Colistin an update on the antibiotic
clinical aspects PK/PD indices and equivalences
Abstract
In the recent 10 years, in this post-antibiotic era, colisitin has reappeared as the last resource to face infections caused by Pseudomonas aeruginosa, Acinetobacter baumannii complex and carbapenemase-producing enterobacteriaceae. At some point the use of colistin was discontinued given its potentially severe side effects, such as nephro and neurotoxicity , although it reemerges today as an essential part of antibiotic plans when facing extremely resistant pathogens. This increase in the use of colistin has led to an antibiotic resistance emergency and thus today we face a potentially catastrophic situation. This happens in particular in connection with the recently described presence of transferable plasmids among species containing genes that confer resistance to colistin (gen mcr-1), a mechanism also identified in our country. This review describes in detail the right dosing with the need to make load doses to achieve the appropriate therapeutic levels, based on current knowledge on pharmacokinetics and pharmacodynamics, as well as practical aspects in the administration of the drug in cases of postsurgical meningitis/ventriculitis and the use by nebulization for the treatment of ventilation associated pneumonia. The study points out the need to use colistin along with another in-vitro active antibiotic, especially in critical patients and those with a creatinine clearance over 80 ml/min. Dual pharmacotherapy is necessary in particular if the pathogen´s minimuminhibitory concentration (MIC) is higher than 1 mg/min, due to intra-treatment risk of sub-dosing and resistance emergency. Likewise, in second section, the study addresses the complex nature of dosing given by the different presentations available in the market at the national level, what has resulted in dosage errors, and thus a higher risk of toxicity. The insets and primary packaging of colistin presentation available in the Uruguayan marketing were reviewed with the purpose of improving understanding in connection with the labeling of the doses to be administered. With that information, the pharmaceutical industries agents will be formally asked in writing to inform the colistin content (active drug) and its prodrug colistimethate sodium. Last, a number of recommendations were prepared as to the Information the authors understand should appear in the different presentations of colistin that is available in the market, to avoid prescription errors.
References
(1) Rodríguez-Baño J, Cisneros JM, Cobos-Trigueros N, Fresco G, Navarro-San Francisco C, Gudiol C, et al. Diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae: guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology. Enferm Infecc Microbiol Clin 2015; 33(5):337.e1-337.e21.
(2) Paciel D, Palacio R, Bálsamo A, Moreira M, Hernández N, Cabeza E. Detección precoz y control de un brote de Pseudomonas aeruginosa productora de metalo-betalactamasa. Poster presentado en 43° Congreso Nacional de Medicina Interna, IV Congreso Nacional de Infectología. 2 al 4 de Noviembre 2016. Montevideo, Uruguay.
(3) Buroni M, Medina Presentado JC, Rieppi G, Paciel D. Consenso: uso de antimicrobianos en infecciones por microorganismos multi y panresistentes y guías para el tratamiento de bacterias productoras de KPC, agosto 2011. Montevideo: Cátedra de Enfermedades Infecciosas. UDELAR, 2011. Disponible en: http://www.infectologia.edu.uy/publicaciones/uso-de-antimicrobianos-en-infecciones-por-microorganismos-multi-y-panresistentes-y-guias-para-el-tratamiento-de-bacterias-productoras-de-kpc-agosto-2011. Consulta: 20 marzo 2017.
(4) Levy Hara G, Gould I, Endimiani A, Pardo PR, Daikos G, Hsueh PR, et al. Detection, treatment, and prevention of carbapenemase-producing Enterobacteriaceae: recommendations from an International Working Group. J Chemother 2013; 25(3):129-40.
(5) Rigatto MH, Oliveira MS, Perdigão-Neto LV, Levin AS, Carrilho CM, Tanita MT, et al. Multicenter prospective cohort study of renal failure in patients treated with colistin versus polymyxin B. Antimicrob Agents Chemother 2016; 60(4):2443-9.
(6) Vardakas KZ, Falagas ME. Colistin versus polymyxin B for the treatment of patients with multidrug-resistant Gram-negative infections: a systematic review and meta-analysis. Int J Antimicrob Agents 2017; 49(2):233-238.
(7) Nation RL, Li J, Cars O, Couet W, Dudley MN, Kaye KS, et al. Consistent global approach on reporting of colistin doses to promote safe and effective use. Clin Infect Dis 2014; 58(1):139-41.
(8) Nation RL, Velkov T, Li J. Colistin and polymyxin B: peas in a pod, or chalk and cheese? Clin Infect Dis 2014; 59(1):88-94.
(9) Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 2016; 16(2):161-8.
(10) Uruguay. Universidad de la República. Facultad de Medicina. Departamento de Bacteriología y Microbiología. Dos aislamientos clínicos de E. coli portadores de mcr-1 provenientes de dos centros de Montevideo. Montevideo: Departamento de Bacteriología y Microbiología, 2016.
(11) Puig JM. Colistin: errores terapéuticos frecuentes con su utilización. Buenos Aires: Universidad Abierta Interamericana, 2015. Disponible en: https://sites.google.com/site/farmacologiamedicinauai/uso-racional-de-medicamentos/colistin-errores-terapeuticos. Consulta: 20 enero 2017.
(12) Gauthier TP, Lantz E, Frederick C, Masmouei H, Ruiz-Serrano L, Smith L, et al. Variability within investigations of intravenous colistin: the scope of the problem. Clin Infect Dis 2014; 58(9):1340-2.
(13) Vidal Group Drug Information Systems. Colistiméthate sodique: mise à jour 24 Avril 2014. Issy-les-Moulineaux, Francia: Vidal Group, 2014. Disponible en: https://www.vidal.fr/substances/3936/colistimethate_sodique/. Consulta: 20 enero 2017.
(14) Landersdorfer CB, Nation RL. Colistin: how should it be dosed for the critically ill? Semin Respir Crit Care Med 2015; 36(1):126-35.
(15) MacLaren G, Spelman D. Colistin: an overview. En: UpToDate, Post TW (ed), UpToDate, Waltham, MA last updated Aug 15, 2016. Disponible en: http://www.uptodate.com/contents/colistin-an-overview. Consulta: 20 enero 2017.
(16) European Committee on Antimicrobial Susceptibility Testing. Recommendations for MIC determination of colistin (polymyxin E) as recommended by the joint CLSI-EUCAST Polymyxin Breakpoints Working Group. Växjö, Sweden: EUCAST, 2016. Disponible en: http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/General_documents/Recommendations_for_MIC-determination_of_colistin_March_2016.pdf. Consulta: 15 abril 2017.
(17) European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters Version 7.1, valid from 2017-03-10. Växjö, Sweden: EUCAST, 2017. Disponible en: http://www.eucast.org/clinical_breakpoints/. Consulta: 15 abril 2017.
(18) Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. CLSI Supplement M100. 27 ed. Wayne, PA: CLSI, 2017.
(19) Gibson GA, Bauer SR, Neuner EA, Bass SN, Lam SW. Influence of colistin dose on global cure in patients with bacteremia due to carbapenem-resistant gram-negative bacilli. Antimicrob Agents Chemother 2015; 60(1):431-6.
(20) Cheah SE, Li J, Tsuji BT, Forrest A, Bulitta JB, Nation RL. Colistin and polymyxin B dosage regimens against acinetobacter baumannii: differences in activity and the emergence of resistance. Antimicrob Agents Chemother 2016; 60(7):3921-33.
(21) Organización Panamericana de la Salud. Alerta epidemiológica: enterobacterias con resistencia tranferible a colistina, implicaciones para la salud pública en las Américas 10 de junio 2016. Washington, DC: OPS, 2016. Disponible en: http://antimicrobianos.com.ar/ATB/wp-content/uploads/2016/06/Enterobacterias-con-resistencia-transferible-a-colistina.pdf. Consulta: 15 abril 2017.
(22) Aguayo A, Mella S, Riedel G, Bello H, Domínguez M, González-Rocha G. Colistín en la era post-antibiótica. Rev Chil Infectol 2016; 33(2):166-76.
(23) Martínez-Martínez L. Muerte bacteriana y heterorresistencia a los antimicrobianos. Enferm Infecc Microbiol Clin 2008; 26(8):481-4.
(24) Li J, Rayner CR, Nation RL, Owen RJ, Spelman D, Tan KE, et al. Heteroresistance to colistin in multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother 2006; 50(9):2946-50.
(25) Nation RL, Garonzik SM, Li J, Thamlikitkul V, Giamarellos-Bourboulis EJ, Paterson DL, et al. Updated US and european dose recommendations for intravenous colistin: how do they perform? Clin Infect Dis 2016; 62(5):552-558.
(26) Markantonis SL, Markou N, Fousteri M, Sakellaridis N, Karatzas S, Alamanos I, et al. Penetration of colistin into cerebrospinal fluid. Antimicrob Agents Chemother 2009; 53(11):4907-10.
(27) Jiménez-Mejías ME, Pichardo-Guerrero C, Márquez-Rivas FJ, Martín-Lozano D, Prados T, Pachón J. Cerebrospinal fluid penetration and pharmacokinetic/pharmacodynamic parameters of intravenously administered colistin in a case of multidrug-resistant Acinetobacter baumannii meningitis. Eur J Clin Microbiol Infect Dis 2002; 21(3):212-4.
(28) Karaiskos I, Galani L, Baziaka F, Giamarellou H. Intraventricular and intrathecal colistin as the last therapeutic resort for the treatment of multidrug-resistant and extensively drug-resistant Acinetobacter baumannii ventriculitis and meningitis: a literature review. Int J Antimicrob Agents 2013; 41(6):499-508.
(29) Fried HI, Nathan BR, Rowe AS, Zabramski JM, Andaluz N, Bhimraj A, et al. The insertion and management of external ventricular drains: an evidence-based consensus statement. A statement for healthcare professionals from the Neurocritical Care Society. Neurocrit Care 2016; 24(1):61-81.
(30) Fotakopoulos G, Makris D, Chatzi M, Tsimitrea E, Zakynthinos E, Fountas K. Outcomes in meningitis/ventriculitis treated with intravenous or intraventricular plus intravenous colistin. Acta Neurochir (Wien) 2016; 158(3):603-10.
(31) Garonzik SM, Li J, Thamlikitkul V, Paterson DL, Shoham S, Jacob J, et al. Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients. Antimicrob Agents Chemother 2011; 55(7):3284-94.
(32) Dudhani RV, Turnidge JD, Coulthard K, Milne RW, Rayner CR, Li J, et al. Elucidation of the pharmacokinetic/pharmacodynamic determinant of colistin activity against Pseudomonas aeruginosa in murine thigh and lung infection models. Antimicrob Agents Chemother 2010; 54(3): 1117-24.
(33) Dudhani RV, Turnidge JD, Nation RL, Li J. fAUC/MIC is the most predictive pharmacokinetic/pharmacodynamic index of colistin against acinetobacter baumannii in murine thigh and lung infection models. J Antimicrob Chemother 2010; 65(9):1984-90.
(34) Falagas ME, Kasiakou SK. Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Crit Care 2006; 10(1):R27.
(35) De Bonis P, Lofrese G, Scoppettuolo G, Spanu T, Cultrera R, Labonia M, et al. Intraventricular versus intravenous colistin for the treatment of extensively drug resistant Acinetobacter baumannii meningitis. Eur J Neurol 2016; 23(1):68-75.
(36) Johns Hopkins Medicine. Antibiotic guidelines 2015-2016: treatment recommendations for adult inpatients. Baltimore, Maryland: Johns Hopkins Medicine, 2016. Disponible en: www.hopkinsmedicine.org/amp/guidelines/antibiotic_guidelines.pdf. Consulta: 15 abril 2017.
(37) Bihan K, Lu Q, Enjalbert M, Apparuit M, Langeron O, Rouby JJ, et al. Determination of colistin and colistimethate levels in human plasma and urine by high-performance liquid chromatography-tandem mass spectrometry. Ther Drug Monit 2016; 38(6):796-803.
(38) Mercier T, Tissot F, Gardiol C, Corti N, Wehrli S, Guidi M, et al. High-throughput hydrophilic interaction chromatography coupled to tandem mass spectrometry for the optimized quantification of the anti-Gram-negatives antibiotic colistin A/B and its pro-drug colistimethate. J Chromatogr A 2014; 1369:52-63.
(39) Nation RL, Garonzik SM, Thamlikitkul V, Giamarellos-Bourboulis EJ, Forrest A, Paterson DL, et al. Dosing guidance for intravenous colistin in critically-ill patients. Clin Infect Dis 2017; 64(5):565-571.
(40) Dalfino L, Puntillo F, Mosca A, Monno R, Spada ML, Coppolecchia S, et al. High-dose, extended-interval colistin administration in critically ill patients: is this the right dosing strategy?: a preliminary study. Clin Infect Dis 2012; 54(12):1720-6.
(41) Tunkel AR, Hasbun R, Bhimraj A, Byers K, Kaplan SL, Michael Scheld W, et al. 2017 Infectious Diseases Society of America's Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis. Clin Infect Dis 2017 Feb 14. Epub ahead of print.
(42) Grille P, Bertullo M. Infecciones posneuroquirúrgicas. En: Biestro A. CTI protocolos. Montevideo: Editorial Cuadrado, 2015: 43-8.
(43) Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016; 63(5):e61-e111.
(44) Wenzler E, Fraidenburg DR, Scardina T, Danziger LH. Inhaled antibiotics for gram-negative respiratory infections. Clin Microbiol Rev 2016; 29(3):581-632.
(45) Ari A. Jet, ultrasonic, and mesh nebulizers: an evaluation of nebulizers for better clinical outcomes. Eurasian J Pulmonol 2014; 16(1):1-7.
(46) Bassetti M, Luyt CE, Nicolau DP, Pugin J. Characteristics of an ideal nebulized antibiotic for the treatment of pneumonia in the intubated patient. Ann Intensive Care 2016; 6(1):35.
(47) Vincent JL, Bassetti M, François B, Karam G, Chastre J, Torres A, et al. Advances in antibiotic therapy in the critically ill. Crit Care 2016; 20(1):133.
(48) Dhanani J, Fraser JF, Chan HK, Rello J, Cohen J, Roberts JA. Fundamentals of aerosol therapy in critical care. Crit Care 2016; 20(1):269.
(49) Rello J, Solé-Lleonart C, Rouby JJ, Chastre J, Blot S, Poulakou G, et al. Use of nebulized antimicrobials for the treatment of respiratory infections in invasively mechanically ventilated adults: a position paper from the European Society of Clinical Microbiology and Infectious Diseases. Clin Microbiol Infect 2017; 23(9):629-39.
(50) Sociedad Argentina de Infectología. Actualización: alerta presentaciones comerciales colistina, disponibilidad de polimixina B en Argentina. Buenos Aires: SADI, 2015. Disponible en: http://antimicrobianos.com.ar/ATB/wp-content/uploads/2015/09/Actualizaci%C3%B3n-alerta-colistina-julio-2015-2.pdf. Consulta: 15 abril 2017.
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