Yenidoğanlarda Kolistin Tedavisinin Etkililiği ve Nefrolojik Yan Etkileri

Year 2020, Volume: 25 Issue: 3, 174 - 179, 29.10.2020

Seyda Ignak , Yesim Coskun Demet Yalcin İpek Akman

https://doi.org/10.21673/anadoluklin.680958

Abstract

Amaç: Toksik yan etkileri nedeniyle kolistin, uzun yıllardır ilk seçenek bir tedavi olarak görülmemektedir. Son zamanlarda ise yenidoğanlarda çoklu ilaç dirençli (ÇİD) gram-negatif bakteri (GNB) enfeksiyonlarına karşı son tedavi seçeneği olarak yeniden değerlendirilmektedir. Bu çalışmada da yenidoğanlarda kolistin kullanımının etkililiğini ve nefrolojik yan etkilerini inceleyerek literatüre katkıda bulunmak amaçlanmıştır.

Gereç ve Yöntemler: Retrospektif çalışmamız Ocak 2015—Şubat 2019 döneminde üçüncü basamak bir üniversite hastanesinin yenidoğan yoğun bakım ünitesinde gerçekleştirildi ve kültürle kanıtlanmış hastane kaynaklı GNB enfeksiyonları nedeniyle intravenöz kolistin tedavisi gören 30 hastayı içerdi. Tedavinin 1., 3. ve 10. günlerinde ölçülen serum sodyum, potasyum, fosfor, kalsiyum ve magnezyum düzeyleri, üre, kreatinin, aspartat aminotransferaz, alanin aminotransferaz değerleri ve idrar çıkışları analiz edildi.

Bulgular: Tüm hastalar en az 10 gün (ortalama 16,07±3,22 gün) kolistin tedavisi görmüştü ve tedavi dozu günde 5 mg/kg idi. Birinci ve 10. gün üre, kreatinin, kalsiyum, magnezyum ve idrar çıkış değerleri arasında istatistiksel olarak anlamlı fark olduğu görüldü (p˂0,05). Benzer biçimde, tedavinin 1. ve 10. gününde kaydedilmiş olan ölçümler karşılaştırıldığında magnezyum ve kalsiyum düzeylerinde anlamlı bir azalma (sırasıyla p=0,008, p=0,038), üre, kreatinin ve idrar çıkış değerlerinde ise anlamlı bir artış (sırasıyla p=0,027, p=0,022, p=0,001) gözlendi.

Tartışma ve Sonuç: Kolistin yenidoğanlarda ÇİD-GNB kaynaklı enfeksiyonların tedavisinde etkili bir ajandır. Yenidoğanlarda kolistin tedavisi sırasında nefrotoksisite yakından izlenmelidir. Yenidoğanlarda kolistin tedavisinin etkililiği ve güvenliliği daha büyük örneklemli, daha ileri çalışmalarla araştırılmalıdır.

Keywords

çoğul ilaç direnci, hastane enfeksiyonu, Kolistin, nefrotoksisite, yenidoğan

Supporting Institution

Bu çalışmada herhangi bir kurumdan maddi destek alınmamıştır.

The Efficacy and Nephrological Side Effects of Treatment with Colistin in Neonates

Abstract

Aim: For many years, colistin has not been considered a first-line treatment due to its toxic side effects. However, its use has recently been reevaluated as a last resort in the treatment of neonatal infections caused by multidrug-resistant (MDR) gram-negative bacteria (GNB). Accordingly, in this study we aimed to contribute to the literature by investigating the efficacy and nephrological effects of colistin use in neonates.

Materials and Methods: The retrospective study was conducted in the neonatal intensive care unit of a tertiary university hospital between January 2015 and February 2019 and included 30 patients who received intravenous treatment with colistin for culture-proven hospital-acquired GNB infections. We analyzed the serum sodium, potassium, phosphate, calcium and magnesium levels, urea, creatinine, aspartate aminotransferase and alanine aminotransferase values, and urine outputs measured on the 1st, 3rd, and 10th days of treatment.

Results: All patients were treated with colistin for at least 10 days (mean 16.07±3.22 days) and the treatment dose was 5 mg/kg per day. We observed a statistically significant difference between the 1st- and 10th-day urea, creatinine, calcium, magnesium, and urine output values (p˂0.05). Similarly, when we compared the measurements recorded on the 1st and 10th days of treatment, we found that the magnesium and calcium levels were significantly decreased (p=0.008 and p=0.038, respectively) while the urea, creatinine, and urine output values were significantly increased (p=0.027, p=0.022, p=0.001, respectively).

Discussion and Conclusion: Colistin is an effective agent in the treatment of MDR-GNB infections in neonates. Neonates should be closely monitored for nephrotoxicity during treatment with colistin. The efficacy and safety of neonatal treatment with colistin should be investigated with further, larger-sample studies.

Keywords

Colistin, multi-drug resistance, neonates, nephrotoxicity, nosocomial infection

References

• 1. Ramasethu J. Prevention and treatment of neonatal nosocomial infections. Matern Health Neonatol Perinatol. 2017;3:5.
• 2. Folgori L, Bielicki J, Heath PT, Sharland M. Antimicrobial-resistant gram-negative infections in neonates: burden of disease and challenges in treatment. Curr Opin Infect Dis. 2017;30(3):281–8.
• 3. Tamma PD, Lee CK. Use of colistin in children. Pediatr Infect Dis J. 2009;28(6):534–5.
• 4. Karaiskos I, Giamarellou H. Multidrug-resistant and extensively drug-resistant gram-negative pathogens: current and emerging therapeutic approaches. Expert Opin Pharmacother. 2014;15(10):1351–70.
• 5. Tekgunduz KS, Kara M, Caner I, Demirelli Y. Safety and efficacy of intravenous colistin in neonates with culture proven sepsis. Iran J Pediatr. 2015;25(4):e453.
• 6. Iosifidis E, Antachopoulos C, Ioannidou M, Mitroudi M, Sdougka M, Drossou-Agakidou V, et al. Colistin administration to pediatric and neonatal patients. Eur J Pediatr. 2010;169(7):867–74.
• 7. Ipek MS, Aktar F, Okur N, Celik M, Ozbek E. Colistin use in critically ill neonates: a case-control study. Pediatr Neonatol. 2017;58(6):490–6.
• 8. Cagan E, Bas EK, Asker HS. Use of colistin in a neonatal intensive care unit: a cohort study of 65 patients. Med Sci Monit. 2017;23:548–54.
• 9. Alan S, Yildiz D, Erdeve O, Cakir U, Kahvecioglu D, Okulu E, et al. Efficacy and safety of intravenous colistin in preterm infants with nosocomial sepsis caused by Acinetobacter baumannii. Am J Perinatol. 2014;31(12):1079–86.
• 10. Lee HY, Chiu CH. Efficacy and safety of using colistin in neonates. Pediatr Neonatol. 2017;58(6):473–4.
• 11. Lewis JR, Lewis SA. Colistin interactions with the mammalian urothelium. Am J Physiol Cell Physiol. 2004;286(4):913–22.
• 12. Falagas ME, Vouloumanou EK, Rafailidis PI. Systemic colistin use in children without cystic fibrosis: a systematic review of the literature. Int J Antimicrob Agents. 2009;33(6):1–3.
• 13. Karbuz A, Özdemir H, Yaman A, Kocabaş BA, Odek Ç, Güriz H, et al. The use of colistin in critically ill children in a pediatric intensive care unit. Pediatr Infect Dis J. 2014;33(1):19–24.
• 14. Levin AS, Barone AA, Penço J, Santos MV, Marinho IS, Arruda EA, et al. Intravenous colistin as therapy for nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Clin Infect Dis. 1999;28(5):1008–11.
• 15. Michalopoulos AS, Tsiodras S, Rellos K, Mentzelopoulos S, Falagas ME. Colistin treatment in patients with ICU-acquired infections caused by multiresistant gram-negative bacteria: the renaissance of an old antibiotic. Clin Microbiol Infect. 2005;11(2):115–21.
• 16. Landman D, Georgescu C, Martin DA, Quale J. Polymyxins revisited. Clin Microbiol Rev. 2008;21(3):449–65.
• 17. Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20(3):629–37.
• 18. Ilhan O, Bor M, Ozdemir SA, Akbay S, Ozer EA. Efficacy and safety of intravenous colistin in very low birth weight preterm infants. Paediatr Drugs. 2018;20(5):475–81.
• 19. Li J, Nation RL, Turnidge JD, Milne RW, Coulthard K, Rayner CR, et al. Colistin: the re-emerging antibiotic for multidrug-resistant gram-negative bacterial infections. Lancet Infect Dis. 2006;6(9):589–601.
• 20. Al-Aloul M, Miller H, Alapati S, Stockton PA, Ledson MJ, Walshaw MJ. Renal impairment in cystic fibrosis patients due to repeated intravenous aminoglycoside use. Pediatr Pulmonol. 2005;39(1):15–20.
• 21. Jajoo M, Kumar V, Jain M, Kumari S, Manchanda V. Intravenous colistin administration in neonates. Pediatr Infect Dis J. 2011;30(3):218–21.
• 22. Celik IH, Demirel G, Tatar Aksoy H, Saygan S, Canpolat FE, Uras N, et al. Acinetobacter baumannii: an important pathogen with multidrug resistance in newborns. Mikrobiyol Bul. 2011;45(4):716–22.
• 23. Celebi S, Hacimustafaoglu M, Koksal N, Ozkan H, Cetinkaya M. Colistimethate sodium therapy for multidrug-resistant isolates in pediatric patients. Pediatr Int. 2010;52(3):410–4.