Toxicidad por colistina: hiperpigmentación cutánea, neurotoxicidad y nefrotoxicidad: Reporte de caso / Colistin toxicity: skin hyperpigmentation, neuro and renal toxicity: A case report

La colistina o polimixina E es un antibiótico cuyo uso fue descontinuado por la toxicidad renal y neurológica relacionadas al uso de colistina sulfato. Estos efectos adversos han disminuido con el uso del profármaco colistimetato sódico. Actualmente el uso de colistina es más frecuente debido al incremento de infecciones ocasionadas por bacilos Gram negativos multirresistentes, sobre todo en las unidades de cuidados intensivos. Presentamos el caso de una mujer de 50 años de edad con antecedente de consumo de anti-inflamatorios no esteroideos y corticoides, pos- operada de perforación gástrica que evolucionó con colecciones abdominales por Acinetobacter sp. multirresistente. Recibió 34 días de colistina endovenosa y desarrolló hiperpigmentación cutánea, ataxia (neurotoxicidad) y falla renal (nefrotoxicidad) de forma secuencial secundaria a la administración de colistina, los efectos adversos desaparecieron con la suspensión del antibiótico. (AU)

Colistin or polymycin E is an antibiotic that was discontinued due to its renal and neurologic toxicity related to its colistin sulfate content. These adverse effects have been reduced with the use of sodium colistemathe. There is currently a more frequent use of colistin due to an increase of multi-resistant Gram negative infections, particularly in intensive care units. We present the case of a 50-year-old woman with history of surgery due to gastric perforation, use of steroids and non-steroidal anti-inflammatory drugs, that developed intra-abdominal abscesses due to multidrug resistant Acinetobacter spp. She received 34 days of intravenous colistin and developed skin hyperpigmentation, ataxia and renal failure. These adverse effects disappeared with discontinuation of the drug. (AU)

Does dexmedetomidine prevent colistin nephrotoxicity? / Dexmedetomidina impede a nefrotoxicidade da colistina?

Abstract Background In this study, we aimed to investigate the effect of dexmedetomidine on colistin nephrotoxicity in rats. Methods Thirty-two Wistar albino rats were allocated into four groups. Intraperitoneal (ip) saline at 1 mL.kg-1 was administered to the control group and 10 mg.kg-1 ip colistin was given to the colistin group. In the DEX10 group 10 mcg.kg-1 dexmedetomidine ip was given 20 min before the injection of 10 mg.kg-1 ip colistin. In the DEX20 group ip 20 mcg.kg-1 dexmedetomidine was injected 20 min before the administration of 10 mg.kg-1 ip colistin. These treatments were continued twice a day for seven days. Samples were taken on the eighth day. BUN, Cr, KIM-1, TAS, and TOS were examined in blood samples and caspase-3 was examined in kidney tissue samples. Results The values for BUN, Cr and TOS were significantly higher in the colistin group than in the control group. BUN, Cr and TOS changes in the DEX10 and DEX20 groups were not significant compared with the control group but they were significantly lower compared with the colistin group. TAS values in the DEX10 group were significantly lower than in the control group. Apoptotic activity was significantly higher in the colistin group compared with the control group, but there was no significant difference in terms of caspase-3 staining activity when DEX10 and DEX20 groups were compared with the control group. Conclusion Oxidative damage and apoptosis played roles in colistin nephrotoxicity, and colistin nephrotoxicity could be prevented by treatment with dexmedetomidine.

Resumo Justificativa Neste estudo, buscamos investigar o efeito da dexmedetomidina sobre a nefrotoxicidade da colistina em ratos. Métodos Trinta e dois ratos Wistar albinos foram alocados em quatro grupos: o grupo controle recebeu 1 mL.kg-1 de solução salina intraperitoneal (ip); o grupo colistina recebeu 10 mg.kg-1 de colistina ip; o grupo DEX10 recebeu 10 mcg.kg-1 de dexmedetomidina ip 20 minutos antes da injeção de 10 mg.kg-1 de colistina ip; o grupo DEX20 recebeu 20 mcg.kg-1 de dexmedetomidina ip 20 minutos antes da administração de 10 mg.kg-1 de colistina ip. Estes tratamentos foram continuados duas vezes ao dia durante sete dias. As amostras foram colhidas no oitavo dia. BUN, Cr, KIM-1, TAS e TOS foram examinados nas amostras de sangue e caspase-3 foi examinada nas amostras de tecido renal. Resultados Os valores de BUN, Cr e TOS foram significativamente maiores no grupo colistina do que no grupo controle. As alterações em BUN, Cr e TOS nos grupos DEX10 e DEX20 não foram significativas em comparação com o grupo controle, mas foram significativamente menores em comparação com o grupo colistina. Os valores de TAS no grupo DEX10 foram significativamente menores do que no grupo controle. A atividade apoptótica foi significativamente maior no grupo colistina em comparação com o grupo controle, mas não houve diferença significativa em termos de atividade na coloração da caspase-3 quando os grupos DEX10 e DEX20 foram comparados com o grupo controle. Conclusão O dano oxidativo e a apoptose desempenharam papéis na nefrotoxicidade da colistina e a nefrotoxicidade de colistina pode ser prevenida pelo tratamento com dexmedetomidina.

Establishment and comparison of nephrotoxicity associated with the use of various doses of colistin in rabbits

Objective: This study was designed to assess the nephrotoxicity associated with various doses of Colistin sulfate in rabbits

Study Design: Laboratory based randomized controlled trials, Place and Duration of Study: This study was held at Army Medical College, Rawalpindi. Study period was from 15[th] April till 30[th] April 2012

Material and Methods: Rabbits were divided into three groups of six rabbits each. Baseline serum urea, serum creatinine and serum electrolytes were estimated. A loading dose of colistin infusion was given followed by I.M injections for six days. Rabbits were sacrificed 24 hours after the last dose and both kidneys were sent for histopathology

Results: There was marked nephrotoxicity in high toxic group where as in low toxic group mild nephrotoxicity was evident

Conclusion: It was established that we may safely escalate dose of colistin up to four times the currently recommended schedule to combat the threat of resistance when using it for one to two weeks