micafungin and Postoperative-Complications

Currently, three echinocandins are available for the treatment of fungal infections. Micafungin is the latest drug to be incorporated into this group of antifungal agents. Although the mechanism of action of micafungin is similar to that of other echinocandins, this molecule has certain pharmacokinetic characteristics that distinguish it from other drugs in this group. Nowadays, there is wide information on the pharmacokinetic behavior of micafungin, mainly from patients included in clinical trials. However, there is far less knowledge of the pharmacokinetics of this echinocandin in special populations. The aim of the current review was to analyze the available information on the pharmacokinetics of micafungin in pediatric patients, the elderly, patients with renal insufficiency or liver failure, and transplant recipient.

Topics: Adolescent; Adult; Age Factors; Aged; Antifungal Agents; Child; Child, Preschool; Clinical Trials as Topic; Comorbidity; Cytochrome P-450 CYP3A; Drug Interactions; Echinocandins; Humans; Infant; Kidney Diseases; Lipopeptides; Liver Diseases; Micafungin; Middle Aged; Mycoses; Postoperative Complications; Transplantation; Young Adult

Micafungin is a semisynthetic lipopeptide developed from Coleophoma empetri, which blocks the synthesis of β-1,3-D-glucan, an essential component of the fungal wall, though non-competitive inhibition of β-1,3-D-glucan synthetase. Micafungin is a dose-dependent candidacidal agent with excellent in vitro efficacy against most Candida spp. including species resistant to amphotericin B, such as Candida lusitaniae, several azoles, such as C. glabrata or C. krusei, and isolates not susceptible to other echinocandins. Moreover, this drug is active against Candida biofilms. Micafungin is a first-line drug for the treatment of candidemias and invasive candidiasis in adults and children (including neonates). This drug is approved for use in the treatment of invasive candidiasis and Candida esophagitis, as well as in the prophylaxis of Candida infections in hematopoietic stem cell transplant recipients or those at risk of prolonged neutropenia. Micafungin can be used both in the treatment and prevention of candidiasis in neonates, children, adolescents, adults, and the elderly, making it highly useful in patient groups in which the use of other antifungal drugs has not been authorized.

Topics: Adolescent; Adult; Aged; Animals; Antifungal Agents; Biofilms; Candida; Candidiasis, Invasive; Cell Wall; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation, Preclinical; Echinocandins; Esophagitis; Fungal Proteins; Glucosyltransferases; Humans; Immunocompromised Host; Infant; Infant, Newborn; Lipopeptides; Micafungin; Mice; Middle Aged; Multicenter Studies as Topic; Postoperative Complications; Species Specificity; Transplantation; Young Adult

Antifungal prophylaxis is the first option to fight against fungal infection in high-risk hematological patients (remission of induction of acute myeloblastic leukemia/myelodysplastic syndrome, allogeneic hematopoietic stem cell transplantation). Fluconazole prophylaxis is not effective in preventing infection with moulds, mainly invasive aspergillosis, and consequently the triazole currently recommended in high-risk hematological patients is posaconazole. Nevertheless, given that posaconazole can only be administered orally, alternative prophylaxis may be required. Antifungal prophylaxis with micafungin is an attractive option. At a dose of 50 mg/day (1 mg/kg if weight is ≤ 40 kg) micafungin is approved for the prophylaxis of candidiasis in hematopoietic stem cell transplant recipients. Higher doses have been evaluated in adults (100 mg/day, 150 mg/day) and in children (3 mg/kg/day) with good efficacy and safety. Because of this agent's spectrum of activity, which includes both Candida and Aspergillus, together with its favorable pharmacokinetic profile regarding to the absence of significant drug interactions, this agent is appropriate in hematopoietic stem cell transplant recipients and in hematological patients following therapeutic protocols with vinca alkaloids. The optimal and most cost-effective dose for prophylaxis, as well as alternative regimens to daily intravenous administration, which would allow the use of this drug beyond conventional hospitalization (day care hospital, domiciliary transplantation therapy), remain to be determined.

Topics: Adult; Ambulatory Care; Antifungal Agents; Chemical and Drug Induced Liver Injury; Child; Clinical Trials as Topic; Dose-Response Relationship, Drug; Echinocandins; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Kidney Diseases; Lipopeptides; Male; Meta-Analysis as Topic; Micafungin; Mycoses; Postoperative Complications; Practice Guidelines as Topic; Triazoles

Micafungin is an echinocandin approved for the prevention of Candida spp. infection in hematopoietic stem cell transplantation and therapy of oesophageal candidiasis, disseminated candidiasis and candidemia in adults, children and neonates.. To evaluate the role of micafungin for candidiasis therapy in solid organ transplant recipients.. A medical literature review according to micafungin role for candidiasis therapy in transplant patients is performed.. Micafungin has shown fungicide activity against Candida species, including strains resistant or poorly susceptible to fluconazole. No dose adjustment is required when micafungin is administered in combination with other drugs used in transplant patients, excluding sirolimus, nifedipine and itraconazol. With these drugs, a minimal dose reduction is recommended. The results observed in transplant patients included in clinical trials are favourable and similar to results obtained in other kind of patients.. The clinical results, its safety profile and the low grade of medical interactions permit micafungin to be considered for therapy in specific groups of transplant patients.

Topics: Adult; Antifungal Agents; Candidiasis; Child; Clinical Trials as Topic; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Drug Interactions; Drug Resistance, Fungal; Echinocandins; Fungemia; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Infant, Newborn; Lipopeptides; Micafungin; Organ Transplantation; Postoperative Complications

Invasive candidiasis is a severe infection among onco-hematological patients, with an attributable mortality around 40%. Micafungin has shown efficacy in antifungal prophylaxis among hematopoietic stem cell transplant recipients and in the treatment of esophageal candidiasis.. To assess the role of micafungin in the treatment of invasive candidiasis among onco-hematological patients.. Literature review.. In a study on 126 patients with candidemia treated with micafungin, an overall response rate of 83% was reported. A double-blind study of 531 patients with invasive candidiasis comparing micafungin (100mg/day) versus liposomal amphotericin B (3mg/kg/day) reported success in 90% of patients in both arms, with a more favorable safety profile with micafungin. Other double blind randomized, phase III study compared two doses of micafungin (100mg/day and 150mg/day) with standard doses of caspofungin (70mg loading dose, then 50mg/day) in adults with invasive candidiasis. Overall success rate was 74% for micafungin 100mg/day, 70% for micafungin 150mg/day, and 71% for caspofungin. A double blind randomized study compared micafungin (2mg/kg/day) to liposomal amphotericin B (3mg/kg/day) in the treatment of invasive candidiasis in children with a predominance of infections with non-albicans Candida spp. Overall success rate was similar (73% for micafungin and 76% for liposomal amphotericin B).. Comparative phase III studies have demonstrated non-inferiority of micafungin compared to standard antifungal agents for invasive candidiasis. Micafungin is safe and effective in the treatment of children and adults with invasive candidiasis. Effectivity in invasive infections caused by non-albicans Candida spp is especially relevant in onco-hematological patients receiving fluconazole prophylaxis.

Topics: Adult; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Candidiasis; Caspofungin; Child; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Double-Blind Method; Echinocandins; Fungemia; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Lipopeptides; Micafungin; Postoperative Complications; Prosthesis-Related Infections; Randomized Controlled Trials as Topic

Micafungin is a echinocandin. It inhibits beta-1,3-D-glucan synthesis, thus achieving fungicidal activity against virtually all Candida spp., including those resistant to fluconazole, and fungistatic activity against Aspergillus spp., as well as several but not all pathogenic molds. Results from in vitro studies, animal models, small clinical trials, hint at possible future indications such as invasive aspergillosis and empirical viantifungal therapy, although currently there is little information published.. To describe published data of micafungin as treatment against invasive mold infections, specially analysing its role in the inmunodepressed host and critical care setting.. A systematic review of literature using the principal medical search engines was performed. Terms such as micafungin, aspergillosis, zygomycosis, invasive fungal infections, emerging fungal infections, antifungal treatment or therapy, antifungal prophylaxis, empiric or pre-emptive therapy were crossed. Febrile neutropenia patients were excluded.. Several studies in these setting were identified and were described in this review. Although there were no blinded randomized clinical trials published, treatment or prophylaxis of invasive aspergillosis and other invasive mould infections with micafungin described in open clinical studies were analyzed.. Micafungin could play a future important role as a primary or rescue therapy, alone or in combination, in the treatment or prophylaxis of invasive fungal infections caused by moulds. New randomized clinical trials are needed to confirm their efficacy.

Topics: Adult; Animals; Antifungal Agents; Aspergillosis; Candidiasis; Child; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation, Preclinical; Echinocandins; Fluconazole; Forecasting; Fungemia; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Lipopeptides; Micafungin; Multicenter Studies as Topic; Mycoses; Organ Transplantation; Postoperative Complications; Premedication; Prospective Studies; Randomized Controlled Trials as Topic; Zygomycosis

Patients undergoing emergency gastrointestinal surgery for intra-abdominal infection are at risk of invasive candidiasis (IC) and candidates for preemptive antifungal therapy.. This exploratory, randomized, double-blind, placebo-controlled trial assessed a preemptive antifungal approach with micafungin (100 mg/d) in intensive care unit patients requiring surgery for intra-abdominal infection. Coprimary efficacy variables were the incidence of IC and the time from baseline to first IC in the full analysis set; an independent data review board confirmed IC. An exploratory biomarker analysis was performed using logistic regression.. The full analysis set comprised 124 placebo- and 117 micafungin-treated patients. The incidence of IC was 8.9% for placebo and 11.1% for micafungin (difference, 2.24%; [95% confidence interval, -5.52 to 10.20]). There was no difference between the arms in median time to IC. The estimated odds ratio showed that patients with a positive (1,3)-β-d-glucan (ßDG) result were 3.66 (95% confidence interval, 1.01-13.29) times more likely to have confirmed IC than those with a negative result.. This study was unable to provide evidence that preemptive administration of an echinocandin was effective in preventing IC in high-risk surgical intensive care unit patients with intra-abdominal infections. This may have been because the drug was administered too late to prevent IC coupled with an overall low number of IC events. It does provide some support for using ßDG to identify patients at high risk of IC.. NCT01122368.

Topics: Adolescent; Adult; Aged; Antifungal Agents; beta-Glucans; Biomarkers; Candidiasis, Invasive; Double-Blind Method; Echinocandins; Female; Humans; Intensive Care Units; Intraabdominal Infections; Lipopeptides; Male; Micafungin; Middle Aged; Postoperative Complications; Pre-Exposure Prophylaxis; Proteoglycans; Young Adult

Disseminated fungal infection is a major cause of morbidity and mortality in children undergoing hematopoietic stem cell transplantation (HSCT). Prophylaxis with amphotericin B can be limited by renal toxicity. Oral triazoles can be limited by poor absorption, large interindividual pharmacokinetic (PK) variability, and hepatic toxicity, leading to interruptions in therapy and breakthrough infections. Intravenous (i.v.) micafungin has potential advantages, because of its better safety profile, specifically in terms of hepatic and renal toxicity, and lack of drug-drug interactions with common medications used in the HSCT setting. We hypothesized that higher dose micafungin (3 mg/kg) every other day will provide drug exposure similar to standard dosing (1 mg/kg) given daily, and improve patient compliance in very young children in whom oral medications can be challenging, at reduced administration costs. Both animal and adult patient data support the use of this approach. Fifteen children (M/F = 11/4, aged < or =10 years; mean: 3.9 years, range: 0.6-10 years) with various hematologic, metabolic, and immune deficiency disorders undergoing HSCT received a single dose of micafungin (3 mg/kg) i.v. over 1 hour. Dose selection was based on published PK data in pediatric patients, and exploration of different dosing regimens using Monte Carlo PK/PD simulation. Blood samples were drawn around this dose and PK analysis was conducted using standard noncompartmental methods. Micafungin at 3 mg/kg dose was well tolerated in all patients. Measurable plasma concentrations were present in all cases at 48 hours. Half-life and clearance observed were comparable to previous pediatric PK data, with clearance being higher than adults as expected. Volume of distribution was higher in our patients compared to published pediatric data, likely because of a larger proportion of very young children in our study cohort. After correction for protein binding, concentrations at the end of the dosing interval during maintenance treatment remain above the minimum inhibitory concentration (MIC) of highly susceptible fungal pathogens. These data suggest that alternate day micafungin dosing, as described here, may provide an attractive alternative for antifungal prophylaxis in HSCT patients and merits further evaluation.

Topics: Antifungal Agents; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Drug Administration Schedule; Echinocandins; Female; Half-Life; Hematopoietic Stem Cell Transplantation; Humans; Hypocalcemia; Hypokalemia; Infant; Lipopeptides; Male; Micafungin; Microbial Sensitivity Tests; Mycoses; Postoperative Complications; Premedication; Prospective Studies

The clinical efficacy of micafungin (MCFG) in surgery, emergency, and intensive-care medicine has been studied in only a limited number of cases. We conducted a multicenter postmarketing study to evaluate MCFG efficacy and safety in Japan. MCFG was given to patients with a temperature exceeding 37.5 degrees C, either with a proven fungal infection based on mycological or histopathological examination, or those who were regarded as having probable or possible fungal infections (patients who had at least one high-risk factor for the development of a systemic fungal infection and for whom fungi had been detected at multiple sites by surveillance culture or a positive beta-D-glucan test). Efficacy was evaluated using the AKOTT algorithm created by our group (AKOTT is an acronym created from the first letter of the surname of each of the five members of the evaluation committee). Of the 180 patients enrolled, 68 were excluded by exclusion criteria or for other reasons, and 112 (58 with proven candidiasis, 1 with proven aspergillosis, and 53 with suspected fungal infection) were evaluated for efficacy. MCFG was administered at a mean daily dose of 104 mg for a mean duration of 14.2 days. It was effective in 72 p 72 patients, ineffective in 28, and the effect was undeterminable in 12, for an overall clinical efficacy 72.0%. MCFG was effective in 78.6% of those with proven candidiasis and in 65.1% with suspected fungal infection, but it was ineffective in the 1 patient with aspergillosis. MCFG eradicated 77.6% (52/67) of fungi isolated. There were 69 drug-related adverse reactions, mainly abnormal hepatic function tests, in 37 of 178 patients evaluated for safety. One adverse reaction, skin eruption, had a probable causal relationship with drug treatment. In conclusion, MCFG had high clinical efficacy and safety in the treatment of deep-seated fungal infections in surgery, emergency, and intensive-care medicine, indicating good potential as a firstline drug for both targeted and empirical therapies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Antifungal Agents; Aspergillosis; Candidiasis; Child; Child, Preschool; Drug Eruptions; Echinocandins; Emergency Service, Hospital; Female; Humans; Intensive Care Units; Japan; Lipopeptides; Liver Diseases; Male; Micafungin; Middle Aged; Postoperative Complications; Product Surveillance, Postmarketing; Treatment Outcome

A 24-year-old man was diagnosed with myelodysplastic syndrome and received a haploidentical hematopoietic stem cell transplant. The patient experienced graft failure posttransplant. Analysis of specific antibodies revealed that the patient had strongly positive donor-specific antibodies; therefore, we changed the donor to the patient's mother and added a single unit of cord blood to perform the second transplant. Corresponding treatments targeting donor-specific antibodies were administered to reverse the graft rejection and to reduce the antibody load. The grafts were implanted successfully, but the patient developed an invasive fungal infection. A lung biopsy was performed, and the pathogen was confirmed to be Aspergillus terreus via gene sequencing and analysis. The combined treatment of micafungin and posaconazole had good efficacy in this case, and this patient now receives close follow-up and receives oral posaconazole for antifungal maintenance treatment.

Topics: Antifungal Agents; Hematopoietic Stem Cell Transplantation; Humans; Male; Micafungin; Myelodysplastic Syndromes; Postoperative Complications; Pulmonary Aspergillosis; Remission Induction; Triazoles; Young Adult

To study the characteristics and prevention and treatment strategies of massive hemorrhage caused by fungal infections after donation-after-cardiac-death (DCD) kidney transplantation.. A total of 91 cases of DCD kidney transplantation between August 25, 2013 and June 30, 2015 in Third Affiliated Hospital of Sun Yat-sen Univservity were retrospectively analyzed. The characteristics of and prevention and treatments strategies for postoperative massive hemorrhage caused by fungal infections were summarized.. Ninety-one cases of DCD kidney transplantation were divided into 2 groups based on regimens for preventing postoperative fungal infections: fluconazole prophylaxis group: a total of 26 cases of renal transplant before June 11, 2014 received fluconazole regimen, from postoperative day 0 to 2 weeks; micafungin prophylaxis group: a total of 65 cases of renal transplant after June 11, 2014 received micafungin regimen, also for 2 weeks from postoperative day 0. Two cases in fluconazole group developed postoperative massive hemorrhage. In case 1, the hemorrhage occurred at 2 weeks after transplantation. Graft nephrectomy was performed during surgical exploration for hemostasis, yet the massive hemorrhage relapsed 2 weeks later. Endoluminal exclusion of external iliac artery using endovascular covered stent-graft at the anastomosis site was performed and the massive bleeding was successfully stopped. The patient was restored to hemodialysis and waited for second kidney transplantation. Candia albicans was detected in the culture of blood and drainage liquid from incision. The other case of hemorrhage occurred at 3 weeks after transplantation. Graft nephrectomy plus endovascular exclusion using covered stent-graft were also performed to stop the massive bleeding. Massive fungal hyphae and spores were observed at the stump of renal graft artery under microscope. The patient received second kidney transplantation after 6 months successfully. No massive hemorrhage caused by fungal infections occurred in micafungin prophylaxis group.. Massive hemorrhage cased by fungal infections after DCD kidney transplantation is usually characterized by delayed and recurrent course, and may result in graft nephrectomy or even death of patients. Endovascular exclusion using covered stent can successfully stop bleeding and rescue life of patients. Two-week preemptive prophylaxis of fungal infections using micafungin can effectively prevent delayed fungal massive hemorrhage in DCD kidney transplantation.

Topics: Antifungal Agents; Echinocandins; Heart Diseases; Hemorrhage; Humans; Kidney; Kidney Transplantation; Lipopeptides; Micafungin; Mycoses; Nephrectomy; Postoperative Complications; Renal Artery; Retrospective Studies; Tissue Donors; Treatment Outcome

To determine the reasons of prescription, the characteristics of patients and factors that affected the outcome of critically ill patients treated with micafungin (MCF) during their stay in Spanish ICUs.. Observational, retrospective and multicenter study. Patients admitted to the ICU between March 2011 and October 2012 (20-month period) treated with MCF for any reason were included in the study. Severity of patients at the beginning of treatment was measured with the APACHE II, SOFA, Child-Pugh and MELD scores. Reasons for the use of MCF were classified as prophylaxis, preemptive treatment, empirical treatment and directed treatment. Continuous variables are expressed as mean and standard deviation or median, and categorical variables as percentages. A multivariate analysis was performed to identify variables related to intra-ICU mortality.. The study population included 139 patients admitted to 19 Spanish ICUs, with a mean age of 57.3 (17.1) years, 89 (64%) men, with surgical (53.2%) and/or medical (44.6%) conditions, APACHE II score of 20.6 (7.7) and SOFA score of 8.4 (4.3), with 84.2% of patients requiring mechanical ventilation, 59% parenteral nutrition, 37.4% extrarenal depuration procedures and 37.4% treatment with steroids. MCF was indicated as empirical treatment of a proven infection in 51 (36.7%) cases, pre-emptive treatment in 50 (36%) especially as a result of the application of the Candida score (32 cases), directed treatment of fungal infection in 23 (16.5%) and as prophylactic treatment in 15 (10.8%) cases. In 108 (77%) cases, a daily dose of 100mg was administered, with a loading dose in only 9 cases (6.5%). The mean duration of treatment was 13.1 (13) days. A total of 59 (42.4%) patients died during their stay in the ICU and 16 after ICU discharge (hospital mortality 53.9%). Independent risk factors for intra-ICU mortality were the Child-Pugh score (OR 1.45, 95% CI 1.162-1.813; P=.001) and the MELD score (OR 1.05, 95% CI 1.011-1.099; P=.014).. MCF is usually administered at a dose of 100mg/day, without loading dose and in 72.7% of cases as pre-emptive or empirical treatment. Factors that better predicted mortality were indicators of liver insufficiency at the time of starting treatment.

Topics: Adult; Aged; Antifungal Agents; Combined Modality Therapy; Critical Care; Echinocandins; Female; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Lipopeptides; Liver Failure; Male; Micafungin; Middle Aged; Mycoses; Postoperative Complications; Retrospective Studies; Severity of Illness Index; Spain

Echinocandins are first-line therapy in critically ill patients with invasive Candida infection (ICI). This study describes our experience with micafungin at Surgical Critical Care Units (SCCUs).. A multicenter, observational, retrospective study was performed (12 SCCUs) by reviewing all adult patients receiving 100 mg/24h micafungin for ≥72h during ad-mission (April 2011-July 2013). Patients were divided by ICI category (possible, probable + proven), 24h-SOFA (<7, ≥7) and outcome.. 72 patients were included (29 possible, 13 probable, 30 proven ICI). Forty patients (55.6%) presented SOFA ≥7. Up to 78.0% patients were admitted after urgent surgery (64.3% with SOFA <7 vs. 90.3% with SOFA ≥7, p=0.016), and 84.7% presented septic shock. In 66.7% the site of infection was intraabdominal. Forty-nine isolates were recovered (51.0% C. albicans). Treatment was empirical (59.7%), microbiologically directed (19.4%), rescue therapy (15.3%), or anticipated therapy and prophylaxis (2.8% each). Empirical treatment was more frequent (p<0.001) in possible versus probable + proven ICI (86.2% vs. 41.9%). Treatment (median) was longer (p=0.002) in probable + proven versus possible ICI (13.0 vs. 8.0 days). Favorable response was 86.1%, without differences by group. Age, blood Candida isolation, rescue therapy, final MELD value and %MELD variation were significantly higher in patients with non-favorable response. In the multivariate analysis (R2=0.246, p<0.001) non-favorable response was associated with positive %MELD variations (OR=15.445, 95%CI= 2.529-94.308, p=0.003) and blood Candida isolation (OR=11.409, 95%CI=1.843-70.634, p=0.009).. High favorable response was obtained, with blood Candida isolation associated with non-favorable response, in this series with high percentage of patients with intraabdominal ICI, septic shock and microbiological criteria for ICI.

Topics: Adult; Aged; Candidiasis, Invasive; Critical Care; Cross Infection; Diagnosis-Related Groups; Echinocandins; Female; Fungemia; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Lipopeptides; Male; Micafungin; Middle Aged; Multiple Organ Failure; Mycoses; Postoperative Complications; Retrospective Studies; Severity of Illness Index; Shock, Septic; Spain; Treatment Outcome

Limited information about the pharmacokinetics of micafungin in the peritoneal cavity is available. The aim of this study was to explore the pharmacokinetics/pharmacodynamics of micafungin in plasma and peritoneal fluid in post-surgical critically ill patients with proven or suspected intra-abdominal fungal infection.. Patients were administered 100 mg/day micafungin. Serial blood and peritoneal fluid samples were collected on day 1 and day 3 (steady-state) of treatment. Concentrations were determined by validated chromatography and were subject to a population pharmacokinetic analysis with Pmetrics(®). Monte Carlo simulations were performed for AUC0-24/MIC ratios in plasma. The PTA was calculated using AUC0-24/MIC cut-offs: 285 for Candida parapsilosis and 3000 for non-parapsilosis Candida spp.. Ten patients were included; six were male. The median (range) age, APACHE II score and Mannheim peritonitis index were 72 (43-85) years, 15 (11-36) and 26 (8-37), respectively. On day 1, median (SD) penetration of micafungin into the peritoneal cavity was 30% (30%-40%). A three-compartment model adequately described the data. The mean (SD) estimates for clearance and volume of distribution of the central compartment were 1.27 (0.75) L/h and 9.26 (1.11) L, respectively. In most patients, the PTA in plasma was ≥ 90% for MICs of 0.008-0.016 mg/L for Candida spp. and 0.125-0.25 mg/L for C. parapsilosis.. After the first dose, micafungin at 100 mg/day achieves pharmacokinetic/pharmacodynamic targets in plasma for Candida spp. and C. parapsilosis MICs of 0.008-0.016 and 0.125-0.25 mg/L, respectively.

Topics: Aged; Aged, 80 and over; Antifungal Agents; Ascitic Fluid; Candidiasis; Critical Illness; Drug Monitoring; Echinocandins; Female; Humans; Lipopeptides; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Peritonitis; Plasma; Postoperative Complications; Prospective Studies; Time Factors

Abstract An 88-year-old man underwent uneventful phacoemulsification and aspiration with an implantation of a preloaded acrylic intraocular lens. Six months later, he developed endophthalmitis with negative aqueous cultures, and the inflammation was refractory to conventional antibacterial therapies. He was treated successfully with vitrectomy and removal of the IOL and the entire lens capsule. A combination of intravitreal voriconazole and systemic micafungin were prescribed, and the inflammation was resolved. As best we know, this is the first case of Aspergillus tubingenesis endophthalmitis that followed the implantation of a preloaded intraocular lens.

Topics: Aged, 80 and over; Antifungal Agents; Aspergillosis; Aspergillus; Device Removal; Drug Therapy, Combination; Echinocandins; Endophthalmitis; Eye Infections, Fungal; Humans; Intravitreal Injections; Lens Implantation, Intraocular; Lipopeptides; Male; Micafungin; Phacoemulsification; Postoperative Complications; Pyrimidines; Triazoles; Visual Acuity; Vitrectomy; Voriconazole

The frequency of invasive fungal sinusitis (IFS) has increased in recent years with the use of steroids, onset of diabetes mellitus, and the administration of antibacterial agents. We report on the clinical features and outcomes of four patients with IFS involving the cavernous sinus and orbit. Prognostic factors facilitating an early diagnosis are described, and the usefulness of combination therapy involving systemic administration of antifungal agents and surgical intervention is discussed.. We treated four patients with IFS between March 2003 and November 2007 at Ehime University Hospital. Patients were two males and two females, aged from 61 to 74 years (mean 67.8 years).. With regard to clinical symptoms, headache was observed in all patients, and cranial nerve paralysis (visual disturbance, blindness, cheek paresthesia) was seen in 3 patients. β-D-Glucan levels in four patients were high compared with normal values. Aspergillus was histopathologically identified from biopsy specimens in all patients. One patient was complicated with Candida in addition to the Aspergillus infection. Orbital exenteration and ESS were performed in 2 patients as surgical debridement. In all patients, systemic administration of antifungal agents was initiated after surgery.. All patients received strategic treatment with surgery and systemic administration of anti-fungal agents. The single fatality was due to brain infarction caused by the spread of Aspergillus, and the remaining three patients are still alive. Our observations in these patients suggest that early diagnosis and strategic treatment may improve the prognosis of IFS.

Topics: Aged; Antifungal Agents; Aspergillosis; Biopsy; Blindness; Brain Infarction; Candidiasis; Cavernous Sinus; Combined Modality Therapy; Debridement; Early Diagnosis; Echinocandins; Fatal Outcome; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Lipopeptides; Magnetic Resonance Imaging; Male; Maxillary Sinusitis; Micafungin; Middle Aged; Orbit Evisceration; Orbital Diseases; Postoperative Complications; Pyrimidines; Sphenoid Sinusitis; Tomography, X-Ray Computed; Triazoles; Voriconazole

Micafungin, the first candin antifungal drug developed in Japan, has a significant therapeutic effect against deep-seated mycoses caused by Candida or Aspergillus. Little is known, however, about the optimal dosage or disposition of micafungin in patients with severe hepatic impairment. Nine liver transplant recipients (5 males and 4 females) were enrolled in this study. In 1 recipient with a markedly small-for-size graft (ratio of graft volume to standard liver volume at the time of transplantation: 25.9%), the areas under the plasma concentration-time curves up to 12 hours postdose (AUC(0-12 h)) at doses of 50 and 100 mg/d were 79.38 and 601.17 mug.h/mL, respectively. The corresponding elimination half-life (T(1/2)) values were 16.01 and 75.75 hours, and saturated elimination was observed only at the dose of 100 mg/d. The mean urinary ratio of 6beta-hydroxycortisol to cortisol (6beta-OHF/F) in the small-for-size graft recipient was significantly (P < .05) lower than that in the other recipients. In conclusion, graft size was an important factor affecting disposition of micafungin. For liver transplant recipients with markedly small-for-size grafts, the optimal dosage of micafungin to reach and maintain therapeutic plasma levels is estimated to be 50 mg/d.

Topics: Antifungal Agents; Area Under Curve; Aspergillosis; Candidiasis; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Echinocandins; Female; Humans; Lipopeptides; Lipoproteins; Liver; Liver Transplantation; Male; Micafungin; Organ Size; Peptides, Cyclic; Postoperative Complications; Postoperative Period