Use of an Animal Model of Disseminated Candidiasis in the Evaluation of Antifungal Therapy

2005 ◽  
pp. 111-128 ◽  
Author(s):  
David Andes
Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4723-4723
Author(s):  
Shenxian Qian ◽  
Kuang Chen

Abstract Abstract 4723 Chronic disseminated candidiasis (CDC) is typically observed during neutrophil recovery in patients with acute leukemia and requires protracted antifungal therapy. Our objective was to document the efficacy and tolerance of corticosteroid therapy (CST) in patients with symptomatic CDC, including those who experienced fever and abdominal pain despite ongoing antifungal therapy. We performed a study involving 6 adult patients who experienced ongoing symptomatic CDC despite receipt of appropriate antifungal therapy for whom adjuvant oral CST therapy was initiated. All cases of CDC were proven or probable, as determined on the basis of the European Organization for Research and Treatment of Cancer-Mycosis Study Group definition criteria, and occurred in patients with leukemia.The common manifestations in these six patients were persistent fever, splenohepatomegalia and percussion pain in hepatic region. Meanwhile, 2 of them were accompanied with appearance of painful and diffuse cataneous nodules, expectoration and dyspnoea. The abnormal laboratory test observed of them was increase of alkaline phosphatase. Computed tomography scan showed multiple hypodense lesions in the liver and spleen in all the five patients; one of them showed multiple nodular patchy shadows in bone. Nuclear magnetic resonance imaging showed multiple abnormal signal in liver, spleen and kidneys in one of the patients. Three patients had positive blood candida tropicalis cultures. liver biopsy in one patient was negative for fungal. Two patients received Fluconazole therapy empirically, but it was replaced by Itraconazole later in one because of unresponsiveness to the drug. Three patients received Itraconazole therapy and in one received voriconazole therapy empirically. CDC-attributable clinical symptoms resolved with CST, which was started an average of 31 day since antifungal therapy was initiated. Fever and abdominal pain disappeared a median of 5–6 days, and serum fibrinogen and C-reactive protein levels returned to normal values within 14–30 days. Hepatosplenic microabscesses decreased or disappeared within a mean period of 45 days (range, 27–167 days). All the six patients received further chemotherapy smoothly after the treatment antifungal therapy combined with CST,No relapses of CDC were observed during a median duration of follow-up of 3.2 years (range, 2.6–3.8 years).CONCLUSION: In adults who experience persistently symptomatic CDC despite ongoing receipt of antifungal therapy, CST involving a prednisone equivalent at a dosage of > or =0.25 mg/kg per day for at least 3 weeks is associated with a prompt resolution of symptoms and of inflammatory response. These findings support the pathophysiological hypothesis that CDC belongs to the spectrum of fungus-related immune reconstitution inflammatory syndrome. Disclosures: No relevant conflicts of interest to declare.


2013 ◽  
Vol 57 (6) ◽  
pp. 2550-2555 ◽  
Author(s):  
Jennifer Le ◽  
Tu T. Tran ◽  
Ivilynn Bui ◽  
Mike K. Wang ◽  
Andrew Vo ◽  
...  

ABSTRACTThe effect of delayed antifungal therapy in critically ill infants with invasive candidiasis has not been studied. Our objective was to evaluate the effect of time to initiation of antifungal therapy (TIA) on mortality, disseminated disease, and postinfection hospital stay. We conducted a cohort study of critically ill infants with cultures positive forCandidafrom 1990 to 2008. TIA was defined as the number of hours from the collection of the first positive culture until the start of antifungal therapy. Of 96 infants, 57% were male, the median gestational age was 27 weeks (range, 23 to 41 weeks), and the median birth weight was 956 g (range, 415 to 6,191 g). Most subjects received amphotericin B deoxycholate. TIA was ≤24 h for 35% of infants, between 25 and 48 h for 42%, and >48 h for 23%. Eleven subjects died during hospitalization, and 22% had disseminated candidiasis. The median duration of hospital stay postinfection was 53 days (range, 6 to 217 days). Both univariate and multivariate analyses demonstrated that TIA was not associated with mortality, disseminated disease, or hospital stay postinfection. However, ventilator use for >60 days significantly increased the risk of death (odds ratio [OR], 9.5; 95% confidence interval [CI], 2.2 to 66.7;P= 0.002). Prolonged candidemia increased the risk of disseminated disease by 10% per day of positive culture (OR, 1.1; 95% CI, 1.08 to 1.2;P= 0.007), and low gestational age was associated with increased neonatal intensive care unit (NICU) stay after the first positiveCandidaculture by 0.94 weeks (95% CI, 0.70 to 0.98;P< 0.001). The TIA was not associated with all-cause mortality, disseminated candidiasis, and postinfection length of hospital stay.


2016 ◽  
pp. fow011 ◽  
Author(s):  
Ian A. Cleary ◽  
Sara M. Reinhard ◽  
Anna L. Lazzell ◽  
Carlos Monteagudo ◽  
Derek P. Thomas ◽  
...  

2010 ◽  
Vol 35 (8) ◽  
pp. 567-570 ◽  
Author(s):  
Bing Xu ◽  
Pengcheng Shi ◽  
Hubing Wu ◽  
Xutao Guo ◽  
Quanshi Wang ◽  
...  

2000 ◽  
Vol 38 (6) ◽  
pp. 2317-2323 ◽  
Author(s):  
Karl A. Andrutis ◽  
Perry J. Riggle ◽  
Carol A. Kumamoto ◽  
Saul Tzipori

2000 ◽  
Vol 38 (6) ◽  
pp. 2317-2323
Author(s):  
Karl A. Andrutis ◽  
Perry J. Riggle ◽  
Carol A. Kumamoto ◽  
Saul Tzipori

2011 ◽  
Vol 55 (7) ◽  
pp. 3491-3497 ◽  
Author(s):  
Amy M. Flattery ◽  
Emily Hickey ◽  
Charles J. Gill ◽  
Mary Ann Powles ◽  
Andrew S. Misura ◽  
...  

ABSTRACTNeonatal candidiasis is an increasingly common occurrence causing significant morbidity and mortality and a higher risk of dissemination to the central nervous system (CNS) than that seen with older patients. The current understanding of optimal antifungal therapy in this setting is limited. We have developed a model of disseminated candidiasis with CNS involvement in juvenile mice to assess the efficacy of the echinocandin caspofungin relative to amphotericin B (AmB). Juvenile mice were inoculated intravenously with 5.64 × 104CFU ofCandida albicansMY1055. Treatment with caspofungin at 1, 2, 4, and 8 mg/kg of body weight/day, AmB at 1 mg/kg/day, or a vehicle control (VC) was initiated 30 h after infection and continued for 7 days. Pharmacokinetic parameters for caspofungin were also determined. Culture and histology showed evidence of disseminated candidiasis with multifocal encephalitis at the start of antifungal therapy. Survival was 100% in all treated groups, while mortality was 100% in the VC by day 11 after infection. By day 5, all mice in the caspofungin treatment (four doses) groups showed reductions in kidney and brain burden relative to the VC, while AmB treatment reduced kidney burden but gave no reduction of brain fungal burden. Systemic levels of caspofungin were similar in infected and uninfected mice, while brain levels were higher in infected animals. In this juvenile mouse model, caspofungin demonstrated dose-dependent activity, equivalent to or better than that of AmB at 1 mg/kg, against disseminated candidiasis with CNS involvement.


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