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Antimicrobial Agents and Chemotherapy Jun 2020Anidulafungin and micafungin were quantified in cerebrospinal fluid (CSF) of critically ill adults and in cerebral cortex of deceased patients. In CSF, anidulafungin...
Anidulafungin and micafungin were quantified in cerebrospinal fluid (CSF) of critically ill adults and in cerebral cortex of deceased patients. In CSF, anidulafungin levels (<0.01 to 0.66 μg/ml) and micafungin levels (<0.01 to 0.16 μg/ml) were lower than those in plasma concentrations (0.77 to 5.07 and 1.21 to 8.70 μg/ml, respectively) drawn simultaneously. In cerebral cortex, anidulafungin and micafungin levels were 0.21 to 2.34 and 0.18 to 2.88 μg/g, respectively. Thus, MIC values of several pathogenic strains exceed concentrations in CSF and in brain.
Topics: Adult; Anidulafungin; Antifungal Agents; Cerebral Cortex; Echinocandins; Humans; Lipopeptides; Micafungin; Microbial Sensitivity Tests
PubMed: 32340985
DOI: 10.1128/AAC.00275-20 -
Expert Review of Anti-infective Therapy Feb 2007Anidulafungin, a new echinocandin, has recently been approved for the treatment of esophageal candidiasis, candidemia and other forms of invasive candidiasis, such as... (Review)
Review
Anidulafungin, a new echinocandin, has recently been approved for the treatment of esophageal candidiasis, candidemia and other forms of invasive candidiasis, such as peritonitis and intra-abdominal abscesses in non-neutropenic patients. It is fungicidal against Candida spp. including those that are azole- and polyene-resistant and fungistatic against Aspergillus spp. Owing to its poor oral bioavailability it can only be administered intravenously. Its pharmacokinetics allow for once-daily dosing and a steady state concentration is easily achieved on day 2 following a loading dose of double the maintenance dose on day 1. It does not need adjustment for hepatic or renal insufficiency; there are no known drug interactions and it has a favorable tolerability profile. Its mechanism of action, which differs from other classes of antifungals, should prevent cross-resistance with azoles and polyenes.
Topics: Anidulafungin; Animals; Candidiasis; Drugs, Investigational; Echinocandins; Fungal Proteins; Humans; Peptides, Cyclic
PubMed: 17266452
DOI: 10.1586/14787210.5.1.45 -
Microbiology Spectrum Dec 2022The proposed life cycle of fungi in the genus Pneumocystis has typically included both an asexual cycle via binary fission and a sexual cycle. Until recently, the...
The proposed life cycle of fungi in the genus Pneumocystis has typically included both an asexual cycle via binary fission and a sexual cycle. Until recently, the strategy used for sexual replication was largely unknown, but genomic and functional assays now support a mode known as primary homothallism (self-fertilization). The question of whether an asexual cycle contributes to the growth of these fungi remains. Treatment of Pneumocystis pneumonia in immunosuppressed rodent models with the class of drugs known as echinocandins is challenging the historical concept of asexual replication. The echinocandins target 1,3-β-D-glucan (BG) synthesis resulting in death for most fungi. Because Pneumocystis species have both non-BG expressing life cycle stages (trophic forms) and BG-expressing asci, treatment with anidulafungin and caspofungin resulted in elimination of asci, with large numbers of non-BG expressing organisms remaining in the lungs. Transcriptional analyses of anidulafungin treated Pneumocystis murina-infected lungs indicated that these agents were blocking the sexual cycle. In the present study, we explored whether there was an asexual or alternative method of replication that could rescue P. murina survival and growth in the context of anidulafungin treatment. The effects of anidulafungin treatment on early events in the sexual cycle were investigated by RT-qPCR targeting specific mating genes, including , and . Results from the and gene expression studies clearly indicated there was no rescue by an asexual cycle, supporting these fungi's reliance on the sexual cycle for survival and growth. Dysregulation of mating-associated genes showed that anidulafungin induced effects early in the mating process. The concept of a sexually obligate fungus is unique among human fungal pathogens. This reliance can be exploited for drug development and here we show a proof of principle for this unusual target. Most human fungal pathogens eschew the mammalian environment with its battery of immune responses. Pneumocystis appear to have evolved to survive in such an environment, perhaps by using sexual replication to help in DNA repair and to introduce genetic variation in its major surface antigen family because the lung is the primary environment of these pathogens. The concept of primary homothallism fits well into its chosen ecosystem, with ready mating partners expressing both mating type receptors, and a sexual cycle that can introduce beneficial genetic variation without the need for outbreeding.
Topics: Animals; Anidulafungin; Echinocandins; Ecosystem; Pneumocystis; Pneumonia, Pneumocystis
PubMed: 36287071
DOI: 10.1128/spectrum.02906-22 -
Revista Iberoamericana de Micologia 2021Candida albicans chorioretinitis is the most common cause of endogenous fungal endophthalmitis. Echinocandins are recommended as first-line therapy in the treatment of...
BACKGROUND
Candida albicans chorioretinitis is the most common cause of endogenous fungal endophthalmitis. Echinocandins are recommended as first-line therapy in the treatment of invasive candidiasis (IC), but in clinically stable patients with IC and endophthalmitis caused by Candida species susceptible to azole compounds these are the first-line treatment due to their better intraocular penetration.
CASE REPORT
A 42-year-old woman admitted to hospital for duodenal perforation after gastrointestinal surgery and treated with broad-spectrum antibiotics developed C. albicans candidemia. According to protocol, an antifungal treatment with anidulafungin was given. The patient presented no visual symptoms but on routinary ophthalmoscopic examination multiple bilateral chorioretinal lesions were observed. Systemic therapy was changed to fluconazole, with good systemic and ocular results.
CONCLUSIONS
Azole compounds are the first-line therapy for endophthalmitis associated with candidemia. However, clinical guidelines often propose echinocandins as the first option for IC. In some cases, C. albicans chorioretinitis will require a change in the systemic treatment to assure better intraocular penetration. According to the current evidence and our own experience, routine funduscopy is not necessary in all IC patients. However, we do recommend fundus examination in patients with visual symptoms or those unable to report them (paediatric patients and patients with an altered level of consciousness), and in those who are being treated with echinocandins in monotherapy.
Topics: Adult; Anidulafungin; Candida albicans; Candidiasis, Invasive; Child; Chorioretinitis; Female; Fluconazole; Humans
PubMed: 34785085
DOI: 10.1016/j.riam.2021.05.002 -
Medicina Oral, Patologia Oral Y Cirugia... Mar 2019Candidiasis is one of the most common opportunistic oral infections that presents different acute and chronic clinical presentations with diverse diagnostic and... (Review)
Review
BACKGROUND
Candidiasis is one of the most common opportunistic oral infections that presents different acute and chronic clinical presentations with diverse diagnostic and therapeutic approaches. The present study carries out a bibliographic review on the therapeutic tools available against oral candidiasis and their usefulness in each clinical situation.
MATERIAL AND METHODS
Recent studies on treatment of oral candidiasis were retrieved from PubMed and Cochrane Library.
RESULTS
Nystatin and miconazole are the most commonly used topical antifungal drugs. Both antifungal drugs are very effective but need a long time of use to eradicate the infection. The pharmacological presentations of miconazole are more comfortable for patients but this drug may interact with other drugs and this fact should be assessed before use. Other topical alternatives for oral candidiasis, such as amphotericin B or clotrimazole, are not available in many countries. Oral fluconazole is effective in treating oral candidiasis that does not respond to topical treatment. Other systemic treatment alternatives, oral or intravenous, less used are itraconazole, voriconazole or posaconazole. Available novelties include echinocandins (anidulafungin, caspofungin) and isavuconazole. Echinocandins can only be used intravenously. Isavuconazole is available for oral and intravenous use. Other hopeful alternatives are new drugs, such as ibrexafungerp, or the use of antibodies, cytokines and antimicrobial peptides.
CONCLUSIONS
Nystatin, miconazole, and fluconazole are very effective for treating oral candidiasis. There are systemic alternatives for treating recalcitrant infections, such as the new triazoles, echinocandins, or lipidic presentations of amphotericin B.
Topics: Administration, Intravenous; Administration, Oral; Administration, Topical; Amphotericin B; Anidulafungin; Antifungal Agents; Azoles; Candidiasis, Oral; Caspofungin; Clotrimazole; Databases, Factual; Drug Interactions; Echinocandins; Fluconazole; Humans; Miconazole; Nitriles; Nystatin; Pyridines; Triazoles
PubMed: 30818309
DOI: 10.4317/medoral.22978 -
Virulence Dec 2022Antifungal resistance to pathogens increases morbidity and mortality of immunosuppressive patients, an emerging crisis worldwide. Understanding the prevalence and... (Review)
Review
Antifungal resistance to pathogens increases morbidity and mortality of immunosuppressive patients, an emerging crisis worldwide. Understanding the prevalence and antifungal susceptibility pattern is necessary to control and treat candidiasis. We aimed to systematically analyse the susceptibility profiles of species published in the last ten years (December 2011 to December 2021) from mainland China. The studies were collected from PubMed, Google Scholar, and Science Direct search engines. Out of 89 included studies, a total of 44,716 isolates were collected, mainly comprising (49.36%), (21.89%), (13.92%), and (11.37%). The lowest susceptibility was detected for azole group; fluconazole susceptibilities against , and were 93.25%, 91.6%, 79.4%, 77.95%, 76%, 50%, and 0% respectively. Amphotericin B and anidulafungin were the most susceptible drugs for all species. Resistance to azole was mainly linked with mutations in , and genes. Mutation in and in and causing resistance to echinocandins was stated in two studies. Gaps in the studies' characteristics were detected, such as 79.77%, 47.19 %, 26.97%, 7.86%, and 4.49% studies did not mention the mortality rates, age, gender, breakpoint reference guidelines, and fungal identification method, respectively. The current study demonstrates the overall antifungal susceptibility pattern of species, gaps in surveillance studies and risk-reduction strategies that could be supportive in candidiasis therapy and for the researchers in their future studies.
Topics: Humans; Amphotericin B; Anidulafungin; Antifungal Agents; Azoles; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Candida tropicalis; Candidiasis; Echinocandins; Fluconazole; Microbial Sensitivity Tests
PubMed: 36120738
DOI: 10.1080/21505594.2022.2123325 -
Revista Iberoamericana de Micologia Jun 2008The latest antifungal drugs introduced for clinical use are echinocandins; they possess a distinctive mechanism of action based on the inhibition of the... (Review)
Review
The latest antifungal drugs introduced for clinical use are echinocandins; they possess a distinctive mechanism of action based on the inhibition of the beta-1,3-D-glucan sintesis, through the damage of the fungal cell wall without impairment of human cells because these do not contain beta-1,3-D-glucan. Among echinocandins, anidulafungin is the last that has received the FDA approval in the USA for the treatment of candidemia in non-neutropenic patients, intra-abdominal abscesses, peritonitis and esofagitis caused by Candida. In Europe, the EMEA has also approved its use for invasive candidiasis in non-neutropenic patients and for candidal esofagitis. The characteristics of anidulafungin are close to those of the ideal antifungal since it has a wide spectrum, is active at low minimal inhibitory concentrations and it is fungicidal for Candida. In addition, it is well tolerated, has few pharmacological interactions, is active intravenously, has a long half life and is auto-biodegradable. Finally, anidulafungin has shown a higher therapeutic efficiency when compared with the conventional treatment of candidemia, since although it is more expensive, the treatment with anidulafungin is highly cost effective.
Topics: Anidulafungin; Antifungal Agents; Candidiasis; Echinocandins; Humans
PubMed: 18473500
DOI: 10.1016/s1130-1406(08)70023-8 -
International Journal of Antimicrobial... Jan 2020Evidence supporting the use of an echinocandin alone as an alternative agent for the treatment of Pneumocystis jirovecii pneumonia (PCP) is limited and controversial....
Evidence supporting the use of an echinocandin alone as an alternative agent for the treatment of Pneumocystis jirovecii pneumonia (PCP) is limited and controversial. This retrospective cohort study was conducted at National Taiwan University Hospital from 1 July 2015 to 31 December 2017. Using multivariable Cox regression analyses, the outcomes of patients receiving trimethoprim/sulfamethoxazole (TMP-SMZ) or anidulafungin single therapy as an alternative treatment for PCP were investigated. A total of 207 patients with PCP were screened and 170 patients were included in the final analysis, among whom 134 (78.8%) received TMP-SMZ and 36 (21.2%) received anidulafungin as alternative anti-PCP treatment. Overall 60-day mortality was 34.1% (58/170), and 60-day mortality did not differ significantly between the anidulafungin group (38.9%; 14/36) and the TMP-SMZ group (32.8%; 44/134) (P = 0.554). Age ≥60 years [hazard ratio (HR) = 1.840, 95% confidence interval (CI) 1.039-3.259; P = 0.036] and HIV infection (HR = 0.102, 95% CI 0.013-0.771; P = 0.027) independently predicted 60-day mortality. Patients with lower SpO/FiO ratio (HR = 0.994, 95% CI 0.990-0.998; P = 0.005) showed a higher 60-day mortality. In the Kaplan-Meier survival analysis, anidulafungin as alternative anti-PCP treatment was not correlated with higher mortality (P = 0.605). Using TMP-SMZ or anidulafungin as alternative anti-PCP treatment had similar 60-day mortality. These findings suggest that anidulafungin therapy may be an effective and alternative treatment for PCP in patients who cannot tolerate TMP-SMZ.
Topics: Adult; Aged; Aged, 80 and over; Anidulafungin; Antifungal Agents; Cohort Studies; Echinocandins; Female; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Taiwan; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult
PubMed: 31622654
DOI: 10.1016/j.ijantimicag.2019.10.001 -
Antimicrobial Agents and Chemotherapy Jul 2019A two-compartment pharmacokinetic (PK) population model of anidulafungin was fitted to PK data from 23 critically ill patients (age, 65 years [range, 28 to 81 years];...
A two-compartment pharmacokinetic (PK) population model of anidulafungin was fitted to PK data from 23 critically ill patients (age, 65 years [range, 28 to 81 years]; total body weight [TBW], 75 kg [range, 54 to 168 kg]). TBW was associated with clearance and incorporated into a final population PK model. Simulations suggested that patients with higher TBWs had less-extensive MIC coverage. Dosage escalation may be warranted in patients with high TBWs to ensure optimal drug exposures for treatment of and infections.
Topics: Adult; Aged; Aged, 80 and over; Anidulafungin; Antifungal Agents; Body Weight; Candida albicans; Candida glabrata; Candidiasis; Critical Illness; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Models, Biological
PubMed: 31061150
DOI: 10.1128/AAC.00378-19 -
The Journal of Antimicrobial... May 2022Increased fluconazole and echinocandin resistance in Candida glabrata requires prompt detection in routine settings. A phenotypic test based on the EUCAST E.DEF 7.3.2...
BACKGROUND
Increased fluconazole and echinocandin resistance in Candida glabrata requires prompt detection in routine settings. A phenotypic test based on the EUCAST E.DEF 7.3.2 protocol was developed for the detection of fluconazole- and anidulafungin-resistant isolates utilizing the colorimetric dye XTT.
METHODS
Thirty-one clinical C. glabrata isolates, 11 anidulafungin resistant and 14 fluconazole resistant, were tested. After optimization studies, 0.5-2.5 × 105 cfu/mL of each isolate in RPMI 1640 + 2% d-glucose medium containing 100 mg/L XTT + 0.78 μΜ menadione and 0.06 mg/L anidulafungin (S breakpoint) or 16 mg/L fluconazole (I breakpoint) in 96-well flat-bottom microtitration plates were incubated at 37°C for 18 h; we also included drug-free wells. XTT absorbance was measured at 450 nm every 15 min. Differences between the drug-free and the drug-treated wells were assessed using Student's t-test at different timepoints. ROC curves were used in order to identify the best timepoint and cut-off.
RESULTS
The XTT absorbance differences between fluconazole-containing and drug-free wells were significantly lower for the resistant isolates compared with susceptible increased exposure isolates (0.08 ± 0.05 versus 0.25 ± 0.06, respectively, P = 0.005) at 7.5 h, with a difference of <0.157 corresponding to 100% sensitivity and 94% specificity for detection of resistance. The XTT absorbance differences between anidulafungin-containing and drug-free wells were significantly lower for the resistant isolates compared with susceptible isolates (0.08 ± 0.07 versus 0.200 ± 0.03, respectively, P < 0.001) at 5 h, with a difference of <0.145 corresponding to 91% sensitivity and 100% specificity, irrespective of underlying mutations.
CONCLUSIONS
A simple, cheap and fast phenotypic test was developed for detection of fluconazole- and anidulafungin-resistant C. glabrata isolates.
Topics: Anidulafungin; Antifungal Agents; Candida glabrata; Drug Resistance, Fungal; Echinocandins; Fluconazole; Humans; Microbial Sensitivity Tests
PubMed: 35323941
DOI: 10.1093/jac/dkac075