Chemotherapy of Systemic Mycoses

Je, Bennett

doi:10.1056/nejm197402072900607

Cited by 123 publications

(44 citation statements)

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“…Fivefluorocytosine (5-FC) has proven to be clinically useful in treating candida infections and is relatively nontoxic (1). To assess the potential value of 5-FC in controlling respiratory tract colonization with candida, a study of 5-FC penetration into bronchial secretions was done, using a dog model.…”

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confidence: 99%

5-Fluorocytosine and Amphotericin B in Bronchial Secretions

Pennington

Block

Reynolds

1974

Antimicrob Agents Chemother

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The penetration into and clearance from bronchial secretions of 5-fluorocytosine and amphotericin B were studied in a dog model. After a single intravenous dose of 35 mg/kg, 5-fluorocytosine intrabronchial concentrations were greater than the minimal inhibitory concentration for 80 to 90% of Candida species. These inhibitory concentrations persisted up to 3 h. In contrast, amphotericin B in intravenous doses of 0.6 and 1.2 mg/kg penetrated the blood-bronchus barrier poorly.Colonization of the tracheobronchial tree with Candida species (usually C. albicans) is not uncommon in debilitated and immunosuppressed patients. Endotracheal intubation or tracheostomy (9), and the use of broad-spectrum antibiotics (18), render patients especially prone to candida colonization. The incidence of candidemia or invasive pulmonary infection which results from this colonization is unkiiown. However, an increasing problem with disseminated candidiasis and candida pneumonia in these patients has been reported (7,8).Antibiotics, administered to respiratory mucosal surfaces via aerosal spray, have been effective in reducing the incidence of gram-negative bacterial colonization of the respiratory tract in certain groups of patients (6, 9). Attempts at eradicating oropharyngeal candida using local nystatin therapy have been less successful, particularly in leukopenic patients (8). Effective control of mucosal candida colonization and infection may depend upon using systemic therapy in such patients (8).Although low-dose amphotericin B therapy has been advocated for certain superficial candida infections (14), use of this potentially toxic drug in a debilitated patient is usually reserved for life-threatening fungal infection. Fivefluorocytosine (5-FC) has proven to be clinically useful in treating candida infections and is relatively nontoxic (1). To assess the potential value of 5-FC in controlling respiratory tract colonization with candida, a study of 5-FC penetration into bronchial secretions was done, using a dog model. For comparison, amphotericin B concentrations in bronchial secretions were also evaluated.MATERIALS AND METHODS Animal studies. A dog model (15) for the study of antibiotic diffusion into and clearance from normal bronchial secretions was used in this study. American foxhounds (approximately 20 kg) were anesthetized with 2.5% sodium thiamylal and intubated with a rubber endotracheal tube. Subcutaneous pilocarpine HCl was given (0.5 mg/kg every 45 min) to stimulate an adequate flow of bronchial secretions (about 1 ml/h) for specimen collection. Volumes were small so that significant dilution did not occur. Previous work has demonstrated little change in the constituents of bronchial secretions after pilocarpine administration (15). Bronchial secretion specimens were aspirated via the endotracheal tube using a small-bore (1.25 mm) plastic catheter inserted to maximal depth within a mainstem bronchus. A syringe attached to the catheter provided adequate suction. Bronchial secretion specimens were each approximately 0....

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confidence: 99%

5-Fluorocytosine and Amphotericin B in Bronchial Secretions

Pennington

Block

Reynolds

1974

Antimicrob Agents Chemother

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“…Amphotericin B is the standard drug but, due to its toxicity (14), it is usually reserved for lifethreatening situations and must be given by slow intravenous infusion for periods up to 16 weeks or longer (2). There is interest in the newer imidazoles as possible chemotherapeutic agents for the systemic mycoses and, of these, miconazole is in clinical investigation (12,13).…”

Section: Resultsmentioning

confidence: 99%

In Vitro and In Vivo Studies of Ambruticin (W7783): New Class of Antifungal Antibiotics

Ringel¹

1978

Antimicrob Agents Chemother

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Ambruticin is a cyclopropyl-pyran acid, representing a new class of antibiotics. It has a relatively broad antifungal spectrum in vitro and is highly active against dimorphic as well as filamentous organisms. Of 24 strains of dermatophytic fungi tested, the majority were susceptible to ambruticin at 0.049 ug/ml or less. The minimal inhibitory concentration for the systemic fungi Histoplasma capsulatum and Blastomyces dermatitidis was 0.049 to 0.39 pg/ml. Ambruticin is fungicidal for metabolizing cells of Microsporum fulvum and does not cause cell leakage of 260-nm absorbing material. The antibiotic is effective orally as well as topically in guinea pigs experimentally infected with Trichophyton mentagrophytes. In mice, a single oral dose of 75 mg/kg produced peak serum levels of 45 pig/ml in 1 h with a serum half-life of 3.1 h. Excretion of the antibiotic is principally by the biliary route.

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“…Among the few chemotherapeutic agents the best choice is probably to combine amphotericin B and 5-fluorcytosine (Bennett 1974, Gustke & Wu 1981, Thurston & Gillespie 1981, Webb et al 1970. If there are contraindications to these drugs, chemotherapy with imidazol derivatives is another possibility.…”

Section: Discussionmentioning

confidence: 99%