Aminoglycoside antibiotics, ototoxicity

Loop diuretics occasionally cause dose-related hearing loss that is usually reversible. It is most common in patients who have diminished renal function or who are also receiving other ototoxic agents such as aminoglycoside antibiotics. 

Paromomycin sulfate is an aminoglycoside antibiotic that until recently was used in parasitology only for oral therapy of intestinal parasitic infections (see previous text). It has recently been developed for the treatment of visceral leishmaniasis. A phase 3 trial in India showed excellent efficacy for this disease, with a daily intramuscular dosage of 11 mg/kg for 21 days yielding a 95% cure rate, and noninferiority compared with amphotericin. The drug was registered for the treatment of visceral leishmaniasis in India in 2006. In initial studies, paromomycin was well tolerated, with common mild injection pain, uncommon ototoxicity and reversible liver enzyme elevations, and no nephrotoxicity. Paromomycin is much less expensive than liposomal amphotericin or miltefosine, the other promising new therapies for visceral leishmaniasis. 

Loop diuretics and aminoglycoside antibiotics are both ototoxic in high dose the chance of an adverse event is greater if they are administered together. 

Ototoxicity is a major adverse effect of aminoglycoside antibiotics (13). They all affect both vestibular and cochlear function, but different members of the family have different relative effects (Table 1). 

In rats, ototoxicity caused by gentamicin or tobramycin was amehorated by melatonin, which did not interfere with the antibiotic action of the aminoglycosides (70). The free radical scavenging agent alpha-lipoic acid has previously been shown to protect against the cochlear adverse effects of systemically administered aminoglycoside antibiotics, and in a recent animal study it also prevented cochlear toxicity after the administration of neomycin 5% directly to the round window membrane over 7 days (71). 

Federspil P. Znr Ototoxizitat der Aminoglykosid-Antibiotika. [Ototoxicity of the aminoglycoside antibiotics.) Infection 1976 4(4) 239 8. 

Henley CM 3rd, Schacht J. Pharmacokinetics of aminoglycoside antibiotics in blood, inner-ear fluids and tissues and their relationship to ototoxicity. Audiology 1988 27(3) 137 6. 

One advantage of bumetanide is that it is less ototoxic than furosemide (1-3). It is sensible to prefer bumetanide to furosemide in patients with hearing problems or who concurrently need ototoxic drugs, such as an aminoglycoside antibiotic. 

Deafness occurred after 5 days treatment with dantrolene 25 mg/day in a patient who was also taking long-term baclofen and diazepam (8). This may have been coincidental, but the authors suggested that dantrolene may have caused the effect by interfering with the release of calcium from the sarcoplasmic reticulum. It is therefore interesting that one hypothesis that explains the ototoxicity of aminoglycoside antibiotics involves disturbance of calcium ion binding and phosphorylation processes (SED-11, 549). 

Furosemide increases the ototoxic risks of aminoglycoside antibiotics (30,31) by reducing their clearance by about 35% (32) permanent deafness has resulted from the use of this combination. 

Key words Ototoxicity, Aminoglycoside antibiotic, Cisplatin, Organ of Corti, Vestibular apparatus,... 

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