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1.
Clin Exp Med ; 24(1): 144, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38960977

ABSTRACT

The primary objective of this study was to assess the incidence, timing, risk factors of fungal infections (FIs) within 3 months after liver transplantation (LT). The secondary objective was to evaluate the impact of FIs on outcomes. Four hundred and ten patients undergoing LT from January 2015 until January 2023 in a tertiary university hospital were included in the present retrospective cohort study to investigate the risk factors of FIs and to assess the impacts of FIs on the prognosis of LT recipients using logistic regression. The incidence of FIs was 12.4% (51/410), and median time from LT to the onset of FIs was 3 days. By univariate analysis, advanced recipient age, prolonged hospital stay prior to LT, high Model for End Stage Liver Disease (MELD) score, use of broad-spectrum antibiotics, and elevated white blood cell (WBC) count, increased operating time, massive blood loss and red blood cell transfusion, elevated alanine aminotransferase on day 1 and creatinine on day 3 after LT, prolonged duration of urethral catheter, prophylactic antifungal therapy, the need for mechanical ventilation and renal replacement therapy were identified as factors of increased post-LT FIs risk. Multivariate logistic regression analysis identified that recipient age ≥ 55 years[OR = 2.669, 95%CI: 1.292-5.513, P = 0.008], MELD score at LT ≥ 22[OR = 2.747, 95%CI: 1.274-5.922, P = 0.010], pre-LT WBC count ≥ 10 × 109/L[OR = 2.522, 95%CI: 1.117-5.692, P = 0.026], intraoperative blood loss ≥ 3000 ml [OR = 2.691, 95%CI: 1.262-5.738, P = 0.010], post-LT duration of urethral catheter > 4 d [OR = 3.202, 95%CI: 1.553-6.602, P = 0.002], and post-LT renal replacement therapy [OR = 5.768, 95%CI: 1.822-18.263, P = 0.003] were independently associated with the development of post-LT FIs. Post-LT prophylactic antifungal therapy ≥ 3 days was associated with a lower risk of the development of FIs [OR = 0.157, 95%CI: 0.073-0.340, P < 0.001]. As for clinical outcomes, FIs had a negative impact on intensive care unit (ICU) length of stay ≥ 7 days than those without FIs [OR = 3.027, 95% CI: 1.558-5.878, P = 0.001] but had no impact on hospital length of stay and 1-month all-cause mortality after LT. FIs are frequent complications after LT and the interval between the onset of FIs and LT was short. Risk factors for post-LT FIs included high MELD score at LT, advanced recipient age, pre-LT WBC count, massive intraoperative blood loss, prolonged post-LT duration of urethral catheter, and the need for post-LT renal replacement therapy. However, post-LT prophylactic antifungal therapy was independently associated with the reduction in the risk of FIs. FIs had a significant negative impact on ICU length of stay.


Subject(s)
Liver Transplantation , Mycoses , Humans , Liver Transplantation/adverse effects , Middle Aged , Male , Female , Retrospective Studies , Risk Factors , Mycoses/epidemiology , Mycoses/prevention & control , Mycoses/etiology , Adult , Incidence , Aged , Postoperative Complications , Prognosis , Tertiary Care Centers , Treatment Outcome , Length of Stay
2.
Radiographics ; 44(7): e230176, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38900682

ABSTRACT

Fungal musculoskeletal infections often have subacute or indolent manifestations, making it difficult to distinguish them from other diseases and infections, given that they are relatively uncommon. Fungal infections occur by hematogenous spread, direct inoculation, or contiguous extension and may be related to different risk factors, including immunosuppression and occupational activity. The infection can manifest in isolation in the musculoskeletal system or as part of a systemic process. The fungi may be endemic to certain regions or may be found throughout the world, and this can help to narrow the diagnosis of the etiologic agent. Infections such as candidiasis, cryptococcosis, aspergillosis, and mucormycosis are often related to immunosuppression. On the other hand, histoplasmosis, paracoccidioidomycosis, coccidioidomycosis, and blastomycosis can occur in healthy patients in geographic areas where these infections are endemic. Furthermore, infections can be classified on the basis of the site of infection in the body. Some subcutaneous infections that can have osteoarticular involvement include mycetoma, sporotrichosis, and phaeohyphomycosis. Different fungi affect specific bones and joints with greater prevalence. Imaging has a critical role in the evaluation of these diseases. Imaging findings include nonspecific features such as osteomyelitis and arthritis, with bone destruction, osseous erosion, mixed lytic and sclerotic lesions, and joint space narrowing. Multifocal osteomyelitis and chronic arthritis with joint effusion and synovial thickening may also occur. Although imaging findings are often nonspecific, some fungal infections may show findings that aid in narrowing the differential diagnosis, especially when they are associated with the patient's clinical condition and history, the site of osteoarticular involvement, and the geographic location. ©RSNA, 2024.


Subject(s)
Mycoses , Humans , Mycoses/diagnostic imaging , Diagnosis, Differential , Musculoskeletal Diseases/diagnostic imaging
3.
Nat Microbiol ; 9(7): 1686-1699, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38898217

ABSTRACT

The continuing emergence of invasive fungal pathogens poses an increasing threat to public health. Here, through the China Hospital Invasive Fungal Surveillance Net programme, we identified two independent cases of human infection with a previously undescribed invasive fungal pathogen, Rhodosporidiobolus fluvialis, from a genus in which many species are highly resistant to fluconazole and caspofungin. We demonstrate that R. fluvialis can undergo yeast-to-pseudohyphal transition and that pseudohyphal growth enhances its virulence, revealed by the development of a mouse model. Furthermore, we show that mouse infection or mammalian body temperature induces its mutagenesis, allowing the emergence of hypervirulent mutants favouring pseudohyphal growth. Temperature-induced mutagenesis can also elicit the development of pan-resistance to three of the most commonly used first-line antifungals (fluconazole, caspofungin and amphotericin B) in different Rhodosporidiobolus species. Furthermore, polymyxin B was found to exhibit potent activity against the pan-resistant Rhodosporidiobolus mutants. Collectively, by identifying and characterizing a fungal pathogen in the drug-resistant genus Rhodosporidiobolus, we provide evidence that temperature-dependent mutagenesis can enable the development of pan-drug resistance and hypervirulence in fungi, and support the idea that global warming can promote the evolution of new fungal pathogens.


Subject(s)
Antifungal Agents , Mutagenesis , Animals , Mice , Humans , Virulence/genetics , Antifungal Agents/pharmacology , China , Body Temperature , Disease Models, Animal , Ascomycota/genetics , Ascomycota/pathogenicity , Ascomycota/drug effects , Caspofungin/pharmacology , Microbial Sensitivity Tests , Fluconazole/pharmacology , Mycoses/microbiology , Drug Resistance, Multiple, Fungal/genetics , Drug Resistance, Fungal/genetics
4.
Med Mycol J ; 65(2): 33-38, 2024.
Article in English | MEDLINE | ID: mdl-38825528

ABSTRACT

Antifungal stewardship (AFS), compared with antimicrobial stewardship (AS), requires more advanced knowledge, skills, and multidisciplinary collaboration in its implementation. Therefore, fewer facilities are performing AFS compared with AS. At our hospital, we started AS and AFS in 2014. Our AFS programs include the following: i) interventions for patients with yeast-positive blood cultures, ii) introduction of a conditional antifungal notification system, and iii) commencement of AS team rounds. AFS for filamentous fungi includes bronchoscopy and microbial identification, including genetic and drug susceptibility testing. These AFS activities have improved several processes and outcome measures. However, our AFS team has faced several problems owing to the impact of COVID-19. This review introduces the practice of AFS, which we initiated at our hospital in 2014, and presents the current problems.


Subject(s)
Antifungal Agents , Antimicrobial Stewardship , Hospitals, University , Humans , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology , Antimicrobial Stewardship/methods , Japan , COVID-19 , SARS-CoV-2/drug effects , Mycoses/drug therapy
5.
PLoS One ; 19(6): e0305228, 2024.
Article in English | MEDLINE | ID: mdl-38870137

ABSTRACT

The chytrid fungus Batrachochytrium salamandrivorans [Bsal] is causing declines in the amphibian populations. After a decade of mapping the pathogen in Europe, where it is causing dramatic outbreaks, and North America, where its arrival would affect to the salamander's biodiversity hotspot, little is known about its current status in Asia, from presumably is native. Japan has several species considered as potential carriers, but no regulation is implemented against Bsal spreading. Previous Bsal known presence detected various cases on the Okinawa Island, southwestern Japan. Previous studies on its sister species, B. dendrobatidis presented a high genomic variation in this area and particularly on Cynops ensicauda. Here, we have done the largest monitoring to date in Japan on the Cynops genus, focusing on Okinawa Island and updating its distribution and providing more information to unravel the still unknown origin of Bsal. Interestingly, we have provided revealing facts about different detectability depending on the used molecular techniques and changes in its Japanese distribution. All in all, the Bsal presence in Japan, together with its low variability in the sequenced amplicons, and the lack of apparent mortalities, may indicate that this part of Asia has a high diversity of chytrids.


Subject(s)
Batrachochytrium , Urodela , Animals , Japan , Urodela/microbiology , Batrachochytrium/genetics , Phylogeny , Genetic Variation , Biodiversity , Chytridiomycota/genetics , Mycoses/microbiology , Mycoses/veterinary , Mycoses/epidemiology , East Asian People
6.
J Zoo Wildl Med ; 55(2): 453-461, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38875202

ABSTRACT

Chytridiomycosis caused by Batrachochytrium dendrobatidis (Bd) has been documented in greater sirens (Siren lacertina) in the wild and in the pet trade. This study evaluated the use of terbinafine-impregnated implants for chytridiomycosis prophylaxis in greater sirens exposed to Bd. Implants were placed intracoelomically in both control (blank implant, n = 4) and treatment (24.5 mg of terbinafine implant, n = 4) groups. Sirens were exposed to Bd zoospores via 24-h immersion bath at 1 and 2 mon postimplant placement. Blood was collected monthly for plasma terbinafine levels, and skin swabs were collected weekly for Bd quantitative PCR. Animals with terbinafine implants had detectable concentrations of plasma terbinafine ranging from 17 to 102 ng/ml. Only one terbinafine-implanted animal had a peak concentration above the published minimum inhibitory concentration for terbinafine against Bd zoospores (63 ng/ml); however, it is unknown how plasma terbinafine concentrations relate to concentrations in the skin. There was no difference between the two treatment groups in clinical signs or Bd clearance rate, and no adverse effects from implants were observed. These findings indicate using intracoelomic drug implants for drug delivery in amphibians is safe; however, terbinafine efficacy in preventing Bd chytridiomycosis in sirens remains unclear. Further investigation of the use of intracoelomic implants and identification of effective drugs and doses in other amphibian species against Bd and other infectious diseases is warranted, as this may provide a practical method for long-term drug delivery in wildlife.


Subject(s)
Antifungal Agents , Terbinafine , Terbinafine/administration & dosage , Terbinafine/therapeutic use , Terbinafine/pharmacology , Animals , Pilot Projects , Antifungal Agents/administration & dosage , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacokinetics , Drug Implants , Batrachochytrium/drug effects , Male , Mycoses/veterinary , Mycoses/drug therapy , Amphibians
7.
J Zoo Wildl Med ; 55(2): 540-546, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38875213

ABSTRACT

This report describes Schizangiella infections in colubrid and viperid snakes. A captive eastern ratsnake (Pantherophis alleghaniensis) was presented for a large intraoral mass associated with the mandible. The mass was debulked and histologic examination revealed severe, granulomatous stomatitis with intralesional fungi exhibiting morphologic features consistent with Schizangiella serpentis. PCR and sequencing of affected tissues confirmed S. serpentis. Because of declining health, the ratsnake was euthanized and postmortem examination identified a disseminated S. serpentis infection involving the skeletal musculature, lung, kidney, mesentery, and mandible. A wild-caught timber rattlesnake (Crotalus horridus) was presented for cutaneous lesions, weakness, and lethargy and later died. Postmortem examination revealed a mass-like structure in the esophagus characterized by high numbers of Schizangiella-like fungi associated with extensive granulomatous inflammation; the snake also had cutaneous mycosis suggestive of ophidiomycosis. This is the first report to document the unique morphologic features of S. serpentis in tissues and the presentation of schizangiellosis in snakes. Schizangiellosis should be considered as a differential diagnosis for nodular lesions involving the oral cavity and/or the gastrointestinal tract of snakes.


Subject(s)
Crotalus , Animals , Colubridae , Mycoses/veterinary , Mycoses/microbiology , Mycoses/pathology , Mycoses/diagnosis , Thelazioidea/isolation & purification , Animals, Zoo , Male , Female , Venomous Snakes
8.
Ital J Pediatr ; 50(1): 113, 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38853280

ABSTRACT

The purpose of this study was to review the literature on the clinical use of voriconazole (VRC) in pediatric patients. MEDLINE, Embase, PubMed, Web of Science, and Cochrane Library were searched from January 1, 2000, to August 15, 2023 for relevant clinical studies on VRC use in pediatric patients. Data were collected based on inclusion and exclusion criteria, and a systematic review was performed on recent research related to the use of VRC in pediatric patients. This systematic review included a total of 35 observational studies among which there were 16 studies investigating factors influencing VRC plasma trough concentrations (Ctrough) in pediatric patients, 14 studies exploring VRC maintenance doses required to achieve target range of Ctrough, and 11 studies focusing on population pharmacokinetic (PPK) research of VRC in pediatric patients. Our study found that the Ctrough of VRC were influenced by both genetic and non-genetic factors. The optimal dosing of VRC was correlated with age in pediatric patients, and younger children usually required higher VRC doses to achieve target Ctrough compared to older children. Establishing a PPK model for VRC can assist in achieving more precise individualized dosing in children.


Subject(s)
Antifungal Agents , Voriconazole , Voriconazole/administration & dosage , Humans , Antifungal Agents/administration & dosage , Child , Dose-Response Relationship, Drug , Mycoses/drug therapy
9.
BMC Infect Dis ; 24(1): 605, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38898444

ABSTRACT

BACKGROUND PAECILOMYCES: and Penicillium are considered as rare opportunistic pathogens in immunocompromised hosts, and pneumonia caused by Paecilomyces and Penicillium is rare. In this study, we present first case of severe pneumonia with pleural effusion caused by co-infection of Paecilomyces variotii (P. variotii) and Penicillium oxalicum (P. oxalicum) in a 66-year-old female with poorly controlled type 2 diabetes. CASE PRESENTATION: A 56-year-old woman patient presented to hospital for nausea, poor appetite, and vomiting for one day. On the second day of admission, blood culture and renal puncture fluid culture grew multidrug-resistant Escherichia coli (imipenem/cilastatin sensitive), and she received combination therapy with imipenem/cilastatin (1 g, every 8 h) and vancomycin (0.5 g, every 12 h). On the fourth day, she developed symptoms of respiratory failure. Pulmonary computed tomography (CT) showed an increase in pneumonia compared to before, with minor pleural effusion on both sides. Two fungi were isolated repeatedly from BALF culture, which were confirmed as P. variotii and P. oxalicum by Internal transcribed spacer (ITS) sequencing. Her pleural effusion was completely absorbed, pneumonia symptoms have significantly improved and discharged with receiving liposomal amphotericin B treatment for four weeks. CONCLUSIONS: It is worth noting that clinicians and laboratory personnel should not simply consider Paecilomyces and Penicillium species as contaminants, especially in immunocompromised patients. Early fungal identification and antifungal drug sensitivity are crucial for clinical drug selection and patient prognosis.


Subject(s)
Coinfection , Diabetes Mellitus, Type 2 , Paecilomyces , Penicillium , Pleural Effusion , Humans , Female , Penicillium/isolation & purification , Pleural Effusion/microbiology , Pleural Effusion/drug therapy , Middle Aged , Aged , Diabetes Mellitus, Type 2/complications , Coinfection/microbiology , Coinfection/drug therapy , Paecilomyces/isolation & purification , Pneumonia/microbiology , Pneumonia/drug therapy , Mycoses/microbiology , Mycoses/drug therapy , Immunocompromised Host , Anti-Bacterial Agents/therapeutic use , Antifungal Agents/therapeutic use
10.
Int J Mol Sci ; 25(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38892165

ABSTRACT

Human mycoses cover a diverse field of fungal diseases from skin disorders to systemic invasive infections and pose an increasing global health problem based on ineffective treatment options, the hampered development of new efficient drugs, and the emergence of resistant fungal strains. Niclosamide is currently applied for the treatment of worm infections. Its mechanisms of action, which include the suppression of mitochondrial oxidative phosphorylation (also known as mitochondrial uncoupling), among others, has led to a repurposing of this promising anthelmintic drug for the therapy of further human diseases such as cancer, diabetes, and microbial infections. Given the urgent need to develop new drugs against fungal infections, the considerable antifungal properties of niclosamide are highlighted in this review. Its chemical and pharmacological properties relevant for drug development are also briefly mentioned, and the described mitochondria-targeting mechanisms of action add to the current arsenal of approved antifungal drugs. In addition, the activities of further salicylanilide-based niclosamide analogs against fungal pathogens, including agents applied in veterinary medicine for many years, are described and discussed for their feasibility as new antifungals for humans. Preliminary structure-activity relationships are determined and discussed. Various salicylanilide derivatives with antifungal activities showed increased oral bioavailabilities when compared with niclosamide. The simple synthesis of salicylanilide-based drugs also vouchsafes a broad and cost-effective availability for poorer patient groups. Pertinent literature is covered until 2024.


Subject(s)
Antifungal Agents , Niclosamide , Salicylanilides , Niclosamide/pharmacology , Salicylanilides/pharmacology , Salicylanilides/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Humans , Animals , Structure-Activity Relationship , Fungi/drug effects , Mycoses/drug therapy , Mitochondria/drug effects , Mitochondria/metabolism
11.
Arch Microbiol ; 206(7): 293, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38850421

ABSTRACT

Fungal infections are incurring high risks in a range from superficial mucosal discomforts (such as oropharyngeal candidiasis and vulvovaginal candidiasis) to disseminated life-threatening diseases (such as invasive pulmonary aspergillosis and cryptococcal meningitis) and becoming a global health problem in especially immunodeficient population. The major obstacle to conquer fungal harassment lies in the presence of increasing resistance to conventional antifungal agents used in newly clinically isolated strains. Although recombinant cytokines and mono-/poly-clonal antibodies are added into antifungal armamentarium, more effective antimycotic drugs are exceedingly demanded. It is comforting that the development of fungal vaccines and adjuvants opens up a window to brighten the prospective way in the diagnosis, prevention and treatment of fungal assaults. In this review, we focus on the progression of several major fungal vaccines devised for the control of Candida spp., Aspergillus spp., Cryptococcus spp., Coccidioides spp., Paracoccidioides spp., Blastomyces spp., Histoplasma spp., Pneumocystis spp. as well as the adjuvants adopted. We then expound the interaction between fungal vaccines/adjuvants and host innate (macrophages, dendritic cells, neutrophils), humoral (IgG, IgM and IgA) and cellular (Th1, Th2, Th17 and Tc17) immune responses which generally experience immune recognition of pattern recognition receptors, activation of immune cells, and clearance of invaded fungi. Furthermore, we anticipate an in-depth understanding of immunomodulatory properties of univalent and multivalent vaccines against diverse opportunistic fungi, providing helpful information in the design of novel fungal vaccines and adjuvants.


Subject(s)
Adjuvants, Immunologic , Fungal Vaccines , Mycoses , Fungal Vaccines/immunology , Humans , Mycoses/prevention & control , Mycoses/immunology , Animals , Fungi/immunology
13.
Prog Mol Biol Transl Sci ; 207: 59-78, 2024.
Article in English | MEDLINE | ID: mdl-38942545

ABSTRACT

The rise of multidrug-resistant bacteria is a well-recognized threat to world health, necessitating the implementation of effective treatments. This issue has been identified as a top priority on the global agenda by the World Health Organization. Certain strains, such as Candida glabrata, Candida krusei, Candida lusitaniae, Candida auris, select cryptococcal species, and opportunistic Aspergillus or Fusarium species, have significant intrinsic resistance to numerous antifungal medicines. This inherent resistance and subsequent suboptimal clinical outcomes underscore the critical imperative for enhanced therapeutic alternatives and management protocols. The challenge of effectively treating fungal infections, compounded by the protracted timelines involved in developing novel drugs, underscores the pressing need to explore alternative therapeutic avenues. Among these, drug repurposing emerges as a particularly promising and expeditious solution, providing cost-effective solutions and safety benefits. In the fight against life-threatening resistant fungal infections, the idea of repurposing existing medications has encouraged research into both established and new compounds as a last-resort therapy. This chapter seeks to provide a comprehensive overview of contemporary antifungal drugs, as well as their key resistance mechanisms. Additionally, it seeks to provide insight into the antimicrobial properties of non-traditional drugs, thereby offering a holistic perspective on the evolving landscape of antifungal therapeutics.


Subject(s)
Antifungal Agents , Drug Repositioning , Mycoses , Humans , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology , Mycoses/drug therapy , Drug Resistance, Fungal , Animals
14.
Methods Mol Biol ; 2813: 205-217, 2024.
Article in English | MEDLINE | ID: mdl-38888780

ABSTRACT

COVID-19 pandemic has heightened the interest toward diagnosis and treatment of infectious diseases. Nuclear medicine, with its powerful scintigraphic, single photon emission computer tomography (SPECT), and positron emission tomography (PET) imaging modalities, has always played an important role in diagnosis of infections and distinguishing them from the sterile inflammation. In addition to the clinically available radiopharmaceuticals, there has been a decades-long effort to develop more specific imaging agents with some examples being radiolabeled antibiotics and antimicrobial peptides for bacterial imaging, radiolabeled antifungals for fungal infections imaging, radiolabeled pathogen-specific antibodies, and molecular engineered constructs. In this chapter, we discuss some examples of the work published in the last decade on developing nuclear imaging agents for bacterial, fungal, and viral infections to generate more interest among nuclear medicine community toward conducting clinical trials of these novel probes, as well as toward developing novel radiotracers for imaging infections.


Subject(s)
COVID-19 , Positron-Emission Tomography , Radiopharmaceuticals , Radiopharmaceuticals/chemistry , Humans , COVID-19/diagnostic imaging , Positron-Emission Tomography/methods , Tomography, Emission-Computed, Single-Photon/methods , SARS-CoV-2 , Bacterial Infections/diagnostic imaging , Bacterial Infections/drug therapy , Bacterial Infections/diagnosis , Mycoses/diagnostic imaging , Mycoses/diagnosis , Mycoses/drug therapy
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 945-951, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38926993

ABSTRACT

OBJECTIVE: To explore the application value of simultaneous monitoring of voriconazole (VRCZ) and voriconazole N-oxide (VNO) in efficacy and safety of VRCZ in the prevention and treatment of fungal infections in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients before engraftment (i.e., days +1 to +30 after transplantation). METHODS: The influencing factors of VRCZ, VNO concentration and MR (CVNO/CVRCZ) and the difference of VRCZ in the prevention and treatment of fungal infection and liver and kidney injury were analyzed. The receiver operating characteristic curve (ROC) was used to analyze the differences (the corresponding to the maximum of the Youden index on the curve was set as the cut-off value) to confirm the critical value. RESULTS: The factors affecting VRCZ concentration (CVRCZ), VNO concentration (CVNO) and MR were patient weight, VRCZ daily dose, and transplantation type (all P < 0.05). CVRCZ and CVNO in the effective group were higher than those in the ineffective group (P < 0.001), the opposite of MR (P < 0.001); the liver and renal injury group had lower MR than the normal group (P < 0.05). ROC showed that CVRCZ, C VNO and MR had important value in predicting VRCZ in the prevention and treatment of invasive fungal infections in allo-HSCT patients before engraftment, and their cutoff of concentrations were 0.95 µg/ml, 1.35 µg/ml and 1.645, respectively (AUC: 0.9677, 0.7634, 0.9564). CVRCZ and MR can assist in indicating liver ï¼»cutoff values: 0.65 µg/ml, 1.96 (AUC: 0.5971, 0.6663)ï¼½ and renal injury ï¼»cutoff values: 0.95 µg/ml, 1.705 (AUC: 0.6039, 0.6164)ï¼½. CONCLUSION: The great value of simultaneous monitoring of VRCZ, VNO and MR can predict in the efficacy and safety of VRCZ in allo-HSCT patients before engraftment. The prediction accuracy of CVRCZ was higher than that of MR, followed by that of CVNO. Increased CVRCZ and decreased MR increase the risk of liver and kidney injury.


Subject(s)
Antifungal Agents , Hematopoietic Stem Cell Transplantation , Transplantation, Homologous , Voriconazole , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Mycoses , Drug Monitoring/methods
16.
Med Mycol ; 62(6)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935909

ABSTRACT

The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal pathogen priority list. This systematic review aimed to evaluate the epidemiology and impact of infections caused by Talaromyces marneffei, Coccidioides species, and Paracoccidioides species. PubMed and Web of Sciences databases were searched to identify studies published between 1 January 2011 and 23 February 2021 reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 25, 17, and 6 articles were included for T. marneffei, Coccidioides spp. and Paracoccidioides spp., respectively. Mortality rates were high in those with invasive talaromycosis and paracoccidioidomycosis (up to 21% and 22.7%, respectively). Hospitalization was frequent in those with coccidioidomycosis (up to 84%), and while the duration was short (mean/median 3-7 days), readmission was common (38%). Reduced susceptibility to fluconazole and echinocandins was observed for T. marneffei and Coccidioides spp., whereas >88% of T. marneffei isolates had minimum inhibitory concentration values ≤0.015 µg/ml for itraconazole, posaconazole, and voriconazole. Risk factors for mortality in those with talaromycosis included low CD4 counts (odds ratio 2.90 when CD4 count <200 cells/µl compared with 24.26 when CD4 count <50 cells/µl). Outbreaks of coccidioidomycosis and paracoccidioidomycosis were associated with construction work (relative risk 4.4-210.6 and 5.7-times increase, respectively). In the United States of America, cases of coccidioidomycosis increased between 2014 and 2017 (from 8232 to 14 364/year). National and global surveillance as well as more detailed studies to better define sequelae, risk factors, outcomes, global distribution, and trends are required.


Subject(s)
Antifungal Agents , Coccidioides , Paracoccidioides , Talaromyces , World Health Organization , Talaromyces/isolation & purification , Talaromyces/classification , Talaromyces/drug effects , Humans , Paracoccidioides/isolation & purification , Paracoccidioides/drug effects , Paracoccidioides/classification , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Coccidioides/isolation & purification , Coccidioides/classification , Coccidioides/drug effects , Mycoses/epidemiology , Mycoses/microbiology , Mycoses/mortality , Paracoccidioidomycosis/epidemiology , Paracoccidioidomycosis/microbiology , Paracoccidioidomycosis/drug therapy , Coccidioidomycosis/epidemiology , Coccidioidomycosis/microbiology , Microbial Sensitivity Tests
18.
Med Mycol ; 62(6)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38935914

ABSTRACT

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of infections caused by Fusarium spp., Scedosporium spp., and Lomentospora prolificans to inform the first FPPL. PubMed and Web of Sciences databases were searched to identify studies published between January 1, 2011 and February 23, 2021, reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 20, 11, and 9 articles were included for Fusarium spp., Scedosporium spp., and L. prolificans, respectively. Mortality rates were high in those with invasive fusariosis, scedosporiosis, and lomentosporiosis (42.9%-66.7%, 42.4%-46.9%, and 50.0%-71.4%, respectively). Antifungal susceptibility data, based on small isolate numbers, showed high minimum inhibitory concentrations (MIC)/minimum effective concentrations for most currently available antifungal agents. The median/mode MIC for itraconazole and isavuconazole were ≥16 mg/l for all three pathogens. Based on limited data, these fungi are emerging. Invasive fusariosis increased from 0.08 cases/100 000 admissions to 0.22 cases/100 000 admissions over the time periods of 2000-2009 and 2010-2015, respectively, and in lung transplant recipients, Scedosporium spp. and L. prolificans were only detected from 2014 onwards. Global surveillance to better delineate antifungal susceptibility, risk factors, sequelae, and outcomes is required.


Subject(s)
Antifungal Agents , Fusarium , Microbial Sensitivity Tests , Scedosporium , Humans , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Fusarium/drug effects , Fusarium/isolation & purification , Scedosporium/drug effects , Scedosporium/isolation & purification , Scedosporium/classification , World Health Organization , Mycoses/epidemiology , Mycoses/microbiology , Fusariosis/microbiology , Fusariosis/epidemiology , Ascomycota/drug effects , Invasive Fungal Infections
19.
Article in English | MEDLINE | ID: mdl-38710584

ABSTRACT

The growing prevalence of fungal infections alongside rising resistance to antifungal drugs poses a significant challenge to public health safety. At the close of the 2000s, major pharmaceutical firms began to scale back on antimicrobial research due to repeated setbacks and diminished economic gains, leaving only smaller companies and research labs to pursue new antifungal solutions. Among various natural sources explored for novel antifungal compounds, antifungal peptides (AFPs) emerge as particularly promising. Despite their potential, AFPs receive less focus than their antibacterial counterparts. These peptides have been sourced extensively from nature, including plants, animals, insects, and especially bacteria and fungi. Furthermore, with advancements in recombinant biotechnology and computational biology, AFPs can also be synthesized in lab settings, facilitating peptide production. AFPs are noted for their wide-ranging efficacy, in vitro and in vivo safety, and ability to combat biofilms. They are distinguished by their high specificity, minimal toxicity to cells, and reduced likelihood of resistance development. This review aims to comprehensively cover AFPs, including their sources-both natural and synthetic-their antifungal and biofilm-fighting capabilities in laboratory and real-world settings, their action mechanisms, and the current status of AFP research. ONE-SENTENCE SUMMARY: This comprehensive review of AFPs will be helpful for further research in antifungal research.


Subject(s)
Antifungal Agents , Biofilms , Fungi , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/therapeutic use , Biofilms/drug effects , Fungi/drug effects , Animals , Humans , Mycoses/drug therapy , Peptides/pharmacology , Peptides/chemistry , Drug Resistance, Fungal , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemistry
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