Polimixinas: revisão com ênfase na sua nefrotoxicidade

Abstract

Polymyxins are polypeptide antibiotics with strong action against Gram-negative bacteria. Their use was almost halted between 1970 and 1980 with the advent of less toxic compounds. The emergence of multiresistant Gram-negative bacterial strains, mainly in intensive care unit patients, and the absence of new antimicrobials that were effective against these pathogens, there has been renewed interest in polymyxins in recent years. The major adverse effect of this class of antibiotics is nephrotoxicity. Currently, only polymyxins B and E are used in clinical practice. Polymyxin E, which is widely employed and investigated, is known as colistin, and is used in the form of colistimethate sodium to reduce nephrotoxicity. There are no consistent data about the prevalence of renal injury associated with the use of polymyxins or about the risk factors these antibiotics pose in terms of nephrotoxicity. The aim of this study is to review the main aspects of polymyxin pharmacodynamics, to provide a better understanding of their mechanisms of renal injury, and to compare the different prevalence rates of renal injury associated with the use of these antibiotics. Polymyxins belong to a group of active antibiotics against several Gram-negative bacteria. Synthesized by Bacillus polimyxa strains, they were independently described in 1947 by U.S. and English researchers and the generic name of polymyxins was adopted for the antibiotics derived from this microorganism. Antimicrobial activityThe antimicrobial spectrum includes only Gram-negative organisms. An epidemiological surveillance program (SENTRY -2001(SENTRY - to 2004 found that polymyxin B was excellent against Pseudomonas aeruginosa (1.3% of resistance) and Acinetobacter spp (2.1% of resistan ce), with an MIC 50 ≤ 1 mg/L and MIC 90 ≤ 2mg/L for both pathogens, and against Citrobacter spp., Escherichia coli and Klebsiella spp (MIC 90 , ≤ 1 mg/L; less than 2% of resistance). Polymyxins are not active against Gram-positive bacteria and fungi. The bactericidal activity of this class of antibiotics has remained virtually unchanged since its introduction, 4, 5 notwithstanding the fact that some resistance has already been observed, and that the combined use of antibiotics in order to potentiate their bactericidal effect has also been reported. 6,7 Chemical structure of polymyxins Polymyxins are cyclic polycationic decapeptides that contain a heptapeptide ring and have a high rate of 2,4-diaminobutyric (Dab) acid and a fatty acid bound to the peptide by an amide bond. The ring is formed by the α-amine and carboxyl groups of the Dab residue in position 4, with an additional peptide chain attached through the g-amino group of this residue. Colistin (polymyxin E) differs from polymyxin B because it has D-leucine in lieu of D-phenylalanine in position 6. Colistimethate sodium (CMS) is a colistin derivative obtained from the reaction with formaldehyde and sodium bisulfite. This derivative is less potent comparatively to the original compound and apparently causes fewer adv...

Resistência a antimicrobianos em Staphylococcus aureus isolados de mastite em bovinos leiteiros de Minas Gerais, Brasil

“…1). Polimixina B não é um antimicrobiano utilizado na rotina de tratamento da mastite, e seu uso é recomendado em casos de mastites ambientais ocasionadas por bactérias gram-negativas, devido à sua capacidade de inativar endotoxinas (LPS) (Mendes;Burdmann, 2009). A avaliação da suscetibilidade à polimixina B é uma prova utilizada para a diferenciação entre S. aureus (resistente) e Staphylococcus intermedius (sensível) (Quinn et al, 1994).…”

Nephrotoxicity Of Polymyxin B: Experimental Study In Cells And Implications For Nursing Practice

“…The adjustment in the dose of the drug is needed to ensure that the correct therapeutic range is reached and the incorrect dosage or maintenance of high doses increases the incidence of AKI (16,23) .…”

Resistência Às Polimixinas Em Bactérias Gram-Negativas: Uma Revisão Microbiológica

“…Elas constituem um grupo de cinco compostos químicos intimamente relacionados, as Polimixinas A, B, C, D e E (MENDES; BURDMANN, 2009). Dentro desse grupo, duas substâncias apresentam aplicação terapêutica.…”

“…As polimixinas são antimicrobianos polipeptídicos que atuam inativando a porção lipídica A da endotoxina presente na membrana externa da bactéria ocasionando a morte bacteriana (MENDES; BURDMANN, 2009). Essa classe de medicamentos possue cinco tipos de fármacos, porém, apenas a Polimixina B e a Polimixina E (colistina) são utilizadas clinicamente (FALAGAS et al, 2010).…”