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Low CL, Bailie GR, Evans A, Eisele G, Venezia RA

Pharmacokinetics of once-daily IP gentamicin in CAPD patients

Perit Dial Int (Aug) 16:379-384 1996

Once daily intraperitoneal (IP) aminoglycoside (either gentamicin or tobramycin) is now recommended for treatment of Gram negative peritonitis in PD patients. The rationale for this approach is that aminoglycosides, since they display concentration-dependent killing, will achieve better cidal activity at higher concentrations; at the same time, since antibiotic otovestibular uptake is a saturable process, less uptake will occur with once daily therapy, thus minimizing toxicity. However, there are few data as to the efficacy of this regimen.

In this study, 10 patients on CAPD (4 daily exchanges) without peritonitis received a single IP dose of 0.6 mg/kg gentamicin in the first exchange and blood and dialysate samples were collected at 0, 0.5, 1, 2, 3, 6 (end of first dwell period) and 24 hrs later. Drug levels were also determined in the last three spent exchanges. The bioavailability of gentamicin was 56% over a six-hour dwell period and the half-life was 36 hours. Mean peak serum concentrations of gentamicin were 1.37 mg/L at the end of the 6 h dwell and 0.9 mg/L at 24 h. Dialysate antibiotic concentrations were > 10 mg/L at all times during the first exchange but < 1 mg/L in all subsequent exchanges.

The authors conclude that once daily IP gentamicin may not produce adequate serum and dialysate antibiotic concnetrations to treat peritonitis.

Comment: This is a well-done pharmacokinetic study; however, it was performed in patients without peritonitis. In the presence of peritonitis, uptake of gentamicin into the systemic circulation may have been much greater, thus altering the results. More importantly, since aminoglycosides have a post-antibiotic effect, it is not clear as to whether cidal levels need to be maintained for more than 6 h of each 24 h period. In clinical practice, treatment with an additional antibiotic (such as oral ciprofloxacin) in addition to the aminoglycoside will supply an additional margin of safety. (David J. Leehey, M.D., Loyola University at Chicago)