Mustafa BAKIR, Eren ÇAĞAN, Nurhayat YAKUT, Ayşe KARAASLAN, Eda KADAYİFCİ KEPENEKLİ, Serkan ATICI, Gülşen AKKOÇ, Sevliya DEMİR ÖCAL, Ahmet SOYSAL

Intravenous Colistin Use for Multidrug-Resistant Gram-Negative Infections in Pediatric Patients

Background: The emergence of infections due to multidrug-resistant Gram-negative bacilli (MDRGNB) has led to the resurrection of colistin use. The data on colistin use and drug-related adverse effects in children are scarce. Aims: In this study, we aimed to evaluate the clinical efficacy and safety of colistin use in critically ill pediatric patients. Study Design: This study has a retrospective study design. Methods: Sixty-one critically ill children were identified through the department's patient files archive during the period from January 2011 to November 2014. Results: Twenty-nine females and thirty-two males with a mean±standard deviation (SD) age of 61±9 months (range 0-216, median 12 months) received IV colistin due to MDR-GNB infections. Bacteremia (n=23, 37.7%) was the leading diagnosis, followed by pneumonia (n=19, 31%), clinical sepsis (n=7, 11.4%), wound infection (n=6, 9.8%), urinary tract infection (n=5, 8.1%) and meningitis (n=1, 1.6%). All of the isolates were resistant to carbapenems; however, all were susceptible to colistin. The isolated microorganisms in decreasing order of frequency were: Acinetobacter baumanni (n=27, 44.2%), Pseudomonas aeruginosa (n=17, 27.8%), Klebsiella pneumoniae (n=6, 9.8%), K. pneumoniae and Stenotrophomonas maltophilia (n=1, 1.6%), K. pneumoniae and A. baumanni (n=1, 1.6%), K. oxytoca (n=1, 1.6%) and Enterobacter cloacae (n=1, 1.6%). In seven patients, no microorganisms were detected; however, five of these patients were colonized by carbapenem-resistant K. pneumoniae. The mean duration of colistin therapy was 12 days (range 3-45). Colistin was administered concomitantly with one of the following antibiotics: carbapenem (n=50, %82), ampicillin-sulbactam (n=5, 8%), quinolones (n=5, 8%), rifampicin (n=1, 1.6%). Carbapenem was the most frequently used antibiotic. Nephrotoxicity was observed in only 1 patient, and we did not observe neurotoxicity in this study. All the patients received intravenous colistin (colisthimethate) at a dosage of 5 mg/kg daily by dividing it in three equal doses. Seven (11.4%) patients died during the study period. Conclusion: Colistin appears to be a safe and efficacious drug for treating MDR-GNB infections in children.

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Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, 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;18:268-81. [CrossRef]
Rice LB. Federal funding for the study of antimicrobial re- sistance in nosocomial pathogens: no ESKAPE. J Infect Dis 2008;197:1079-81. [CrossRef]
Perl TM, Dvorak L, Hwang T, Wenzel RP. Long-term surviv- al and function after suspected Gram-negative sepsis. JAMA 1995;274:338-45. [CrossRef]
Falagas ME, Karageorgopoulos DE, Nordmann P. Therapeutic options for infections with Enterobacteriaceae producing car- bapenem-hydrolyzing enzymes. Future Microbiol 2011;6:653- 66. [CrossRef]
Falagas ME, Kasiakou SK. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacte- rial infections. Clin Infect Dis 2005;40:1333-41. [CrossRef]
Spapen H, Jacobs R, Van Gorp V, Troubleyn J, Honoré PM. Renal and neurological side effects of colistin in critically ill patients. Ann Intensive Care 2011;1:14. [CrossRef]
Yahav D, Farbman L, Leibovici L, Paul M. Colistin: new les- sons on an old antibiotic. Clin Microbiol Infect 2012;18:18-29. [CrossRef]
Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections. Am J Infect Con- trol 1988;16:128-40. Erratum in: Am J Infect Control 1988;16: 177. [CrossRef]
Falagas ME, Karageorgopoulos DE. Pandrug resistance (PDR), extensive drug resistance (XDR), and multidrug resistance (MDR) among gram-negative bacilli: Need for international harmonization in terminology. Clin Infect Dis 2008;46:1121-2. [CrossRef]
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;6:589-601. [CrossRef]
X-Gen Pharmaceuticals Inc. Colistimethate for injection, USP: for intramuscular and intravenous use. [Accessed April 9, 2010]; Available from: http://x-gen.us/wp-content/uploads/2014/03/ Colistimethate_pi.pdf
European Medicines Agency completes review of polymyxin- based medicines. (Published in 24/10/2014); Available from: http://www.ema.europa.eu/docs/en_GB/document_library/ Press_release/2014/10/WC500176334.pdf
Falagas ME, Sideri G, Vouloumanou EK, Papadatos JH, Kaf- etzis DA. Intravenous colistimethate (Colistin) use in criti- cally Ill children without cystic fibrosis. Pediatr Infect Dis J 2009;28:123-7. [CrossRef]
Cheng CY, Sheng WH, Wang JT, Chen YC, Chang SC. Safety and efficacy of intravenous colistin (colistin methanesulpho- nate) for severe multidrug-resistant gram-negative bacterial in- fections. Int J Antimicrob Agents 2010;35:297-300. [CrossRef]
Karbuz A, Özdemir H, Yaman A, Kocabaş BA, Ödek C, Güriz H, et al. The use of colistin in critically Ill children in a pediatric in- tensive care unit. Pediatr Infect Dis J 2014;33:19-24. [CrossRef]
Clinical and Laboratory Standards Institute. Performance stan- dards for antimicrobial susceptibility testing: twenty-first infor- mational supplement M100-S21. Wayne, PA, USA: CLSI; 2011.
The European Committee on Antimicrobial Susceptibility Test- ing (EUCAST). Clinical MIC breakpoints. Available from: http://www.eucast.org/clinical_breakpoints.
Furtado GH, d'Azevedo PA, Santos AF, Gales AC, Pignatari AC, Medeiros EA. Intravenous polymyxin B for the treatment of nosocomial pneumonia caused by multidrug-resistant Pseu- domonas aeruginosa. Int J Antimicrob Agents 2007;30:315-9. [CrossRef]
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;33:503. [CrossRef]
Ouderkirk JP, Nord JA, Turett GS, Kislak JW. Polymyxin B nephrotoxicity and efficacy against nosocomial infections caused by multiresistant Gram-negative bacteria. Antimicrob Agents Chemother 2003;47:2659-62. [CrossRef]
Nation RL, Li J. Polymyxins. In: The Use of Antibiotics, Kucers A. editor. London: Heinemann; 2010:955. [CrossRef]
Plachouras D, Karvanen M, Friberg LE, Papadomichelakis E, Antoniadou A, Tsangaris I, et al. Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intra- venous administration in critically ill patients with infections caused by gram-negative bacteria. Antimicrob Agents Chemoth- er 2009;53:3430-6. [CrossRef]
Dalfino L, Puntillo F, Mosca A, Monno R, Spada ML, Cop- polecchia S, et al. High-dose, extended-interval colistin admin- istration in critically ill patients: is this the right dosing strategy? A preliminary study. Clin Infect Dis 2012;54:1720-6. [CrossRef]
Hartzell JD, Neff R, Ake J, Howard R, Olson S, Paolino K, et al. Nephrotoxicity associated with intravenous colistin (colisti- methate sodium) treatment at a tertiary care medical center. Clin Infect Dis 2009;48:1724-8. [CrossRef]
Falagas ME, Rizos M, Bliziotis IA, Rellos K, Kasiakou SK, Mi- chalopoulos A. Toxicity after prolonged (more than four weeks) administration of intravenous colistin. BMC Infect Dis 2005; 5:1. [CrossRef]
Ziad Daoud, Najwa Mansour, Khalil Masri. Synergistic Combi- nation of Carbapenems and Colistin against P. aeruginosa and A. baumannii. J Med Microbiol 2013;3:253-8. [CrossRef]
Falagas ME, Sideri G, Vouloumanou EK, Papadatos JH, Kaf- etzis DA. Intravenous colistimethate (colistin) use in criti- cally ill children without cystic fibrosis. Pediatr Infect Dis J 2009;28:123-7. [CrossRef]
Kapoor K, Jajoo M, Dublish S, Dabas V, Gupta S, Manchanda V. Intravenous colistin for multidrug-resistant gram-negative in- fections in critically ill pediatric patients. Pediatr Crit Care Med 2013;14:268-72. [CrossRef]