Safety and efficacy of non-reduced use of caspofungin in patients with Child-Pugh B or C cirrhosis: a real-world study.

Caspofungin Cirrhosis Efficacy Fungal infection Safety

Journal

Infection
ISSN: 1439-0973
Titre abrégé: Infection
Pays: Germany
ID NLM: 0365307

Informations de publication

Date de publication:
24 Jan 2024
Historique:
received: 18 09 2023
accepted: 17 12 2023
medline: 24 1 2024
pubmed: 24 1 2024
entrez: 24 1 2024
Statut: aheadofprint

Résumé

The need for dose adjustment of caspofungin in patients with hepatic impairment is controversial, especially for those with Child-Pugh B or C cirrhosis. The purpose of this study was to investigate the safety and efficacy of standard-dose caspofungin administration in Child-Pugh B and C cirrhotic patients in a real-world clinical setting. The electronic medical records of 258 cirrhotic patients, including 67 Child-Pugh B patients and 191 Child-Pugh C patients, who were treated with standard-dose of caspofungin at the Second Affiliated Hospital of Chongqing Medical University, China, from March 2018 to June 2023 were reviewed retrospectively. The white blood cells (WBC), hepatic, renal and coagulation function results before administration and post administration on days 7, 14 and 21 were collected, and the efficacy was assessed in all patients at the end of caspofungin therapy. Favorable responses were achieved in 137 (53.1%) patients while 34 (13.2%) patients died. We observed that some patients experienced an increase of prothrombin time (PT) or international normalized ratio (INR), or a decrease of WBC, but no exacerbation of hepatic or renal dysfunction were identified and no patient required dose interruption or adjustment because of an adverse drug reaction during treatment with caspofungin. Standard-dose of caspofungin can be safely and effectively used in patients with Child-Pugh B or C cirrhosis, and we appealed to re-assess the most suitable dosing regimen in this population to avoid a potential subtherapeutic exposure.

Sections du résumé

BACKGROUND AND PURPOSE OBJECTIVE
The need for dose adjustment of caspofungin in patients with hepatic impairment is controversial, especially for those with Child-Pugh B or C cirrhosis. The purpose of this study was to investigate the safety and efficacy of standard-dose caspofungin administration in Child-Pugh B and C cirrhotic patients in a real-world clinical setting.
PATIENTS AND METHODS METHODS
The electronic medical records of 258 cirrhotic patients, including 67 Child-Pugh B patients and 191 Child-Pugh C patients, who were treated with standard-dose of caspofungin at the Second Affiliated Hospital of Chongqing Medical University, China, from March 2018 to June 2023 were reviewed retrospectively. The white blood cells (WBC), hepatic, renal and coagulation function results before administration and post administration on days 7, 14 and 21 were collected, and the efficacy was assessed in all patients at the end of caspofungin therapy.
RESULTS RESULTS
Favorable responses were achieved in 137 (53.1%) patients while 34 (13.2%) patients died. We observed that some patients experienced an increase of prothrombin time (PT) or international normalized ratio (INR), or a decrease of WBC, but no exacerbation of hepatic or renal dysfunction were identified and no patient required dose interruption or adjustment because of an adverse drug reaction during treatment with caspofungin.
CONCLUSIONS CONCLUSIONS
Standard-dose of caspofungin can be safely and effectively used in patients with Child-Pugh B or C cirrhosis, and we appealed to re-assess the most suitable dosing regimen in this population to avoid a potential subtherapeutic exposure.

Identifiants

pubmed: 38265608
doi: 10.1007/s15010-023-02162-0
pii: 10.1007/s15010-023-02162-0
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : China Health Promotion Foundation
ID : 20200816220986909

Informations de copyright

© 2024. The Author(s).

Références

GBD 2017 Cirrhosis Collaborators. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020;5:245–266. https://doi.org/10.1016/S2468-1253(19)30349-8
Arvaniti V, D’Amico G, Fede G, et al. Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis. Gastroenterology. 2010;139:1246-1256.e12565. https://doi.org/10.1053/j.gastro.2010.06.019 .
doi: 10.1053/j.gastro.2010.06.019 pubmed: 20558165
Kyriakidis I, Tragiannidis A, Munchen S, Groll AH. Clinical hepatotoxicity associated with antifungal agents. Expert Opin Drug Saf. 2017;16:149–65. https://doi.org/10.1080/14740338.2017.1270264 .
doi: 10.1080/14740338.2017.1270264 pubmed: 27927037
Spernovasilis N, Kofteridis DP. Pre-existing liver disease and toxicity of antifungals. J Fungi (Basel). 2018;4:133. https://doi.org/10.3390/jof4040133 .
doi: 10.3390/jof4040133 pubmed: 30544724
Parakh A, Dubey AP, Samanta D. Caspofungin. Indian Pediatr. 2008;45:905–10.
pubmed: 19029563
Martial LC, Brüggemann RJ, Schouten JA, et al. Dose reduction of caspofungin in intensive care unit patients with Child Pugh B will result in suboptimal exposure. Clin Pharmacokinet. 2016;55:723–33. https://doi.org/10.1007/s40262-015-0347-2 .
doi: 10.1007/s40262-015-0347-2 pubmed: 26649870
Gustot T, Ter Heine R, Brauns E, et al. Caspofungin dosage adjustments are not required for patients with Child-Pugh B or C cirrhosis. J Antimicrob Chemother. 2018;73:2493–6. https://doi.org/10.1093/jac/dky189 .
doi: 10.1093/jac/dky189 pubmed: 29860319
van der Elst KC, Veringa A, Zijlstra JG, et al. Low caspofungin exposure in patients in intensive care units. Antimicrob Agents Chemother. 2017;61:e01582-e1616. https://doi.org/10.1128/AAC.01582-16 .
doi: 10.1128/AAC.01582-16 pubmed: 27855112 pmcid: 5278683
Spriet I, Meersseman W, Annaert P, de Hoon J, Willems L. Pharmacokinetics of caspofungin in a critically ill patient with liver cirrhosis. Eur J Clin Pharmacol. 2011;67:753–5. https://doi.org/10.1007/s00228-011-1066-8 .
doi: 10.1007/s00228-011-1066-8 pubmed: 21638033
Segal BH, Herbrecht R, Stevens DA, et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clin Infect Dis. 2008;47:674–83. https://doi.org/10.1086/590566 .
doi: 10.1086/590566 pubmed: 18637757
Balani SK, Xu X, Arison BH, et al. Metabolites of caspofungin acetate, a potent antifungal agent, in human plasma and urine. Drug Metab Dispos. 2000;28:1274–8.
pubmed: 11038152
Mistry GC, Migoya E, Deutsch PJ, et al. Single- and multiple-dose administration of caspofungin in patients with hepatic insufficiency: implications for safety and dosing recommendations. J Clin Pharmacol. 2007;47:951–61. https://doi.org/10.1177/0091270007303764 .
doi: 10.1177/0091270007303764 pubmed: 17660480
Kofla G, Ruhnke M. Pharmacology and metabolism of anidulafungin, caspofungin and micafungin in the treatment of invasive candidosis: review of the literature. Eur J Med Res. 2011;16:159–66. https://doi.org/10.1186/2047-783x-16-4-159 .
doi: 10.1186/2047-783x-16-4-159 pubmed: 21486730 pmcid: 3352072
Li F, Zhou M, Jiao Z, et al. Caspofungin pharmacokinetics and probability of target attainment in ICU patients in China. J Glob Antimicrob Resist. 2021;25:238–63. https://doi.org/10.1016/j.jgar.2021.03.011 .
doi: 10.1016/j.jgar.2021.03.011 pubmed: 33845162
Kurland S, Furebring M, Löwdin E, et al. Pharmacokinetics of caspofungin in critically ill patients in relation to liver dysfunction: differential impact of plasma albumin and bilirubin levels. Antimicrob Agents Chemother. 2019;63:e02466-e2518. https://doi.org/10.1128/AAC.02466-18 .
doi: 10.1128/AAC.02466-18 pubmed: 30962329 pmcid: 6535551
Dong Y, Li Y, Zhang Y, et al. Cefoperazone/sulbactam therapeutic drug monitoring in patients with liver cirrhosis: potential factors affecting the pharmacokinetic/pharmacodynamic target attainment. Basic Clin Pharmacol Toxicol. 2019;125:353–9. https://doi.org/10.1111/bcpt.13245 .
doi: 10.1111/bcpt.13245 pubmed: 31056857
Gallagher J, Biesboer AN, Killian AJ. Pharmacologic issues in liver disease. Crit Care Clin. 2016;32:397–410. https://doi.org/10.1016/j.ccc.2016.02.003 .
doi: 10.1016/j.ccc.2016.02.003 pubmed: 27339679
Märtson AG, van der Elst KCM, Veringa A, et al. Caspofungin weight-based dosing supported by a population pharmacokinetic model in critically ill patients. Antimicrob Agents Chemother. 2020;64:e00905-e920. https://doi.org/10.1128/AAC.00905-20 .
doi: 10.1128/AAC.00905-20 pubmed: 32660990 pmcid: 7449215
Bailly S, Gautier-Veyret E, Lê MP, et al. Impact of loading dose of caspofungin in pharmacokinetic-pharmacodynamic target attainment for severe candidiasis infections in patients in intensive care units: the CASPOLOAD study. Antimicrob Agents Chemother. 2020;64:e01545-e1620. https://doi.org/10.1128/AAC.01545-20 .
doi: 10.1128/AAC.01545-20 pubmed: 32958709 pmcid: 7674046
Betts RF, Nucci M, Talwar D, et al. A multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis. Clin Infect Dis. 2009;48:1676–84. https://doi.org/10.1086/598933 .
doi: 10.1086/598933 pubmed: 19419331
Cornely OA, Vehreschild JJ, Vehreschild MJ, et al. Phase II dose escalation study of caspofungin for invasive Aspergillosis. Antimicrob Agents Chemother. 2011;55:5798–803. https://doi.org/10.1128/AAC.05134-11 .
doi: 10.1128/AAC.05134-11 pubmed: 21911573 pmcid: 3232774
Bai Z, Méndez-Sánchez N, Romeiro FG, et al. Use of albumin infusion for cirrhosis-related complications: an international position statement. JHEP Rep. 2023;5:100785. https://doi.org/10.1016/j.jhepr.2023.100785 .
doi: 10.1016/j.jhepr.2023.100785 pubmed: 37456673 pmcid: 10339261
Chen F, Hu S, Zhang S, et al. Liver injury associated with caspofungin: a real-worldstudy. Chin J Hosp Pharm. 2021;41:1337–40. https://doi.org/10.13286/j.1001-5213.2021.13.12 .
doi: 10.13286/j.1001-5213.2021.13.12
Sun B, Karin M. NF-kappaB signaling, liver disease and hepatoprotective agents. Oncogene. 2008;27:6228–44. https://doi.org/10.1038/onc.2008.300 .
doi: 10.1038/onc.2008.300 pubmed: 18931690
Yoshiji H, Nagoshi S, Akahane T, et al. Evidence-based clinical practice guidelines for liver cirrhosis 2020. Hepatol Res. 2021;51:725–49. https://doi.org/10.1111/hepr.13678 .
doi: 10.1111/hepr.13678 pubmed: 34228859
Yan T, Wang H, Cao L, et al. Glycyrrhizin alleviates nonalcoholic steatohepatitis via modulating bile acids and meta-inflammation. Drug Metab Dispos. 2018;46:1310–9. https://doi.org/10.1124/dmd.118.082008 .
doi: 10.1124/dmd.118.082008 pubmed: 29959134 pmcid: 6081736
Gillessen A, Schmidt HH. Silymarin as supportive treatment in liver diseases: a narrative review. Adv Ther. 2020;37:1279–301. https://doi.org/10.1007/s12325-020-01251-y .
doi: 10.1007/s12325-020-01251-y pubmed: 32065376 pmcid: 7140758
Guo T, Chang L, Xiao Y, et al. S-adenosyl-L-methionine for the treatment of chronic liver disease: a systematic review and meta-analysis. PLoS ONE. 2015;10:e0122124. https://doi.org/10.1371/journal.pone.0122124 .
doi: 10.1371/journal.pone.0122124 pubmed: 25774783 pmcid: 4361566
Ran X, Wang P, Zhang A, Tang B. Efficacy and safety of caspofungin for patients with hepatic insufficiency. BMC Infect Dis. 2022;22:560. https://doi.org/10.1186/s12879-022-07527-8 .
doi: 10.1186/s12879-022-07527-8 pubmed: 35725403 pmcid: 9208193
Itoh K, Shigemi H, Kinoshita K, et al. Efficacy and safety of caspofungin treatment in febrile neutropenic patients with hematological disorders: a multicenter consecutive case series. Intern Med. 2022;61:3037–44. https://doi.org/10.2169/internalmedicine.9070-21 .
doi: 10.2169/internalmedicine.9070-21 pubmed: 35314551 pmcid: 9646351
Maertens J, Raad I, Petrikkos G, et al. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis. 2004;39:1563–71. https://doi.org/10.1086/423381 .
doi: 10.1086/423381 pubmed: 15578352
Viscoli C, Herbrecht R, Akan H, et al. An EORTC phase II study of caspofungin as first-line therapy of invasive Aspergillosis in haematological patients. J Antimicrob Chemother. 2009;64:1274–81. https://doi.org/10.1093/jac/dkp355 .
doi: 10.1093/jac/dkp355 pubmed: 19841031
Herbrecht R, Maertens J, Baila L, et al. Caspofungin first-line therapy for invasive aspergillosis in allogeneic hematopoietic stem cell transplant patients: an European Organisation for Research and Treatment of Cancer study. Bone Marrow Transplant. 2010;45:1227–33. https://doi.org/10.1038/bmt.2009.334 .
doi: 10.1038/bmt.2009.334 pubmed: 20062093

Auteurs

Shi-Dan Yuan (SD)

Department of Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, 76# Linjiang Road, Yuzhong District, Chongqing, 400016, China.

Ke-Li Wen (KL)

Department of Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, 76# Linjiang Road, Yuzhong District, Chongqing, 400016, China.

Yun-Xing Cao (YX)

Department of Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, 76# Linjiang Road, Yuzhong District, Chongqing, 400016, China.

Wen-Qi Huang (WQ)

Department of Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, 76# Linjiang Road, Yuzhong District, Chongqing, 400016, China.

An Zhang (A)

Department of Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, 76# Linjiang Road, Yuzhong District, Chongqing, 400016, China. 300704@hospital.cqmu.edu.cn.

Classifications MeSH