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A cystic fibrosis child with lung function decline
JCF-01849; No of Pages 3 Journal of Cystic Fibrosis xxx (2019) xxx
Contents lists available at ScienceDirect
Journal of Cystic Fibrosis journal homepage: www.elsevier.com/locate/jcf
A cystic fibrosis child with lung function decline Ersilia Vita Fiscarelli a,⁎, Gabriella Ricciotti a, Martina Rossitto a, Arianna Pompilio b, Vanessa Tuccio Guarna Assanti a, Vincenzina Lucidi c a b c
Laboratory Department, Children's Hospital and Research Institute Bambino Gesù, Rome, Italy Department of Medical, Oral and Biotechnological Sciences, and Center of Excellence on Aging and Translational Medicine, “G. d'Annunzio” University of Chieti-Pescara, Italy Cystic Fibrosis Center, Children's Hospital and Research Institute Bambino Gesù, Rome, Italy
a r t i c l e
i n f o
Article history: Received 8 April 2019 Revised 25 June 2019 Accepted 27 June 2019 Available online xxxx Keywords: Arthrographis kalrae Cystic_fibrosis Pulmonary_exacerbation Lung_function_decline BAL
a b s t r a c t Respiratory infections are a major threat to cystic fibrosis patients. Besides bacteria, many fungi colonize the cystic fibrosis respiratory tract where an important fungal biota has been described. We report here the case of a 7-year-old cystic fibrosis child with pulmonary exacerbation and Arthrographis kalrae isolated from bronchoalveolar lavage fluid. To the best of our knowledge, this is the first reported case of lung infection due to Arhtrographis kalrae in a cystic fibrosis pediatric patient. © 2019 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
1. Introduction Cystic fibrosis (CF) is a multiple organ disease; however, the respiratory tract is mainly involved and lung infections remain a major threat to CF patients. The CF lung has impaired mucociliary clearance and a build-up of thick mucus, which creates an ideal environment for microbial colonization. The bacteria most commonly believed to be pathogenic in CF include Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Burkholderia species [1]. Besides bacteria, many fungi also colonize the respiratory tract and an important fungal biota has been described in respiratory secretions of patients suffering from CF. Candida species, especially Candida albicans and, less frequently, Candida parapsilosis, Candida tropicalis and Candida glabrata, may be isolated. Opportunistic molds are the most common agents of fungal colonization and/or infection of CF patients' airways. Among them, Aspergillus fumigatus may cause various diseases, the most common being allergic bronchopulmonary aspergillosis (ABPA). In addition, other Aspergillus species, including Aspergillus flavus and Aspergillus niger, may be present as transient colonizers of the airways, usually without any associated clinical signs. The relatively high frequency of the Scedosporium species and Aspergillus terreus, which rank second and third, respectively, among filamentous fungi associated with CF should be highlighted. The description of other fungal ⁎ Corresponding author at: Children's Hospital and Research Institute Bambino Gesù, Piazza Sant'Onofrio, 4, 00165 Rome, Italy. E-mail address: evita.fi[email protected] (E.V. Fiscarelli).
species, such as Exophiala dermatitidis, Lomentospora prolificans, Rasamsonia argillacea species complex, Acrophialophora fusispora and Arthrographis kalrae in CF patients suggest that the fungal biota colonizing the airways of these patients could be even more complex [2–4]. We report here the case of a 7-year-old CF child with pulmonary disease exacerbation and Arthrographis kalrae (A. kalrae) isolated from bronchoalveolar lavage (BAL) fluid. 2. Case A 7-year-old boy with a clinical history of CF in follow-up at our CF Center was hospitalized because of low-grade fever for 3 days (38 °C), persistent cough and an increase in sputum production. The patient was diagnosed at neonatal screening with typical CF disease (genotype F508del/F508del). The respiratory tract was chronically colonized with Methicillin-sensitive Staphylococcus aureus and intermittently with Pseudomonas aeruginosa. His regular daily medications included pancreatic enzymes, salbutamol, inhalation of hypertonic saline solution, recombinant human deoxyribonuclease (rhDNAase), vitamin supplements and inhaled tobramycin prophylaxis. On admission (day 0), physical examination revealed widespread rales especially in the left lung lobe. The white blood cell count was 14.5 × 109/L (range: 4–13.5) and Creactive protein was 18 mg/L (n.v.: ≤0.5). The patient's immunological profile (total and specific Aspergillus IgE, eosinophilia) proved to be normal. His forced expiratory volume in 1 s (FEV1) was 87% predicted, much lower than the baseline measured the previous month (117% predicted).
https://doi.org/10.1016/j.jcf.2019.06.015 1569-1993/© 2019 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
Please cite this article as: E.V. Fiscarelli, G. Ricciotti, M. Rossitto, et al., A cystic fibrosis child with lung function decline, Journal of Cystic Fibrosis, https://doi.org/10.1016/j.jcf.2019.06.015
2
E.V. Fiscarelli et al. / Journal of Cystic Fibrosis xxx (2019) xxx
A computerized tomography (CT) scan showed areas of dense consolidation in the lower lobe suggestive of an infectious process (Fig. 1). Based on clinical picture, laboratory parameters and radiological signs, the diagnosis of pulmonary exacerbation was made. The patient was started on intravenous broad-spectrum antibiotics (amoxicillin plus clavulanic acid 2.8 g/die; tobramycin 180 mg/die) based on previous sputum culture positive for Methicillin-sensitive Staphylococcus aureus, performed a month before. However, his clinical picture did not improve. On day 7 post-admission (dpa), in order to determine if there were any other pathogens that could account for failure to respond to antibacterial therapy, bronchoscopy was performed and bronchoalveolar lavage (BAL) fluid was sent to the laboratory for bacterial and mycological cultures. BAL fluid specimen was processed according to local standardized microbiological Guidelines (Italian Guidelines for CF, Italian Cystic Fibrosis Society 2018), i.e. sample plating on: Columbia, MacConkey, chocholate with and without bacitracin, mannitol salt and Sabouraud with and without chloramphenicol agar media. After 5 day incubation at 37 °C (13 dpa), a large number (106 colony forming unit/mL) of small yeast-like colonies were detected in pure culture on Columbia and Sabouraud; they gradually became pale yellow in colour and 7 days later velvety and hairy. A lactophenol cotton blue preparation of the fungal colonies revealed hyaline septate hyphae with arthroconidia production. The arthrospores were one-celled smooth-walled, rectangular to cylindrical, arranged in chains. Rare blastoconidia were alsoobserved. The isolate was identified as A. kalrae by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF MS) system (Bruker Daltonics, Inc. Billerica; MA); (logscore values: 2.16, 2.26). The identification was confirmed by ribosomal DNA sequencing of internal transcribed spacer 1 (ITS1) using universal primers ITS1 and ITS2.
Fig. 1. Computed tomography (CT) scan of the chest at the time of hospitalization. CT shows an extended area of consolidation at the lower lingual segment and basal pyramid of the left lower lobe.
As we could not test antifungal susceptibility of our isolate, according to data reported in literature [7], the patient was empirically treated with itraconazole (100 mg x os daily) for 6 weeks. The clinical picture improved and the pulmonary function returned to baseline. The treatment was stopped when inflammatory markers and radiographic investigations proved a complete recovery. Up to now, the following microbiological cultures of respiratory secretions are still negative for A. kalrae.
3. Discussion Increased risk factors, including extensive use of immunosuppressive drugs, sudden climate changes, wide use of azole antifungals in agriculture, have enlarged the spectrum and augmented the incidence of some human diseases due to common environmental arthroconidial fungi, such as filamentous basidiomycetes (e.g. Schizophyllum commune) and ascomycetes. Among ascomycetous arthroconidial fungi, Arthrographis species (A. kalrae, A. arxii, A. chlamidospora, A. curvata, A. globosa and A. longispora) are generally found in soil, wood, air and water and, occasionally, in opportunistic infections in humans [5,6]. As far as we know, up to now only 15 cases of A. kalrae infection have been described worldwide (i.e. Europe, China, USA, Japan, Australia) in both immunocompetent and immunocompromised subjects. In particular, A. kalrae is accounted for endocarditis, keratomycosis in contact lens-wearing subjects, pulmonary infection, fatal invasive fungal cerebral vasculitis in an immunocompetent patient and invasive fungal sinusitis and meningitis in a patient with AIDS. More recently, a paper, reporting for the first time the onset of A. kalrae fungemia in a CF patient, was published. The Authors described the case of a 19-year-old woman presenting a permanent pulmonary colonization by, among the others, A. kalrae. The patient developed septic shock the first day after bilateral lung transplantation. A. kalrae was detected from blood, BAL, tracheal secretions and explanted lung. The treatment with caspofungin associated with liposomal amphotericin B determined the resolution of the fungemia with negativization of the microbiological cultures [4]. Our case, besides supporting the potential pathogenic role of A. kalrae in CF, suggests that most likely its incidence is underestimated. In fact, in the routinary clinical CF laboratory practice, bacteria are the focus of microbial examinations of airways secretions. Therefore, the mycological cultures are performed only for selected clinical cases. Furthermore, in some laboratories the identification of yeast-like fungi, other than Candida albicans, is not carried out. We could then speculate that A. kalrae may colonize the respiratory tract of CF patients more often than we believe. In consideration of the fact that bacteria are the most common cause of pneumonia in CF, initially the boy was treated with i.v. broadspectrum antibacterial therapy. As his clinical conditions did not improve, we suspected a different airway infection etiology; therefore, a BAL was performed. BAL fluid culture is the gold standard method for the microbial diagnosis of lung infection diseases. Although there is not a common consensus on the microbial load suggestive of infection, 105 cfu/mL is the usual bacteria cut-off for pediatric patients. In the present case, A. kalrae had grown in pure culture on agar plates and the colonies count was higher than the threshold value. Both the presence of A. kalrae in BAL fluid with a high load, and the resolution of the clinical picture only when antifungal therapy was administered, suggest the role of A. kalrae as a causing agent of the pulmonary exacerbation and lung function decline in our patient, raising A. kalrae to the status of the possible pathogenic fungus in CF people. The available data on the susceptibility patterns of this fungal species are scarce. Itraconazole and voriconazole are, as reported in literature, the most used drugs; we decided to treat our patient with itraconazole that has proved to be more efficacious [7].
Please cite this article as: E.V. Fiscarelli, G. Ricciotti, M. Rossitto, et al., A cystic fibrosis child with lung function decline, Journal of Cystic Fibrosis, https://doi.org/10.1016/j.jcf.2019.06.015
E.V. Fiscarelli et al. / Journal of Cystic Fibrosis xxx (2019) xxx
4. Conclusions Lung transplantation has become a care opportunity in selected CF patients with end-stage lung disease. Patients who have undergone lung transplantation present a high risk of developing invasive infections including fungemia. Therefore, it is necessary to always detect and identify molds and yeast species colonizing the respiratory tract of CF patients. Recently, a standardized protocol for current mycological procedures has been published to ensure an efficient recovery of fungi from CF sputum samples. Implementation is nowadays mandatory in order to harmonize laboratory practice and reach an accurate level of mycological diagnosis reliability [8]. To the best of our knowledge, this is the first reported case of lung infection due to A. kalrae in a CF pediatric patient and highlights the strong impact that fungi may have on CF patients' health. Declarations of Competing Interests The Authors have no competing interests to declare.
3
References [1] Burns Jane L, Rolain Jean-Marc. Culture-based diagnostic microbiology in cystic fibrosis: can we simplify the complexity? J Cyst Fibros 2014;13(1):1–9. [2] Pihet M, Carrere J, Cimon B, Chabasse D, Delhaes L, Symoens F, et al. Occurrence and relevance of filamentous fungi in respiratory secretions of patients with cystic fibrosis - a review. Med Mycol 2009 Jun;47(4):387–97. [3] Schwarz C, Bouchara JP, Buzina W, Chrenkova V, Dmenska H, et al. Organization of patient management and fungal epidemiology in cystic fibrosis. Mycophatologia 2018 Feb;183(1):7–19. https://doi.org/10.1007/s11046-017-0205-x [Epub 2017 Nov 3]. [4] Denis Julie, Sabou Marcela, Degot Tristan, Candolfi Ermanno, Letscher-Bru Valérie. First case of Arthrographis kalrae fungemia in a patient with cystic fibrosis. Med Mycol Case Rep 2016;14:8–11. [5] Chowdhary A, Kathuria S, Agarwal K, Meis JF. Recognizing filamentous basidiomycetes as agents of human disease: a review. Med Mycol 2014 Nov;52(8):782–97. [6] Giraldo A, Gené J, Sutton DA, Madrid H, Cano J, Crous PW, et al. Phylogenetic circumscription of Arthrographis (Eremomycetaceae, Dothideomycetes). Persoonia 2014 June; 32:102–14. [7] Sandoval-Denis M, Giraldo A, Sutton DA, Fothergill AW, Guarro J. In vitro antifungal susceptibility of clinical isolates of Arthrographis kalrae, a poorly known opportunistic fungus. Mycoses 2014 Apr;57(4):247–8. [8] Delhaes L, Touati K, Faure-Cognet O, Cornet M, Botterel F, et al. Prevalence, geographic risk factor, and development of a standardized protocol for fungal isolation in cystic fibrosis: results from the international prospective study “MFIP”. J Cyst Fibros 2019 Mar;18(2):212–20.
Acknowledgements The Authors thank Andreina Santoro for language revision.
Please cite this article as: E.V. Fiscarelli, G. Ricciotti, M. Rossitto, et al., A cystic fibrosis child with lung function decline, Journal of Cystic Fibrosis, https://doi.org/10.1016/j.jcf.2019.06.015
Contents lists available at ScienceDirect
Journal of Cystic Fibrosis journal homepage: www.elsevier.com/locate/jcf
A cystic fibrosis child with lung function decline Ersilia Vita Fiscarelli a,⁎, Gabriella Ricciotti a, Martina Rossitto a, Arianna Pompilio b, Vanessa Tuccio Guarna Assanti a, Vincenzina Lucidi c a b c
Laboratory Department, Children's Hospital and Research Institute Bambino Gesù, Rome, Italy Department of Medical, Oral and Biotechnological Sciences, and Center of Excellence on Aging and Translational Medicine, “G. d'Annunzio” University of Chieti-Pescara, Italy Cystic Fibrosis Center, Children's Hospital and Research Institute Bambino Gesù, Rome, Italy
a r t i c l e
i n f o
Article history: Received 8 April 2019 Revised 25 June 2019 Accepted 27 June 2019 Available online xxxx Keywords: Arthrographis kalrae Cystic_fibrosis Pulmonary_exacerbation Lung_function_decline BAL
a b s t r a c t Respiratory infections are a major threat to cystic fibrosis patients. Besides bacteria, many fungi colonize the cystic fibrosis respiratory tract where an important fungal biota has been described. We report here the case of a 7-year-old cystic fibrosis child with pulmonary exacerbation and Arthrographis kalrae isolated from bronchoalveolar lavage fluid. To the best of our knowledge, this is the first reported case of lung infection due to Arhtrographis kalrae in a cystic fibrosis pediatric patient. © 2019 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
1. Introduction Cystic fibrosis (CF) is a multiple organ disease; however, the respiratory tract is mainly involved and lung infections remain a major threat to CF patients. The CF lung has impaired mucociliary clearance and a build-up of thick mucus, which creates an ideal environment for microbial colonization. The bacteria most commonly believed to be pathogenic in CF include Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Burkholderia species [1]. Besides bacteria, many fungi also colonize the respiratory tract and an important fungal biota has been described in respiratory secretions of patients suffering from CF. Candida species, especially Candida albicans and, less frequently, Candida parapsilosis, Candida tropicalis and Candida glabrata, may be isolated. Opportunistic molds are the most common agents of fungal colonization and/or infection of CF patients' airways. Among them, Aspergillus fumigatus may cause various diseases, the most common being allergic bronchopulmonary aspergillosis (ABPA). In addition, other Aspergillus species, including Aspergillus flavus and Aspergillus niger, may be present as transient colonizers of the airways, usually without any associated clinical signs. The relatively high frequency of the Scedosporium species and Aspergillus terreus, which rank second and third, respectively, among filamentous fungi associated with CF should be highlighted. The description of other fungal ⁎ Corresponding author at: Children's Hospital and Research Institute Bambino Gesù, Piazza Sant'Onofrio, 4, 00165 Rome, Italy. E-mail address: evita.fi[email protected] (E.V. Fiscarelli).
species, such as Exophiala dermatitidis, Lomentospora prolificans, Rasamsonia argillacea species complex, Acrophialophora fusispora and Arthrographis kalrae in CF patients suggest that the fungal biota colonizing the airways of these patients could be even more complex [2–4]. We report here the case of a 7-year-old CF child with pulmonary disease exacerbation and Arthrographis kalrae (A. kalrae) isolated from bronchoalveolar lavage (BAL) fluid. 2. Case A 7-year-old boy with a clinical history of CF in follow-up at our CF Center was hospitalized because of low-grade fever for 3 days (38 °C), persistent cough and an increase in sputum production. The patient was diagnosed at neonatal screening with typical CF disease (genotype F508del/F508del). The respiratory tract was chronically colonized with Methicillin-sensitive Staphylococcus aureus and intermittently with Pseudomonas aeruginosa. His regular daily medications included pancreatic enzymes, salbutamol, inhalation of hypertonic saline solution, recombinant human deoxyribonuclease (rhDNAase), vitamin supplements and inhaled tobramycin prophylaxis. On admission (day 0), physical examination revealed widespread rales especially in the left lung lobe. The white blood cell count was 14.5 × 109/L (range: 4–13.5) and Creactive protein was 18 mg/L (n.v.: ≤0.5). The patient's immunological profile (total and specific Aspergillus IgE, eosinophilia) proved to be normal. His forced expiratory volume in 1 s (FEV1) was 87% predicted, much lower than the baseline measured the previous month (117% predicted).
https://doi.org/10.1016/j.jcf.2019.06.015 1569-1993/© 2019 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
Please cite this article as: E.V. Fiscarelli, G. Ricciotti, M. Rossitto, et al., A cystic fibrosis child with lung function decline, Journal of Cystic Fibrosis, https://doi.org/10.1016/j.jcf.2019.06.015
2
E.V. Fiscarelli et al. / Journal of Cystic Fibrosis xxx (2019) xxx
A computerized tomography (CT) scan showed areas of dense consolidation in the lower lobe suggestive of an infectious process (Fig. 1). Based on clinical picture, laboratory parameters and radiological signs, the diagnosis of pulmonary exacerbation was made. The patient was started on intravenous broad-spectrum antibiotics (amoxicillin plus clavulanic acid 2.8 g/die; tobramycin 180 mg/die) based on previous sputum culture positive for Methicillin-sensitive Staphylococcus aureus, performed a month before. However, his clinical picture did not improve. On day 7 post-admission (dpa), in order to determine if there were any other pathogens that could account for failure to respond to antibacterial therapy, bronchoscopy was performed and bronchoalveolar lavage (BAL) fluid was sent to the laboratory for bacterial and mycological cultures. BAL fluid specimen was processed according to local standardized microbiological Guidelines (Italian Guidelines for CF, Italian Cystic Fibrosis Society 2018), i.e. sample plating on: Columbia, MacConkey, chocholate with and without bacitracin, mannitol salt and Sabouraud with and without chloramphenicol agar media. After 5 day incubation at 37 °C (13 dpa), a large number (106 colony forming unit/mL) of small yeast-like colonies were detected in pure culture on Columbia and Sabouraud; they gradually became pale yellow in colour and 7 days later velvety and hairy. A lactophenol cotton blue preparation of the fungal colonies revealed hyaline septate hyphae with arthroconidia production. The arthrospores were one-celled smooth-walled, rectangular to cylindrical, arranged in chains. Rare blastoconidia were alsoobserved. The isolate was identified as A. kalrae by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF MS) system (Bruker Daltonics, Inc. Billerica; MA); (logscore values: 2.16, 2.26). The identification was confirmed by ribosomal DNA sequencing of internal transcribed spacer 1 (ITS1) using universal primers ITS1 and ITS2.
Fig. 1. Computed tomography (CT) scan of the chest at the time of hospitalization. CT shows an extended area of consolidation at the lower lingual segment and basal pyramid of the left lower lobe.
As we could not test antifungal susceptibility of our isolate, according to data reported in literature [7], the patient was empirically treated with itraconazole (100 mg x os daily) for 6 weeks. The clinical picture improved and the pulmonary function returned to baseline. The treatment was stopped when inflammatory markers and radiographic investigations proved a complete recovery. Up to now, the following microbiological cultures of respiratory secretions are still negative for A. kalrae.
3. Discussion Increased risk factors, including extensive use of immunosuppressive drugs, sudden climate changes, wide use of azole antifungals in agriculture, have enlarged the spectrum and augmented the incidence of some human diseases due to common environmental arthroconidial fungi, such as filamentous basidiomycetes (e.g. Schizophyllum commune) and ascomycetes. Among ascomycetous arthroconidial fungi, Arthrographis species (A. kalrae, A. arxii, A. chlamidospora, A. curvata, A. globosa and A. longispora) are generally found in soil, wood, air and water and, occasionally, in opportunistic infections in humans [5,6]. As far as we know, up to now only 15 cases of A. kalrae infection have been described worldwide (i.e. Europe, China, USA, Japan, Australia) in both immunocompetent and immunocompromised subjects. In particular, A. kalrae is accounted for endocarditis, keratomycosis in contact lens-wearing subjects, pulmonary infection, fatal invasive fungal cerebral vasculitis in an immunocompetent patient and invasive fungal sinusitis and meningitis in a patient with AIDS. More recently, a paper, reporting for the first time the onset of A. kalrae fungemia in a CF patient, was published. The Authors described the case of a 19-year-old woman presenting a permanent pulmonary colonization by, among the others, A. kalrae. The patient developed septic shock the first day after bilateral lung transplantation. A. kalrae was detected from blood, BAL, tracheal secretions and explanted lung. The treatment with caspofungin associated with liposomal amphotericin B determined the resolution of the fungemia with negativization of the microbiological cultures [4]. Our case, besides supporting the potential pathogenic role of A. kalrae in CF, suggests that most likely its incidence is underestimated. In fact, in the routinary clinical CF laboratory practice, bacteria are the focus of microbial examinations of airways secretions. Therefore, the mycological cultures are performed only for selected clinical cases. Furthermore, in some laboratories the identification of yeast-like fungi, other than Candida albicans, is not carried out. We could then speculate that A. kalrae may colonize the respiratory tract of CF patients more often than we believe. In consideration of the fact that bacteria are the most common cause of pneumonia in CF, initially the boy was treated with i.v. broadspectrum antibacterial therapy. As his clinical conditions did not improve, we suspected a different airway infection etiology; therefore, a BAL was performed. BAL fluid culture is the gold standard method for the microbial diagnosis of lung infection diseases. Although there is not a common consensus on the microbial load suggestive of infection, 105 cfu/mL is the usual bacteria cut-off for pediatric patients. In the present case, A. kalrae had grown in pure culture on agar plates and the colonies count was higher than the threshold value. Both the presence of A. kalrae in BAL fluid with a high load, and the resolution of the clinical picture only when antifungal therapy was administered, suggest the role of A. kalrae as a causing agent of the pulmonary exacerbation and lung function decline in our patient, raising A. kalrae to the status of the possible pathogenic fungus in CF people. The available data on the susceptibility patterns of this fungal species are scarce. Itraconazole and voriconazole are, as reported in literature, the most used drugs; we decided to treat our patient with itraconazole that has proved to be more efficacious [7].
Please cite this article as: E.V. Fiscarelli, G. Ricciotti, M. Rossitto, et al., A cystic fibrosis child with lung function decline, Journal of Cystic Fibrosis, https://doi.org/10.1016/j.jcf.2019.06.015
E.V. Fiscarelli et al. / Journal of Cystic Fibrosis xxx (2019) xxx
4. Conclusions Lung transplantation has become a care opportunity in selected CF patients with end-stage lung disease. Patients who have undergone lung transplantation present a high risk of developing invasive infections including fungemia. Therefore, it is necessary to always detect and identify molds and yeast species colonizing the respiratory tract of CF patients. Recently, a standardized protocol for current mycological procedures has been published to ensure an efficient recovery of fungi from CF sputum samples. Implementation is nowadays mandatory in order to harmonize laboratory practice and reach an accurate level of mycological diagnosis reliability [8]. To the best of our knowledge, this is the first reported case of lung infection due to A. kalrae in a CF pediatric patient and highlights the strong impact that fungi may have on CF patients' health. Declarations of Competing Interests The Authors have no competing interests to declare.
3
References [1] Burns Jane L, Rolain Jean-Marc. Culture-based diagnostic microbiology in cystic fibrosis: can we simplify the complexity? J Cyst Fibros 2014;13(1):1–9. [2] Pihet M, Carrere J, Cimon B, Chabasse D, Delhaes L, Symoens F, et al. Occurrence and relevance of filamentous fungi in respiratory secretions of patients with cystic fibrosis - a review. Med Mycol 2009 Jun;47(4):387–97. [3] Schwarz C, Bouchara JP, Buzina W, Chrenkova V, Dmenska H, et al. Organization of patient management and fungal epidemiology in cystic fibrosis. Mycophatologia 2018 Feb;183(1):7–19. https://doi.org/10.1007/s11046-017-0205-x [Epub 2017 Nov 3]. [4] Denis Julie, Sabou Marcela, Degot Tristan, Candolfi Ermanno, Letscher-Bru Valérie. First case of Arthrographis kalrae fungemia in a patient with cystic fibrosis. Med Mycol Case Rep 2016;14:8–11. [5] Chowdhary A, Kathuria S, Agarwal K, Meis JF. Recognizing filamentous basidiomycetes as agents of human disease: a review. Med Mycol 2014 Nov;52(8):782–97. [6] Giraldo A, Gené J, Sutton DA, Madrid H, Cano J, Crous PW, et al. Phylogenetic circumscription of Arthrographis (Eremomycetaceae, Dothideomycetes). Persoonia 2014 June; 32:102–14. [7] Sandoval-Denis M, Giraldo A, Sutton DA, Fothergill AW, Guarro J. In vitro antifungal susceptibility of clinical isolates of Arthrographis kalrae, a poorly known opportunistic fungus. Mycoses 2014 Apr;57(4):247–8. [8] Delhaes L, Touati K, Faure-Cognet O, Cornet M, Botterel F, et al. Prevalence, geographic risk factor, and development of a standardized protocol for fungal isolation in cystic fibrosis: results from the international prospective study “MFIP”. J Cyst Fibros 2019 Mar;18(2):212–20.
Acknowledgements The Authors thank Andreina Santoro for language revision.
Please cite this article as: E.V. Fiscarelli, G. Ricciotti, M. Rossitto, et al., A cystic fibrosis child with lung function decline, Journal of Cystic Fibrosis, https://doi.org/10.1016/j.jcf.2019.06.015