Activity of Combined Antifungal Agents Against Multidrug-Resistant Candida glabrata Strains

Denardi, Laura Bedin; Keller, Jéssica Tairine; Oliveira, Vanessa; Mario, Débora Alves Nunes; Santúrio, Jânio Morais; Alves, Sydney Hartz

doi:10.1007/s11046-017-0141-9

Cited by 20 publications

(16 citation statements)

References 36 publications

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“…In recent years, many approaches for the combination therapy have been proposed to treat infectious diseases. [11][12][13][14][15] This is very important, particularly, to counter the phenomenon of the multi-drug resistance.…”

Section: Discussionmentioning

confidence: 99%

“…10 The use of antibiotic combinations seems to be an important strategy to counter the phenomenon of drug resistance. [11][12][13] Chloroquine (CQ) and fluconazole (FLZ) exhibited a synergistic effect against FLZ-resistant isolates of C. albicans. 14 We earlier showed that liposomal-CQ increased the efficacy of FLZ against less susceptible isolate of Cryptococcus neoformans.…”

Section: Introductionmentioning

confidence: 99%

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Coadministration of Ginger Extract and Fluconazole Shows a Synergistic Effect in the Treatment of Drug-Resistant Vulvovaginal Candidiasis

Khan

Azam

Allemailem

et al. 2021

IDR

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Background Azoles are the most common antifungal drugs used in the treatment of vulvovaginal candidiasis (VVC). The frequency of azole-resistant Candida isolates has increased dramatically in the last two decades. Here, we assessed the antifungal activity of a combination of fluconazole (FLZ) and methanolic extract of ginger (Meth-Gin) against drug-resistant vulvovaginal candidiasis (VVC) in a murine model. Methods The in vitro activity of FLZ or a combination of FLZ and Meth-Gin was determined against Candida albicans by the agar well diffusion, macrodilution, time-kill and the biofilm eradication methods. The therapeutic efficacy of the formulations was assessed by analyzing the fungal load, pro-inflammatory cytokines, percent apoptotic cells and the histological changes in the vaginal tissues of the mice. Moreover, the renal toxicity the drug formulation was evaluated by analyzing the levels of the blood urea nitrogen (BUN) and creatinine. Results The results of in vitro study demonstrated that FLZ did not show any activity against C. albicans , whereas a combination of FLZ and Meth-Gin demonstrated greater activity as shown by the data of the zone of growth inhibition, MIC and time-kill assay. FLZ or Meth-Gin treatment could not completely cure VVC, whereas a combination of FLZ and Meth-Gin was greatly effective in the treatment of VVC. The vaginal tissue from mice of the infected control group had the highest fungal load of 155370 ± 20617 CFUs. Treatment with FLZ at a dose of 40 mg/kg reduced the fungal load to 120863 ± 10723 CFUs. Interestingly, the mice treated with a combination of FLZ (40 mg/kg) and Meth-Gin (200 mg/kg) had a fungal load of 256 ± 152 CFUs. Besides, FLZ and Meth-Gin combination effectively reduced the pro-inflammatory cytokines (IL-1β, TNF-α and IL-17) and the percentage of apoptotic cells in the vaginal tissues. Likewise, the histological analysis revealed the epithelial necrosis, shedding and ulceration in the vaginal tissue, whereas treatment with FLZ and Meth-Gin combination reversed the histopathological changes in the vaginal epithelium and lamina propria. Conclusion The findings of the current study suggest that the co-administration of Meth-Gin and FLZ may have a potential therapeutic effect in the treatment of azole-resistant candidiasis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Coadministration of Ginger Extract and Fluconazole Shows a Synergistic Effect in the Treatment of Drug-Resistant Vulvovaginal Candidiasis

Khan

Azam

Allemailem

et al. 2021

IDR

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“…As indicated afore, susceptibility testing of molds to echinocandins may be problematic due to inability to establish clear-cut MIC values, but is evaluated by the MEC. A recent study in Brazil ( Denardi et al, 2017 ) explored by the broth micro-dilution method of EUCAST and using the EUCAST-proposed breakpoints the in vitro susceptibility of 105 clinical and environmental strains of A. fumigatus and A. flavus to the antifungal drugs: amphotericin B, azoles, and echinocandins. They found that there were differences among the echinocandins (caspofungin, micafungin, and anidulafungin) as to activity and also variability as to susceptibility of the Aspergillus spp.…”

Section: Human Aspergillosis: In Vitro Assessment mentioning

confidence: 99%

“…As to in vitro susceptibility testing of antifungal combinations against Aspergillus spp.—here too are a number of reports in the literature. A recent article by Denardi et al (2017) reports on susceptibility testing of A. fumigatus to antifungal–drug combinations. The authors evaluated combinations of triazoles and echinocandins on itraconazole-resistant strains, using two methods: the checkerboard assay and the E -test.…”

Section: Human Aspergillosis: In Vitro Assessment mentioning

confidence: 99%

Diagnostic Aspects of Veterinary and Human Aspergillosis

Elad

Segal

2018

Front. Microbiol.

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The genus Aspergillus is composed of more than 300 species, a fraction of which are involved in animal or human infections mostly following environmental exposure. Various risk factors (i.e., immunosuppression, tuberculosis) have been recognized for human whereas for veterinary infections, unhygienic management, trauma, anatomical conformation of the skull, or suspected immunological deficiencies have been suggested. In animals, aspergillosis is mostly sporadic but in some circumstance such as infections on poultry farms may involve the whole flock. Since the high prevalence of immunosuppression in human patients has not been mirrored in veterinary medicine, and although to the best of our knowledge, no comprehensive data on the prevalence of aspergillosis in animals has been published, their epidemiology has not changed during the last decades. The impact of these infections may be economic or if they are incurable, sentimental. The objective of the first part is to describe the diagnosis of the main clinical entities caused by Aspergillus spp. in animals. It includes disseminated canine aspergillosis, canine and feline sino-nasal and sino-orbital aspergillosis, guttural pouch mycosis in horses, mycotic abortion in cattle, mycotic keratitis in horses, and avian aspergillosis. When pathogenesis and clinical aspects are relevant for diagnosis—they will be addressed as well. The second part deals with human aspergillosis, which is a multifaceted disease, manifested in a spectrum of clinical entities affecting one or more organs. Diagnosis is based on the clinical manifestation, supported and confirmed by laboratory means, involving the classical approach of demonstrating the etiological agent in the clinical specimens and in culture. Noncultural methods, such as antigen detection and/or molecular assays to detect fungal nucleic acids or protein profiles, are used as well. The isolation and identification of the fungus allows the determination of its susceptibility to antifungal drugs. Thus, antifungal susceptibility testing maybe considered as part of the diagnostic process, which is of relevance for management of the infection. In this review article, the part dealing with diagnostic aspects of aspergillosis in humans concentrates on susceptibility testing of Aspergillus spp. to antifungal drugs and drug combinations. The technologies and methods of susceptibility testing are described and evaluated.

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“…Another study found a similar degree of synergism with anidulafungin against various species of Candida [ 31 ]. Conversely, other studies with C. glabrata demonstrated a lack of synergy with the combinations of amphotericin B and echinocandins [ 32 ]. Although most interactions were deemed indifferent by the checkerboard method in the study of Serena et al on the combination of amphotericin B with micafungin, there was synergism against some strains that were further analysed by time–kill methodology and the combination demonstrated a fast-killing activity against them [ 33 ].…”

Section: Discussionmentioning

confidence: 95%

In Vitro Interaction and Killing-Kinetics of Amphotericin B Combined with Anidulafungin or Caspofungin against Candida auris

et al. 2021

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Treatment of invasive infections caused by Candida auris is challenging due to the limited therapeutic options. The combination of antifungal drugs may be an interesting and feasible approach to be investigated. The aim of this study was to examine the in vitro activity of amphotericin B in combination with anidulafungin or caspofungin against C. auris. In vitro static time–kill curve experiments were conducted for 48 h with different combinations of amphotericin B with anidulafungin or caspofungin against six blood isolates of C. auris. The antifungal activity of 0.5 mg/L of amphotericin B was limited against the six isolates of C. auris. Similarly, echinocandins alone had a negligible effect, even at the highest tested concentrations. By contrast, 1 mg/L of amphotericin B showed fungistatic activity. Synergy was rapidly achieved (8 h) with 0.5 mg/L of amphotericin B plus 2 mg/L of anidulafungin or caspofungin. These combinations lead to a sustained fungistatic effect, and the fungicidal endpoint was reached against some C. auris isolates. Additionally, ≥0.5 mg/L of either of the two echinocandins with 1 mg/L of amphotericin B resulted in fungicidal effect against all C. auris isolates. In conclusion, combinations of amphotericin B with anidulafungin or caspofungin provided greater killing with a lower dose requirement for amphotericin B compared to monotherapy, with synergistic and/or fungicidal outcomes.

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Activity of Combined Antifungal Agents Against Multidrug-Resistant Candida glabrata Strains

Cited by 20 publications

References 36 publications

Coadministration of Ginger Extract and Fluconazole Shows a Synergistic Effect in the Treatment of Drug-Resistant Vulvovaginal Candidiasis

Coadministration of Ginger Extract and Fluconazole Shows a Synergistic Effect in the Treatment of Drug-Resistant Vulvovaginal Candidiasis

Diagnostic Aspects of Veterinary and Human Aspergillosis

In Vitro Interaction and Killing-Kinetics of Amphotericin B Combined with Anidulafungin or Caspofungin against Candida auris

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