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Currently, the therapeutic effect on cryptococcal infection patients is hindered by toxicity and drug resistance, making it urgent to discover alternative antifungals. Calcium channel blockers, verapamil (VER), have shown effective antifungal effects in several fungi. Here, we found that VER has a significant antifungal effect on Cryptococcus neoformans (C. neoformans). Furthermore, VER has significant synergistic effects with multiple antifungals, even caspofungin (CAS). We confirmed that VER and CAS had a synergistic antifungal effect in the Galleria mellonella. We conducted in-depth research on the possible mechanism of the synergistic impact of VER and CAS. After treatment with VER, the chitosan content of C. neoformans ' cell wall decreased and in dopamine liquid culture medium, we observed the leakage of melanin. Through cell wall fluorescence staining and stress sensitivity analysis, we further demonstrated that VER impaired the integrity of the C. neoformans' cell wall. Another side, VER+CAS modification of C. neoformans membrane permeability, leading to intracellular ROS accumulation and mitochondrial membrane potential changes. VER eliminated the cytoplasmic calcium fluctuations caused by CAS stimulation and down-regulated the genes expression associated with the calcineurin pathway. In addition, we found that the enzyme activity of chitin deacetylase of C. neoformans is significantly influenced by the presence of Ca2+, suggesting that the use of VER may affect the activity. In summary, the synergistic antifungal effect of VER and CAS makes them effective and promising candidates for fungal treatment.
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Here, we present the case of a patient with a metastatic neuroendocrine tumor with cytologically negative ascites treated for spontaneous bacterial peritonitis (SBP). Ascitic cultures remained negative for bacterial growth but were positive for Candida albicans 8 days after SBP diagnosis. ß-D-glucan was only positive in ascites, while being negative in blood. Blood cultures remained negative throughout the whole admission. Fungal peritonitis presumably originated from an impending bowl perforation or an increasing vascular permeability caused by an increase in VEGF secondary to diffuse infiltration by the underlying malignant disease.
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BACKGROUND: Echinocandins belong to the fourth generation of antifungals, and there are no systematic studies on their risk in coagulation dysfunction; this study will predict the risk of coagulation dysfunction of echinocandins using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHOD: Data from January 2004 to March 2024 were obtained from FAERS. We examined the clinical characteristics of the coagulation dysfunction events and conducted disproportionality analysis by using reporting odds ratios (ROR) to compare echinocandins with the full database. RESULTS: There were 313 reports of coagulation dysfunction related to echinocandins as the primary suspect (PS) drug. The median time to incident for coagulation dysfunction was 3 (interquartile range [IQR] 1-9) days. Compared to triazoles and polyenes, echinocandins have a stronger signal (ROR 3.18, 95%CI 2.81-3.51, p < 0.01) of coagulation dysfunction. Compared to caspofungin and micafungin, anidulafungin has a stronger signal (ROR 6.84, 95%CI 4.83-9.70, p < 0.01). The strongest signal corresponding to disseminated intravascular coagulation (DIC), platelet count decreased, thrombocytopenia, gastrointestinal haemorrhage, cerebral haemorrhage, pulmonary haemorrhage and thrombotic thrombocytopenic purpura (TTP) is micafungin (ROR 27.19, 95%CI 18.49-39.98), micafungin (ROR 3.50, 95%CI 2.36-5.19), anidulafungin (ROR 9.75, 95%CI 5.22-18.19), micafungin (ROR 3.17, 95%CI 2.02-4.97), micafungin (ROR 4.95, 95%CI 2.81-8.72), caspofungin (ROR 20.76, 95%CI 11.77-36.59), micafungin (ROR 20.43, 95%CI 8.49-49.14), respectively. CONCLUSIONS: For coagulation dysfunction, we found stronger signals for echinocandins than triazoles and polyenes, and stronger signals for anidulafungin than micafungin and caspofungin. Coagulation parameters should be closely monitored while using the respective drugs.
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Aim: This study focuses on the development of a Caspofungin liposome for efficient ocular delivery by enhancing corneal penetration. Method: Quality by design (QbD) approach was adopted to identify critical factors that influence final liposomal formulation. The liposome developed using thin film hydration after optimization was subjected to characterization for physicochemical properties, irritation potential and corneal uptake. Results: The numerical optimization suggests an optimal formulation with a desirability value of 0.706, using CQAs as optimization goals with 95% prediction intervals. The optimized formulation showed no signs of irritation potential along with observation of significant corneal permeation. Conclusion: The liposomal formulation increased the permeability of Caspofungin, which could enhance the efficacy for the treatment of conditions, like fungal keratitis.
[Box: see text].
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BACKGROUND: Although combination therapy of echinocandins with trimethoprim-sulfamethoxazole (TMP-SMX) has been reported for patients with Pneumocystis jirovecii pneumonia (PCP), the effectiveness of this combination therapy in patients with PCP without human immunodeficiency virus (HIV) infection remains unknown. METHODS: Data from the Japanese Diagnosis Procedure Combination inpatient database was used to identify non-HIV patients who underwent their first hospitalisation for PCP between April 2012 and March 2022. The patients were divided into those treated with TMP-SMX alone and those treated with TMP-SMX combined with echinocandins. We performed propensity-score overlap-weighting analysis to estimate in-hospital mortality. RESULTS: Among the 1,324 eligible patients, 122 received TMP-SMX plus echinocandins, while 1,202 received TMP-SMX alone. The propensity-score overlap-weighting analysis showed that the combination therapy was not associated with reduced in-hospital mortality in comparison with TMP-SMX alone (22.2% vs. 26.9%; risk difference, 4.6%; 95% confidence interval, -6.1% to 15.3%; P = 0.398). CONCLUSIONS: Echinocandins combined with TMP-SMX may not improve in-hospital mortality due to PCP in patients without HIV infection.
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Invasive candidiasis poses a worldwide threat because of the rising prevalence of antifungal resistance, resulting in higher rates of morbidity and mortality. Additionally, Candida species, which are opportunistic infections, have significant medical and economic consequences for immunocompromised individuals. This study explores the antifungal potential of chitosan to mitigate caspofungin resistance in caspofungin-resistant Candida albicans, C. krusei, and C. tropicalis isolates originating from human and animal sources using agar well diffusion, broth microdilution tests, and transmission electron microscope (TEM) analysis of treated Candida cells. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was performed to assess the expression of SAGA complex genes (GCN5 and ADA2) and the caspofungin resistance gene (FKS) in Candida species isolates after chitosan treatment. The highest resistance rate was observed to ketoconazole (80%) followed by clotrimazole (62.7%), fluconazole (60%), terbinafine (58%), itraconazole (57%), miconazole (54.2%), amphotericin B (51.4%), voriconazole (34.28%), and caspofungin (25.7%). Nine unique FKS mutations were detected, including S645P (n = 3 isolates), S645F, L644F, S645Y, L688M, E663G, and F641S (one isolate in each). The caspofungin minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values before chitosan treatment ranged from 2 to 8 µg/mL and 4 to 16 µg/mL, respectively. However, the MIC and MFC values were decreased after chitosan treatment (0.0625-1 µg/mL) and (0.125-2 µg/mL), respectively. Caspofungin MIC was significantly decreased (p = 0.0007) threefold following chitosan treatment compared with the MIC values before treatment. TEM analysis revealed that 0.5% chitosan disrupted the integrity of the cell surface, causing irregular morphologies and obvious aberrant changes in cell wall thickness in caspofungin-resistant and sensitive Candida isolates. The cell wall thickness of untreated isolates was 0.145 µm in caspofungin-resistant isolate and 0.125 µm in sensitive isolate, while it was significantly lower in chitosan-treated isolates, ranging from 0.05 to 0.08 µm when compared with the cell wall thickness of sensitive isolate (0.03 to 0.06 µm). Moreover, RT-qPCR demonstrated a significant (p < 0.05) decrease in the expression levels of histone acetyltransferase genes (GCN5 and ADA2) and FKS gene of caspofungin-resistant Candida species isolates treated with 0.5% chitosan when compared with before treatment (fold change values ranged from 0.001 to 0.0473 for GCN5, 1.028 to 4.856 for ADA2, and 2.713 to 12.38 for FKS gene). A comparison of the expression levels of cell wall-related genes (ADA2 and GCN5) between caspofungin-resistant and -sensitive isolates demonstrated a significant decrease following chitosan treatment (p < 0.001). The antifungal potential of chitosan enhances the efficacy of caspofungin against various caspofungin-resistant Candida species isolates and prevents the development of further antifungal resistance. The results of this study contribute to the progress in repurposing caspofungin and inform a development strategy to enhance its efficacy, appropriate antifungal activity against Candida species, and mitigate resistance. Consequently, chitosan could be used in combination with caspofungin for the treatment of candidiasis.
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BACKGROUND: Caspofungin is an echinocandin antifungal agent commonly used as the first-line therapy for invasive candidiasis, salvage therapy for invasive aspergillosis, and empirical therapy for presumed fungal infections. Pharmacokinetic (PK) variabilities and suboptimal exposure have been reported for caspofungin, increasing the risk of insufficient efficacy. OBJECTIVE: This work aimed to develop a caspofungin population pharmacokinetic (popPK) library and demonstrate its utility by assessing the probability of target attainment across diverse settings. METHODS: We established a caspofungin popPK model library following a rigorous literature review, re-implementing selected models in R with rxode2. Quality control procedures included a comparison of different studies and assessing covariate impacts. Model libraries were primarily used to perform Monte Carlo simulations to estimate target attainment and guide personalized dosing in Candida infections. RESULTS: A total of 13 models, one- or two-compartment models, were included. The most significant covariates were body size (weight and body surface area), liver function, and albumin level. The results show that children and adults showed considerable differences in pharmacokinetics. For C. albicans and C. parapsilosis, none of the populations achieved a PTA of ≥90% at their respective susceptible MIC values. In contrast, for C. glabrata, 70% of the adult studies reached a PTA of ≥90%, while all pediatric studies achieved the same PTA level. CONCLUSION: At the recommended dosage, adult patients showed notably lower exposure to caspofungin compared to pediatric patients. Considering body size, liver function, and serum albumin is crucial when determining caspofungin dosage regimens. Furthermore, further research is required to comprehensively understand the pharmacokinetics of caspofungin in pediatric patients.
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Cryptococcus neoformans causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug against C. neoformans. BRI can affect the organization of the cell membrane, increasing the fungal cell permeability. We also investigated the effects of BRI against the model system Saccharomyces cerevisiae by analyzing libraries of mutants grown in the presence of BRI. In S. cerevisiae, BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism. In vivo experiments show BRI significantly reduces C. neoformans survival inside macrophages and partially clears C. neoformans lung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis. We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action against C. neoformans. BRI + CAS affects endocytic movement, calcineurin, and mitogen-activated protein kinases. Our results indicate that BRI is a novel antifungal drug against cryptococcosis. IMPORTANCE: Invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Cryptococcosis, one of the most prevalent fungal diseases, is generally characterized by meningitis and is mainly caused by two closely related species of basidiomycetous yeasts, Cryptococcus neoformans and Cryptococcus gattii. There are few therapeutic options for treating cryptococcosis, and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a potential antifungal agent against C. neoformans. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. BRI alone was shown to inhibit the growth of C. neoformans, acting as a fungicidal drug, but surprisingly also potentiated the activity of caspofungin (CAS) against this species. We investigated the mechanism of action of BRI and BRI + CAS against C. neoformans. We propose BRI as a new antifungal agent against cryptococcosis.
Subject(s)
Antifungal Agents , Cryptococcosis , Cryptococcus neoformans , Saccharomyces cerevisiae , Antifungal Agents/pharmacology , Cryptococcus neoformans/drug effects , Animals , Mice , Cryptococcosis/drug therapy , Cryptococcosis/microbiology , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/genetics , Disease Models, Animal , Macrophages/microbiology , Macrophages/drug effects , Macrophages/immunology , Microbial Sensitivity Tests , Caspofungin/pharmacology , Female , Cell Membrane/drug effects , Cell Membrane/metabolism , Amphotericin B/pharmacologyABSTRACT
The efficacy of different echinocandins is assessed by evaluating the in vitro activity of a novel antifungal, rezafungin, against invasive fungal isolates in comparison with anidulafungin and caspofungin. Using the broth microdilution (BMD) method, the susceptibility of 1000 clinical Candida isolates (including 400 C. albicans, 200 C. glabrata, 200 C. parapsilosis, 150 C. tropicalis and 50 C. krusei) and 150 Aspergillus isolates (100 A. fumigatus and 50 A. flavus) from the Eastern China Invasive Fungi Infection Group (ECIFIG) was tested for the antifungals including anidulafungin, rezafungin, caspofungin and fluconazole. The echinocandins showed strong activity against C. albicans that was maintained against fluconazole-resistant isolates. The GM MIC (geometric mean minimum inhibitory concentration) value of rezafungin was found to be comparable to that of anidulafungin or caspofungin against the five tested common Candida species. C. tropicalis exhibited higher resistance rates (about 8.67-40.67% in different antifungals) than the other four Candida species. Through the sequencing of FKS genes, we searched for mutations in echinocandin-resistant C. tropicalis isolates and found that all displayed alterations in FKS1 S654P. The determined MEC (minimal effective concentration) values against A. fumigatus and A. flavus for rezafungin (0.116 µg/mL, 0.110 µg/mL) are comparable to those of caspofungin (0.122 µg/mL, 0.142 µg/mL) but higher than for anidulafungin (0.064 µg/mL, 0.059 µg/mL). Thus, the in vitro activity of rezafungin appears comparable to anidulafungin and caspofungin against most common Candida and Aspergillus species. Rezafungin showed higher susceptibility rates against C. glabrata. Rezafungin indicates its potent activity for potential clinical application.
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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 in vitro 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.
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Background: The effect of drug-drug interaction between tacrolimus and caspofungin on the pharmacokinetics of tacrolimus in different CYP3A5 genotypes has not been reported in previous studies. Objectives: To investigate the effect of caspofungin on the blood concentration and dose of tacrolimus under different CYP3A5 genotypes. Design: We conducted a retrospective cohort study in The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital from January 2015 to December 2022. All kidney transplant patients were divided into the combination or non-combination group based on whether tacrolimus was combined with caspofungin or not. Patients were subdivided into CYP3A5 expressers (CYP3A5*1/*1 or CYP3A5*1/*3) and CYP3A5 non-expressers (CYP3A5*3/*3). Methods: Data from the combination and the non-combination groups were matched with propensity scores to reduce confounding by SPSS 22.0. A total of 200 kidney transplant patients receiving tacrolimus combined with caspofungin or not were enrolled in this study. Statistical analysis was conducted on the dose-corrected trough concentrations (C0/D) and dose requirements (D) of tacrolimus using independent sample two-sided t-test and nonparametric tests to investigate the impact on patients with different. Results: In this study, the C0/D values of tacrolimus were not significantly different between the combination and non-combination groups (p = 0.054). For CYP3A5 expressers, there was no significant difference in tacrolimus C0/D or D values between the combination and non-combination groups (p = 0.359; p = 0.851). In CYP3A5 nonexpressers, the C0/D values of tacrolimus were significantly lower in the combination than in the non-combination groups (p = 0.039), and the required daily dose of tacrolimus was increased by 11.11% in the combination group. Conclusion: Co-administration of caspofungin reduced tacrolimus blood levels and elevated the required daily dose of tacrolimus. In CYP3A5 non-expressers, co-administration of caspofungin had a significant effect on tacrolimus C0/D values. An approximate 10% increase in the weight-adjusted daily dose of tacrolimus in CYP3A5 non-expressers is recommended to ensure the safety of tacrolimus administration.
Differential drug interactions of caspofungin on tacrolimus in Chinese kidney transplant patients with different CYP3A5 genotypes Why was the study done? Currently, there have been studies reporting the effect of caspofungin on tacrolimus blood concentrations, but the conclusions are conflicting, and no study has focused on the effect of CYP3A5 genotypes on the drug-drug interaction. We explored a number of research questions: 1. Does caspofungin have an effect on the pharmacokinetics of the immunosuppressant tacrolimus? 2. How does CYP3A5*3, which affects tacrolimus metabolism significantly, affect tacrolimus blood concentration levels? 3. How should the dose of tacrolimus be adjusted when combined with caspofungin? What did the researchers do? By reviewing literature, we understood the problems related with the kidney transplant patients better, which led to the development of strict inclusion and exclusion criteria. The patients (from January 2015 to December 2022) were categorized into combination and non-combination groups according to whether they were co-administered with caspofungin or not. The results of the study were analyzed using SPSS 22.0. What did the researchers find? The study finally included 200 patients. We found no statistically significant differences in the dose-corrected trough concentrations (C0/D) and dose requirements (D) of tacrolimus between the combination and non-combination groups. However, in patients with CYPA5*3/*3 genotype, tacrolimus C0/D values were significantly lower in the combination group than in the non-combination group, and the required daily tacrolimus dose was increased. What do the findings mean? This study has found that co-administration of caspofungin in patients with CYP3A5*3/*3 genotype resulted in a significant decrease in the C0/D value of tacrolimus, therefore, an appropriate increase in the daily dose of tacrolimus is recommended. The implication is that it is important and necessary to monitor the concentrations of tacrolimus and the CYP3A5 genotypes, and adjust the dose when combined or discontinuing with caspofungin in kidney transplant patients.
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OBJECTIVES: We assessed the efficacy of a 3-week primary or salvage caspofungin regimen in patients with chronic obstructive pulmonary disease (COPD) and concomitant proven or suspected invasive pulmonary aspergillosis (IPA). METHODS: Forty-four patients were treated with an initial loading caspofungin dose of 70 mg, followed by a daily dose of 50 mg for 20 days. The main efficacy endpoint was clinical effectiveness. Secondary endpoints included the clinical efficacy of caspofungin after 1 week, therapeutic efficacy based on the European Organization for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium (EORTC/MSG) criteria, the sensitivity of different Aspergillus strains to caspofungin in vitro, and the safety of caspofungin. RESULTS: An assessment of 42 patients in the intention-to-treat group revealed efficacy rates of 33.33% within 1 week and 38.10% within 3 weeks. According to the EORTC/MSG criteria, the treatment success rate was 38.10%. The success rate of first-line treatment was 54.76%, whereas salvage treatment had a success rate of 45.24%. No adverse events were reported among the participants. CONCLUSIONS: Caspofungin is effective and safe as an initial or salvage treatment for patients with IPA and COPD.
Subject(s)
Aspergillosis , Invasive Pulmonary Aspergillosis , Pulmonary Disease, Chronic Obstructive , Humans , Caspofungin/therapeutic use , Invasive Pulmonary Aspergillosis/complications , Invasive Pulmonary Aspergillosis/drug therapy , Invasive Pulmonary Aspergillosis/chemically induced , Antifungal Agents/adverse effects , Echinocandins/adverse effects , Lipopeptides/therapeutic use , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapyABSTRACT
INTRODUCTION: Aspergillus species are ubiquitously found in the environment worldwide and are important causative agents for infection. Drug resistance among Aspergillus species is emerging, hence the present study was undertaken to look for antifungal susceptibility profiles of clinical and environmental isolates of Aspergillus species. MATERIALS AND METHODS: During the period from January 2018 to June 2019, a total of 102 Aspergillus isolates (40 clinical, 40 hospital, and 22 community environment) were tested for antifungal susceptibility testing for determination of minimum inhibitory concentration (MIC)/minimum effective concentration (MEC) as per Clinical and Laboratory Standards Institute (CLSI) M38-A3 method for itraconazole, voriconazole, amphotericin B, and caspofungin. RESULTS: Out of these 102 Aspergillus isolates, A. flavus was the most common species present. Aspergillus species were found to have low MIC values to azoles such as itraconazole and voriconazole except for one clinical isolate, which showed a MIC value of 2 µg/ml to voriconazole. Two isolates were non-wild-type for amphotericin B, but all isolates were wild-type for caspofungin. CONCLUSION: Antifungal susceptibility testing among clinical Aspergillus isolates and environmental surveillance studies in view of emerging drug resistance should be undertaken at a larger scale.
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Meningitis in patients with ventriculo-peritoneal shunt (VP shunt) caused by various species of Candida have been widely described in literature. However, reports describing Candida auris as a cause of meningitis is limited. In this case report we describe a case of multidrug resistant Candida auris meningitis secondary to VP shunt infection successfully treated with intrathecal amphotericin B deoxycholate and intravenous liposomal amphotericin B. This is the second case report of successful treatment of Candida auris meningitis from India. More literature regarding the use of intrathecal/intraventricular echinocandins including optimal dosing and duration of therapy is needed.
Subject(s)
Amphotericin B , Antifungal Agents , Candidiasis , Deoxycholic Acid , Meningitis, Fungal , Ventriculoperitoneal Shunt , Humans , Ventriculoperitoneal Shunt/adverse effects , Amphotericin B/therapeutic use , Amphotericin B/administration & dosage , Antifungal Agents/therapeutic use , Antifungal Agents/administration & dosage , Candidiasis/drug therapy , Candidiasis/microbiology , Deoxycholic Acid/therapeutic use , Meningitis, Fungal/drug therapy , Meningitis, Fungal/microbiology , Meningitis, Fungal/diagnosis , Candida auris , Male , India , Drug Combinations , Drug Resistance, Multiple, Fungal , Treatment Outcome , Adult , FemaleABSTRACT
Scedosporium, a widespread filamentous fungus found in diverse environments, has experienced a rise in cases due to escalating malignancies and chronic immunosuppression. Clinical manifestations span mycetoma, airway involvement, and various infections, with osteomyelitis being a notable complication. We present a case of a 77-year-old female initially displaying cutaneous Scedosporium signs, which progressed to osteomyelitis. The patient, with a history of trauma, chronic low dose steroid use, and underlying conditions, presented with a foot injury caused by her dog. Despite initial management, worsening symptoms led to the identification of Scedosporium. A comprehensive approach involving debridement, antimicrobial therapy, and reduction of immunosuppression resulted in clinical improvement. The rarity of zoonotic transmission, diagnostic challenges, and antifungal efficacy are also discussed. The patient's positive trajectory emphasizes early diagnosis, targeted treatment, and vigilance in managing immunosuppression. An adaptable treatment protocol is proposed based on risk factors. Considering the rising opportunistic fungal infections and delayed culture results, initiating empirical antifungals based on clinical judgment and regional prevalence is vital for favorable outcomes.
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BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is a life-threatening and severe disease in immunocompromised hosts. A synergistic regimen based on the combination of sulfamethoxazole-trimethoprim (SMX-TMP) with caspofungin and glucocorticosteroids (GCSs) may be a potential first-line therapy for PJP. Therefore, it is important to explore the efficacy and safety of this synergistic therapy for treating non-HIV-related PJP patients. METHODS: We retrospectively analysed the data of 38 patients with non-HIV-related PJP at the First Affiliated Hospital of Xi'an Jiaotong University. Patients were divided into two groups: the synergistic therapy group (ST group, n = 20) and the monotherapy group (MT group, n = 18). All patients were from the ICU and were diagnosed with severe PJP. In the ST group, all patients were treated with SMX-TMP (TMP 15-20 mg/kg per day) combined with caspofungin (70 mg as the loading dose and 50 mg/day as the maintenance dose) and a GCS (methylprednisolone 40-80 mg/day). Patients in the MT group were treated only with SMX-TMP (TMP 15-20 mg/kg per day). The clinical response, adverse events and mortality were compared between the two groups. RESULTS: The percentage of patients with a positive clinical response in the ST group was significantly greater than that in the MT group (100.00% vs. 66.70%, P = 0.005). The incidence of adverse events in the MT group was greater than that in the ST group (50.00% vs. 15.00%, P = 0.022). Furthermore, the dose of TMP and duration of fever in the ST group were markedly lower than those in the MT group (15.71 mg/kg/day vs. 18.35 mg/kg/day (P = 0.001) and 7.00 days vs. 11.50 days (P = 0.029), respectively). However, there were no significant differences in all-cause mortality or duration of hospital stay between the MT group and the ST group. CONCLUSIONS: Compared with SMZ/TMP monotherapy, synergistic therapy (SMZ-TMP combined with caspofungin and a GCS) for the treatment of non-HIV-related PJP can increase the clinical response rate, decrease the incidence of adverse events and shorten the duration of fever. These results indicate that synergistic therapy is effective and safe for treating severe non-HIV-related PJP.
Subject(s)
Pneumocystis carinii , Pneumonia, Pneumocystis , Humans , Pneumonia, Pneumocystis/drug therapy , Trimethoprim, Sulfamethoxazole Drug Combination/adverse effects , Caspofungin/therapeutic use , Retrospective Studies , Tertiary Care Centers , Adrenal Cortex Hormones/therapeutic useABSTRACT
BACKGROUND AND PURPOSE: The need for dose adjustment of caspofungin in patients with hepatic impairment is controversial, especially for those with Child-Pugh B or C cirrhosis. The purpose of this study was to investigate the safety and efficacy of standard-dose caspofungin administration in Child-Pugh B and C cirrhotic patients in a real-world clinical setting. PATIENTS AND METHODS: The electronic medical records of 258 cirrhotic patients, including 67 Child-Pugh B patients and 191 Child-Pugh C patients, who were treated with standard-dose of caspofungin at the Second Affiliated Hospital of Chongqing Medical University, China, from March 2018 to June 2023 were reviewed retrospectively. The white blood cells (WBC), hepatic, renal and coagulation function results before administration and post administration on days 7, 14 and 21 were collected, and the efficacy was assessed in all patients at the end of caspofungin therapy. RESULTS: Favorable responses were achieved in 137 (53.1%) patients while 34 (13.2%) patients died. We observed that some patients experienced an increase of prothrombin time (PT) or international normalized ratio (INR), or a decrease of WBC, but no exacerbation of hepatic or renal dysfunction were identified and no patient required dose interruption or adjustment because of an adverse drug reaction during treatment with caspofungin. CONCLUSIONS: Standard-dose of caspofungin can be safely and effectively used in patients with Child-Pugh B or C cirrhosis, and we appealed to re-assess the most suitable dosing regimen in this population to avoid a potential subtherapeutic exposure.
Subject(s)
Antifungal Agents , Caspofungin , Liver Cirrhosis , Humans , Caspofungin/therapeutic use , Male , Female , Middle Aged , Liver Cirrhosis/drug therapy , Liver Cirrhosis/complications , Retrospective Studies , Aged , Antifungal Agents/therapeutic use , Antifungal Agents/adverse effects , Antifungal Agents/administration & dosage , Treatment Outcome , Adult , ChinaABSTRACT
(1) Background: Previous studies reported the promising inhibitory effect of cold atmospheric plasma (CAP) on Candida albicans. However, the exact mechanisms of CAP's action on the fungal cell are still poorly understood. This study aims to elucidate the CAP effect on C. albicans cell wall, by evaluating the alterations on its structure and biochemical composition; (2) Methods: C. albicans cells treated with Helium-CAP were analyzed by atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR) in order to detect morphological, topographic and biochemical changes in the fungal cell wall. Cells treated with caspofungin were also analyzed for comparative purposes; (3) Results: Expressive morphological and topographic changes, such as increased roughness and shape modification, were observed in the cells after CAP exposure. The alterations detected were similar to those observed after the treatment with caspofungin. The main biochemical changes occurred in polysaccharides content, and an overall decrease in glucans and an increase in chitin synthesis were detected; (4) Conclusions: Helium-CAP caused morphological and topographic alterations in C. albicans cells and affected the cell wall polysaccharide content.