This week isavuconazole (Cresemba) will be available in Europe for the first time. Following the FDA approval of this new antifungal in the US in March 2015, the European Commission approved isavuconazole in October, for the treatment of adult patients with invasive aspergillosis (first line) or mucormycosis, for whom amphotericin B is inappropriate. The European marketing authorization for isavuconazole is valid in all 28 EU member states, as well as in Iceland, Liechtenstein and Norway.
Isavuconazole is provided as a highly soluble pro-drug available intravenously or orally with excellent bioavailability which may be switched without dose adjustment. After the inital drug loading it is a once daily dose due largely to its slow elimination, good tissue distribution and high protein binding.
Isavuconazole is active against a number of clinically important yeasts and molds, including Candida spp, Aspergillus spp, Cryptococcus neoformans, and Trichosporon spp and has variable activity against Mucorales spp.
The most commonly reported adverse events, which are mild, include nausea, diarrhoea and raised liver function tests. It exhibits less toxicity than voriconazole but for aspergillosis it is just as effective, suggesting isavuconazole may become the preferred drug of choice. Its drug interaction potential appears to be less than other azole antifungals - also a beneficial feature.
It remains to be ascertained whether plasma drug levels will require continuous monitoring; whether it has efficacy in sanctuary sites such as eye, brain and prostate; whether it can be used in paediatric patients; whether it has a role in chronic and allergic aspergillosis treatment and lastly its full spectrum of toxicity will only become clearer as its prescribing increases.
As an addition to the azole antifungal repertoire it promises to be useful. Review
Allergic fungal rhinosinusitis (AFRS) very common in Israel compared to India
Fungal diseases are a significant cause of morbidity and mortality in Israel, with invasive candidiasis and invasive aspergillosis accounting for the largest number of fungal related deaths. Estimations on disease burdens were recently published. Fungal rhinosinusitis takes many forms and is often associated with asthma, but not always. Around 800,000 (10%) Israelis are thought to suffer from rhinitis, and some 40,000 individuals were thought to have AFRS (5% of the total 800,000 chronic rhinosinusitis population).
A descriptive epidemiological study of fungal rhinosinusitis (FRS) was conducted in rural northern India in the form of house-to-house survey of villages of two districts each of Punjab and Haryana. Suspected cases were evaluated in the lab. Seasonal air counts of aspergillus spores showed raised counts (up 20%) of A.flavus in the winter months in the wheat threshing areas of Punjab. The study revealed a population prevalence of 0.11% of CFS with a possible association with the wheat harvesting season- which could be 1.3 million people if generalised to the whole population. They sub-classified most of these cases and found allergic FRS in 41 (56.1%), chronic granulomatous FRS in 13 (17.8%), eosinophilic FRS in 11 (15.0%), fungal ball in 7 (9.5%) and chronic invasive FRS in one (1.3%) (Chakrabarti et al, 2015).The worldwide burden of allergic fungal rhinosinusitis is clearly highly variable and many more population studies are required to address this relatively common problem.
Burden of diseases in 636 million people and across 15 new countries
Fungal diseases have been regarded as low priority problems in many countries and expertise is sadly lacking. Just published in "Mycoses" is a series of 15 articles covering population rates of serious fungal disease, varying from 1.7% to 12.5%, in the following countries Belgium, Czech Republic, Denmark, Hungary, Nepal, Qatar, Tanzania, Trinidad and Tobago, Uganda, Germany, Mexico, Senegal, Tanzania, Ukraine, Vietnam. These estimates have never been attempted before.
The largest burdens are always recurrent vulvovaginal candidiasis and ‘fungal asthma’ (ABPA and SAFS). AIDS and TB related disease reflect the burdens of these problems in each country and how well HIV is treated.
The burden of serious fungal diseases has now been estimated in around 5 billion - or 71% of the global population, as presented recently at the Trends in Medical Mycology meeting in Lisbon (info)
More information and view the papers
World's first guidelines for chronic pulmonary aspergillosis presented at ERS
The world’s first guidelines for chronic fungal lung infections for doctors and laboratories were presented at the European Respiratory Society (ERS meeting) and will shortly be published in the European Respiratory Journal (January issue). The guidelines have been drawn up in conjunction with the ERS and ESCMID.
Chronic pulmonary aspergillosis (CPA) is a subtle and insidious problem in patients with already damaged lungs. It kills about 80% of sufferers over five years, unless diagnosed and treated with long-term antifungals. Across Europe, an estimated 240,000 people have CPA, and worldwide around 3 million.
The guidelines describe the 5 clinical phenotypes of CPA and how to diagnose and manage these patients.
The three minimum requirements for diagnosis and initial therapy include a. Imaging (radiological & CT scan) (grade A II) alongside b. Testing for Aspergillus IgG serology (grade A II); and c. Itraconazole treatment (grade A II) or other azole therapy depending on the patient.
The publication of these guidelines will assist and guide the training of medical professionals working with CPA patients. Image shows CPA with TB, chest X ray. More information