Highlights of this month...
Invasive fungal sinusitis
(IFS) in adults is predominantly an infection seen in immunocompromised patients undergoing treatment for malignancies but also frequently associated with diabetes in adults.
For a good prognosis diagnosis must be swift and treament aggressive with surgical debridement and antifungal therapy.
Smith et.al.. have
conducted an in depth review of acute sinusitis in people aged <18 years old. This is a rare (100 cases reviewed) but important (mortality 46%) IFS patient group. 45% of patients identified had underlying acute lymphoid leukaemia, 31 % acute myeloid leukaemia. 99% of all cases had an absolute neutrophil count <600, average length of neutropaenia 2 weeks. Treatment focusses on restoration of immunocompetance.
Presenting symptoms that were positively associated with mortality were fever, orbital involvement, edema, rhinorrhea, congestion and headaches. Only facial pain was negatively associated with overall mortality, possibly becasue it is often an early sign of infection.
Aspergillus was the predominant fungal pathogen (47%) amongst the study group that had a media age of 11 years old.
The authors noted that almost half of patients had nasal involvement as well as sinus infection, in fact nasal infection often preceded sinus involvement. Consequently they propose that this disease is renamed Fungal Invasive Rhinosinus Disease (FIRD)
We have recently collected a series of papers and written a summary for a new website section on Antifungal Stewardship
. Some of the papers originate from the 2015 conference on Antimicrobial Stewardship that took place in Madrid organized by the Stering Committee of the Continuing Antifungal Research and Education (CARE
) program, funded by Gilead Sciences Europe Ltd.
We will endeavour to add new papers and summarise new commentaries as they arise.
Sensititre YeastOne® panels were assessed for in vitro
susceptibility testing of echinocandins against 39 isolates of A.
fumigatus, A. flavus and A. terreus, including two
echinocandin-resistant A. fumigatus, using different inocula (103, 104
and 105 cfu/mL), incubation times (16-48h) and endpoints (first blue or
purple) and compared with CLSI M38-A2.
The best agreement was found with inoculum of 104 cfu/mL, incubation
time of 20h for A. flavus and 30h for A. fumigatus and A. terreus and
reading the first purple well. The reproducibility within ±1 two-fold
dilution was 100% for all three echinocandins. The essential agreement
(±2 log2 dilutions) between the two methods was good for anidulafungin
(67-100%) and micafungin (77-100%), but poor for caspofungin (0-54%).
Nevertheless, resistant isolates were detected after 24h of incubation.
This prospective observational study included a total of 244 patients
(244 eyes) who underwent penetrating keratoplasty (PK, 118 patients) or
lamellar keratoplasty (LK, 126 patients) for fungal keratitis. Topical
administration of steroid eye drops was initiated at 1 week after
Anterior segment inflammation was aggravated within 1 week after
surgery, with ocular pain, photophobia, redness, and tearing, but was
controlled at 7.51 ± 1.76 days after steroid use. Fungal keratitis
recurred in three eyes (1.23 %) at 3 to 5 days after administration of
corticosteroids, including two eyes receiving PK and one eye receiving
LK. Recurrence was controlled with antifungal medications. Allograft
rejection occurred in eight (6.78 %) of 118 patients treated by PK, but
did not occur in patients treated by LK.
The authors conclude that the use of topical steroids one week after keratoplasty helps control inflammation and immune rejection with no increase in fungal infection reoccurence.
Therapy of invasive aspergillosis is becoming more difficult due to the
emergence of azole resistance in Aspergillus fumigatus
. A majority of
resistant strains carries mutations in the CYP51A gene. Due to a lack of
sensitivity of culture-based methods, molecular detection of A.
has become an important diagnostic tool. The authors set up the
database FunResDB (www.nrz-myk.de/funresdb
to gather all available information about CYP51A-dependent azole
resistance from published literature. In summary, the screening resulted
in 79 CYP51A variants, which are linked to 59 nonsynonymous mutations. A
tailor-made online sequence analysis tool allows for genotypic
susceptibility testing of A. fumigatus
A total of 1648 journal articles were retrieved by the authors with an average of 20.46
citations per article. Annual growth of triazole resistance showed an
increasing pattern during the study period. The United States of America
(n=446; 27.06%) ranked first in productivity followed by the United
Kingdom (UK) (n=176; 10.68%), and China (n=133; 8.07%). Radboud
University Nijmegen Medical Centre (n=69, 4.19%) in the Netherlands
ranked first in productivity, while the journal Antimicrobial Agents and
Chemotherapy ranked first (n=255; 15.47%) in publishing articles on
triazole resistance. Mapping mechanisms of resistance showed that efflux
pump and mutations in target enzyme are major mechanisms described in
resistance to triazoles.
There was a growth of publications on triazole resistance in the past
two decades with the bulk of publications on triazole resistance in
Candida species. The data presented here will serve as baseline
information for future comparative purposes.
The demand for novel antibiotics to combat the global spread of multi
drug-resistant pathogens continues to grow. Pathogenic bacteria and
fungi that cause fatal human infections can also kill silkworms and the
infected silkworms can be cured by the same antibiotics used to treat
infections in the clinic. As an invertebrate model, silkworm model is
characterized by its convenience, low cost, no ethical issues. The
presence of conserved immune response and similar pharmacokinetics
compared to mammals make silkworm infection model suitable to examine
the therapeutic effectiveness of antimicrobial agents.
In this review, the authors summarize the advantages of the silkworm model and
propose that the utilization of silkworm infection model will facilitate
the discovery of novel therapeutically effective antimicrobial agents.
Antifungal therapy for systemic mycosis is limited, most of times
expensive and causes important toxic effects. Nanotechnology has become
an interesting strategy to improve efficacy of traditional antifungal
drugs, which allows lower toxicity, better biodistribution, and drug
targeting, with promising results in vitro and in vivo. In this review,the authors provide a discussion about conventional antifungal and nanoantifungal
therapies for systemic mycosis.
In last 30 to 40 years there has been a significant increase in the
incidence of allergy. This increase cannot be explained by genetic
factors alone. Increasing air pollution and its interaction with
biological allergens along with changing lifestyles are contributing
factors. Dust mites, molds, and animal allergens contribute to most of
the sensitization in the indoor setting. Tree and grass pollens are the
leading allergens in the outdoor setting. Worsening air pollution and
increasing particulate matter worsen allergy symptoms and associated
morbidity. Cross-sensitization of allergens is common. Treatment
involves avoidance of allergens, modifying lifestyle, medical treatment,
Panfungal polymerase chain reaction was tested on DNA isolated from paraffin-embedded tissue blocks taken from a range of animal species with an array of infected sites (canine, feline, equine, and bovine tissues with cutaneous, nasal, pulmonary, and systemic fungal infections). 117 out of 128 blocks (91%) yielded PCR product and high quality DNA obtained from 70%. Sequence and histological identifications matched in 62% of blocks. The authors claimed that this assay was capable of providing genus- and species-level
identification when histopathology could not and, thus, is a beneficial
complementary tool for diagnosis of fungal diseases.
Allergy has long been part of aspergillosis, particularly to fungal spores that float in the air all around us and especially for those who have an allergic form of aspergillosis (e.g. ABPA). We have long wanted to have a talk from an allergist to our patients community so it was great to finally find Dr Susana Marinho to be our speaker on 5th May.
University Hospital of South Manchester (UHSM) North West Lung Centre (NWLC) is actually something of a pioneer in the clinical assessment and treatent of allergy and Susana was the first full time allergy consultant to be appointed anywhere in the UK! Her appointment tells us something about how new the treatment of allergy is in the NHS so we are very fortunate to have easy access to Susana’s team’s expertise.
The topic of the talk on the 5th May was how we can become allergic many of the medications we have to take, especially when we have to take them for a long time. In particular we looked at allergy to aspirin and how that impacts on the respiratory symptoms of people with aspergillosis and asthma.
The talk is one and a half hours full of information on this important aspect of our health – after all nearly all of us has problems with allergies at some point! Susana also offered to answer any questions on allergy coming from our patients so if you have a question lat me know what it is via email or in one of our facebook groups, or even phone us on 0161 291 5866.
We are also running a successful Skype meeting every week
! We are a chatty group of 8 - 12 most weeks but we can accomodate up to 24. If you have a computer or phone that has APP's you will be able to install Skype and join in - instructions at the link below. Skype at 11am BST every Thursday
. Instructions will change over the next few weeks so go to http://www.nacpatients.org.uk/content/skype-group
for the latest information.
Aspergillosis Community (National Aspergillosis Centre) normally meets on the first friday of each month (with the exception of June 2017 when it will be held on 9th June) at the Altounyan Suite, North West Lung Centre, Manchester at 1.30pm BST/GMT. If you can't make it in person, you are welcome to listen in to our live broadcast.
If you want a text reminder when each meeting is approaching (UK only) then send us an email at email@example.com with your mobile phone number.