Efficacy of intravenous itraconazole against invasive pulmonary aspergillosis in neutropenic mice

Tansho, Shigeru; Abe, Shigeru; Ishibashi, Hidetoshi; Torii, Shinichi; Otani, Hisaya; Ono, Yasuo; Yamaguchi, Hideyo

doi:10.1007/s10156-006-0479-2

Cited by 7 publications

(6 citation statements)

References 16 publications

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“…Oral and IM usage of aminosides was rarer (Supplementary Material 4). Injectable glycopeptides and carbapenems were sporadically used to prevent infections due to multi-resistant staphylococci and enterobacteriae (Melchers et al, 1994; Hashimoto et al, 1998; Yonezawa et al, 2000; Benjamim et al, 2005; Steinbach et al, 2006; Tansho et al, 2006; van Vianen et al, 2006; Cramer et al, 2008; Pinchai et al, 2009; Rivera et al, 2009; Petrik et al, 2010, 2012, 2014; Grahl et al, 2011; Martinez et al, 2013; Verwer et al, 2013). Likewise, multi-antibiotic associations were sometimes reported, like the following scheme: ciprofloxacin (660 mg/L) and polymyxin B (100 mg/L) in water, plus IM amoxicillin (40 mg/kg/day) and a single shot of IM gentamicin (6 mg/kg) at time of experimental infection (Leenders et al, 1996; Dams et al, 1999; Becker et al, 2000, 2002a,b, 2003, 2006; Van Etten et al, 2000; Ruijgrok et al, 2001, 2005, 2006).…”

Section: Resultsmentioning

confidence: 99%

“…Globally, investigators always privileged the usage of referenced A. fumigatus strains that had been first isolated from clinical samples during invasive aspergillosis course in patients. For instance, AFB62 (Sugui et al, 2011, 2014; Losada et al, 2015), TIMM 2920 (Tansho et al, 2006), AF210 also named as NCPF 7101 or 2.06013 (Denning et al, 1997a,b; Verweij et al, 1998; Johnson et al, 2000; Paisley et al, 2005), IFM 4942 (Yamada et al, 1993), or BMU 01200 were isolated in hematopoietic stem cell transplants (Sun et al, 2012; Zhang et al, 2015), as well as A22 and AF65 (also referred to as NCPF 7097 or ATCC® MYA772 for the latter) were collected in lung biopsy from immunocompromised patients (Denning et al, 1997a; Verweij et al, 1998; Denning and Warn, 1999; Johnson et al, 2000; Paisley et al, 2005; Speth et al, 2013). Likewise, Zhao et al relevantly used a A. fumigatus strain that came from fungal endophthalmitis for their work about eye aspergillosis (Zhao et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

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Rodent Models of Invasive Aspergillosis due to Aspergillus fumigatus: Still a Long Path toward Standardization

Désoubeaux

Cray

2017

Front. Microbiol.

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Invasive aspergillosis has been studied in laboratory by the means of plethora of distinct animal models. They were developed to address pathophysiology, therapy, diagnosis, or miscellaneous other concerns associated. However, there are great discrepancies regarding all the experimental variables of animal models, and a thorough focus on them is needed. This systematic review completed a comprehensive bibliographic analysis specifically-based on the technical features of rodent models infected with Aspergillus fumigatus. Out the 800 articles reviewed, it was shown that mice remained the preferred model (85.8% of the referenced reports), above rats (10.8%), and guinea pigs (3.8%). Three quarters of the models involved immunocompromised status, mainly by steroids (44.4%) and/or alkylating drugs (42.9%), but only 27.7% were reported to receive antibiotic prophylaxis to prevent from bacterial infection. Injection of spores (30.0%) and inhalation/deposition into respiratory airways (66.9%) were the most used routes for experimental inoculation. Overall, more than 230 distinct A. fumigatus strains were used in models. Of all the published studies, 18.4% did not mention usage of any diagnostic tool, like histopathology or mycological culture, to control correct implementation of the disease and to measure outcome. In light of these findings, a consensus discussion should be engaged to establish a minimum standardization, although this may not be consistently suitable for addressing all the specific aspects of invasive aspergillosis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Rodent Models of Invasive Aspergillosis due to Aspergillus fumigatus: Still a Long Path toward Standardization

Désoubeaux

Cray

2017

Front. Microbiol.

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“…The benefit, however, may not be achieved by increasing the dose of ITC alone. Previous studies have shown that the antifungal effect of ITC in vivo is not dose-dependent (Tansho et al, 2006). An increased dose of ITC does not always result in enhanced survival.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo Efficacy of a Synergistic Combination of Itraconazole and Verapamil Against Aspergillus fumigatus

et al. 2019

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The incidence of aspergillosis continues to rise sharply, while the progress made in expanding the antifungal drug arsenal remains extremely slow, indicating an urgent need for new strategies. Previous studies have shown that the calcium signaling pathway, which is evolutionarily conserved in mammals and fungi, is involved in regulating the tolerance of azoles in fungi. In this study, we performed a preliminary screening among various combinations of different clinical calcium channel blockers and different antifungal drugs. We found that the combination of itraconazole and verapamil showed the best synergistic effect against Aspergillus fumigatus . Thereafter, using the checkboard assays we observed synergistic effects of the combination treatment against most of the A. fumigatus strains tested, including itraconazole-sensitive and itraconazole-resistant strains, with a fractional inhibitory concentration index (FICI) < 0.5. Furthermore, we showed that verapamil strongly decreased the cytosolic calcium transients following itraconazole stimulation by an aequorin-mediated method. Moreover, verapamil influenced the efflux of rhodamine 6G, an azole mimic substance. An ergosterol assay revealed that verapamil alone had no effect on ergosterol biosynthesis, but the combination of itraconazole and verapamil treatment decreased the ergosterol level. Further murine assays were performed using a luciferase-probed bioluminescence imaging method. Drug combination therapy reduced lung burden and improved survival rate. In conclusion, verapamil is a promising candidate to enhance the antifungal activity of itraconazole against A. fumigatus . In addition, our study suggests the effectiveness of an emerging approach based on bioluminescence imaging in monitoring the efficacy of drug combination therapy for invasive aspergillosis.

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“…In mice infected with invasive aspergillosis, weight loss is universal and is preceded by mortality [12]. The ability to obtain a weight loss history may be an excellent marker for the early identification of patients who may be a higher risk for IA.…”

Section: Discussionmentioning

confidence: 99%

“…While survival of this disease has recently improved with the use of Voriconazole versus conventional therapy with amphotericin therapy [8-12], the mortality rate is still elevated. If the diagnosis is missed after more than a month in the hospital, the mortality rate will likely be quite high as in our sentinel case.…”

Section: Discussionmentioning

confidence: 99%

Weight loss and diabetes are new risk factor for the development of invasive aspergillosis infection in non-immunocompromized humans

Ghanaat

Tayek

2017

clinical-practice

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Well-established risk factors for aspergillosis include HIV, cancer, recent corticosteroid (prednisone) therapy, chemotherapy, or thoracic surgery. Non-established risk factors may include weight loss and a history of diabetes. Twenty-three patients without the classical risk factors for IA were identified retrospectively at Harbor UCLA Medical Center by discharge diagnosis over a 20 year period (1992-2012). None of the well-known risk factors are for Invasive Apergillious (IA). A history of weight loss was seen in 66% of the patients with IA (15 of 23). The weight loss ranged from 3.3 lbs to 43 lbs. In patients with weight loss the average loss was 22±3 lbs (mean±SEM). In this small group of patients with IA, diabetes was seen in 8 of the 23 (34%), which is significantly higher than the 19% incidence of diabetes seen in 100 patients with severe sepsis (p<0.05). Likewise, the 34% incidence of diabetes was higher than the 21% incidence reported in immunocompromised patients with invasive aspergillus (IA) infection (p<0.05). A reduced serum albumin concentration was seen in 33% of the study patients, which was less common than the 87% incidence seen in patients with severe sepsis or candidaemia (54%). Seventeen of the 23 patients had pulmonary involvement. While no one had a well-established risk factor for aspergillious, four patients had alcoholism as a potential risk factor. Eleven of the 23 (48%) died during the hospital stay despite antifungal therapy. Immunocompromised patients are known to have a mortality rate of approximately 45% for pulmonary or disseminated disease. Conclusion The incidence of diabetes was greater than seen in immunocompromised patients and may be considered an additional risk factor for the development of aspergillois infection. In addition, a history of weight loss should increase the suspicion for the diagnosis of IA in otherwise a non-immunocompromised patient. Early recognition and treatment of aspergillosis in the non-immunocompromised patient may improve outcome. Weight loss and diabetes should be added to the list of well-known risk factors for invasive aspergillosis and its high mortality rate.

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Efficacy of intravenous itraconazole against invasive pulmonary aspergillosis in neutropenic mice

Cited by 7 publications

References 16 publications

Rodent Models of Invasive Aspergillosis due to Aspergillus fumigatus: Still a Long Path toward Standardization

Rodent Models of Invasive Aspergillosis due to Aspergillus fumigatus: Still a Long Path toward Standardization

In vitro and in vivo Efficacy of a Synergistic Combination of Itraconazole and Verapamil Against Aspergillus fumigatus

Weight loss and diabetes are new risk factor for the development of invasive aspergillosis infection in non-immunocompromized humans

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