RESUMO
Genetic polymorphism studies of cytokines may provide an insight into the understanding of acute kidney injury (AKI) and death in intensive care unit (ICU) patients. The aim of this study was to investigate whether the genetic polymorphisms of -308 G < A tumour necrosis factor (TNF)-α, -174 G > C interleukin (IL)-6 and -1082 G > A IL-10 may predispose ICU patients to the development of AKI and/or death. In a prospective nested case-control study, 303 ICU patients and 244 healthy individuals were evaluated. The study group included ICU patients who developed AKI (n = 139) and 164 ICU patients without AKI. The GG genotype of TNF-α (low producer phenotype) was significantly lower in the with AKI than without AKI groups and healthy individuals (55 versus 62 versus 73%, respectively; P = 0·01). When genotypes were stratified into four categories of TNF-α/IL-10 combinations, it was observed that low TNF-α plus low IL-10 producer phenotypes were more prevalent in patients with AKI, renal replacement therapy and death (P < 0·05). In logistic regression analysis, low TNF-α producer plus low IL-10 producer phenotypes remained as independent risk factors for AKI and/or death [odds ratio (OR) = 2·37, 95% confidence interval (CI): 1·16-4·84; P = 0·02] and for renal replacement therapy (RRT) and/or death (OR = 3·82, 95% CI: 1·19-12·23; P = 0·02). In this study, the combination of low TNF-α plus low IL-10 producer phenotypes was an independent risk factor to AKI and/or death and RRT and/or death in critically ill patients. Our results should be validated in a larger prospective study with long-term follow-up to emphasize the combination of these genotypes as potential risk factors to AKI in critically ill patients.
Assuntos
Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/imunologia , Interleucina-10/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Injúria Renal Aguda/genética , Injúria Renal Aguda/mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Humanos , Unidades de Terapia Intensiva , Interleucina-10/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Fator de Necrose Tumoral alfa/genéticaRESUMO
We evaluated the in vitro activity of ampicillin-sulbactam in comparison with that of broad-spectrum antimicrobial agents against Acinetobacter baumannii isolates. Two hundred and twelve clinical isolates collected between January 1993 and March 1995 from two tertiary hospitals located in São Paulo, Brazil were tested for susceptibility by the disk diffusion method against several broad-spectrum antimicrobial agents, including imipenem, ciprofloxacin, ceftazidime, aztreonam, amikacin, and polymyxin B. All strains were susceptible to polymyxin B. The second most active compound was the combination ampicillin-sulbactam (88% susceptibility). Only 79% of the isolates were susceptible to imipenem. Ciprofloxacin was active against 60 (28%) and amikacin against 34 (16%) isolates. Ceftazidime was the most active cephalosporin; however, only 9% of the isolates were susceptible to this compound. Both aztreonam and ampicillin alone showed very poor activity against this species (1% susceptibility). The prevalence of severe infections due to A. baumannii is increasing very rapidly in the tertiary hospitals of São Paulo and there are very few options for the treatment of these infections. Polymyxin B is invariably in vitro active against this species; however, this compound can cause severe side effects and is not commercially available for intravenous use in Brazil and in several other countries. Our results indicated that the combination ampicillin-sulbactam may be an alternative drug for the treatment of infections due to multiresistant A. baumannii; however, further studies are necessary to evaluate the clinical role of this compound for the treatment of severe infections.