Safety Of Antifungal Agents Research Articles

Efficacy and Safety of Prophylactic Antifungal Agents in Preventing Invasive Fungal Infection and Mortality among Infants Weighing Less than 1500 Grams: A Meta-analysis

Background. Preterm infants with very low birth weight are at increased risk of invasive fungal infections. Preventive strategies are needed to improve their clinical course and survival.
 Objectives. To assess the efficacy and safety of antifungal agents as prophylaxis in controlling invasive fungal infection and mortality in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants in neonatal intensive care units.
 Methods. We searched MEDLINE (PubMed), Cochrane databases, Google Scholar, Trip database, Herdin, and ClinicalTrials.gov without language restriction and publications from January 1988 to May 2021. We included randomized controlled trials or controlled clinical trials that compared the effect of prophylactic oral or systemic antifungal agents versus placebo in preterm infants < 37 weeks age of gestation and with birth weight lower than 1500 grams. We conducted a meta-analysis using RevMan 5.4.1 and certainty of evidence rating using GRADEpro software.
 Results. A total of 14 studies (including 3,001 preterm infants with VLBW) were included. We found that prophylactic use of nystatin significantly reduced the incidence of invasive fungal infections (IFI) (pooled RR 0.16; 95% CI 0.11, 0.23; 4 RCTs, N = 1295; P < 0.00001; moderate certainty evidence) in preterm infants compared to placebo but had no significant effect on the mortality (RR 0.87; 95% CI 0.62, 1.23; 4 RCTs, N = 1295; P = 0.43; low certainty evidence). Similarly, fluconazole decreased the incidence of IFI (RR 0.38; 95% CI 0.28, 0.53; P = 0.02) and showed statistically significant reduction in mortality (RR 0.78; 95% CI 0.61, 0.99; RCTs, N = 1484; P = 0.04; high certainty evidence). The comparison of the two antifungals showed a trend favoring fluconazole, however the difference was not statistically significant in decreasing IFI (RR 1.60; 95% CI 0.68, 3.77; P = 0.28) and mortality (RR 1.62; 95% CI 0.76, 3.45; P = 0.21).
 Conclusion. Administration of antifungal prophylaxis proves to be beneficial and can probably decrease invasive fungal infection and mortality. The evidence showed that Fluconazole is superior as antifungal prophylaxis compared to placebo while there is no significant difference between fluconazole and nystatin in decreasing fungal infection and mortality among preterm neonates.

Comparative Efficacy and Safety of Antifungal Agents in the Prophylaxis of Oropharyngeal Candidiasis among HIV-Infected Adults: A Systematic Review and Network Meta-Analysis

The objective of the study was to compare the efficacy and safety of antifungal agents used in the prevention of oropharyngeal candidiasis among HIV-infected adults. A systematic search was conducted in four databases (MEDLINE, Scopus, CENTRAL, and Embase) for eligible randomized control trials (RCTs). The network meta-analyses (NMA) were performed using a random-effects model. Interventions were ranked based on the efficacy and safety using the surface under the cumulative ranking curve (SUCRA). The quality of evidence was assessed using the GRADE approach. From a total of 1574 studies screened, 7 RCTs comprising 959 participants were included in NMA. The use of fluconazole as a prophylactic agent was associated with a significant reduction in incidence of OPC compared to placebo (RR, 0.45 (95% CI: 0.27–0.77)) in HIV-infected adults. The overall quality of evidence was graded as moderate. Fluconazole was ranked the best antifungal for efficacy (SUCRA—95.6%) as well as safety (SUCRA—39.3%) in HIV-infected adults. Overall, the quality of evidence was graded as moderate. Fluconazole can be considered as an effective agent with a better safety profile for the prophylaxis of OPC in HIV-infected adults. However, similar to any other antimicrobial agent, the risk of possibility of resistance must be weighed against the benefits.

The effects of antifungal therapy on the recurrence of aspergillus infection after pulmonary aspergilloma resection: a study protocol for a single-center, prospective, non-blind, randomized, 24-month, parallel group study

BackgroundIn recent years, the incidence of pulmonary aspergilloma has increased. The harm of aspergilloma is life-threatening massive hemoptysis, and the conventional treatment is surgical treatment. However, whether the antifungal treatment after surgery is required and the course of treatment before and after surgery are still unclear.MethodsIn this study, patients with pulmonary aspergilloma confirmed pathologically after surgery will be selected as subjects to conduct a single-center, randomized, parallel grouping, prospective, 2-year clinical study. Through regular visits, the recurrence of aspergillus infection, quality of life, lung function indicators, safety of antifungal therapy and other indicators were recorded to evaluate the recurrence risk of aspergillus infection and safety of antifungal agents. Cox proportional risk regression model was used to analyze the influencing factors of antifungal therapy on aspergillus infection recurrence after aspergillus bulbectomy. Cox multiple regression model was used for optimal model fitting, and regression coefficient (β), relative risk (RR) and 95% confidence interval of RR were calculated.DiscussionThe study will explore whether antifungal therapy could improve the quality of life, reduce the recurrence of aspergillus infection, and ultimately improve the prognosis of patients with aspergilloma. The study results will provide high-quality evidence-based medical evidence for the formulation, revision and optimization of international and domestic clinical guidelines and expert consensus on chronic aspergillus lung disease, effectively improve the clinical treatment effect of aspergilloma, and form the latest concept of diagnosis and treatment of aspergilloma.Trial registration: The trial was registered on the Chinese Clinical Trial Registry website (https://www.chictr.org.cn/showprojen.aspx?proj=33231). Registration number: ChiCTR1800019990.

Antifungal agents in preventing oral candidiasis in clinical oncology: A network meta-analysis.

This review examined the comparative efficacy and safety of antifungal agents in preventing oral candidiasis among patients on cancer treatment. We performed a systematic review and network meta-analysis based on randomised controlled trials that compared antifungal agents to placebo or other antifungal agents used in patients undergoing cancer treatment. Relative ranking of antifungal agents was evaluated with surface under the cumulative ranking (SUCRA) probability score. A total of 20 randomised controlled trials (3,215 participants) comparing 11 interventions were included. Compared with placebo, clotrimazole was ranked the best agent for preventing the incidence of oral candidiasis (risk ratio (RR), 0.21 [95% CI 0.08 to 0.55]; SUCRA=0.89). Fluconazole was ranked the safest among other antifungal agents (SUCRA=0.80), whereas clotrimazole (SUCRA=0.36) and amphotericin B (SUCRA=0.18) were ranked low for safety. Amphotericin B was associated with highest risk of adverse events (RR, 3.52 [95% CI 1.27 to 9.75]). Clotrimazole is the most effective in preventing oral candidiasis, whereas fluconazole has the most favourable risk-benefit profile in patients undergoing cancer treatment. However, we are unable to recommend clotrimazole as the best choice to prevent oral candidiasis due to unavailability of studies comparing clotrimazole with other antifungal agents.

Pharmacokinetics of antifungal agents in children

Invasive fungal infections in immunocompromised children are common and often fatal. The first antifungal agents such as amphotericin B and fluconazole offered effective treatment, but their use was often limited by toxicity and resistance. Numerous new antifungal agents have since been developed and appear to be as effective. Most dosing and safety trials have been done in adults, and extrapolation of this data to children has proven inadequate. We reviewed the literature regarding the pharmacokinetics/pharmacodynamics (PK/PD) and safety of antifungal agents with an emphasis on the newer azoles and echinocandins. From a small but growing number of PK/PD trials, better dosing guidelines have been developed.