Considerations regarding clinical safety and tolerability of antibiotics in serious and nosocomial infections.

Patients with severe gram-negative infections are often treated with aminoglycosides, cephalosporins, or a combination of these. Aminoglycosides cause nephrotoxicity and ototoxicity. Duration of treatment and dose are directly related to the incidence of toxicity. Nephrotoxicity occurs in 10% to 20% of patients, is mild to moderate in severity, and is often reversible. Tobramycin causes nephrotoxicity less frequently than does gentamicin. Ototoxicity may be associated with auditory or vestibular changes. Auditory toxicity occurs at high frequencies in 10% of patients and is rarely clinically apparent, but it may not be reversible. Cephalosporins cause different adverse effects, which can be classified as those due to: (1) the physical-chemical properties of the cephalosporin--pain on injection and thrombophlebitis; (2) drug hypersensitivity--rash, exfoliative dermatitis, hemolytic anemia, eosinophilia, thrombocytopenia, fever, interstitial nephritis, and anaphylaxis, (3) dose--positive Coombs reaction, glomerulotubular dysfunction, central nervous system dysfunction, platelet dysfunction, leukopenia, and agranulocytosis; and (4) other causes--diarrhea, pseudomembranous colitis, prolonged prothrombin time, disulfiram-like effect, colonization, and super-infection. Use of cephalothin with gentamicin or tobramycin increases the incidence of nephrotoxicity. In patients with severe infections, election of an aminoglycoside or cephalosporin may depend on the relative toxicity of the drugs. Well-designed comparative studies are needed to determine the relative frequency and clinical significance of these adverse effects.