Prophylaxis Of Candida Infections Research Articles

Micafungin

Intravenous micafungin (Mycamine®; Fungard®), an echinocandin, is approved in the EU for the treatment of adult (aged ≥ 16 years) and paediatric patients with invasive candidiasis and for the treatment of adult patients with oesophageal candidiasis. It is also approved in the EU as prophylactic treatment to prevent Candida infections in adult and paediatric patients undergoing haematopoietic stem cell transplant (HSCT) or patients who are expected to have neutropenia for ≥ 10 days. This article reviews the therapeutic use of micafungin for the treatment and prophylaxis of Candida infections in adult and paediatric patients, focusing on approved indications in Europe, and briefly discusses the pharmacology of the drug. Micafungin shows very good in vitro activity against clinically relevant isolates of Candida spp., with a low propensity to be associated with the emergence of resistant isolates. The drug has a convenient once-daily dosage regimen and is associated with relatively few drug-drug interactions. In large, multinational trials in adult and/or paediatric patients with invasive candidiasis, micafungin was noninferior to intravenous caspofungin or liposomal amphotericin B. In similarly designed trials in adult patients with oesophageal candidiasis, treatment with micafungin was noninferior to that with intravenous fluconazole or caspofungin. As prophylactic treatment in adult and paediatric patients who had undergone HSCT, micafungin was superior to fluconazole therapy and noninferior to oral itraconazole in large, multicentre trials. Micafungin was generally well tolerated by participants in these clinical trials, given the severe morbidity of the underlying conditions of patients, with a similar tolerability profile to caspofungin and, in general, to fluconazole. It was better tolerated than liposomal amphotericin B or oral itraconazole. Thus, micafungin is a valuable first-line or alternative option to other antifungal agents for the management of candidaemia and invasive candidiasis in adult and paediatric patients, including neonates, and as prophylaxis against fungal infections in patients undergoing HSCT.

Micafungin use in children

Invasive fungal infections (IFIs) are one of the major reasons for morbidity and mortality in immunocompromised children. The majority of IFIs are caused by Candida and Aspergillus species. Early diagnosis and prompt initiation of appropriate antifungal therapy is essential for favorable outcome. Micafungin is a member of the echinocandins, a novel class of antifungal agents that target the biosynthesis of β-1,3-D-glucan, a key fungal cell wall component. It has concentration-dependent fungicidal activity against Candida species and fungistatic activity against Aspergillus species. Although optimal dosing of micafungin in children has not been established, the recommended dosage in children is 2 mg/kg/day (100 mg/day if >40 kg bodyweight) for invasive candidiasis, 1 mg/kg/day (50 mg/day if >40 kg bodyweight) for the prophylaxis of Candida infections in patients with anticipated prolonged and severe neutropenia or in allogeneic hematopoietic stem cell transplantation recipients. Micafungin has a favorable safety and drug–drug interaction profile. The most common adverse effects in children are diarrhea, epistaxis, abdominal pain, headache, nausea, vomiting, fever, chills, elevation of alanine aminotransferase/aspartate aminotransferase values, hypokalemia, thrombocytopenia, mucositis, and rash. Because of its different mechanisms of action, micafungin shows promise as part of the prophylactic and therapeutic management of IFIs, but larger prospective and comparative trials are needed for widespread use in children.

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.

Very-low-birth-weight infants, prophylactic micafungin or fluconazole

Sir, I read with great interest the article by Grover in a previous issue of the journal.[1] The author states that micafungin is approved for prophylaxis of candida infections in patients undergoing hematopoietic stem cell transplant (HSCT). It is not the only the use of prophylactic micafungin, but also it also prevents candida infection in very-low-birth-weight preterm neonates. The authors support the idea of micafungin as a second-line treatment after failure with fluconazole. However, both drugs have been assessed and the comparison in prophylaxis is favorable to micafungin.[2] The pharmacokinetic profile of micafungin in very-low-birth-weight preterms has been studied, and its safety and efficacy in that population has been confirmed.[3] As it has been reported, the efficacy of micafungin in the clearance of candida infection compared with fluconazole is favorable to micafungin.[4] Therefore, we should recognize that micafungin is at least an alternative to fluconazole as the preferred drug for antifungal prophylaxis in very-low-birth-weight preterm patients.

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.

Prophylaxis of Candida infections in adult trauma and surgical intensive care patients: a systematic review and meta-analysis

To determine whether systemic antifungal prophylaxis decreases infectious morbidity and mortality in nonneutropenic, critically ill, trauma and surgical intensive care unit (ICU) adult patients. Systematic review and meta-analysis of randomized clinical trials. We used a fixed effect model, with risk ratio (RR) and 95% confidence intervals (CI). Patients admitted to ICU after surgery or trauma, with multiple risk factors for fungal infections. Nine studies (seven double blind) with a total of 1,226 patients compared ketoconazole (three) or fluconazole (six) to placebo (eight) or no treatment (one). Prophylaxis with azole was associated with reduced rates of candidemia (RR 0.30, 95% CI 0.10-0.82), mortality attributable to Candida infection (RR 0.25, 95% CI 0.08-0.80), and overall mortality (RR 0.60, 95% CI 0.45-0.81). Time to event analysis showed a significantly lower probability of fungal infections in treated patients. There was no evidence of statistical heterogeneity between studies, and publication bias assessment gave a negative results. There was, however, wide variability in the definition and reporting of some relevant clinical outcomes (e.g., confirmed or suspected infections, colonization) and pooling of these outcome measures was not feasible. Prophylaxis of candidal infection among critically ill ICU patients has beneficial effect on certain outcome measures, but additional data from well designed clinical trials and long-term epidemiological observations are needed to provide firm recommendations for the selection of subgroups of patients who would most benefit from prophylaxis and to determine the effect of prophylaxis on fungal resistance patterns.

Prophylaxis of Candida infections in transplanted patients.

Prophylaxis of Candida infections in transplanted patients.

What's New in Fungal Infection in Leukemic Patients

Fungal infections have become an important cause of mortality in patients with hematological malignancies. In recent years, fungi such as Candida tropicalis, Aspergillus spp, Fusarium spp and Trichosporon spp have emerged as important pathogens. Amphotericin B remains the antifungal agent with the broadest spectrum of activity, although some of the newer pathogens may be resistant. The administration of this drug in lipid vehicles reduces the toxicities, permitting the administration of higher doses that may be more effective. The new agents, fluconazole and itraconazole, have activity against some fungal pathogens, although their role in therapy has not been fully determined. Fluconazole has been shown to be effective for prophylaxis of Candida infections.