TLC G-65, a liposome-encapsulated gentamicin, was given intravenously twice weekly for 4 weeks to AIDS patients with Mycobacterium avium-M. intracelulare complex (MAC) bacteremia at 1.7 mg of gentamicin per kg of body weight per infusion (4 patients), 3.4 mg/kg (10 patients), and 5.1 mg/kg (7 patients). MAC colony counts in blood fell by 75% or more in all three groups (P < 0.005). Drug resistance did not emerge during the study period. Transient renal insufficiency developed in one patient; no other adverse effects were detected. Liposome-encapsulated gentamicin is a potential therapy for MAC infections in AIDS patients.Disseminated Mycobacterium avium-M. intracellulare complex (MAC) infection frequently causes morbidity and mortality in AIDS patients. While the incidence of MAC bacteremia is only about 5% at the time of AIDS diagnosis, it is over 50% by 30 months after AIDS diagnosis. It appears that all human immunodeficiency virus-positive patients who do not succumb to some other opportunistic event will eventually develop MAC infection (9).Aminoglycosides are among the recommended treatments for disseminated MAC infection (3, 7). Recently, liposomeencapsulated aminoglycosides, including amikacin (1, 2, 4, 6), gentamicin (8, 11), and streptomycin (5), have been shown to be more effective than their unencapsulated counterparts in animal models of MAC infection. Those reports led us to perform a phase I/II safety and dose-finding study of TLC G-65, a liposome-encapsulated gentamicin, in AIDS patients with MAC bacteremia. MATERIALS AND METHODSHuman immunodeficiency virus-infected men and nonpregnant women over 18 years of age with MAC cultured from their blood within 8 weeks of the time of entry into the study were eligible for the study. Patients were required to have a serum creatinine level of <1.5 mg/dl, normal audiometry and vestibular functions, no antimycobacterial therapy within 28 days of entry into the study, and liver function tests less than five times the upper limit of normal. Written informed consent was obtained prior to entry into the study.TLC G-65 is a plurilamellar liposome made from egg phosphatidylcholine by The Liposome Company, Princeton, N.J. TLC G-65 contains 50 mg of phospholipid and 5 mg of gentamicin per ml. Over 80% of the gentamicin is encapsulated in the liposome, and 85% of the liposomes are between 1.2 and 10.0 ,um in diameter. The preparation is stable at 5°C for 18 months.Subjects were infused with TLC G-65 on study days 1, 4, 8, 11, 15, 18, 22, and 25. Infusions were performed at a uniform rate over a 2-h period. The first subjects received 1.7 * Corresponding author. mg gentamicin per kg of body weight per infusion. Dose escalations of 1.7 mg of gentamicin per kg were mandated by the protocol whenever (i) less than four of six patients receiving a given dose experienced less than a 99% reduction in MAC colony counts in blood by the end of the study and (ii) no serious or life-threatening toxicities were observed at that dose level.An audiogram, blood culture for MAC, CD4 ...
Miltefosine is an alkylphosphocholine compound that is used primarily for treatment of leishmaniasis and demonstrates in vitro and in vivo antiamebic activity against Acanthamoeba species. Recommendations for treatment of amebic encephalitis generally include miltefosine therapy. Data indicate that treatment with an amebicidal concentration of at least 16 μg/ml of miltefosine is required for most Acanthamoeba species. Although there is a high level of mortality associated with amebic encephalitis, a paucity of data regarding miltefosine levels in plasma and cerebrospinal fluid in vivo exists in the literature. We found that despite aggressive dosing (oral miltefosine 50 mg every 6 h) and therapeutic plasma levels, the miltefosine concentration in cerebrospinal fluid was negligible in a patient with AIDS and Acanthamoeba encephalitis.
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