scholarly journals Correlation of Fluconazole MICs with Clinical Outcome in Cryptococcal Infection

2000 ◽  
Vol 44 (6) ◽  
pp. 1544-1548 ◽  
Author(s):  
A. I. Aller ◽  
E. Martin-Mazuelos ◽  
F. Lozano ◽  
J. Gomez-Mateos ◽  
L. Steele-Moore ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Maintenance Therapy ◽  
National Committee ◽  
Yeast Nitrogen Base ◽  
Nitrogen Base ◽  
Cryptococcal Infection ◽  
Microdilution Method ◽  
Cryptococcal Disease ◽  
Fluconazole Therapy

ABSTRACT We have correlated the in vitro results of testing the susceptibility of Cryptococcus neoformans to fluconazole with the clinical outcome after fluconazole maintenance therapy in patients with AIDS-associated cryptococcal disease. A total of 28 isolates of C. neoformans from 25 patients (24 AIDS patients) were tested. The MICs were determined by the broth microdilution technique by following the modified guidelines described in National Committee for Clinical Standards (NCCLS) document M27-A, e.g., use of yeast nitrogen base medium and a final inoculum of 104 CFU/ml. The fluconazole MIC at which 50% of isolates are inhibited (MIC50) and MIC90, obtained spectrophotometrically after 48 h of incubation, were 4 and 16 μg/ml, respectively. Of the 25 patients studied, 4 died of active cryptococcal disease and 2 died of other causes. Therapeutic failure was observed in five patients who were infected with isolates for which fluconazole MICs were ≥16 μg/ml. Four of these patients had previously had oropharyngeal candidiasis (OPC); three had previously had episodes of cryptococcal infection, and all five treatment failure patients had high cryptococcal antigen titers in either serum or cerebrospinal fluid (titers, >1:4,000). Although 14 of the 18 patients who responded to fluconazole therapy had previously had OPC infections, they each had only a single episode of cryptococcal infection. It appears that the clinical outcome after fluconazole maintenance therapy may be better when the infecting C. neoformans strain is inhibited by lower concentrations of fluconazole for eradication (MICs, <16 μg/ml) than when the patients are infected with strains that require higher fluconazole concentrations (MICs, ≥16 μg/ml). These findings also suggest that the MICs determined by the modified NCCLS microdilution method can be potential predictors of the clinical response to fluconazole therapy and may aid in the identification of patients who will not respond to fluconazole therapy.

scholarly journals Effect of pH on the In Vitro Activities of Amphotericin B, Itraconazole, and Flucytosine against Aspergillus Isolates

2004 ◽  
Vol 48 (8) ◽  
pp. 3147-3150 ◽  
Author(s):  
D. T. A. Te Dorsthorst ◽  
J. W. Mouton ◽  
C. J. P. van den Beukel ◽  
H. A. L. van der Lee ◽  
J. F. G. M. Meis ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Poor Correlation ◽  
Yeast Nitrogen Base ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Nitrogen Base ◽  
The Poor

ABSTRACT The in vitro susceptibilities of 21 Aspergillus isolates were tested against three antifungal agents in RPMI 1640 and yeast nitrogen base at pH 5.0 and 7.0 by a broth microdilution format of the NCCLS method. The MICs of amphotericin B and itraconazole were higher, while those of flucytosine were lower, at pH 5.0 than at pH 7.0. The poor correlation between in vitro results and clinical outcome could be due to a difference in pH between the in vitro susceptibility test and at the site of infection.

scholarly journals Pentamidine Is Active In Vitro against Fusarium Species

2003 ◽  
Vol 47 (10) ◽  
pp. 3252-3259 ◽  
Author(s):  
Michail S. Lionakis ◽  
Russell E. Lewis ◽  
George Samonis ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Clinical Laboratory ◽  
Fusarium Species ◽  
Tissue Perfusion ◽  
In Vivo Studies ◽  
National Committee ◽  
Yeast Nitrogen Base ◽  
Nitrogen Base ◽  
Minimum Fungicidal Concentration

ABSTRACT Fusariosis is an emerging opportunistic mycosis against which currently used antifungals have limited activity. Here, we investigated the in vitro activities of pentamidine (PNT) against 10 clinical isolates of Fusarium species (five Fusarium solani isolates and five non-F. solani isolates) by using the National Committee for Clinical Laboratory Standards microdilution method in three different media (RPMI, RPMI-2, and a yeast nitrogen base medium), disk diffusion testing, and viability dye staining. PNT had significant activities against all 10 Fusarium isolates. Non-F. solani isolates were more susceptible than F. solani isolates (P < 0.05). Additionally, PNT was fungicidal against all non-F. solani isolates, whereas it had fungistatic effects against four of the five F. solani isolates. PNT also exhibited greater activity against conidial than against hyphal development of the fungus. This fungicidal activity against non-F. solani Fusarium isolates was confirmed microscopically after staining of PNT-treated Fusarium oxysporum hyphae with the fluorescent viability dyes 5,(6)-carboxyfluorescein diacetate (CFDA) and bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC). The MICs at which 50% of the isolates were inhibited (2 μg/ml for non-F. solani isolates and 4 μg/ml for F. solani isolates) and the minimum fungicidal concentration at which 50% of the isolates were killed (8 μg/ml for non-F. solani isolates) were much lower than the PNT tissue concentrations previously reported in humans using conventional daily intravenous PNT dosing. Finally, PNT was more active against Fusarium isolates in a hypoxic environment of in vitro growth (P < 0.05). This finding may be clinically significant, because Fusarium, an angiotropic mold, causes tissue infarcts with resultant low tissue perfusion. Our findings suggest that PNT may have a role in the management of Fusarium infections. Future in vivo studies are needed to verify these in vitro findings.

scholarly journals Detection of Resistance to Amphotericin B amongCryptococcus neoformans Clinical Isolates: Performances of Three Different Media Assessed by Using E-Test and National Committee for Clinical Laboratory Standards M27-A Methodologies

1998 ◽  
Vol 36 (10) ◽  
pp. 2817-2822 ◽  
Author(s):  
M. Lozano-Chiu ◽  
V. L. Paetznick ◽  
M. A. Ghannoum ◽  
J. H. Rex
Keyword(s):  
Amphotericin B ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
Diffusion Method ◽  
National Committee ◽  
Yeast Nitrogen Base ◽  
Nitrogen Base ◽  
Agar Diffusion ◽  
Agar Diffusion Method

Although reliable detection of resistance in vitro is critical to the overall performance of any susceptibility testing method, the recently released National Committee for Clinical Laboratory Standards M27-A methodology for susceptibility testing of yeasts discriminates poorly between resistant and susceptible isolates ofCandida spp. We have previously shown that both substitution of antibiotic medium 3 for RPMI 1640 medium in the microdilution variant of the M27-A method and use of the E-test agar diffusion methodology permit detection of amphotericin B-resistantCandida isolates. To determine the relevance of these observations to Cryptococcus neoformans, we have evaluated the performances of both the M27-A and the E-test methodologies with this yeast using three different media (RPMI 1640 medium, antibiotic medium 3, and yeast nitrogen base). As with Candida, we found that only antibiotic medium 3 permitted consistent detection of resistant isolates when testing was performed in broth by the M27-A method. When testing was performed by the E-test agar diffusion method, both RPMI 1640 medium and antibiotic medium 3 agar permitted ready detection of the resistant isolates. Reading of the results after 48 h of incubation was required for testing in broth by the M27-A method, while the MIC could be determined after either 48 or 72 h when the agar diffusion method was used.

scholarly journals Results Obtained with Various Antifungal Susceptibility Testing Methods Do Not Predict Early Clinical Outcome in Patients with Cryptococcosis

2006 ◽  
Vol 50 (7) ◽  
pp. 2464-2470 ◽  
Author(s):  
E. Dannaoui ◽  
M. Abdul ◽  
M. Arpin ◽  
A. Michel-Nguyen ◽  
M. A. Piens ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Amphotericin B ◽  
Antifungal Susceptibility ◽  
Yeast Nitrogen Base ◽  
Broth Microdilution ◽  
Nitrogen Base ◽  
First Line Therapy ◽  
Multicenter Prospective Study ◽  
In Vitro Antifungal Susceptibility

ABSTRACT The in vitro susceptibilities of Cryptococcus neoformans isolates from consecutive human immunodeficiency virus-positive and -negative patients to the antifungal agents fluconazole, amphotericin B, and flucytosine were determined by different techniques, including the CLSI method, Etest, and broth microdilution in yeast nitrogen base (YNB) medium, during a multicenter prospective study in France. The relationship between the in vitro data and the clinical outcome 2 weeks after the initiation of antifungal therapy was assessed. In addition, the correlation between the strain serotype and the in vitro activities of the antifungals was determined, and the susceptibility results obtained with the different techniques were also compared. Thirty-seven patients received a combination of amphotericin B with flucytosine as first-line therapy, 22 were treated with amphotericin B alone, and 15 received fluconazole alone. Whatever the antifungal tested, there was no trend toward higher MICs for strains isolated from patients who failed to respond to a given therapy compared to those from patients who did not with either the CLSI method, Etest, or broth microdilution in YNB medium. The MICs obtained by the CLSI or Etest method were significantly lower for serotype D strains than for serotype A strains for both fluconazole and amphotericin B, while flucytosine MICs were not different according to serotype. These findings suggest that the in vitro antifungal susceptibility of C. neoformans, as determined with the techniques used, is not able to predict the early clinical outcome in patients with cryptococcosis.

scholarly journals In Vitro Activities of Pentamidine, Pyrimethamine, Trimethoprim, and Sulfonamides against Aspergillus Species

2002 ◽  
Vol 46 (6) ◽  
pp. 2029-2031 ◽  
Author(s):  
Javier Afeltra ◽  
Jacques F. G. M. Meis ◽  
Roxana G. Vitale ◽  
Johan W. Mouton ◽  
Paul E. Verweij
Keyword(s):  
Aspergillus Species ◽  
Yeast Nitrogen Base ◽  
Sulfa Drugs ◽  
Nitrogen Base ◽  
Microdilution Method

ABSTRACT The susceptibilities of 70 strains of Aspergillus species were tested against seven different sulfa drugs and pentamidine by a microdilution method with RPMI 1640 and yeast nitrogen base media. Sulfamethoxazole, sulfadiazine, and pentamidine were active in vitro. The MICs obtained with RPMI 1640 were significantly higher than those with yeast nitrogen base. More studies are needed to further elucidate the action of these drugs.

scholarly journals In Vitro Activities of the New Antifungal Triazole SCH 56592 against Common and Emerging Yeast Pathogens

2000 ◽  
Vol 44 (1) ◽  
pp. 226-229 ◽  
Author(s):  
Francesco Barchiesi ◽  
Daniela Arzeni ◽  
Annette W. Fothergill ◽  
Luigi Falconi Di Francesco ◽  
Francesca Caselli ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Clinical Development ◽  
National Committee ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Vitro Data ◽  
In Vitro Data

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.

scholarly journals Growth Media for Mixed Multispecies Oropharyngeal Biofilm Compositions on Silicone

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Matthias Leonhard ◽  
Beata Zatorska ◽  
Doris Moser ◽  
Berit Schneider-Stickler
Keyword(s):  
Culture Conditions ◽  
Microbial Colonization ◽  
Future Research ◽  
Growth Media ◽  
Yeast Nitrogen Base ◽  
Microbial Composition ◽  
Nitrogen Base ◽  
Voice Prostheses

Aims. Microbial colonization of silicone voice prostheses by bacteria and Candida species limits the device lifetime of modern voice prostheses in laryngectomized patients. Thus, research focuses on biofilm inhibitive properties of novel materials, coatings, and surface enhancements. Goal of this in vitro study was the evaluation of seven commonly used growth media to simulate growth of mixed oropharyngeal species as mesoscale biofilms on prosthetic silicone for future research purposes. Methods and Results. Yeast Peptone Dextrose medium (YPD), Yeast Nitrogen Base medium (YNB), M199 medium, Spider medium, RPMI 1640 medium, Tryptic Soy Broth (TSB), and Fetal Bovine Serum (FBS) were used to culture combined mixed Candida strains and mixed bacterial-fungal compositions on silicone over the period of 22 days. The biofilm surface spread and the microscopic growth showed variations from in vivo biofilms depending on the microbial composition and growth medium. Conclusion. YPD and FBS prove to support continuous in vitro growth of mixed bacterial-fungal oropharyngeal biofilms deposits over weeks as needed for longterm in vitro testing with oropharyngeal biofilm compositions. Significance and Impact of Study. The study provides data on culture conditions for mixed multispecies biofilm compositions that can be used for future prosthesis designs.

scholarly journals Clinical Characteristics of Turkish Women withCandida kruseiVaginitis and Antifungal Susceptibility of theC. kruseiIsolates

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Ahmet Bariş Güzel ◽  
Merve Aydın ◽  
Melda Meral ◽  
Ayşe Kalkancı ◽  
Macit Ilkit
Keyword(s):  
Clinical Characteristics ◽  
Antifungal Susceptibility ◽  
Turkish Women ◽  
Microdilution Method ◽  
Fluconazole Therapy ◽  
Dose Dependent ◽  
Susceptibility Patterns ◽  
Selection Of

Objective.Candida kruseicauses approximately 1% of vulvovaginal candidiasis (VVC) cases and is naturally resistant to fluconazole. Antifungal testing may be required ifC. kruseivaginitis fails to respond to non-fluconazole therapy, particularly in patients with recurrent infections.Design. We investigated the clinical characteristics and antifungal susceptibility profile of vaginalC. kruseiisolates. Between 2009 and 2012, we identified 560 unrelatedCandidaspp.-positive vaginal cultures, of which 28 (5.0%) wereC. krusei. These isolates were analyzed according to host factors and the clinical forms of VVC, and theirin vitrosusceptibility to 10 antifungal agents was tested using a reference microdilution method.Results. We observed that perineal laceration and increased age (>50 years) were significant predictors ofC. kruseiin vaginal samples (P<0.05). All isolates were susceptible to amphotericin B, caspofungin, ketoconazole, and miconazole. Additionally, susceptible dose-dependent and resistant rates were found for fluconazole as 42.9% and 57.1%, respectively. Remarkably, only 42.9% and 67.9% of the isolates were susceptible to itraconazole and voriconazole, respectively.Conclusions. Understanding local susceptibility patterns, especially those of non-C. albicans Candidaspecies, can significantly aid in the selection of an effective antifungal agent. Thein vivoresponse ofC. kruseivaginitis to various antifungal therapeutics remains unknown and requires further research.

scholarly journals In Vitro Activity of A-192411.29, a Novel Antifungal Lipopeptide

2000 ◽  
Vol 44 (5) ◽  
pp. 1242-1246 ◽  
Author(s):  
Angela M. Nilius ◽  
Patti M. Raney ◽  
Dena M. Hensey-Rudloff ◽  
Weibo Wang ◽  
Qun Li ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Clinical Laboratory ◽  
Vitro Activity ◽  
National Committee ◽  
In Vitro Activity ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Structural Template ◽  
Better Than

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.

scholarly journals Attenuation of Itraconazole Fungicidal Activity following Preexposure of Aspergillus fumigatus to Fluconazole

2003 ◽  
Vol 47 (11) ◽  
pp. 3592-3597 ◽  
Author(s):  
Wei Liu ◽  
Michail S. Lionakis ◽  
Russell E. Lewis ◽  
Nathan Wiederhold ◽  
Gregory S. May ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Fungicidal Activity ◽  
Clinical Laboratory ◽  
Marrow Transplant ◽  
National Committee ◽  
In Vitro Susceptibility ◽  
Fourfold Increase ◽  
Microdilution Method

ABSTRACT Fluconazole (FLC), a triazole with limited activity against Aspergillus species, is frequently used as prophylaxis in leukemia patients and bone marrow transplant recipients. Prior FLC use has been associated with an increasing incidence of invasive aspergillosis in these patients. We hypothesized that prior exposure of Aspergillus fumigatus to FLC could result in altered in vitro susceptibility of this fungus to other, more active triazoles. Thus, we performed serial passages of conidia of 10 clinical isolates of A. fumigatus (all itraconazole [ITC] susceptible) on FLC-containing yeast agar glucose plates. The MICs and minimal fungicidal concentrations (MFCs) of amphotericin B, FLC, ITC, and voriconazole (VRC) for A. fumigatus conidia were measured following four passages on FLC-containing medium according to the National Committee for Clinical Laboratory Standards microdilution method. Serial passages on FLC-containing plates resulted in a fourfold increase in the MFCs (but not the MICs) of ITC for nine isolates. The attenuated ITC fungicidal activity against A. fumigatus following FLC preexposure was medium independent and was also observed against FLC-preexposed A. fumigatus hyphae with the viability staining FUN-1 dye. Moreover, FLC preexposure of A. fumigatus conidia resulted in an analogous increase in the MFCs (but not the MICs) of VRC. Our findings suggest that preexposure of A. fumigatus to FLC attenuates the in vitro fungicidal activity of subsequent ITC use against it. This phenotypic adaptation is not captured by a routine MIC determination but requires MFC measurement. The in vivo significance of this in vitro phenomenon requires further investigation.

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