A prospective study was undertaken in 16 patients with chronic renal failure on continuous ambulatory peritoneal dialysis, with 22 episodes of peritonitis treated with vancomycin, a known ototoxic agent. Twelve patients had one episode each, and four had recurrent peritonitis. Each treatment course consisted of two infusions of vancomycin (30 mg/kg body weight) in 2 L of peritoneal dialysate administered at 6-day intervals. Serum vancomycin analyzed by enzyme immunoassay showed a mean trough level of 11.00 microg/ml on day 6 and mean serum levels of 33.8 and 38.6 microg/ml about 12 hours after administration on days 1 and 7, respectively. Similar levels, well within the therapeutic range, were encountered with repeated vancomycin therapy for recurrent episodes of peritonitis, suggesting that no changes occurred in the pharmacokinetic profile of the drug. Pure-tone audiometry, electronystagmography, and clinical assessment performed during each course of treatment showed no evidence of ototoxicity even on repeated courses of vancomycin therapy. The results suggest that vancomycin therapy when given in appropriate concentrations as a single therapeutic agent is both effective and safe. We believe, however, that vancomycin administered in combination with an aminoglycoside may produce ototoxic effects that may be greatly aggravated, possibly because of synergism.
In a prospective study on 47 patients, 16 mg of gentamicin per two litres dialysate was administered intraperitoneally at every cycle of intermittent peritoneal dialysis, carried out over the course of several days. Serum gentamicin sampling, pure tone audiometry and caloric tests were performed before and during the treatment. The gentamicin levels reached at the end of the thirtieth cycle were observed to be low. In view of this, the risk of acute ototoxicity was considered to be minimal. This was confirmed by the absence of clinical audiometric or vestibulometric evidence of toxicity.
A prospective study was undertaken of 10 chronic renal failure patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) complicated by repeated bouts of peritonitis treated with gentamicin. Each 10-day treatment course consisted of a 120 mg loading dose, followed by 16 mg in 21 of peritoneal dialysate, given four times a day. Serum gentamicin analysed by enzyme immunoassay showed a mean level of 5.2 micrograms/ml, (range 3.7 to 6.6 mg/ml) four hours after the loading dose. Similar levels, well within the therapeutic range, were maintained on the 3rd, 5th, 7th and 9th days of intraperitoneal gentamicin therapy, suggesting no accumulation of gentamicin in the serum. Pure tone audiometry, electronystagmography and clinical assessment were performed during each course of treatment. Although no evidence of ototoxicity was found during the first two courses of gentamicin, but disequilibrium and bobbing oscillopsia were present during the third and fourth courses of gentamicin. These findings could be explained by cumulative injury to the vestibular apparatus caused by repeated therapeutic insults.