In Vitro Activities of Voriconazole in Combination with Three Other Antifungal Agents against Candida glabrata

ABSTRACT Candida glabrata has recently emerged as a significant pathogen involved in both superficial and deep-seated infections. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of voriconazole (VOR) in combination with terbinafine (TRB), amphotericin B (AMB), and flucytosine (5FC) against 20 clinical isolates of C. glabrata. Synergy, defined as a fractional inhibitory concentration (FIC) index of ≤0.50, was observed in 75% of VOR-TRB, 10% of VOR-AMB, and 5% of VOR-5FC interactions. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination. In particular, the MICs were reduced to ≤1.0 μg/ml as a result of the combination for all isolates for which the AMB MIC at the baseline was ≥2.0 μg/ml. By a disk diffusion assay, the halo diameters produced by antifungal agents in combination were greater that those produced by each drug alone. Finally, killing curves showed that VOR-AMB exhibited synergistic interactions, while VOR-5FC sustained fungicidal activities against C. glabrata. These studies demonstrate that the in vitro activity of VOR against this important yeast pathogen can be enhanced upon combination with other drugs that have different modes of action or that target a different step in the ergosterol pathway. Further studies are warranted to elucidate the potential beneficial effects of such combination regimens in vivo.

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In Vitro Antibacterial Effect of the Methanolic Extract of the Korean Soybean Fermented Product Doenjang against Staphylococcus aureus

Animals ◽

10.3390/ani11082319 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2319

Author(s):

Klara Lalouckova ◽

Lucie Mala ◽

Petr Marsik ◽

Eva Skrivanova

Keyword(s):

Staphylococcus Aureus ◽

High Performance ◽

Methanolic Extract ◽

Bioactive Substances ◽

Microdilution Method ◽

Antibacterial Compound ◽

Fermented Product ◽

Broth Microdilution Method

Ultra-high performance liquid chromatography/mass spectrometry showed soyasaponin I and the isoflavones daidzein, genistein, and glycitein to be the main components of the methanolic extract of the Korean soybean fermented product doenjang, which is known to be a rich source of naturally occurring bioactive substances, at average contents of 515.40, 236.30, 131.23, and 29.00 ng/mg, respectively. The antimicrobial activity of the methanolic extract of doenjang against nine Staphylococcusaureus strains was determined in vitro by the broth microdilution method to investigate its potential to serve as an alternative antibacterial compound. The results suggest that the extract is an effective antistaphylococcal agent at concentrations of 2048–4096 µg/mL. Moreover, the tested extract also showed the ability to inhibit the growth of both methicillin-sensitive and methicillin-resistant animal and clinical S. aureus isolates. The growth kinetics of the chosen strains of S. aureus at the minimum inhibitory concentration of the methanolic extract of doenjang support the idea that the tested extract acts as an antibacterial compound. To the best of our knowledge, this is the first report on the antistaphylococcal action of the methanolic extract of doenjang thus, additional studies including in vivo testing are necessary to confirm this hypothesis.

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Evaluation of a Modified EUCAST Fragmented-Mycelium Inoculum Method forIn VitroSusceptibility Testing of Dermatophytes and the Activity of Novel Antifungal Agents

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04381-14 ◽

2015 ◽

Vol 59 (6) ◽

pp. 3675-3682 ◽

Cited By ~ 4

Author(s):

B. Risslegger ◽

C. Lass-Flörl ◽

G. Blum ◽

M. Lackner

Keyword(s):

Antifungal Agents ◽

Susceptibility Testing ◽

Preparation Method ◽

Antifungal Susceptibility ◽

Broth Microdilution ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Inoculum Preparation ◽

Minimal Effective Concentration

ABSTRACTFor antifungal susceptibility testing of nonsporulating or poorly sporulating dermatophytes, a fragmented-mycelium inoculum preparation method was established and compared to broth microdilution testing according to CLSI and EUCAST guidelines. Moreover, thein vitroactivity of new antifungal agents against dermatophytes was evaluated. Agreement between the mycelial inoculum method and the CLSI broth microdilution method was high (93% to 100%). Echinocandins (minimal effective concentration [MEC], ≤0.5 mg/liter) and posaconazole (MIC, ≤3.00 mg/liter) showed good activity against all tested dermatophytes.

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Correlation of In Vitro Activity, Serum Levels, and In Vivo Efficacy of Posaconazole against Rhizopus microsporus in a Murine Disseminated Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01026-09 ◽

2009 ◽

Vol 53 (12) ◽

pp. 5022-5025 ◽

Cited By ~ 26

Author(s):

M. Mar Rodríguez ◽

F. Javier Pastor ◽

Enrique Calvo ◽

Valentina Salas ◽

Deanna A. Sutton ◽

...

Keyword(s):

Serum Levels ◽

Rhizopus Microsporus ◽

In Vitro Susceptibility ◽

In Vivo Efficacy ◽

Susceptibility Data ◽

Microdilution Method ◽

Drug Concentrations ◽

Broth Microdilution Method

ABSTRACT A broth microdilution method was used to evaluate the in vitro activities of seven antifungal agents against 15 clinical strains of Rhizopus microsporus. Amphotericin B (AMB) and posaconazole (POS) were the most active drugs. In a model of disseminated R. microsporus infection in immunosuppressed mice, we studied the efficacy of POS administered once or twice daily against four of the strains previously tested in vitro and compared it with that of liposomal AMB (LAMB). LAMB was the most effective treatment for the two strains with intermediate susceptibility to POS. For the two POS-susceptible strains, LAMB and POS at 20 mg/kg of body weight twice a day orally showed similar efficacies. The in vivo efficacy of POS administered twice a day orally correlated with the in vitro susceptibility data and the serum drug concentrations.

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In Vitro Interaction of Caspofungin Acetate with Voriconazole against Clinical Isolates of Aspergillus spp

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.46.9.3039-3041.2002 ◽

2002 ◽

Vol 46 (9) ◽

pp. 3039-3041 ◽

Cited By ~ 144

Author(s):

Sofia Perea ◽

Gloria Gonzalez ◽

Annette W. Fothergill ◽

William R. Kirkpatrick ◽

Michael G. Rinaldi ◽

...

Keyword(s):

Inhibitory Concentration ◽

Fractional Inhibitory Concentration ◽

Broth Microdilution ◽

Microdilution Method ◽

Broth Microdilution Method ◽

In Vitro Interaction ◽

Vitro Data ◽

In Vitro Data

ABSTRACT The interaction between caspofungin acetate and voriconazole was studied in vitro by using 48 clinical Aspergillus spp. isolates obtained from patients with invasive aspergillosis. MICs were determined by the NCCLS broth microdilution method. Synergy, defined as a fractional inhibitory concentration (FIC) index of <1, was detected in 87.5% of the interactions; an additive effect, defined as an FIC index of 1.0, was observed in 4.2% of the interactions; and a subadditive effect, defined as an FIC index of 1.0 to 2.0, was found in 8.3% of the interactions. No antagonism was observed. Animal models are required to validate the in vivo significance of these in vitro data presented for the combination of caspofungin and voriconazole.

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New sulfone and sulfanyl derivatives with antifungal activity

Medycyna Doświadczalna i Mikrobiologia ◽

10.32394/mdm.70.2.7 ◽

2018 ◽

pp. 175-184

Author(s):

Małgorzata Gizińska ◽

Marzena Połaska ◽

Zbigniew Ochal ◽

Monika Staniszewska

Keyword(s):

Antifungal Agents ◽

Fungal Infections ◽

In Vitro Susceptibility ◽

Microdilution Method ◽

Alternative Approach ◽

Broth Microdilution Method ◽

Fungal Morphogenesis ◽

In Vitro Susceptibility Testing ◽

Base Structure

Introduction: Increasing occurrence of fungal infections raises the need to develop novel antifungal agents. In this context, an inhibition of morphological switch may provide an alternative approach to find compounds with a potential to control the Candida albicans infections. Methods: A series of 17 sulfone and sulfanyl derivatives was synthesized and evaluated for activity against the C. albicans wild type (SC5314, ATCC) and SAP-deficient mutant strains using the broth microdilution method M27-A3. Afterwards, phase-contrast microscopy was applied to evaluate the inhibition of fungal morphogenesis under the influence of randomly selected active compounds: 1, 5 and 6. Results: By in vitro susceptibility testing of C. albicans, we identified the effective antifungal agents displaying moderate-to-good activity. Newly synthesized sulfanyl and sulfone derivatives strongly inhibited the C. albicans morphogenetic transition under the hyphae inducing conditions. Conclusions: The leading compound 6 has the potential to be used as a base structure in antifungal drug development, however further structural optimalization and toxicity studies are required.

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Comparative resistance of Candida albicans clinical isolates to fluconazole and itraconazole in vitro and in vivo in a murine model.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.6.1342 ◽

1996 ◽

Vol 40 (6) ◽

pp. 1342-1345 ◽

Cited By ~ 18

Author(s):

A Valentin ◽

R Le Guennec ◽

E Rodriguez ◽

J Reynes ◽

M Mallie ◽

...

Keyword(s):

Candida Albicans ◽

Murine Model ◽

Survival Rates ◽

Drug Regimen ◽

Clinical Isolates ◽

In Vitro Susceptibility ◽

Microdilution Method ◽

Broth Microdilution Method

Relationships between azole susceptibility and in vivo response to antifungal therapy in a murine model of candidiasis were investigated for Candida albicans isolates sampled from human immunodeficiency virus type 1-positive patients with oropharyngeal candidiasis. The susceptibilities of seven clinical isolates and two reference strains to fluconazole (FCZ) and itraconazole (ITZ) were determined in vitro by the broth microdilution method. Four isolates were resistant to FCZ and ITZ, two were susceptible to both azoles, and three were resistant to FCZ and susceptible to ITZ (dissociated resistance). CD1 mice were inoculated with each isolate and treated with either FCZ or ITZ (drug regimen, 5 mg/kg of body weight twice daily for 5 days). Quantitative cultures of kidneys were performed at the end of the treatment. On the other hand, the survival rates of the mice were followed daily. These two parameters were clearly correlated with in vitro susceptibility. Thus, the phenomenon of a dissociation of resistance to FCZ and ITZ may be found in vivo as well as in vitro.

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In Vitro Susceptibility Testing of Tedizolid against Isolates of Nocardia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01537-17 ◽

2017 ◽

Vol 61 (12) ◽

Cited By ~ 8

Author(s):

Barbara A. Brown-Elliott ◽

Richard J. Wallace

Keyword(s):

Common Species ◽

Multidrug Resistant ◽

In Vitro Susceptibility ◽

Content Type ◽

Nocardia Brasiliensis ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Clinically Significant

ABSTRACT There is a paucity of efficacious antimicrobials (especially oral) against clinically relevant species of Nocardia. To date, all species of Nocardia have been susceptible to linezolid, the first commercially available oxazolidinone. Tedizolid is a new oxazolidinone with previously reported improved in vitro and in vivo (intracellular) potency against multidrug-resistant strains of Mycobacterium sp. and Nocardia brasiliensis. Using the current Clinical and Laboratory Standards Institute-recommended broth microdilution method, 101 isolates of Nocardia spp., including 29 Nocardia cyriacigeorgica, 17 Nocardia farcinica, 13 Nocardia nova complex, 21 Nocardia brasiliensis, 5 Nocardia pseudobrasiliensis, and 5 Nocardia wallacei isolates and 11 isolates of less common species, were tested for susceptibility to tedizolid and linezolid. For the most common clinically significant species of Nocardia, tedizolid MIC50 values were 0.25 μg/ml for N. nova complex, N. brasiliensis, N. pseudobrasiliensis, and N. wallacei, compared to linezolid MIC50 values of 1, 2, 0.5, and 1 μg/ml, respectively. Tedizolid and linezolid MIC90 values were 2 μg/ml for N. nova complex and N. brasiliensis. Tedizolid MIC50 and MIC90 values for both N. cyriacigeorgica and N. farcinica were 0.5 μg/ml and 1 μg/ml, respectively, compared to linezolid MIC50 and MIC90 values of 2 and 4 μg/ml, respectively. Based on MIC90 values, this study showed that tedizolid was 2- to 3-fold more active than linezolid in vitro against most common species of Nocardia, with the exception of the N. nova complex and N. brasiliensis, for which values were the same. These results may warrant evaluation of tedizolid as a potential treatment option for Nocardia infections.

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Caspofungin in Combination with Amphotericin B against Candida parapsilosis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00880-06 ◽

2006 ◽

Vol 51 (3) ◽

pp. 941-945 ◽

Cited By ~ 22

Author(s):

Francesco Barchiesi ◽

Elisabetta Spreghini ◽

Serena Tomassetti ◽

Daniele Giannini ◽

Giorgio Scalise

Keyword(s):

Amphotericin B ◽

Candida Parapsilosis ◽

Inhibitory Concentration ◽

Positive Interaction ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Disk Diffusion Assay ◽

Higher Doses ◽

Diffusion Assay

ABSTRACT Candida parapsilosis has emerged as an important nosocomial pathogen. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of caspofungin (CAS) in combination with amphotericin B (AMB) against three clinical isolates of C. parapsilosis. Although there was a significant reduction of the MIC of one or both drugs used in combination, an indifferent interaction (fractional inhibitory concentration index greater than 0.50 and less than or equal to 4.0) was observed in 100% of cases. This finding was confirmed by killing curve studies. By a disk diffusion assay, the halo diameters produced by antifungal agents in combination were often significantly greater than those produced by each drug alone. Antagonism was never observed. In a murine model of systemic candidiasis, CAS at either 0.25 or 1 mg/kg/day combined with AMB at 1 mg/kg/day was significantly more effective than each single drug at reducing the colony counts in kidneys. Higher doses of the echinocandin (i.e., 5 and 10 mg/kg/day) combined with the polyene did not show any advantage over CAS alone. Overall, our study showed a positive interaction of CAS and AMB against C. parapsilosis.

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In VitroandIn VivoAntimicrobial Activities of Minocycline in Combination with Azithromycin, Clarithromycin, or Tigecycline against Pythium insidiosum

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01480-15 ◽

2015 ◽

Vol 60 (1) ◽

pp. 87-91 ◽

Cited By ~ 27

Author(s):

Francielli P. K. Jesus ◽

Érico S. Loreto ◽

Laerte Ferreiro ◽

Sydney H. Alves ◽

David Driemeier ◽

...

Keyword(s):

Geometric Mean ◽

Rabbit Model ◽

Antimicrobial Activities ◽

Infection Model ◽

Pythium Insidiosum ◽

Content Type ◽

Microdilution Method ◽

Broth Microdilution Method

ABSTRACTThe present study investigated thein vitroand thein vivointeractions among azithromycin, clarithromycin, minocycline, and tigecycline againstPythium insidiosum.In vitroantimicrobial activities were determined by the broth microdilution method in accordance with CLSI document M38-A2, and the antibiotic interactions were assayed using the checkerboard MIC format.In vivoefficacy was determined using a rabbit infection model. The geometric mean MICs of azithromycin, clarithromycin, minocycline, and tigecycline againstP. insidiosumwere, respectively, 1.91, 1.38, 0.91, and 0.79 μg/ml. By checkerboard testing, all combinations resulted inin vitrosynergistic interactions (>60%). Antagonism was not observed. Thein vivostudies showed that azithromycin (20 mg/kg/day twice daily) alone or in combination with minocycline (10 mg/kg/day twice daily) significantly decreased the fungal burden. This study demonstrates that azithromycin possesses potent curative efficacy against subcutaneous pythiosis in the rabbit model.

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In Vitro Antifungal Susceptibility Profiles of 12 Antifungal Drugs against 55 Trichophyton schoenleinii Isolates from Tinea Capitis Favosa Patients in Iran, Turkey, and China

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01753-16 ◽

2016 ◽

Vol 61 (2) ◽

Cited By ~ 6

Author(s):

Shuwen Deng ◽

Saham Ansari ◽

Macit Ilkit ◽

Haleh Rafati ◽

Mohammad T. Hedayati ◽

...

Keyword(s):

Antifungal Agents ◽

Antifungal Susceptibility ◽

Antifungal Drugs ◽

Content Type ◽

Microdilution Method ◽

Broth Microdilution Method ◽

In Vitro Antifungal Susceptibility ◽

Trichophyton Schoenleinii ◽

Susceptibility Profiles

ABSTRACT Trichophyton schoenleinii is an anthropophilic dermatophyte mainly causing tinea favosa of the scalp in certain regions of the world, especially Africa and Asia. We investigated the in vitro susceptibilities of 55 T. schoenleinii isolates collected over the last 30 years from Iran, Turkey, and China to 12 antifungals using the CLSI broth microdilution method. Our results revealed that terbinafine and ketoconazole were the most potent antifungal agents among those tested, independently of the geographic regions where strains were isolated.

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