Candidiasis In Adults Research Articles

Regulatory Considerations in the Approval of Rezafungin (Rezzayo) for the Treatment of Candidemia and Invasive Candidiasis in Adults.

On 22 March 2023, the FDA approved rezafungin (Rezzayo) for the treatment of candidemia and invasive candidiasis in adults with limited or no alternative treatment options. Rezafungin is an echinocandin that supports weekly dosing, enabling outpatient parenteral treatment that potentially avoids the need for a central venous catheter. Approval of rezafungin was based on a single adequate and well-controlled phase 3 study designed with a day 30 all-cause mortality primary end point and 20% noninferiority margin, which demonstrated that rezafungin is noninferior to the comparator echinocandin. Nonclinical studies of rezafungin in nonhuman primates identified a neurotoxicity safety signal; however, rezafungin's safety profile in the completed clinical studies was similar to other Food and Drug Administration-approved echinocandins. Here we describe the rationale for this approval and important considerations during the review process for a flexible development program intended to expedite the availability of antimicrobial therapies to treat serious infections in patients with limited treatment options. Clinical Trials Registration . NCT02734862 and NCT03667690.

Efficacy and acceptability of different anti-fungal interventions in oropharyngeal or esophageal candidiasis in HIV co-infected adults: a pilot network meta-analysis

ABSTRACT Background: Oropharyngeal/esophageal candidiasis are the most common opportunistic infections observed in patients with human immunodeficiency virus (HIV). While the commonly recommended treatment is fluconazole, relapse of oropharyngeal or esophageal candidiasis has been gradually increasing in recent decades. Methods: The current network meta-analysis (NMA) included randomized controlled trials (RCTs) investigating the efficacy and acceptability (i.e. drop-out rate) of different anti-fungal interventions against oropharyngeal or esophageal candidiasis in adults with HIV. All NMA procedures were conducted using the frequentist model. Results: Twenty-seven RCTs and 6277 participants were included. For oropharyngeal candidiasis, photosensitizer-based antimicrobial photodynamic therapy (aPDT) with laser irradiation plus methylene blue was associated with the highest cure rate and the lowest relapse rate among the investigated interventions [odds ratio (OR) = 6.82, 95% confidence intervals (95%CIs) = 0.19 to 244.42, p = 0.293, and OR = 0.03, 95%CIs = 0.00 to 0.77, p = 0.034, compared to fluconazole]. None of the investigated anti-fungal interventions were superior to fluconazole for esophageal candidiasis in respect of cure rates/relapse rates. All investigated anti-fungal interventions were well-accepted. Conclusions: aPDT could be the preferred strategy to manage oropharyngeal candidiasis; however the evidence for esophageal candidiasis still remained inconclusive.

A Regulatory Review Approach for Evaluation of Micafungin for Treatment of Neonatal Candidiasis.

Pathogenesis of neonatal candidiasis (NC) is distinct from systemic candidiasis in adults and older pediatric patients due to the significant incidence of central nervous system involvement in neonates. Thus, although adequate and well-controlled trials in NC are often unfeasible due to difficulty enrolling patients, extrapolation of efficacy from antifungal drug trials in adults is generally not appropriate. However, treatment of NC is an area of great unmet need. We describe a regulatory review approach that combined the assessment of limited clinical efficacy, pharmacokinetics, and safety data from neonates and young infants along with microbiology outcomes and pharmacokinetic data from relevant nonclinical models of candidemia/invasive candidiasis to inform the use of micafungin in pediatric patients younger than 4 months, while communicating areas of remaining uncertainty in labeling.

How do antifungal drugs compare with placebo for preventing oral candidiasis in adults and children undergoing cancer treatment?

How do antifungal drugs compare with placebo for preventing oral candidiasis in adults and children undergoing cancer treatment?

How do antifungals absorbed in the gastrointestinal tract (GI) compare with antifungals partially or not absorbed in the GI tract for preventing oral candidiasis in adults and children undergoing cancer treatment?

How do antifungals absorbed in the gastrointestinal tract (GI) compare with antifungals partially or not absorbed in the GI tract for preventing oral candidiasis in adults and children undergoing cancer treatment?

Efficacy and Tolerability of Micafungin Monotherapy for Candidemia and Deep-Seated Candidiasis in Adults with Cancer

The response rate among 58 patients with cancer and candidemia or deep-seated candidiasis treated with micafungin monotherapy was 81%. Intensive care unit (ICU) stay, concomitant nonfungal infections, and acute kidney injury were significantly associated with the 30-day crude mortality rate. Severe neutropenia was an independent predictor of micafungin failure. The efficacy and safety of micafungin in cancer patients with invasive candidiasis were comparable to those reported for patients without malignancy and for cancer patients treated with caspofungin.

European expert opinion on the management of invasive candidiasis in adults

This report discusses the present status of antifungal therapy and treatment options for candidaemia, considered by experts in the field in Europe. A conference of 26 experts from 13 European countries was held to discuss strategies for the treatment and prevention of invasive candidiasis, with the aim of providing a review on optimal management strategies. Published and unpublished comparative trials on antifungal therapy were analysed and discussed. Commonly asked questions about the management of candidaemia were selected, and possible responses to these questions were discussed. Panellists were then asked to respond to each question by using a touchpad answering system. After the initial conference, the viewpoint document has been reviewed and edited to include new insights and developments since the initial meeting. For many situations, consensus on treatment could not be reached, and the responses indicate that treatment is likely to be modified on a patient-to-patient basis, depending on factors such as degree of illness, prior exposure to azole antifungals, and the presence of potentially antifungal drug-resistant Candida species.

Evidencias científicas que respaldan el uso de micafungina en el tratamiento de la candidiasis invasora

Micafungin is a semisynthetic lipopeptide developed from Coleophoma empetri, which blocks the synthesis of β-1,3-D-glucan, an essential component of the fungal wall, though non-competitive inhibition of β-1,3-D-glucan synthetase. Micafungin is a dose-dependent candidacidal agent with excellent in vitro efficacy against most Candida spp. including species resistant to amphotericin B, such as Candida lusitaniae, several azoles, such as C. glabrata or C. krusei, and isolates not susceptible to other echinocandins. Moreover, this drug is active against Candida biofilms. Micafungin is a first-line drug for the treatment of candidemias and invasive candidiasis in adults and children (including neonates). This drug is approved for use in the treatment of invasive candidiasis and Candida esophagitis, as well as in the prophylaxis of Candida infections in hematopoietic stem cell transplant recipients or those at risk of prolonged neutropenia. Micafungin can be used both in the treatment and prevention of candidiasis in neonates, children, adolescents, adults, and the elderly, making it highly useful in patient groups in which the use of other antifungal drugs has not been authorized.

Multilocus Microsatellite Markers for Molecular Typing of Candida glabrata : Application to Analysis of Genetic Relationships between Bloodstream and Digestive System Isolates

Candida glabrata has emerged as the second most common etiologic agent, after Candida albicans, of superficial and invasive candidiasis in adults. Strain typing is essential for epidemiological investigation, but easy-to-use and reliable typing methods are still lacking. We report the use of a multilocus microsatellite typing method with a set of eight markers on a panel of 180 strains, including 136 blood isolates from hospitalized patients and 34 digestive tract isolates from nonhospitalized patients. A total of 44 different alleles were observed, generating 87 distinct genotypes. In addition to perfect reproducibility, typing ability, and stability, the method had a discriminatory power calculated at 0.97 when all 8 markers were associated, making it suitable for tracing strains. In addition, it is shown that digestive tract isolates differed from blood culture isolates by exhibiting a higher genotypic diversity associated with different allelic frequencies and preferentially did not group in clonal complexes (CCs). The demonstration of the occurrence of microevolution in digestive strains supports the idea that C. glabrata can be a persistent commensal of the human gut.

Canadian Clinical Practice Guidelines for Invasive Candidiasis in Adults

Candidemia and invasive candidiasis (C/IC) are life-threatening opportunistic infections that add excess morbidity, mortality and cost to the management of patients with a range of potentially curable underlying conditions. The Association of Medical Microbiology and Infectious Disease Canada developed evidence-based guidelines for the approach to the diagnosis and management of these infections in the ever-increasing population of at-risk adult patients in the health care system. Over the past few years, a new and broader understanding of the epidemiology and pathogenesis of C/IC has emerged and has been coupled with the availability of new antifungal agents and defined strategies for targeting groups at risk including, but not limited to, acute leukemia patients, hematopoietic stem cell transplants and solid organ transplants, and critical care unit patients. Accordingly, these guidelines have focused on patients at risk for C/IC, and on approaches of prevention, early therapy for suspected but unproven infection, and targeted therapy for probable and proven infection.

Voriconazole: a broad-spectrum triazole for the treatment of invasive fungal infections

Over the last 20 years, the frequency of life-threatening, invasive fungal infections has risen dramatically, corresponding to an increase in the number of immunocompromised patients. Thus, the development of newer, better tolerated, more effective antifungal drugs has become critically important. Voriconazole was the first second-generation triazole to be approved by the US FDA and the EMEA, both in 2002. Voriconazole is currently approved for the treatment of invasive aspergillosis, candidemia, candidal esophagitis and disseminated candidiasis in adults, and serious fungal infections due to Scedosporium apiospermum and Fusarium species. In addition to providing an alternative treatment option for Candida infections and many emerging and refractory invasive fungal infections, voriconazole is currently the treatment of choice for invasive aspergillosis. Voriconazole has excellent in vitro activity against a wide spectrum of yeasts and molds, with only a few notable exceptions. Although it has the potential for some unique and interesting side effects, as well as important drug–drug interactions, the use of therapeutic drug monitoring can be used to optimize its efficacy and safety.

Neonatal liver abscesses due to Candida infection effectively treated with caspofungin

Candidiasis is relatively frequent in neonatal and pediatric intensive care units (ICUs), particularly in preterm infants less than 28 weeks of gestational age. Neonatal candidiasis shows high mortality and is often associated to poor neurodevelopmental prognosis in survivor patients. Amphotericin B and fluconazole are the first choice drugs for the treatment of neonatal candidiasis. Caspofungin is an alternative antifungal agent, which is recommended for invasive candidiasis in adults, but has been poorly experienced in neonates and infants as far as now. We report the first two infants with Candida liver abscesses treated with caspofungin. In the first infant bloodstream and liver lesions were cleared by combination therapy with fluconazole, liposomal amphotericin and caspofungin, while in the second one by caspofungin alone. Our observations confirm the efficacy and tolerability of caspofungin in the treatment of neonatal candidiasis refractory to conventional antifungal drugs. More extensive data are recommended in order to asses a specific neonatal schedule.

Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America.

Guidelines for the management of patients with invasive candidiasis and mucosal candidiasis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections. Since 2004, several new antifungal agents have become available, and several new studies have been published relating to the treatment of candidemia, other forms of invasive candidiasis, and mucosal disease, including oropharyngeal and esophageal candidiasis. There are also recent prospective data on the prevention of invasive candidiasis in high-risk neonates and adults and on the empiric treatment of suspected invasive candidiasis in adults. This new information is incorporated into this revised document.

Micafungin for the prophylaxis and treatment of Candida infections

Invasive fungal infection is a significant cause of morbidity and mortality worldwide. The incidence of these infections is steadily increasing. In addition, strains resistant to many commonly used antifungal agents are becoming more prevalent. Many new antifungals have become commercially available in recent years, which have vastly improved the ability to treat these infections effectively. Micafungin is one of three commercially available echinocandins available for use in the USA. This class of agents possess a unique mechanism of action that helps to reduce toxicity while maintaining potent antifungal activity. Micafungin is currently approved for the treatment of esophageal candidiasis in adults and is the only in its class approved for the prophylaxis of Candida infection in patients who have undergone hematopoietic stem cell transplantation. It was also recently approved in the USA for the treatment of candidemia and other forms of invasive candiaisis (acute disseminated candiaisis, Candida peritonitis and abscess). In general, micafungin is well tolerated and has favorable safety and drug-interaction profiles.

Caspofungine, place dans les stratégies thérapeutiques antifongiques

Caspofungin is an antifungal agent belonging to a new class of antifungal agents, the echinocandins. Its low oral bioavailability leads to a parenteral administration. Caspofungin has in vitro activity against most Candida spp. (including azole-resistant species, regardless of the mechanism of azole resistance) and Aspergillus spp. In France, indications are invasive candidiasis in adults without neutropenia and invasive aspergillosis when amphotericin B deoxycholate, lipid-associated formulations of amphotericin B or itraconazole failed or are associated with serious adverse effects. According to recent trials, it is possible that caspofungin becomes a suitable choice for initial therapy of candidemia or disseminated candidiasis in adults infected with an unspeciated isolate for which fluconazole activity is unknown. Similarly, caspofungin could be used for treatment of invasive aspergillosis, when pulmonary involvement is bilateral and/or rapidly extensive, in combination with voriconazole or lipid-associated formulations of amphotericin B. Finally, its efficacy for empirical antifungal therapy of persistently febrile neutropenic patients has been recently reported. Consequently, such a therapy could represent an alternative to lipid-associated formulations of amphotericin B.

Primary Renal Candidiasis

Candida organisms are common fungal saprophytes of the gastrointestinal tract, oral cavity, and vagina.¹However, if host resistance is altered by chronic disease, malignancy, diabetes mellitus, adrenocorticosteroids, or antibiotics, Candida species may be found in sites normally free of saprophytic infection. When these organisms become systemic invaders of man, they usually produce a fatal, fulminant clinical course with candidemia, fever, hypotension, tachycardia, and invasion of the lungs, heart, and kidney.^2-5On rare occasion, they may become a primary, pathogenic invader of the kidneys without the presence of candidemia or other systemic organ involvement.⁶A total of nine well-documented cases of primary renal candidiasis in adults have been reported since Albers⁷described the first two patients in 1953.^7-13The purpose of this communication is to review the nine previous patients with adult primary renal candidiasis and report two additional patients with very unusual features. Both of our patients had juvenile diabetes, and neither demonstrated generalized systemic candidiasis or candidemia. One patient presented to the hospital after he passed on urination several large fungus balls which consisted of C albicans pseudomycelial elements (Fig 1 and 2). The second patient developed a C albicans perinephric abscess which is believed to be the result of metastatic seeding from a previous C albicans skin abscess. The passage of fungus balls or the occurrence of a perinephric abscess has not been previously observed in primary renal candidiasis. Both patients were treated with intravenous doses of amphotericin B, and both have survived for a long interval with no evidence of recurrent C albicans infection.

Disseminated Moniliasis.

s1 April 1963Disseminated Moniliasis.D. B. Louria, M.D.D. B. Louria, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-58-4-738_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptReports of systemic candidiasis in adults (excluding subacute monilial endocarditis) have increased markedly during the past 10 years. Experimental studies on mice performed in this laboratory and our observations on 30 patients with disseminated moniliasis, together with a review of 50 cases recorded by others, permit the following conclusions:1. Predisposing factors include treatment with multiple antibiotics, adrenal gluco-corticoids, or both, the use of indwelling vascular catheters or needles, and probably diabetes. The most frequent manifestations are fever, tachycardia, and clinical deterioration. Severe lethargy, coma, chills, hypotension, a petechial rash, or splenomegaly occur in a minority of patients.2. In... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y. (CS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1963Volume 58, Issue 4Page: 738-739KeywordsCandidiasisCathetersComaEndocarditisFeversHypotensionRashesResearch laboratoriesSplenomegalyTachycardia Issue Published: 1 April 1963 PDF downloadLoading ...