Echinocandins provided optimal first-line antifungal treatment for invasive candidiasis infection, according to findings published in the International Journal of Antimicrobial Agents.
Researchers conducted a systematic review and network meta-analysis of the literature, identifying 2689 potential studies for inclusion within PubMed and Scopus databases. The final analysis comprised 13 randomized controlled trials representing 3632 patients with invasive candidiasis infection, all of whom received systemic antifungal treatment. All included studies were published between 1996 and 2020. The researchers compared the safety, efficacy, and the incidence of adverse events among the antifungal agents used in the trials. They also assessed the overall treatment response to each agent, defined as the rate of mycologic eradication and clinical cure, as well as the rate of recurrent infection within the follow-up period.
Of patients included in the final analysis (N=3632), the median age was 63.4 (IQR, 16-97) years, 57% were men, 39.6% were previously treated with antibiotics, and 51% previously had a central venous catheter. The most common comorbidities included neutropenia in 16.8% of patients, cancer in 15.3%, and diabetes in 13.8%. In regard to causative pathogens of candidiasis among the patients, the most common species were Candida albicans (~41%), followed by C tropicalis (15%), C parapsilosis (~12%), C glabrata (11%), and C krusei (<5%).
The 13 trials assessed the safety and efficacy of different dosages of antifungals, including echinocandins such as anidulafungin, caspofungin, micafungin and rezafungin; and azoles such as fluconazole and isavuconazole. Both the conventional and liposomal versions of amphotericin B were also assessed.
The researchers classified the overall quality of the 13 trials as moderate, with 12 demonstrating a high risk of bias.
Results showed that a 150-mg dose of caspofungin was the most efficacious treatment for invasive candidiasis infection in terms of both overall (clinical and microbiologic) and microbiologic responses, with probability of success rates of 72% and 75%, respectively. For patients who received a 100-mg dose of micafungin, the probability of overall treatment success was 65% and the probability of microbiologic success was 75%. They also assessed the effects of rezafungin, an echinocandin currently under development. Of patients who received rezafungin, the probability of overall and microbiologic treatment success was 65% and 54%, respectively. Fluconazole and isavuconazole demonstrated the lowest probability of overall and microbiologic success, with response rates of 17% and 8%, respectively.
The rate of treatment discontinuation secondary to adverse effects and invasive candidiasis recurrence did not statistically significantly differ among the assessed antifungal agents. Of note, the lowest rates of discontinuation were observed among patients who received either rezafungin, capsofungin, or micafungin (<45% for each).
The likelihood of treatment discontinuation due to impaired liver function was increased among patients who received conventional amphotericin B compared with those who received caspofungin (odds ratio, 0.08; 95% CI, 0.00-0.95). Amphotericin B and fluconazole were observed to increase the risk for abnormal liver function by 87% and 68%, respectively, whereas caspofungin was the safest treatment option.
When combining both efficacy and safety profiles for each antifungal treatment, caspofungin, micafungin, and rezafungin were the most efficacious against invasive candidiasis infection (>60% for each).
Limitations included the use of only 2 databases for the literature search, and the variability of efficacy endpoints. Other limitations included heterogeneity, potential bias, and the low quality of reporting among some of the included trials.
The researchers noted that “this evidence should be further investigated in well-designed clinical trials with standard outcomes.” They concluded “evaluations should be performed to strengthen the evidence on the benefits of these drugs and guide the decision-making process.”
Domingos EL, Vilhena RO, Santos JMMF, et al. Comparative efficacy and safety of systemic antifungal agents for candidemia: A systematic review with network meta-analysis and multicriteria acceptability analyses. Int J Antimicrob Agents. Published online June 9, 2022. doi:10.1016/j.ijantimicag.2022.106614