PDF herunterladen
Semin Respir Crit Care Med 2019; 40(06): 727-736
DOI: 10.1055/s-0039-1698464
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Microbiology of Cystic Fibrosis Airway Disease

Ana C. Blanchard
1   Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
,
Valerie J. Waters
1   Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
30. Dezember 2019 (online)

    Lizenzen und Reprints

Abstract

Although survival of individuals with cystic fibrosis (CF) has been continuously improving for the past 40 years, respiratory failure secondary to recurrent pulmonary infections remains the leading cause of mortality in this patient population. Certain pathogens such as Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and species of the Burkholderia cepacia complex continue to be associated with poorer clinical outcomes including accelerated lung function decline and increased mortality. In addition, other organisms such as anaerobes, viruses, and fungi are increasingly recognized as potential contributors to disease progression. Culture-independent molecular methods are also being used for diagnostic purposes and to examine the interaction of microorganisms in the CF airway. Given the importance of CF airway infections, ongoing initiatives to promote understanding of the epidemiology, clinical course, and treatment options for these infections are needed.

Keywords

cystic fibrosis - microbiology - bacteria - fungi - viruses - microbiome
 

  • References

  • 1 Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med 2005; 352 (19) 1992-2001
    CrossrefPubMedGoogle Scholar
  • 2 Cohen TS, Prince A. Cystic fibrosis: a mucosal immunodeficiency syndrome. Nat Med 2012; 18 (04) 509-519
    CrossrefPubMedGoogle Scholar
  • 3 Konstan MW, Morgan WJ, Butler SM. , et al; Scientific Advisory Group and the Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis. Risk factors for rate of decline in forced expiratory volume in one second in children and adolescents with cystic fibrosis. J Pediatr 2007; 151 (02) 134-139 , 139.e1
    CrossrefPubMedGoogle Scholar
  • 4 Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med 2003; 168 (08) 918-951
    CrossrefPubMedGoogle Scholar
  • 5 Liou TG, Adler FR, Fitzsimmons SC, Cahill BC, Hibbs JR, Marshall BC. Predictive 5-year survivorship model of cystic fibrosis. Am J Epidemiol 2001; 153 (04) 345-352
    CrossrefPubMedGoogle Scholar
  • 6 Ryan C, Ross S, Davey P. , et al. Prevalence and causes of prescribing errors: the PRescribing Outcomes for Trainee Doctors Engaged in Clinical Training (PROTECT) study. PLoS One 2014; 9 (01) e79802
    CrossrefPubMedGoogle Scholar
  • 7 Goss CH, Muhlebach MS. Review: Staphylococcus aureus and MRSA in cystic fibrosis. J Cyst Fibros 2011; 10 (05) 298-306
    CrossrefPubMedGoogle Scholar
  • 8 Labandeira-Rey M, Couzon F, Boisset S. , et al. Staphylococcus aureus Panton-Valentine leukocidin causes necrotizing pneumonia. Science 2007; 315 (5815): 1130-1133
    CrossrefPubMedGoogle Scholar
  • 9 Besier S, Smaczny C, von Mallinckrodt C. , et al. Prevalence and clinical significance of Staphylococcus aureus small-colony variants in cystic fibrosis lung disease. J Clin Microbiol 2007; 45 (01) 168-172
    CrossrefPubMedGoogle Scholar
  • 10 Hoffman LR, Déziel E, D'Argenio DA. , et al. Selection for Staphylococcus aureus small-colony variants due to growth in the presence of Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 2006; 103 (52) 19890-19895
    CrossrefPubMedGoogle Scholar
  • 11 Høiby N. Understanding bacterial biofilms in patients with cystic fibrosis: current and innovative approaches to potential therapies. J Cyst Fibros 2002; 1 (04) 249-254
    CrossrefPubMedGoogle Scholar
  • 12 Molina A, Del Campo R, Máiz L. , et al. High prevalence in cystic fibrosis patients of multiresistant hospital-acquired methicillin-resistant Staphylococcus aureus ST228-SCCmecI capable of biofilm formation. J Antimicrob Chemother 2008; 62 (05) 961-967
    CrossrefPubMedGoogle Scholar
  • 13 Hudson VL, Wielinski CL, Regelmann WE. Prognostic implications of initial oropharyngeal bacterial flora in patients with cystic fibrosis diagnosed before the age of two years. J Pediatr 1993; 122 (06) 854-860
    CrossrefPubMedGoogle Scholar
  • 14 Chambers HF. Methicillin resistance in staphylococci: molecular and biochemical basis and clinical implications. Clin Microbiol Rev 1997; 10 (04) 781-791
    CrossrefPubMedGoogle Scholar
  • 15 International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements (IWG-SCC). Classification of Staphylococcal Cassette Chromosome mec (SCCmec): guidelines for reporting novel SCCmec elements. Antimicrob Agents Chemother 2009; 53: 4961-4967
    CrossrefPubMedGoogle Scholar
  • 16 Ito T, Kuwahara-Arai K, Katayama Y. , et al. Staphylococcal Cassette Chromosome mec (SCCmec) analysis of MRSA. Methods Mol Biol 2014; 1085: 131-148
    PubMedGoogle Scholar
  • 17 Deurenberg RH, Stobberingh EE. The evolution of Staphylococcus aureus. Infect Genet Evol 2008; 8 (06) 747-763
    CrossrefPubMedGoogle Scholar
  • 18 McDougal LK, Thornsberry C. The role of beta-lactamase in staphylococcal resistance to penicillinase-resistant penicillins and cephalosporins. J Clin Microbiol 1986; 23 (05) 832-839
    CrossrefPubMedGoogle Scholar
  • 19 Massidda O, Montanari MP, Varaldo PE. Evidence for a methicillin-hydrolysing beta-lactamase in Staphylococcus aureus strains with borderline susceptibility to this drug. FEMS Microbiol Lett 1992; 71 (03) 223-227
    PubMedGoogle Scholar
  • 20 Nadarajah J, Lee MJ, Louie L. , et al. Identification of different clonal complexes and diverse amino acid substitutions in penicillin-binding protein 2 (PBP2) associated with borderline oxacillin resistance in Canadian Staphylococcus aureus isolates. J Med Microbiol 2006; 55 (Pt 12): 1675-1683
    CrossrefPubMedGoogle Scholar
  • 21 Glikman D, Siegel JD, David MZ. , et al. Complex molecular epidemiology of methicillin-resistant staphylococcus aureus isolates from children with cystic fibrosis in the era of epidemic community-associated methicillin-resistant S aureus. Chest 2008; 133 (06) 1381-1387
    CrossrefPubMedGoogle Scholar
  • 22 Muhlebach MS, Heltshe SL, Popowitch EB. , et al; STAR-CF Study Team. Multicenter observational study on factors and outcomes associated with various methicillin-resistant Staphylococcus aureus types in children with cystic fibrosis. Ann Am Thorac Soc 2015; 12 (06) 864-871
    CrossrefPubMedGoogle Scholar
  • 23 Ren CL, Morgan WJ, Konstan MW. , et al; Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis. Presence of methicillin resistant Staphylococcus aureus in respiratory cultures from cystic fibrosis patients is associated with lower lung function. Pediatr Pulmonol 2007; 42 (06) 513-518
    CrossrefPubMedGoogle Scholar
  • 24 Dasenbrook EC, Merlo CA, Diener-West M, Lechtzin N, Boyle MP. Persistent methicillin-resistant Staphylococcus aureus and rate of FEV1 decline in cystic fibrosis. Am J Respir Crit Care Med 2008; 178 (08) 814-821
    CrossrefPubMedGoogle Scholar
  • 25 Mandell GLBJ, Dolin R. Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2015
    Google Scholar
  • 26 Feldman M, Bryan R, Rajan S. , et al. Role of flagella in pathogenesis of Pseudomonas aeruginosa pulmonary infection. Infect Immun 1998; 66 (01) 43-51
    CrossrefPubMedGoogle Scholar
  • 27 Mahenthiralingam E, Campbell ME, Speert DP. Nonmotility and phagocytic resistance of Pseudomonas aeruginosa isolates from chronically colonized patients with cystic fibrosis. Infect Immun 1994; 62 (02) 596-605
    CrossrefPubMedGoogle Scholar
  • 28 Chew SC, Kundukad B, Seviour T. , et al. Dynamic remodeling of microbial biofilms by functionally distinct exopolysaccharides. MBio 2014; 5 (04) e01536-14
    CrossrefPubMedGoogle Scholar
  • 29 Kidd TJ, Canton R, Ekkelenkamp M. , et al; Antimicrobial Resistance in Cystic Fibrosis International Working Group. Defining antimicrobial resistance in cystic fibrosis. J Cyst Fibros 2018; 17 (06) 696-704
    CrossrefPubMedGoogle Scholar
  • 30 Blanchard AC, Horton E, Stanojevic S, Taylor L, Waters V, Ratjen F. Effectiveness of a stepwise Pseudomonas aeruginosa eradication protocol in children with cystic fibrosis. J Cyst Fibros 2017; 16 (03) 395-400
    CrossrefPubMedGoogle Scholar
  • 31 Mayer-Hamblett N, Ramsey BW, Kulasekara HD. , et al. Pseudomonas aeruginosa phenotypes associated with eradication failure in children with cystic fibrosis. Clin Infect Dis 2014; 59 (05) 624-631
    CrossrefPubMedGoogle Scholar
  • 32 Vidya P, Smith L, Beaudoin T. , et al. Chronic infection phenotypes of Pseudomonas aeruginosa are associated with failure of eradication in children with cystic fibrosis. Eur J Clin Microbiol Infect Dis 2016; 35 (01) 67-74
    CrossrefPubMedGoogle Scholar
  • 33 Hogardt M, Heesemann J. Adaptation of Pseudomonas aeruginosa during persistence in the cystic fibrosis lung. Int J Med Microbiol 2010; 300 (08) 557-562
    CrossrefPubMedGoogle Scholar
  • 34 Pamukcu A, Bush A, Buchdahl R. Effects of pseudomonas aeruginosa colonization on lung function and anthropometric variables in children with cystic fibrosis. Pediatr Pulmonol 1995; 19 (01) 10-15
    PubMedGoogle Scholar
  • 35 Gibson RL, Emerson J, McNamara S. , et al; Cystic Fibrosis Therapeutics Development Network Study Group. Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis. Am J Respir Crit Care Med 2003; 167 (06) 841-849
    CrossrefPubMedGoogle Scholar
  • 36 Ratjen F, Döring G, Nikolaizik WH. Effect of inhaled tobramycin on early Pseudomonas aeruginosa colonisation in patients with cystic fibrosis. Lancet 2001; 358 (9286): 983-984
    CrossrefPubMedGoogle Scholar
  • 37 Treggiari MM, Retsch-Bogart G, Mayer-Hamblett N. , et al; Early Pseudomonas Infection Control (EPIC) Investigators. Comparative efficacy and safety of 4 randomized regimens to treat early Pseudomonas aeruginosa infection in children with cystic fibrosis. Arch Pediatr Adolesc Med 2011; 165 (09) 847-856
    CrossrefPubMedGoogle Scholar
  • 38 Schelstraete P, Haerynck F, Van daele S, Deseyne S, De Baets F. Eradication therapy for Pseudomonas aeruginosa colonization episodes in cystic fibrosis patients not chronically colonized by P. aeruginosa. J Cyst Fibros 2013; 12 (01) 1-8
    CrossrefPubMedGoogle Scholar
  • 39 Beaudoin T, Lafayette S, Nguyen D, Rousseau S. Mucoid Pseudomonas aeruginosa caused by mucA mutations result in activation of TLR2 in addition to TLR5 in airway epithelial cells. Biochem Biophys Res Commun 2012; 428 (01) 150-154
    CrossrefPubMedGoogle Scholar
  • 40 Drevinek P, Mahenthiralingam E. Burkholderia cenocepacia in cystic fibrosis: epidemiology and molecular mechanisms of virulence. Clin Microbiol Infect 2010; 16 (07) 821-830
    CrossrefPubMedGoogle Scholar
  • 41 LiPuma JJ, Spilker T, Coenye T, Gonzalez CF. An epidemic Burkholderia cepacia complex strain identified in soil. Lancet 2002; 359 (9322): 2002-2003
    CrossrefPubMedGoogle Scholar
  • 42 Mahenthiralingam E, Vandamme P, Campbell ME. , et al. Infection with Burkholderia cepacia complex genomovars in patients with cystic fibrosis: virulent transmissible strains of genomovar III can replace Burkholderia multivorans. Clin Infect Dis 2001; 33 (09) 1469-1475
    CrossrefPubMedGoogle Scholar
  • 43 Sun L, Jiang RZ, Steinbach S. , et al. The emergence of a highly transmissible lineage of cbl+ Pseudomonas (Burkholderia) cepacia causing CF centre epidemics in North America and Britain. Nat Med 1995; 1 (07) 661-666
    CrossrefPubMedGoogle Scholar
  • 44 Zlosnik JE, Speert DP. The role of mucoidy in virulence of bacteria from the Burkholderia cepacia complex: a systematic proteomic and transcriptomic analysis. J Infect Dis 2010; 202 (05) 770-781
    CrossrefPubMedGoogle Scholar
  • 45 Huber B, Riedel K, Hentzer M. , et al. The cep quorum-sensing system of Burkholderia cepacia H111 controls biofilm formation and swarming motility. Microbiology 2001; 147 (Pt 9): 2517-2528
    PubMedGoogle Scholar
  • 46 Loutet SA, Valvano MA. A decade of Burkholderia cenocepacia virulence determinant research. Infect Immun 2010; 78 (10) 4088-4100
    CrossrefPubMedGoogle Scholar
  • 47 Mahenthiralingam E, Urban TA, Goldberg JB. The multifarious, multireplicon Burkholderia cepacia complex. Nat Rev Microbiol 2005; 3 (02) 144-156
    CrossrefPubMedGoogle Scholar
  • 48 Hancock RE. Resistance mechanisms in Pseudomonas aeruginosa and other nonfermentative gram-negative bacteria. Clin Infect Dis 1998; 27 (Suppl. 01) S93-S99
    CrossrefPubMedGoogle Scholar
  • 49 Govan JR, Brown PH, Maddison J. , et al. Evidence for transmission of Pseudomonas cepacia by social contact in cystic fibrosis. Lancet 1993; 342 (8862): 15-19
    CrossrefPubMedGoogle Scholar
  • 50 Biddick R, Spilker T, Martin A, LiPuma JJ. Evidence of transmission of Burkholderia cepacia, Burkholderia multivorans and Burkholderia dolosa among persons with cystic fibrosis. FEMS Microbiol Lett 2003; 228 (01) 57-62
    CrossrefPubMedGoogle Scholar
  • 51 LiPuma JJ, Spilker T, Gill LH, Campbell III PW, Liu L, Mahenthiralingam E. Disproportionate distribution of Burkholderia cepacia complex species and transmissibility markers in cystic fibrosis. Am J Respir Crit Care Med 2001; 164 (01) 92-96
    CrossrefPubMedGoogle Scholar
  • 52 Chen JS, Witzmann KA, Spilker T, Fink RJ, LiPuma JJ. Endemicity and inter-city spread of Burkholderia cepacia genomovar III in cystic fibrosis. J Pediatr 2001; 139 (05) 643-649
    CrossrefPubMedGoogle Scholar
  • 53 Coenye T, LiPuma JJ. Multilocus restriction typing: a novel tool for studying global epidemiology of Burkholderia cepacia complex infection in cystic fibrosis. J Infect Dis 2002; 185 (10) 1454-1462
    CrossrefPubMedGoogle Scholar
  • 54 Drevinek P, Vosahlikova S, Cinek O. , et al. Widespread clone of Burkholderia cenocepacia in cystic fibrosis patients in the Czech Republic. J Med Microbiol 2005; 54 (Pt 7): 655-659
    CrossrefPubMedGoogle Scholar
  • 55 Johnson WM, Tyler SD, Rozee KR. Linkage analysis of geographic and clinical clusters in Pseudomonas cepacia infections by multilocus enzyme electrophoresis and ribotyping. J Clin Microbiol 1994; 32 (04) 924-930
    CrossrefPubMedGoogle Scholar
  • 56 Speert DP, Henry D, Vandamme P, Corey M, Mahenthiralingam E. Epidemiology of Burkholderia cepacia complex in patients with cystic fibrosis, Canada. Emerg Infect Dis 2002; 8 (02) 181-187
    CrossrefPubMedGoogle Scholar
  • 57 Baldwin A, Mahenthiralingam E, Drevinek P. , et al. Elucidating global epidemiology of Burkholderia multivorans in cases of cystic fibrosis by multilocus sequence typing. J Clin Microbiol 2008; 46 (01) 290-295
    CrossrefPubMedGoogle Scholar
  • 58 Govan JR, Brown AR, Jones AM. Evolving epidemiology of Pseudomonas aeruginosa and the Burkholderia cepacia complex in cystic fibrosis lung infection. Future Microbiol 2007; 2 (02) 153-164
    CrossrefPubMedGoogle Scholar
  • 59 Zlosnik JE, Zhou G, Brant R. , et al. Burkholderia species infections in patients with cystic fibrosis in British Columbia, Canada. 30 years' experience. Ann Am Thorac Soc 2015; 12 (01) 70-78
    CrossrefPubMedGoogle Scholar
  • 60 Saiman L, Siegel JD, LiPuma JJ. , et al; Cystic Fibrous Foundation; Society for Healthcare Epidemiology of America. Infection prevention and control guideline for cystic fibrosis: 2013 update. Infect Control Hosp Epidemiol 2014; 35 (Suppl. 01) S1-S67
    PubMedGoogle Scholar
  • 61 Whiteford ML, Wilkinson JD, McColl JH. , et al. Outcome of Burkholderia (Pseudomonas) cepacia colonisation in children with cystic fibrosis following a hospital outbreak. Thorax 1995; 50 (11) 1194-1198
    CrossrefPubMedGoogle Scholar
  • 62 Stephenson AL, Sykes J, Berthiaume Y. , et al. Clinical and demographic factors associated with post-lung transplantation survival in individuals with cystic fibrosis. J Heart Lung Transplant 2015; 34 (09) 1139-1145
    CrossrefPubMedGoogle Scholar
  • 63 Murray S, Charbeneau J, Marshall BC, LiPuma JJ. Impact of burkholderia infection on lung transplantation in cystic fibrosis. Am J Respir Crit Care Med 2008; 178 (04) 363-371
    CrossrefPubMedGoogle Scholar
  • 64 Jones AM, Dodd ME, Govan JR. , et al. Burkholderia cenocepacia and Burkholderia multivorans: influence on survival in cystic fibrosis. Thorax 2004; 59 (11) 948-951
    CrossrefPubMedGoogle Scholar
  • 65 Blackburn L, Brownlee K, Conway S, Denton M. ‘Cepacia syndrome’ with Burkholderia multivorans, 9 years after initial colonization. J Cyst Fibros 2004; 3 (02) 133-134
    PubMedGoogle Scholar
  • 66 Waters VJ, Gómez MI, Soong G, Amin S, Ernst RK, Prince A. Immunostimulatory properties of the emerging pathogen Stenotrophomonas maltophilia. Infect Immun 2007; 75 (04) 1698-1703
    CrossrefPubMedGoogle Scholar
  • 67 Di Bonaventura G, Spedicato I, D'Antonio D, Robuffo I, Piccolomini R. Biofilm formation by Stenotrophomonas maltophilia: modulation by quinolones, trimethoprim-sulfamethoxazole, and ceftazidime. Antimicrob Agents Chemother 2004; 48 (01) 151-160
    CrossrefPubMedGoogle Scholar
  • 68 Pompilio A, Crocetta V, Confalone P. , et al. Adhesion to and biofilm formation on IB3-1 bronchial cells by Stenotrophomonas maltophilia isolates from cystic fibrosis patients. BMC Microbiol 2010; 10: 102
    CrossrefPubMedGoogle Scholar
  • 69 Crossman LC, Gould VC, Dow JM. , et al. The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants. Genome Biol 2008; 9 (04) R74
    CrossrefPubMedGoogle Scholar
  • 70 Demko CA, Stern RC, Doershuk CF. Stenotrophomonas maltophilia in cystic fibrosis: incidence and prevalence. Pediatr Pulmonol 1998; 25 (05) 304-308
    CrossrefPubMedGoogle Scholar
  • 71 Ballestero S, Vírseda I, Escobar H, Suárez L, Baquero F. Stenotrophomonas maltophilia in cystic fibrosis patients. Eur J Clin Microbiol Infect Dis 1995; 14 (08) 728-729
    CrossrefPubMedGoogle Scholar
  • 72 Cystic Fibrosis Foundation. Patient Registry Report. Bethesda, MD: 2016
    Google Scholar
  • 73 Canada Cystic Fibrosis. Canadian Patient Data Registry Report. Toronto, Canada: 2016
    Google Scholar
  • 74 Talmaciu I, Varlotta L, Mortensen J, Schidlow DV. Risk factors for emergence of Stenotrophomonas maltophilia in cystic fibrosis. Pediatr Pulmonol 2000; 30 (01) 10-15
    CrossrefPubMedGoogle Scholar
  • 75 Burns JL, Van Dalfsen JM, Shawar RM. , et al. Effect of chronic intermittent administration of inhaled tobramycin on respiratory microbial flora in patients with cystic fibrosis. J Infect Dis 1999; 179 (05) 1190-1196
    CrossrefPubMedGoogle Scholar
  • 76 Denton M, Todd NJ, Littlewood JM. Role of anti-pseudomonal antibiotics in the emergence of Stenotrophomonas maltophilia in cystic fibrosis patients. Eur J Clin Microbiol Infect Dis 1996; 15 (05) 402-405
    CrossrefPubMedGoogle Scholar
  • 77 Goss CH, Mayer-Hamblett N, Aitken ML, Rubenfeld GD, Ramsey BW. Association between Stenotrophomonas maltophilia and lung function in cystic fibrosis. Thorax 2004; 59 (11) 955-959
    CrossrefPubMedGoogle Scholar
  • 78 Goss CH, Otto K, Aitken ML, Rubenfeld GD. Detecting Stenotrophomonas maltophilia does not reduce survival of patients with cystic fibrosis. Am J Respir Crit Care Med 2002; 166 (03) 356-361
    CrossrefPubMedGoogle Scholar
  • 79 Waters V, Atenafu EG, Salazar JG. , et al. Chronic Stenotrophomonas maltophilia infection and exacerbation outcomes in cystic fibrosis. J Cyst Fibros 2012; 11 (01) 8-13
    CrossrefPubMedGoogle Scholar
  • 80 Waters V, Atenafu EG, Lu A, Yau Y, Tullis E, Ratjen F. Chronic Stenotrophomonas maltophilia infection and mortality or lung transplantation in cystic fibrosis patients. J Cyst Fibros 2013; 12 (05) 482-486
    CrossrefPubMedGoogle Scholar
  • 81 Waters V, Yau Y, Prasad S. , et al. Stenotrophomonas maltophilia in cystic fibrosis: serologic response and effect on lung disease. Am J Respir Crit Care Med 2011; 183 (05) 635-640
    CrossrefPubMedGoogle Scholar
  • 82 Ridderberg W, Nielsen SM, Nørskov-Lauritsen N. Genetic adaptation of Achromobacter sp. during persistence in the lungs of cystic fibrosis patients. PLoS One 2015; 10 (08) e0136790
    CrossrefPubMedGoogle Scholar
  • 83 Filipic B, Malesevic M, Vasiljevic Z. , et al. Uncovering differences in virulence markers associated with Achromobacter species of CF and non-CF origin. Front Cell Infect Microbiol 2017; 7: 224
    CrossrefPubMedGoogle Scholar
  • 84 Tom SK, Yau YC, Beaudoin T, LiPuma JJ, Waters V. Effect of high-dose antimicrobials on biofilm growth of Achromobacter species isolated from cystic fibrosis patients. Antimicrob Agents Chemother 2015; 60 (01) 650-652
    PubMedGoogle Scholar
  • 85 Bador J, Amoureux L, Blanc E, Neuwirth C. Innate aminoglycoside resistance of Achromobacter xylosoxidans is due to AxyXY-OprZ, an RND-type multidrug efflux pump. Antimicrob Agents Chemother 2013; 57 (01) 603-605
    CrossrefPubMedGoogle Scholar
  • 86 Decré D, Arlet G, Danglot C. , et al. A beta-lactamase-overproducing strain of Alcaligenes denitrificans subsp. xylosoxydans isolated from a case of meningitis. J Antimicrob Chemother 1992; 30 (06) 769-779
    CrossrefPubMedGoogle Scholar
  • 87 Spilker T, Vandamme P, Lipuma JJ. Identification and distribution of Achromobacter species in cystic fibrosis. J Cyst Fibros 2013; 12 (03) 298-301
    CrossrefPubMedGoogle Scholar
  • 88 De Baets F, Schelstraete P, Van Daele S, Haerynck F, Vaneechoutte M. Achromobacter xylosoxidans in cystic fibrosis: prevalence and clinical relevance. J Cyst Fibros 2007; 6 (01) 75-78
    CrossrefPubMedGoogle Scholar
  • 89 Pereira RH, Carvalho-Assef AP, Albano RM. , et al. Achromobacter xylosoxidans: characterization of strains in Brazilian cystic fibrosis patients. J Clin Microbiol 2011; 49 (10) 3649-3651
    CrossrefPubMedGoogle Scholar
  • 90 Van Daele S, Verhelst R, Claeys G. , et al. Shared genotypes of Achromobacter xylosoxidans strains isolated from patients at a cystic fibrosis rehabilitation center. J Clin Microbiol 2005; 43 (06) 2998-3002
    CrossrefPubMedGoogle Scholar
  • 91 Dunne Jr WM, Maisch S. Epidemiological investigation of infections due to Alcaligenes species in children and patients with cystic fibrosis: use of repetitive-element-sequence polymerase chain reaction. Clin Infect Dis 1995; 20 (04) 836-841
    CrossrefPubMedGoogle Scholar
  • 92 Kanellopoulou M, Pournaras S, Iglezos H, Skarmoutsou N, Papafrangas E, Maniatis AN. Persistent colonization of nine cystic fibrosis patients with an Achromobacter (Alcaligenes) xylosoxidans clone. Eur J Clin Microbiol Infect Dis 2004; 23 (04) 336-339
    CrossrefPubMedGoogle Scholar
  • 93 Lambiase A, Catania MR, Del Pezzo M. , et al. Achromobacter xylosoxidans respiratory tract infection in cystic fibrosis patients. Eur J Clin Microbiol Infect Dis 2011; 30 (08) 973-980
    CrossrefPubMedGoogle Scholar
  • 94 Somayaji R, Stanojevic S, Tullis DE, Stephenson AL, Ratjen F, Waters V. Clinical outcomes associated with Achromobacter species infection in patients with cystic fibrosis. Ann Am Thorac Soc 2017; 14 (09) 1412-1418
    CrossrefPubMedGoogle Scholar
  • 95 Versalovic J, Carroll KC, Pfaller MA. , et al., eds. Manual of Clinical Microbiology. 10th ed. Washington, DC: ASM Press; 2011
    Google Scholar
  • 96 Hofstad T. Virulence factors in anaerobic bacteria. Eur J Clin Microbiol Infect Dis 1992; 11 (11) 1044-1048
    CrossrefPubMedGoogle Scholar
  • 97 Lambiase A, Catania MR, Rossano F. Anaerobic bacteria infection in cystic fibrosis airway disease. New Microbiol 2010; 33 (03) 185-194
    PubMedGoogle Scholar
  • 98 Rogers GB, Carroll MP, Serisier DJ. , et al. Use of 16S rRNA gene profiling by terminal restriction fragment length polymorphism analysis to compare bacterial communities in sputum and mouthwash samples from patients with cystic fibrosis. J Clin Microbiol 2006; 44 (07) 2601-2604
    CrossrefPubMedGoogle Scholar
  • 99 Tunney MM, Field TR, Moriarty TF. , et al. Detection of anaerobic bacteria in high numbers in sputum from patients with cystic fibrosis. Am J Respir Crit Care Med 2008; 177 (09) 995-1001
    CrossrefPubMedGoogle Scholar
  • 100 Worlitzsch D, Rintelen C, Böhm K. , et al. Antibiotic-resistant obligate anaerobes during exacerbations of cystic fibrosis patients. Clin Microbiol Infect 2009; 15 (05) 454-460
    CrossrefPubMedGoogle Scholar
  • 101 Hogan DA, Willger SD, Dolben EL. , et al. Analysis of lung microbiota in bronchoalveolar lavage, protected brush and sputum samples from subjects with mild-to-moderate cystic fibrosis lung disease. PLoS One 2016; 11 (03) e0149998
    CrossrefPubMedGoogle Scholar
  • 102 Rogers GB, Carroll MP, Serisier DJ, Hockey PM, Jones G, Bruce KD. Characterization of bacterial community diversity in cystic fibrosis lung infections by use of 16s ribosomal DNA terminal restriction fragment length polymorphism profiling. J Clin Microbiol 2004; 42 (11) 5176-5183
    CrossrefPubMedGoogle Scholar
  • 103 Tunney MM, Klem ER, Fodor AA. , et al. Use of culture and molecular analysis to determine the effect of antibiotic treatment on microbial community diversity and abundance during exacerbation in patients with cystic fibrosis. Thorax 2011; 66 (07) 579-584
    CrossrefPubMedGoogle Scholar
  • 104 Mirković B, Murray MA, Lavelle GM. , et al. The role of short-chain fatty acids, produced by anaerobic bacteria, in the cystic fibrosis airway. Am J Respir Crit Care Med 2015; 192 (11) 1314-1324
    CrossrefPubMedGoogle Scholar
  • 105 Sherrard LJ, Tunney MM, Elborn JS. Antimicrobial resistance in the respiratory microbiota of people with cystic fibrosis. Lancet 2014; 384 (9944): 703-713
    CrossrefPubMedGoogle Scholar
  • 106 Goddard AF, Staudinger BJ, Dowd SE. , et al. Direct sampling of cystic fibrosis lungs indicates that DNA-based analyses of upper-airway specimens can misrepresent lung microbiota. Proc Natl Acad Sci U S A 2012; 109 (34) 13769-13774
    CrossrefPubMedGoogle Scholar
  • 107 Prevaes SM, de Steenhuijsen Piters WA, de Winter-de Groot KM. , et al. Concordance between upper and lower airway microbiota in infants with cystic fibrosis. Eur Respir J 2017; 49 (03) 49
    PubMedGoogle Scholar
  • 108 Phan J, Gallagher T, Oliver A, England WE, Whiteson K. Fermentation products in the cystic fibrosis airways induce aggregation and dormancy-associated expression profiles in a CF clinical isolate of Pseudomonas aeruginosa. FEMS Microbiol Lett 2018; 365 (10) 365
    PubMedGoogle Scholar
  • 109 Sherrard LJ, McGrath SJ, McIlreavey L. , et al. Production of extended-spectrum β-lactamases and the potential indirect pathogenic role of Prevotella isolates from the cystic fibrosis respiratory microbiota. Int J Antimicrob Agents 2016; 47 (02) 140-145
    CrossrefPubMedGoogle Scholar
  • 110 Zemanick ET, Harris JK, Wagner BD. , et al. Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations. PLoS One 2013; 8 (04) e62917
    CrossrefPubMedGoogle Scholar
  • 111 Zemanick ET, Wagner BD, Robertson CE. , et al. Airway microbiota across age and disease spectrum in cystic fibrosis. Eur Respir J 2017; 50 (05) 50
    CrossrefPubMedGoogle Scholar
  • 112 Zemanick ET, Wagner BD, Robertson CE. , et al. Assessment of airway microbiota and inflammation in cystic fibrosis using multiple sampling methods. Ann Am Thorac Soc 2015; 12 (02) 221-229
    CrossrefPubMedGoogle Scholar
  • 113 Muhlebach MS, Hatch JE, Einarsson GG. , et al. Anaerobic bacteria cultured from cystic fibrosis airways correlate to milder disease: a multisite study. Eur Respir J 2018; 52 (01) 52
    CrossrefPubMedGoogle Scholar
  • 114 O'Neill K, Bradley JM, Johnston E. , et al. Reduced bacterial colony count of anaerobic bacteria is associated with a worsening in lung clearance index and inflammation in cystic fibrosis. PLoS One 2015; 10 (05) e0126980
    CrossrefPubMedGoogle Scholar
  • 115 Filkins LM, Hampton TH, Gifford AH. , et al. Prevalence of streptococci and increased polymicrobial diversity associated with cystic fibrosis patient stability. J Bacteriol 2012; 194 (17) 4709-4717
    CrossrefPubMedGoogle Scholar
  • 116 Scagnolari C, Turriziani O, Monteleone K, Pierangeli A, Antonelli G. Consolidation of molecular testing in clinical virology. Expert Rev Anti Infect Ther 2017; 15 (04) 387-400
    CrossrefPubMedGoogle Scholar
  • 117 Wang EE, Prober CG, Manson B, Corey M, Levison H. Association of respiratory viral infections with pulmonary deterioration in patients with cystic fibrosis. N Engl J Med 1984; 311 (26) 1653-1658
    CrossrefPubMedGoogle Scholar
  • 118 van Ewijk BE, van der Zalm MM, Wolfs TF, van der Ent CK. Viral respiratory infections in cystic fibrosis. J Cyst Fibros 2005; 4 (Suppl. 02) 31-36
    CrossrefPubMedGoogle Scholar
  • 119 Asner S, Waters V, Solomon M. , et al. Role of respiratory viruses in pulmonary exacerbations in children with cystic fibrosis. J Cyst Fibros 2012; 11 (05) 433-439
    CrossrefPubMedGoogle Scholar
  • 120 Collinson J, Nicholson KG, Cancio E. , et al. Effects of upper respiratory tract infections in patients with cystic fibrosis. Thorax 1996; 51 (11) 1115-1122
    CrossrefPubMedGoogle Scholar
  • 121 Smyth AR, Smyth RL, Tong CY, Hart CA, Heaf DP. Effect of respiratory virus infections including rhinovirus on clinical status in cystic fibrosis. Arch Dis Child 1995; 73 (02) 117-120
    CrossrefPubMedGoogle Scholar
  • 122 Wat D, Doull I. Respiratory virus infections in cystic fibrosis. Paediatr Respir Rev 2003; 4 (03) 172-177
    CrossrefPubMedGoogle Scholar
  • 123 van Ewijk BE, van der Zalm MM, Wolfs TF. , et al. Prevalence and impact of respiratory viral infections in young children with cystic fibrosis: prospective cohort study. Pediatrics 2008; 122 (06) 1171-1176
    CrossrefPubMedGoogle Scholar
  • 124 Wat D, Gelder C, Hibbitts S. , et al. The role of respiratory viruses in cystic fibrosis. J Cyst Fibros 2008; 7 (04) 320-328
    CrossrefPubMedGoogle Scholar
  • 125 Scheithauer S, Haase G, Häusler M, Lemmen S, Ritter K, Kleines M. Association between respiratory and herpes viruses on pulmonary exacerbations in cystic fibrosis patients. J Cyst Fibros 2010; 9 (03) 234-236
    CrossrefPubMedGoogle Scholar
  • 126 Goffard A, Lambert V, Salleron J. , et al. Virus and cystic fibrosis: rhinoviruses are associated with exacerbations in adult patients. J Clin Virol 2014; 60 (02) 147-153
    CrossrefPubMedGoogle Scholar
  • 127 Hiatt PW, Grace SC, Kozinetz CA. , et al. Effects of viral lower respiratory tract infection on lung function in infants with cystic fibrosis. Pediatrics 1999; 103 (03) 619-626
    CrossrefPubMedGoogle Scholar
  • 128 Ramsey BW, Gore EJ, Smith AL, Cooney MK, Redding GJ, Foy H. The effect of respiratory viral infections on patients with cystic fibrosis. Am J Dis Child 1989; 143 (06) 662-668
    PubMedGoogle Scholar
  • 129 Schögler A, Stokes AB, Casaulta C. , et al. Interferon response of the cystic fibrosis bronchial epithelium to major and minor group rhinovirus infection. J Cyst Fibros 2016; 15 (03) 332-339
    CrossrefPubMedGoogle Scholar
  • 130 Flight WG, Bright-Thomas RJ, Tilston P. , et al. Incidence and clinical impact of respiratory viruses in adults with cystic fibrosis. Thorax 2014; 69 (03) 247-253
    CrossrefPubMedGoogle Scholar
  • 131 Esther Jr CR, Lin FC, Kerr A, Miller MB, Gilligan PH. Respiratory viruses are associated with common respiratory pathogens in cystic fibrosis. Pediatr Pulmonol 2014; 49 (09) 926-931
    CrossrefPubMedGoogle Scholar
  • 132 Etherington C, Naseer R, Conway SP, Whitaker P, Denton M, Peckham DG. The role of respiratory viruses in adult patients with cystic fibrosis receiving intravenous antibiotics for a pulmonary exacerbation. J Cyst Fibros 2014; 13 (01) 49-55
    CrossrefPubMedGoogle Scholar
  • 133 Simoes EA. Respiratory syncytial virus infection. Lancet 1999; 354 (9181): 847-852
    CrossrefPubMedGoogle Scholar
  • 134 Kristensen K, Hjuler T, Ravn H, Simões EA, Stensballe LG. Chronic diseases, chromosomal abnormalities, and congenital malformations as risk factors for respiratory syncytial virus hospitalization: a population-based cohort study. Clin Infect Dis 2012; 54 (06) 810-817
    CrossrefPubMedGoogle Scholar
  • 135 Abman SH, Ogle JW, Butler-Simon N, Rumack CM, Accurso FJ. Role of respiratory syncytial virus in early hospitalizations for respiratory distress of young infants with cystic fibrosis. J Pediatr 1988; 113 (05) 826-830
    CrossrefPubMedGoogle Scholar
  • 136 de Almeida MB, Zerbinati RM, Tateno AF. , et al. Rhinovirus C and respiratory exacerbations in children with cystic fibrosis. Emerg Infect Dis 2010; 16 (06) 996-999
    CrossrefPubMedGoogle Scholar
  • 137 Ortiz JR, Neuzil KM, Victor JC, Wald A, Aitken ML, Goss CH. Influenza-associated cystic fibrosis pulmonary exacerbations. Chest 2010; 137 (04) 852-860
    CrossrefPubMedGoogle Scholar
  • 138 Johansen HK, Høiby N. Seasonal onset of initial colonisation and chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis in Denmark. Thorax 1992; 47 (02) 109-111
    CrossrefPubMedGoogle Scholar
  • 139 Armstrong D, Grimwood K, Carlin JB. , et al. Severe viral respiratory infections in infants with cystic fibrosis. Pediatr Pulmonol 1998; 26 (06) 371-379
    CrossrefPubMedGoogle Scholar
  • 140 Hendricks MR, Lashua LP, Fischer DK. , et al. Respiratory syncytial virus infection enhances Pseudomonas aeruginosa biofilm growth through dysregulation of nutritional immunity. Proc Natl Acad Sci U S A 2016; 113 (06) 1642-1647
    CrossrefPubMedGoogle Scholar
  • 141 Miró-Cañís S, Capilla-Rubio S, Marzo-Checa L. , et al. Multiplex PCR reveals that viruses are more frequent than bacteria in children with cystic fibrosis. J Clin Virol 2017; 86: 1-4
    CrossrefPubMedGoogle Scholar
  • 142 Kim SH, Clark ST, Surendra A. , et al. Global analysis of the fungal microbiome in cystic fibrosis patients reveals loss of function of the transcriptional repressor Nrg1 as a mechanism of pathogen adaptation. PLoS Pathog 2015; 11 (11) e1005308
    CrossrefPubMedGoogle Scholar
  • 143 Cassagne C, Normand AC, L'Ollivier C, Ranque S, Piarroux R. Performance of MALDI-TOF MS platforms for fungal identification. Mycoses 2016; 59 (11) 678-690
    CrossrefPubMedGoogle Scholar
  • 144 Valenza G, Tappe D, Turnwald D. , et al. Prevalence and antimicrobial susceptibility of microorganisms isolated from sputa of patients with cystic fibrosis. J Cyst Fibros 2008; 7 (02) 123-127
    CrossrefPubMedGoogle Scholar
  • 145 Agarwal R, Chakrabarti A, Shah A. , et al; ABPA complicating asthma ISHAM working group. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy 2013; 43 (08) 850-873
    CrossrefPubMedGoogle Scholar
  • 146 Kraemer R, Deloséa N, Ballinari P, Gallati S, Crameri R. Effect of allergic bronchopulmonary aspergillosis on lung function in children with cystic fibrosis. Am J Respir Crit Care Med 2006; 174 (11) 1211-1220
    CrossrefPubMedGoogle Scholar
  • 147 Stevens DA, Moss RB, Kurup VP. , et al; Participants in the Cystic Fibrosis Foundation Consensus Conference. Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis 2003; 37 (Suppl. 03) S225-S264
    CrossrefPubMedGoogle Scholar
  • 148 Amin R, Dupuis A, Aaron SD, Ratjen F. The effect of chronic infection with Aspergillus fumigatus on lung function and hospitalization in patients with cystic fibrosis. Chest 2010; 137 (01) 171-176
    CrossrefPubMedGoogle Scholar
  • 149 Aaron SD, Vandemheen KL, Freitag A. , et al. Treatment of Aspergillus fumigatus in patients with cystic fibrosis: a randomized, placebo-controlled pilot study. PLoS One 2012; 7 (04) e36077
    CrossrefPubMedGoogle Scholar
  • 150 Massam J, Bitnun A, Solomon M. , et al. Invasive aspergillosis in cystic fibrosis: a fatal case in an adolescent and review of the literature. Pediatr Infect Dis J 2011; 30 (02) 178-180
    CrossrefPubMedGoogle Scholar
  • 151 Horré R, Marklein G, Siekmeier R, Nidermajer S, Reiffert SM. Selective isolation of Pseudallescheria and Scedosporium species from respiratory tract specimens of cystic fibrosis patients. Respiration 2009; 77 (03) 320-324
    CrossrefPubMedGoogle Scholar
  • 152 Rodriguez-Tudela JL, Berenguer J, Guarro J. , et al. Epidemiology and outcome of Scedosporium prolificans infection, a review of 162 cases. Med Mycol 2009; 47 (04) 359-370
    CrossrefPubMedGoogle Scholar
  • 153 Horré R, Schaal KP, Siekmeier R, Sterzik B, de Hoog GS, Schnitzler N. Isolation of fungi, especially Exophiala dermatitidis, in patients suffering from cystic fibrosis. A prospective study. Respiration 2004; 71 (04) 360-366
    CrossrefPubMedGoogle Scholar
  • 154 Griffard EA, Guajardo JR, Cooperstock MS, Scoville CL. Isolation of Exophiala dermatitidis from pigmented sputum in a cystic fibrosis patient. Pediatr Pulmonol 2010; 45 (05) 508-510
    PubMedGoogle Scholar
  • 155 Chotirmall SH, O'Donoghue E, Bennett K, Gunaratnam C, O'Neill SJ, McElvaney NG. Sputum Candida albicans presages FEV1 decline and hospital-treated exacerbations in cystic fibrosis. Chest 2010; 138 (05) 1186-1195
    CrossrefPubMedGoogle Scholar
  • 156 Coburn B, Wang PW, Diaz Caballero J. , et al. Lung microbiota across age and disease stage in cystic fibrosis. Sci Rep 2015; 5: 10241
    CrossrefPubMedGoogle Scholar
  • 157 Cox MJ, Allgaier M, Taylor B. , et al. Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients. PLoS One 2010; 5 (06) e11044
    CrossrefPubMedGoogle Scholar
  • 158 Laguna TA, Wagner BD, Williams CB. , et al. Airway microbiota in bronchoalveolar lavage fluid from clinically well infants with cystic fibrosis. PLoS One 2016; 11 (12) e0167649
    CrossrefPubMedGoogle Scholar
  • 159 van der Gast CJ, Cuthbertson L, Rogers GB. , et al. Three clinically distinct chronic pediatric airway infections share a common core microbiota. Ann Am Thorac Soc 2014; 11 (07) 1039-1048
    CrossrefPubMedGoogle Scholar
  • 160 Zhao J, Schloss PD, Kalikin LM. , et al. Decade-long bacterial community dynamics in cystic fibrosis airways. Proc Natl Acad Sci U S A 2012; 109 (15) 5809-5814
    CrossrefPubMedGoogle Scholar
  • 161 Layeghifard M, Li H, Wang PW. , et al. Microbiome networks and change-point analysis reveal key community changes associated with cystic fibrosis pulmonary exacerbations. NPJ Biofilms Microbiomes 2019; 5: 4
    CrossrefPubMedGoogle Scholar
  • 162 Carmody LA, Caverly LJ, Foster BK. , et al. Fluctuations in airway bacterial communities associated with clinical states and disease stages in cystic fibrosis. PLoS One 2018; 13 (03) e0194060
    CrossrefPubMedGoogle Scholar
  • 163 Hisert KB, Heltshe SL, Pope C. , et al. Restoring cystic fibrosis transmembrane conductance regulator function reduces airway bacteria and inflammation in people with cystic fibrosis and chronic lung infections. Am J Respir Crit Care Med 2017; 195 (12) 1617-1628
    CrossrefPubMedGoogle Scholar