Vancomycin- and erythromycin-induced hearing loss in humans

Purpose of review:Vancomycin is a first-line agent in the treatment of serious Gram-positive infections in the neonatal population. The published evidence on vancomycin toxicity in neonates is limited. This review summarises pre-clinical studies and clinical trials describing vancomycin toxicity. We discuss proposed pathophysiology and summarise evidence supporting dose-response relationships, genetic and environmental determinants, and consider future research required to further define vancomycin toxicity. Recent findings:Current dosing regimens for vancomycin result in sub-therapeutic levels in a large proportion of patients. Higher daily doses have been proposed, which have led to concerns regarding increased toxicity. Nephrotoxicity occurs in 1-9% of neonates receiving currently recommended doses. The incidence is highest in those receiving concomitant nephrotoxic drugs. Vancomycin-associated ototoxicity is rare in patients of all ages. Exposure-toxicity relationships in relation to nephro-and ototoxicity have not been clearly defined in neonates receiving vancomycin. Summary:Current evidence supports the favourable safety profile of vancomycin in neonates.Further studies that address safety concerns relating to high-dose intermittent dosing regimens are needed. Such studies must include robust and standardised definitions of renal and hearing impairment, and include follow-up of sufficient length to establish the long-term implications of experimental findings.

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“…(86,87) Overall, the available recent literature on vancomycin-associated ototoxicity are heterogeneous and in many cases causation is uncertain.…”

Section: Clinical Studiesmentioning

confidence: 99%

Vancomycin toxicity in neonates

Lestner

Hill

Heath

et al. 2016

Current Opinion in Infectious Diseases

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“…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.…”

mentioning

confidence: 99%

Vancomycin Ototoxicity: a Reevaluation in an Era of Increasing Doses

Forouzesh

Moise

Sakoulas

2009

Antimicrob Agents Chemother

109

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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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“…In addition to that it has been observed nausea, chills, phlebitis, severe hypotension, wheezing, dyspnoea, urticaria, pruritus with the treatment of vancomycin in human [55,56,57,58]. In some instances, with prolonged therapy neutropenia was detected [59].…”

Section: Adverse Effect Of Vancomycinmentioning

confidence: 99%

<strong>Review on Usage of Vancomycin in Livestock and Humans: Maintaining its Efficacy, Prevention of Resistance and Alternative Therapy</strong>

Wijesekara

Kumbukgolla

Jayaweera

et al. 2016

Preprint

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Vancomycin is one of the 'last-line' classes of antibiotics used in the treatment of life-threatening infections caused by Gram-positive bacteria. Even though vancomycin was discovered in 1950s it was widely used after 1980s for the treatment of infections caused by methicillin-resistant Staphylococci as prevalence of such strains were increased.However, currently it is evident that vancomycin resistant Staphylococcusaureusandvancomycin-resistant Enterococci have been developed as a result of variousreasons including use of avaparcin, which is an analog of vancomycin, as feed additive in livestock. In present day context, more attention should be paid on prevention of emergence of resistance for the antibiotics in order to keep antibiotics effective. In order to prevent emergence of resistance, proper guidance for the responsible use of antimicrobials is indispensable. Therefore, almost all stakeholders who use antibiotics should have in depth understanding on the antibiotic they use. As such, it is imperative to be aware of the important aspects of vancomycin. In the present review, efforts have been made to discussthe pharmacokinetics and pharmacodynamics, indications, emergence of resistance, control of resistance, adverse effects and alternative therapy for vancomycin.

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Vancomycin- and erythromycin-induced hearing loss in humans

Cited by 103 publications

References 53 publications

Vancomycin toxicity in neonates

Vancomycin toxicity in neonates

Vancomycin Ototoxicity: a Reevaluation in an Era of Increasing Doses

<strong>Review on Usage of Vancomycin in Livestock and Humans: Maintaining its Efficacy, Prevention of Resistance and Alternative Therapy</strong>

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