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1.
Indian J Pharmacol ; 55(4): 229-236, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37737075

RESUMO

OBJECTIVES: Our study aimed to evaluate the real-world data on renal and neurological adverse effects and effectiveness of colistimethate sodium (CMS) and polymyxin B (PMB). MATERIALS AND METHODS: An observational prospective study was performed on inpatients receiving CMS and PMB for multidrug-resistant Gram-negative bacterial infections. CMS dose was titrated to renal function, and serum creatinine was assessed daily. The incidence of nephrotoxicity, the primary outcome, was evaluated based on an increase in serum creatinine from baseline as well as by the Risk, Injury, Failure, Loss of kidney function, and End-stage renal disease criteria. Neurological adverse effects were assessed based on clinical signs and symptoms, and the causality and severity were assessed by the Naranjo scale and modified Hartwig-Siegel scale, respectively. The effectiveness of polymyxin therapy was ascertained by a composite of microbiological eradication of causative bacteria and achievement of clinical cure. Thirty-day all-cause mortality was also determined. RESULTS: Between CMS and PMB, the incidence of nephrotoxicity (59.3% vs. 55.6%, P = 0.653) or neurotoxicity (8.3% vs. 5.6%, P = 0.525) did not significantly differ. However, reversal of nephrotoxicity was significantly more with patients receiving CMS than PMB (48.4% vs. 23.3%, P = 0.021). Favorable clinical outcomes (67.6% vs. 37%, P < 0.001) and microbiological eradication of causative bacteria (73.1% vs. 46.3%, P = 0.001) were significantly more with CMS than PMB. Patients treated with CMS had lower all-cause mortality than those with PMB treatment (19.4% vs. 42.6%, P = 0.002). CONCLUSION: There is no significant difference in the incidence of renal and neurotoxic adverse effects between CMS and PMB when CMS is administered following renal dose modification. CMS shows better effectiveness and lower mortality compared to PMB.


Assuntos
Injúria Renal Aguda , Infecções por Bactérias Gram-Negativas , Humanos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/diagnóstico , Antibacterianos/efeitos adversos , Colistina/efeitos adversos , Creatinina , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Rim/fisiologia , Polimixina B/efeitos adversos , Estudos Prospectivos
2.
Curr Drug Discov Technol ; 17(3): 357-364, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30714529

RESUMO

BACKGROUND: Although antibiotic-induced hepatotoxicity is recoverable with mild impairment, and some cases were reported to cause morbidity. However, an adjuvant is essential in reducing such incidences. OBJECTIVE: The aim of this study is to evaluate the protective effect of ascorbic acid on antibiotic induced liver toxicity using liver slices. METHOD: Fresh liver slices were incubated with different concentrations of sulfamethoxazole tetracycline and clavulanic acid along with ascorbic acid (200µg/ml) for 2 hours. The liver homogenate was assessed for markers like ALT, AST, MDA and CAT levels. Cytotoxicity assessment was performed using MTT assay. RESULTS: Incubating liver slices with all three antibiotics shows elevated levels of aminotransferases, MDA and CAT enzyme when compared to the control groups which indicates the level of hepatotoxicity. In the presence of ascorbic acid, the elevated levels of TBARS, ALT and AST were significantly reduced which showcases the protective effect of ascorbic acid. The percentage survival of cell was also shown to have improved while accessed using cell viability assay. CONCLUSION: Obtained data suggests that consuming vitamin C or vitamin C containing food like citrus fruits or green leafy vegetables equivalent to 3g/day during antibiotic treatment, perhaps put down the risk of liver toxicity to a greater extent.


Assuntos
Antibacterianos/efeitos adversos , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fígado/efeitos dos fármacos , Animais , Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Galinhas , Ácido Clavulânico/efeitos adversos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Hepatócitos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/patologia , Camundongos , Estresse Oxidativo , Cultura Primária de Células , Sulfametoxazol/efeitos adversos , Tetraciclina/efeitos adversos
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