micafungin and Sepsis

Emerging fungal pathogens, such as Geotrichum capitatum, are often associated with poor prognosis and represent a new challenge in modern medicine. Invasive Geotrichum capitatum infection is rare and has been reported exclusively in patients who showed signs of severe immunodeficiency, particularly those affected by haematological malignancies. The optimal therapy against systemic geotricosis has not yet been identified due to limited data about its antifungal susceptibility. The use of several therapeutic strategies and the low number of cases treated does not allow identification of specific therapeutic protocols. Furthermore, in spite of antifungal therapy, mortality rates reach very high levels. We report a case of systemic Geotrichum capitatum infection in a 78-year-old male treated with salvage therapy after acute myeloid leukaemia (AML) relapse. Geotrichum capitatum was isolated from his blood culture and identified by using Vitek 2 and Maldi time-of-flight system (MALDI-TOF). The infection was unsuccessfully treated, despite in vitro susceptibility, with micafungin and liposomal amphotericin B.

Topics: Aged; Amphotericin B; Antifungal Agents; Coma; Drug Therapy, Combination; Echinocandins; Fatal Outcome; Geotrichum; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Lipopeptides; Male; Micafungin; Recurrence; Sepsis; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Treatment Failure

: Candidal fungal infection rates in neonates are increasing and are a significant cause of mortality, especially in low birth weight infants. Micafungin is an echinocandin that works by inhibiting 1,3-beta-D-glucan synthase, an enzyme responsible for fungal cell wall synthesis. The objective of this study was to determine the safety and pharmacokinetics of micafungin in premature infants.. : This was a phase I, single-dose, multicenter, open-label, sequential-dose trial of intravenous micafungin investigating 3 doses (0.75 mg/kg, 1.5 mg/kg and 3.0 mg/kg) in 18 premature infants weighing >1000 g (n = 6 in each dosage group). A further 5 infants (500-1000 g) were enrolled in the 0.75 mg/kg dosage group only.. : The mean +/- standard deviation gestational age in the >1000 g dosage group was 26.4 +/- 2.4 weeks and, on entry, patients had one or more of a variety of underlying conditions, including sepsis, pneumonia and other infections caused by Candida or other species. Micafungin pharmacokinetics in preterm infants appears linear. However, premature infants >1000 g on average displayed a shorter half-life (8 hours) and a more rapid rate of clearance (approximately 39 mL/h per kg) compared with published data in older children and adults. All doses of micafungin were well tolerated and no serious drug-related adverse events were observed.. : Single doses of micafungin, ranging up to 3.0 mg/kg, appear well tolerated in premature infants weighing >1000 g. The drug's elimination half-life and total plasma clearance in preterm infants appear dissimilar to published values for these parameters in older children and adults. The reason(s) for this apparent difference remain to be investigated.

Topics: Antifungal Agents; Candidiasis; Echinocandins; Female; Half-Life; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Injections, Intravenous; Lipopeptides; Lipoproteins; Male; Metabolic Clearance Rate; Micafungin; Peptides, Cyclic; Pneumonia; Sepsis

To describe micafungin pharmacokinetic (PK) alterations of sepsis induced in piglets and to determine whether the porcine septic model is able to predict the PK of micafungin in septic patients at the plasma and peritoneal sites.. From healthy (n = 8) and septic piglet group (n = 16), total micafungin concentrations were subject to a population PK analysis using Monolix®. Data from 16 septic humans patients from others studies was used to compare micafungin PK between septic piglets and septic patients.. Sepsis induced in piglets slightly alters the total clearance and the volume of distribution, while inter-compartment clearance is increased (from 3.88 to 5.74 L/h) as well as the penetration into peritoneal cavity (from 61 to 90%). In septic human patients, PK parameters are similar except for the Vd, which is corrected by an allometric factor based on the body weight of each species. Micafungin penetration into peritoneal cavity of humans is lower than in septic piglets (40 versus 90%).. The sepsis induced in the porcine model alters the PK of micafungin comparable to that in humans. In addition, micafungin PK is similar between these two species at the plasma level taking into account the allometric relationship of the body weight of these species on the central volume of distribution. The porcine septic plasma model would be able to predict the micafungin PK in the septic patients. However, further studies on peritoneal penetration are necessary to characterize this inter-species difference.

Topics: Animals; Antifungal Agents; Biological Variation, Population; Disease Models, Animal; Female; Humans; Micafungin; Peritoneum; Sepsis; Species Specificity; Swine

This study aimed to identify parameters that influence micafungin pharmacokinetics in Chinese patients with sepsis in the intensive care unit and optimize micafungin dosage by determining the probability of reaching pharmacodynamic targets.. Blood samples were collected from 32 Chinese patients with sepsis who were treated with micafungin. The samples were analyzed and used to build a population pharmacokinetic model. Monte Carlo simulations were performed to estimate the probability of achieving adequate plasma levels of micafungin against Candida species.. Alanine aminotransferase and sequential organ failure assessment score were found to significantly influence the clearance and peripheral distribution volume of micafungin, respectively. Monte Carlo simulations based on area under the plasma concentration-time curve over 24 h showed that patients must be administered at least 200 and 250 mg micafungin daily to reach minimum inhibitory concentration breakpoints of 0.032 and 0.064 mg/L for Candida glabrata and Candida tropicalis, respectively. Additionally, a probability of target attainment of ≥ 90% could not be achieved for Candida krusei or Candida parapsilosis with a 300 mg daily dose.. The recommended daily dose of micafungin (100 mg) may produce low clinical success ratios in non-Candida albicans infections; therefore, higher doses should be administered to improve clinical outcomes.

Topics: Adult; Aged; Aged, 80 and over; Biological Variation, Population; Candida; Candidiasis; China; Dose-Response Relationship, Drug; Female; Humans; Intensive Care Units; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Models, Biological; Monte Carlo Method; Prospective Studies; Sepsis; Young Adult

Invasive candidiasis is an important cause of sepsis in extremely low birth weight infants (ELBW, < 1000 g), is often fatal, and frequently results in neurodevelopmental impairment (NDI) among survivors. We sought to assess the antifungal minimum inhibitory concentration (MIC) distribution for Candida in ELBW infants and evaluate the association between antifungal resistance and death or NDI.. This was a secondary analysis of a National Institute of Child Health and Human Development Neonatal Research Network study. MIC values were determined for fluconazole, amphotericin B and micafungin. NDI was assessed at 18-22 months adjusted age using the Bayley Scales of Infant Development. An infant was defined as having a resistant Candida isolate if ≥ 1 positive cultures from normally sterile sites (blood, cerebrospinal fluid, or urine) were resistant to ≥ 1 antifungal agent. In addition to resistance status, we categorized fungal isolates according to MIC values (low and high). The association between death/NDI and MIC level was determined using logistic regression, controlling for gestational age and Bayley Scales of Infant Development (II or III).. Among 137 ELBW infants with IC, MICs were determined for 308 isolates from 110 (80%) infants. Three Candida isolates from 3 infants were resistant to fluconazole. None were resistant to amphotericin B or micafungin. No significant difference in death, NDI, or death/NDI between groups with low and high MICs was observed.. Antifungal resistance was rare among infecting Candida isolates, and MIC level was not associated with increased risk of death or NDI in this cohort of ELBW infants.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis, Invasive; Cohort Studies; Drug Resistance, Fungal; Female; Fluconazole; Gestational Age; Humans; Infant; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Newborn, Diseases; Intensive Care Units, Neonatal; Male; Micafungin; Microbial Sensitivity Tests; Neurodevelopmental Disorders; Prospective Studies; Sepsis; Treatment Outcome

A 21-year-old woman was admitted to the emergency department (ED) with severe sepsis. Both the mechanism of infection and organisms discovered were unusual.

Topics: Analgesics, Opioid; Anti-Bacterial Agents; Antifungal Agents; Ciprofloxacin; Echinocandins; Emergency Service, Hospital; Female; Fluconazole; Humans; Lipopeptides; Malingering; Micafungin; Opioid-Related Disorders; Sepsis; Staphylococcal Infections; Young Adult

The purpose of the current study was to prevent bloodstream infection and invasive fungal infection (IFI) by administering prophylactic antibiotic and antifungal agents during intensive chemotherapy in patients being treated for acute leukemia.. Prophylaxis treatment was administered during intensive chemotherapy in children with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) from January 1, 2010 to December 31, 2012. Oral ciprofloxacin (at a dose of 300 mg/m(2) /12 hours) was administered after chemotherapy when a patient with AML or ALL became neutropenic and > 7 days of neutropenia was expected. Voriconazole (at a dose of 4 mg/kg/12 hours) was initiated at the onset of neutropenia in patients with AML and after 7 days of neutropenia in patients with ALL. Micafungin (at a dose of 2 mg/kg/day) was substituted for voriconazole when patients with ALL received vincristine. Prophylaxis treatment was discontinued when the absolute neutrophil count recovered to > 100/μL. All episodes of bloodstream infection, IFI, febrile neutropenia, and intensive care unit stays related to severe infection occurring between January 1, 2005 and December 31, 2012 were recorded.. During the preprophylaxis period, 62 children with ALL and 24 children with AML experienced a total of 44 episodes of bloodstream infection and 22 episodes of IFI. Seven patients died of severe infection. In contrast, in the prophylaxis period, 10 episodes of bloodstream infection occurred and no IFIs were reported to occur in 51 patients with ALL and 14 patients with AML. Moreover, no patient died of severe infection. Episodes of febrile neutropenia and intensive care unit stay were significantly reduced during the prophylaxis period.. Prophylaxis with ciprofloxacin and voriconazole or micafungin was found to reduce the rates of bloodstream infection and IFI in children with acute leukemia undergoing intensive chemotherapy.

Topics: Adolescent; Antibiotic Prophylaxis; Antifungal Agents; Antineoplastic Agents; Child; Child, Preschool; Ciprofloxacin; Cohort Studies; Drug Costs; Echinocandins; Female; Humans; Infant; Leukemia, Myeloid, Acute; Lipopeptides; Male; Micafungin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrimidines; Sepsis; Triazoles; Voriconazole

KB425796-C is a novel antifungal metabolite produced by the newly isolated bacterial strain Paenibacillus sp. No. 530603. This compound is a 40-membered macrocyclic lipopeptidolactone consisting of 12 amino acids and a 3-hydroxy-15-methylpalmitoyl moiety. KB425796-C displayed antifungal activity against micafungin-resistant fungi and was fungicidal to Trichosporon asahii in vitro. In a murine systemic infection model of T. asahii, KB425796-C showed excellent efficacy upon i.p. administration at 32 mg kg(-1). In addition, KB425796-C induced morphological changes in the hyphae of Aspergillus fumigatus and had fungicidal effects in combination with micafungin. In a mouse model of septic A. fumigatus infection, although non-treated mice survived for a maximum of only 6 days, the survival rate of micafungin-treated mice (0.1 mg kg(-1)) increased to 20%, while the survival rate of mice treated with a combination of micafungin (0.1 mg kg(-1)) and KB425796-C (32 mg kg(-1)) increased to 100% during the 31-day post-infection period. Our findings suggest that KB425796-C is a good candidate for the treatment of aspergillosis in combination with micafungin.

Topics: Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Depsipeptides; Disease Models, Animal; Drug Resistance, Fungal; Drug Synergism; Drug Therapy, Combination; Echinocandins; Female; Injections, Intraperitoneal; Lipopeptides; Micafungin; Mice; Mice, Inbred DBA; Mice, Inbred ICR; Paenibacillus; Sepsis; Survival Rate; Trichosporon; Trichosporonosis

The Sporopachydermia cereana species lives in decaying stems of cactus and is exceptionally rare as a human pathogen. A 57-year-old man with therapy-refractory acute promyelocytic leukaemia developed severe neutropaenia. After about 3 weeks of micafungin used as prophylaxis, he developed high fever, multiple pulmonary nodular infiltrates and a painful leg lesion. Blood culture yielded a yeast which was not identified by the Vitek 2 system. On ITS1-5.8S-ITS2 gene sequencing, the isolate was identified as S. cereana. Antifungal sensitivity by the Etest showed that the minimum inhibitory concentration for fluconazole was 0.75 μg/mL, and for anidulafungin, it was >32 μg/mL. He responded to liposomal amphotericin B but later died of Escherichia coli septicaemia. There were no cactus plants in the vicinity, suggesting that S. cereana might have alternative habitats.

Topics: Antifungal Agents; Chemoprevention; DNA, Fungal; DNA, Ribosomal; DNA, Ribosomal Spacer; Echinocandins; Escherichia coli Infections; Fatal Outcome; Fungemia; Humans; Immunocompromised Host; Leukemia, Promyelocytic, Acute; Lipopeptides; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Opportunistic Infections; Radiography, Thoracic; Saccharomycetales; Sepsis; Sequence Analysis, DNA; Skin; Tomography, X-Ray Computed

Prior analyses suggest that empiric fluconazole for ICU patients with sepsis is cost-effective. Using updated estimates of efficacy and cost, Zilberberg and colleagues compare the use of micafungin with that of fluconazole. The authors conclude that micafungin is an attractive alternative to fluconazole. This conclusion is driven by recent reduction in micafungin's cost and by better activity of micafungin against azole-resistant Candida species. Their results are limited by inflated estimates of efficacy, life expectancy and risk of Candida sepsis. This commentary explores the rationale for early anti-Candida strategies in the ICU and highlights the contribution and limitations of the article by Zilberberg and colleagues.

Topics: Antifungal Agents; Candida; Candidiasis; Clinical Protocols; Echinocandins; Fluconazole; Humans; Intensive Care Units; Lipopeptides; Micafungin; Sepsis

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by recurrent infections with certain types of bacteria and fungi. Presented herein is the case of a 29 year old woman with CGD who suffered from bacteria-associated haemophagocytic syndrome and a septic pulmonary embolism following a uterine infection and sepsis, caused by Burkholderia cepacia complex.

Topics: Adult; Anti-Bacterial Agents; Antifungal Agents; Burkholderia cepacia complex; Burkholderia Infections; Echinocandins; Female; Granulomatous Disease, Chronic; Humans; Lipopeptides; Lipoproteins; Lymphohistiocytosis, Hemophagocytic; Micafungin; Minocycline; Peptides, Cyclic; Pulmonary Embolism; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination