Gentamicin.Methods of estimating antibiotic therapeutic effectiveness have been discussed elsewhere (chapter 14). Several antibiotics possess therapeutic ranges whose upper limits border on toxicity. Serum assays for several of these have been developed, most commonly using some type of immunoassay. One example will be used to illustrate general principles. Gentamicin (Garamycin) is one of the aminoglycoside antibiotics that is active against gram-negative organisms, including Pseudomonas aeruginosa. Unfortunately, side effects include ototoxicity and nephrotoxicity. Drug excretion is mainly through renal glomerular filtration. Serum peak levels and residual (trough) levels both provide valuable information. Residual levels are measured just before the next dose. Values at this time correlate best with nephrotoxicity, especially when serum levels are greater than 2 µg/ml. Specimens for peak level determination are obtained approximately 30 minutes after the end of IV infusion and 1 hour after intramuscular injection. Peak levels correlate best with therapeutic effectiveness (i.e., whether adequate serum levels are present) and possibly with ototoxicity. Normal peak values are usually considered 4-8 µg/ml. Values less than 4 µg/ml may be ineffective, whereas those greater than 10 µg/ml predispose to toxicity. Gentamicin assay is desirable because serum levels differ considerably among patients receiving the same dose, and serum gentamicin half-life is equally variable. Standard doses or nomograms based on serum creatinine level fail to predict blood concentration accurately for peak or residual levels in a substantial number of patients even with adequate renal function. When renal function is impaired or when nephrotoxic antibiotics have previously been administered, serum assay becomes essential. It should be mentioned that peak or residual levels within accepted reference limits do not guarantee safety, since some studies have shown onset of renal function decrease in the presence of acceptable serum values.

Vancomycin. Only a small mount of oral vancomycin is absorbed, so that the oral form is used to kill GI tract bacteria such as Clostridium difficile. Intravenous medication is used for other infections. Intravenous vancomycin is about 50%-60% bound to serum albumin, and 80%-90% is excreted unchanged in the urine. The serum half-life is 2-3 hours in children and 4-8 hours in adults with normal renal function. In renal failure, the serum half-life becomes 7-8 days (range, 4-9 days), and instead of the usual adult IV dose of 500 mg every 6 hours, only 500-1,000 mg once per week is sufficient. Peak and residual (trough) levels are usually recommended. Residual levels are usually obtained just before a dose is given; the reference values are 5-10 mg/100 ml. Unfortunately, different investigators do not agree when to draw specimens after the end of IV infusion for peak values, with times suggested including immediately, 15 minutes, 30 minutes, and 2 hours after the infusion. Vancomycin serum levels apparently fall rapidly for a time after the end of IV infusion and then more slowly. At 15 minutes after the end of infusion, serum values of 25-30 mg/100 ml are equivalent to 30-40 mg/100 ml levels (the most commonly accepted peak value range) at the end of infusion.