Efficacy of nikkomycin Z against experimental pulmonary blastomycosis.

Abstract

Nikkomycin Z is a chitin synthetase inhibitor. In vitro, nikkomycin Z had good activity against Blastomyces dermatitidis, with an MIC of 0.78 microg/ml and a minimal fungicidal concentration of 3.1 microg/ml. The efficacies of various treatment durations (3, 5, or 10 days) and doses (200, 400, or 1,000 mg/kg of body weight) of nikkomycin Z given twice daily were compared with those of itraconazole at 200 mg/kg given twice daily and amphotericin B at 6.25 mg/kg in a murine model of pulmonary blastomycosis. All treatments prolonged survival compared with untreated controls (P < 0.05 to 0.01); 100% survival was achieved with 5 or 10 days of any nikkomycin Z dose or with amphotericin B. Amphotericin B and nikkomycin Z, but not itraconazole, reduced infection compared with controls. Amphotericin B and the 10-day regimens of all nikkomycin Z doses were equivalent and superior to itraconazole or nikkomycin Z for < or = 5 days at any dose (P < 0.05 to 0.01). Increased duration and/or dosage improved the efficacy of nikkomycin Z, with 10 days of each dose curing 50 to 90% of the animals. Only a 1,000-mg/kg/day dose of nikkomycin Z was curative when treatment lasted less than 10 days. In contrast, itraconazole cured no mice, while amphotericin B cured all mice. Based on the total amount of drug given, amphotericin B was estimated to be 32 times as active as nikkomycin Z and nikkomycin Z was estimated to be 3 times as active as itraconazole. Overall, nikkomycin Z given orally was well tolerated, had good activity against blastomycosis, and could result in biological cure, thus producing results equivalent to those of parenteral amphotericin B.

• Authors: K V Clemons, D A Stevens
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 41 Issue 9 Pg. 2026-8 (Sep 1997) ISSN: 0066-4804 [Print] United States
• PMID: 9303408 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminoglycosides
• Anti-Bacterial Agents
• Antifungal Agents
• Enzyme Inhibitors
• Itraconazole
• Amphotericin B
• nikkomycin
• Chitin Synthase

Topics

• Aminoglycosides
• Amphotericin B (pharmacology)
• Animals
• Anti-Bacterial Agents (pharmacology)
• Antifungal Agents (pharmacology)
• Blastomycosis (drug therapy)
• Chitin Synthase (antagonists & inhibitors)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Enzyme Inhibitors (pharmacology)
• Itraconazole (pharmacology)
• Lung Diseases, Fungal (drug therapy)
• Male
• Mice
• Mice, Inbred Strains