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Multicenter Study
. 2021 Aug;23(4):e13608.
doi: 10.1111/tid.13608. Epub 2021 May 3.

Breakthrough invasive fungal infection after liver transplantation in patients on targeted antifungal prophylaxis: A prospective multicentre study

Matteo Rinaldi  1 , Michele Bartoletti  1   2 , Alberto Ferrarese  3 , Erica Franceschini  4 , Caterina Campoli  1 , Simona Coladonato  1 , Renato Pascale  1 , Sara Tedeschi  1   2 , Milo Gatti  2 , Monica Cricca  5 , Simone Ambretti  4 , Antonio Siniscalchi  6 , Maria Cristina Morelli  7 , Matteo Cescon  2   8 , Umberto Cillo  9 , Fabrizio Di Benedetto  10 , Patrizia Burra  3 , Cristina Mussini  4 , Francesco Cristini  11 , Russell Lewis  1   2 , Pierluigi Viale  1   2 , Maddalena Giannella  1   2
Affiliations
Multicenter Study

Breakthrough invasive fungal infection after liver transplantation in patients on targeted antifungal prophylaxis: A prospective multicentre study

Matteo Rinaldi et al. Transpl Infect Dis. 2021 Aug.

Abstract

Objective: To investigate the rate of and the risk factors for breakthrough-IFI (b-IFI) after orthotopic liver transplantation (OLT) according to the new definition proposed by Mycoses-Study-Group-Education-and-Research-Consortium (MSG-ERC) and the European-Confederation-of-Medical-Mycology (ECMM).

Methods: Multicenter prospective study of adult patients who underwent OLT at three Italian hospitals, from January 2015 to December 2018. Targeted antifungal prophylaxis (TAP) protocol was developed and shared among participating centers. Follow-up was 1-year after OLT. B-IFI was defined as infection occurring during exposure to antifungal prophylaxis. Risk factors for b-IFI were analyzed among patients exposed to prophylaxis by univariable analysis.

Results: We enrolled 485 OLT patients. Overall compliance to TAP protocol was 64.3%, 220 patients received antifungal prophylaxis, 172 according to TAP protocol. Twenty-nine patients were diagnosed of IFI within 1 year after OLT. Of them, 11 presented with b-IFI within 17 (IQR 11-33) and 16 (IQR 4-30) days from OLT and from antifungal onset, respectively. Then out of 11 patients with b-IFI were classified as having high risk of IFI and were receiving anti-mould prophylaxis, nine with echinocandins and one with polyenes. Comparison of patients with and without b-IFI showed significant differences for prior Candida colonization, need of renal replacement therapy after OLT, re-operation, and CMV infection (whole blood CMV-DNA >100 000 copies/mL). Although non-significant, a higher rate of b-IFI in patients on echinocandins was observed (8.2% vs 1.8%, P = .06).

Conclusions: We observed 5% of b-IFI among OLT patients exposed to antifungal prophylaxis. The impact of echinocandins on b-IFI risk in this setting should be further explored.

Keywords: antifungal prophylaxis; breakthrough IFI; infection risk; invasive fungal infection; liver transplantation.

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Conflict of interest statement

Authors have no conflict of interest related to the present study.

Figures

FIGURE 1
FIGURE 1
Study flow‐chart
FIGURE 2
FIGURE 2
Kaplan‐Meier curves of cumulative risk of b‐IFI among low (panel a) and high‐risk (panel b) patients according to the antifungal prophylaxis
See this image and copyright information in PMC

References

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