Combination and Sequential Antifungal Therapy for Invasive Aspergillosis: Review of Published In Vitro and In Vivo Interactions and 6281 Clinical Cases from 1966 to 2001

Steinbach, William J.; Stevens, David A.; Denning, David W.

doi:10.1086/376524

Cited by 176 publications

(117 citation statements)

References 282 publications

(230 reference statements)

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“…In patients with invasive Aspergillus infection who do not improve with a single antifungal agent, consideration should be given to combination antifungal therapy. 8 We hope to heighten the awareness of this often fatal disease and urge prompt and aggressive measures to obtain tissue for diagnosis, and perhaps to start appropriate antifungal treatment even before the diagnosis is made. …”

Section: Discussionmentioning

confidence: 99%

Invasive Aspergillosis in an Immunocompetent Patient with Fever and a Cardiac Mass

LaBarbera

Jacobson

2011

Infectious Disease Reports

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Invasive aspergillosis is an often fatal disease that usually occurs in immunocompromised patients. We report a case of invasive aspergillosis presenting as a febrile respiratory infection with a cardiac mass in an immunocompetent patient. Invasive aspergillosis should be considered in the differential diagnosis of an otherwise undiagnosed invasive febrile respiratory illness, even in immunocompetent patients. Echocardio graphy should be performed to evaluate for endocarditis in such cases. Prompt initiation of appropriate antifungal therapy is warranted, even before the diagnosis of invasive aspergillosis is confirmed. Brief ReportA generally healthy 53 year-old male plumber with suboptimally-controlled noninsulin dependent diabetes mellitus (Hb A1c 8) and coronary artery disease s/p CABG 10 years earlier presents to the ED with 10 days of fever and cough. Physical exam reveals a temperature of 36.6°C, blood pressure of 111/70 mmHg, pulse of 108 bpm, respiratory rate of 30, and pulse oxygen saturation of 80% on room air which rises to 95% on 4 liter nasal cannula. There is a regular tachycardia without murmur; rales are present one-quarter up the lung fields bilaterally. Labs are notable for a wbc 15.2 with 73% neutrophils and 8% bands. Electrocardiogram demonstrates sinus tachycardia at 110 beats per minute with an incomplete right bundle branch block pattern. Chest radiography reveals bilateral interstitial infiltrates with small nodules in the right upper and left lower lobes. Moxifloxacin is started for treatment of community-acquired pneumonia. On HD #2 CT angiogram of the pulmonary arteries reveals a small left upper lobe pulmonary embolism and extensive bilateral ground-glass opacities. Lower extremity venous Doppler ultrasound study reveals bilateral DVTs below the knee. Therapeutic enoxaparin injections are started. On HD #3 a bronchoalveolar lavage is performed with washings sent for Gram stain, and bacterial, fungal, AFB, and viral cultures, all of which are negative. Serum human immunodeficiency virus test is negative.Transthoracic echocardiogram performed on HD #3 to assess pulmonary artery pressures and cardiac function reveals normal left ventricular systolic function, an estimated right ventricular systolic pressure of 58 mmHg,

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Section: Discussionmentioning

confidence: 99%

Invasive Aspergillosis in an Immunocompetent Patient with Fever and a Cardiac Mass

LaBarbera

Jacobson

2011

Infectious Disease Reports

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“…The following criteria are commonly followed: synergy, a Ն2-log 10 decrease in CFU/ ml compared to the most active constituent; antagonism, a Ն2-log 10 increase in CFU/ml compared to the least active agent; additivity, a Ͻ2-but Ͼ1-log 10 decrease in CFU/ml compared to the most active agent; and indifference, a Ͻ2-but Ͼ1-log 10 increase in CFU/ml compared to the least active agent. (97,98,130,154,156,211), rats (140), or rabbits (172). Factors that need to be considered while performing in vivo studies include variable drug absorption, distribution, and metabolism among animal species.…”

Section: Methods To Determine the In Vivo Efficacy Of Antifungal Agenmentioning

confidence: 99%

“…Similarly, prior treatment of mice with ITRA abolished the protective effect of AmB, even when ITRA treatment was stopped before AmB therapy was started (199). A recent review of 6,281 clinical cases (from 1966 to 2001) of invasive aspergillosis showed that simultaneous combination and sequential antifungal therapy led to improvement in 63 and 68% of the cases, respectively (211).…”

Section: Dual Combinations In the Practice Guidelines For Aspergillosmentioning

confidence: 99%

Combination Treatment of Invasive Fungal Infections

et al. 2005

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The persistence of high morbidity and mortality from systemic fungal infections despite the availability of novel antifungals points to the need for effective treatment strategies. Treatment of invasive fungal infections is often hampered by drug toxicity, tolerability, and specificity issues, and added complications often arise due to the lack of diagnostic tests and to treatment complexities. Combination therapy has been suggested as a possible approach to improve treatment outcome. In this article, we undertake a historical review of studies of combination therapy and also focus on recent studies involving newly approved antifungal agents. The limitations surrounding antifungal combinations include nonuniform interpretation criteria, inability to predict the likelihood of clinical success, strain variability, and variations in pharmacodynamic/pharmacokinetic properties of antifungals used in combination. The issue of antagonism between polyenes and azoles is beginning to be addressed, but data regarding other drug combinations are not adequate for us to draw definite conclusions. However, recent data have identified potentially useful combinations. Standardization of assay methods and adoption of common interpretive criteria are essential to avoid discrepancies between different in vitro studies. Larger clinical trials are needed to assess whether combination therapy improves survival and treatment outcome in the most seriously debilitated patients afflicted with life-threatening fungal infections

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“…While it appears that combination antifungal therapy as primary therapy for IA may confer some benefit, this has not yet been rigorously tested in a controlled trial and the decision regarding what combination to use is based primarily on in vitro data, retrospective cohort outcomes, and animal data [102]. Only one, small, prospective randomized trial of combination anti-Aspergillus therapy has been published to date.…”

Section: Aspergillusmentioning

confidence: 99%