Safety Of Antifungal Prophylaxis Research Articles

A Review of Candida Prophylaxis in the Neonatal Intensive Care Population

To review the efficacy and safety of antifungal prophylaxis in the neonatal intensive care setting. English-language literature was accessed using MEDLINE (January 1988- December 2010). The following Medical Subject Heading (MeSH) search terms were used: "amphotericin B," "fluconazole," "nystatin," "itraconazole," "caspofungin," "voriconazole," "Candida," "prevention and control," and "critically ill." Literature was further limited to studies focusing on patient birth to 6 months of age. Abstracts and original research articles were included. Preference was given to published controlled trials. Articles providing descriptions of the safety and effectiveness of antifungal prophylaxis in neonatal intensive care patients were also used in this review. Twenty-two studies have evaluated the impact of antifungal prophylaxis on Candida colonization or invasive infections in the Neonatal Intensive Care Unit (NICU). The two antifungal agents most commonly studied were nystatin and fluconazole. All of the nystatin studies demonstrated that nystatin is effective at reducing fungal colonization and invasive fungal infections. All of the studies designed to evaluate the impact of fluconazole prophylaxis on fungal colonization demonstrated a reduction in the incidence of fungal colonization with fluconazole prophylaxis. A total of 12 of 16 studies that evaluated the impact of fluconazole prophylaxis on the incidence of invasive fungal infections demonstrated a reduction in invasive fungal infections with fluconazole prophylaxis. Two studies found no difference between fluconazole and nystatin when used for prophylaxis. Antifungal prophylaxis appears to be effective in reducing the incidence of Candida colonization and invasive Candida infections in the NICU. Antifungal prophylaxis also appears to be safe in the NICU population. The impact of antifungal prophylaxis on resistance patterns could be significant and needs to be evaluated long term before widespread prophylaxis can be recommended.

Efficacy and safety of antifungal prophylaxis with oral itraconazole solution among patients receiving corticosteroids: who should be given prophylaxis?

The incidence of systemic fungal infections has risen, as shown by increases in the numbers of immunosuppressed or immunocompromised patients. The consequences of these fungal infections are occasionally serious. However, the efficacy of antifungal prophylaxis in patients receiving corticosteroid treatment has not been well investigated, even though they are susceptible to severe fungal infections. Therefore, we retrospectively evaluated the prophylactic efficacy of an antifungal agent-oral itraconazole solution (ITCZ-OS)-for immunosuppressed patients receiving corticosteroids in a single institution. Of 39 patients, 18 received prophylaxis with ITCZ-OS at a dose of 200mg/day, and 21 did not. As a result, no fungal infections developed in the prophylactic group, but 7 of the 21 patients (33%) in the non-prophylactic group suffered from fungal infections consisting of 3 non-invasive candidiases, 2 invasive candidiases, and 2 invasive pulmonary aspergilloses. Among the non-prophylactic group, aging and hypoalbuminemia were statistically significantly associated with incidence of invasive fungal infections. Of the four patients with invasive fungal infections, three had concomitant chronic illness such as diabetes. Toxicity among the prophylactic group was not statistically significantly different from that of the non-prophylactic group. In addition, none needed discontinuation of the drug. These results indicate the potential antifungal prophylactic effect of ITCZ-OS for a subset of patients treated with moderate or high doses of corticosteroids.

Antifungal prophylaxis in immunocompromised hosts.

To review the literature on the efficacy and safety of antifungal agents for prophylaxis of fungal infections in populations of immunocompromised hosts (key words: hematology-oncology, surgical, solid organ transplant, HIV infection), and to develop guidelines and recommendations regarding safe and effective drug regimens for antifungal prophylaxis in this patient population. Comprehensive review of clinical trials of antifungal prophylaxis published in the English literature, with an emphasis on controlled trials, and discussion of key clinical trials illustrating efficacy and safety of agents for antifungal prophylaxis in immunocompromised patients. Much of the clinical data evaluating the efficacy and safety of antifungal prophylaxis has been generated in cancer patients. The choice of antifungal agent for prophylaxis in this population remains controversial. However, azole compounds such as clotrimazole, ketoconazole and fluconazole appear to be more effective and better tolerated than nystatin suspension. Although ketoconazole has been shown to reduce fungal colonization in surgical patients, current data do not support the routine use of antifungal prophylaxis in this population. In renal transplant recipients, clotrimazole troches have been shown to be more effective than placebo or nystatin suspension. Selective bowel decontamination with nonabsorbable antibiotics and nystatin may be useful in reducing Candida colonization in liver transplant patients but no definitive recommendations may be made at this time regarding optimal antifungal prophylaxis in these patients. In patients with advanced HIV disease or history of prior fungal disease prophylaxis for oropharyngeal candidiasis is indicated, although the agent of choice remains controversial. Fluconazole is the drug of choice for prevention of relapse of cryptococcal meningitis in patients with AIDS. Finally, only limited data exist assessing the relationship between local colonization and systemic fungal infection. Adverse effects associated with antifungal prophylaxis, generally limited to nausea and vomiting and transient elevations in hepatic transaminases, occur with similar frequency among available oral or topical agents. However, the incidence of nausea and vomiting with resultant poor patient tolerance and compliance is usually higher with nystatin. Based on available data from controlled clinical trials, azole agents are currently the most effective and best-tolerated drugs for antifungal prophylaxis in immunocompromised hosts. Choice of one agent in this group over another may be dictated by cost. As new antifungal treatments are released onto the market, these drugs should be compared with existing agents in controlled clinical trials. Future studies should be designed to evaluate the relationship between local colonization and disseminated infection.