Cotrimoxazole enhances the in vitro susceptibility of Coccidioides posadasii to antifungals

Centro Especializado em Micologia Médica, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
Memórias do Instituto Oswaldo Cruz (Impact Factor: 1.59). 12/2011; 106(8):1045-8. DOI: 10.1590/S0074-02762011000800024
Source: PubMed


The aim of the present study was to evaluate the effect of cotrimoxazole on the in vitro susceptibility of Coccidioides posadasii strains to antifungals. A total of 18 strains of C. posadasii isolated in Brazil were evaluated in this study. The assays were performed in accordance with the Clinical and Laboratory Standards Institute guidelines and the combinations were tested using the checkerboard method. The minimum inhibitory concentrations were reduced by 11, 2.4, 4.3 and 3.5 times for amphotericin B, itraconazole, fluconazole and voriconazole, respectively. Moreover, it was seen that cotrimoxazole itself inhibited C. posadasii strains in vitro. The impairment of folic acid synthesis may be a potential antifungal target for C. posadasii.

Download full-text


Available from: Zoilo Pires de Camargo, Aug 06, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Cryptococcus neoformans species complex contains the most important agents of fungal meningoencephalitis. Therapeutic choices are limited and issues related to toxicity and resistance to antifungals have been described. The present study evaluated the inhibitory effect of the antifolate combinations sulfamethoxazole-trimethoprim (SMX/TMP) and sulfadiazine-pyrimethamine (SDZ/PYR) against planktonic cells and biofilms of C. neoformans and C. gattii. The influence of the antifolate combinations on the amphotericin minimum inhibitory concentration (MIC) of planktonic cells was also investigated. In addition, the effect of these combinations on the cellular ergosterol content of planktonic cells was studied. Strains of C. neoformans (n = 15) and C. gattii (n = 15) obtained from environmental or clinical sources were evaluated by the broth microdilution method. SMX/TMP and SDZ/PYR showed antifungal activity against free living cells and sessile cells of Cryptococcus spp. Moreover, planktonic cells showed increased susceptibility to amphotericin B after pre-incubation with sub-inhibitory concentrations of SMX/TMP or SDZ/PYR. The drug combinations SMX/TMP and SDZ/PYR were able to prevent the biofilm formation and showed inhibitory effect against mature biofilms of both species. Additionally, the study showed that antifolate drugs reduced the ergosterol content in C. neoformans and C. gattii planktonic cells. Our results highlight the antifungal potential of antifolate drugs.
    No preview · Article · Nov 2012 · European Journal of Clinical Microbiology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Opportunistic fungi are the most important pathogens in modern world. They are responsible for severe infections in majority of immunocompromised patients. These microorganisms are commonly present in our environment which is natural reservoir of new, resistant species. For this reason mycoses are mainly chronic or long-lasting diseases. Our arsenal of antifungal drugs is growing but still insufficient for emerging resistant pathogens. An alternative for novel chemical entity drugs is the multidrug approach. This exploiting the drugs being currently on market applying simultaneously for better efficacy or to eradicate resistance. Synergy is the term that describes the phenomenon of increased potency of two or more drugs administered in combination. In the last decades it gains more interest and numbers of synergy claimed reports is growing exponentially. However these have rather low impact on clinical trials or practical use of antimycotics. In present review we wish to discuss current status of synergy between antifungal drugs. Both theoretical point of view and practical applicability in clinical terms are covered. There are serious differences between the assumptions, methods and interpretations of the results and sometimes even obvious mistakes in the procedure that was applied or in the outcomes discussed. On the other hands the specificity of fungal infections introduce dozens of factors affecting the observed results. Shift form in vitro studies to clinical trials reveal further difficulties. Hopefully multi-drug approach seems to be effective even if no strong synergy is displayed.
    Full-text · Article · Dec 2013 · Current Medicinal Chemistry
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A reliable multiclass method has been developed and validated for the determination of eight antibiotics from distinct classes (sulfonamides, macrolides, fluoroquinolones, tetracyclines, cephalosporins and dihydrofolate reductase inhibitors) in wastewater – influent and effluent – and surface water from Porto Alegre, Brazil. The pre-concentration and clean-up was conducted with a simple and fast protocol using solid-phase extraction allowing a 100-fold concentration factor. The proposed method was validated by using spiked blank wastewater samples in terms of linearity, repeatability, reproducibility, recovery, matrix effects and limits of detection and quantification. Recovery was obtained in the range of 66–149%. Method limit of quantification ranged between 1.6 and 61.7 ng L−1. Samples (n = 16) were taken from January to August 2011 in one wastewater treatment plant, which uses conventional biological treatment. Sulfamethoxazole and trimethoprim show higher concentration, ranging from >10 to <6500 ng L−1, whereas erythromycin presented the lower amount. Differences between influent and effluent profiles were discussed. Surface water samples (n = 8) were collected in Arroio Diluvio, in four sampling points, in February 2012. From the eight antibiotics analysed, five were detected: sulfamethoxazole, trimethoprim, azythromicyn, ciprofloxacin and norfloxacin, in a concentration range of 376–572 ng L−1, 27–94 ng L−1, 24–40 ng L−1, 16–66ng L−1 and 30–54 ng L−1, respectively.
    Full-text · Article · Mar 2014 · International Journal of Environmental Analytical Chemistry