Prevention Of Invasive Candidiasis Research Articles

Dectin-1 Facilitates IL-18 Production for the Generation of Protective Antibodies Against Candida albicans.

Invasive candidiasis (IC) is one of the leading causes of death among immunocompromised patients. Because of limited effective therapy treatment options, prevention of IC through vaccine is an appealing strategy. However, how to induce the generation of direct candidacidal antibodies in host remains unclear. Gpi7 mutant C. albicans is an avirulent strain that exposes cell wall β-(1,3)-glucans. Here, we found that vaccination with the gpi7 mutant strain could protect mice against invasive candidiasis caused by C. albicans and non-albicans Candida spp. The protective effects induced by gpi7 mutant relied on long-lived plasma cells (LLPCs) secreting protective antibodies against C. albicans. Clinically, we verified a similar profile of IgG antibodies in the serum samples from patients recovering from IC to those from gpi7 mutant-vaccinated mice. Mechanistically, we found cell wall β-(1,3)-glucan of gpi7 mutant facilitated Dectin-1 receptor dependent nuclear translocation of non-canonical NF-κB subunit RelB in macrophages and subsequent IL-18 secretion, which primed protective antibodies generation in vivo. Together, our study demonstrate that Dectin-1 engagement could trigger RelB activation to prime IL-18 expression and established a new paradigm for consideration of the link between Dectin-1 mediated innate immune response and adaptive humoral immunity, suggesting a previously unknown active vaccination strategy against Candida spp. infection.

Optimization of Dosage Regimen of Rezafungin against <i>Candida spp. </i>Based on Pharmacokinetic/Pharmacodynamic Analysis

Invasive candidiasis was the most common nosocomial fungal infection with high morbidity and mortality, which is mainly occurring in immunodeficiency and critical patients. Echinocandins were recommended as first-line drugs for the treatment and prevention of invasive candidiasis. In our study, we aimed to optimize the dosage of Rezafungin against Candida spp. based on pharmacokinetic/pharmacodynamics (PK/PD) analysis. We collected the published data about pharmacokinetic parameters of rezafungin and the MIC distribution of Candida spp. on rezafungin. Monte Carlo simulation was used to calculate probability of target attainment and a cumulative fraction of response to assess the best dosing regimen. The optimal dosage regimen for C. albicans and C. glabrata was 50 mg IV, and the optimal dosage regimen for C. parapsilosis was 100 mg IV. Lastly, rezafungin has an excellent antifungal effect on C. albicans, C. glabrata and C. parapsilosis.

Colombian consensus on the diagnosis, treatment, and prevention of Candida Spp. disease in children and adults*,+

Invasive Candidiasis (IC) and candidemia (as its most frequent manifestation) have become the main cause of opportunistic mycosis at hospital settings. This study, made by members of the Colombian Association of Infectious Diseases (ACIN), was aimed at providing a set of recommendations for the management, follow-up and prevention of IC / candidemia and mucous membrane candida infection in adult, pediatric and neonatal patients in a hospital setting, including the hemato-oncological and critical care units. All the data obtained through an exhaustive search were reviewed and analyzed in a comprehensive manner by all the members of the group, and the recommendations issued are being made after a careful review of the scientific literature available and the consensus of all specialists involved; the emergence of Candida Spp. problem is highlighted and a correct orientation to health professionals regarding the management of patients with candidiasis is provided in a rational and practical way, emphasizing patient evaluation, diagnostic strategies, prophylaxis, empirical treatment, directed treatment and preventative therapy.

Fluconazole Prophylaxis for the Prevention of Candidiasis in Premature Infants: A Meta-analysis Using Patient-level Data.

Invasive candidiasis (IC) is an important cause of sepsis in premature infants and is associated with a high risk of death and neurodevelopmental impairment. Prevention of IC has become a major focus in very low birth weight infants, with fluconazole increasingly used as prophylaxis. We identified all randomized, placebo-controlled trials evaluating fluconazole prophylaxis in premature infants conducted in the United States. We obtained patient-level data from the study investigators and performed an aggregated analysis. The occurrence of each endpoint in infants who received prophylaxis with fluconazole vs placebo was compared. Endpoints evaluated were IC or death, IC, death, Candida colonization, and fluconazole resistance among tested isolates. Safety endpoints evaluated included clinical and laboratory parameters. Fluconazole prophylaxis reduced the odds of IC or death, IC, and Candida colonization during the drug exposure period compared with infants given placebo: odds ratios of 0.48 (95% confidence interval [CI], .30-.78), 0.20 (95% CI, .08-.51), and 0.28 (95% CI, .18-.41), respectively. The incidence of clinical and laboratory adverse events was similar for infants who received fluconazole compared with placebo. There was no statistically significant difference in the proportion of tested isolates that were resistant to fluconazole between the fluconazole and placebo groups. Fluconazole prophylaxis is effective and safe in reducing IC and Candida colonization in premature infants, and has no impact on resistance.

Human milk oligosaccharides: potential use in prevention of invasive candidiasis (623.6)

In premature infants, the opportunistic fungal pathogen Candida albicans is a leading cause of life‐threatening infections; the primary site for invasion being the intestine. The goal of this study was to test the hypothesis that Human Milk Oligosaccharides (HMOs) protect premature intestinal epithelial cells (IEC) from invasion by C. albicans. We used H4 cells, an established, primary, human fetal IEC line and measured fungal invasion immunohistochemically. The presence of HMOs, at concentrations present in human milk, resulted in an ~60% reduction in fungal invasion of H4 cells (p<0.05). Further, the HMO effect on invasion followed a dose‐response relationship. At slightly higher than physiologic concentrations, HMOs decreased the ability of C. albicans to make contact with H4 cells (p<0.05). In addition, at physiologic concentrations and above, HMOs reduced the overall lengths of C. albicans hyphae (p<0.05), the morphology associated with tissue invasion and injury. HMOs did not, however, reduce overall C. albicans growth rates in liquid or on solid growth media. In conclusion, HMOs decrease the ability of C. albicans to invade H4 cells, supporting a protective role for HMOs in the premature intestine. We speculate that this function of HMOs is attributed to their negative effect on C. albicans hyphal growth as well as blockade of physical interactions between host and fungal cells.

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.

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.

Prevention of invasive fungal infections in patients with neoplastic disease.

Invasive fungal infections are important causes of morbidity and mortality among patients with neoplastic diseases, particularly those with protracted granulocytopenia, those receiving corticosteroids, and those undergoing allogeneic bone marrow transplantation. These mycoses are often difficult to diagnose early, and their treatment is frequently unsuccessful. Antifungal compounds have been used in studies of a variety of preventive strategies including prophylaxis, early empirical therapy, empirical therapy, and secondary prophylaxis. Among all compounds studied thus far, fluconazole has demonstrated the most promising activity in prevention of invasive candidiasis, particularly in adult allogeneic bone marrow transplant recipients. However, fluconazole does not have activity at currently approved dosages against Candida krusei, Torulopsis glabrata, and most filamentous fungi, including Aspergillus species. Empirically administered amphotericin B significantly decreases the frequency of invasive fungal infections in persistently or recurrently febrile granulocytopenic patients. The use of itraconazole for prevention of aspergillosis warrants study. The current lack of reliable preventive regimens against infections due to Aspergillus and against those due to several emerging fungal pathogens presents an ongoing challenge. The use of recombinant human cytokines, transfusion of effector cells, and administration of newer antifungal compounds are new potential modalities for prevention of invasive mycoses.

PREVENTION OF MYCOSES IN IMMUNOCOMPROMISED PATIENTS

Invasive fungal infections remain a major complication in immunocompromised hosts. The prognosis in these infections is poor, particularly for neutropenic patients with cancer. Candidiasis and aspergillosis are common in these patients, and numerous attempts have been made to evaluate potential prophylactic methods. Despite the fact that various agents (polyenes and/or imidazoles) and various formulations have been tested, the reported data on their effectiveness are still controversial. No single regimen can be recommended at this time for prevention of invasive candidiasis. The potential emergence of fungal strains resistant to the polyenes and the selection of Torulopsis glabrata by the imidazoles should also be taken into consideration. Aspergillosis, which is an airborne infection, may be prevented by isolation of patients at risk in rooms equipped with high-efficiency particulate air (HEPA) filters. In addition, the prophylactic administration of nasal sprays of amphotericin B has shown encouraging results, and this approach should be further investigated.