title: Antibiotic management of lung infections in cystic fibrosis. I. The microbiome, methicillin-resistant Staphylococcus aureus, gram-negative bacteria, and multiple infections.
abstract: Despite significant advances in treatment strategies targeting the underlying defect in cystic fibrosis (CF), airway infection remains an important cause of lung disease. In this two-part series, we review recent evidence related to the complexity of CF airway infection, explore data suggesting the relevance of individual microbial species, and discuss current and future treatment options. In Part I, the evidence with respect to the spectrum of bacteria present in the CF airway, known as the lung microbiome is discussed. Subsequently, the current approach to treat methicillin-resistant Staphylococcus aureus, gram-negative bacteria, as well as multiple coinfections is reviewed. Newer molecular techniques have demonstrated that the airway microbiome consists of a large number of microbes, and the balance between microbes, rather than the mere presence of a single species, may be relevant for disease pathophysiology. A better understanding of this complex environment could help define optimal treatment regimens that target pathogens without affecting others. Although relevance of these organisms is unclear, the pathologic consequences of methicillin-resistant S. aureus infection in patients with CF have been recently determined. New strategies for eradication and treatment of both acute and chronic infections are discussed. Pseudomonas aeruginosa plays a prominent role in CF lung disease, but many other nonfermenting gram-negative bacteria are also found in the CF airway. Many new inhaled antibiotics specifically targeting P. aeruginosa have become available with the hope that they will improve the quality of life for patients. Part I concludes with a discussion of how best to treat patients with multiple coinfections.
authors.affiliation: 1 Department of Pediatrics, Case Western Reserve University School of Medicine and Rainbow Babies and Children's Hospital, Cleveland, Ohio.
authors.forename: James F
authors.initials: JF
authors.lastname: Chmiel
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Aksamit
authors.forename: Sanjay H
authors.initials: SH
authors.lastname: Chotirmall
authors.forename: Elliott C
authors.initials: EC
authors.lastname: Dasenbrook
authors.forename: J Stuart
authors.initials: JS
authors.lastname: Elborn
authors.forename: John J
authors.initials: JJ
authors.lastname: LiPuma
authors.forename: Sarath C
authors.initials: SC
authors.lastname: Ranganathan
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Waters
authors.forename: Felix A
authors.initials: FA
authors.lastname: Ratjen
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D019317:Evidence-Based Medicine; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D064307:Microbiota; D011379:Prognosis; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology; D018570:Risk Assessment; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents
keywords: Burkholderia cepacia; Pseudomonas aeruginosa; Stenotrophomonas maltophilia; methicillin-resistant Staphylococcus aureus; microbiome
references.citation: JAMA. 2010 Jun 16;303(23):2386-92
references.pmid: 20551409
references.citation: J Clin Microbiol. 2006 Jul;44(7):2601-4
references.pmid: 16825392
references.citation: Am J Dis Child. 1946 Jul;72:17-61
references.pmid: 20994054
references.citation: J Bacteriol. 2012 Sep;194(17):4709-17
references.pmid: 22753064
references.citation: Chest. 2012 Feb;141(2):485-493
references.pmid: 21835906
references.citation: J Cyst Fibros. 2014 May;13(3):296-305
references.pmid: 24176390
references.citation: Am J Respir Crit Care Med. 2008 May 1;177(9):995-1001
references.pmid: 18263800
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20529-33
references.pmid: 18077362
references.citation: J Cyst Fibros. 2013 May;12(3):194-205
references.pmid: 23402821
references.citation: J Cyst Fibros. 2011 Jan;10(1):54-61
references.pmid: 21075062
references.citation: J Cyst Fibros. 2013 Sep;12(5):482-6
references.pmid: 23294530
references.citation: Am J Respir Crit Care Med. 2008 Nov 1;178(9):921-8
references.pmid: 18658109
references.citation: Thorax. 2012 Oct;67(10):867-73
references.pmid: 22707521
references.citation: Thorax. 2011 Jul;66(7):579-84
references.pmid: 21270069
references.citation: Am J Respir Crit Care Med. 2010 Sep 1;182(5):627-32
references.pmid: 20463179
references.citation: PLoS One. 2012;7(9):e45001
references.pmid: 23049765
references.citation: J Pediatr. 1985 Sep;107(3):382-7
references.pmid: 4032134
references.citation: Clin Infect Dis. 2011 Feb 1;52(3):285-92
references.pmid: 21217178
references.citation: J Cyst Fibros. 2013 May;12(3):302
references.pmid: 22959655
references.citation: Pediatr Pulmonol. 2009 Feb;44(2):148-54
references.pmid: 19137597
references.citation: Am J Respir Crit Care Med. 2013 Apr 1;187(7):680-9
references.pmid: 23540878
references.citation: Acta Paediatr Scand. 1983 Sep;72(5):651-7
references.pmid: 6637463
references.citation: Cochrane Database Syst Rev. 2012 Nov 14;11:CD009528
references.pmid: 23152277
references.citation: Thorax. 2004 Apr;59(4):334-6
references.pmid: 15047956
references.citation: Antimicrob Agents Chemother. 2013 Mar;57(3):1546-8
references.pmid: 23295930
references.citation: J Cyst Fibros. 2010 Mar;9(2):104-9
references.pmid: 20051329
references.citation: Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5809-14
references.pmid: 22451929
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15070-5
references.pmid: 18812504
references.citation: Clin Rev Allergy Immunol. 2002 Aug;23(1):5-27
references.pmid: 12162106
references.citation: ISME J. 2011 May;5(5):780-91
references.pmid: 21151003
references.citation: Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13769-74
references.pmid: 22872870
references.citation: Am J Respir Crit Care Med. 2007 Nov 15;176(10):957-69
references.pmid: 17761616
references.citation: Expert Rev Respir Med. 2013 Aug;7(4):385-96
references.pmid: 23964628
references.citation: Chest. 2011 May;139(5):1148-1155
references.pmid: 20864609
references.citation: Pediatr Pulmonol. 2015 Jun;50(6):552-9
references.pmid: 25559432
references.citation: Antimicrob Agents Chemother. 2011 Jul;55(7):3393-8
references.pmid: 21518837
references.citation: Cochrane Database Syst Rev. 2013 Feb 28;(2):CD009650
references.pmid: 23450608
references.citation: Am J Respir Crit Care Med. 2011 Mar 1;183(5):635-40
references.pmid: 20889901
references.citation: Antimicrob Agents Chemother. 2011 Jun;55(6):2636-40
references.pmid: 21444699
references.citation: J Cyst Fibros. 2012 Dec;11(6):461-79
references.pmid: 23137712
references.citation: Eur Respir J. 2000 Oct;16(4):749-67
references.pmid: 11106223
references.citation: PLoS One. 2010 Jun 23;5(6):e11044
references.pmid: 20585638
references.citation: J Antimicrob Chemother. 2009 Apr;63(4):728-32
references.pmid: 19193658
references.citation: Am J Respir Crit Care Med. 2009 Nov 1;180(9):802-8
references.pmid: 19729669
references.citation: mBio. 2012 Aug 21;3(4):
references.pmid: 22911969
references.citation: J Cyst Fibros. 2013 Mar;12(2):130-40
references.pmid: 22985692
references.citation: Pediatr Pulmonol. 2007 Apr;42(4):307-13
references.pmid: 17352404
references.citation: Am J Respir Crit Care Med. 2008 Oct 15;178(8):814-21
references.pmid: 18669817
references.citation: J Antimicrob Chemother. 1997 Mar;39(3):431-3
references.pmid: 9096197
references.citation: Thorax. 2013 Sep;68(9):818-25
references.pmid: 23749840
references.citation: J Clin Pharmacol. 2001 Jun;41(6):645-54
references.pmid: 11402633
references.citation: Pediatr Pulmonol. 2007 Nov;42(11):1008-17
references.pmid: 17902147
references.citation: Adv Drug Deliv Rev. 2002 Dec 5;54(11):1425-43
references.pmid: 12458153
references.citation: J Antimicrob Chemother. 2006 Feb;57(2):306-11
references.pmid: 16396919
references.citation: Respir Res. 2003;4:8
references.pmid: 14511398
references.citation: J Cyst Fibros. 2012 Jul;11(4):288-92
references.pmid: 22436723
references.citation: Environ Microbiol. 2010 May;12(5):1293-303
references.pmid: 20192960
references.citation: J Clin Microbiol. 2004 Nov;42(11):5176-83
references.pmid: 15528712
references.citation: Am J Transplant. 2008 May;8(5):1025-30
references.pmid: 18318775
references.citation: Am J Respir Crit Care Med. 2012 Jan 15;185(2):171-8
references.pmid: 22095545
references.citation: J Cyst Fibros. 2011 Sep;10(5):298-306
references.pmid: 21719362
references.citation: Curr Pharm Des. 2012;18(5):696-725
references.pmid: 22229574
references.citation: ISME J. 2011 Jan;5(1):20-9
references.pmid: 20631810
references.citation: Chest. 2001 Sep;120(3 Suppl):118S-123S
references.pmid: 11555566
references.citation: Am J Epidemiol. 1996 May 15;143(10):1007-17
references.pmid: 8629607
references.citation: J Antimicrob Chemother. 2012 Nov;67(11):2673-81
references.pmid: 22843834
references.citation: Am J Respir Crit Care Med. 2011 Jun 1;183(11):1510-6
references.pmid: 21471106
references.citation: Thorax. 2012 Oct;67(10):851-2
references.pmid: 22752196
references.citation: Antimicrob Agents Chemother. 2011 Apr;55(4):1684-92
references.pmid: 21263048
references.citation: Ann Am Thorac Soc. 2013 Jun;10(3):179-87
references.pmid: 23802813
references.citation: FEMS Immunol Med Microbiol. 2011 Mar;61(2):141-6
references.pmid: 21073547