Use of poly-l-aspartic acid to inhibit aminoglycoside cochlear ototoxicity.
Gentamicin is an extremely effective antibiotic against a wide variety of organisms. However, its use is limited by its nephrotoxic and ototoxic effects. Recent studies in rats have shown that poly-l-aspartic acid (PAA) effectively blocks the nephrotoxic effects of the aminoglycosides and does not decrease the antibiotic effectiveness of gentamicin against those organisms tested. A controlled test was undertaken to evaluate the effect of PAA on cochlear ototoxicity. Test solutions were administered to four groups of guinea pigs for 10 days. Group 1, the controls, received distilled water, group 2 received gentamicin, group 3 received PAA, and group 4 received gentamicin plus PAA. Auditory brainstem response thresholds at 20, 16, 8, and 4 kHz were obtained before therapy, after completion of the 10-day course, and 21 days following the completion of therapy. Two-dimensional diffusion assays in human serum were performed to evaluate the effect of PAA on the antimicrobial activity. Histologic evaluation of the cochleae was performed at the conclusion of the experiment. Threshold shifts following 10 days of therapy were not statistically significant in group 4 compared to controls, while the gentamicin group (group 2) was significantly different for all frequencies tested. At 21 days following therapy, group 4 (PAA + gentamicin) maintained significance in the higher frequencies studied. Antimicrobial studies demonstrated that PAA has no effect on the antimicrobial activity of gentamicin and has no antimicrobial effect against Bacillus subtilis when used alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Hulka
G F
GF
Division of Otolaryngology-Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill.
Prazma
J
J
Brownlee
R E
RE
Pulver
S
S
Pillsbury
H C
HC
D000818:Animals; D001224:Aspartic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects* / Q000302:isolation & purification; D003051:Cochlea / Q000187:drug effects* / Q000382:microbiology; D003404:Creatinine / Q000097:blood; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000382:microbiology; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects
D005839:Gentamicins; D001224:Aspartic Acid; D003404:Creatinine