Download PDF
CC BY 4.0 · Aorta (Stamford) 2019; 07(02): 035-041
DOI: 10.1055/s-0039-1693468
State-of-the-Art Review
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Fluoroquinolones and Aortic Diseases: Is There a Connection

Davide Carino 
1   Department of Surgery, Aortic Institute at Yale-New Haven, Yale University School of Medicine, New Haven, Connecticut
,
Mohammad A. Zafar
1   Department of Surgery, Aortic Institute at Yale-New Haven, Yale University School of Medicine, New Haven, Connecticut
,
Mrinal Singh
1   Department of Surgery, Aortic Institute at Yale-New Haven, Yale University School of Medicine, New Haven, Connecticut
,
Bulat A. Ziganshin
1   Department of Surgery, Aortic Institute at Yale-New Haven, Yale University School of Medicine, New Haven, Connecticut
,
John A. Elefteriades
1   Department of Surgery, Aortic Institute at Yale-New Haven, Yale University School of Medicine, New Haven, Connecticut
› Author Affiliations Funding None.
Further Information

Publication History

07 May 2017

25 April 2019

Publication Date:
17 September 2019 (online)

   Permissions and Reprints

Abstract

Fluoroquinolones (FQs) are one of the most commonly prescribed classes of antibiotics. Their high tissue distribution and broad-spectrum antibacterial coverage make their use very attractive in numerous infectious diseases. Although generally well tolerated, FQs have been associated with different adverse effects including dysglycemia and arrhythmias. FQs have been also associated with a series of adverse effects related to collagen degradation, such as Achilles tendon rupture and retinal detachment. Recently, an association between consumption of FQs and increased risk of aortic aneurysm and dissection has been proposed. This article reviews the pathogenesis of thoracic aortic diseases, the molecular mechanism of FQ-associated collagen toxicity, and the possible contribution of FQs to aortic diseases.

Keywords

aortic disease - aortic dissection - fluoroquinolones
 

  • References

  • 1 Zhanel GG, Walkty A, Vercaigne L. , et al. The new fluoroquinolones: a critical review. Can J Infect Dis 1999; 10 (03) 207-238
    PubMedGoogle Scholar
  • 2 Zhanel GG, Ennis K, Vercaigne L. , et al. A critical review of the fluoroquinolones: focus on respiratory infections. Drugs 2002; 62 (01) 13-59
    CrossrefPubMedGoogle Scholar
  • 3 Linder JA, Huang ES, Steinman MA, Gonzales R, Stafford RS. Fluoroquinolone prescribing in the United States: 1995 to 2002. Am J Med 2005; 118 (03) 259-268
    CrossrefPubMedGoogle Scholar
  • 4 Mamdani M, McNeely D, Evans G. , et al. Impact of a fluoroquinolone restriction policy in an elderly population. Am J Med 2007; 120 (10) 893-900
    CrossrefPubMedGoogle Scholar
  • 5 Owens Jr RC, Ambrose PG. Antimicrobial safety: focus on fluoroquinolones. Clin Infect Dis 2005; 41 (Suppl. 02) S144-S157
    CrossrefPubMedGoogle Scholar
  • 6 Falagas ME, Rafailidis PI, Rosmarakis ES. Arrhythmias associated with fluoroquinolone therapy. Int J Antimicrob Agents 2007; 29 (04) 374-379
    CrossrefPubMedGoogle Scholar
  • 7 Bailey RR, Kirk JA, Peddie BA. Norfloxacin-induced rheumatic disease. N Z Med J 1983; 96 (736) 590
    PubMedGoogle Scholar
  • 8 Wise BL, Peloquin C, Choi H, Lane NE, Zhang Y. Impact of age, sex, obesity, and steroid use on quinolone-associated tendon disorders. Am J Med 2012; 125 (12) 1228.e23-1228.e28
    PubMedGoogle Scholar
  • 9 Daneman N, Lu H, Redelmeier DA. Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study. BMJ Open 2015; 5 (11) e010077
    CrossrefPubMedGoogle Scholar
  • 10 van der Linden PD, Sturkenboom MC, Herings RM, Leufkens HM, Rowlands S, Stricker BH. Increased risk of Achilles tendon rupture with quinolone antibacterial use, especially in elderly patients taking oral corticosteroids. Arch Intern Med 2003; 163 (15) 1801-1807
    CrossrefPubMedGoogle Scholar
  • 11 Ponsioen TL, van Luyn MJ, van der Worp RJ, van Meurs JC, Hooymans JM, Los LI. Collagen distribution in the human vitreoretinal interface. Invest Ophthalmol Vis Sci 2008; 49 (09) 4089-4095
    CrossrefPubMedGoogle Scholar
  • 12 Etminan M, Forooghian F, Brophy JM, Bird ST, Maberley D. Oral fluoroquinolones and the risk of retinal detachment. JAMA 2012; 307 (13) 1414-1419
    CrossrefPubMedGoogle Scholar
  • 13 Chui CS, Man KK, Cheng CL. , et al. An investigation of the potential association between retinal detachment and oral fluoroquinolones: a self-controlled case series study. J Antimicrob Chemother 2014; 69 (09) 2563-2567
    CrossrefPubMedGoogle Scholar
  • 14 Lee CC, Lee MT, Chen YS. , et al. Risk of aortic dissection and aortic aneurysm in patients taking oral fluoroquinolone. JAMA Intern Med 2015; 175 (11) 1839-1847
    CrossrefPubMedGoogle Scholar
  • 15 Lee CC, Lee MG, Hsieh R. , et al. Oral fluoroquinolone and the risk of aortic dissection. J Am Coll Cardiol 2018; 72 (12) 1369-1378
    CrossrefPubMedGoogle Scholar
  • 16 Pasternak B, Inghammar M, Svanström H. Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study. BMJ 2018; 360: k678
    PubMedGoogle Scholar
  • 17 O'Brien M. Functional anatomy and physiology of tendons. Clin Sports Med 1992; 11 (03) 505-520
    CrossrefPubMedGoogle Scholar
  • 18 Amiel D, Frank C, Harwood F, Fronek J, Akeson W. Tendons and ligaments: a morphological and biochemical comparison. J Orthop Res 1984; 1 (03) 257-265
    CrossrefPubMedGoogle Scholar
  • 19 Tsai WC, Hsu CC, Chen CP. , et al. Ciprofloxacin up-regulates tendon cells to express matrix metalloproteinase-2 with degradation of type I collagen. J Orthop Res 2011; 29 (01) 67-73
    CrossrefPubMedGoogle Scholar
  • 20 Brinckerhoff CE, Matrisian LM. Matrix metalloproteinases: a tail of a frog that became a prince. Nat Rev Mol Cell Biol 2002; 3 (03) 207-214
    CrossrefPubMedGoogle Scholar
  • 21 Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP. Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol 1997; 74 (02) 111-122
    PubMedGoogle Scholar
  • 22 Mayne R. Collagenous proteins of blood vessels. Arteriosclerosis 1986; 6 (06) 585-593
    PubMedGoogle Scholar
  • 23 Halushka MK. Chapter 13 - Genetic diseases of the aorta (including aneurysms) A2 - Willis, Monte S. In: Homeister JW, Stone JR. , eds. Cellular and Molecular Pathobiology of Cardiovascular Disease. San Diego, CA: Academic Press; 2014: 239-255
    CrossrefGoogle Scholar
  • 24 Humphrey JD. Possible mechanical roles of glycosaminoglycans in thoracic aortic dissection and associations with dysregulated transforming growth factor-β. J Vasc Res 2013; 50 (01) 1-10
    PubMedGoogle Scholar
  • 25 Coady MA, Rizzo JA, Goldstein LJ, Elefteriades JA. Natural history, pathogenesis, and etiology of thoracic aortic aneurysms and dissections. Cardiol Clin 1999; 17 (04) 615-635 , vii.
    CrossrefPubMedGoogle Scholar
  • 26 Koullias G, Modak R, Tranquilli M, Korkolis DP, Barash P, Elefteriades JA. Mechanical deterioration underlies malignant behavior of aneurysmal human ascending aorta. J Thorac Cardiovasc Surg 2005; 130 (03) 677-683
    PubMedGoogle Scholar
  • 27 Ziganshin BA, Elefteriades JA. Yale milestones in reading the playbook of thoracic aortic aneurysms. Conn Med 2012; 76 (10) 589-598
    PubMedGoogle Scholar
  • 28 Scholl FG, Coady MA, Davies R. , et al. Interval or permanent nonoperative management of acute type A aortic dissection. Arch Surg 1999; 134 (04) 402-405 , discussion 405–406
    PubMedGoogle Scholar
  • 29 Albornoz G, Coady MA, Roberts M. , et al. Familial thoracic aortic aneurysms and dissections-incidence, modes of inheritance, and phenotypic patterns. Ann Thorac Surg 2006; 82 (04) 1400-1405
    CrossrefPubMedGoogle Scholar
  • 30 Elefteriades JA. Thoracic aortic aneurysm: reading the enemy's playbook. World J Surg 2008; 32 (03) 366-374
    CrossrefPubMedGoogle Scholar
  • 31 Biddinger A, Rocklin M, Coselli J, Milewicz DM. Familial thoracic aortic dilatations and dissections: a case control study. J Vasc Surg 1997; 25 (03) 506-511
    CrossrefPubMedGoogle Scholar
  • 32 Koullias GJ, Ravichandran P, Korkolis DP, Rimm DL, Elefteriades JA. Increased tissue microarray matrix metalloproteinase expression favors proteolysis in thoracic aortic aneurysms and dissections. Ann Thorac Surg 2004; 78 (06) 2106-2110 , discussion 2110–2111
    CrossrefPubMedGoogle Scholar
  • 33 LeMaire SA, Wang X, Wilks JA. , et al. Matrix metalloproteinases in ascending aortic aneurysms: bicuspid versus trileaflet aortic valves. J Surg Res 2005; 123 (01) 40-48
    CrossrefPubMedGoogle Scholar
  • 34 Ikonomidis JS, Jones JA, Barbour JR. , et al. Expression of matrix metalloproteinases and endogenous inhibitors within ascending aortic aneurysms of patients with bicuspid or tricuspid aortic valves. J Thorac Cardiovasc Surg 2007; 133 (04) 1028-1036
    CrossrefPubMedGoogle Scholar
  • 35 Elefteriades JA, Hatzaras I, Tranquilli MA. , et al. Weight lifting and rupture of silent aortic aneurysms. JAMA 2003; 290 (21) 2803
    CrossrefPubMedGoogle Scholar
  • 36 Hatzaras I, Tranquilli M, Coady M, Barrett PM, Bible J, Elefteriades JA. Weight lifting and aortic dissection: more evidence for a connection. Cardiology 2007; 107 (02) 103-106
    CrossrefPubMedGoogle Scholar
  • 37 Hatzaras IS, Bible JE, Koullias GJ, Tranquilli M, Singh M, Elefteriades JA. Role of exertion or emotion as inciting events for acute aortic dissection. Am J Cardiol 2007; 100 (09) 1470-1472
    CrossrefPubMedGoogle Scholar
  • 38 Williams III RJ, Attia E, Wickiewicz TL, Hannafin JA. The effect of ciprofloxacin on tendon, paratenon, and capsular fibroblast metabolism. Am J Sports Med 2000; 28 (03) 364-369
    CrossrefPubMedGoogle Scholar
  • 39 Shakibaei M, Pfister K, Schwabe R, Vormann J, Stahlmann R. Ultrastructure of Achilles tendons of rats treated with ofloxacin and fed a normal or magnesium-deficient diet. Antimicrob Agents Chemother 2000; 44 (02) 261-266
    CrossrefPubMedGoogle Scholar
  • 40 Sendzik J, Shakibaei M, Schäfer-Korting M, Stahlmann R. Fluoroquinolones cause changes in extracellular matrix, signalling proteins, metalloproteinases and caspase-3 in cultured human tendon cells. Toxicology 2005; 212 (01) 24-36
    CrossrefPubMedGoogle Scholar
  • 41 Sendzik J, Shakibaei M, Schäfer-Korting M, Lode H, Stahlmann R. Synergistic effects of dexamethasone and quinolones on human-derived tendon cells. Int J Antimicrob Agents 2010; 35 (04) 366-374
    CrossrefPubMedGoogle Scholar
  • 42 LeMaire SA, Zhang L, Luo W. , et al. Effect of ciprofloxacin on susceptibility to aortic dissection and rupture in mice. JAMA Surg 2018; 153 (09) e181804
    CrossrefPubMedGoogle Scholar
  • 43 Tam PK, Ho CT. Fluoroquinolone-induced Achilles tendinitis. Hong Kong Med J 2014; 20 (06) 545-547
    CrossrefPubMedGoogle Scholar
  • 44 Corrao G, Zambon A, Bertù L. , et al. Evidence of tendinitis provoked by fluoroquinolone treatment: a case-control study. Drug Saf 2006; 29 (10) 889-896
    CrossrefPubMedGoogle Scholar
  • 45 van der Linden PD, Sturkenboom MC, Herings RM, Leufkens HG, Stricker BH. Fluoroquinolones and risk of Achilles tendon disorders: case-control study. BMJ 2002; 324 (7349): 1306-1307
    CrossrefPubMedGoogle Scholar
  • 46 Schwald N, Debray-Meignan S. Suspected role of ofloxacin in a case of arthralgia, myalgia, and multiple tendinopathy. Rev Rhum Engl Ed 1999; 66 (7-9): 419-421
    PubMedGoogle Scholar
  • 47 Tsai WC, Yang YM. Fluoroquinolone-associated tendinopathy. Chang Gung Med J 2011; 34 (05) 461-467
    PubMedGoogle Scholar
  • 48 Yu C, Giuffre B. Achilles tendinopathy after treatment with fluoroquinolone. Australas Radiol 2005; 49 (05) 407-410
    CrossrefPubMedGoogle Scholar
  • 49 Khaliq Y, Zhanel GG. Fluoroquinolone-associated tendinopathy: a critical review of the literature. Clin Infect Dis 2003; 36 (11) 1404-1410
    CrossrefPubMedGoogle Scholar
  • 50 Kuo SC, Chen YT, Lee YT. , et al. Association between recent use of fluoroquinolones and rhegmatogenous retinal detachment: a population-based cohort study. Clin Infect Dis 2014; 58 (02) 197-203
    CrossrefPubMedGoogle Scholar
  • 51 Akhtar S, Meek KM, James V. Ultrastructure abnormalities in proteoglycans, collagen fibrils, and elastic fibers in normal and myxomatous mitral valve chordae tendineae. Cardiovasc Pathol 1999; 8 (04) 191-201
    CrossrefPubMedGoogle Scholar
  • 52 Akhtar S, Meek KM, James V. Immunolocalization of elastin, collagen type I and type III, fibronectin, and vitronectin in extracellular matrix components of normal and myxomatous mitral heart valve chordae tendineae. Cardiovasc Pathol 1999; 8 (04) 203-211
    CrossrefPubMedGoogle Scholar
  • 53 Moesgaard SG, Aupperle H, Rajamäki MM. , et al. Matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and transforming growth factor-β (TGF-β) in advanced canine myxomatous mitral valve disease. Res Vet Sci 2014; 97 (03) 560-567
    CrossrefPubMedGoogle Scholar
  • 54 Aupperle H, Thielebein J, Kiefer B. , et al. Expression of genes encoding matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in normal and diseased canine mitral valves. J Comp Pathol 2009; 140 (04) 271-277
    CrossrefPubMedGoogle Scholar
  • 55 Balistreri CR, Allegra A, Crapanzano F. , et al. Associations of rs3918242 and rs2285053 MMP-9 and MMP-2 polymorphisms with the risk, severity, and short- and long-term complications of degenerative mitral valve diseases: a 4.8-year prospective cohort study. Cardiovasc Pathol 2016; 25 (05) 362-370
    CrossrefPubMedGoogle Scholar
  • 56 Dreger SA, Taylor PM, Allen SP, Yacoub MH. Profile and localization of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in human heart valves. J Heart Valve Dis 2002; 11 (06) 875-880 , discussion 880
    PubMedGoogle Scholar
  • 57 Icardo JM, Colvee E, Revuelta JM. Structural analysis of chordae tendineae in degenerative disease of the mitral valve. Int J Cardiol 2013; 167 (04) 1603-1609
    CrossrefPubMedGoogle Scholar
  • 58 Information for Healthcare Professionals: Fluoroquinolone Antimicrobial Drugs [ciprofloxacin (marketed as Cipro and generic ciprofloxacin), ciprofloxacin extended-release (marketed as Cipro XR and Proquin XR), gemifloxacin (marketed as Factive), levofloxacin (marketed as Levaquin), moxifloxacin (marketed as Avelox), norfloxacin (marketed as Noroxin), and ofloxacin (marketed as Floxin)]. 2016 http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm126085.htm . (Accessed January 16, 2016)
    PubMed
  • 59 European Medicines Agency Pharmacovigilance Risk Assessment Committee. Recommendation on Signals. 2018 https://www.ema.europa.eu/documents/prac-recommendation/prac-recommendations-signals-adopted-3-6-september-2018-prac-meeting_en-0.pdf . (Accessed February 18, 2019)
    PubMed
  • 60 US Food and Drug Administration. Safety Announcement. 2018 https://www.fda.gov/Drugs/DrugSafety/ucm628753.htm . (Accessed February 18, 2019)
    PubMed