Ototoxicity vancomycin

Kavanagh KT, McCabe BF Ototoxicity of oral neomycin and vancomycin. Laryngoscope 1983 93 649-653. 

Antibiotics with activity against urease-producing bacteria, such as neomycin [42], paromomycin [44] or metronidazole [45], also reduce the production of intestinal ammonia and have proved to be of value. Vancomycin has also been used in patients with lactulose-resistant chronic encephalopathy [46]. The efficacy of neomycin is similar to that of lactulose [42]. However, a small percentage of this drug is absorbed from the gastrointestinal tract and may cause ototoxic and nephrotoxic effects, especially with continuous use over several months [47]. This drug should be used with particular caution by patients with renal insufficiency. The efficacy of metronidazole for... 

Gentamicin is an aminoglycoside. All aminoglycosides tend to be nephrotoxic and ototoxic. The dose must be reduced and serum concentrations must be monitored in patients with impaired renal function. Concomitant administration of aminoglycosides and other nephrotoxic drugs, such as certain diuretics, ciclosporin, teicoplanin and vancomycin should be avoided. 

Ototoxicity Ototoxicity has occurred in patients receiving vancomycin. It may be transient or permanent. It has occurred mostly in patients who have been given excessive doses, who have an underlying hearing loss, or who are receiving concomitant therapy with another ototoxic agent. 

Vancomycin can cause red-man syndrome consisting of diffuse flushing, presumably mediated by histamine-release. This problem can be prevented by limiting the infusion rate. The most serious adverse reactions are ototoxicity and nephrotoxicity. The toxicity for both organ systems is potentiated by aminoglycosides. Vancomycin will cross the placenta barrier and has the potential to cause fetal ototoxicity. 

The major adverse effect associated with vancomycin therapy is ototoxicity, which may result in tinnitus, high-tone hearing loss, and deafness in extreme instances. More commonly, the intravenous infusion of vancomycin can result in chills, fever, and a maculopapular skin rash often involving the head and upper thorax (red man syndrome). Red man syndrome is associated with increased levels of serum histamine. Vancomycin is rarely nephrotoxic when used alone. Teicoplanin rarely causes red man syndrome or nephrotoxicity. 

PLATINUM COMPOUNDS AMINOGLYCOSIDES, CAPREOMYCIN, COLISTIN, STREPTOMYCIN, VANCOMYCIN t risk of renal toxicity and renal failure and of ototoxicity. The ototoxicity tends to occur when cisplatin is administered early during the course of aminoglycoside therapy Additive renal toxicity Monitor renal function prior to and during therapy, and ensure an intake of at least 2 L of fluid daily. Monitor serum potassium and magnesium and correct any deficiencies. Most side-effects of aminoglycosides are dose-related, and it is necessary to t interval between doses and 1 dose of aminoglycoside if there is impaired renal function... 

Vancomycin and teicoplanin are completely excreted unchanged in the urine by glomerular filtration. Vancomycin also partly undergoes hepatic metabolism. They are ototoxic and nephrotoxic. 

AMINOGLYCOSIDES TEICOPLANIN, VANCOMYCIN t risk of nephrotoxicity and ototoxicity Additive effect Hearing and renal function should be carefully monitored... 

VANCOMYCIN CICLOSPORIN Risk of renal toxicity and ototoxicity Additive toxic effects Monitor renal function closely... 

The use of intravenous vancomycin in prolonged therapy, in concomitant or sequential use with other ototoxic or nephrotoxic drugs, or in patients with impaired renal function has caused permanent deafness and... 

In a retrospective cost analysis, the records of 527 patients with acute leukemia were studied (11). They had been treated in a multicenter, randomized trial for febrile neutropenia with ceftazidime and amikacin plus either teicoplanin (6 mg/kg in a single dose n — 275) or vancomycin (30 mg/kg/day in 2 doses n — 252). Qinical responses were equivalent. Again the higher acquisition costs for teicoplanin were counterbalanced by the lower incidence of adverse events and easier administration, resulting in overall similar costs for both regimens. A total of 8% of patients treated with vancomycin reported adverse events compared with 3.2% of patients treated with teicoplanin. Rashes occurred in 6.0 versus 1.4% respectively. Nephrotoxicity, ototoxicity, fever, and hypotension occurred in very few patients. 

Vancomycin is a narrow-spectrum glycopeptide antibiotic with potent antistaphylococcal activity. It was developed in the early 1950s. Early formulations contained substantial impurities, which were presumably responsible for some adverse reactions (1). When rapid infusion rates are avoided, vancomycin is rarely associated with serious toxicity. Reviews have suggested that the potential for vancomycin to cause significant ototoxicity or nephrotoxicity has been exaggerated (2,3). Improved manufacturing has resulted in a purer product and fewer toxic effects, but vancomycin is still associated with potentially serious adverse reactions (4). 

It is still controversial whether vancomycin can cause ototoxicity when given alone. However, vancomycin can augment the ototoxicity of aminoglycosides (30). Tinnitus and dizziness have been noted, resolving on withdrawal (31). Hearing loss can be transient or permanent. If vancomycin is combined with aminoglycosides, toxicity may be additive (32). 

In a prospective study to determine if standardized vancomycin doses could produce adequate serum concentrations in 25 full-term neonates with sepsis 13 had adequate peak vancomycin serum concentrations (20-40 mg/ml) and one had a peak concentration with a risk of ototoxicity (over 40 qg/ml) (130). Only 12 had adequate trough concentrations (5-10 mg/ml) and 7 had a risk of nephrotoxicity (over 10 qg/ml). There was no significant difference between peak or trough concentrations and good or bad clinical outcomes. 

Brummett RE. Ototoxicity of vancomycin and analogues. Otolaryngol Clin North Am 1993 26(5) 821-8. 

Gendeh BS, Gibb AG, Aziz NS, Kong N, Zahir ZM. Vancomycin administration in continuous ambulatory peritoneal dialysis the risk of ototoxicity. Otolaryngol Head Neck Surg 1998 118(4) 551-8. 

Vancomycin exhibits predictable pharmacokinetic properties and its clinical use has been guided by the pharmacokinetic monitoring of serum levels to determine the dose and frequency of administration. Pharmacokinetic monitoring of vancomycin, however, has become increasingly controversial given the improved safety of this antibiotic and the lack of data to support what are considered the therapeutic and toxic serum levels. Historically, the most severe toxicities of vancomycin were ototoxicity and nephrotoxicity. The incidence of nephrotoxicity has declined since its introduction possibly due to the availability of purer forms of the antibiotic. Ototoxicity has always been a rare adverse event of vancomycin, but it has been observed with excessively high concentrations of the drug in plasma [170-172]. The purpose of this section is to describe the nephrotoxicity associated with the clinical use of vancomycin. 

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