Abstract
The paranasal sinuses can be a focus for colonisation of the cystic fibrosis (CF) lungs with pathogens. In the sinuses, bacteria can adapt to the lung environment and enhance their antibiotic resistance, with biofilm formation thought to be the most important adaptive mechanism, causing recalcitrant disease. The presence of biofilms in CF sinuses is sparsely described. In this descriptive cross-sectional study, the sinus mucosa from 16 CF patients were analysed by fluorescence in situ hybridization using specific peptide nucleic acid (PNA-FISH) probes for Pseudomonas aeruginosa and Staphylococcus aureus to demonstrate the presence of biofilms. Small clusters of biofilm were visualised lining the sinus mucosa of CF patients. Biofilms were found in 10 out of 18 cases; 7 with intermittent lung colonisation, 2 chronically infected, and one lung transplanted patient. Finding P. aeruginosa biofilms in intermittently lung-colonised patients encourage us to intensify the attempt to eradicate pathogenic bacteria from the CF sinuses in an early stage using combined antibiotic therapy in the prolonged exposure of the sinus-mucosal surface.
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Boucher JC, Yu H, Mudd MH, Deretic V (1997) Mucoid Pseudomonas aeruginosa in cystic fibrosis: characterization of muc mutations in clinical isolates and analysis of clearance in a mouse model of respiratory infection. Infect Immun 65:3838–3846
Rubin BK (2007) Mucus structure and properties in cystic fibrosis. Paediatr Respir 8:4–7
Cystic Fibrosis Foundation (2009) Patient Registry 2007 Annual Report
Ciofu O, Johansen HK, Aanaes K, Wassermann T, Alhede M, Buchwald C, Hoiby N (2013) P. aeruginosa in the paranasal sinuses and transplanted lungs have similar adaptive mutations as isolates from chronically infected CF lungs. J Cyst Fibros 12:729–736
Mainz JG, Naehrlich L, Schien M, Kading M, Schiller I, Mayr S, Schneider G, Wiedemann B, Wiehlmann L, Cramer N, Pfister W, Kahl BC, Beck JF, Tummler B (2009) Concordant genotype of upper and lower airways P. aeruginosa and S. aureus isolates in cystic fibrosis. Thorax 64:535–540
Hansen SK, Rau MH, Johansen HK, Ciofu O, Jelsbak L, Yang L, Folkesson A, Jarmer HO, Aanaes K, Buchwald C, Hoiby N, Molin S (2011) Evolution and diversification of Pseudomonas aeruginosa in the paranasal sinuses of cystic fibrosis children have implications for chronic lung infection. ISME J 6:31–45
Bjarnsholt T, Jensen PO, Fiandaca MJ, Pedersen J, Hansen CR, Andersen CB, Pressler T, Givskov M, Hoiby N (2009) Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients. Pediatr Pulmonol 44:547–558
Hoiby N, Ciofu O, Bjarnsholt T (2010) Pseudomonas aeruginosa biofilms in cystic fibrosis. Future Microbiol 5:1663–1674
Burmolle M, Thomsen TR, Fazli M, Dige I, Christensen L, Homoe P, Tvede M, Nyvad B, Tolker-Nielsen T, Givskov M, Moser C, Kirketerp-Moller K, Johansen HK, Hoiby N, Jensen PO, Sorensen SJ, Bjarnsholt T (2010) Biofilms in chronic infections—a matter of opportunity—monospecies biofilms in multispecies infections. FEMS Immunol Med Microbiol 59:324–336
Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaerts P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang DY, Wormald PJ (2012) EPOS 2012: european position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology 50:1–12
Berkhout MC, van Rooden CJ, Rijntjes E, Fokkens WJ, El Bouazzaoui LH, Heijerman HG (2013) Sinonasal manifestations of cystic fibrosis: a correlation between genotype and phenotype? J Cyst Fibros 13:442–448
Rudkjobing VB, Aanaes K, Wolff TY, Buchwald C, Johansen HK, Thomsen TR (2014) An exploratory study of microbial diversity in sinus infections of cystic fibrosis patients by molecular methods. J Cyst Fibros. doi:10.1016/j.jcf.2014.02.008
Johansen HK, Aanaes K, Pressler T, Nielsen KG, Fisker J, Skov M, Hoiby N, Buchwald C (2012) Colonisation and infection of the paranasal sinuses in cystic fibrosis patients is accompanied by a reduced PMN response. J Cyst Fibros 11:525–531
Aanaes K, Buchwald C, Hjuler T, Skov M, Alanin M, Johansen HK (2013) The effect of sinus surgery with intensive follow-up on pathogenic sinus bacteria in patients with cystic fibrosis. Am J Rhinol Allergy 27:1–4
Frederiksen B, Koch C, Hoiby N (1999) Changing epidemiology of Pseudomonas aeruginosa infection in Danish cystic fibrosis patients (1974–1995). Pediatr Pulmonol 28:159–166
Pressler T, Karpati F, Granstrom M, Knudsen PK, Lindblad A, Hjelte L, Olesen HV, Meyer P, Hoiby N (2009) Diagnostic significance of measurements of specific IgG antibodies to Pseudomonas aeruginosa by three different serological methods. J Cyst Fibros 8:37–42
Lee TW, Brownlee KG, Conway SP, Denton M, Littlewood JM (2003) Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. J Cyst Fibros 2:29–34
Koch C, Hoiby N (2000) Diagnosis and treatment of cystic fibrosis. Respiration 67:239–247
Aanaes K, Johansen HK, Skov M, Buchvald FF, Hjuler T, Pressler T, Hoiby N, Nielsen KG, Buchwald C (2013) Clinical effects of sinus surgery and adjuvant therapy in cystic fibrosis patients—can chronic lung infections be postponed? Rhinology 51:222–230
Høiby N, Frederiksen B (2000) Microbiology of cystic fibrosis. In: Hodson ME (ed) Cystic fibrosis. Arnold, pp 83–107
Hall-Stoodley L, Stoodley P, Kathju S, Hoiby N, Moser C, Costerton JW, Moter A, Bjarnsholt T (2012) Towards diagnostic guidelines for biofilm-associated infections. FEMS Immunol Med Microbiol 65:127–145
Pressler T, Frederiksen B, Skov M, Garred P, Koch C, Høiby N (2006) Early rise of anti-pseudomonas antibodies and a mucoid phenotype of Pseudomonas aeruginosa are risk factors for development of chronic lung infection-a case control study. J Cyst Fibros 5:9–15
Vital D, Hofer M, Benden C, Holzmann D, Boehler A (2012) Impact of sinus surgery on pseudomonal airway colonization, bronchiolitis obliterans syndrome and survival in cystic fibrosis lung transplant recipients. Respiration 86:25–31
Suh JD, Cohen NA, Palmer JN (2010) Biofilms in chronic rhinosinusitis. Curr Opin Otolaryngol Head Neck Surg 18:27–31
Jain R, Douglas R (2014) When and how should we treat biofilms in chronic sinusitis? Curr Opin Otolaryngol Head Neck Surg 22:16–21
Apatzidou DA (2012) Modern approaches to non-surgical biofilm management. Front Oral Biol 15:99–116
Scali C, Kunimoto B (2013) An update on chronic wounds and the role of biofilms. J Cutan Med Surg 17:371–376
Grobler A, Weitzel EK, Buele A, Jardeleza C, Cheong YC, Field J, Wormald PJ (2008) Pre- and postoperative sinus penetration of nasal irrigation. Laryngoscope 118:2078–2081
Jervis-Bardy J, Boase S, Psaltis A, Foreman A, Wormald PJ (2012) A randomized trial of mupirocin sinonasal rinses versus saline in surgically recalcitrant staphylococcal chronic rhinosinusitis. Laryngoscope 122:2148–2153
Hengzhuang W, Wu H, Ciofu O, Song Z, Hoiby N (2011) Pharmacokinetics/pharmacodynamics of colistin and imipenem on mucoid and nonmucoid Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 55:4469–4474
Hoiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O (2010) Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents 35:322–332
Pamp SJ, Gjermansen M, Johansen HK, Tolker-Nielsen T (2008) Tolerance to the antimicrobial peptide colistin in Pseudomonas aeruginosa biofilms is linked to metabolically active cells, and depends on the pmr and mexAB-oprM genes. Mol Microbiol 68:223–240
Jelsbak L, Johansen HK, Frost AL, Thogersen R, Thomsen LE, Ciofu O, Yang L, Haagensen JA, Hoiby N, Molin S (2007) Molecular epidemiology and dynamics of Pseudomonas aeruginosa populations in lungs of cystic fibrosis patients. Infect Immun 75:2214–2224
Herrmann G, Yang L, Wu H, Song Z, Wang H, Hoiby N, Ulrich M, Molin S, Riethmuller J, Doring G (2010) Colistin-tobramycin combinations are superior to monotherapy concerning the killing of biofilm Pseudomonas aeruginosa. J Infect Dis 202:1585–1592
Thomsen TR, Aasholm MS, Rudkjobing VB, Saunders AM, Bjarnsholt T, Givskov M, Kirketerp-Moller K, Nielsen PH (2010) The bacteriology of chronic venous leg ulcer examined by culture-independent molecular methods. Wound Repair Regen 18:38–49
Bjarnsholt T, Alhede M, Alhede M, Eickhardt-Sorensen SR, Moser C, Kuhl M, Jensen PO, Hoiby N (2013) The in vivo biofilm. Trends Microbiol 21:466–474
Hensley DM, Tapia R, Encina Y (2009) An evaluation of the advandx Staphylococcus aureus/CNS PNA FISH assay. Clin Lab Sci 22:30–33
Stender H, PNA FISH (2003) an intelligent stain for rapid diagnosis of infectious diseases. Expert Rev Mol Diagn 3:649–655
Bjarnsholt T (2013) The role of bacterial biofilms in chronic infections. APMIS 121(Suppl):1–51
Boase S, Foreman A, Cleland E, Tan L, Melton-Kreft R, Pant H, Hu FZ, Ehrlich GD, Wormald PJ (2013) The microbiome of chronic rhinosinusitis: culture, molecular diagnostics and biofilm detection. BMC Infect Dis 13:210
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The Novo Nordisk Foundation supported HKJ as a clinical research stipend. The Lundbeck Foundation supported SE by a grant to TB.
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Aanaes, K., Eickhardt, S., Johansen, H.K. et al. Sinus biofilms in patients with cystic fibrosis: is adjusted eradication therapy needed?. Eur Arch Otorhinolaryngol 272, 2291–2297 (2015). https://doi.org/10.1007/s00405-014-3322-x
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DOI: https://doi.org/10.1007/s00405-014-3322-x