Adverse effects of antifungal therapies in invasive fungal infections: review and meta-analysis

Abstract

Amphotericin B is the main therapeutic agent for the treatment of invasive fungal infections; however, it is associated with significant toxicities that limit its use. Other systemic antifungal agents have been developed to improve tolerability while maintaining the efficacy profile of conventional amphotericin B. Fifty-four studies involving 9,228 patients were assessed for the frequency of adverse effects of the main systemic antifungal agents. While the results suggest that liposomal amphotericin B is the least nephrotoxic of the lipid formulations (14.6%), that conventional amphotericin B is the most nephrotoxic (33.2%), and that itraconazole is the most hepatotoxic (31.5%), the lack of standard definitions of antifungalrelated adverse effects limits the validity of these results. Furthermore, heterogeneous patient pools and differing protocols make it difficult to draw direct comparisons between studies. With the advent of newer classes of systemic antifungal agents, future trials should conform to definitions that are universally applicable and clinically relevant to allow for such comparisons and to enable evidence-based decision-making.

<p>Epidemiology and Mortality-Associated Factors of Invasive Fungal Disease in Elderly Patients: A 20-Year Retrospective Study from Southern China</p>

“…These reasons could explain the difference in the incidence of adverse effects in our study and previous reports. 29,30 The all-cause mortality in elderly patients with IFD is extremely high. In consistent with previous reports, 9 neutropenia, prolonged use of GC and immunosuppressants were significant in non-survivors with invasive mold infection.…”

Adverse effects of amphotericin B in children; a retrospective comparison of conventional and liposomal formulations

“…In addition, there are various strategies relating to drug administration that can reduce the risk of adverse effects. These include sodium pre-infusion, routine premedication with an antihistamine and antipyretic, rationalizing concomitant nephrotoxic drugs and administration of c-amB as an extended or continuous infusion [6,[18][19][20]. The routine use of these strategies when administering c-amB is not included in any guideline and was not standard practice at our institution during the study period.…”

“…Randomized controlled trials and meta-analyses have reported no significant difference in the frequency of hypokalaemia between c-amB and l-amB [9,23,24]. However, there is substantial heterogeneity in the definition of hypokalaemia between studies [9,20]. Previously, studies have been limited by using end-of-treatment potassium as a marker of treatment-associated hypokalaemia.…”

“…Hepatotoxicity due to amphotericin B treatment is idiosyncratic and may relate to a combination of genetic predisposition and direct cell membrane damage, though this is difficult to clinically differentiate from liver damage due to fungal infection or an underlying comorbidity [26][27][28]. Amphotericin-associated hepatotoxicity is usually mild and infrequent [20,28,29]. No significant difference in the rate of hepatotoxicity between conventional and liposomal formulations in both paediatric and adult studies have been reported (10-17% for c-amB, 14-18% for l-amB) [9,12,20].…”

“…Amphotericin-associated hepatotoxicity is usually mild and infrequent [20,28,29]. No significant difference in the rate of hepatotoxicity between conventional and liposomal formulations in both paediatric and adult studies have been reported (10-17% for c-amB, 14-18% for l-amB) [9,12,20]. By contrast, the patients in this study treated with l-amB were significantly more likely to experience hepatotoxicity compared with c-amB (82.8% vs. 55.6%).…”