micafungin and Cross-Infection

Topics: Antifungal Agents; Candidiasis; Catheters; Contraindications; Cross Infection; Disease Susceptibility; Echinocandins; Fluconazole; Humans; Immunocompromised Host; Immunosuppressive Agents; Lipopeptides; Micafungin; Risk Factors; Transplantation

Topics: Anidulafungin; Antifungal Agents; beta-Glucans; Candida; Candidiasis; Caspofungin; Cross Infection; Echinocandins; Fungemia; Humans; Infusions, Intravenous; Lipopeptides; Lipoproteins; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Peptides, Cyclic; Practice Guidelines as Topic

Although frequently used in treating intensive care unit (ICU) patients with sepsis, empirical antifungal therapy, initiated for suspected fungal infection, has not been shown to improve outcome.. To determine whether empirical micafungin reduces invasive fungal infection (IFI)-free survival at day 28.. Multicenter double-blind placebo-controlled study of 260 nonneutropenic, nontransplanted, critically ill patients with ICU-acquired sepsis, multiple Candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between July 2012 and February 2015 in 19 French ICUs.. Empirical treatment with micafungin (100 mg, once daily, for 14 days) (n = 131) vs placebo (n = 129).. The primary end point was survival without proven IFI 28 days after randomization. Key secondary end points included new proven fungal infections, survival at day 28 and day 90, organ failure, serum (1-3)-β-D-glucan level evolution, and incidence of ventilator-associated bacterial pneumonia.. Among 260 patients (mean age 63 years; 91 [35%] women), 251 (128, micafungin group; 123, placebo group) were included in the modified intent-to-treat analysis. Median values were 8 for Sequential Organ Failure Assessment (SOFA) score, 3 for number of Candida-colonized sites, and 99 pg/mL for level of (1-3)-β-D-glucan. On day 28, there were 82 (68%) patients in the micafungin group vs 79 (60.2%) in the placebo group who were alive and IFI free (hazard ratio [HR], 1.35 [95% CI, 0.87-2.08]). Results were similar among patients with a (1-3)-β-D-glucan level of greater than 80 pg/mL (n = 175; HR, 1.41 [95% CI, 0.85-2.33]). Day-28 IFI-free survival in patients with a high SOFA score (>8) was not significantly different when compared between the micafungin vs placebo groups (HR, 1.69 [95% CI, 0.96-2.94]). Use of empirical micafungin decreased the rate of new invasive fungal infection in 4 of 128 patients (3%) in the micafungin group vs placebo (15/123 patients [12%]) (P = .008).. Among nonneutropenic critically ill patients with ICU-acquired sepsis, Candida species colonization at multiple sites, and multiple organ failure, empirical treatment with micafungin, compared with placebo, did not increase fungal infection-free survival at day 28.. clinicaltrials.gov Idenitfier: NCT01773876.

Topics: Aged; Anti-Bacterial Agents; Antifungal Agents; Candidiasis; Candidiasis, Invasive; Critical Illness; Cross Infection; Disease-Free Survival; Double-Blind Method; Drug Administration Schedule; Echinocandins; Female; Humans; Lipopeptides; Male; Micafungin; Middle Aged; Multiple Organ Failure; Time Factors

The potential interest of antifungal treatment of non-immunocompromized patients with sepsis, extra-digestive Candida colonization and multiple organ failure is unknown. It represents three-quarters of antifungals prescribed in Intensive Care Units. It may allow early treatment of invasive fungal infection in the incubation phase but expose patients to unnecessary antifungal treatments with subsequent cost and fungal selection pressure. As early diagnostic tests for invasive candidiasis are still considered to be insufficient, the potential interest in this strategy needs to be demonstrated.. This prospective multicenter, double blind, randomized-controlled trial is conducted in 23 French Intensive Care Units. All adult patients, mechanically ventilated for more than four days with sepsis of unknown origin and with at least one extradigestive fungal colonization site and multiple organ failure are eligible for randomization. Patients with proven invasive candidiasis are not included. After a complete mycological screening, patients are allocated to receive micafungin 100 mg intravenously once a day or placebo for 14 days. We plan to enroll 260 patients. The main objective is to demonstrate that micafungin increases survival of patients without invasive candidiasis at day 28 as compared to placebo. Other outcomes include day 28 and 90 survival and organ failure evolution. Additionally, pharmacokinetics of micafungin in enrolled patients will be measured and evolution of fungal biomarkers and susceptibility profiles of infecting fungi will also be followed.. This study will help to provide guidelines for treating non-immunocompromized patients with fungal colonization multiple organ failure and sepsis of unknown origin.. Clinicaltrials.gov number NCT01773876.

Topics: Antifungal Agents; Candidemia; Clinical Protocols; Cross Infection; Double-Blind Method; Echinocandins; Humans; Intensive Care Units; Lipopeptides; Micafungin; Multiple Organ Failure; Prospective Studies

Micafungin (MCFG), an echinocandin antifungal agent, exhibits antifungal activity against Candida albicans and non-albicans Candida. The fungicidal activity of MCFG against clinical isolates of Candida species was investigated, and the clinical efficacy of MCFG in therapy of deep mycosis in surgery was studied using the AKOTT algorithm. The minimum inhibitory concentration and minimum fungicidal concentration values of fluconazole were ≤0.06-4 and >64 μg/ml, respectively, for each strain, whereas these values of MCFG were 0.008-0.5 and 0.016-1 μg/ml, suggesting that MCFG provided superior fungicidal ability against Candida albicans and non-albicans Candida. The subjects were separated into two groups: group A consisted of 20 subjects with both persisting fever refractory to broad-spectrum antibiotics and positive reaction to β-D-glucan test, and group B consisted of 20 subjects with either of those conditions. The overall response was evaluated as "effective" in 17 patients (85%) and 20 patients (100%) in groups A and B, respectively. In total, response was evaluated as "effective" in 37 patients (92.5%) and "ineffective" in 3 patients (7.5%). These findings suggest that MCFG administration should be used as empirical therapy for deep mycosis in surgically ill patients as it was shown to be an effective antifungal drug lacking serious adverse effects.

Topics: Adult; Aged; Aged, 80 and over; Antifungal Agents; Candida; Candidiasis, Invasive; Cross Infection; Digestive System Neoplasms; Digestive System Surgical Procedures; Echinocandins; Female; Humans; Lipopeptides; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Surgical Wound Infection; Treatment Outcome

Invasive candidiasis and candidemia are life-threatening nosocomial infections in intensive care patients.. A post hoc analysis of a phase 3 trial assessing micafungin (100 mg/day for subjects > 40 kg; 2 mg/kg/day for subjects

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Cross Infection; Echinocandins; Female; Humans; Intensive Care Units; Lipopeptides; Male; Micafungin; Middle Aged; Multivariate Analysis

The molecular epidemiology and antifungal susceptibility of Aspergillus nidulans species complex has not been well studied. To evaluate the genetic diversity and antifungal susceptibility patterns of clinical and environmental isolates of A. nidulans complex. Sixty clinical and environmental isolates of Aspergillus section Nidulantes were collected from five countries (Iran, The Netherlands, Spain, Portugal and Greece). The species were molecularly identified by sequencing of β-tubulin gene. The genetic diversity of A nidulans complex isolates (n = 54) was determined with a microsatellite genotyping assay. Antifungal susceptibility profile was determined using EUCAST method. The isolates were classified as A nidulans (46.7%), A spinulosporus (26.6%), A quadrilineatus (10%), A pachycristatus (3.3%), A rugulosus (3.3%), A unguis (5%), A creber, (1.7%), A olivicola (1.7%) and A sydowii (1.7%). Thirty-four sequence types (STs) were identified among the 54 A nidulans complex isolates. A high level of genetic diversity was found among A nidulans sensu stricto strains but low diversity was found among A spinulosporus strains. Amphotericin B showed high MICs to all species. The most active azole was posaconazole (GM = 0.64 mg/L), while itraconazole showed the highest MICs among azoles (GM = 2.95 mg/L). A spinulosporus showed higher MICs than A nidulans sensu stricto for all antifungals except for micafungin and anidulafungin. Interspecies variations may result in differences in antifungal susceptibility patterns and challenge antifungal therapy in infections caused by A nidulans. Differences in the distribution of STs or persistence of multiple STs might be related to the sources of isolation and niche specialisation.

Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Aspergillosis; Aspergillus; Aspergillus fumigatus; Aspergillus nidulans; Azoles; Cross Infection; Environmental Microbiology; Genetic Variation; Greece; Humans; Iran; Micafungin; Microbial Sensitivity Tests; Microsatellite Repeats; Molecular Epidemiology; Netherlands; Phylogeny; Phylogeography; Portugal; Spain; Tubulin

Candida auris, a multidrug-resistant species, has the propensity of nosocomial transmission despite normal decontamination procedures. Here, we describe the isolation of C auris from patients in various hospitals in Kuwait during 2014-2018. Susceptibility to antifungal drugs and molecular basis of resistance to fluconazole, voriconazole and micafungin were also studied.. Candida auris (n = 314) obtained from 126 patients in eight hospitals were studied. All isolates were identified by PCR amplification and/or PCR-sequencing of ribosomal DNA (rDNA). Antifungal susceptibility was determined by Etest. Molecular basis of resistance to fluconazole and micafungin was studied by PCR-sequencing of ERG11 and FKS1 genes, respectively.. Bloodstream (n = 58), urine (n = 124), respiratory (n = 98) and other (n = 34) specimens yielded 314 C auris isolates. The proportion of bloodstream C auris among all yeast isolates was higher (42 of 307, 13.7%) in 2018 as compared to 2014-2017 (16 of 964, 1.7%) (P = .001). More bloodstream isolates (42 of 139) were cultured in 2018 than during 2014-2017 (16 of 175) (P = .001). Resistance to amphotericin B, fluconazole, voriconazole and micafungin was detected in 27.1%, 100%, 41.1% and 1.7% isolates, respectively. Fluconazole-resistant isolates contained either Y132F or K143R mutation in ERG11. Isolates with K143R mutation were additionally resistant to voriconazole. Micafungin-resistant isolates contained S639F mutation in hot spot 1 of FKS1.. Our study highlights spreading of C auris in major hospitals across Kuwait and its increasing role as a bloodstream pathogen in 2018. Cross-resistance to voriconazole was also seen in isolates with K143R mutation in ERG11, while micafungin-resistant isolates harboured S639F mutation in hot spot 1 of FKS1.

Topics: Antifungal Agents; Candida; Candidemia; Candidiasis; Cross Infection; Drug Resistance, Fungal; Fluconazole; Genes, Fungal; Humans; Kuwait; Micafungin; Microbial Sensitivity Tests; Pathology, Molecular; Voriconazole

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

The frequency of breakthrough invasive fungal diseases (IFDs) during echinocandin therapy is unclear. We retrospectively analyzed 534 hematologic patients treated with echinocandin (caspofungin, N = 55; micafungin, N = 306; anidulafungin, N = 173). Four proven IFDs were found, caused by Candida parapsilosis (N = 2), C. parapsilosis and Candida glabrata (N = 1), and Fusarium species (N = 1). Four cases of possible IFDs were observed, all showing pulmonary infection. One case showed features suggestive of hepatosplenic candidiasis. Six of these eight cases had previously received the purine analog clofarabine. Breakthrough IFD during echinocandin treatment occurred infrequently (1.5 %), caused predominantly by Candida species. Clofarabine usage was an important risk factor.

Topics: Adenine Nucleotides; Adult; Anidulafungin; Antibiotic Prophylaxis; Antifungal Agents; Antimetabolites, Antineoplastic; Arabinonucleosides; Candida; Candidiasis, Invasive; Caspofungin; China; Clofarabine; Cohort Studies; Cross Infection; Echinocandins; Fusariosis; Fusarium; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Lipopeptides; Lung Diseases, Fungal; Micafungin; Retrospective Studies; Risk Factors

The results of a 3-year experience with voriconasole in oncologic practice are presented. Rational schemes for the use of caspofungin and mycofungin in the treatment of oncologic inpatients and the criteria of their use in the therapy of fungal nosocomial infections were developmed. Good clinical and microbiological efficacy of caspofungin and mycofungin against Candida non-albicans was shown.

Topics: Aged; Antifungal Agents; Candida; Candidiasis; Caspofungin; Cross Infection; Drug Resistance, Fungal; Echinocandins; Female; Humans; Intensive Care Units; Lipopeptides; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Neoplasms

Recent epidemiologic literature indicates that candidal species resistant to azoles are becoming more prevalent in the face of increasing incidence of hospitalizations with candidemia. Echinocandins, a new class of antifungal agents, are effective against resistant candidal species. As delaying appropriate antifungal coverage leads to increased mortality, we evaluated the cost-effectiveness of 100 mg daily empiric micafungin (MIC) vs. 400 mg daily fluconazole (FLU) for suspected intensive care unit-acquired candidemia (ICU-AC) among septic patients.. We designed a decision model with inputs from the literature in a hypothetical 1000-patient cohort with suspected ICU-AC treated empirically with either MIC or FLU or no treatment accompanied by a watchful waiting strategy. We examined the differences in the number of survivors, acquisition costs of antifungals, and lifetime costs among survivors in the cohort under each scenario, and calculated cost per quality adjusted life year (QALY). We conducted Monte Carlo simulations and sensitivity analyses to determine the stability of our estimates.. In the base case analysis, assuming ICU-AC attributable mortality of 0.40 and a 52% relative risk reduction in mortality with appropriate timely therapy, compared with FLU (total deaths 31), treatment with MIC (total deaths 27) would result in four fewer deaths at an incremental cost/death averted of $61,446. Similarly, in reference case, incremental cost-effectiveness of MIC over FLU was $34,734 (95% confidence interval $26,312 to $49,209) per QALY. The estimates were most sensitive to the QALY adjustment factor and the risk of candidemia among septic patients.. Given the increasing likelihood of azole resistance among candidal isolates, empiric treatment of ICU-AC with 100 mg daily MIC is a cost-effective alternative to FLU.

Topics: Antifungal Agents; Candidiasis; Cost-Benefit Analysis; Cross Infection; Decision Trees; Drug Costs; Drug Resistance, Fungal; Echinocandins; Fluconazole; Fungemia; Humans; Incidence; Intensive Care Units; Lipopeptides; Micafungin; Models, Econometric; Monte Carlo Method; Quality-Adjusted Life Years