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Cassyano Januario Correr – 1st expert on this subject based on the ideXlab platform
efficacy of topical Antifungals in the treatment of dermatophytosis a mixed treatment comparison meta analysis involving 14 treatmentsJAMA Dermatology, 2013Co-Authors: Inajara Rotta, Michel Fleith Otuki, Patricia Klarmann Ziegelmann, Bruno Salgado Riveros, Noemia L M C Bernardo, Cassyano Januario CorrerAbstract:
Importance Considering that most randomized controlled trials compare Antifungals with placebo instead of other Antifungals, conventional meta-analysis is insufficient to define superiority between the evaluated strategies. To our knowledge, this is the first mixed-treatment comparison meta-analysis on antifungal treatments in the literature and shows all the evidence available at the time of the study. Objective To evaluate and compare the efficacy of topical Antifungals used in dermatophytosis treatment, using mixed-treatment comparisons. Evidence Acquisition We performed a comprehensive search (up to July 31, 2012) for all entries in MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, Literatura Latino Americana e do Caribe em Ciencias da Saude, and International Pharmaceutical Abstracts. Randomized controlled trials that compared topical Antifungals with one another or with placebo in dermatophytosis treatment were selected for analysis. Methodologic quality of the trials was assessed using the Jadad scale. We excluded studies that scored less than 3 points. The outcomes evaluated were mycologic cure at the end of treatment and sustained cure. A random-effects Bayesian mixed-treatment comparisons model was applied to combine placebo-controlled and direct topical Antifungals comparison trials. Results Pooled data of the 65 trials identified did not show any statistically significant differences among the Antifungals concerning the outcome of mycologic cure at the end of treatment. Regarding the sustained cure outcome, butenafine hydrochloride and terbinafine hydrochloride were significantly more efficacious than were clotrimazole, oxiconazole nitrate, and sertaconazole nitrate. Terbinafine also demonstrated statistical superiority when compared with ciclopirox (ciclopiroxolamine), and naftifine hydrochloride showed better response compared with oxiconazole. No inconsistency was detected in the network of evidence for both outcomes, sustaining the validity of the mixed-treatment comparisons results. Conclusions and Relevance With the outcome mycologic cure at the end of treatment, there was no significant difference among the Antifungals. Butenafine, naftifine, and terbinafine might be the best strategies for maintaining cured status. Because of the different costs of the Antifungals, pharmacoeconomic analysis is required to identify the most efficient strategy for dermatophytosis management.
efficacy and safety of topical Antifungals in the treatment of dermatomycosis a systematic reviewBritish Journal of Dermatology, 2012Co-Authors: Inajara Rotta, A Sanchez, Patricia Rodrigues Goncalves, Michel Fleith Otuki, Cassyano Januario CorrerAbstract:
The analysis of comparative efficacy and safety of topical Antifungals in the literature is restricted to the treatment of tinea pedis and onychomycosis. Therefore our objective was to evaluate and compare the efficacy and safety of topical Antifungals used in the treatment of dermatomycosis, we performed a comprehensive search for randomized controlled trials (RCTs) in the following databases: Medline, Cochrane Central Register of Controlled Trials, EMBASE, Lilacs and International Pharmaceutical Abstracts, we identified studies that compared the use of topical Antifungals with other Antifungals or with placebo published up to July 2010 in English, Spanish or Portuguese. The quality of reporting was assessed according to the Jadad scale; only studies with a score of 3 or more were included. The outcomes evaluated were mycological cure at the end of treatment, sustained cure, occurrence of adverse events and tolerability, including withdrawals due to adverse events. A total of 104 RCTs satisfied the inclusion criteria, containing a total of 135 comparisons, with 55 out of 120 possible comparisons among the 16 drugs evaluated. Pooled data on efficacy showed that all the Antifungals were better than placebo. There were no significant differences among antifungal classes. No differences were found in safety or tolerability in any direct comparison. Sensitivity analysis indicated the robustness of the findings. Our results indicate the clear superiority of topical Antifungals over placebo but that there is no consistent difference among classes. Mixed treatment comparisons are necessary to rank Antifungals, as direct comparisons among many of them are lacking.
Oscar Marchetti – 2nd expert on this subject based on the ideXlab platform
multiplex ultra performance liquid chromatography tandem mass spectrometry method for simultaneous quantification in human plasma of fluconazole itraconazole hydroxyitraconazole posaconazole voriconazole voriconazole n oxide anidulafungin and caspofuAntimicrobial Agents and Chemotherapy, 2010Co-Authors: Laurent A Decosterd, Bertrand Rochat, Benoit Pesse, Thomas Mercier, Frederic Tissot, Nicolas Widmer, Jacques Bille, Thierry Calandra, Boris Zanolari, Oscar MarchettiAbstract:
Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several Antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method requiring 100 μl of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, hydroxyitraconazole, posaconazole, voriconazole, voriconazole- N -oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, Antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole Antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (
D A Enoch – 3rd expert on this subject based on the ideXlab platform
introduction of an antifungal stewardship programme targeting high cost Antifungals at a tertiary hospital in cambridge englandJournal of Antimicrobial Chemotherapy, 2015Co-Authors: Christianne Micallef, Sani H Aliyu, Reem Santos, Nicholas M Brown, Denise Rosembert, D A EnochAbstract:
BACKGROUND: Antifungal stewardship aims to promote the optimal use of Antifungals through the careful selection of agents based on patient profile, target organism, toxicity, costs and the likelihood of emergence and spread of resistance. METHODS: We report on an observational prospective 12 month study conducted by an antifungal stewardship team targeting the use of echinocandins (caspofungin and micafungin), voriconazole and liposomal amphotericin B in a tertiary referral hospital in the UK. RESULTS: One-hundred-and-seventy-three patients were reviewed on 294 occasions. Clinical advice was given and implemented during review of 45 (88.2%) of micafungin prescriptions, 70 (78.7%) of those receiving voriconazole, 78 (62.4%) of those receiving liposomal amphotericin B and 3 (27.3%) of those receiving caspofungin. Except for voriconazole, nearly half of all treatments reviewed were stopped or changed. This study found that a crude cost saving of ∼£180 000 in antifungal drugs was generated compared with the previous year. CONCLUSIONS: Using a multidisciplinary team, antifungal stewardship can achieve significant improvements in patient management and it may reduce costs.