The Use of Intravenous and Aerosolized Polymyxins for the Treatment of Infections in Critically Ill Patients: A Review of the Recent Literature

Falagas, Matthew E.; Kasiakou, Sofia K.; Tsiodras, Sotirios; Michalopoulos, Argyris

doi:10.3121/cmr.4.2.138

Cited by 139 publications

(95 citation statements)

References 47 publications

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“…The drug acts on outer cell membrane of Gram-negative bacteria (GNB) and releases lipopolysaccharides [15]. This in turn results into disruption of cell membrane leading to leakage of cell content, causing cell lysis and finally cell death [16,17]. Within years after the reuse of colistin, there have been reports of colistin-resistant strains [18].…”

Section: Discussionmentioning

confidence: 99%

Colistin Resistance in Carbapenem-Resistant Klebsiella Pneumoniae Strains

Bhaskar

Mulki

Joshi

et al. 2017

Asian J Pharm Clin Res

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Objective: There is an increasing use of colistin consequent to increase in the infections caused by carbapenem-resistant Klebsiella pneumoniae. The present study was conducted to determine the minimum inhibitory concentration (MIC) of colistin and the resistance pattern of colistin in carbapenem-resistant K. pneumoniae (CRKP) strains in our intensive care unit (ICU).Methods: Antibiotic susceptibility testing for other antimicrobial agents was done by Kirby-Bauer disk diffusion method. MIC of colistin was determined by agar dilution method. The results of antibiotic susceptibility testing were interpreted as per Clinical Laboratory Standard Institute guidelines 2016 and MIC of colistin were interpreted as per European Committee on Antimicrobial susceptibility testing. The carbapenem resistance was phenotypically detected by modified hodge test and imipenem/imipenem ethylenediaminetetraacetic acid disk method.Results: Out of 518 K. pneumoniae, 329 were resistant to carbapenems, and 91 isolates showed resistance to colistin. The MIC of colistin ranged between 4 and >512 ug/ml and MIC 90 was 16 ug/L and MIC 50 was 4 ug/ml. A majority of the colistin-resistant isolates were found in multidisciplinary ICU (85/91). Conclusion:The emergence of colistin-resistant strains is a major problem due to limited treatment options for infections caused by CRKP carbapenemase producing K. pneumoniae. Colistin should not be used alone, combination therapy should be preferred.

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Section: Discussionmentioning

confidence: 99%

Colistin Resistance in Carbapenem-Resistant Klebsiella Pneumoniae Strains

Bhaskar

Mulki

Joshi

et al. 2017

Asian J Pharm Clin Res

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“…La utilización habitual de un frasco cada 8 horas no permite alcanzar las dosis recomendadas por kilo de peso que se proponen en el Reino Unido. En los pacientes sin falla renal en nuestra serie, el promedio diario de dosis utilizado fue de 3,24 mg/kg, inferior al rango 4 a 6 mg/kg propuesto en ese país 16,17 . El no alcanzar una dosis mínima, limita el efecto terapéutico, ya que no permite un efecto bactericida concentración dependiente 2,12 .…”

Section: Discussionunclassified

“…Si en Chile se tuviera disponible la presentación estadounidense, las dosis podrían ajustarse entre 2 y 5 mg/kg/ día, ya que la presentación de ese país indica los mg de colistín sulfato disponibles en el frasco (independiente al hecho de que venga como colistimetato sódico) y, además, el envase trae 150 mg del compuesto base 16,17 . Matthew Falagas, un experto en el área, propone que para evitar esta confusión es mejor utilizar una dosificación basada en unidades internacionales y recomienda una dosis de 50.000 a 75.000 UI/kg/día en tres dosis en pacientes con función renal normal 16 . Él y otros autores griegos utilizan habitualmente tres millones de UI cada ocho horas; el triple de la dosis utilizada en nuestros pacientes sin falla renal 6,11 .…”

Section: Discussionunclassified

Colistín en infecciones nosocomiales por bacilos gramnegativos pan-resistentes

et al. 2007

Rev. chil. infectol.

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Emergence of panresistant gram negative bacilli has lead to the progressive reintroduction of intravenous colistin. Aim: To describe the clinical experience observed with this compound. Methodology: A retrospective analysis was performed for all treatments lasting > 48 hours. Medical records were analyzed to obtain clinical parameters and microbiological data, evaluate clinical response and evolution until discharge. Main results: 24 treatments lasting > 48 hours were applied between June 2005 and September 2006. Intravenous colistin was indicated to treat cases of ventilator-associated (VA) pneumonia (n = 10; 41.7%), abscess or collections (12.5%), bloodstream infections, non-VA pneumonia or urinary tract infections (4.2% each one, respectively). Treatment was initiated on average at 3.2 days (± 2.85) from diagnosis of infection. All courses were microbiologically-guided, and involved P. aeruginosa or A. baumannii isolates. Susceptibility was evaluated by E-test in 11 isolates (MIC 90 3.6 µg/mL, range 0.38 to 4 µg/mL). One isolate was resistant to colistin (9%). A favorable response was observed in 12 treatments (50%) with a relapse in 5 cases (41.7%). Being treated for pneumonia was the only factor associated to failure. (p = 0.04) Eradication was documented in 8 cases (33.3%) and persistence in 11 (45.8%). In 5 cases a microbiological follow-up was not available. Survival at time of discharge was 45.5%. (n = 10) None of the treatment courses was associated with nefrotoxicity. Conclusions: Intravenous colistin is a safe compound useful to treat various nosocomial infections due to pan-resistant gram negative bacilli. Nonetheless, its clinical efficacy is limited, especially among patients treated for nosocomial pneumonia.Key words: colistin, sepsis, Gram negative bacilli, panresistance. Palabras claves: colistín, bacilos gramnegativos, infecciones, pan-resistencia.Los datos epidemiológicos sobre la frecuencia de bacilos gramnegativos multi o pan-resistentes son escasos en el país, debido a que sólo recientemente se ha creado un sistema de vigilancia activo. Se trata, sin embargo, de un hecho progresivo radicado, especialmente, en las unidades de cuidados intensivos de hospitales de la Región Metropolitana. En el Hospital Clínico de la Universidad de Chile, la frecuencia de aislados de A. baumannii o P. aeruginosa pan-resistentes ha aumentado en forma constante desde el año 2004, motivando la importación de colistín para el manejo de estas infecciones.Colistín endovenoso es un fármaco de alto costo, no exento de toxicidad renal y carece de una evaluación rigurosa de su eficacia clínica. Por ejemplo, el costo diario de tratamiento con este antimicrobiano supera los 60 mil pesos chilenos (aproximadamente 120 U$). Habitualmente, los pacientes son tratados por 10 o más días. Introducciónas infecciones nosocomiales son un problema frecuente y se asocian a morbilidad, aumento de los costos y letalidad atribuible. Están asociadas a microorganismos multi o pan-resistentes que limitan, seriamente, las posibilidades de m...

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“…Ayrıca son yıllar-da elde edilen klinik deneyimler polimiksinlerin önceden sanıldığı kadar toksik olmadığını da göstermiş, bu antibiyotiklerin çoklu ilaç direnci gösteren Gram negatif bakterilerin sebep olduğu SSS infeksiyonlarında intratekal ya da intraventriküler olarak kullanımının yararı gösteril-miş, nebulize polimiksinin pnömonili hastalarda i.v. tedaviye ek olarak ya da tek başına kullanı-labileceği bildirilmiştir (5) . Antimikrobiyallere duyarlılık coğrafi böl-geler, hastaneler, hatta hastanelerin bölümleri arasında farklılık gösterebilmektedir.…”

Section: Introductionunclassified