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1.
In this study we investigated the antifungal susceptibility of 285 strains of Candida albicans isolates at Kinki University Hospital from March 1995 to December 1996. The antifungal agents tested were fluconazole, miconazole, intraconazole, amphotericin B and flucytosine. The susceptibility testing were performed according to the broth microdilution method standardized by National Committee for Clinical Laboratory Standards (M27-T). Most isolates of C. albicans showed relatively a low MIC value and the MIC90S were calculated at 1 microgram/ml; fluconazole, 0.125 microgram/mg; miconazole, 0.06 microgram/ml; itraconazole, 1 microgram/ml; amphotericin B, 0.25 microgram/ml; flucytosine. There was only one strain that showed high resistance against fluconazole and it showed cross-resistance against miconazole and itraconazole. There were two flucytosine resistant strains. The MICs of amphotericin B were tightly clustered and resistant strain were not observed.  相似文献   

2.
The in vitro activity of voriconazole (UK-109, 496), a new antifungal triazole derivative, against 650 clinical isolates of yeasts, moulds and dermatophytes was compared with that of itraconazole, ketoconazole, amphotericin B and griseofulvin. The geometric means of the minimum inhibitory concentrations (MICs) of voriconazole were 0.05 microgram ml-1 against yeasts (n = 187), 0.58 microgram ml-1 against moulds (n = 260) and 0.08 microgram ml-1 against dermatophytes (n = 203). The overall activity of voriconazole against yeasts and moulds was good, being similar to that of itraconazole, ketoconazole and amphotericin B. Voriconazole was highly effective against Aspergillus fumigatus (mean MIC 0.23 microgram ml-1) and other Aspergillus species and showed noteworthy activity (mean MICs 0.08-0.78 microgram ml-1) against emerging and less common clinical isolates of opportunistic moulds, such as Alternaria spp., Cladosporium spp., Acremonium spp., Chrysosporium spp. and Fusarium spp. On the other hand, voriconazole was less active in vitro than the comparative agents studied against various species of zygomycetes, such as Mucor spp., Rhizopus spp. and Absidia spp. Voriconazole and the other two azoles, itraconazole and ketoconazole, were more active than griseofulvin in vitro against most dermatophytes tested.  相似文献   

3.
The in vitro activity of a naturally occurring complex carbohydrate, CAN-296, was evaluated by testing 132 clinical and ATCC isolates of yeast and Aspergillus fumigatus, many of which were azole-resistant. The in vitro susceptibility tests were performed by standardized broth micro- and macrodilution methods and results were compared with those obtained for amphotericin B, fluconazole, ketoconazole, flucytosine and the pneumocandin L-733,560. All tested Candida species showed highly uniform susceptibility to CAN-296 at concentrations of 0.078 to 0.312 microgram/ml; non-albicans Candida were as susceptible to CAN-296 as the Candida albicans strains. Multi-azole-resistant Candida species were highly sensitive to CAN-296. Minimum inhibitory concentration measurements did not differ from minimum lethal concentrations by more than two-fold for all tested Candida species. Aspergillus fumigatus, on the other hand, showed only moderate susceptibility to CAN-296. The kinetics of the anti-Candida activity of CAN-296 was investigated by kill-curve experiments using C. albicans and C. glabrata and the results were compared with those obtain for amphotericin B. CAN-296 was found to be rapidly fungicidal in concentrations ranging from 4-16 fold the mean MIC value. The broad spectrum of anti-Candida activity together with the rapid fungicidal effect make this complex carbohydrate a promising agent for clinical use.  相似文献   

4.
The in vitro activity of the fluoroquinolone trovafloxacin (CP-99,219) against 257 blood isolates of Streptococcus pneumoniae obtained from Swedish hospitals was compared with those of commonly prescribed oral antibiotics and also with those of ciprofloxacin and ofloxacin against a collection of strains resistant (n = 6) or intermediately resistant (n = 22) to penicillin (Pc-R). The MICs of trovafloxacin for Pc-R strains of pneumococci ranged from 0.032 to 0.25 mg/l. No difference was seen between the clinical isolates and the Pc-R strains (MIC50 = 0.064 mg/l and MIC90 = 0.125 mg/l for both collections). For the Pc-R strains, the MIC50 and MIC90 values of ciprofloxacin were 0.5 and 1 mg/l, and those of ofloxacin 2 and 4 mg/l. The incidence of resistance in the two collections (clinical isolates/Pc-R strains) was 3%/39% for tetracycline, 1%/18% for macrolides, and 3%/57% for trimethoprim/sulfamethoxazole. The results of the current study suggest that the clinical efficacy of trovafloxacin in the treatment of pneumococcal infections should be investigated.  相似文献   

5.
Three susceptibility testing procedures were compared to determine fluconazole, itraconazole, and ketoconazole MICs against 47 Candida albicans strains isolated sequentially from the oral cavities of five AIDS patients undergoing azole therapy. They included the broth microdilution method (BM), performed according to the National Committee for Clinical Laboratory Standards' tentative standard, the agar dilution method (AD), and the Etest; the latter two tests were performed both in Casitone agar (AD-Cas and Etest-Cas) and in RPMI (AD-RPMI and Etest-RPMI). Twenty-four- and 48-h MICs obtained by AD and Etest were compared with 48-h MICs obtained by BM. The MICs of all the azoles determined by BM were usually lower than those obtained by the other methods, mainly due to different reading criteria. In order to assess the most appropriate way of evaluating the agreement of MICs obtained by different methods with those produced by the proposed reference method (BM), we used the mean differences calculated according to Bland and Altman's method. Comparison of fluconazole MICs obtained by BM and AD-Cas yielded a mean difference of 3, and the percentages of agreement within +/-2 dilutions were 98 and 100% at 24 and 48 h, respectively. For ketoconazole and itraconazole MICs, lower mean differences were noted, and agreement ranged from 96 to 100%. Agreement between the AD-RPMI and BM results was poor for all azoles, and an increase in MICs was always observed between the 1st- and 2nd-day readings. Similarly, Etest-Cas gave better agreement with BM than did Etest-RPMI for all the azoles. BM, AD-Cas, and Etest-Cas each demonstrated a progressive increase in fluconazole MICs against strains isolated sequentially from a given patient, in accordance with the decreased clinical response to fluconazole.  相似文献   

6.
In this study, we investigated the in vitro activity of SCH-56592 (SCH), a new triazole antifungal agent. We compared the activity of SCH with those of itraconazole (ITZ) and amphotericin B (AB) against 60 clinical isolates of Aspergillus spp. by using a microtiter format. Incubation was done at 37 degrees C for 48 h, and MIC endpoints (no growth) were read visually. The medium used for all of the drugs was RPMI 1640 buffered with morpholinepropanesulfonic acid (MOPS) and supplemented with 2% glucose. MICs and minimum fungicidal concentrations (MFCs; killing of > or = 99.99%) were measured for all isolates. The geometric mean (GM) MICs and ranges (in micrograms per milliliter) were as follows: SCH, 0.09 and < or = 0.01 to 1; ITZ, 0.25 and 0.06 to 32; AB, 1.46 and 0.25 to 32. Aspergillus terreus (n = 7) was markedly more susceptible to SCH (GM, 0.05 microg/ml) and ITZ (GM, 0.07 microg/ml) than to AB (GM, 8.8 microg/ml). For all isolates, the GM MFCs and ranges (in micrograms per milliliter) were as follows: SCH, 3.64 and 0.125 to 16; ITZ, 15.09 and 0.125 to 32; AB, 10.3 and 1 to 32. In the drug concentration range tested, 71, 32, and 64% of the isolates against which SCH, ITZ, and AB, respectively, were tested were killed. A reproducibility study was performed with 20% of the isolates; for 11 of the 12 isolates retested, the MIC was the same or within 1 well of the original MIC of each drug. Therefore, in vitro mould testing of SCH is feasible and reproducible. SCH was found to be very active against all species of Aspergillus and at lower concentrations than either ITZ or AB.  相似文献   

7.
The effects of bovine lactoferrin (LF) or the LF-derived antimicrobial peptide lactoferricin B (LFcin B) on the growth of Candida albicans hyphae, including those of three azole-resistant strains, were investigated by a crystal violet staining method. The hyphae of two highly azole-resistant strains were more susceptible to inhibition by LF or LFcin B than the azole-susceptible strains tested. One moderately azole-resistant strain was defective in the formation of hyphae and showed a susceptibility to LF greater than that of the susceptible strains but a susceptibility to LFcin B similar to that of the susceptible strains. The highly azole-resistant strain TIMM3317 showed trailing growth in the presence of fluconazole or itraconazole, while the extent of growth was reduced by the addition of LF or LFcin B at a sub-MIC. Thus, the addition of LF or LFcin B at a sub-MIC resulted in a substantial decrease in the MICs of fluconazole and itraconazole for two highly azole-resistant strains; e.g., the MIC of fluconazole for TIMM3317 was shifted from > 256 to 0.25 micrograms/ml by LF, but the MICs were not decreased for the susceptible strains. The combination effects observed with triazoles and LF-related compounds in the case of the two highly azole-resistant strains were confirmed to be synergistic by the fractional inhibitory concentration index. These results demonstrate that for some azole-resistant C. albicans strains, LF-related compounds combined with triazoles can inhibit the growth of hyphae, an important form of this organism in pathogenesis.  相似文献   

8.
OBJECTIVES: To determine the proportion of fluconazole-resistant Candida albicans isolates that have clinically significant cross-resistance to itraconazole or ketoconazole, that is sufficient to result in failure of these agents at their standard doses (200 and 400 mg daily for 7 days, respectively). METHODS: Seven hundred C. albicans isolates from HIV-positive patients with oral candidosis underwent susceptibility testing using a relative growth method, for which cut-off values corresponding to clinical drug failure have been established. RESULTS: A total of 431 isolates were fully azole-susceptible and three main resistance patterns were detected: isolates resistant to fluconazole alone (n = 100); isolates resistant to fluconazole and ketoconazole but susceptible to itraconazole (n = 94); and isolates resistant to all three drugs (n = 50). No isolates were consistently resistant to ketoconazole without being fluconazole-resistant, and no itraconazole resistance was detected without ketoconazole resistance. Resistance to fluconazole alone was more common in specimens obtained soon after first clinical fluconazole failure, whereas specimens from patients with a longer history of fluconazole-unresponsive candidosis were more likely to be infected with cross-resistant isolates. Median days of prior azole exposure and cumulative fluconazole dose were significantly less for those with isolates resistant to fluconazole alone than for those with ketoconazole cross-resistant isolates, who had received less azole therapy and smaller cumulative fluconazole doses than those with isolates cross-resistant to all three drugs (although not statistically significant). After the diagnosis of fluconazole-unresponsive candidosis, increasing cumulative doses of itraconazole solution were associated with increasing likelihood of cross-resistance. CONCLUSIONS: Clinically significant cross-resistance to other azoles may occur in fluconazole-resistant isolates of C. albicans, although initially most isolates are not cross-resistant and the detection of cross-resistant isolates is associated with a history of greater prior azole exposure. Patients who have been treated for fluconazole-resistant candidosis for longer and with greater cumulative doses of itraconazole solution tend to become infected with increasingly cross-resistant isolates of C. albicans.  相似文献   

9.
The antifungal susceptibility of 35 Candida lusitaniae isolates was determined in vitro by the National Committee for Clinical Laboratory Standards (NCCLS) M27-P macrodilution methodology. All the isolates were susceptible to ketoconazole, itraconazole and fluconazole. Of the 35 isolates, eight (23%) were resistant to flucytosine. For amphotericin B, M27-P yielded a narrow range of MICs (0.06-0.5 mg/L). We therefore investigated the activity of this drug by reading MICs at 72 h and by using alternative media, namely casitone complex medium (CCM) and antibiotic medium 3 (M-3). Reading at 72 h did not generate reproducible results. CCM and M-3 provided better discrimination between the isolates but did not change the rank order of the MICs. We thus concluded that all the isolates were susceptible to amphotericin B. We also conducted an evaluation with the Etest method according to the manufacturer's instructions with RPMI 1640 agar, CCM and the alternative semi-synthetic medium (SSM). For RPMI 1640, agreements +/-2 dilutions were 58% for amphotericin B, 92% for flucytosine, 57% for ketoconazole, 92% for fluconazole and 74% for itraconazole. CCM did not improve the agreement rates between the two methods but it led to better growth of all the isolates. The suitability of SSM was pointed out with itraconazole. The poor agreement rates for amphotericin B and ketoconazole call for further evaluation of the Etest method to assess several drug-organism combinations.  相似文献   

10.
A method using a commercially prepared colorimetric microdilution panel (ASTY; Kyokuto Pharmaceutical Industrial Co., Ltd.) was compared in four different laboratories with the National Committee for Clinical Laboratory Standards (NCCLS) reference microdilution method by testing 802 clinical isolates of Candida spp. (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei, C. lusitaniae, C. guilliermondii, C. lipolytica, C. rugosa, and C. zeylanoides) against amphotericin B, 5-fluorocytosine (5FC), fluconazole, and itraconazole. Reference MIC endpoints were established after 48 h of incubation, and ASTY endpoints were established after 24 and 48 h of incubation. ASTY endpoints were determined to be the time at which the color of the first well changed from red (indicating growth) to purple (indicating growth inhibition) or blue (indicating no growth). Excellent agreement (within 2 dilutions) between the reference and colorimetric MICs was observed. Overall agreement was 93% at 24 h and 96% at 48 h. Agreement ranged from 90% with itraconazole and 5FC to 96% with amphotericin B at 24 h and from 92% with itraconazole to 99% with amphotericin B and 5FC at 48 h. The ASTY colorimetric microdilution panel method appears to be comparable to the NCCLS reference method for testing the susceptibilities of Candida spp. to a variety of antifungal agents.  相似文献   

11.
The minimal inhibitory (MICs) and bactericidal concentrations of 14 antimicrobial drugs were determined against 17 clinical isolates of Enterococcus faecium, including 4 glycopeptide-resistant strains. Both teicoplanin and vancomycin lacked bactericidal activity against all 13 susceptible isolates. Time-kill experiments served to test various antibiotic combinations chiefly against glycopeptide-resistant strains in Mueller-Hinton broth (MHB) and in MHB supplemented with 65% (v/v) fresh defibrinated human blood. Co-trimoxazole, fusidic acid, and novobiocin yielded bacteriostatic effects. Rifampin was bactericidally active against rifampin-susceptible strains (MICs = 0.125 micrograms/ml), but less so against low-level-rifampin-resistant (MICs = 2-8 micrograms/ml) strains in MHB. However, in the presence of human blood, rifampin (2 micrograms/ml) combined with co-trimoxazole (0.25/4.75 micrograms/ml) killed rifampin-susceptible and low-level-rifampin-resistant, but not moderate-level-rifampin-resistant (MICs = 16-32 micrograms/ml) strains of E. faecium. Of two topical drugs examined, mupirocin merely inhibited strains of E. faecium; conversely, taurolidine at 2,000 micrograms/ml was efficacious against all strains examined, although the kinetics of bactericidal activity were retarded somewhat in the presence of 65 vol% human blood.  相似文献   

12.
L-733,560 and L-743,872 are water-soluble pneumocandins with potent antifungal activity. By beginning with the NCCLS M27-T method and varying test format (microdilution vs macrodilution), time of reading (24 h vs 48 h), and test medium (RPMI 1640 vs Antibiotic Medium 3), we have demonstrated that the MICs for these compounds can be altered significantly: the microdilution format, reading after 24 h and use of Antibiotic Medium 3 all reduced the measured MIC. No cross-resistance was demonstrated with either fluconazole or amphotericin B.  相似文献   

13.
The pneumocandins are natural lipopeptide products of the echinocandin class which inhibit the synthesis of 1,3-beta-D-glucan in susceptible fungi. The lack of a corresponding pathway in mammalian hosts makes this mode of action an attractive one for treating systemic infections. Substitution by an aminoethyl ether at the hemiaminal and dehydration and reduction of the glutamine of pneumocandin B0 produced a semisynthetic compound (L-733,560) with intrinsic water solubility, significantly increased potency, and a broader antifungal spectrum. To evaluate the mechanism for the improved antifungal efficacy, we determined that L-733,560 was a more potent inhibitor of glucan synthase activity in vitro, did not affect the other membrane-bound enzymes tested, conferred susceptibility to lysis in the absence of osmotic support, and did not disrupt currents in liposomal bilayers or 86Rb+ fluxes from liposomes. In Aspergillus species L-733,560 also produced the same morphological alterations as pneumocandin B0. A stereoisomer of L-733,560 with poor antifungal activity was a weak inhibitor of glucan synthase. All of these results support the notion that the enhanced antifungal activity of L-733,560 is achieved by superior inhibition of glucan synthesis and not by nonspecific membrane effects or a second mode of action.  相似文献   

14.
A total of 435 clinical isolates of anaerobes were tested with a broth microdilution method to determine the activity of BAY y 3118 compared with those of other agents against anaerobic bacteria. All strains of Bacteroides capillosus, Prevotella spp., Porphyromonas spp., Fusobacterium spp., Clostridium spp., Eubacterium spp., Peptostreptococcus spp., and Veillonella parvula were susceptible (MICs of < or = 2 micrograms/ml) to BAY y 3118. Against the 315 strains of the Bacteroides fragilis group, five strains required elevated MICs (> or = 4 micrograms/ml) of BAY y 3118. Only imipenem and metronidazole were active against all anaerobes. Overall, BAY y 3118 was more active than ciprofloxacin, sparfloxacin, piperacillin, cefotaxime, and clindamycin against the test isolates.  相似文献   

15.
A simple screening method for fluconazole susceptibility using CHROMagar Candida with fluconazole was compared with the National Committee for Clinical Laboratory Standards (NCCLS) macrobroth method. In this agar dilution method, susceptible Candida albicans colonies are smaller on medium with fluconazole than on fluconazole-free medium. Yeasts with decreased susceptibility have normal-sized colonies on medium containing fluconazole. On agar with 16 micrograms of fluconazole per ml, 32 of 34 strains with NCCLS MICs of > or = 16 micrograms/ml were correctly predicted, as were 66 of 68 with MICs of < 16, an agreement of 96%. On agar with 8 micrograms of fluconazole per ml, 38 of 41 isolates with MICs of > or = 8 were correctly predicted, as were 59 of 61 isolates with MICs of < 8, an agreement of 95%. This agar dilution methods appears to highly correlate with NCCLS macrobroth methods for detection of C. albicans and may be an effective screen for fluconazole susceptibility.  相似文献   

16.
Candida dubliniensis has been associated with oropharyngeal candidiasis in patients infected with human immunodeficiency virus (HIV). C. dubliniensis isolates may have been improperly characterized as atypical Candida albicans due to the phenotypic similarity between the two species. Prospective screening of oral rinses from 63 HIV-infected patients detected atypical dark green isolates on CHROMagar Candida compared to typical C. albicans isolates, which are light green. Forty-eight atypical isolates and three control strains were characterized by germ tube formation, differential growth at 37, 42, and 45 degreesC, identification by API 20C, fluorescence, chlamydoconidium production, and fingerprinting by Ca3 probe DNA hybridization patterns. All isolates were germ tube positive. Very poor or no growth occurred at 42 degreesC with 22 of 51 isolates. All 22 poorly growing isolates at 42 degreesC and one isolate with growth at 42 degreesC showed weak hybridization of the Ca3 probe with genomic DNA, consistent with C. dubliniensis identification. No C. dubliniensis isolate but only 18 of 28 C. albicans isolates grew at 45 degreesC. Other phenotypic or morphologic tests were less reliable in differentiating C. dubliniensis from C. albicans. Antifungal susceptibility testing showed fluconazole MICs ranging from 相似文献   

17.
Ninety-eight isolates of Cryptococcus neoformans were collected from 30 patients at the University of Iowa Hospitals and Clinics from December 1987 through December 1994. The susceptibility of each isolate was determined against fluconazole, itraconazole, amphotericin B, and flucytosine. Of the 98 isolates, 53 were recovered from blood, 19 were recovered from cerebrospinal fluid (CSF), and 26 were recovered from other sources. Although the strains were isolated from the same institution, DNA typing by electrophoretic karyotype (EK) revealed wide genetic variation. Overall, 23 different EK profiles were identified by computer-aided analysis. An isolate exhibiting a single EK was isolated from 24 of 30 patients (80%), whereas multiple strains with unique EKs were isolated from 6 of 30 (20%) patients. Of the six patients who had multiple strains recovered, only one individual had two strains isolated from unique body sites, one strain from the blood and the other from the CSF. Six strains were isolated from multiple patients. Nine patients had multiple sequential isolates recovered over periods of time ranging from 3 days to 4 months. EK analysis revealed persistence of the same genotype in six of the cases. Three patients, however, appeared to have an isolate with a second distinct EK emerge during therapy. Of the patients with sequential positive cultures, an increase in the MICs for test agents was observed in only one case. C. neoformans isolates were collected over a period of 7 years, during which time MICs at our institution remained stable.  相似文献   

18.
The in vitro susceptibilities of three hundred eighty-one isolates representing two classes, five orders, nine families, 30 genera, and 51 species of ascomycetous fungi to voriconazole, itraconazole, and amphotericin B were tested by using a modification of the National Committee for Clinical Laboratory Standards M27-A reference method. For those fungi of known phylogenetic relatedness, drug MICs were consistently low for isolates among all clades, except for members of the family Microascaceae. The highest MICs of all drugs tested were consistently for the Microascaceae, supporting the observation of fungal phylogeny and corresponding susceptibility to antifungal drugs. Itraconazole and voriconazole have a broad range of activity against phylogenetically similar agents of hyalohyphomycosis, phaeohyphomycosis, chromoblastomycosis, and mycetoma.  相似文献   

19.
Twenty analogues of pentamidine, 7 primary metabolites of pentamidine, and 30 dicationic substituted bis-benzimidazoles were screened for their inhibitory and fungicidal activities against Candida albicans and Cryptococcus neoformans. A majority of the compounds had MICs at which 80% of the strains were inhibited (MIC80s) comparable to those of amphotericin B and fluconazole. Unlike fluconazole, many of these compounds were found to have potent fungicidal activity. The most potent compound against C. albicans had an MIC80 of 相似文献   

20.
National Committee for Clinical Laboratory Standards (NCCLS) standard guidelines are available for the antifungal susceptibility testing of common Candida spp. and Cryptococcus neoformans, but NCCLS methods may not be the most efficient and convenient procedures for use in the clinical laboratory. MICs of amphotericin B, fluconazole, flucytosine, itraconazole, and ketoconazole were determined by the commercially prepared Sensititre YeastOne Colorimetric Antifungal Panel and by the NCCLS M27-A broth microdilution method for 1,176 clinical isolates of yeasts and yeast-like organisms, including Blastoschizomyces capitatus, Cryptococcus spp., 14 common and emerging species of Candida, Hansenula anomala, Rhodotorula spp., Saccharomyces cerevisiae, Sporobolomyces salmonicolor, and Trichosporon beigelii. Colorimetric MICs of amphotericin B corresponded to the first blue well (no growth), and MICs of the other agents corresponded to the first purple or blue well. Three comparisons of MIC pairs by the two methods were evaluated to obtain percentages of agreement: 24- and 48-h MICs and 24-h colorimetric versus 48-h reference MICs. The best performance of the YeastOne panel was with 24-h MICs (92 to 100%) with the azoles and flucytosine for all the species tested, with the exception of C. albicans (87 to 90%). For amphotericin B, the best agreement between the methods was with 48-h MIC pairs (92 to 99%) for most of the species tested. The exception was for isolates of C. neoformans (76%). These data suggest the potential value of the YeastOne panel for use in the clinical laboratory.  相似文献   

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