The present study investigated the association of the non-steroidal anti-inflammatory drug ibuprofen with itraconazole, fluconazole and amphotericin B against Cryptococcus neoformans isolates. The minimal inhibitory concentration (MIC) was found according to M27-A3 protocol and in vitro interactions were evaluated using checkerboard microdilution method. Synergism was demonstrated between azoles and ibuprofen for most isolates. However, no synergistic effects were seen when amphotericin B was combined with ibuprofen. Therefore, our results suggest that ibuprofen presents clinical potential when combined with azole drugs in the treatment of cryptococcosis.

Candida glabrata has emerged as a common cause of serious life-threatening fungal infections, largely owing to their low susceptibility to azole antifungals. Recent guidance indicates the use of echinocandins as the first-choice drug for the treatment of systemic infections of C. glabrata; however, C. glabrata resistance to echinocandins is reportedly increasing. Herein, we present the induction of anidulafungin resistance in planktonic and sessile cells of C. glabrata and the development of fluconazole cross-resistance. MICs of 21 clinical C. glabrata strains were determined by a broth microdilution method using anidulafungin and fluconazole. Biofilm formation on a tracheal catheter was determined using 1- × 1-cm2 polyvinyl polychloride catheter fragments. Induction of anidulafungin resistance in planktonic and sessile cells and evaluation of its stability were performed by exposing the strains to successively higher concentrations of the antifungal. The induction resulted in strains strongly resistant to anidulafungin (MICs: 1-2 µg/mL) and fluconazole (≥64 µg/mL). Most of the sessile cells of C. glabrata presented slightly reduced susceptibility compared with the planktonic cells. Clinically, this cross-resistance could lead to therapeutic failure while using fluconazole in patients previously exposed to subinhibitory concentrations of anidulafungin for extended periods.

ABSTRACT Griseofulvin (GF) and terbinafine (TF) are commonly used drugs to treat dermatophytosis, a fungal infection of the skin. Today there is an increase in drug resistance to these antifungals which highlight the need for alternative synergistic therapies. Minimum Inhibitory Concentration (MIC) of GF and TF were determined against fungi clinical isolates from local hospitals with values ranging 0.03-2.0 µg mL-1 and 0.24-4.0 µg mL-1, respectively. A checkboard test was used to determine the combination of GF:TF which could induce an additive effect against the fungi isolates Multidrug-resistant isolates showed susceptibility after treatment with 16:2 µg mL-1 GF:TF. An MTT assay further verified that GF and TF combinations have greater additive effect against pathological and multidrug-resistant isolates than antifungals alone. Herein we disclose GF:TF combinations that could constitute as a possible new anti-dermatophyte therapy.

ABSTRACT Hypericum species, Hypericaceae, are recognized as a source of therapeutical agents. Purified fractions and isolated compounds have been shown antimicrobial activity. As the indiscriminate use of antifungals and the increase of infections caused by emerging species are leading to the search of new alternative treatments, the aim of this study was to continue the study with Hypericum carinatum Griseb. lipophilic fraction, rich in phloroglucinol derivatives, investigating the effect of its association with fluconazole against emerging yeasts (Candida krusei, C. famata, C. parapsilosis and Cryptococcus neoformans). The synergistic activity between H. carinatum lipophilic fraction and fluconazole was assessed by two methodologies for multiple dose–response analysis: checkerboard and isobologram. Regarding synergistic experiments, the effect of the association was higher than the effect of fluconazole alone against Candida krusei and C. famata isolates (MIC fluconazole decreased about eight and four folds, respectively), suggesting that, somehow, H. carinatum lipophilic fraction compounds are facilitating the action of this drug. On the other hand, when tested against Cryptococcus neoformans and C. parapsilosis, fluconazole showed better results than the association. Thus, against Candida krusei and C. famata, the lipophilic fraction of H. carinatum was able to reduce the MIC values of fluconazole and could be considered as a potential alternative to be used against emerging yeast species.

Embora a anestesia injetável previamente a raspagem e alisamento subgengival (RASUB) reduza a dor, muitos pacientes relatam medo e amortecimento prolongado dos tecidos adjacentes. O objetivo deste estudo foi comparar o efeito de uma mistura eutética contendo 25mg/g de lidocaína e 25 mg/g de prilocaína, lidocaína 2% injetável, benzocaína 2% tópica e um placebo na redução da dor durante a RASUB. Neste ensaio clínico randomizado, cego de boca dividida, trinta e dois pacientes que apresentavam mais que dois dentes com profundidade de sondagem e nível de inserção clínica ≥ 5 mm, em no mínimo 4 sextantes, foram randomicamente alocados em 4 grupos: EMLA(r), lidocaína 2% injetável, benzocaína 2% tópica ou placebo. Dor e desconforto foram mensurados usando uma Escala Visual Analógica (EVA) e Escala Verbal (EV). A satisfação dos pacientes com a anestesia foi determinada ao final de cada consulta. Análise de variância de medidas repetidas e regressão de Poisson foram usadas para análise. Os escores da EVA e EV não demonstraram diferenças estatisticamente significantes entre lidocaína injetável e EMLA(r) (p > 0,05) e ambas as substâncias demonstraram significativamente melhor controle da dor comparadas a benzocaína 2% e placebo (p<0,05). 93,7% e 81,2% dos indivíduos ficaram satisfeitos com o anestésico injetável e EMLA(r), respectivamente (p=0,158). A insatisfação com a benzocaína e placebo foi aproximadamente 10 vezes maior do que com a anestesia injetável (p=0,001). Em conclusão, o EMLA(r) demonstrou um efeito equivalente no controle da dor quando comparado com a anestesia injetável e melhor do que a benzocaína 2% em RASUB. Assim, o EMLA(r) é uma opção anestésica viável durante a raspagem e alisamento radicular, apesar da necessidade frequente de segunda aplicação.

Although the use of injectable anesthesia prior to subgingival scaling and root planing (SRP) reduces pain, many patients report fear and prolonged numbness of adjacent tissues. The aim of the present study was to compare the effects of a eutectic mixture containing 25 mg/g of lidocaine and 25 mg/g of prilocaine, injectable 2% lidocaine, topical 2% benzocaine and a placebo substance on reducing pain during SRP. In this randomized, split-mouth, masked clinical trial, thirty-two patients presenting more than two teeth with probing depth and clinical attachment level ≥5 mm in at least 4 sextants were randomly allocated to four groups: EMLA(r); injectable 2% lidocaine; topical 2% benzocaine and placebo. Pain and discomfort were measured using a visual analogue scale (VAS) and verbal scale (VS). Repeated-measures analysis of variance and Poisson regression were used for analysis. Patient satisfaction with the anesthesia was determined at the end of each treatment session. VAS and VS scores did not differ between injectable 2% lidocaine and EMLA (p>0.05) and both substances showed significantly better pain control compared to 2% benzocaine and placebo (p<0.05). 93.7% and 81.2% of the individuals were satisfied with the injectable anesthetic and EMLA, respectively (p=0.158). Dissatisfaction with benzocaine and placebo was approximately 10 times greater than injectable anesthesia (p=0.001). In conclusion, EMLA showed an equivalent effect on pain control when compared to the injectable anesthesia and performed better than 2% benzocaine in SRP. Thus, EMLA is a viable anesthetic option during scaling and root planning, despite the frequent need for second application.

Dermatomycosis causes highly frequent dermal lesions, and volatile oils have been proven to be promising as antifungal agents. The antifungal activity of geraniol, nerol, citral, neral and geranial (monoterpenes), and terbinafine and anidulafungin (control drugs) against seven opportunistic pathogenic yeasts and four dermatophyte species was evaluated by the Clinical and Laboratory Standards Institute microdilution tests. Monoterpenes were more active against dermatophytes than yeasts (geometric mean of minimal inhibitory concentration (GMIC) of 34.5 and 100.4 µg.ml-1, respectively). Trichophyton rubrum was the fungal species most sensitive to monoterpenes (GMIC of 22.9 µg.ml-1). The trans isomers showed higher antifungal activity than the cis. The mechanism of action was investigated evaluating damage in the fungal cell wall (Sorbitol Protection Assay) and in the cell membrane (Ergosterol Affinity Assay). No changes were observed in the MIC of monoterpenes in the sorbitol protection assay.The MIC of citral and geraniol was increased from 32 to 160 µg.ml-1 when the exogenous ergosterol concentrations was zero and 250 µg.ml-1, respectively. The monoterpenes showed an affinity for ergosterol relating their mechanism of action to cell membrane destabilization.