Gülşah KAYA AKSOY, Sariye Elif ÖZYAZICI ÖZKAN, Gönül TEZEL, Gülperi TİMURTAŞ DAYAR, Muhammet KÖŞKER, Çağla Serpil DOĞAN

Assesment of colistin related side effects in premature neonates

Background. Colistin is an antibiotic in the polymyxin group and is especially important in the elimination of multi-drug resistant gram negative bacteria. To date, there are many studies investigating colistin related side effects, especially nephrotoxicity. However, there are few studies involving premature neonates, and this study aimed to investigate the side effects of colistin in this particular patient group. Methods. Between January 2016 and May 2019, the medical records of premature neonates treated with colistin were retrospectively reviewed. The diagnosis of acute kidney injury (AKI) was performed according to the modified neonatal KDIGO criteria. Serum electrolyte levels were recorded at the initiation of colistin treatment and 4-7 days after. Results. A total of 47 premature neonates; with a median gestational age of 27 weeks and median weight of 970 g at birth were included in the study. The median postnatal day of colistin initiation was 24 days and mean duration of colistin therapy was 15.95 ± 3.70 days. Colistin was combined with aminoglycosides in 44.6% of the patients. Acute kidney injury was documented in 17.0% of premature neonates. (n = 6 for stage 1, n = 2 for stage 2, none of the patients had stage 3). In univariate analysis, gestational age and concomitant aminoglycoside use were associated with AKI development (OR, 0.446; 95% CI 0.238-0.832; p = 0.011 and OR, 1.324; 95% CI 1.023-7.584; p = 0.024). Mean magnesium level significantly decreased after colistin treatment (1.70 ± 0.84 vs. 1.57 ± 0.29, p = 0.017) and the frequency of hypomagnesemia increased after colistin use (78.7% vs. 91.5%, p = 0.031). Frequency of elevated AST increased from 23.4% to 44.7% following colistin use (p = 0.031).Conclusions. Colistin-related side effects observed in premature neonates are not as common as in pediatric patients. Electrolyte imbalance is observed more frequently in this age group following colistin use. We suggest strict serum electrolyte level monitoring, especially magnesium, in premature neonates that are receiving colistin.

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1.Stoll BJ, Hansen N, Fanaroff AA, et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002; 110 (2 Pt 1): 285-291.
2.Oliveira PMN, Buonora SN, Souza CLP, et al. Surveillance of multidrug-resistant bacteria in pediatric and neonatal intensive care units in Rio de Janeiro State, Brazil. Rev Soc Bras Med Trop 2019; 52: e20190205.
3.Yusef D, Shalakhti T, Awad S, Algharaibeh H, Khasawneh W. Clinical characteristics and epidemiology of sepsis in the neonatal intensive care unit in the era of multi-drug resistant organisms: a retrospective review. Pediatr Neonatol 2018; 59: 35-41.
4.Tsai MH, Chu SM, Hsu JF, et al. Risk factors and outcomes for multidrug-resistant gram-negative bacteremia in the NICU. Pediatrics 2014; 133: e322-e329.
5.Grégoire N, Aranzana-Climent V, Magréault S, Marchand S, Couet W. Clinical pharmacokinetics and pharmacodynamics of colistin. Clin Pharmacokinet 2017; 56: 1441-1460.
6.Antachopoulos C, Iosifidis E. Colistin use in neonates and children with infections due to carbapenem-resistant bacteria. Pediatr Infect Dis J 2017; 36: 905-907.
7.Hoeprich PD. The polymyxins. Med Clin North Am 1970; 54: 1257-1265.
8.Falagas ME, Kasiakou SK. Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Crit Care 2006; 10: R27.
9.Suzuki T, Yamaguchi H, Ogura J, Kobayashi M, Yamada T, Iseki K. Megalin contributes to kidney accumulation and nephrotoxicity of colistin. Antimicrob Agents Chemother 2013; 57: 6319-6324.
10.Sahbudak Bal Z, Kamit Can F, Yazici P, et al. The evaluation of safety and efficacy of colistin use in pediatric intensive care unit: results from two reference hospitals and review of literature. J Infect Chemother 2018; 24: 370-375.
11.Jajoo M, Kumar V, Jain M, Kumari S, Manchanda V. Intravenous colistin administration in neonates. Pediatr Infect Dis J 2011; 30: 218-221.
12.Kumar PP, Giri SR, Shaikh FAR, Panigrahy N, Chirla D. Safety and efficacy of intravenous colistin in children. Indian Pediatr 2015; 52: 129-130.
13.Alan S, Yildiz D, Erdeve O, et al. Efficacy and safety of intravenous colistin in preterm infants with nosocomial sepsis caused by Acinetobacter baumannii. Am J Perinatol 2014; 31: 1079-1086.
14.Kramer MS. Determinants of low birth weight: methodological assessment and meta-analysis. Bull World Health Organ 1987; 65: 663-737.
15.Walsh MC, Kliegman RM. Necrotizing enterocolitis: treatment based on staging criteria. Pediatr Clin North Am 1986; 33: 179-201.
16.Selewski DT, Charlton JR, Jetton JG, et al. Neonatal acute kidney injury. Pediatrics 2015; 136: e463-e473.
17.Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18: 268-281.
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: 475-481.
19.İpek MS, Aktar F, Okur N, Celik M, Ozbek E. Colistin use in critically ill neonates: a case-control study. Pediatr Neonatol 2017; 58: 490-496.
20.Tamma PD, Newland JG, Pannaraj PS, et al. The use of intravenous colistin among children in the United States: results from a multicenter, case series. Pediatr Infect Dis J 2013; 32: 17-22.
21.Temocin F, Erdinc S, Tulek N, Demirelli M, Bulut C, Ertem G. Incidence and risk factors for colistin-associated nephrotoxicity. Jpn J Infect Dis 2015; 68: 318-320.
22.Al-Lawama M, Aljbour H, Tanash A, Badran E. Intravenous colistin in the treatment of multidrug-resistant Acinetobacter in neonates. Ann Clin Microbiol Antimicrob 2016; 15: 8.
23.Cakir U, Alan S, Zeybek C, et al. Acquired Bartter-like syndrome associated with colistin use in a preterm infant. Ren Fail 2013; 35: 411-413.
24.Jetton JG, Askenazi DJ. Acute kidney injury in the neonate. Clin Perinatol 2014; 41: 487-502.