Pre-Existing Liver Disease and Toxicity of Antifungals

Spernovasilis, Nikolaos; Kofteridis, Diamantis P.

doi:10.3390/jof4040133

Cited by 35 publications

(26 citation statements)

References 142 publications

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“…is was mainly triggered by the existing hypalbuminemia. e question to what extent this should lead to a dose reduction of caspofungin in order to avoid an overdose is still open [8,14]. A potentially considered conversion to anidulafungin, another echinocandin, was not possible for us, because this drug is not listed in our hospital [16].…”

Section: Discussionmentioning

confidence: 97%

“…A second septic crisis occurred on 10-11 th July (hd33/34) with elevation of leucocytes up to 47.7/µL, CRP 141 mg/L and relapsing renal failure with the need for hemodialysis ( Figure 4). Liver enzymes increased to ASAT 372 U/l and ALAT 225 [8]. Other parameters of septic shock showed an increase of lactate (2.78 mmol/L) and interleukin 6 (746.1 pg/mL) ( Figure 5).…”

Section: Case Presentationmentioning

confidence: 98%

“…erefore, we decided to continue systemic therapy with caspofungin until 11 th August (hd65). Only rare severe hepatic side e ects are reported for caspofungin [8]. Another reason for continuing the established medication was the clinical recovery of the patient.…”

Section: Case Presentationmentioning

confidence: 99%

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Dosing of Antimycotic Treatment in Sepsis–Induced Liver Dysfunction by Functional Liver Testing with LiMAx®

Kirchner

Sibai

Schwier

et al. 2019

Case Reports in Critical Care

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Background. Sepsis-treatment is one of the major challenges in our time. Especially fungal infections play an important role in patient’s morbidity and mortality. In patients with septic shock, liver function is often significantly impaired and therefore also hepatic drug metabolism is altered. Case Presentation. We report about a 56-year-old man suffering from invasive fungal infection with multiorgan failure, after complicated medical history due to symptomatic infrarenal aortic aneurysm. On the first postoperative day, a CT scan was undertaken due to massive back pain showing renal infarction on both sides. As qualitative and quantitative renal function was impaired, hemodialysis was started immediately. Subsequently, the patient developed a compartment syndrome of the left leg and underwent fasciotomy. On admission day 7, the patient presented with hematochezia leading to colonoscopy. During this procedure, an ischemic colitis was observed. As conservative treatment failed, the patient underwent Hartmann’s procedure due to progredient ischemia followed by a worsening of the clinical status due to sepsis. The patient suffered from an invasive fungal infection with Candida spp. and Aspergillus spp. Systemic antifungal treatment was initiated. Although azoles are considered first-line treatment in these cases we chose the echinocandin caspofungin for its presumed lower impact on liver function compared to azoles like voriconazole or Amphothericin B. However, caspofungin is also metabolised in the liver and can cause hepatotoxic effects. Therefore we measured metabolic liver function capacity using LiMAx®and adapted the patient’s dose of caspofungin to the evaluated liver function capacity to achieve an effective and liver-protective level of the active drug. After complicated medical history with 15 weeks of hospital stay, the patient was discharged in general good condition. Conclusions. To our knowledge, this is the first report that relates antimycotic drug dosing to a functional liver test. We provide a new approach for sepsis treatment considering liver function capacity to optimize dosage of hepatically metabolised drugs with potential hepatotoxic effects.

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Section: Discussionmentioning

confidence: 97%

Section: Case Presentationmentioning

confidence: 98%

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Dosing of Antimycotic Treatment in Sepsis–Induced Liver Dysfunction by Functional Liver Testing with LiMAx®

Kirchner

Sibai

Schwier

et al. 2019

Case Reports in Critical Care

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“…Therapeutic options for intracranial mycosis with severe liver dysfunction are limited. Liposomal amphotericin-B is often the preferred drug due to broad-spectrum, and relative lack of toxicity in liver failure patients 16. The use of voriconazole is often limited in patients with decompensated cirrhosis due to markedly prolonged elimination, potential toxicity and drug interactions 1715.…”

Section: Discussionmentioning

confidence: 99%

“…The use of voriconazole is often limited in patients with decompensated cirrhosis due to markedly prolonged elimination, potential toxicity and drug interactions 1715. Posaconazole merits the therapeutic drug monitoring, and echinocandins have limited efficacy against aspergillosis and mucroales 16. Surgical intervention for source control is often limited in patients with liver disease due to sickness profile and coexistent coagulopathy.…”

Section: Discussionmentioning

confidence: 99%

Intracranial invasive mycosis mimicking hepatic encephalopathy in a patient with cirrhosis

2019

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A 45-year-old man with alcohol-related decompensated cirrhosis presented with jaundice, fever, headache and altered sensorium. At presentation, he had tachycardia, disorientation to time and place, asterixis, icterus and upgoing plantar response. Investigations showed anaemia, thrombocytopenia, leucocytosis, hyperbilirubinemia and elevated arterial ammonia. Despite management with antihepatic coma measures and normalisation of ammonia, broad-spectrum antibiotics, 20% albumin, the patient worsened. On day 3, the patient developed generalised tonic–clonic seizure prompting mechanical ventilation. Examination showed right proptosis, chemosis and pupillary anisocoria. MRI brain showed multifocal infarcts in the right temporal lobe, right cerebellum and brainstem with inflammation in the right orbit, infratemporal fossa with right internal carotid artery thrombosis, and suspicious maxillary sinus thickening. Nasal scrapings showed aseptate fungal hyphae and serum galactomannan index was positive. Despite receiving liposomal amphotericin-B, patient had an unfavourable outcome. Intracranial invasive mycosis can mimic hepatic encephalopathy and is associated with high mortality in cirrhotics. A high index of suspicion, positive biomarkers and diagnostic radiology may provide the key to the diagnosis.

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Design of an epitope‐based peptide vaccine against Cryptococcus neoformans

Omer,

Khalil,

Abdalmumin

et al. 2024

FEBS Open Bio

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Cryptococcus neoformans is the highest‐ranked fungal pathogen in the Fungal Priority Pathogens List (FPPL) released by the World Health Organization (WHO). In this study, through in silico simulations, a multi‐epitope vaccine against Cryptococcus neoformans was developed using the mannoprotein antigen (MP88) as a vaccine candidate. Following the retrieval of the MP88 protein sequences, these were used to predict antigenic B‐cell and T‐cell epitopes via the bepipred tool and the artificial neural network, respectively. Conserved B‐cell epitopes AYSTPA, AYSTPAS, PASSNCK, and DSAYPP were identified as the most promising B‐cell epitopes. While YMAADQFCL, VSYEEWMNY, and FQQRYTGTF were identified as the best candidates for CD8+ T‐cell epitopes; and YARLLSLNA, ISYGTAMAV, and INQTSYARL were identified as the most promising CD4+ T‐cell epitopes. The vaccine construct was modeled along with adjuvant and peptide linkers and the expasy protparam tool was used to predict the physiochemical properties. According to this, the construct vaccine was predicted to be antigenic, nontoxic, nonallergenic, soluble, stable, hydrophilic, and thermostable. Furthermore, the three‐dimensional structure was also used in docking analyses with Toll‐like receptor (TLR4). Finally, the cDNA of vaccine was successfully cloned into the E. coli pET‐28a (+) expression vector. The results presented here could contribute towards the design of an effective vaccine against Cryptococcus neoformans.

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Pre-Existing Liver Disease and Toxicity of Antifungals

Cited by 35 publications

References 142 publications

Dosing of Antimycotic Treatment in Sepsis–Induced Liver Dysfunction by Functional Liver Testing with LiMAx®

Dosing of Antimycotic Treatment in Sepsis–Induced Liver Dysfunction by Functional Liver Testing with LiMAx®

Intracranial invasive mycosis mimicking hepatic encephalopathy in a patient with cirrhosis

Design of an epitope‐based peptide vaccine against Cryptococcus neoformans

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