Skip to main content
SpringerLink
Log in

Moxifloxacin intrakameral: Eine sichere Option zur Endophthalmitisprophylaxe?

In-vitro-Sicherheitsprofil zur intraokularen Anwendung

Intracameral moxifloxacin: a safe option for endophthalmitis prophylaxis?

In vitro safety profile for intraocular application

  • Originalien
  • Published:
Der Ophthalmologe Aims and scope Submit manuscript

Zusammenfassung

Hintergrund

Die Wirksamkeit von Moxifloxacin (Vigamox®) umfasst die meisten für bakterielle Endophthalmitiden verantwortlichen Keime. Die systemische und topische Anwendung von Moxifloxacin ist erprobt, es gibt aber bisher nur wenig Erfahrung über die Sicherheit bei der intrakameralen Anwendung zur Vorbeugung der bakteriellen Endophthalmitis.

Methoden

Die Endotheltoxizität von Moxifloxacin (Vigamox®) wurde an humanen, kultivierten Spenderhornhäuten untersucht. Primäre humane retinale Pigmentepithelzellen (RPE), Trabekelmaschenwerkzellen (TMC), humane Linsenepithelzellen (LEC) und korneale Endothelzellen (CEC) wurden mit Vigamox® in unterschiedlichen Konzentrationen (10–750 µg/ml Moxifloxacin) behandelt. Mögliche toxische Effekte wurden nach 24 h untersucht (MTT-Assay, Live-Dead-Assay). Um die Sicherheit von Vigamox® im entzündeten Auge zu untersuchen, wurden die Zellen zusätzlich oxidativem Stress und proinflammatorischen Zytokinen (TNF-α, LPS und IL-6) ausgesetzt.

Ergebnisse

Nach 30 Tagen Behandlung mit 500 µg/ml Moxifloxacin zeigte sich kein Hinweis auf endotheliale Toxizität an Spenderhornhäuten. Bis zu einer Konzentration von 150 µg/ml Moxifloxacin zeigten sich bei keiner der untersuchten Zelllinien Hinweise auf Toxizität. Auch in Anwesenheit von oxidativem Stress und proinflammtorischen Zytokinen wurde bis zu einer Konzentration von 150 µg/ml Moxifloxacin keine signifikante Zunahme der toxischen Effekte beobachtet.

Zusammenfassung

Diese Studie zeigt, dass Vigamox® (Moxifloxacin) bis zu einer Konzentration von 150 µg/ml keine toxische Wirkung auf CEC-, TMC-, LEC- und RPE-Zellen hat. Die MIC90 von Moxifloxacin für die häufigsten Erreger der bakteriellen Endophthalmitis liegt zwischen 0,25 mg/ml und 2,5 µg/ml. Daher erscheint die intrakamerale Injektion von Vigamox® zur Vorbeugung der bakteriellen Endophthalmitis in therapeutischen Konzentrationen sicher.

Abstract

Background

Moxifloxacin (Vigamox®), a 4th-generation fluoroquinolone, covers most isolates causing endophthalmitis. It is safe and effective for systemic and topical use; however, only very limited data are available on prophylactic intracameral administration to prevent endophthalmitis. This study investigated the safety of Vigamox® for intracameral application in a cell-culture model.

Methods

The endothelial toxicity of moxifloxacin (Vigamox®) was evaluated in cultured human corneas. Primary human retinal pigment epithelium cells (RPEs), trabecular meshwork cells (TMCs), lens epithelium cells (LECs), and corneal endothelial cells (CECs) were treated with concentrations of Vigamox. Toxic effects were evaluated after 24 h (MTT assay and live–dead assay). By treating TMC, CEC, and RPE cells either with oxidative stress or tumor necrosis factor-alpha (TNF-a), lipopolysaccharide (LPS), and interleukin-6 (IL-6), the effects of moxifloxacin on cellular viability under conditions of inflammation were investigated.

Results

No corneal endothelial toxicity could be detected after 30 days of treatment with moxifloxacin 500 µg/ml. Primary RPEs, TMCs, LECs, and CECs showed adverse effects on proliferation and viability only at concentrations higher than 150 µg/ml moxifloxacin. After preincubation with TNF-a, LPS, and IL-6 for 24 h and subsequent treatment with moxifloxacin at concentrations of 10–150 µg/ml for 24 h, no significant decrease in proliferation or viability was observed. H2O2 exposure did not increase cellular toxicity

Conclusion

Vigamox® did not show significant toxicity on primary RPEs, TMCs, LECs, CECs, or human corneal endothelium at concentrations up to 150 µg/ml. The MIC90 of moxifloxacin for pathogens commonly encountered in endophthalmitis is known to be in the range of 0.25–2.5 µg/ml. Therefore, intracameral use of Vigamox® at concentrations up to 150 µg/ml may be safe and effective for preventing endophthalmitis after intraocular surgery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5

Literatur

  1. (n a) (2007) Prophylaxis of postoperative endophthalmitis following cataract surgery: results of the ESCRS multicenter study and identification of risk factors. J Cataract Refract Surg 33:978–988

  2. (n a) (1995) Results of the Endophthalmitis Vitrectomy Study. A randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Endophthalmitis Vitrectomy Study Group. Arch Ophthalmol 113:1479–1496

  3. Aaberg TM Jr, Flynn HW Jr, Murray TG (1994) Intraocular ceftazidime as an alternative to the aminoglycosides in the treatment of endophthalmitis. Arch Ophthalmol 112:18–19

    PubMed  Google Scholar 

  4. Aaberg TM Jr, Flynn HW Jr, Schiffman J, Newton J (1998) Nosocomial acute-onset postoperative endophthalmitis survey. A 10-year review of incidence and outcomes. Ophthalmology 105:1004–1010

    Article  PubMed  Google Scholar 

  5. Axer-Siegel R, Stiebel-Kalish H, Rosenblatt I et al (1999) Cystoid macular edema after cataract surgery with intraocular vancomycin. Ophthalmology 106:1660–1664

    Article  CAS  PubMed  Google Scholar 

  6. Aydin E, Kazi AA, Peyman GA, Esfahani MR (2006) Intravitreal toxicity of moxifloxacin. Retina 26:187–190

    Article  PubMed  Google Scholar 

  7. Benz MS, Scott IU, Flynn HW Jr et al (2004) Endophthalmitis isolates and antibiotic sensitivities: a 6-year review of culture-proven cases. Am J Ophthalmol 137:38–42

    Article  PubMed  Google Scholar 

  8. Blondeau JM (2004) Fluoroquinolones: mechanism of action, classification, and development of resistance. Surv Ophthalmol 49(Suppl 2):S73–S78

    Article  PubMed  Google Scholar 

  9. Callegan MC, Ramirez R, Kane ST et al (2003) Antibacterial activity of the fourth-generation fluoroquinolones gatifloxacin and moxifloxacin against ocular pathogens. Adv Ther 20:246–252

    Article  CAS  PubMed  Google Scholar 

  10. Congdon N, Vingerling JR, Klein BE et al (2004) Prevalence of cataract and pseudophakia/aphakia among adults in the United States. Arch Ophthalmol 122:487–494

    Article  PubMed  Google Scholar 

  11. Deramo VA, Lai JC, Fastenberg DM, Udell IJ (2006) Acute endophthalmitis in eyes treated prophylactically with gatifloxacin and moxifloxacin. Am J Ophthalmol 142:721–725

    Article  CAS  PubMed  Google Scholar 

  12. Ermis SS, Cetinkaya Z, Kiyici H et al (2007) Effects of intravitreal moxifloxacin and dexamethasone in experimental Staphylococcus aureus endophthalmitis. Curr Eye Res 32:337–344

    Article  CAS  PubMed  Google Scholar 

  13. Ermis SS, Cetinkaya Z, Kiyici H, Ozturk F (2005) Treatment of Staphylococcus epidermidis endophthalmitis with intravitreal moxifloxacin in a rabbit model. Tohoku J Exp Med 205:223–229

    Article  CAS  PubMed  Google Scholar 

  14. Espiritu CR, Caparas VL, Bolinao JG (2007) Safety of prophylactic intracameral moxifloxacin 0.5% ophthalmic solution in cataract surgery patients. J Cataract Refract Surg 33:63–68

    Article  PubMed  Google Scholar 

  15. Feys J, Emond JP, Salvanet-Bouccara A, Dublanchet A (1994) Interleukin-6 and other cytokines in the aqueous humor in uveitis and endophthalmitis. J Fr Ophtalmol 17:634–639

    CAS  PubMed  Google Scholar 

  16. Gao H, Pennesi ME, Qiao X et al (2006) Intravitreal moxifloxacin: retinal safety study with electroretinography and histopathology in animal models. Invest Ophthalmol Vis Sci 47:1606–1611

    Article  PubMed  Google Scholar 

  17. Giese MJ, Sumner HL, Berliner JA, Mondino BJ (1998) Cytokine expression in a rat model of Staphylococcus aureus endophthalmitis. Invest Ophthalmol Vis Sci 39:2785–2790

    CAS  PubMed  Google Scholar 

  18. Hariprasad SM, Blinder KJ, Shah GK et al (2005) Penetration pharmacokinetics of topically administered 0.5% moxifloxacin ophthalmic solution in human aqueous and vitreous. Arch Ophthalmol 123:39–44

    Article  CAS  PubMed  Google Scholar 

  19. Javitt JC, Street DA, Tielsch JM et al (1994) National outcomes of cataract extraction. Retinal detachment and endophthalmitis after outpatient cataract surgery. Cataract Patient Outcomes Research Team. Ophthalmology 101:100–105; discussion 106

    CAS  PubMed  Google Scholar 

  20. Kattan HM, Flynn HW Jr, Pflugfelder SC et al (1991) Nosocomial endophthalmitis survey. Current incidence of infection after intraocular surgery. Ophthalmology 98:227–238

    CAS  PubMed  Google Scholar 

  21. Kernt M, Neubauer AS, HM DEK, Kampik A (2008) INTRAVITREAL VORICONAZOLE: In Vitro Safety-Profile for Fungal Endophthalmitis. Retina 29:362–370

    Article  Google Scholar 

  22. Kernt M, Neubauer AS, Liegl RG et al (2009) Intracameral Moxifloxacin: In Vitro Safety on Human Ocular Cells. Cornea

  23. Kernt M, Neubauer AS, Ulbig MW et al (2008) In vitro safety of intravitreal moxifloxacin for endophthalmitis treatment. J Cataract Refract Surg 34:480–488

    Article  PubMed  Google Scholar 

  24. Kernt M, Welge-Lussen U, Yu A et al (2007) Bevacizumab is not toxic to human anterior- and posterior-segment cultured cells. Ophthalmologe 104:965–971

    Article  CAS  PubMed  Google Scholar 

  25. Kim SY, Park YH, Lee YC (2008) Comparison of the effect of intracameral moxifloxacin, levofloxacin and cefazolin on rabbit corneal endothelial cells. Clin Experiment Ophthalmol 36:367–370

    Article  PubMed  Google Scholar 

  26. Koss MJ, Eder M, Blumenkranz MS et al (2007) The effectiveness of the new fluoroquinolones against the normal bacterial flora of the conjunctiva. Ophthalmologe 104:21–27

    Article  CAS  PubMed  Google Scholar 

  27. Kowalski RP, Romanowski EG, Mah FS et al (2005) Intracameral Vigamox (moxifloxacin 0.5%) is non-toxic and effective in preventing endophthalmitis in a rabbit model. Am J Ophthalmol 140:497–504

    CAS  PubMed  Google Scholar 

  28. Kunimoto DY, Das T, Sharma S et al (1999) Microbiologic spectrum and susceptibility of isolates: part I. Postoperative endophthalmitis. Endophthalmitis Research Group. Am J Ophthalmol 128:240–242

    Article  CAS  PubMed  Google Scholar 

  29. Kunimoto DY, Sharma S, Garg P, Rao GN (1999) In vitro susceptibility of bacterial keratitis pathogens to ciprofloxacin. Emerging resistance. Ophthalmology 106:80–85

    Article  CAS  PubMed  Google Scholar 

  30. Mamalis N, Edelhauser HF, Dawson DG et al (2006) Toxic anterior segment syndrome. J Cataract Refract Surg 32:324–333

    Article  PubMed  Google Scholar 

  31. Masket S (1998) Preventing, diagnosing, and treating endophthalmitis. J Cataract Refract Surg 24:725–726

    CAS  PubMed  Google Scholar 

  32. Mather R, Karenchak LM, Romanowski EG, Kowalski RP (2002) Fourth generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics. Am J Ophthalmol 133:463–466

    Article  CAS  PubMed  Google Scholar 

  33. McCulley JP, Caudle D, Aronowicz JD, Shine WE (2006) Fourth-generation fluoroquinolone penetration into the aqueous humor in humans. Ophthalmology 113:955–959

    Article  CAS  PubMed  Google Scholar 

  34. Metzler K, Hansen GM, Hedlin P et al (2004) Comparison of minimal inhibitory and mutant prevention drug concentrations of 4 fluoroquinolones against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus. Int J Antimicrob Agents 24:161–167

    Article  CAS  PubMed  Google Scholar 

  35. Miller JJ, Scott IU, Flynn HW Jr et al (2005) Acute-onset endophthalmitis after cataract surgery (2000-2004): incidence, clinical settings, and visual acuity outcomes after treatment. Am J Ophthalmol 139:983–987

    Article  PubMed  Google Scholar 

  36. Mo JS, Streilein JW (2001) Immune privilege persists in eyes with extreme inflammation induced by intravitreal LPS. Eur J Immunol 31:3806–3815

    Article  CAS  PubMed  Google Scholar 

  37. Rossi C, Sternon J (2001) Flouroquinolones of the third and fourth generations. J Pharm Belg 56:137–148

    CAS  PubMed  Google Scholar 

  38. Satofuka S, Ichihara A, Nagai N et al (2006) Suppression of ocular inflammation in endotoxin-induced uveitis by inhibiting nonproteolytic activation of prorenin. Invest Ophthalmol Vis Sci 47:2686–2692

    Article  PubMed  Google Scholar 

  39. Schentag JJ (2002) Pharmacokinetic and pharmacodynamic predictors of antimicrobial efficacy: moxifloxacin and Streptococcus pneumoniae. J Chemother 14(Suppl 2):13–21

    CAS  PubMed  Google Scholar 

  40. Smith A, Pennefather PM, Kaye SB, Hart CA (2001) Fluoroquinolones: place in ocular therapy. Drugs 61:747–761

    Article  CAS  PubMed  Google Scholar 

  41. Thomas J, Kanangat S, Rouse BT (1998) Herpes simplex virus replication-induced expression of chemokines and proinflammatory cytokines in the eye: implications in herpetic stromal keratitis. J Interferon Cytokine Res 18:681–690

    Article  CAS  PubMed  Google Scholar 

  42. Villada JR, Vicente U, Javaloy J, Alio JL (2005) Severe anaphylactic reaction after intracameral antibiotic administration during cataract surgery. J Cataract Refract Surg 31:620–621

    Article  PubMed  Google Scholar 

  43. West ES, Behrens A, McDonnell PJ et al (2005) The incidence of endophthalmitis after cataract surgery among the U.S. Medicare population increased between 1994 and 2001. Ophthalmology 112:1388–1394

    Article  PubMed  Google Scholar 

  44. Yoeruek E, Spitzer MS, Saygili O et al (2008) Comparison of in vitro safety profiles of vancomycin and cefuroxime on human corneal endothelial cells for intracameral use. J Cataract Refract Surg 34:2139–2145

    Article  PubMed  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehung hin: Die Durchführung der Untersuchung wurde durch die ALCON Pharma GmbH, Freiburg, unterstützt.

Author information

Authors and Affiliations

  1. Augenklinik der Ludwig-Maximilians-Universität, Mathildenstraße 8, 80336, München, Deutschland

    M. Kernt, C. Hirneiss, A.S. Neubauer, R.G. Liegl, K.H. Eibl, A. Wolf, H. de Kaspar, M.W. Ulbig & A. Kampik

  2. Department of Ophthalmology, Stanford University School of Medicine, Stanford, CA, USA

    H. de Kaspar

Authors
  1. M. Kernt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Hirneiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A.S. Neubauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R.G. Liegl
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K.H. Eibl
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Wolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H. de Kaspar
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M.W. Ulbig
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A. Kampik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Kernt.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kernt, M., Hirneiss, C., Neubauer, A. et al. Moxifloxacin intrakameral: Eine sichere Option zur Endophthalmitisprophylaxe?. Ophthalmologe 107, 720–727 (2010). https://doi.org/10.1007/s00347-009-2027-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00347-009-2027-9

Schlüsselwörter

Keywords

Search

Navigation