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Medical Mycology Jun 2024Though echinocandins are the first line of therapy for C.auris candidemia, there is little clinical data to guide the choice of therapy within this class. This was the...
Though echinocandins are the first line of therapy for C.auris candidemia, there is little clinical data to guide the choice of therapy within this class. This was the first study to compare the three echinocandins in terms of efficacy and outcomes for C.auris candidemia. This was a retrospective analysis of 82 episodes of candidemia caused by C.auris comparing outcomes across the three echinocandins. Majority patients in our study were treated with micafungin. Susceptibility rates were the lowest for caspofungin (35.36% resistance), with no resistance reported for the other two echinocandins. When a susceptible echinocandin was chosen, caspofungin resistance was not a factor significantly associated with mortality. Also when a susceptible echinocandin was used for therapy, the choice within the class did not affect clinical cure, microbiological cure or mortality (p > 0.05 for all). Failure to achieve microbiological cure (p = 0.018) and receipt of immune-modulatory therapy (p = 0.01) were significantly associated with increased mortality. Significant cost variation was noted amongst the echinocandins. Considering the significant cost variation, comparable efficacies can be reassuring for the prescribing physician.
PubMed: 38918058
DOI: 10.1093/mmy/myae065 -
Drugs in Context 2024Invasive fungal infections (IFIs) are important infectious complications amongst critically ill children. The most common fungal infections are due to species. , and... (Review)
Review
BACKGROUND
Invasive fungal infections (IFIs) are important infectious complications amongst critically ill children. The most common fungal infections are due to species. , and are also emerging because of the empirical use of antifungal drugs. This updated review discusses the epidemiology of IFIs as well as antifungal drugs, dosing and potential adverse effects in critically ill children.
METHODS
A PubMed search was conducted with Clinical Queries using the key terms "antifungal", "children", "critical care" AND "paediatric intensive care unit" OR "PICU". The search strategy included clinical trials, randomized controlled trials, meta-analyses, observational studies and reviews and was limited to the English literature in paediatrics.
RESULTS
and spp. are the most prevalent fungi in paediatric IFIs, causing invasive candidiasis infections (ICIs) and invasive aspergillosis infections (IAIs), respectively. These IFIs are associated with high morbidity, mortality and healthcare costs. is the principal spp. associated with paediatric ICIs. The risks and epidemiology for IFIs vary if considering previously healthy children treated in the paediatric intensive care unit or children with leukaemia, malignancy or a severe haematological disease. The mortality rate for IAIs in children is 2.5-3.5-fold higher than for ICIs. Four major classes of antifungals for critically ill children are azoles, polyenes, antifungal antimetabolites and echinocandins.
CONCLUSIONS
Antifungal agents are highly efficacious. For successful treatment outcomes, it is crucial to determine the optimal dosage, monitor pharmacokinetics parameters and adverse effects, and individualized therapeutic monitoring. Despite potent antifungal medications, ICIs and IAIs continue to be serious infections with high mortality rates. Pre-emptive therapy has been used for IAIs. Most guidelines recommend voriconazole as initial therapy of invasive aspergillosis in most patients, with consideration of combination therapy with voriconazole plus an echinocandin in selected patients with severe disease. The challenge is to identify critically ill patients at high risks of ICIs for targeted prophylaxis. Intravenous/per os fluconazole is first-line pre-emptive treatment for spp. whereas intravenous micafungin or intravenous liposomal amphotericin B is alternative pre-emptive treatment.This article is part of the Special Issue: https://www.drugsincontext.com/special_issues/challenges-and-strategies-in-the-management-of-invasive-fungal-infections.
PubMed: 38915918
DOI: 10.7573/dic.2023-9-2 -
The Medical Letter on Drugs and... Jun 2024
Topics: Humans; Antifungal Agents; Candidiasis, Invasive; Echinocandins
PubMed: 38905526
DOI: 10.58347/tml.2024.1705d -
Open Forum Infectious Diseases Jun 2024is a World Health Organization critical priority fungal pathogen. We conducted a systematic review to describe its epidemiology in Africa. PubMed and Google scholar... (Review)
Review
is a World Health Organization critical priority fungal pathogen. We conducted a systematic review to describe its epidemiology in Africa. PubMed and Google scholar databases were searched between January 2009 and September 2023 for clinical studies on cases and/or isolates from Africa. Reviews were excluded. We included 19 studies, involving at least 2529 cases from 6 African countries with the most, 2372 (93.8%), reported from South Africa. Whole-genome sequencing of 127 isolates identified 100 (78.7%) as clade III. Among 527 isolates, 481 (91.3%) were resistant to fluconazole, 108 (20.5%) to amphotericin B, and 9 (1.7%) to micafungin. Ninety of 211 (42.7%) patients with clinical outcomes died. is associated with high mortality and antifungal resistance, yet this critical pathogen remains underreported in Africa. Collaborative surveillance, fungal diagnostics, antifungals, and sustainable infection control practices are urgently needed for containment.
PubMed: 38887473
DOI: 10.1093/ofid/ofad681 -
Clinical Laboratory Jun 2024The aim of this study was to evaluate the therapeutic regimen of a patient with myelodysplastic syndrome (MDS) who developed invasive fungal infections caused by...
BACKGROUND
The aim of this study was to evaluate the therapeutic regimen of a patient with myelodysplastic syndrome (MDS) who developed invasive fungal infections caused by drug-resistant Candida tropicalis after chemotherapy and to investigate the effect of drug treatment.
METHODS
We referred to the Diagnostic Criteria and Treatment Principles of invasive fungal diseases in patients with hematological diseases and malignant tumors (2013, fourth revised edition) and the Expert Consensus on Clinical Application of Posaconazole (2022 Edition). In addition, the drug treatment regimens of drug-resistant Candida tropicalis were reviewed. The doctors in charge were involved in the drug treatment process, and the ra-tional drug use was selected according to evidence-based medicine.
RESULTS
After 4 months of use, the nodules around the body disappeared, and there was no further fever during follow-up. After 6 months of use, posaconazole was discontinued, and the patient continued to follow-up for 1 month without further fever or nodules.
CONCLUSIONS
The combination of posaconazole, amphotericin B liposome, and micafungin is effective in the treatment of fluconazole-resistant Candida tropicalis infection.
Topics: Humans; Myelodysplastic Syndromes; Antifungal Agents; Drug Resistance, Fungal; Triazoles; Amphotericin B; Candida tropicalis; Male; Invasive Fungal Infections; Micafungin; Aged; Middle Aged; Treatment Outcome
PubMed: 38868888
DOI: 10.7754/Clin.Lab.2023.231213 -
Open Forum Infectious Diseases Jun 2024No guidelines currently exist for the management of bloodstream infection in patients with left ventricular assist devices (LVADs). We aim to share our management...
No guidelines currently exist for the management of bloodstream infection in patients with left ventricular assist devices (LVADs). We aim to share our management experience through this retrospective case series outlining 15 episodes of candidemia identified in 7 patients over 18 months. The initial source of candidemia was central venous catheter in 5 patients, driveline exit site infection in 1 patient, and possible pump infection in 1 patient. All patients were initially treated with micafungin. Despite susceptibility to micafungin, 4 patients experienced recurrent candidemia. All patients died within 1 year of their first episode of candidemia. Source control is challenging in patients with LVADs, and strict infection prevention measures should be practiced. More studies are needed to evaluate the role of newer antifungal agents, use of combination antifungal regimens, and impact on morbidity in patients with LVADs.
PubMed: 38868314
DOI: 10.1093/ofid/ofae286 -
Turkish Journal of Ophthalmology Jun 2024A 78-year-old man with a history of lung cancer, chemotherapy, radiotherapy, and coronavirus disease 2019 infection experienced visual deterioration of two-weeks’...
A 78-year-old man with a history of lung cancer, chemotherapy, radiotherapy, and coronavirus disease 2019 infection experienced visual deterioration of two-weeks’ duration in his right eye. There was multifocal, yellowish-white retinitis foci, vascular engorgement, and scattered intraretinal hemorrhages extending from posterior pole to retinal periphery in the right eye, whereas the left eye was normal. Intravitreal vancomycin, ceftazidime, clindamycin, and dexamethasone were given for endogenous endophthalmitis initially. Vitreous culture confirmed the presence of Aspergillus lentulus, and he was treated with intravitreal amphotericin-B and voriconazole injections together with systemic amphotericin-B, voriconazole, posaconazole, and micafungin therapy. During follow-up, vitreoretinal surgery was performed because of rhegmatogenous retinal detachment, and he received one additional cycle of chemotherapy due to recurrence of the cancer. Although the retina was attached, enucleation was eventually required due to painful red eye. Atypical squamous cells beneath the neurosensory retina suggesting metastasis were noted on histopathological examination. Timely ocular examination is crucial for any immunocompromised patient having ocular symptoms. High level of suspicion for a fungal etiology is a must in these patients.
Topics: Humans; Endophthalmitis; Male; Aged; Eye Infections, Fungal; Immunocompromised Host; Lung Neoplasms; Aspergillosis; Aspergillus; Antifungal Agents; COVID-19; Vitreous Body; Intravitreal Injections; SARS-CoV-2
PubMed: 38860516
DOI: 10.4274/tjo.galenos.2024.44045 -
Medical Mycology Jun 2024Acrophialophora is implicated in superficial and invasive infections, especially in immunosuppressed individuals. The present study was undertaken to provide clinical,...
Acrophialophora is implicated in superficial and invasive infections, especially in immunosuppressed individuals. The present study was undertaken to provide clinical, microbiological, phylogenetic, and antifungal susceptibility testing (AFST) profile of Acrophialophora isolated from India. All the isolates identified as Acrophialophora species at National Culture Collection for Pathogenic Fungi, Chandigarh, India were revived. Phenotypic and molecular characterization was performed, followed by temperature studies, scanning electron microscopy (SEM) and AFST. We also performed systematic review of all the cases of Acrophialophora species reported till date. A total of nine isolates identified as Acrophialophora species were identified by molecular method as A. fusispora (n = 8) and A. levis (n = 1), from brain abscess (n = 4), respiratory tract (n = 3) and corneal scraping (n = 2). All patients but two had predisposing factors/co-morbidities. Acrophialophora was identified as mere colonizer in one. Temperature studies and SEM divulged variation between both species. Sequencing of the ITS ribosomal DNA and beta-tubulin loci could distinguish species, while the LSU ribosomal DNA locus could not. AFST showed lowest MICs for triazoles and highest for echinocandins. Systematic literature review revealed 16 cases (11 studies), with ocular infections, pulmonary and central nervous system infections, and A. fusispora was common species. All the patients except three responded well. High MICs were noted for fluconazole, micafungin and caspofungin. This is the first study delineating clinical, phenotypic, and genotypic characteristics of Acrophialophora species from India. The study highlights microscopic differences between both species and emphasizes the role of molecular methods in precise identification. Triazoles appear to be the most effective antifungals for managing patients.
PubMed: 38857886
DOI: 10.1093/mmy/myae061 -
The Journal of Antimicrobial... Jun 2024Candidaemia is associated with poor outcomes including high mortality rates. Controversy remains regarding whether fluconazole or an echinocandin is the optimal choice...
BACKGROUND
Candidaemia is associated with poor outcomes including high mortality rates. Controversy remains regarding whether fluconazole or an echinocandin is the optimal choice for initial candidaemia treatment, particularly among high-risk patients such as the immunocompromised or critically ill.
OBJECTIVES
To understand optimal initial treatment of candidaemia.
METHODS
We conducted a retrospective study of immunocompromised or ICU adult patients with candidaemia from 2010 to 2014. Patients who received ≥3 consecutive days of initial treatment with fluconazole or micafungin were included. The primary outcome was complete response at day 14, defined as clinical improvement and blood culture sterilization. Secondary outcomes included microbiological and clinical success, survival and recurrent candidaemia.
RESULTS
A total of 197 patients were included; 76 received fluconazole and 121 received micafungin. There was no difference in complete response between the fluconazole and micafungin groups (ICU: 38% versus 40%, P = 0.87; immunocompromised: 57% versus 59%, P = 0.80). Secondary outcomes including survival were also similar. In multivariable analysis, among ICU patients, Pitt bacteraemia score < 4 (P = 0.002) and time to antifungal (P = 0.037) were associated with meeting the primary outcome; white blood cell count > 11 cells × 103/µL on day 0 (P < 0.001) and Candida isolated from a non-blood site (P = 0.025) were associated with not meeting the primary outcome. Among immunocompromised patients, white blood cells > 11 × 103/µL (P = 0.003) and Candida isolated from a non-blood site (P = 0.026) were associated with not meeting the primary outcome.
CONCLUSIONS
These data suggest that among ICU or immunocompromised patients, severity of illness rather than initial antifungal choice drove clinical outcomes.
PubMed: 38831614
DOI: 10.1093/jac/dkae175 -
Frontiers in Pediatrics 2024Urinary tract infections (UTIs) associated with indwelling urinary catheterization (IUC) in premature newborns (PNBs) pose a significant challenge in neonatal intensive...
Urinary tract infections (UTIs) associated with indwelling urinary catheterization (IUC) in premature newborns (PNBs) pose a significant challenge in neonatal intensive care units (NICUs) due to the vulnerability of this population to infections and the necessity of invasive procedures. While bacterial UTIs have historically been predominant, there is a rising incidence of fungal pathogens, particularly non- strains like and , attributed to broad-spectrum antibiotic use. Diagnosis of fungal UTIs in a PNB relies on culturing spp. from properly collected urine samples, particularly critical in very low birth weight (VLBW) PNBs because of the risk of invasive candidiasis and associated complications. We present a case of an extremely premature newborn (EPNB) successfully treated for a UTI caused by with micafungin. Our case exhibits micafungin as a potentially safe and effective alternative for treating UTIs in neonates.
PubMed: 38827222
DOI: 10.3389/fped.2024.1397456