scholarly journals Do high MICs predict the outcome in invasive fusariosis?

2020 ◽  
Author(s):  
Marcio Nucci ◽  
Jeffrey Jenks ◽  
George R Thompson ◽  
Martin Hoenigl ◽  
Marielle Camargo dos Santos ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Death Rate ◽  
Liposomal Amphotericin ◽  
Antifungal Agents ◽  
Fusarium Species ◽  
Primary Treatment ◽  
Clear Cut ◽  
The Poor ◽  
Immunocompromised Hosts ◽  
High Mics

Abstract Background Invasive fusariosis (IF) affects mostly severely immunocompromised hosts and is associated with poor outcome. Since Fusarium species exhibit high MICs for most antifungal agents, this could explain the poor prognosis. However, a clear-cut correlation between MIC and outcome has not been established. Objective To evaluate the correlation between MIC and outcome (6 week death rate) in patients with IF. Methods We performed a multicentre retrospective study of patients with IF who received treatment and had MIC levels determined by EUCAST or CLSI for the drug(s) used during treatment. We compared the MIC50 and MIC distribution among survivors and patients who died within 6 weeks from the diagnosis of IF. Results Among 88 patients with IF, 74 had haematological diseases. Primary treatment was monotherapy in 52 patients (voriconazole in 27) and combination therapy in 36 patients (liposomal amphotericin B + voriconazole in 23). The MIC50 and range for the five most frequent agents tested were: voriconazole 8 mg/L (range 0.5–64), amphotericin B 2 mg/L (range 0.25–64), posaconazole 16 mg/L (range 0.5–64), itraconazole 32 mg/L (range 4–64), and isavuconazole 32 mg/L (range 8–64). There was no difference in MIC50 and MIC distribution among survivors and patients who died. By contrast, persistent neutropenia and receipt of corticosteroids were strong predictors of 6 week mortality. Conclusions Our study did not show any correlation between MIC and mortality at 6 weeks in patients with IF.

scholarly journals Disseminated fusariosis in a pediatric patient with acute lymphoblastic leukemia and prolonged fever - a case report

2018 ◽  
Vol 71 (9-10) ◽  
pp. 314-318
Author(s):  
Natasa Kacanski ◽  
Branislava Radisic ◽  
Jovanka Kolarovic
Keyword(s):  
Case Report ◽  
Acute Lymphoblastic Leukemia ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Lymphoblastic Leukemia ◽  
Fusarium Species ◽  
Water System ◽  
Liposomal Amphotericin B ◽  
Fusarium Infection ◽  
Days Of Therapy

Introduction. Infections caused by fungi of Fusarium species occur in immunocompromised individuals as disseminated diseases. Case Report. This case report presents a 5-year-old boy with acute lymphoblastic leukemia who developed a disseminated fusarium infection during reinduction chemotherapy. Fever was the main symptom and it lasted for 15 weeks. Refractory fever despite broad-spectrum antibiotics, as well as nausea, myalgia, pulmonary symptoms with detection of pulmonary infiltrates, liver and spleen involvement indicated an invasive fungal infection. The patient received fluconazole, voriconazole, liposomal amphotericin B and caspofungin. Since high temperature was persistent, diagnostic laparoscopy of the abdomen was done. Scattered lesions, up to 2 mm in diameter, were observed macroscopically on the surface of the liver and spleen. The liver culture was positive for Acinetobacter and Fusarium species. After 38 days of therapy with liposomal amphotericin B and 3 days of ciprofloxacin, the patient became afebrile. Itraconazole (according to the antimycogram) was continued during maintenance therapy. Abdominal ultrasound was completely normal after 5 months of treatment with itraconazole. This boy was our first patient with a disseminated fusarium infection. At that time, Fusarium was detected in the hospital water system and in hospital air samples. Conclusion. A timely diagnosis of invasive fungal diseases in children is a big challenge. Over the past decade, there has been an increase in survival rate of patients with invasive fusariosis due to much more common use of voriconazole or combined antifungal therapy.

scholarly journals Effect of pH on the In Vitro Activities of Amphotericin B, Itraconazole, and Flucytosine against Aspergillus Isolates

2004 ◽  
Vol 48 (8) ◽  
pp. 3147-3150 ◽  
Author(s):  
D. T. A. Te Dorsthorst ◽  
J. W. Mouton ◽  
C. J. P. van den Beukel ◽  
H. A. L. van der Lee ◽  
J. F. G. M. Meis ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Poor Correlation ◽  
Yeast Nitrogen Base ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Nitrogen Base ◽  
The Poor

ABSTRACT The in vitro susceptibilities of 21 Aspergillus isolates were tested against three antifungal agents in RPMI 1640 and yeast nitrogen base at pH 5.0 and 7.0 by a broth microdilution format of the NCCLS method. The MICs of amphotericin B and itraconazole were higher, while those of flucytosine were lower, at pH 5.0 than at pH 7.0. The poor correlation between in vitro results and clinical outcome could be due to a difference in pH between the in vitro susceptibility test and at the site of infection.

scholarly journals Comparative Efficacies of Conventional Amphotericin B, Liposomal Amphotericin B (AmBisome), Caspofungin, Micafungin, and Voriconazole Alone and in Combination against Experimental Murine Central Nervous System Aspergillosis

2005 ◽  
Vol 49 (12) ◽  
pp. 4867-4875 ◽  
Author(s):  
Karl V. Clemons ◽  
Marife Espiritu ◽  
Rachana Parmar ◽  
David A. Stevens
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Antifungal Agents ◽  
Severe Disease ◽  
Fungal Burden ◽  
Enhanced Activity ◽  
Current Therapies ◽  
Immunosuppressed Mice

ABSTRACT Central nervous system (CNS) aspergillosis is a severe disease that responds poorly to current therapies. The current studies examined the efficacies of several antifungal agents alone or in combination with a murine model of CNS aspergillosis. Immunosuppressed mice were infected intracerebrally with Aspergillus fumigatus and treated with an amphotericin B preparation, an echinocandin, or voriconazole (VCZ) given alone or in combination. Monotherapy studies showed that micafungin (MICA), caspofungin (CAS), VCZ, conventional amphotericin B (AMB), Abelcet (ABLC) (a lipid-carried AMB formulation; Enzon Pharmaceuticals, Inc.), and AmBisome (AmBi) (liposomal AMB; Gilead Sciences, Inc.) were efficacious. However, doses of AmBi above 15 mg/kg of body weight showed reduced efficacy. Neither MICA nor CAS showed dose responsiveness at the doses tested (1, 5, or 10 mg/kg). Only the 40-mg/kg dose of VCZ was effective. AmBi and ABLC showed dose responsiveness, with 10-mg/kg doses causing a significant reduction in fungal burden; they had equivalent activities at the 10-mg/kg dose. Suboptimal dosages of AmBi in combination with MICA, CAS, or VCZ were effective in prolonging survival. However, significantly enhanced activity was demonstrated only with AmBi and VCZ in combination. AmBi in combination with MICA or CAS showed a trend toward enhanced activity, but the combination was not significantly superior to monotherapy. The use of AmBi with CAS or VCZ at optimal doses did not improve efficacy. Cure was not attained with any dosage combinations. These results indicate that AmBi in combination with VCZ may be superior for treatment of CNS aspergillosis; combinations of AmBi and MICA or CAS were not antagonistic and may have a slight benefit.

scholarly journals Mucormycosis: Effect of Comorbidities and Repeated Debridement on the Outcome

2019 ◽  
Vol 27 (1) ◽  
pp. 8-14
Author(s):  
Harshavardhan N Reddy ◽  
Sanjay B Patil ◽  
Chandrakiran Channegowda ◽  
Aiswarya Muralidharan
Keyword(s):  
Diabetes Mellitus ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Liposomal Amphotericin B ◽  
Invasive Infection ◽  
Comorbid Conditions ◽  
Tissue Necrosis ◽  
Immunocompromised Hosts ◽  
Vessel Thrombosis

Introduction: Mucormycosis is an aggressive, invasive infection caused by ubiquitous filamentous fungibelonging to the subphylum Mucormycotina, order Mucorales. Mucormycosis most commonly affects immunocompromised hosts, but are rarely reported in immunocompetent hosts as well. The most common reported sites of invasive mucormycosis have been the sinuses (39%), lungs (24%), and skin (19%). The hallmark of mucormycosis is angioinvasion resulting in vessel thrombosis and hence, tissue necrosis.   Materials and Methods: Ambispective study of 20 cases with mucormycosis seen and treated in our hospital between 2009 and 2015 and followed up to 2017 to compare the prognosis of the cases of repeated debridement with that of single debridement and effect of comorbidities in the outcome of patients mortality .   Results: Out of 20 patients 19 (95%) received Liposomal Amphotericin B. 11 (55%) were male and 9 (45%) were female. All the 7 (35%) who underwent repeated debridement survived. Out of 13 (65%) patients who underwent single debridement, 5 (25%) did not survive. 2 (10%) patients were lost for follow up. The survival amongst the patients undergoing multiple debridement and single debridement was statistically significant (p=0.042) Conclusion: The chances of survival are better in cases with better controlled comorbid conditions like diabetes mellitus. Repeated debridement with Liposomal Amphotericin B is the most effective mode of management.

Cryptococcosis in Australasia and the treatment of cryptococcal and other fungal infections with liposomal amphotericin B

2002 ◽  
Vol 49 (suppl_1) ◽  
pp. 57-61 ◽  
Author(s):  
Sharon C. A. Chen
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Fungal Infections ◽  
Randomized Study ◽  
Initial Therapy ◽  
Liposomal Amphotericin B ◽  
Lipid Complex ◽  
Reduced Toxicity ◽  
Main Barrier ◽  
Immunocompromised Hosts

Abstract Cryptococcus neoformans is an important fungal pathogen in both immunocompromised and immunocompetent hosts. The mean annual incidence during 1994–1997 was 6.6 cases per million people per year in Australia, and 2.2 cases per million people per year in New Zealand. C. neoformans var. neoformans caused 85% of 312 episodes (98% of episodes in immunocompromised hosts) and C. neoformans var. gattii caused 15% (44% in immunocompetent hosts). The AIDS-specific incidence declined significantly over the 3 years. Mortality from cryptococcosis remains substantial. In trials involving small numbers of AIDS patients, liposomal amphotericin B (AmBisome) was found to be active against C. neoformans, with mycological response rates of 67–85%; however, maintenance therapy with an oral antifungal agent is required indefinitely. In a randomized study of patients with cryptococcal meningitis, AmBisome (4 mg/kg/day) produced mycological eradication in 73% of patients compared with 38% with conventional amphotericin. AmBisome resulted in significantly earlier sterilization of cerebrospinal fluid than conventional amphotericin (7–14 days versus 21 days) and was less nephrotoxic. The benefit of this reduced toxicity is denied to many patients because of an enormous cost barrier. In a survey of the practices of clinical mycologists in Australia, 11 experts responded to a questionnaire survey regarding the use of available lipid preparations. Their indications for use as initial therapy were mucormycosis (7/10), renal failure (7/10), Fusarium infection (2/10) and aspergillosis (2/10). Cryptococcosis, candidosis and febrile neutropenia were rarely regarded as an indication; failed therapy with conventional amphotericin was an indication to use AmBisome for 8/11 respondents. The majority believed that AmBisome was equivalent to conventional amphotericin, with amphotericin B lipid complex and AmBisome equivalent to each other in terms of efficacy. The main barrier to replacement of conventional amphotericin with lipid preparations was seen as an issue of cost.

scholarly journals Primary treatment of zygomycosis with liposomal amphotericin B: analysis of 28 cases

2010 ◽  
Vol 48 (3) ◽  
pp. 511-517 ◽  
Author(s):  
Shmuel Shoham ◽  
Shelley S. Magill ◽  
William G. Merz ◽  
Corina Gonzalez ◽  
Nita Seibel ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Primary Treatment ◽  
Liposomal Amphotericin B
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