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IDCases 2024is an emerging opportunistic yeast in the Mediterranean region typically isolated from immunocompromised patients, usually affected by blood malignancies. We reported a...
is an emerging opportunistic yeast in the Mediterranean region typically isolated from immunocompromised patients, usually affected by blood malignancies. We reported a rare case of infection, isolated from a drainage fluid in a patient affected by lung cancer recovered in the University Hospital of Campania "Luigi Vanvitelli", Naples, Italy. The isolate was identified by phenotypic methods, i.e., Gram and Lactophenol cotton blue (LCB) staining, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis. We identified on the third day from Sabouraud Dextrose Agar supplemented with chloramphenicol and gentamicin. Antifungal susceptibility test revealed that 5-fluorocytosine was the most active drug against , followed by itraconazole and voriconazole, micafungin, amphotericin B and fluconazole, posaconazole, anidulafungin, and caspofungin. Our data showed the importance of an early cultural and fast microbiology diagnosis based on the characteristic morphologic features observed in Gram-stained smears of blood culture positive bottles, and the validation via MALDI-TOF MS. This dual approach has significant impact in the clinical management of infectious diseases and antibiotic stewardship, by integrating sample processing, fluid handling, and detection for rapid bacterial diagnosis.
PubMed: 38681078
DOI: 10.1016/j.idcr.2024.e01959 -
Journal of Fungi (Basel, Switzerland) Apr 2024Vascular catheter-related infections, primarily caused by and , pose significant challenges due to the formation of biofilms on catheters, leading to refractory disease...
Vascular catheter-related infections, primarily caused by and , pose significant challenges due to the formation of biofilms on catheters, leading to refractory disease and considerable morbidity. We studied the efficacy of micafungin in systemic and lock therapies to eliminate catheter-based biofilms and deep tissue infections in experimental central venous catheter (CVC)-related candidemia in neutropenic rabbits. Silastic CVCs in rabbits were inoculated with 1 × 10 CFU/mL of or , establishing catheter-based biofilm, and subjected to various treatments. Neutropenic rabbits treated with a combination of lock therapy and systemic micafungin demonstrated the most significant reduction in fungal burden, from 5.0 × 10 to 1.8 × 10 CFU/mL of and from 5.9 × 10 to 2.7 × 10 CFU/mL of ( ≤ 0.001), in the CVC after 24 h, with full clearance of blood cultures after 72 h from treatment initiation. The combination of lock and systemic micafungin therapy achieved eradication of from all studied tissues (0.0 ± 0.0 log CFU/g) vs. untreated controls (liver 7.5 ± 0.22, spleen 8.3 ± 0.25, kidney 8.6 ± 0.07, cerebrum 6.3 ± 0.31, vena cava 6.6 ± 0.29, and CVC wash 2.3 ± 0.68 log CFU/g) ( ≤ 0.001). Rabbits treated with a combination of lock and systemic micafungin therapy demonstrated a ≥2 log reduction in in all treated tissues ( ≤ 0.05) except kidney. Serum (1→3)-β-D-glucan levels demonstrated significant decreases in response to treatment. The study demonstrates that combining systemic and lock therapies with micafungin effectively eradicates catheter-based biofilms and infections caused by or , particularly in persistently neutropenic conditions, offering promising implications for managing vascular catheter-related candidemia and providing clinical benefits in cases where catheter removal is not feasible.
PubMed: 38667964
DOI: 10.3390/jof10040293 -
Journal of Fungi (Basel, Switzerland) Mar 2024The species is a multidrug-resistant yeast capable of causing systemic and lethal infections. Its virulence and increase in outbreaks are a global concern, especially...
The species is a multidrug-resistant yeast capable of causing systemic and lethal infections. Its virulence and increase in outbreaks are a global concern, especially in hospitals where outbreaks are more recurrent. In many cases, monotherapy is not effective, and drug combinations are opted for. However, resistance to antifungals has increased over the years. In view of this, nanoemulsions (NEs) may represent a nanotechnology strategy in the development of new therapeutic alternatives. Therefore, this study developed a co-encapsulated nanoemulsion with amphotericin B (AmB) and micafungin (MICA) (NEMA) for the control of infections caused by . NEs were developed in previous studies. Briefly, the NEs were composed of a mixture of 10% sunflower oil and cholesterol as the oil phase (5:1), 10% Polyoxyethylene (20) cetyl ether (Brij 58) and soy phosphatidylcholine as surfactant/co-surfactant (2:1), and 80% PBS as the aqueous phase. The in vivo assay used BALB/c mice weighing between 25 and 28 g that were immunosuppressed (CEUA/FCF/CAr n° 29/2021) and infected with CDC B11903. The in vivo results show the surprising potentiate of the antifungal activity of the co-encapsulated drugs in NE, preventing yeast from causing infection in the lung and thymus. Biochemical assays showed a higher concentration of liver and kidney enzymes under treatment with AmB and MICAmB. In conclusion, this combination of drugs to combat the infection caused by can be considered an efficient therapeutic option, and nanoemulsions contribute to therapeutic potentiate, proving to be a promising new alternative.
PubMed: 38667924
DOI: 10.3390/jof10040253 -
Letters in Applied Microbiology May 2024Species from Candida parapsilosis complex are frequently found in neonatal candidemia. The antifungal agents to treat this infection are limited and the occurrence of...
Species from Candida parapsilosis complex are frequently found in neonatal candidemia. The antifungal agents to treat this infection are limited and the occurrence of low in vitro susceptibility to echinocandins such as micafungin has been observed. In this context, the chaperone Hsp90 could be a target to reduce resistance. Thus, the objective of this research was to identify isolates from the C. parapsilosis complex and verify the action of Hsp90 inhibitors associated with micafungin. The fungal identification was based on genetic sequencing and mass spectrometry. Minimal inhibitory concentrations were determined by broth microdilution method according to Clinical Laboratory and Standards Institute. The evaluation of the interaction between micafungin with Hsp90 inhibitors was realized using the checkerboard methodology. According to the polyphasic taxonomy, C. parapsilosis sensu stricto was the most frequently identified, followed by C. orthopsilosis and C. metapsilosis, and one isolate of Lodderomyces elongisporus was identified by genetic sequencing. The Hsp90 inhibitor geladanamycin associated with micafungin showed a synergic effect in 31.25% of the isolates, a better result was observed with radicicol, which shows synergic effect in 56.25% tested yeasts. The results obtained demonstrate that blocking Hsp90 could be effective to reduce antifungal resistance to echinocandins.
Topics: Humans; Infant, Newborn; Antifungal Agents; Benzoquinones; Candida parapsilosis; Candidemia; Drug Resistance, Fungal; Drug Synergism; Echinocandins; HSP90 Heat-Shock Proteins; Lactams, Macrocyclic; Lipopeptides; Micafungin; Microbial Sensitivity Tests
PubMed: 38658187
DOI: 10.1093/lambio/ovae044 -
Mycoses Apr 2024Candidaemia is a life-threatening disease that is associated with high mortality, especially in intensive care units (ICUs). The number of comprehensive studies dealing...
BACKGROUND
Candidaemia is a life-threatening disease that is associated with high mortality, especially in intensive care units (ICUs). The number of comprehensive studies dealing with the epidemiologic characteristics of biofilm-related properties is limited.
OBJECTIVE
This study evaluated the clinical characteristics of candidaemia, to assess the biofilm-forming properties of isolates, and to identify the risk factors of mortality.
PATIENTS AND METHODS
A total of 149 candidaemia episodes from the University of Debrecen, Clinical Centre, between January 2020 and December 2023 were investigated retrospectively. The susceptibility of Candida isolates to fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin was evaluated and compared to the susceptibility of 1-day-old biofilms. Multivariate logistic regression analysis was applied to identify the independent predictors of 30-day mortality rate.
RESULTS
The most common Candida species was Candida albicans (41%), followed by C. parapsilosis (20%), C. glabrata (14%), C. tropicalis (13%), rare Candida species (7%), and C. krusei (5%). Sixty-six percent of Candida isolates were biofilm formers and 44% had high metabolic activity. The 30-day mortality rate was 52%, which was higher in ICUs (65%). The logistic regression analysis revealed several factors significantly influencing mortality including ICU admission (odds ratio [OR] 2.99, 95% confidence interval [CI] 1.17-8.04, p = 0.025), fluconazole treatment (OR 4.12, 95% CI 1.62-11.42, p = .004), and pneumonia (OR 0.261, 95% CI 0.1-0.67, p = .006).
CONCLUSIONS
This comprehensive analysis supports the better characterisation of candidaemia in healthcare settings, which ultimately may reduce mortality among patients.
Topics: Humans; Candidemia; Biofilms; Retrospective Studies; Female; Male; Hungary; Antifungal Agents; Candida; Middle Aged; Aged; Microbial Sensitivity Tests; Adult; Risk Factors; Intensive Care Units; Aged, 80 and over; Fluconazole
PubMed: 38650397
DOI: 10.1111/myc.13727 -
Pediatric Transplantation May 2024Pediatric lung transplant patients are at risk for developing invasive fungal infections post-transplant. No consensus exists on optimal antifungal regimens and...
BACKGROUND
Pediatric lung transplant patients are at risk for developing invasive fungal infections post-transplant. No consensus exists on optimal antifungal regimens and voriconazole, a common first-line agent, has been shown to cause hepatotoxicity. We describe a single-center experience utilizing a novel antifungal regimen of intravenous micafungin and nebulized amphotericin B immediately post-transplant with conversion to an azole at the time of hospital discharge and compare it to a historical cohort of patients who received voriconazole monotherapy throughout their immediate post-operative course.
METHODS
This is a retrospective review of patients in the age 0-18 who received a lung transplant from June 2016-May 2021. Data points collected included: demographic data, transplant date and discharge date, Aspergillus colonization, type of lung transplant, hospitalization and level of care information, induction and antifungal medication regimen; AST, ALT, GGT, bilirubin, and direct bilirubin at various timepoints; and respiratory and blood culture results. The two patient groups were compared by assessment of changes in LFTs and culture results.
RESULTS
Forty-two patients were included in the analysis, with 24 patients receiving micafungin and nebulized amphotericin and 18 patients receiving voriconazole. All patients in both groups experienced a post-operative elevation in at least one transaminase or bilirubin. More patients in the micafungin/amphotericin group had resolution of all abnormal LFTs by 1 month post-transplant (p = .036). Additionally, patients in the micafungin/amphotericin group experienced faster normalization of their LFTs compared with the voriconazole group (p < .001). Ten patients in the micafungin/amphotericin group and five patients in the voriconazole group were found to have fungal growth on culture post-transplant, but this difference was not found to be statistically significant (p = .507).
CONCLUSIONS
An antifungal regimen of micafungin and nebulized amphotericin B liposomal may be useful at decreasing the duration of elevated liver enzymes in pediatric patients in the immediate post-lung transplant period when compared with voriconazole monotherapy. Larger prospective studies looking at antifungal regimens in pediatric patients post-lung transplant are warranted.
Topics: Humans; Child; Infant, Newborn; Infant; Child, Preschool; Adolescent; Antifungal Agents; Amphotericin B; Voriconazole; Micafungin; Transplant Recipients; Prospective Studies; Bilirubin; Lung; Chemical and Drug Induced Liver Injury
PubMed: 38616325
DOI: 10.1111/petr.14740 -
Expert Opinion on Drug Safety Apr 2024Evaluating antibiotics most commonly associated with pseudomembranous colitis (PMC) based on the real-world data is of great significance.
BACKGROUND
Evaluating antibiotics most commonly associated with pseudomembranous colitis (PMC) based on the real-world data is of great significance.
RESEARCH DESIGN AND METHODS
We used the data from FAERS to evaluate the potential association between antibiotics and PMC by disproportionality analyzes.
RESULTS
Eighty-one antibiotics which met the three algorithms simultaneously were enrolled. There were 1683 reports of PMC associated with the enrolled antibiotics. In the top 24 antibiotics, cefoxitin, streptomycin, fosfomycin, and micafungin had a high risk of PMC, but there were few reports in the literature.
CONCLUSIONS
This study was of great significance for healthcare professionals to realize the potential PMC risks of antibiotics.
PubMed: 38603461
DOI: 10.1080/14740338.2024.2341813 -
Frontiers in Pharmacology 2024Echinocandins, a prominent class of antifungals, are known for their broad-spectrum activity and favorable safety profiles. However, their bioavailability and efficacy...
Echinocandins, a prominent class of antifungals, are known for their broad-spectrum activity and favorable safety profiles. However, their bioavailability and efficacy via oral route are suboptimal. In this study, caspofungin and micafungin, the two most commonly used echinocandins, were evaluated in various environments simulating intestinal lumen. The results revealed that while both antifungals are effective in standard medium, their efficacy significantly diminishes in the presence of human small bowel aspirates and bovine bile. The study suggests that bowel contents and specifically bile acids may be a suppressive component, hindering the antifungal effects of echinocandins. This novel exploration sheds light on the poor oral bioavailability of echinocandins. The findings imply that echinocandins alone, regardless of administration route, may not be optimal for gastrointestinal (GI) fungal infections or invasive fungal infections originating from intestinal translocation. Further clinical investigations are warranted to validate and expand upon these observations.
PubMed: 38601473
DOI: 10.3389/fphar.2024.1376656 -
Journal of Community Hospital Internal... 2023Drug-induced urine discoloration, although usually benign, can still raise concern in healthcare facilities. This case report presents the second case of purple urine...
Drug-induced urine discoloration, although usually benign, can still raise concern in healthcare facilities. This case report presents the second case of purple urine discoloration associated with cefiderocol in a 64-year-old male admitted to the intensive care unit for ventilator-associated pneumonia. The patient required broad-spectrum antibiotic treatment with vancomycin, cefiderocol, amikacin, and micafungin. On the fourth day after initiating antibiotics, the presence of purplish urine in the foley bag was noted. Urinalysis showed 11-25 red blood cells/hpf, but cultures ruled out urinary tract infection. Further laboratory workup did not reveal any evidence of hemolysis or rhabdomyolysis. Cultures from the endotracheal aspirate grew multidrug-resistant Pseudomonas. Cefiderocol and amikacin were continued to complete a seven-day course. Two days after completion of the cefiderocol course, the urine discoloration cleared up, providing strong evidence that cefiderocol was the cause of the discoloration.
PubMed: 38596538
DOI: 10.55729/2000-9666.1256 -
Journal of Clinical and Experimental... 2024We report the case of a 52-year-old male who presented to our hospital with cervical lymphadenopathy. Lymph node biopsy revealed small atypical lymphoid cells positive...
We report the case of a 52-year-old male who presented to our hospital with cervical lymphadenopathy. Lymph node biopsy revealed small atypical lymphoid cells positive for CD3 and CD5 and negative for CD56 and Epstein-Barr virus (EBV)-encoded small RNA (EBER) by in situ hybridization. CD4-positive cells and CD8-positive cells were mixed in almost equal numbers. He was diagnosed with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). The patient received one cycle of chemotherapy, resulting in severe sepsis. While undergoing treatment in the intensive care unit with an antimicrobial agent and prednisone, ascitic fluid appeared. Abdominal aspiration revealed neutrophil-predominant ascites and microbiological studies revealed Candida albicans. However, ascites did not improve when treated with micafungin for Candida peritonitis. Abdominal aspiration was re-performed, and atypical lymphoid cells that were positive for CD3 and CD56 were detected. EBV-DNA levels in whole blood were significantly elevated. Atypical lymphoid cells were positive for EBER by in situ hybridization and Southern blot analysis showed EBV terminal repeat monoclonal patterns. Bone marrow examination revealed the same atypical lymphoid cells. Therefore, the patient was diagnosed with extranodal natural killer/T-cell lymphoma (ENKTL) with bone marrow involvement 3 months after the diagnosis of PTCL-NOS. Complications associated with PTCL-NOS and ENKTL are rare. PTCL-NOS, chemotherapy, sepsis, and prednisone might have led to immunodeficiency and reactivation of EBV, which might be one of the pathophysiologies for developing ENKTL. Our case indicates that measuring EBV-DNA in the blood is a simple and prompt examination to detect complications of EBV-associated lymphoma.
Topics: Male; Humans; Middle Aged; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Lymphoma, T-Cell, Peripheral; Prednisone; Lymphoma, Extranodal NK-T-Cell; Ascites; Killer Cells, Natural; DNA
PubMed: 38538319
DOI: 10.3960/jslrt.23049