In Vitro and In Vivo Efficacy of Amphotericin B Combined with Posaconazole against Experimental Disseminated Sporotrichosis

We evaluated the combination of posaconazole with amphotericin B in vitro and in a murine model of systemic infections caused by Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. In vitro data demonstrated a synergistic effect, and although posaconazole alone was effective against sporotrichosis, efficacy in terms of survival and burden reduction was increased with the combination. This combination might be an option against disseminated sporotrichosis, especially when itraconazole or amphotericin B at optimal doses are contraindicated.     

In vitro activities of antifungal agents alone and in combination against fluconazole-susceptible and -resistant strains of Candida dubliniensis

In the present study we used two groups of Candida dubliniensis strains: one containing fluconazole-susceptible clinical isolates and another containing fluconazole-resistant laboratory derivative from the former to examine the changes on susceptibility accompanying the development of resistance to fluconazole. Our findings confirmed the ability of C. dubliniensis isolates to become resistant to fluconazole and indicated that this resistance was crossed with ketoconazole, itraconazole, ravuconazole and terbinafine. We also tested combinations of terbinafine, amphotericin B, itraconazole and voriconazole against both groups of isolates in a checkerboard assay. Surprisingly, most combinations evidenced indifferent interactions, and the best synergism appeared when terbinafine and itraconazole were combined against the fluconazole-resistant group.     

Do antibacterial and antifungal combinations have better activity against clinically relevant fusarium species? in vitro synergism

The aim of this study was to evaluate the susceptibility of 20 clinical isolates of Fusarium spp. to classic antifungals [amphotericin B (AmB), itraconazole (ITR), voriconazole (VRC) and caspofungin (CAS)] and to non-antifungal agents [amiodarone (AMD), doxycycline (DOX) and moxifloxacin (MFX)] by the broth microdilution method. Combinations between these antifungal and non-antifungal agents were also evaluated to determine the fractional inhibitory concentration indices using the chequerboard technique. Synergistic interactions were observed for the following combinations (% synergism): AMD?+?VRC, 80%; MFX?+?AmB, 75%; AMD?+?AmB, 65%; DOX?+?VRC, 60%; MFX?+?VRC, 55%; DOX?+?AmB, 50%; and AMD?+?CAS, 30%. Synergism was not observed for associations with ITR. Antagonism was not seen in any combination. These findings suggest that the combinations of AMD, DOX or MFX with AmB or VRC to have potential for future in vivo investigations.     

Caspofungin in vitro and in vivo activity against Brazilian Pythium insidiosum strains isolated from animals

OBJECTIVES: The present study evaluated the susceptibility of 27 clinical isolates of Pythium insidiosum to caspofungin in vitro and correlated the results with the therapeutic response in vivo in rabbits with experimental pythiosis. METHODS: The macrodilution method was performed in accordance with the CLSI document M38-A technique. Three reading criteria for MICs were adopted: MIC0, MIC1 and MIC2 (100%, 90% and 50% growth inhibition, respectively). The minimum fungicidal concentration was also determined. Ten rabbits inoculated with viable P. insidiosum zoospores were divided into two groups: group 1 (control) and group 2 (treated with caspofungin at a dosage of 1 mg/kg/day for 20 consecutive days). RESULTS: Of the isolates 51.8% had an MIC0 of 64 mg/L, 88.8% of isolates had an MIC1 between 8 and 64 mg/L and 62.9% of isolates had a minimum fungicidal concentration of 64 mg/L. In the in vivo assay, growth of subcutaneous lesions reduced during treatment, but rapidly resumed when treatment was stopped. CONCLUSIONS: The results showed that caspofungin has limited fungistatic activity against P. insidiosum. This work is the first study to analyse the susceptibility of this oomycete to inhibitors of beta-glucans of the cellular wall.     

Multidetector row CT of the liver

CT has always played a major role in the imaging of the liver despite continuous challenge by ultrasound and MR imaging. Introduction of multidetector row CT technology has helped CT to excel in its already established indications and has expanded its capabilities by adding new clinical indications, such as CT angiography or liver perfusion. This article discusses the advantages of multidetector row CT scanners in liver imaging, examines the guidelines to improve image quality by optimizing scanning protocols and contrast administration strategies, and reviews the current and potential clinical applications.     

Evaluation of the efficacy of a posaconazole and anidulafungin combination in a murine model of pulmonary aspergillosis due to infection with Aspergillus fumigatus

Posaconazole (PSC) in combination with anidulafungin (AFG) was evaluated in a murine model of pulmonary aspergillosis. Immunosuppressed animals were infected via the nasal cavity with 2 different A. fumigatus strains. The animals received PSC (oral, 20 mg/kg per day) and/or AFG (i.p., 10 mg/kg per day) for 7 days. On Day 8, the mice were euthanized and fungal burdens were determined from the lungs. Survival curves were constructed for mortality analysis. Compared to untreated groups, groups singly treated with PSC or AFG showed a reduced fungal burden in the lungs (P = 0.0001–0.006) and prevention of mortality (66.66–83.33% of survival). Combination treatment with PSC and AFG significantly reduced the fungal burden (or sterilized the lungs) compared to the findings in the untreated and monotherapy groups and improved the survival rate to 100%. The PSC and AFG combination therapy was highly effective and should be evaluated in larger-scale experiments.     

In vitro activities of voriconazole, itraconazole, and terbinafine alone or in combination against Pythium insidiosum isolates from Brazil

We evaluated the in vitro activities of voriconazole, itraconazole, and terbinafine against 30 clinical isolates of Pythium insidiosum using a checkerboard macrodilution method. The combined activity of terbinafine plus itraconazole or plus voriconazole was synergic against 17% of the strains. Antagonism was not observed.