pattern of Staphylococcus aureus isolates against newly marketed antibiotics: a report from Imam Reza Hospital of Mashhad, Iran. Razavi Int J Med. 2015;3(4):e31568.
  • 31. Rudresh MS, Ravi GS, Motagi A, Alex AM, Sandhya P, Navaneeth BV. Prevalence of mupirocin resistance among staphylococci, its clinical significance and relationship to clinical use. Journal of laboratory physicians. 2015;7(02):103-7.
  • 32. Sareyyüpoğlu B, Ozyurt M, Haznedaroğlu T, Ardiç N. Detection of methicillin and mupirocin resistance in staphylococcal hospital isolates with a touchdown multiplex polymerase chain reaction. Folia microbiologica. 2008;53(4):363-7.
  • 33. Hiramatsu K, Hanaki H, Ino T, Yabuta K, Oguri T, Tenover F. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. The Journal of antimicrobial chemotherapy. 1997;40(1):135-6.
  • 34. Krishnamurthy V, Saha A, Renushri BV, Nagaraj ER. Methicillin Resistant Staphylococcus aureus Carriage, Antibiotic Resistance and Molecular Pathogenicity among Healthy Individuals Exposed and Not Exposed to Hospital Environment. Journal of clinical and diagnostic research : JCDR. 2014;8(7):Dc04-8.
  • 35. Fomda BA, Thokar MA, Khan A, Bhat JA, Zahoor D, Bashir G, et al. Nasal carriage of Methicillin-resistant Staphylococcus aureus among healthy population of Kashmir, India. Indian journal of medical microbiology. 2014;32(1):39-43.
  • 36. Cosgrove SE, Qi Y, Kaye KS, Harbarth S, Karchmer AW, Carmeli Y. The impact of methicillin resistance in Staphylococcus aureus bacteremia on patient outcomes: mortality, length of stay, and hospital charges. Infection control and hospital epidemiology. 2005;26(2):166-74.
Toplam 36 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Klinik Tıp Bilimleri
Bölüm Araştırma
Yazarlar

Ümmühan Çay 0000-0001-5803-878X

Umit Celik 0000-0002-1200-0142

Adnan Barutçu 0000-0001-8930-1122

Ulaş Özdemir 0000-0003-4498-6142

Nevzat Ünal 0000-0001-5121-3100

Yayımlanma Tarihi 30 Haziran 2022
Kabul Tarihi 12 Mart 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 47 Sayı: 2

Kaynak Göster

MLA Çay, Ümmühan vd. “Clinical Characteristics and Resistance Patterns of Staphylococcus Aureus Infections in Children at a Tertiary Care Hospital in Southern Turkey”. Cukurova Medical Journal, c. 47, sy. 2, 2022, ss. 580-8.