Antimicrobial nephrotoxicity

Porter GA. Antimicrobial nephrotoxicity. In Textbook of nephrology. Massry SG, Glassock JR (editors). Baltimore, Williams Wilkins 1989 p 812-818. 

Porter G. Antimicrobial nephrotoxicity. In Massry SG GR, ed. Textbook of Nephrology. Baltimore Williams Wilkins 1989 812-8. 

Appel GB, Neu HC The nephrotoxicity of antimicrobial agents (second of three parts). N Engl J Med 1977 296 722-728. 

Rougier F, Claude D, Maurin M, Sedoglavic A, Ducher M, Corvaisier S, Jelliffe R and Maire P. Aminoglycoside Nephrotoxicity Modeling, simulation and control. Antimicrobial Agents Chemother. 2003 47 1010-1016... 

Since the discovery of streptomycin in 1944, aminoglycosides have endured as indispensable agents in the antimicrobial armamentarium. This is despite their well described potential for serious nephrotoxicity and otoxicity and the emergence of other classes of antibiotics with similar antibacterial spectrums. The major aminoglycoside antibiotics in... 

Sandoval RM, Reilly JP, Running W, Campos SB, Santos JR, Phillips CL, Molitoris BA, A non-nephrotoxic gentamicin congener that retains antimicrobial efficacy, J Am Soc Nephrol, 17 2697-2705. 

Deray G. Amphotericin B nephrotoxicity. Journal of Antimicrobial Chemotherapy 2002 49 37-41. 

Imipenem, a carbapenem antimicrobial, also possesses nephrotoxic potential. In animal models, nephrotoxicity is dose dependent and characterized by tubular necrosis. Interestingly, imipenem nephrotoxicity is markedly attenuated by co-administration of cilastatin, an inhibitor of the cytosolic and brush border enzyme dehydropeptidase I (DHP). Although DHP is responsible for hydrolyzing imipenem to inactive metabolites, the major protective effect of cilastatin appears to be due to inhibition of renal imipenem accumulation rather than DHP inhibition. 

Supportive measures that would complement antimicrobial effectiveness and assist recovery of the animal from the infection should be provided. In neonatal animals, care must be taken to avoid a too-rapid rate of intravenous fluid administration. Fever may serve a useful purpose in infectious diseases, and the change in body temperature may be used to assess the progress of the infection. In the presence of an infectious diseased, the only indication for an antipyretic drug, e.g. aspirin or paracetamol (acetaminophen) in dogs but not in cats metamizole (dipyrone) or sodium salicylate administered intravenously to horses, is to decrease body temperature to below a dangerous level, 41°C (105.8°F). Concurrent therapy with a NSAID and an aminoglycoside antibiotic increases the risk of nephrotoxicity. If the infection is suspected to be contagious, the diseased and in-contact animals should be isolated. 

The prevention of aminoglycoside-induced nephrotoxicity has received considerable attention in recent years. Alternative antibiotics should be used whenever possible and as soon as microbial sensitivities are known. Commonly used alternatives include fluoroquinolones (e.g., ciprofloxacin or levofloxacin) and third-generation cephalosporins (e.g., ceftazidime). When aminoglycosides are necessary, the specific drug used does not appear to significantly affect the risk of nephrotoxicity, and therapy should be selected to optimize antimicrobial efficacy. Furthermore, it is imperative to avoid volume depletion, limit the total aminoglycoside dose administered, and avoid concomitant therapy with other nephrotoxic drugs. 

Patients treated for intraabdominal infections should be assessed for the occurrence of drug-related adverse effects, particularly hypersensitivity reactions (/ -lactam antimicrobials), diarrhea (most agents), fungal infections (most agents), and nephrotoxicity (aminoglycosides). 

LeBrun, M., L. Grenier, M. G. Bergeron, L. Tibault, G. Labrecque, and D. Beauchamp. 1999. Effects of fasting on temporal variation in the nephrotoxicity of amphotericin B in rats. Antimicrobial Agents and Chemotherapy 43 520-524. 

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