Gentamicin and tobramycin are frequently used for empiric treatment of continuous ambulatory peritoneal dialysis (CAPD) related peritonitis. The intraperitoneal concentrations of gentamicin or tobramycin most commonly targeted are 4 to 8 mg/L of dialysate. Patients with systemic illness may receive an intravenous loading dose.
Intermittent hemodialysis can decrease pre-dialysis concentrations by 50%. Therefore, patients undergoing intermittent hemodialysis generally require supplemental doses of gentamicin or tobramycin after each dialysis, depending on the time lapsed after the first dose and characteristics of the dialysis delivered.
Similar to that observed in patients with intermittent hemodialysis, significant inter-patient variability exists among patients undergoing continuous arteriovenous (AV) hemofiltration. Empiric initial daily gentamicin or tobramycin doses of 2.5 mg/kg administered once daily should be followed by serum concentration monitoring to assure adequate peak and trough concentrations.
Both the volume of distribution and clearance of aminoglycosides is greatly increased in patients with cystic fibrosis, necessitating higher starting doses with both traditional intermittent and extended-interval dosing to achieve target serum concentrations.
Patients with significant burns may exhibit larger volumes of distribution. As a result, larger maintenance doses of gentamicin and tobramycin per day in divided doses may be needed to attain therapeutic serum aminoglycoside concentrations. Serum concentration monitoring and individualized dosing correlates with survival in this patient population.
Septic patients undergoing aggressive fluid resuscitation in resolving or evolving acute renal failure often warrant especially close monitoring. Some suggest individualized monitoring for such patients. Peak concentrations of aminoglycosides may be affected by high volumes of intravenous fluids or extravascular fluid shifts, requiring adjustments in pharmacokinetics determination, such as distribution volume.
Since many elderly patients have reduced renal function or are receiving concomitant nephrotoxic agents, caution should be used in prescribing aminoglycosides. Reduced muscle mass and the resulting reductions in serum creatinine concentration in the elderly may result in overestimating renal function when formulas such as the Cockcroft-Gault equation are utilized. Therefore, relatively normal serum creatinine may be associated with a substantial renal function loss in this patient population. A creatinine increase greater than 50% over baseline requires careful evaluation of urine output and urinalysis for evidence of drug-induced nephrotoxicity.