amphotericin-b and Pleurisy

Pneumonia with pleuritis is a rare presentation of histoplasmosis infection. We present a 12-year old previously healthy boy in whom histoplasmosis presented with pleuritis, confirmed by detection of antigen in empyema fluid.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antigens, Fungal; Bronchoalveolar Lavage Fluid; Child; Debridement; Glycoproteins; Histoplasmosis; Humans; Itraconazole; Male; Pleurisy; Pleuropneumonia; Tomography, X-Ray Computed

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Hepatitis, Viral, Human; Humans; Itraconazole; Male; Pleurisy; Superinfection

Three lipid-based delivery systems (AmBisome, Amphocil, and Abelcet) for amphotericin B (AmB) have been marketed to overcome the disadvantages associated with the clinical use of AmB. However, to show their efficacy, they need to be administered at higher doses than the conventional dosage form, Fungizone. In this study, we compared LNS-AmB, our new low-dose therapeutic system for AmB using lipid nano-sphere (LNS), with these commercial formulations in terms of their pharmacokinetics and efficacy. The plasma AmB levels yielded by LNS-AmB after intravenous administration to rats were much higher than those yielded by Amphocil or Abelcet, and similar to those yielded by AmBisome, but in dogs LNS-AmB yielded plasma AmB concentrations about three times higher than did AmBisome. In a carrageenin-induced pleurisy model in rats, LNS-AmB yielded AmB levels in the pleural exudate over 20 times those yielded by Amphocil or Abelcet, and similar to those yielded by AmBisome. From these pharmacokinetic results, it is clear that Amphocil and Abelcet are based on a quite distinct drug-delivery concept from LNS-AmB. In a rat model of localized candidiasis, LNS-AmB significantly inhibited the growth of Candida albicans in the pouch, whereas AmBisome did not, even though the AmB concentrations in the pouch were similar. This difference in antifungal activity between LNS-AmB and AmBisome was also found in vitro. That is, the antifungal activity of LNS-AmB against C. albicans was similar to that of Fungizone and dimethyl sulfoxide-solubilized AmB, while AmBisome showed weaker antifungal activity than did other formulations. Based on these results, the release of AmB from AmBisome was judged to be slow and slight. In a mouse model of systemic candidiasis, LNS-AmB (1.0mg/kg) was much more effective than AmBisome (8.0mg/kg) or Fungizone (1.0mg/kg). These results suggest that LNS-AmB maintained the potent activity of AmB against fungal cells even though the AmB was incorporated into LNS particles. We conclude that LNS-AmB may offer an improved therapeutic profile at lower doses than Fungizone and commercial lipid-based formulations.

Topics: Amphotericin B; Animals; Antifungal Agents; Area Under Curve; Candida albicans; Carbon Isotopes; Carrageenan; Chemistry, Pharmaceutical; Colonic Pouches; Dogs; Dose-Response Relationship, Drug; Drug Carriers; Drug Evaluation, Preclinical; In Vitro Techniques; Inflammation; Lipids; Models, Animal; Nanotubes; Pleurisy; Radiochemistry; Rats; Species Specificity; Survival Rate