micafungin and Peritonitis

To describe the clinical and microbiological features associated with fungal peritonitis in peritoneal dialysis (PD) patients at Hôpital Maisonneuve-Rosemont, from August 1996 to July 2006.. Cases were retrieved from the microbiology laboratory culture registry. Antifungal susceptibility was determined by the Clinical and Laboratory Standards Institute M27A3 method.. Among 288 PD patients (total follow-up of 7258 patient-months), nine were found with fungal peritonitis. Candida spp were identified in all of them, with a majority of non-albicans Candida species. Resistance to fluconazole, itraconazole, or voriconazole was as frequent as potential resistance to amphotericin B. No isolate was resistant to caspofungin and one was resistant to micafungin. Prior bacterial peritonitis was frequent (67%). All patients had their PD catheter removed and all of them survived.. In our institution, fungal peritonitis in PD patients is rare. All cases were caused by Candida species. Variable susceptibility patterns were observed, which may influence the initial empirical antifungal therapy and underscore the importance of individual speciation and susceptibility testing of invasive Candida isolates.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candida; Caspofungin; Drug Resistance, Fungal; Echinocandins; Female; Fluconazole; Follow-Up Studies; Humans; Itraconazole; Lipopeptides; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Mycoses; North America; Peritoneal Dialysis; Peritonitis; Pyrimidines; Triazoles; Voriconazole

A possible increase in Candida resistance, especially in Candida glabrata, has been speculated according to poor diffusion of echinocandins to peritoneal fluid.. 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 high-performance liquid chromatography (HPLC/F), whereas caspofungin concentrations were established by bioassay.. 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.

Topics: Adult; Anidulafungin; Antifungal Agents; Candida glabrata; Candidiasis; Caspofungin; Critical Illness; Echinocandins; Female; Humans; Male; Micafungin; Microbial Sensitivity Tests; Peritonitis; Prospective Studies

Candida peritonitis is a crucial disease, however the optimal antifungal therapy regimen has not been clearly defined. Peritoneal fibrosis (PF) can be caused by abdominal surgery, intra-abdominal infection, and malignant diseases, and is also widely recognized as a crucial complication of long-term peritoneal dialysis. However, the influence of PF on Candida peritonitis prognosis remains unknown. Here, we evaluated the severity of Candida peritonitis within the context of PF and the efficacy of micafungin using mice. A PF mouse model was generated by intraperitoneally administering chlorhexidine gluconate. Candida peritonitis, induced by intraperitoneal inoculation of Candida albicans, was treated with a 7-day consecutive subcutaneous administration of micafungin. Candida infection caused a higher mortality rate in the PF mice compared with the control mice on day 7. Proliferative Candida invasion into the peritoneum and intra-abdominal organs was confirmed pathologically only in the PF mice. However, all mice in both groups treated with micafungin survived until day 20. Micafungin treatment tends to suppress inflammatory cytokines in the plasma 12 h after infection in both groups. Our results suggest that PF enhances early mortality in Candida peritonitis. Prompt initiation and sufficient doses of micafungin had good efficacy for Candida peritonitis, irrespective of the underlying PF.

Topics: Animals; Antifungal Agents; Biomarkers; Candida; Cytokines; Disease Models, Animal; Histocytochemistry; Humans; Micafungin; Mice; Peritoneal Fibrosis; Peritonitis; Prognosis; Treatment Outcome

A 32-year-old man on peritoneal dialysis (PD) was hospitalized for seven days due to fever. A diagnosis of yeast-like fungal peritonitis was made by Gram staining. The patient was started on intravenous micafungin and oral fluconazole therapy following removal of the PD catheter. A fungal pathogen was isolated from the peritoneal fluid and identified as Cryptococcus species. Based on antifungal susceptibility testing, the treatment was changed to voriconazole and continued for 3 months. A genetic analysis identified the isolate as Cryptococcus laurentii (C. laurentii). This patient was diagnosed with C. laurentii PD-related peritonitis and was successfully treated with voriconazole and removal of the PD catheter.

Topics: Adult; Antifungal Agents; Catheterization; Catheters, Indwelling; Cryptococcus; Device Removal; Echinocandins; Fluconazole; Humans; Lipopeptides; Male; Micafungin; Mycoses; Peritoneal Dialysis; Peritonitis

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

Lachancea fermentati is an environmental yeast that is also used in the fermentation of alcoholic drinks. It has not previously been described as a human pathogen although the closely related yeast, Saccharomyces boulardii, can cause fungemia. Here we report a case of L. fermentati acting as a pathogen in a septic patient with cultures positive from blood, peritoneal fluid, bile, and sputum.. A 36 year-old Caucasian man was hospitalized with acute alcoholic hepatitis complicated by Escherichia coli spontaneous bacterial peritonitis. Three days after admission, he developed new fevers with sepsis requiring mechanical ventilation and vasopressor support. He was found to have a bowel perforation. Cultures from blood, peritoneal fluid, and sputum grew a difficult-to-identify yeast. Micafungin was started empirically. On hospital day 43 the yeast was identified as L. fermentati with low minimum inhibitory concentrations (by Epsilometer test) to all antifungals tested. Micafungin was changed to fluconazole to complete a 3-month course of therapy. Serial peritoneal fluid cultures remained positive for 31 days. One year after his initial hospitalization the patient had ongoing cirrhosis but had recovered from fungemia.. This case demonstrates the need for clinicians to consider host factors when interpreting culture results with normally non-pathogenic organisms. In this immunocompromised host L. fermentati caused disseminated disease. We believe his hobby of brewing alcohol led to colonization with L. fermentati, which then resulted in invasive disease when the opportunity arose.

Topics: Adult; Antifungal Agents; Echinocandins; Fluconazole; Fungemia; Hepatitis, Alcoholic; Humans; Immunocompromised Host; Lipopeptides; Male; Micafungin; Peritonitis; Yeasts

A 49 year-old woman with chronic renal failure (CRF) on continuous ambulatory peritoneal dialysis (CAPD) because of Goodpasture Syndrome was admitted to our hospital since she had a high fever and severe abdominal pain. A diagnosis of peritonitis was made from the physical examination and laboratory findings. The peritonitis was refractory to conventional antibiotics therapy. Candida parapsilosis was detected from dialysite. The peritonitis was aggravated although the antibiotic was changed to an antifungal agent (fluconazole 400mg/day). Fluconazole was replaced to micafungin (MCFG) and the catheter for CAPD was removed. The fungal peritonitis improved dramatically and beta-D glucan was decreased from 104 to 12.6 (pg/ml). No adverse effect was observed after using MCFG. It has been known that fungal peritonitis of CRF patients is refractory to treatment and the mortality rate is high. To our best knowledge, there is no report that MCFG was used for CRF patients with fungal peritonitis. However, we used MCFG safely and effectively for CRF patients. Therefore, it is suggested that MCFG is a new effective and safe antifungal agent for Candida parapsilosis peritonitis with CRF.

Topics: Antifungal Agents; Candida; Candidiasis; Echinocandins; Female; Humans; Kidney Failure, Chronic; Lipopeptides; Lipoproteins; Micafungin; Middle Aged; Peptides, Cyclic; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis