Vancomycin Ototoxicity: a Reevaluation in an Era of Increasing Doses

Abstract

Nephrotoxicity and ototoxicity have historically been documented as relatively rare complications of vancomycin monotherapy. Recent reports have linked aggressive vancomycin dosing strategies to significant risks of nephrotoxicity. We evaluated the rate of high-frequency hearing loss detected by audiometry for patients on vancomycin therapy. For this purpose, we used retrospective case-control analysis of audiometry results for patients on vancomycin therapy for whom baseline and follow-up exams were available. Analysis of 89 patients for whom audiograms were performed after an average of 27 days of vancomycin therapy showed a 12% rate of high-frequency hearing loss, with a trend in univariate analysis toward a higher rate with advanced age. The mean of the highest vancomycin trough levels for both patients with worsening audiograms and those without worsening audiograms was 19 mg/liter. Regression tree modeling demonstrated that for patients <53 years old, the rate of high-frequency hearing loss detected by audiogram was 0%, while for patients >53 years old, the incidence was 19% (P ‫؍‬ 0.008). We conclude that a significant rate of high-frequency hearing loss in older patients receiving vancomycin monotherapy was detected by audiometry. While these data urge caution against continued indiscriminate vancomycin dose escalation to treat infections caused by Staphylococcus aureus strains for which vancomycin MICs are 2 mg/liter, further prospective studies are needed to determine the clinical significance and reversibility of these effects.Vancomycin has been available to clinicians for 50 years, but its use has increased dramatically in the past 2 decades to keep pace with the increase in methicillin-resistant Staphylococcus aureus (MRSA) infections seen in both community and health care settings (6, 7). In addition, recent increases in vancomycin MICs among clinical MRSA isolates (12,16,18) have prompted many clinicians to use higher-dose therapy, although data supporting positive outcomes with higher doses are lacking (4). On the contrary, several reports have emerged suggesting a higher incidence of nephrotoxicity with high-dose vancomycin therapy (5,8).Ototoxicity is a less common adverse event previously documented with vancomycin therapy (2, 13, 17). While considered less severe because, unlike renal failure, it has not been linked to inferior clinical outcomes and antibiotic treatment failure (11), ototoxicity from antibiotics has potential qualityof-life implications. It is also less likely to be caused by factors encountered among hospitalized patients, such as those for nephrotoxicity. Given that there is no contemporary evaluation of the ototoxicity of vancomycin in a setting of aggressive dosing, we sought to evaluate the ototoxic effects of vancomycin by using audiometry. MATERIALS AND METHODSPatient selection. All patients with anticipated long-term (Ͼ14-day) vancomycin therapy at Westchester Medical Center are routinely referred for baseline and follow-up audiometry. All patients on therapy between...

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“…However, HD-vancomycin regimens have been associated with an increased risk of nephrotoxicity compared to that from standard dosing, particularly when vancomycin is combined with another nephrotoxic agent (15). Concerns regarding a significant risk for vancomycin-induced ototoxicity among older patients treated with HD-vancomycin have also been raised (11). Furthermore, recent expert panel recommendations regarding vancomycin therapeutic drug monitoring have proposed a target AUC/MIC ratio of Ͼ400 (25).…”

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“…Some practitioners have extrapolated these dosing recommendations with associated trough concentration goals to all vancomycin use. However, evidence of superior efficacy is lacking, and results of several single-center, mostly retrospective trials have suggested that this more aggressive dosing may be related to an increased incidence of vancomycin-related nephrotoxicity (12,14,18,20,27) and ototoxicity (9). The results and conclusions of these studies have been questioned, to varying degrees, due to design limitations, including the failure to account for other risk factors for renal compromise, and/or their single-center nature.…”

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“…This child was treated with amikacin and vancomycin at mean doses of 180 mg/m 2 /day and 120 mg/m 2 /day, respectively. The ototoxic effect of vancomycin has already been proven (11,12) . It is especially notable when vancomycin is used in association with other potentially ototoxic drugs (13) , which was not the case with this child.…”