Anidulafungin Pharmacokinetics in Ascites Fluid and Pleural Effusion of Critically Ill Patients

Welte, René; Eller, Philipp; Lorenz, Ingo; Joannidis, Michael; Bellmann, Romuald

doi:10.1128/aac.02326-17

Cited by 15 publications

(11 citation statements)

References 21 publications

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“…A recent study involving seven patients (Welte et al, 2018), reported anidulafungin concentrations in the range of 0.12-0.99 mg/l in ascitic fluid, which is consistent with the average obtained from the data in the present study.…”

Section: Resultssupporting

confidence: 93%

Pharmacokinetics of anidulafungin in critically ill patients with Candida peritonitis

Civantos

Marcos

Perea

et al. 2019

International Journal of Infectious Diseases

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Objective: To describe the pharmacokinetic (PK) profile of anidulafungin and to evaluate its concentration in the peritoneal fluid (PF) of patients suspected of suffering from peritoneal infection undergoing abdominal surgery, in order to ensure that therapeutic levels are achieved within the peritoneal cavity. Methods:A descriptive, open, prospective, observational, multicentre and non-interventional study was performed. Anidulafungin was used at conventional doses. Blood and PF samples were obtained on day 2 of treatment or on any of the following days. Results: A total of 31 patients in a serious clinical condition, as demonstrated by high mean clinical severity scale scores (APACHE II and SOFA scores), were included in the study. The mean area under the curve (AUC) in PF was 30% (31 AE 19%) of that determined in the plasma and the maximum concentration (Cmax) reached in PF (mg/l) was close to 1 (0.9 AE 0.5). No adverse effects were observed in any of the 31 patients.Conclusions: Anidulafungin at conventional doses reaches PF concentrations that exceed the minimum inhibitory concentration of the usual Candida spp, which explains the proven efficacy of this echinocandin in the treatment of Candida peritonitis in critically ill patients.

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Section: Resultssupporting

confidence: 93%

Pharmacokinetics of anidulafungin in critically ill patients with Candida peritonitis

Civantos

Marcos

Perea

et al. 2019

International Journal of Infectious Diseases

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“…The levels obtained in PF in the current patients were similar to those obtained by other authors, and they confirmed a moderate penetration of echinocandins into the PF in patients with IAC. Perez-Civantos et al confirmed anidulafungin levels between 0.7-0.9 mg/mL, with an average AUC 0À24 of 57.9 mg Â h/L, (Pérez Civantos et al, 2019) which was similar to the levels obtained by Welte et al (0.12-0.99 mg Â h/mL) (Welte et al, 2018). Andes et al (2011) demonstrated that the AUC/MIC ratio, APACHE II score and history of corticosteroid use were significant independent predictors of a favourable response for all Candida species.…”

Section: Discussionsupporting

confidence: 70%

“…The low sensitivity of echinocandins to Candida parapsilosis (C. parapsilosis) and development of resistance, especially in Candida glabrata (C. glabrata) in patients receiving prolonged treatment with echinocandins have recently been the focus of diffusion studies on these antifungals at an intra-abdominal level (Grau et al, 2015;Pérez Civantos et al, 2019;Welte et al, 2018;Dupont et al, 2017;Sganga et al, 2019). Different pharmacokinetic/pharmacodynamic (PK/PD) studies have recently been published for echinocandins (Luque et al, 2019;Andes et al, 2011;Hall et al, 2013;Aguilar et al, 2014a;Aguilar et al, 2014b;Andes et al, 2010), but very few have focused on candidiasic peritonitis or intra-abdominal fungal infection.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of echinocandins in suspected candida peritonitis: A potential risk for resistance

Gioia

Gómez-López

Álvarez

et al. 2020

International Journal of Infectious Diseases

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Introduction: A possible increase in Candida resistance, especially in Candida glabrata, has been speculated according to poor diffusion of echinocandins to peritoneal fluid. Materials/methods: Peritoneal and serum concentrations of caspofungin, micafungin and anidulafungin were analysed in surgical patients with suspected candida peritonitis. After 4 days of starting therapy, serum and peritoneal samples (through peritoneal drainage) were obtained at baseline, 1, 6, 12 and 24 h of drug administration. Micafungin and anidulafungin concentrations were determined using highperformance liquid chromatography (HPLC/F), whereas caspofungin concentrations were established by bioassay. Results: Twenty-three critically ill patients with suspected abdominal fungal infection who were receiving an echinocandin were prospectively recruited. No specific criteria were applied to prescribe one specific echinocandin. No special clinical differences were observed among the three groups of patients. All were receiving antibiotic therapy, 80% required inotropic drugs, and fungal peritonitis was confirmed in 74% of them. The AUC 0_24h (mg Â h/L) obtained in serum and peritoneal fluid were: 126.84 and 34.38, 98.52 and 18.83, and 66.9 and 8.78 for anidulafungin, micafungin and caspofungin, respectively. The median concentration in peritoneal fluid ranged from 0.66 to 1.82 mg/mL for anidulafungin, 0.68-0.88 mg/mL for micafungin and 0.21-0.46 mg/mL for caspofungin. Conclusion:The results showed moderate penetration of echinocandins into the peritoneal fluid of these patients. These levels are below the threshold of resistance mutant selection published by other authors. This could justify a potential risk of resistance in patients with prolonged treatment with echinocandins and suboptimal control of abdominal infection.

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“…Interestingly, almost 20% of patients with IC broke through systemic prophylaxis, nearly always with micafungin. Micafungin breakthrough IFIs in the setting of invasive disease outside of the bloodstream raise the question of inadequate tissue penetration of echinocandins, particularly into the pleural space [33][34][35]. In addition, micafungin breakthroughs among patients requiring EMCO may also reflect decreased drug exposure related to micafungin extraction by the ECMO circuit [36].…”

Section: Discussionmentioning

confidence: 99%

Invasive Fungal Infection After Lung Transplantation: Epidemiology in the Setting of Antifungal Prophylaxis

Baker

Maziarz

Arnold

et al. 2019

Clinical Infectious Diseases

121

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Background Lung transplant recipients commonly develop invasive fungal infections (IFIs), but the most effective strategies to prevent IFIs following lung transplantation are not known. Methods We prospectively collected clinical data on all patients who underwent lung transplantation at a tertiary care academic hospital from January 2007–October 2014. Standard antifungal prophylaxis consisted of aerosolized amphotericin B lipid complex during the transplant hospitalization. For the first 180 days after transplant, we analyzed prevalence rates and timing of IFIs, risk factors for IFIs, and data from IFIs that broke through prophylaxis. Results In total, 156 of 815 lung transplant recipients developed IFIs (prevalence rate, 19.1 IFIs per 100 surgeries, 95% confidence interval [CI] 16.4–21.8%). The prevalence rate of invasive candidiasis (IC) was 11.4% (95% CI 9.2–13.6%), and the rate of non-Candida IFIs was 8.8% (95% CI 6.9–10.8%). First episodes of IC occurred a median of 31 days (interquartile range [IQR] 16–56 days) after transplant, while non-Candida IFIs occurred later, at a median of 86 days (IQR 40–121 days) after transplant. Of 169 IFI episodes, 121 (72%) occurred in the absence of recent antifungal prophylaxis; however, IC and non-Candida breakthrough IFIs were observed, most often representing failures of micafungin (n = 16) and aerosolized amphotericin B (n = 24) prophylaxis, respectively. Conclusions Lung transplant recipients at our hospital had high rates of IFIs, despite receiving prophylaxis with aerosolized amphotericin B lipid complex during the transplant hospitalization. These data suggest benefit in providing systemic antifungal prophylaxis targeting Candida for up to 90 days after transplant and extending mold-active prophylaxis for up to 180 days after surgery.

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Anidulafungin Pharmacokinetics in Ascites Fluid and Pleural Effusion of Critically Ill Patients

Cited by 15 publications

References 21 publications

Pharmacokinetics of anidulafungin in critically ill patients with Candida peritonitis

Pharmacokinetics of anidulafungin in critically ill patients with Candida peritonitis

Pharmacokinetics of echinocandins in suspected candida peritonitis: A potential risk for resistance

Invasive Fungal Infection After Lung Transplantation: Epidemiology in the Setting of Antifungal Prophylaxis

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