Faculty Opinions recommendation of Pharmacokinetics and pharmacodynamics of posaconazole for invasive pulmonary aspergillosis: clinical implications for antifungal therapy.

A 47-year-old Caucasian man on long-standing antifungal therapy for chronic necrotising aspergillosis and a history of recurrent pseudomonas pneumonias presented to the outpatient pulmonary clinic with dyspnoea and chest discomfort for 3 days. A CT angiography of the chest demonstrated angioinvasion from the previously noted left upper lobe cavitary lesion into the left main pulmonary artery, along with new consolidating lesions. Due to the high risk for massive haemoptysis, he was evaluated by thoracic surgery and underwent a successful left pneumonectomy. As invasive pulmonary aspergillosis is associated with high mortality, surgical intervention should always be considered, especially in those who develop extensive disease, despite being on aggressive antifungal therapy. Though minimally described in literature, invasive pulmonary pseudomonas also carries a high mortality risk. In our patient, cultures from the resected lung only demonstrated Pseudomonas aeruginosa.

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Combination antifungal therapy for invasive pulmonary aspergillosis

BMJ Case Reports ◽

10.1136/bcr-2012-007824 ◽

2012 ◽

Vol 2012 (dec14 1) ◽

pp. bcr2012007824-bcr2012007824 ◽

Cited By ~ 2

Author(s):

S. Abdulaziz ◽

H. Al Jahdali ◽

S. Baharoon

Keyword(s):

Antifungal Therapy ◽

Invasive Pulmonary Aspergillosis ◽

Pulmonary Aspergillosis

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Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management

European Respiratory Journal ◽

10.1183/13993003.00583-2015 ◽

2015 ◽

Vol 47 (1) ◽

pp. 45-68 ◽

Cited By ~ 268

Author(s):

David W. Denning ◽

Jacques Cadranel ◽

Catherine Beigelman-Aubry ◽

Florence Ader ◽

Arunaloke Chakrabarti ◽

...

Keyword(s):

Antifungal Therapy ◽

Clinical Guidelines ◽

Bronchial Artery ◽

Invasive Pulmonary Aspergillosis ◽

Immunological Response ◽

Surgical Excision ◽

Immunocompromised Patients ◽

Pulmonary Aspergillosis ◽

Thoracic Imaging ◽

Chronic Pulmonary Aspergillosis

Chronic pulmonary aspergillosis (CPA) is an uncommon and problematic pulmonary disease, complicating many other respiratory disorders, thought to affect ∼240 000 people in Europe. The most common form of CPA is chronic cavitary pulmonary aspergillosis (CCPA), which untreated may progress to chronic fibrosing pulmonary aspergillosis. Less common manifestations include:Aspergillusnodule and single aspergilloma. All these entities are found in non-immunocompromised patients with prior or current lung disease. Subacute invasive pulmonary aspergillosis (formerly called chronic necrotising pulmonary aspergillosis) is a more rapidly progressive infection (<3 months) usually found in moderately immunocompromised patients, which should be managed as invasive aspergillosis. Few clinical guidelines have been previously proposed for either diagnosis or management of CPA. A group of experts convened to develop clinical, radiological and microbiological guidelines. The diagnosis of CPA requires a combination of characteristics: one or more cavities with or without a fungal ball present or nodules on thoracic imaging, direct evidence ofAspergillusinfection (microscopy or culture from biopsy) or an immunological response toAspergillusspp. and exclusion of alternative diagnoses, all present for at least 3 months.Aspergillusantibody (precipitins) is elevated in over 90% of patients. Surgical excision of simple aspergilloma is recommended, if technically possible, and preferablyviavideo-assisted thoracic surgery technique. Long-term oral antifungal therapy is recommended for CCPA to improve overall health status and respiratory symptoms, arrest haemoptysis and prevent progression. Careful monitoring of azole serum concentrations, drug interactions and possible toxicities is recommended. Haemoptysis may be controlled with tranexamic acid and bronchial artery embolisation, rarely surgical resection, and may be a sign of therapeutic failure and/or antifungal resistance. Patients with singleAspergillusnodules only need antifungal therapy if not fully resected, but if multiple they may benefit from antifungal treatment, and require careful follow-up.

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Invasive Pulmonary Aspergillosis in Patients With Severe Fever With Thrombocytopenia Syndrome

Clinical Infectious Diseases ◽

10.1093/cid/ciz673 ◽

2019 ◽

Cited By ~ 1

Author(s):

Seongman Bae ◽

Hye Jeon Hwang ◽

Mi Young Kim ◽

Min Jae Kim ◽

Yong Pil Chong ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Antifungal Therapy ◽

Invasive Pulmonary Aspergillosis ◽

Pulmonary Aspergillosis ◽

Severe Fever

Abstract Sixteen of 45 patients with severe fever with thrombocytopenia (36%) were admitted to an intensive care unit; 9 (56%) developed invasive pulmonary aspergillosis (IPA) within a median of 8 days (range, 2–11). Mortality was higher in the IPA vs non-IPA patients and in those without vs with antifungal therapy.

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Aspergillus-Specific Lateral-Flow Device and Real-Time PCR Testing of Bronchoalveolar Lavage Fluid: a Combination Biomarker Approach for Clinical Diagnosis of Invasive Pulmonary Aspergillosis

Journal of Clinical Microbiology ◽

10.1128/jcm.00110-15 ◽

2015 ◽

Vol 53 (7) ◽

pp. 2103-2108 ◽

Cited By ~ 29

Author(s):

Gemma L. Johnson ◽

Shah-Jalal Sarker ◽

Francesco Nannini ◽

Arianna Ferrini ◽

Emma Taylor ◽

...

Keyword(s):

Bronchoalveolar Lavage ◽

Real Time ◽

Antifungal Therapy ◽

Real Time Pcr ◽

Invasive Pulmonary Aspergillosis ◽

Lateral Flow ◽

Pulmonary Aspergillosis ◽

Lateral Flow Device ◽

Flow Device ◽

The Impact

Clinical experience with the impact of serum biomarkers for invasive fungal disease (IFD) varies markedly in hemato-oncology. Invasive pulmonary aspergillosis (IPA) is the most common manifestation, so we evaluated biomarkers in bronchoalveolar lavage (BAL) fluid. AnAspergillus-specific lateral-flow device (LFD), quantitative real-time PCR (qPCR), and the galactomannan (GM) test were used with 32 BAL fluid samples from 32 patients at risk of IPA. Eight patients had proven IPA, 3 had probable IPA, 6 had possible IPA, and 15 patients had no IPA by European Organization for Research and Treatment of Cancer Invasive Fungal Infections Cooperative Group/Mycoses Study Group of the National Institute of Allergy and Infectious Diseases (EORTC/MSG) criteria. The diagnostic accuracies of the tests were evaluated, and pairwise agreement between biomarkers was calculated. The diagnostic performance of the EORTC/MSG criteria was evaluated against the test(s) identified to be the most useful for IPA diagnosis. Using the EORTC/MSG criteria, the sensitivities of qPCR and LFD were 100% and the sensitivity of the GM test was 87.5% (GM test index cutoff, >0.8), with the tests having specificities of between 66.7 and 86.7%. The agreement between the results of qPCR and LFD was almost perfect (Cohen's kappa coefficient = 0.93, 95% confidence interval, 0.81 to 1.00). LFD and qPCR combined had a sensitivity of 100% and a specificity of 85.7%. Calcofluor staining and culture of all BAL fluid samples were negative for fungal infection. The median time from the start of mold-active antifungal therapy to the time of collection of BAL fluid was 6 days. Reversing roles and using dual testing by LFD and qPCR to classify cases, the EORTC/MSG criteria had a sensitivity of 83.3%. All three tests are useful for the diagnosis of IPA in BAL fluid samples. Despite the significant delays between the start of antifungal therapy and bronchoscopy, unlike microscopy and culture, the biomarkers remained informative. In particular, the combination of LFD and qPCR allows the sensitive and specific detection of IPA.

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