cystic fibrosis ( cf ) is a genetic disease characterized by increased viscosity of the bronchial mucus and impaired mucocilliary clearance which predisposes to microbial colonization and infections of the respiratory tract .
adult patients with cf have a high incidence of fungal colonization ( 42% ) and invasive disease ( 11% ) .
a variety of yeasts and filamentous fungi have been recovered from their respiratory samples , before and after lung transplantation .
are the most common fungal species isolated , responsible of invasive infection after lung transplantation in patients with cf .
recently , invasive pulmonary infections with emerging molds like scedosporium spp . , rasamsonia argillacea or exophiala dermatitidis have been described , associated with fungemia for some of them : scedosporium apiospermum and fusarium solani 
 .
arthrographis kalrae , an emerging mold is an environmental saprophytic fungus , mainly found in soil and compost . in recent years
, cases of opportunistic infections attributed to this pathogen were described : pulmonary infection , endocarditis , sinusitis , meningitis , keratitis , onychomycosis and mycetoma , affecting both immunocompromised and immunocompetent patients .
our patient , a 19-year - old woman , was diagnosed with cystic fibrosis at the age of 4 months .
she developed an exocrine pancreatic insufficiency , an insulin - dependent diabetes , a moderate chronic renal failure and a severe malnutrition ( bmi 14 ) .
she also presented a permanent bacterial pulmonary colonization with staphylococcus aureus and pseudomonas aeruginosa , treated by aerosols of colistin . from 1998 to 2005
the lung colonization by a. fumigatus became permanent ( positive sputa culture , presence of anti - aspergillus antibodies ) for which a treatment with itraconazole 200  mg / day was initiated , increased up to 500  mg / day due to low serum levels . in march 2012 ,
a. kalrae and various aspergillus species ( a. fumigatus , a. flavus and a. nidulans ) were regularly isolated in sputa cultures .
itraconazole was then stopped and replaced by voriconazole 2200  mg / day , later increased to 2250  mg / day .
the pre - transplant sputum culture found bacteria colonies ( p. aeruginosa , s. aureus ) , one colony of a. terreus , three of a. fumigatus and ten of a. kalrae . on day 1 post - transplant ,
blood cultures , broncho - alveolar lavage ( bal ) and two tracheal aspirations were made .
the patient received a probabilistic antibiotic treatment associating ceftazidime , ciprofloxacin , teicoplanin , aerosols of colistin and voriconazole 2200  mg twice a day . on day 3
, mold colonies were isolated in blood cultures , bal , tracheal aspirations and in a bronchial smear of the explanted lung cultures . on day 4 , molds were identified as a. kalrae , associated with one colony of a. terreus in the bal . given these results , antifungal therapy was modified on day 4 for caspofungin 50  mg / day in combination with liposomal amphotericin b i.v . 3 
three colonies of a. kalrae and three colonies of a. fumigatus were found in another bal performed on day 5 post - transplant .
the ct - scans and the chest radiographies performed during this acute episode ( day 0 , 3 and 21 ) were not contributory
. only the first ct - scan showed signs of pulmonary infection of the lingula and lower lobe on day 21 . on day 33 , the liposomal amphotericin b i.v .
was replaced by aerosols of liposomal amphotericin b 3/week , maintained until day 110 post - transplant . despite the negativation of pulmonary samples and the resolution of this acute fungal infection in the following months , the patient died 8 months after her transplantation because of a bacterial septic shock in a context of humoral rejection and a state of severe malnutrition .
after two days of incubation at 35  c on chromogenic medium chromid candida ( biomerieux , france ) for the respiratory samples and on bactec plus aerobic f ( beckton dickinson , france ) at 37  c , there was growth of small yeast - like colonies .
identification was performed based on three methods : a morphological examination , the biochemical characteristics and a mass spectrometry study .
macroscopically , we observed small creamy , beige yeast - like colonies after two days of growth on chromogenic medium chromid candida ( fig .
1 ) . after 7 days of incubation , the colonies became dry and grainy .
the same aspects were observed on sabouraud chloramphenicol ( biorad , france ) and sabouraud chloramphenicol actidione ( biorad , france ) at 37  c and 27  c ( fig .
3 ) . however , growth on sabouraud chloramphenicol medium with actidione was slower ( 5 days for yeast - like colonies ) than without .
a slide culture incubated for 48  h at 27  c on pcb medium ( biorad , france ) showed characteristic hyaline , septate hyphae with one - celled , smooth - walled arthroconidia and irregularly branched hyphae , with dendritic conidiophores ( fig .
the isolate was also inoculated into wells of an i d 32 plate ( biomerieux , france ) .
after 72  h of incubation , the profile code obtained did not correspond to any taxon scored in the manufacturer 's database . in parallel , mass spectrometry was performed using the microflex lt mass spectrometer ( bruker daltonics , france ) , and analyzed using the maldi biotyper software ( version 3.1 with enlarged database version 3.3.1.0 containing 4613 entries ) .
mass spectrometry technique allowed to identify a. kalrae with logscore values > 2.0 ( 2.28 , 2.24 ) , according to the manufacturer 's recommendations .
the identification was confirmed by a dna sequencing ( using the internal transcribed spacer , its1 and its4 ) and comparison of obtained sequences to genbank ( http://www.ncbi.nlm.nih.gov/genbank , accession number for closest hit km588309.1 ) and cbs ( http://www.cbs.knaw.nl , accession number for closest hit cbs 10896_ex24366_12125_its ) databases .
a. kalrae was identified with an e - value of 0 ( genbank ) , an overlap of 100% ( cbs ) and 100% identification concordance .
the blood culture strain mics measured by etest gave the following results : amphotericin b 0.75  mg / ml , flucytosine > 32  mg / ml , voriconazole 0.125  mg / ml , posaconazole 0.50  mg / ml , fluconazole > 32  mg / ml , micafungin 0.012  mg / ml , caspofungin 0.047  mg / ml . the strain was sent to the national reference center , at pasteur institute .
there , the mics values were determined according to the eucast method and gave the following results : amphotericin b 0.125  mg / ml , flucytosin>64  mg / ml , voriconazole 0.125  mg / ml , posaconazole 0.125  mg / ml , fluconazole 64  mg / ml , micafungin 4  mg / ml and caspofungin>4  mg / ml .
arthrographis is a genus containing 5 species : a. kalrae , a. cuboidea , a. lignicola , a. pinicola and a. alba .
a. kalrae is a saprophytic fungus with a worldwide distribution , found in soil and compost . in recent years , clinical cases of invasive infections attributed to this pathogen
currently , one case of infection with arthrographis sp . and 14 cases of infection with a. kalrae have been reported ( table 1 ) : two onychomycosis , , one mycetoma , five keratitis , , , ,   one of which associated with sinusitis , two knee joint infection , , one endocarditis , two pulmonary infections , , one meningitis   and one fungal stroke .
these cases have a worldwide distribution : seven cases in europe , one in china , one in japan , three in usa , one in mexico , one in malaysia and one in australia .
three of the five patients with keratitis were soft contact lens wearers ; the other two and the two patients with the knee joint infections have had an injury contaminated with soil .
the rest of the patients had predisposing infection factors like malnutrition , systemic corticosteroids , radiotherapy , aids , allogeneic hematopoietic stem cell transplant .
diagnoses were always based on phenotypic characteristics and microscopic morphology using de hoog and sigler , and carmichael descriptions . in most cases ,
identification of the species was confirmed by molecular biology techniques ( its , d1/d2 sequencing ) .
no data were available about the most appropriate treatment for this kind of infection . in the previous described cases , when tested the strains were sensitive to azoles , amphotericin b and terbinafin and resistant to flucytosin , but no sensibility results were showed for echinocandins .
the azoles showed high activity ( mean mic 0.46  g / ml ) , amphotericin b very little activity ( mean mic : 2  g / ml ) and echinocandins showed no in vitro activity ( mean mec at 24  h>8  g / ml ) .
these results are different from ours but concordant with those of the national reference center for invasive mycoses and antifungals , which is using the eucast method .
all patients described except the one with onychomycosis were treated with azoles associated or not with amphotericin b. some reported patients also required surgery ( keratitis and knee joint infection ) .
three patients died during their a. kalrae infection , one of them because of the fungus ( patient with fungal stroke ) .
given the fact that our patient developed a septic shock with a fungemia despite a prophylaxis with voriconazole , the choice was made to treat her with caspofungin in combination with liposomal amphotericin b. the clinical response was favorable with this treatment , regardless the resistance to the caspofungin detected by the national reference center . in the case of our patient , the evolution of the fungal infection was favorable with a rapid negativity of blood cultures and respiratory samples .
the combination of caspofungin and liposomal amphotericin b was effective in our patient whose colonization by the fungus could not be eliminated by a long - term treatment with voriconazole .
we therefore describe here the first case , to our knowledge , of an a. kalrae fungemia in a cystic fibrosis patient with an assumed pulmonary portal of entry .
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 arthrographis kalrae is a hyalin fungus . 
 it is a saprophyte of the environment , mainly found in soil and compost . in recent years 
 , cases of opportunistic infections attributed to this pathogen have been described . 
 our patient was a 19-year - old woman with cystic fibrosis . 
 she presented a bacterial and fungal pulmonary colonization with aspergillus fumigatus and arthrographis . 
 kalrae . after her lung transplantation 
 , she developed an a. kalrae fungemia , treated with caspofungin 50  mg / day associated to liposomal amphotericin b i.v . 
 3  mg / kg / day . 
 the patient died 8 months after her transplantation as the result of a bacterial septic shock . 
Introduction
Case
Discussion
Ethical form
Conflict of interest