GAFFI (Global Action Fund for Fungal Infections) has campaigned for these three antifungals to be on the EML in conjunction with colleagues from the Instituto de Salud Carlos III, International Foundation for Dermatology, London School of Hygiene of Tropical Medicine and The University of Manchester. The WHO ruling puts itraconazole (capsules and oral suspension), voriconazole (capsules and intravenous solution) and natamycin 5% ophthalmic solution on the Essential Medicine List (EML).
The antifungal medicines itraconazole and voriconazole are critical to reduce deaths and illness, and natamycin to reduce blindness. They are very inexpensive in most countries.
Prof Denning form GAFFI said "This endorsement by the WHO of their essentiality is a key step in reducing mortality from fungal diseases. We are delighted that our campaign has WHO recognition. Our challenge now will be to make sure these drugs get to the people who desperately need them.”
The proposed indications for itraconazole capsules are chronic cavitary pulmonary aspergillosis, invasive aspergillosis, histoplasmosis (therapy, primary and secondary prophylaxis), sporotrichosis, paracoccidioidomycosis, infections caused by Talaromyces marneffei (penicilliosis) (therapy, primary and secondary prophylaxis) and chromoblastomycosis. These are all conditions for which fluconazole is ineffective. Itraconazole oral solution is preferred in late stage AIDS patients, leukaemia patients and children.
The proposed indications for voriconazole are invasive and chronic pulmonary aspergillosis, with intravenous therapy preferred initially, in invasive disease.
The important indication for topical natamycin 5% in the eye is fungal (mycotic) keratitis - 3 randomised studies have shown it to be more efficacious than other topical medicines, given alone.
Prevalence, clinical and economic burden of mucormycosis related admissions in the USA
There were 555 cases of mucormycosis in hospitals among 47 million inpatient episodes, a prevalence of 0.16 per 10,000 discharges. The median length of stay was ~17 days and mean cost was $112,419.
Mucormycosis is an uncommon, opportunistic fungal infection primarily caused by Mucorales, a filamentous fungus of the Mucormycetes class. This fungal infection particularly affects patients with diabetes mellitus (especially following ketoacidosis) or those with hematologic malignancies on chemotherapy (especially with neutropenia), stem cell and solid organ transplants.
The study used the Premier’s Perspective™ Comparative Database, a large, U.S hospital based database covering more than 560 participating hospitals across the U.S and 104 million patients. Data was collected from January 2005 to June 2014. Mucormycosis related-hospitalisations were identified with an ICD-9 code of 17.7 or a positive laboratory microbiology result for Mucorales.
Fluconazole, voriconazole and echinocandins are not effective antifungal therapy against mucormycosis. Amphotericin B , liposomal amphotericin B, posaconazole and isavuconazole are effective treatments. The projection of the total costs associated with mucormycosis in the USA is $48 million.
Delivering on antimicrobial resistance not possible without improving diagnostic capabilities
Ignorance of fungal disease and lack of fungal diagnostics is causing doctors to unknowingly overprescribe antibiotics - a new report warns.
In a paper published today in the cutting edge US Journal Emerging Infectious Diseases (click here), several leading authors from GAFFI warn of the gross misuse of antibacterial antibiotics, because doctors treat patients without knowing what is wrong with them. The authors focus on common scenarios, where the lack of the best diagnostic tests, prevents the correct antimicrobial being given.
Examples include mis-diagnosis of TB where the patient actually has chronic pulmonary aspergillosis- which is diagnosable with a simple antibody test and chest imaging. Also many asthma and patients with emphysema (COPD) get exacerbations, which are treated with antibacterials and steroids. Some have fungal asthma or are admitted to hospital with COPD. There are over 200 million asthmatics and an estimated 6-15 million have fungal asthma, which is diagnosable with skin prick testing or IgE blood tests, and which responds to antifungal agents, minimizing antibacterial use.
David Denning president of GAFFI, said on the lack of fungal diagnostics:" Solving AMR is not possible without accurate and timely diagnosis. Fungal disease diagnostics are critical in the AMR fight, and will improve survival from fungal disease across the world. The close link between fungal diagnostics and antibacterial prescribing needs a great deal more attention".
More information. Article
Invasive Fungal Infections in the Middle East: High mortality and new underlying diseases
A retrospective study of 102 hospitalised patients with invasive candidiasis or aspergillosis in Saudi Arabia and Lebanon (Alothman et al, 2017) identifies several non-traditional common co-morbidities including coronary artery disease (24%), congestive heart failure (15%), moderate-to-severe renal disease (16%), and diabetes (41%). In selected and diagnosed patients, some immunocompromising factors were also present, notably corticosteroids prior to admission (20%) and chemotherapy in the prior 3 months (26%). The authors caution their peers: “Earlier consideration .. of IFI in medically comorbid patients may reduce the time to antifungal treatment and improve outcomes.”
This study highlights a high mortality of 42%, mean hospitalisation period of 32 days, the low use of Aspergillus galactomannan testing (11%), and the delay before a diagnosis of invasive fungal infection was made. They note that the median time from admission to diagnosis was 6 days (range 0 to 92 days), and it took another day for antifungal therapy to be started. A median of 2.5 days (range −3 to 80 days) elapsed between culture collection and treatment given. Fluconazole was the favoured antifungal, but over 50% of the infections were resistant to it.
Read more; Article
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LIFE would also appreciate your help to tell us if you have antifungal eyedrops in your country. GAFFI is seeking to map the availability of eyedrops globally.