Efficacy and safefy of Polymyxin B treatment for neutropenic patients suffering from refractory Gram-negative bacterial bloodstream infection / 中华血液学杂志

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.

Dois casos de hiperpigmentação cutânea induzido pela polimixina B / Two cases of skin hyperpigmentation induced by polymyxin B

INTRODUÇÃO: O processo de hiperpigmentação cutânea envolve mecanismos bioquímicos e imunológicos que estimulam a melanogênese e apesar da nefrotoxicidade consistir na reação adversa mais relevante da polimixina B, o antimicrobiano também está associado a esta alteração. RELATO DE CASO: Caso 1: paciente masculino diagnosticado com Linfoma de Hodgkin, que desenvolveu hiperpigmentação cutânea após iniciar tratamento com meropenem, anidulafungina e polimixina B devido a um quadro de choque séptico. Caso 2: paciente masculino admitido na UTI por rebaixamento do nível de consciência e suspeita de IAMCSST, diagnosticado com endocardite e pericardite, que também apresentou hiperpigmentação cutânea durante terapia com anfotericina B e polimixina B. CONCLUSÃO: Após criteriosa avaliação da ordem cronológica e medicamentos utilizados pelos pacientes, concluímos que a polimixina B desencadeou a hiperpigmentação em ambos. Por fim, baseado ao mecanismo desta reação e aos achados científicos, estudos clínicos que possam evidenciar um provável efeito farmacológico com o uso de antagonistas H2 são necessários.

INTRODUCTION: The skin hyperpigmentation process involves biochemical and immunological mechanisms that stimulate melanogenesis and although nephrotoxicity consists of the most relevant adverse reaction of polymyxin B, it is also associated with this changes. CASE REPORT: Case 1: male patient, diagnosed with Hodgkin's Lymphoma, who developed skin hyperpigmentation after starting treatment with meropenem, anidulafungin and polymyxin B due to a septic shock. Case 2: male patient, admitted to the ICU for decreased level of consciousness and suspected STEMI, diagnosed with endocarditis and pericarditis, who also presented skin hyperpigmentation during therapy with amphotericin B and polymyxin B. CONCLUSION: After careful evaluation of chronological order and drugs used by patients, we conclude that polymyxin B caused hyperpigmentation in both patients. Finally, based on the mechanism of this reaction and the scientific findings, clinical studies that may evidence a probable pharmacological effect with the use of H2 antagonists are required.

Factores asociados a nefrotoxicidad por polimixina B en un hospital universitario de Neiva, Colombia. 2011-2015 / Risk factors for acute kidney injury in patients treated with polymyxin B experience from 139 cases at a tertiary university hospital in Colombia

Background: The rise of infections caused by multidrug-resistant Gram negative bacilli (MDR-GNB), added to paucity of newer therapy, have led to increase polymyxin B use, despite adverse renal toxicity profile. Aim: To determine the incidence and risk factors associated to acute kidney injury (AKI) and polymyxin B use, in patients with infections caused by MDR-GNB. Methods: A retrospective cohort, with a nested case-control study of adults who received polymyxin B for more than 48 hours at a tertiary university hospital in Colombia (2011-2015) was performed. AKI was defined by AKIN criteria. Results: Of 139 patients included in our study, 102 were male with median age of 49 years (IQR:28-64). Sixty-one patients (44%) developed AKI. Independent risk factors for development of AKI included: total polymyxin B daily dose (OR = 2.19, 95% CI, 1.04-4.64); length of stay at ICU (OR = 1.03, 95% CI, 1.00-1.06); nosocomial infection (OR = 6.43, 95% CI, 2.12, -19.47); and vasopressor use (OR = 5.38, 95% CI, 2.40-12.07). Mortality was higher among AKI-patients (58.6%) compared with non-AKI patients (25.6%) (p = 0.001). Conclusion: In this study, the rate of AKI associated to polymyxin B use was greater than reported in studies from last decade, and associated with increased mortality. AKI associated to polymyxin B use is likely multifactorial and aggravated by the critically ill state of patients suffering nosocomial infections caused by mdr-gnb.

Introducción: El surgimiento de infecciones graves causadas por bacilos gramnegativos multi-resistentes (BGN-MR), sumado a la carencia de nuevas opciones terapéuticas efectivas, ha llevado a retomar el uso de polimixina B, a pesar de su perfil de nefrotoxicidad. Objetivo: Determinar la incidencia y factores relacionados con el desarrollo de nefrotoxicidad asociada al uso de polimixina B, en pacientes adultos con infecciones causadas por BGN-MR. Materiales y Métodos: Estudio observacional, analítico, tipo cohorte histórica, con un análisis de casos y controles anidado, realizado en un hospital universitario de tercer nivel de Colombia entre 2011 y 2015, en pacientes que recibieron polimixina B intravenosa por más de 48 h. Resultados: De 139 pacientes incluidos en el estudio, 61 (44%) desarrollaron falla renal aguda por criterios AKIN. Los factores de riesgo independientes para nefrotoxicidad fueron: dosis diaria de polimixina B (OR 2,19; IC 95% 1,04-4,64), días de estancia en UCI (OR 1,03; IC 95% 1,00-1,06), presencia de infección nosocomial (OR 6,43; IC 95% 2,12-19,47) y requerimiento de fármacos vasopresores (OR 5,38; IC 95%: 2,40-12,07). Conclusión: La tasa de nefrotoxicidad observada en pacientes que recibieron polimixina B es considerable; su origen probablemente multifactorial y agravada por estado crítico de pacientes con infecciones nosocomiales por BGN-MR.

Fatores de risco associados à lesão renal aguda em pacientes tratados com polimixina B em um hospital terciário / Risk factors for acute kidney injury in patients treated with polymyxin B at a Tertiary Care Medical Center

Resumo Introdução: O uso de polimixinas foi praticamente abandonado nos anos 1970 devido as altas taxas de nefropatia. Entretanto, foram reintroduzidas na prática médica devido a sua ação contra bactérias gram negativas resistentes a carbapenemicos. A literatura recente sugere uma taxa de nefropatia mais baixa do que a historicamente reportada. Objetivo: Determinar a incidência de nefropatia associada ao uso de polimixina utilizando os critérios de RIFLE. Métodos: Foi realizada coorte retrospectiva de todos pacientes adultos que receberam polimixina B no Hospital Nossa Senhora da Conceição de dezembro de 2010 até março de 2011. Resultados: 61 pacientes (43%) preencheram os critérios de rifle para injúria renal e 28 (13,7%) necessitaram de diálise. Preditores independentes para nefrotoxicidade foram hipotensão (OR, 2.79; CI 1.14-5.8; p = 0.006) e uso concomitante de vancomicina (OR, 2.86; CI, 1.27-6.4; p = 0.011). Conclusão: Nessa coorte retrospectiva, nefrotoxicidade (definida pelos criterios de RIFLE) ocorreu em 43% dos pacientes tratados com polimixina B. O uso concomitante de vancomicina e hipotensão foram fatores de risco independentes para desenvolvimento de nefropatia. Mais estudos são necessarios, particularmente com polimixina B, para esclarecer se as caracteristicas dessa droga e da colistina são sobreponíveis.

Abstract Introduction: Polimyxins were originally abandoned due to high rates of nephrotoxicity. However they have been recently reintroduced due to activity against carbapenem-resistant Gram-negative organisms. Recent literature suggests a lower rate of nephrotoxicity than historically reported. Objective: To determine the rate of polymixins-associated nephrotoxicity as defined by the RIFLE criteria. Methods: A retrospective cohort of all adult patients who received polymixin B at a terciary hospital from December 2010 to March 2011was performed. Results: 61 patients (43%) fulfilled the RIFLE criteria for renal injury and 28 patients (13.7%) needed dialysis. Independent predictors for nephrotoxicity were hypotension (OR, 2.79; CI 1.14-5.8; p = 0.006) and concomitant use of vancomycin (OR, 2.86; CI, 1.27-6.4; p = 0.011). Conclusions: In this retrospective cohort, nephrotoxicity (as defined by RIFLE criteria) occurred among 43% of treated patients. The concomitant use of vancomycin and hypotension were independent risk factors of nephropathy. Further studies are needed, particularly with polymyxin B, to clarify if the characteristics of this drug and colistin are overlapping.

Nephrotoxicity Of Polymyxin B: Experimental Study In Cells And Implications For Nursing Practice / La Nefrotoxicidad De Polimixina B: Estudio Experimental En Las Células Y Implicaciones Para La Práctica De Enfermería / Nefrotoxicidade da polimixina B: estudo experimental em células e implicações para a prática de enfermagem

The aim of the study was to characterize the cell damage mechanisms involved in the pathophysiology of cytotoxicity of polymyxin B in proximal tubular cells (LLC - PK1) and discuss about the nurses interventions to identify at risk patients and consider prevention or treatment of nephrotoxicity acute kidney injury. This is a quantitative experimental in vitro study, in which the cells were exposed to 375μM polymyxin B sulfate concentration. Cell viability was determined by exclusion of fluorescent dyes and morphological method with visualization of apoptotic bodies for fluorescence microscopy. Cells exposed to polymyxin B showed reduced viability, increased number of apoptotic cells and a higher concentration of the enzyme lactate dehydrogenase. The administration of polymyxin B in vitro showed the need for actions to minimize adverse effects such as nephrotoxicity.
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El objetivo del estudio fue caracterizar los mecanismos de daño celular implicado en la fisiopatología de la citotoxicidad de la polimixina B en las células tubulares proximales (LLC-PK1) y discutir las propuestas de intervención de enfermería para identificar a los pacientes de riesgo y considerar la prevención o el tratamiento de la lesión renal aguda nefrotóxica. Corresponde a un estudio experimental cuantitativo in vitro, en el cual las células fueron expuestas a sulfato de polimixina B. La viabilidad celular se determinó por exclusión de los colorantes fluorescentes y el método morfológico con la visualización de cuerpos apoptóticos a la microscopía de fluorescencia. Las células expuestas a polimixina B demostraron reducción de la viabilidad, aumento de células apoptóticas y mayor concentración de la enzima lactato deshidrogenasa. La administración de polimixina B in vitro demostró la necesidad de realizar acciones en la práctica clínica para minimizar los efectos adversos como la nefrotoxicidad.

O objetivo do estudo foi caracterizar os mecanismos de lesão celular envolvidos na fisiopatologia da citotoxicidade da polimixina B em células tubulares proximais (LLC-PK1) e discutir as proposições de intervenção do enfermeiro para identificar os pacientes de risco e considerar a prevenção ou o tratamento para lesão renal nefrotóxica. Estudo experimental in vitro , onde as células foram expostas ao sulfato de polimixina B. A viabilidade celular foi determinada pela exclusão dos corantes fluorescentes e o método morfológico com visualização de corpos apoptóticos à microscopia de fluorescência. As células expostas à polimixina B apresentaram redução de viabilidade, aumento do número de células em apoptose e maior concentração da enzima desidrogenase láctea. A administração de polimixina B in vitro demonstrou a necessidade de ações na prática clínica para minimizar os efeitos adversos como a nefrotoxicidade.

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HPLC determination of polymyxin-B-sulphate, gramicidin and benzalkonium chloride in pharmaceutical formulations

A rapid and sensitive method is described for the determination of gramicidin, polymyxin-B-sulphate and benzalkonium chloride in pharmaceutical preparations using high-performance liquid chromatography. The analysis was performed on 5u-Nuclosil-cyano 250x4.6mm column, water [pH 1.9 with perchloric acid]: Acetonitrile: Isopropanol [60: 30: 15] as a mobile phase, detection at 214nm and at 35[degree]C. The method was applied on Neo-myxidin Eye Drops which contains the same concentrations of this mixture and the results are in agreement with manufacture's specification. With good accuracy and precision as shown from the percentage recovery and relative standard deviation from 0.2 to 1.64%