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Species distribution and fluconazole susceptibility of Candida clinical isolates in a medical center in 2002.

Wang JL, Chang SC, Hsueh PR, Chen YC.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC.

Fluconazole disk-diffusion susceptibility was evaluated in 230 blood isolates and 344 non-blood clinical isolates of Candida spp. collected in 2002 at National Taiwan University Hospital. Up to 93.5% of blood isolates were susceptible to fluconazole, 3% were susceptible dose-dependent, and 3.5% were resistant. The minimum inhibitory concentrations at which 50% of tested isolates were inhibited (MIC50) of fluconazole against Candida blood isolates were highest for Candida glabrata (5 microg/mL), followed by Candida tropicalis (2.4 microg/mL), Candida albicans (2.4 microg/mL), and Candida parapsilosis (0.41 microg/mL). C. glabrata had less fluconazole-susceptible strains (76.7%) than C. albicans (98.2%), C. tropicalis (98%) and C. parapsilosis (93.8%) [p<0.05]. The proportions of fluconazole resistance in the non-blood isolates of C. albicans, C. glabrata and C. parapsilosis were similar to those of the blood isolates. However, the proportions of fluconazole resistance in the non-blood isolates of C. tropicalis surpassed those of the blood isolates (14.7% vs 2%, p<0.05). Comparison of species distribution of Candida blood isolates obtained in 2002 to those in 1981-2000 demonstrated that C. albicans remained the leading pathogen, and the proportion of C. albicans in blood isolates was lowest in 1996 (38%) and did not change significantly thereafter. However, the proportion of C. tropicalis increased from 14% during 1981-1993 to 22-23% during 1996-2002. Overall, the MIC50, MIC90 and the proportion of Candida blood isolates with fluconazole resistance remained stable during 1994-2002.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15340652&dopt=Abstract fluconazole Diflucan



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Colony size can be used to determine the MIC of fluconazole for pathogenic yeasts.

Xu J, Vilgalys R, Mitchell TG.

Department of Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.

This report describes a new statistical method for estimating the MIC of fluconazole for yeasts pathogenic to humans. This method is based on comparison of the colony sizes on solid media containing different concentrations of fluconazole. By this method, the MICs of fluconazole for 10 yeast strains were comparable to results obtained by the standard method recommended by the National Committee for Clinical Laboratory Standards. This method is simple to perform and easy to interpret. The turnaround time is faster than other methods. The method should be applicable to the determination MICs of other antifungal drugs for yeasts.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9666032&dopt=Abstract fluconazole Diflucan



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Enhanced activity of antifungal drugs by lysozyme against Cryptococcus neoformans.

Nakamura Y, Kano R, Watanabe S, Takahashi H, Hasegawa A.

Teikyo University School of Medicine, Department of Dermatology, Tokyo, Japan.

The in vitro susceptibility of 16 isolates of Cryptococcus neoformans to three antifungal drugs and lysozyme in combination was determined using an urea broth microdilution method. The antifungal activities of each drug alone against 16 isolates of Cr. neoformans were determined as mean minimal inhibitory concentrations (MICs). MICs of fluconazole, itraconazole and terbinafine were 2.0 micrograms ml-1, 0.004 microgram ml-1 and 0.25 microgram ml-1, respectively. Lysozyme alone inhibited the growth of Cr. neoformans in a dose-dependent manner, although the lysozyme was unable to kill the cells of Cr. neoformans at the highest concentration of 20 micrograms ml-1. The mean MICs of fluconazole, itraconazole and terbinafine in combination with lysozyme were 0.13 microgram ml-1, 0.004 microgram ml-1 and 0.03 microgram ml-1 respectively. The antifungal activity of fluconazole and terbinafine in combination with lysozyme against Cr. neoformans was greatly enhanced compared with that of each drug alone. Itraconazole was unable to enhance the antifungal activity, as it demonstrated higher activity against Cr. neoformans when alone rather than in combination. Lysozyme was confirmed to enhance the antifungal activity of fluconazole and terbinafine in vitro.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9715633&dopt=Abstract fluconazole Diflucan



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Cross-sectional study of oral Candida carriage in a human immunodeficiency virus (HIV)-seropositive population: predisposing factors, epidemiology and antifungal susceptibility.

Schoofs AG, Odds FC, Colebunders R, Ieven M, Goossens H.

Department of Microbiology, University Hospital Antwerp, Belgium.

The Candida species isolated from oral rinses of 130 human immunodeficiency virus (HIV) infected patients were compared with those of 130 healthy non-matched volunteers. The oral rinses were plated on CHROMagar Candida medium (CAC) and on CAC supplemented with 10 micrograms (CF10) and 100 micrograms (CF100) of fluconazole per ml. The prevalence of non-albicans Candida spp. in oral rinses of HIV-infected patients and their correlation with the clinical and epidemiological characteristics of the patients were studied. Susceptibility of the Candida spp. isolated was determined by a microbroth dilution method based on the NCCLS reference procedure. Results of susceptibility tests of the yeast isolates were compared with their growth at the time of isolation on CAC supplemented with fluconazole. Thirty-five (30.7%) strains of non-albicans Candida spp. were isolated from the HIV-positive population, vs. seven (15.9%) from the immunocompetent population. Growth on CF10 correlated in 96% of the cases with fluconazole minimum inhibitory concentration (MIC) > 8 micrograms ml-1. Smoking and use of azoles were significantly associated with oral carriage of non-albicans Candida spp. (P < 0.05). The prevalence of non-albicans Candida spp. in HIV-positive persons in oral rinse samples is twice as high as in the HIV-negative population. Smoking and treatment with azoles are risk factors for the oral carriage of non-albicans Candida spp. The isolation of yeasts on CAC plates supplemented with fluconazole allows combination of presumptive yeast identification and fluconazole susceptibility testing.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9715634&dopt=Abstract fluconazole Diflucan



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Pharmacokinetics of oral fluconazole in premature infants.

Wenzl TG, Schefels J, Hornchen H, Skopnik H.

Kinderklinik der Medizinischen Fakultat der RWTH Aachen, Germany.

Systemic infections with Candida albicans in neonates are a frequent and well recognized problem. The therapeutic gold standard in this situation is the combined intravenous antimycotic treatment with amphotericin B and flucytosine. Potential adverse effects of this regimen have encouraged the search for desirable alternatives. We report on the use of oral fluconazole in neonates with Candida albicans septicaemia. Three premature infants were treated with four courses of therapy. Pharmacokinetic studies were performed during each course. At oral doses of 4.5-6 mg/kg once a day, serum levels of fluconazole were within the therapeutic range during the entire dosage interval. Follow up showed microbiological and clinical cure in all patients with no side-effects. In one patient a dosage of 4 mg/kg per day lead to a microbiological relapse with sub-therapeutic serum levels. CONCLUSIONS: Oral fluconazole seems to be a safe and effective treatment for Candida albicans septicaemia even in premature infants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9727851&dopt=Abstract fluconazole Diflucan



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Efficacy of nikkomycin Z in the treatment of murine histoplasmosis.

Graybill JR, Najvar LK, Bocanegra R, Hector RF, Luther MF.

Audie Murphy Memorial Veterans Hospital, San Antonio, Texas 78284, USA.

Immune-competent ICR and BALB/c athymic (nude) mice were infected intravenously with Histoplasma capsulatum and treated with either fluconazole or nikkomycin Z or 5% dextrose (controls). In immune-competent ICR mice, fluconazole and nikkomycin Z both prolonged survival when given at 5 mg/kg of body weight twice daily. When administered in doses as low as 2.5 mg/kg twice daily, nikkomycin Z reduced fungal counts in both the spleen and liver. When both drugs were combined, there was no antagonism, and in combined therapy spleen and liver counts were reduced more than for either drug alone. However, nikkomycin Z had no effect on brain fungal burden. In nude mice fluconazole and nikkomycin Z had an additive effect in prolongation of survival and reduction of liver and spleen burden. Nikkomycin Z is well tolerated, is at least as effective as fluconazole, and may interact beneficially with fluconazole for treatment of murine histoplasmosis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9736565&dopt=Abstract fluconazole Diflucan



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Fluconazole susceptibility testing of Cryptococcus neoformans: comparison of two broth microdilution methods and clinical correlates among isolates from Ugandan AIDS patients.

Jessup CJ, Pfaller MA, Messer SA, Zhang J, Tumberland M, Mbidde EK, Ghannoum MA.

Mycology Reference Laboratory, Center for Medical Mycology, Department of Dermatology, Case Western Reserve University and University Hospitals of Cleveland, Ohio, USA.

We compared the yeast nitrogen base (YNB) broth microdilution method with the National Committee for Clinical Laboratory Standards (NCCLS) M27-A microdilution reference method for measuring the in vitro susceptibility of Cryptococcus neoformans isolates to fluconazole. A total of 149 isolates of C. neoformans var. neoformans from Ugandan AIDS patients was tested by both methods. An overall agreement of 88% between the two microdilution methods was observed. All isolates grew well in both RPMI 1640 and YNB media, and MICs could be read after 48 h of incubation by both methods. The range of fluconazole MICs obtained with the YNB method was broader than that obtained with the NCCLS method. The extended range of MICs provided by the YNB method may be of clinical value, as it appears that the clinical outcome may be better among patients infected with strains inhibited by lower concentrations of fluconazole as determined by the YNB method. The YNB method appears to be a viable option for testing C. neoformans against fluconazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9738036&dopt=Abstract fluconazole Diflucan



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In-vitro susceptibility of Cryptococcus neoformans isolates to fluconazole and itraconazole.

Davey KG, Johnson EM, Holmes AD, Szekely A, Warnock DW.

PHLS Mycology Reference Laboratory, Public Health Laboratory, Kingsdown, Bristol, UK.

The in-vitro susceptibilities of 143 isolates of Cryptococcus neoformans, collected from British patients between 1994 and 1996, to fluconazole and itraconazole were compared with those of 36 isolates collected between 1971 and 1985, 41 isolates collected between 1986 and 1989, and 43 Ugandan isolates collected in 1996. Testing was done with a broth microdilution method in YNB medium supplemented with glucose, incubation at 30 degrees C for 72 h, and an endpoint of 50% inhibition. The results showed that the MIC ranges, MIC50s and MIC90s of fluconazole and itraconazole for C. neoformans isolates from the UK have remained unchanged despite the recent widespread use of triazoles for long-term maintenance of patients with AIDS-associated cryptococcal meningitis. The MIC ranges, MIC50s and MIC90s of the 43 isolates from untreated Ugandan patients with AIDS were similar to those of the British isolates. Examination of our records for 1994-96 revealed six cases in which a four-fold or greater rise in the MIC of fluconazole was associated with relapsed cryptococcal meningitis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9738839&dopt=Abstract fluconazole Diflucan