title: Use of bolus intraperitoneal aminoglycosides for treating peritonitis in end-stage renal disease patients receiving continuous ambulatory peritoneal dialysis and continuous cycling peritoneal dialysis.
abstract: Peritonitis is the most common complication of peritoneal dialysis (PD) and accounts for the most drop-out from PD among patients with end-stage renal disease (ESRD). Antibiotic protocols to treat peritonitis recommend initial treatment for both gram-positive and gram-negative infections, pending culture results. Current literature also suggests comparable therapeutic success using bolus (single-dose) parenteral aminoglycosides to treat systemic gram-negative infections compared to conventional divided-dose aminoglycosides. The single bolus dose antibiotic regimen has the potential for reduced nephrotoxicity and ototoxicity. We therefore hypothesized that intermittent bolus dose intraperitoneal (i.p.) aminoglycosides may be superior to conventional continuous dose i.p. aminoglycosides in treating dialysis-associated peritonitis, and have fewer side effects. Six patients with clinical peritonitis were treated with single, bolus-dose, i.p. gentamicin or tobramycin (5 mg/kg ideal body weight), range 250-440 mg (mean: 355 +/- 68.25 mg) at the start of therapy. No patient grew gram-negative organisms; aminoglycosides were therefore not repeated. Three patients used four continuous ambulatory peritoneal dialysis (CAPD) exchanges per day; three patients used six nightly continuous cycling peritoneal dialysis (CCPD) exchanges with a daytime dwell. Mean PD aminoglycoside clearance was 6.75 +/- 2.27 mm3/min; mean urinary aminoglycoside clearance was 5.75 +/- 1.14 mm3/min. Mean blood aminoglycoside elimination t1/2 was 29.27 +/- 3.55 hours, with a mean blood level of 3.18 +/- 1.45 micrograms/mL 72 hours after initial therapy, and 1.52 +/- 0.81 micrograms/mL 96 hours after initial therapy. Peritoneal equilibration test (PET) scores before and after aminoglycoside administration (performed a mean of 4.6 months apart) were 0.672 +/- 0.097 and 0.705 +/- 0.092 respectively (p = 0.321). Comparative audiograms using pure-air tone conduction with frequencies from 250-12,000 Hz were done within 24 hours of aminoglycosides and again when therapy was complete (mean: 17 days). No significant changes were seen. While efficacy of bolus versus conventional-use aminoglycosides could not be definitely established, the kinetics of bolus aminoglycosides suggests that therapeutic blood levels persist for 72-96 hours and that the risk for oto/vestibular toxicity is negligible. We conclude that use of bolus i.p. aminoglycosides is safe, achieves therapeutic blood levels for extended intervals, demonstrates no clinical oto/vestibular toxicity, is cost-effective, and is a convenient strategy for patients and nursing staff.
authors.affiliation: University of Florida Health Science Center, Division of Nephrology and Hypertension, Jacksonville, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Mars
authors.forename: K
authors.initials: K
authors.lastname: Moles
authors.forename: K
authors.initials: K
authors.lastname: Pope
authors.forename: P
authors.initials: P
authors.lastname: Hargrove
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects; D010538:Peritonitis / Q000188:drug therapy* / Q000209:etiology; D013203:Staphylococcal Infections / Q000188:drug therapy; D013290:Streptococcal Infections / Q000188:drug therapy; D014031:Tobramycin / Q000008:administration & dosage
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D014031:Tobramycin