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No treatment was established for disseminated M. avium intracellulare (MAC) infection, a common disease of end stage of AIDS. An open study was conducted to assess in 173 AIDS patients, the activity of clarithromycin. Initial bacteriologic eradication from blood was observed in 136/147 evaluable patients (93%). Acquired resistance to clarithromycin associated with relapse appeared to develop after 2 to 7 months of drug treatment in 31/136 patients with initial success. Early bacteriological relapse was associated with clinical deterioration. Side effects of drug treatment were elevated liver enzymes (26%) and impaired hearing (4%). Side effects conducted to stop treatment in 14 cases (8%) to modified treatment in 8 cases (5%). Our study gave new argues for activity of clarithromycin in disseminated MAC infection.

Recent experiments using autoradiographic and immunohistochemical labelling of gentamicin have demonstrated that GM penetrates specifically into the sensory cells of the inner ear, with a good correlation between the intensity of the labelling and the respective degrees and localisations of ototoxic damages. In the sensory hair cells GM ils localised below the cuticular plate, in an area rich in lysosomes during the ototoxic treatment. This penetration precedes the development of ototoxicity and there seems to be a threshold of intracellular concentration of GM for development of intracellular ototoxic processes. Clearance is very slow since GM can still be observed 11 months after the end of a non toxic treatment (60 mg/kg/day for 6 consecutive days). This observation is of clinical interest, in view of the delayed development of ototoxicity often observed clinically, and with respect to other hazards, including new ototoxic treatments, to which the cells can be exposed while loaded with the aminoglycoside molecule.

Gentamicin, as the other aminoglycosides, has a very narrow therapeutic index. The pharmaco-kinetics parameters in neonates depend on the renal maturation which is a function of post-conceptional age. Using an unit dose of 2 mg/kg and adapted time intervals, longer for premature babies and in the first week of life, the frequency of too high trough levels is decreased. A convenient method is proposed for determining when to reduce the time interval between injections. Audiotoxicity is both cochlear and vestibular and can be, only in part, detected by evoked potentials. Nephrotoxicity is initially, a tubular injury with an increase of enzymuria (NAG) and beta 2 microglobulinuria, followed by alterations of glomerular filtration. Blood concentrations monitoring is indicated in all gentamicin treated neonates.

The authors have performed a series of high frequency audiograms in order to assess its value in routine otological practice. Initially, they conducted a statistical study on subjects with so-called normal hearing in order to establish standardised normal values. As in the earlier studies, a physiological alteration was observed in the high frequencies which was progressively accentuated with age. Audiometric results should therefore always be considered in relation to the patient's age. A standard graph is proposed for the presentation of the results. The authors subsequently performed high frequency audiometry in patients with internal ear disorders. High frequency audiometry allowed early detection of an alteration in the internal ear, when conventional audiometry was normal. The authors believe that high frequency audiometry should be part of the otological assessment as its allows early detection of internal ear disease.

Tobramycin, gentamicin, sisomicin and amikacin are aminoglycoside antibiotics that are used clinically. A significant side effect of aminoglycoside antibiotics is the production of hearing loss. Our study was done to determine the relative ototoxic liability of these 4 drugs. All drugs were given in daily doses of 0, 50,100 or 150 mg/kg to guinea pigs subcutaneously for 4 weeks. In addition, 200 mg/kg was was given to the animals receiving amikacin and sisomicin. There were 10 animals in each dosage group. Seven animals were used for auditory study and 3 were used for pharmacokinetic study. Auditory damage was assessed by determining the Preyer pinna reflex, the ability of the cochlea to generate the AC cochlear potential, and the number of sensory hair cells missing from the organ of Corti. The concentration of aminoglycoside antibiotics is determined in the cochlear perilymph and plasma by a radioenzymatic assay. On a equal dose basis the ototoxic liability of gentamicin and sisomicin were very similar and tobramycin and amikacin being less ototoxic than the gentamicin and sisomicin. The pharmacokinetics of single 150 mg/gk doses of the drugs were similar. The exception was that tobramycin reached lower peak levels in plasma and perilymph and its time to peak level in perilymph was delayed relative to the other drugs. Analysis of plasma and perilymph following chronic administration revealed higher concentration of gentamicin and sisomicin than of tobramycin and amikacin.