Canadian AIDS Treatment Information Exchange (CATIE) TreatmentUpdate48, Vol. 4, No. 8 - March 1994
Sean Hosein

BACKGROUND

Packed into tiny spheres of fat, the antibiotic gentamycin might become part of a treatment regimen for MAC infection. The theory behind liposomal drugs in general and liposomal gentamycin in particular, is that these repackage drugs may be more effective and less toxic than the normal form of the drugs. We now report preliminary results from early human studies.

STUDY DETAILS

The researchers released data on 21 subjects (they did not state how many were male or female). All subjects were adults and had an average CD4+ cell count of 8 cells. The study doctors did not release CD8+ cell counts. Subjects received one of three doses of TLC G-65; 1.7 mg/kilogram of body weight per infusion; 3.4 mg/kg/dose; and 5.1 mg/kg/dose. The drug was slowly infused over a period of 2 hours. During the 4 weeks following their first dose, subjects received at least 8 doses of liposomal gentamycin.

RESULTS

Subjects did report some decrease in severe night sweats and fevers while being given TLC G-65. These changes were not statistically significant. During the study most subjects continued to lose weight. The average weight loss was less than 2.3 kg.

In most subjects the amount of MAC in their blood decreased over a period of 32 days. Subjects received their last dose of liposomal gentamycin on the 32nd day. Blood samples taken 8 days later had a small increase in the amount of MAC compared to blood samples taken over the first 32 days of the study.

TOXICITY

No subject developed hearing damage from the gentamycin. One subject had kidney dysfunction as his blood levels of creatinine increased. When doctors stopped giving him liposomal gentamycin his blood levels of creatinine returned to normal over a period of 3 weeks.

ARE COMBINATIONS NEXT?

In this study liposomal gentamycin reduced blood levels of MAC. This reduction had more to do with the length of time subjects received the drug than a particular dose. At the end of the study MAC had not become resistant to the antibiotic. Researchers are not sure which of the three doses used is best. Various doses and schedules are being tested in the USA. In laboratory experiments on bacteria with clarithromycin and gentamycin, the combination was better than either drug alone.

REFERENCES:

1. Nightingale SD, Saleton SL, Swenson CE, et al. Liposome- encapsulated gentamycin treatment of Mycobacterium avium Mycobacterium intracellulare complex bacteremia in AIDS patients. Antimicrob Agents Chemother. 1993 Sep;37(9):1869-72.

2. Heifets LB, Lindholm-Levy PJ and Comstock RD. Bacteriostatic and bactericidal activities of gentamycin alone and in combination with clarithromycin against Mycobacterium aviums. Antimicrob Agents Chemother. 1992 Aug;36(8):1695-8.

3. Hengge UR, Brochneyer NH, Baumann M, et al. Liposomal doxorubicin in AIDS-related Kaposi's sarcoma. Lancet. 1993 Aug 21;342(8869):497.

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