Breakthrough invasive fungal infections in liver transplant recipients exposed to prophylaxis with echinocandins vs other antifungal agents: A systematic review and meta‐analysis

Abstract

Introduction:Although echinocandins are recommended as first-line prophylaxis for high-risk orthotopic liver transplant (OLT) recipients, occurrence of breakthroughinvasive fungal infections (IFIs) remains a serious concern. We aim to assess the risk of breakthrough IFIs among OLT recipients exposed to prophylaxis with echinocandins compared to other antifungals. Materials and methods: Two authors independently searched PubMed-MEDLINE, Embase, study registries and reference lists from inception to March 2021, to retrieve randomised controlled trials (RCTs) or observational studies comparing efficacy and safety of echinocandins vs other antifungals for prophylaxis in OLT recipients. Data were independently extracted from two authors, and the quality of included studies was independently assessed according to ROB 2.0 tool for RCTs and ROBINS-I tool for observational studies. The primary outcome was occurrence of breakthrough IFI at the end of prophylaxis (EOP).Results: 698 articles were screened, and ten studies (3 RCTs and 7 observational) were included. No difference between echinocandins and other antifungals in terms of breakthrough IFIs at the EOP emerged both from RCTs (odds ratio [OR] 0.85, 95% CI 0.24-2.99) and observational studies (OR 1.43, 95% CI 0.28-7.40). No difference emerged also for secondary outcomes. In the subgroup comparison between echinocandins and polyenes, a trend for higher risk of breakthrough IFI at the EOP (OR 4.82, 95% CI 0.97-24.03) was noted.Conclusions: Echinocandins do not seem to be associated with increased risk of breakthrough IFIs in OLT recipients. However, the large diversity in the comparator group hinders a definitive interpretation. Further studies exploring the relationship between echinocandin use and breakthrough IFIs according to specific comparators are warranted.

Prophylaxis of Fungal Infections in Transplant Patients:What has Changed in Recent Years?

“…Similarly, Wang et al, in a recent systematic review and meta-analysis of 69 randomized clinical trials that reported comparisons of 12 treatments with a total of 14,789 patients, concluded that voriconazole would be the best choice for patients undergoing HSCT, thus contrasting with some past studies that gave preference to posaconazole. 53 In any case, as posaconazole is not available in UHS, voriconazole (available for hospital use) is the viable option in Brazil's public health system. 20,28,[30][31][32][33]54 Micafungin may also be a beneficial option for prophylaxis of IFIs in HSCT patients.…”

Profilaxia de Infecções Fúngicas em Pacientes Transplantados: O que Mudou nos Últimos Anos?

“…Da mesma forma, Wang et al, em uma revisão sistemática e metanálise recente sobre 69 ensaios clínicos randomizados que relataram comparações de 12 tratamentos com um total de 14.789 pacientes, concluíram que o voriconazol seria a melhor opção para pacientes submetidos a TCTH, contrastando, dessa forma, com alguns estudos passados que davam preferência ao posaconazol. 53 De qualquer maneira, como não há disponibilidade do posaconazol no SUS, o voriconazol (disponível para uso hospitalar) é a opção viável no sistema público de saúde do Brasil. 20,28,[30][31][32][33]54 A micafungina também pode se apresentar como uma opção benéfica para profilaxia de IFIs em pacientes com TCTH, podendo ser usada em combinação com itraconazol ou fluconazol, e esse consenso não mudou na atualidade.…”

Bring it on: Top five antimicrobial stewardship challenges in transplant infectious diseases and practical strategies to address them

“…47 Echinocandins are associated with fewer toxicities and drug-drug interactions, but there are significant pharmacokinetic-pharmacodynamic limitations. Echinocandins achieve limited therapeutic concentrations intra-abdominally because of their molecular characteristics, 48 predisposing patients to the emergence of echinocandin resistance. 49 An 8% acquired resistance rate 50 and breakthrough invasive fungal infections 48 while on echinocandin therapy have been noted.…”

“…Echinocandins achieve limited therapeutic concentrations intra-abdominally because of their molecular characteristics, 48 predisposing patients to the emergence of echinocandin resistance. 49 An 8% acquired resistance rate 50 and breakthrough invasive fungal infections 48 while on echinocandin therapy have been noted. To help prevent the emergence of fluconazole and echinocandin resistance, AMS programs can assist in optimizing dosing for patients who are critically ill, who require renal replacement therapy, or who have infections at sites of known poor drug penetration.…”

“…To help prevent the emergence of fluconazole and echinocandin resistance, AMS programs can assist in optimizing dosing for patients who are critically ill, who require renal replacement therapy, or who have infections at sites of known poor drug penetration. 47,48 The risk of invasive aspergillosis in high-risk liver recipients is another crucial consideration. 51 The decision to administer antimold coverage involves weighing the local incidence of and a recipient's risk for invasive aspergillosis 52 against potential toxicities, drug-drug interactions, and emergence of azole-resistant Aspergillus.…”