PubMed Health⌕ Search

Biomedical subjects

D W Warnock

Publications and source records attributed to D W Warnock.

At least 91 records · Page 5Linked to original sources
PubMed1992

In-vitro effects of liposome-encapsulated amphotericin B (AmBisome) and amphotericin B-deoxycholate (Fungizone) on the phagocytic and candidacidal function of human polymorphonuclear leucocytes.

Liposomal amphotericin B (AmBisome), at concentrations > or = 20 mg/L, and amphotericin B-deoxycholate (DC) (Fungizone), at concentrations > or = 1 mg/L, both caused a significant reduction in neutrophil uptake of Candida albicans blastospores following simultaneous addition of the drug with the blastospores. The reduction in uptake was seen also in tests in which blastospores were pre-treated with the drugs for 60 min, but was not detected in tests in which neutrophils were pre-treated for 60 min. Neither formulation affected neutrophil killing of C. albicans blastospores following simultaneous addition of the drug with the blastospores. However, previous treatment of the neutrophils with either formulation at a concentration of 20 mg/L led to enhanced killing of ingested blastospores. The results suggest that much higher concentrations of liposomal amphotericin B (AmBisome) are required to produce deleterious effects on neutrophil phagocytic function than with the conventional formulation of the drug.

Amphotericin B↗
PubMed1992

Standardized susceptibility testing of fluconazole: an international collaborative study.

An international collaborative study of broth dilution (MIC) and disk diffusion susceptibility testing of fluconazole was conducted by using a chemically defined medium (High-Resolution Antifungal Assay Medium; Oxoid Ltd., Basingstoke, United Kingdom) and standard test methods performed in eight reference laboratories. Ten yeast isolates were tested by each test method in duplicate on each of 3 separate days. The intralaboratory reproducibility of the MIC test was excellent; 95.7% of the replicate tests (n = 220) were within 2 doubling dilutions of the other values in the set for the eight laboratories. The intralaboratory reproducibility of the disk test was also good, with 91% of the replicate tests (n = 234) agreeing with each other within an arbitrarily chosen value of 4 mm. Interlaboratory agreement of MIC test results was acceptable, with 84% of the MICs agreeing within 2 doubling dilutions. In contrast, the interlaboratory agreement of the disk test was not good, with only 59% of test results agreeing within 4 mm. Comparison of the rank order of MICs obtained in each laboratory with the reference rank order gave an agreement of 70 to 80% (median, 80%) with the MIC test and 70 to 90% (median, 80%) with the disk test. These preliminary results are encouraging for the development of standardized testing methods for testing fluconazole.

Culture Media↗
PubMed1991

An outbreak of aspergillosis in a general ITU.

Over a 5-month period, six patients in a general intensive therapy unit became colonized by Aspergillus species including Aspergillus fumigatus, and invasive infection occurred in at least two of them. Broncho-alveolar lavage was unhelpful in discriminating between infection and colonization. The source of infection was presumed to be disturbance of an accumulation of spores in fibrous insulation material above the perforated metal ceiling. Patients in such units without clearly identifiable defects of defence against infection may be at risk from aspergillosis. The risk can be reduced by improved hospital design, satisfactory ventilation and thorough regular cleaning of environmental surfaces.

Adult↗
PubMed1991

Comparison of the multiple dose pharmacokinetics of two formulations of itraconazole during remission induction for acute myeloblastic leukaemia.

This double-blind cross-over study compares the serum pharmacokinetics of a polyethylene glycol formulation of itraconazole (ITRA-PEG; 4 x 50 mg once daily) with a new pelleted formulation (ITRA-PEL; 2 x 100 mg once daily) during remission induction for acute myeloblastic leukaemia. Each formulation was administered for 28 days with a seven day washout period. Five of eight patients (median age 52 years, range 18-65) entering completed both arms of the study. At day 7 for ITRA-PEL (n = 8) the mean +/- one standard deviation and median maximum concentrations (Cmax) were 307 +/- 155 ng/mL and 275 ng/mL respectively and for ITRA-PEG (n = 6) 272 +/- 212 ng/mL and 193 ng/mL. At day 14 for ITRA-PEL (n = 8) the mean +/- S.D. and median Cmax were 412 +/- 227 ng/mL and 375 ng/mL respectively and for ITRA-PEG (n = 5), 315 +/- 177 ng/mL and 327 ng/mL. The Cmax mean and median values were therefore greater with ITRA-PEL but the differences between the two formulations were not statistically significant. Adequate therapeutic levels of itraconazole can be achieved in this clinical setting. However, the wide variation within and between patients suggests that an ITRA-PEL dosage of 400 mg/day may ensure earlier and more consistent therapeutic levels. Measurement of serum levels may be indicated in suspected failure of prophylaxis or treatment.

Adolescent↗
PubMed1991

Amphotericin B: an introduction.

Amphotericin B has a broad spectrum of action that includes most of the major fungal pathogens of man. This drug binds to the membrane sterols of fungal cells, causing impairment of their barrier function and loss of cell constituents. Metabolic disruption and cell death are consequent upon membrane alterations. Investigations of the sterol content of mutant strains of Candida albicans and Cryptococcus neoformans has demonstrated that resistance is often associated with alterations in membrane sterol composition. Treatment failure due to the development of amphotericin B resistance is an uncommon problem. It has tended to occur in patients receiving treatment with cytotoxic drugs. Interactions between amphotericin B and a number of other antimicrobial drugs have been observed in tests in vitro and in vivo. However, apart from one report that the combination with flucytosine is superior to amphotericin B on its own in the treatment of cryptococcal meningitis, there have been no controlled trials to support the use of drug combinations in human infections.

Amphotericin B↗
PubMed1989

Effect of antimicrobial and antineoplastic drugs alone and in combination on the phagocytic and candidacidal function of human polymorphonuclear leucocytes.

Four antimicrobial and three antineoplastic drugs were screened for their effects on phagocytosis and killing of Candida albicans blastospores by human neutrophil polymorphonuclear leucocytes. Amphotericin B caused significant impairment of both phagocytosis and killing, but cefuroxime and ketoconazole had no effect. Tobramycin did not affect phagocytosis, but impaired killing. Methotrexate, prednisolone and vinblastine all caused significant impairment of phagocytosis, but did not affect killing. Combinations of these seven drugs, such as are used in the treatment of acute lymphoblastic leukaemia in childhood, were also shown to inhibit phagocytosis, although no additive effects were detected. None of the drug combinations tested affected killing.

Amphotericin B↗
PubMed1989

Effect of methotrexate alone and in combination with antifungal drugs on the growth of Candida albicans.

Methotrexate, at concentrations corresponding to drug levels found in vivo, caused a marked reduction in blastospore growth of Candida albicans strains in vitro, but did not affect germ tube elongation during the first 6 h after blastospores were shifted to conditions favouring hyphal formation. Combinations of methotrexate with amphotericin B, flucytosine and itraconazole showed no potentiation or antagonism of the antifungal effect of either component in tests with the blastospore form of C. albicans. In contrast, potentiation occurred when methotrexate-itraconazole combinations were tested for their effect on germ tube elongation of an azole-sensitive strain of C. albicans. This effect was not seen in tests with an azole-resistant strain.

Amphotericin B↗
PubMed1988

Comparison of high performance liquid chromatographic and microbiological methods for determination of itraconazole.

A reversed-phase high-performance liquid chromatographic (HPLC) method, with internal standard quantification, is described for the analysis of itraconazole in human serum. No interference was encountered from over 60 drugs tested. The standard curve was linear from 10 to 10,000 micrograms/l. The detection limit of the method was 10 micrograms/l, with coefficients of variation from 2.2 to 7.8% over a range of itraconazole concentrations from 20 to 1600 micrograms/l. An agar diffusion method is also described with a lowest reproducible limit of 100 micrograms/l. This method had coefficients of variation from 11.0 to 17.1% over a range of itraconazole concentrations from 100 to 1600 micrograms/l. Comparison of the methods showed that HPLC gave much lower values of itraconazole concentrations in patient serum samples than did the microbiological method.

Antifungal Agents↗
PubMed1988

Pharmacokinetic study of the interaction between rifampicin and ketoconazole.

This study assessed the potential pharmacokinetic interaction between rifampicin and ketoconazole, two drugs used to treat the increasingly common combination of Mycobacterium tuberculosis and Candida albicans infection in AIDS patients. The peak plasma rifampicin concentrations in six healthy male subjects were not altered when taken in conjunction with ketoconazole. However, the peak plasma ketoconazole levels were significantly diminished when taken in conjunction with rifampicin, compared to when taken alone (P less than 0.015). The mean area under the curve (AUC) for ketoconazole was significantly diminished when taken with oral or intravenous rifampicin (P less than 0.001).

Drug Interactions↗