Vancomycin administration in continuous ambulatory peritoneal dialysis: The risk of ototoxicity,☆☆,,★★

Presented at 6th ASEAN, ORL Head and Neck Congress, Chiangrai, Thailand, Nov. 14-18, 1994.
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Abstract

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 μg/ml on day 6 and mean serum levels of 33.8 and 38.6 μg/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. (Otolaryngol Head Neck Surg 1998;118:551-8.)

Section snippets

METHODS AND MATERIAL

The study covered a one-year period (November 1991 to October 1992) and was carried out in inpatients with end-stage renal disease on CAPD in whom gram-positive peritonitis developed and who were monitored by audiovestibular assessment. Patients in the following categories were excluded from the study: (1) those who were too ill to respond appropriately, (2) those with preexisting sensorineural hearing loss, (3) those with narrow auditory canals, (4) those with a discharging ear or perforated

RESULTS

A total of 16 patients with 22 episodes of peritonitis were included in the study. Twelve of these patients had one episode of peritonitis each, and the other four had recurrent peritonitis. All were subsequently treated with vancomycin. The average age was 50.0 ± 13.5 years (mean ± SD), and the average weight was 56.4 ± 10.65 kg. In all patients the serum creatinine level before the dialysis was above 1000 μmol/L. Data on serum vancomycin and peritoneal fluid levels during the first course of

Evidence of Ototoxicity

The toxic potential of vancomycin is less significant than previously thought. Presently vancomycin is still considered an ototoxic drug, and the likely reason for this belief is based on its initial published reports. 5, 6 This could well be because of the impurities in the early preparations of vancomycin or the concomitant use of vancomycin with aminoglycosides in cases complicated by renal failure. 7 From the literature review of both the clinical and experimental animal studies, the

CONCLUSION

Appropriately administered intraperitoneal vancomycin (30 mg/kg body weight) given 6 days apart in a single course of therapy is both effective and safe. Furthermore, repeated courses of this regimen for recurrent peritonitis in patients receiving CAPD carries no additional risk of ototoxicity. We suggest that to maximize early detection of ototoxic changes, it is essential to incorporate ultra-high frequencies in the monitoring protocol.

Acknowledgements

We thank the staff nurses of the CAPD unit, Miss P. M. Hui and Mr. F. M. Hussain of the audiology unit, and Mr. M. S. Hashim and Miss Safinaz Sabri for technical and clerical assistance. We are indebted to Dr. K. G. Rampal and Dr. Abdullah Sani (Head Department of Otorhinolaryngology) for helpful comments and support. We also thank Dr. Khalid Kadir (Dean) of UKM and the Director General of Health (Dr. Abu Bakar Sulaiman) for permission to publish these data. We also thank Dr. Eugene N. Myers,

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    From the Departments of Otorhinolaryngology (Dr. Gendeh), Pharmacology (Dr. Aziz), and Nephrology (Dr. Kong), National University of Malaysia, Kuala Lumpur; the Department of Nephrology (Dr. Zahir), Hospital Kuala Lumpur; and the Department of Otorhinolaryngology (Dr. Gibb), National University of Singapore.

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    Funded by UKM grant no. 75/92.

    Reprint requests: B. S. Gendeh, Department of Otorhinolaryngology–Head and Neck Surgery, Faculty of Medicine, Hospital National University of Malaysia, Jalan Tenteram, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia.

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