scholarly journals In vitro activities of semisynthetic pneumocandin L-733,560 against fluconazole-resistant and -susceptible Candida albicans isolates.

1996 ◽  
Vol 40 (5) ◽  
pp. 1277-1279 ◽  
Author(s):  
J V Martinez-Suarez ◽  
J L Rodriguez-Tudela

Lipopeptide L-733,560 is a water-soluble derivative of pneumocandin B0 that exhibits enhanced anti-Candida activity. We investigated the in vitro activity of L-733,560 compared with those of amphotericin B, flucytosine, and itraconazole, against fluconazole-resistant (n = 44) and fluconazole-susceptible (n = 46) Candida albicans isolates. Tests were performed with a photometer-read broth microdilution method with RPMI-2% glucose and National Committee for Clinical Laboratory Standards reference strains. Except for those of itraconazole, MICs were not significantly different between the two groups of isolates, as expected for agents with different mechanisms of action. L-733,560 was the most active agent against C.albicans, with MICs for 50 and 90% of the strains tested of 0.01 and 0.06 microgram/ml, respectively.

1996 ◽  
Vol 40 (9) ◽  
pp. 1998-2003 ◽  
Author(s):  
J L Rodríguez-Tudela ◽  
J Berenguer ◽  
J V Martínez-Suárez ◽  
R Sanchez

The National Committee for Clinical Laboratory Standards has proposed a reference broth macrodilution method for in vitro antifungal susceptibility testing of yeasts (the M27-P method). This method is cumbersome and time-consuming and includes MIC endpoint determination by visual and subjective inspection of growth inhibition after 48 h of incubation. An alternative microdilution procedure was compared with the M27-P method for determination of the amphotericin B, flucytosine, and fluconazole susceptibilities of 8 American Type Culture Collection strains (6 of them were quality control or reference strains) and 50 clinical isolates of candida albicans. This microdilution method uses as culture medium RPMI 1640 supplemented with 18 g of glucose per liter (RPMI-2% glucose). Preparation of drugs, basal medium, and inocula was done by following the recommendations of the National Committee for Clinical Laboratory Standards. The MIC endpoint was calculated objectively from the turbidimetric data read at 24 h. Increased growth of C. albicans in RPMI-2% glucose and its spectrophotometric reading allowed for the rapid (24 h) and objective calculation of MIC endpoints compared with previous microdilution methods with standard RPMI 1640. Nevertheless, good agreement was shown between the M27-P method and this microdilution test. The MICs obtained for the quality control or reference strains by the microdilution method were in the ranges published for those strains. For clinical isolates, the percentages of agreement were 100% for amphotericin B and fluconazole and 98.1% for flucytosine. These data suggest that this microdilution method may serve as a less subjective and more rapid alternative to the M27-P method for antifungal susceptibility testing of yeasts.


2000 ◽  
Vol 44 (1) ◽  
pp. 226-229 ◽  
Author(s):  
Francesco Barchiesi ◽  
Daniela Arzeni ◽  
Annette W. Fothergill ◽  
Luigi Falconi Di Francesco ◽  
Francesca Caselli ◽  
...  

ABSTRACT A broth microdilution method performed in accordance with the National Committee for Clinical Laboratory Standards guidelines was used to compare the in vitro activity of the new antifungal triazole SCH 56592 (SCH) to that of fluconazole (FLC), itraconazole (ITC), and ketoconazole (KETO) against 257 clinical yeast isolates. They included 220 isolates belonging to 12 different species of Candida, 15 isolates each of Cryptococcus neoformans andSaccharomyces cerevisiae, and seven isolates ofRhodotorula rubra. The MICs of SCH at which 50% (MIC50) and 90% (MIC90) of the isolates were inhibited were 0.06 and 2.0 μg/ml, respectively. In general, SCH was considerably more active than FLC (MIC50 and MIC90 of 1.0 and 64 μg/ml, respectively) and slightly more active than either ITC (MIC50 and MIC90 of 0.25 and 2.0 μg/ml, respectively) and KETO (MIC50 and MIC90 of 0.125 and 4.0 μg/ml, respectively). Our in vitro data suggest that SCH has significant potential for clinical development.


2000 ◽  
Vol 44 (5) ◽  
pp. 1242-1246 ◽  
Author(s):  
Angela M. Nilius ◽  
Patti M. Raney ◽  
Dena M. Hensey-Rudloff ◽  
Weibo Wang ◽  
Qun Li ◽  
...  

ABSTRACT A-192411.29 is a novel antifungal agent derived from the structural template of the natural product echinocandin. The in vitro activity of A-192411.29 against common pathogenic yeasts was assessed by National Committee for Clinical Laboratory Standards method M27-A. It demonstrated broad-spectrum, fungicidal activity and was active against the most clinically relevant yeasts, such as Candida albicans, Candida tropicalis, and Candida glabrata, as well as less commonly encounteredCandida species; in general, its potency on a weight basis was comparable to that of amphotericin B. It maintained potent in vitro activity against Candida strains with reduced susceptibilities to fluconazole and amphotericin B. The in vitro activity of A-192411.29 against Cryptococcus neoformans was comparable to its activity against Candida spp. However, A-192411.29 did not demonstrate complete growth inhibition ofAspergillus fumigatus by the broth microdilution method used. A-192411.29 possesses an antifungal profile comparable to or better than those of fluconazole and amphotericin B against pathogenic yeasts, including strains resistant to fluconazole or amphotericin B, suggesting that it may be a therapeutically useful new antifungal drug.


2000 ◽  
Vol 44 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Shuichi Tawara ◽  
Fumiaki Ikeda ◽  
Katsuyuki Maki ◽  
Yoshihiko Morishita ◽  
Kazumi Otomo ◽  
...  

ABSTRACT The in vitro antifungal activity and spectrum of FK463 were compared with those of amphotericin B, fluconazole, and itraconazole by using a broth microdilution method specified by National Committee for Clinical Laboratory Standards document M27-A (National Committee for Clinical Laboratory Standards, Wayne, Pa., 1997). FK463 exhibited broad-spectrum activity against clinically important pathogens including Candida species (MIC range, ≦0.0039 to 2 μg/ml) and Aspergillus species (MIC range, ≦0.0039 to 0.0313 μg/ml), and its MICs for such fungi were lower than those of the other antifungal agents tested. FK463 was also potently active against azole-resistant Candida albicans as well as azole-susceptible strains, and there was no cross-resistance with azoles. FK463 showed fungicidal activity against C. albicans, i.e., a 99% reduction in viability after a 24-h exposure at concentrations above 0.0156 μg/ml. The minimum fungicidal concentration (MFC) assays indicated that FK463 was fungicidal against most isolates of Candida species. In contrast, the MFCs of FK463 for A. fumigatus isolates were much higher than the MICs, indicating that its action is fungistatic against this species. FK463 had no activity against Cryptococcus neoformans,Trichosporon species, or Fusarium solani. Neither the test medium (kind and pH) nor the inoculum size greatly affected the MICs of FK463, while the addition of 4% human serum albumin increased the MICs for Candida species and A. fumigatus more than 32 times. Results from preclinical in vitro evaluations performed thus far indicate that FK463 should be a potent parenteral antifungal agent.


Author(s):  
Bilal Ahmad Wani ◽  
Mohd Rafiq Lone ◽  
Najmus Saqib

Background: In this study, our aim was to identify and isolate Candida species from patients admitted in ICU,s of our hospital and to determine their susceptibilities to various antifungal agents so as to find the local resistance pattern and guide for empirical treatment.Methods: In our study 37 strains of candida were isolated (4 Candida albicans, 33 Non-albicans Candida strains). Candida species were identified by conventional, biochemical and molecular methods. Antifungal susceptibility tests for amphotericin B, fluconazole, itraconazole, ketoconazole and voriconazole were performed with broth microdilution method and E- tests as described by National Committee for Clinical Laboratory Standards (NCCLS).Results: Out of 37 Candida strains, the most prevalent species were C. tropicalis (43.2%), C. parapsilosis (24.3%), C. krusei (16.2%), C. albicans (10.8%), and C. glabrata (2.7%). Among all strains four strains (10.8 %) were resistant, two Candida albicans where found resistant to fluconazole one Candida krusei and one Candida parapsilosis were found to be resistant to all azoles.Conclusions: Candidemia continues to be associated with substantial morbidity and mortality and non albicans Candida species are the commonly isolated pathogen from those patients admitted in tertiary care hospitals in Indian scenario. Thus, it is imperative to perform antifungal susceptibility to select appropriate and effective antifungal therapy.


1999 ◽  
Vol 45 (10) ◽  
pp. 871-874 ◽  
Author(s):  
Eric Dannaoui ◽  
Florence Persat ◽  
Marie-France Monier ◽  
Elisabeth Borel ◽  
Marie-Antoinette Piens ◽  
...  

A comparative study of visual and spectrophotometric MIC endpoint determinations for antifungal susceptibility testing of Aspergillus species was performed. A broth microdilution method adapted from the National Committee for Clinical Laboratory Standards (NCCLS) was used for susceptibility testing of 180 clinical isolates of Aspergillus species against amphotericin B and itraconazole. MICs were determined visually and spectrophotometrically at 490 nm after 24, 48, and 72h of incubation, and MIC pairs were compared. The agreement between the two methods was 99% for amphotericin B and ranged from 95 to 98% for itraconazole. It is concluded that spectrophotometric MIC endpoint determination is a valuable alternative to the visual reference method for susceptibility testing of Aspergillus species.Key words: antifungal, susceptibility testing, Aspergillus, spectrophotometric reading.


1998 ◽  
Vol 36 (6) ◽  
pp. 1578-1583 ◽  
Author(s):  
Anna Maria Tortorano ◽  
Maria Anna Viviani ◽  
Francesco Barchiesi ◽  
Daniela Arzeni ◽  
Anna Lisa Rigoni ◽  
...  

Three susceptibility testing procedures were compared to determine fluconazole, itraconazole, and ketoconazole MICs against 47Candida 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.


1998 ◽  
Vol 42 (4) ◽  
pp. 762-766 ◽  
Author(s):  
Scott Walker ◽  
Sandra A. N. Tailor ◽  
Mark Lee ◽  
Lisa Louie ◽  
Marie Louie ◽  
...  

ABSTRACT Newer formulations of amphotericin B (AmB) complexed with liposomes or lipid suspensions have been developed. Preliminary studies have suggested that AmB in Intralipid (IL) may be as effective as, but less toxic than, conventional formulations of AmB, but few data are available regarding its stability, compatibility, or in vitro antifungal activity. A compatibility study was done to evaluate the effects of AmB concentrations in IL containing either 10 or 20% soybean oil. The effects of temperature, shaking, and AmB and IL concentrations on the stability of AmB-IL suspensions were analyzed by visual inspection and liquid chromatography. The in vitro antifungal activity of AmB-IL, compared to that of AmB alone against reference strains of Candida species was determined by using a broth macrodilution method in accordance with National Committee for Clinical Laboratory Standards guidelines (M27-T). Samples of AmB-IL which were lightly shaken retained more than 90% of the AmB concentration over 21 days when stored at either 4 or 23°C. Varying the AmB concentration did not appear to affect the stability of AmB-IL. However, a precipitate was formed when mixtures with more than 30% lipid as a proportion of the total volume were centrifuged. AmB-IL and AmB alone had similar in vitro antifungal activities against reference strains of yeasts. Further pharmacologic and clinical studies with AmB-IL are warranted, although AmB should not be combined with IL in concentrations capable of producing a precipitate.


2001 ◽  
Vol 9 (1) ◽  
pp. 41-45 ◽  
Author(s):  
Jose A. Simoes ◽  
Alla A. Aroutcheva ◽  
Susan Shott ◽  
Sebastian Faro

Objective:To determine whether metronidazole has an adverse effect on the growth ofLactobacillus.Methods:Hydrogen peroxide- and bacteriocin-producing strains ofLactobacilluswere used as test strains. Concentrations of metronidazole used ranged from 128 to 7000 μg/ml. Susceptibility to metronidazole was conducted by the broth microdilution method recommended by the National Committee for Clinical Laboratory Standards.Results:Growth ofLactobacilluswas partially inhibited at concentrations between 1000 and 4000 μg/ml (p= 0.014). Concentrations ≥ 5000 μg/ml completely inhibited growth ofLactobacillus. Concentrations between 128 and 256 μg/ml stimulated growth ofLactobacillus(p= 0.025 and 0.005, respectively). Concentrations of metronidazole between 64 and 128 μg/ml or ≥ 512 μg/ml did not have an inhibitory or a stimulatory effect on the growth ofLactobacilluscompared to the control.Conclusions:High concentration of metronidazole, i.e. between 1000 and 4000 μg/ml, partially inhibited the growth ofLactobacillus. Concentrations ≥ 5000 μg/ml completely suppressed the growth ofLactobacillus. Concentrations between ≥ 128 and ≤ 256 μg/ml stimulated the growth ofLactobacillus. Further investigation to determine the ideal concentration of metronidazole is needed in order to use the antimicrobial agent effectively in the treatment of bacterial vaginosis.


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