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Toxicity and clearance of intravitreal cefotetan

  • Clinical Investigations
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Abstract

Direct, intravitreal injection of antibiotics plays an important role in the management of bacterial endophthalmitis. In the present study we investigated the toxicity and clearance of intravitreally injected cefotetan in a rabbit model. No toxic ocular side effects could be detected by electroretinography (ERG) or light and electron microscopy up to and including a single intravitreal dose of 1000 μg. Intravitreal injection of 2000 μg cefotetan resulted in mild degeneration of photoreceptor outer segments and, sporadically, in cataract formation. After intravitreal injection of 4000 μg, moderate toxic degeneration of photoreceptors occurred, with displacement and mitochondrial swelling of inner segments. In addition, lysosomal lamellar inclusion bodies could be detected in pigment epithelial cells. After a single intravitreal injection of 1000 μg cefotetan, concentrations greater than the minimum necessary for the inhibition of most commonly occurring intraocular pathogens (exceptPseudomonas aeruginosa andStaphylococcus epidermidis) were maintained in the vitreous humor for > 48 h. Cefotetan may be a potentially important drug for intravitreal injection, especially in cases of gram-negative and suspected anaerobic endophthalmitis.

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References

  1. Affeldt JC, Flynn HW, Forster RK, Mandelbaum S, Clarkson JG, Jarus GD (1987) Microbial endophthalmitis resulting from ocular trauma. Ophthalmology 94:407–413

    PubMed  Google Scholar 

  2. Allen HF, Margiaracine AB (1964) Bacterial endophthalmitis after cataract extraction: a study of 22 infections in 20,000 operations. Arch Ophthalmol 72:454–462

    PubMed  Google Scholar 

  3. Bartlett JG (1983) Recent developments in the management of anaerobic infections. Rev Infect Dis 5:235–245

    PubMed  Google Scholar 

  4. Barza M (1978) Factors affecting the intraocular penetration of antibiotics: the influence of route, inflammation, animal species and tissue pigmentation. Scand J Infect Dis 14 [Suppl]:151–159

    Google Scholar 

  5. Barza M (1980) Treatment of bacterial infections of the eye. In: Remington J, Swartz M (eds) Current clinical topics in infectious disease. McGraw-Hill, New York, pp 158–194

    Google Scholar 

  6. Barza M, Kane A, Baum J (1982) The effects of infection and probenecid on the transport of carbenicillin from the rabbit vitreous humor. Invest Ophthalmol Vis Sci 22:720–726

    PubMed  Google Scholar 

  7. Barza M, Kane A, Baum J (1983) Pharmacokinetics of intravitreal carbenicillin, cefazolin and gentamicin in rhesus monkeys. Invest Ophthalmol Vis Sci 24:1602–1606

    PubMed  Google Scholar 

  8. Bauernfeind A (1983) Cefotetan: profile of in-vitro activity. J Antimicrob Chemother 11 [Suppl A]:19–29

    PubMed  Google Scholar 

  9. Baum I, Peyman GA, Barza M (1982) Intravitreal administration of antibiotics in the treatment of bacterial endophthalmitis: III. Consensus. Surv Ophthalmol 26:204–206

    PubMed  Google Scholar 

  10. Bawdon RE, Crane LR, Palchaudhuri S (1982) Antibiotic resistance in anaerobic bacteria: molecular biology and clinical aspects. Rev Infect Dis 4:1075–1095

    PubMed  Google Scholar 

  11. Böhme H, Hartke K (1978) Europäisches Arzneibuch Band I und Band 11, Kommentar. Wissenschaftliche Verlagsgesellschaft, Stuttgart, pp 178–184

    Google Scholar 

  12. Bohigian GM, Olk RJ (1986) Factors associated with a poor visual result in endophthalmitis. Am J Ophthalmol 101:332–334

    PubMed  Google Scholar 

  13. Brinton GS, Topping TM, Hyndiuk RA, Aaberg TM, Reeser FH, Abrams GW (1984) Posttraumatic endophthalmitis. Arch Ophthalmol 102:547–550

    PubMed  Google Scholar 

  14. Conway BP, Tabatabay CA, Campochiaro PA, D'Amico DJ, Hanninen LA, Kenyon KR (1989) Gentamicin toxicity in the primate retina. Arch Ophthalmol 107:107–112

    PubMed  Google Scholar 

  15. D'Amico DJ, Caspers-Velu L, Libert J, Shanks E, Schrooyen M, Hanninen LA, Kenyon KR (1985) Comparative toxicity of intravitreal aminoglycoside antibiotics. Am J Ophthalmol 100:264–275

    PubMed  Google Scholar 

  16. Declercge SS, Meredith PCA, Rosenthal AR (1977) Experimental siderosis in the rabbit. Correlation between electroretinography and histopathology. Arch Ophthalmol 95:1051–1058

    PubMed  Google Scholar 

  17. Ernest JT (1973) In vivo measurement of optic-disc oxygen tension. Invest Ophthalmol 12:927–931

    PubMed  Google Scholar 

  18. Finegold SM (1977) Anaerobic bacteria in human disease. Academic Press, New York, pp 1–40

    Google Scholar 

  19. Forster RK, Abbott RL, Gelender H (1980) Management of infectious endophthalmitis. Ophthalmology 87:313–318

    PubMed  Google Scholar 

  20. Hattenhauer JM, Lipsich MP (1971) Late endophthalmitis after filtering surgery. Am J Ophthalmol 72:1097–1101

    PubMed  Google Scholar 

  21. Jones DB, Robinson NM (1977) Anaerobic ocular infections. Trans Am Acad Ophthalmol Otolaryngol 83:309–331

    Google Scholar 

  22. Kane A, Barza M, Baum J (1981) Intravitreal injection of gentamicin in rabbits. Effect of inflammation and pigmentation on half-life and ocular distribution. Invest Ophthalmol Vis Sci 20:593–597

    PubMed  Google Scholar 

  23. Kasbeer RT, Peyman GA (1975) Intravitreal oxacillin in experimental staphylococcal endophthalmitis. Graefe's Arch Clin Exp Ophthalmol 196:279–287

    Google Scholar 

  24. Lawwill T (1972) Practical rabbit electroretinography. Am J Ophthalmol 74:135–141

    PubMed  Google Scholar 

  25. Matuura H (1971) Anaerobes in the bacterial flora of the conjunctival sac. Jpn J Ophthalmol 15:116–124

    Google Scholar 

  26. Maurice DM (1976) Injection of drugs into the vitreous body. In: Leopold IH, Burns RP (eds) Symposium on ocular therapy, vol 9. Wiley, New York, pp 59–72

    Google Scholar 

  27. McNatt J, Allen SD, Wilson LA, Dowell VR Jr (1978) Anaerobic flora of the normal human conjunctival sac. Arch Ophthalmol 96:1448–1450

    PubMed  Google Scholar 

  28. Morel C, Vergnaud M, Langeard MM, Dupuy L (1983) Cefotetan: comparative study in vitro against 226 gram-negative clinical isolates. J Antimicrob Chemother 11 [Suppl A]:31–36

    PubMed  Google Scholar 

  29. Nelsen P, Peyman GA, Bennett TO (1974) BB-K8: a new aminoglycoside for intravitreal injection in bacterial endophthalmitis. Am J Ophthalmol 78:82–89

    PubMed  Google Scholar 

  30. Ormerod LD, Paton BG, Haaf J, Topping TM, Baker AS (1987) Anaerobic bacterial endophthalmitis. Ophthalmology 94:799–808

    PubMed  Google Scholar 

  31. Perkins RE, Kundsin RB, Pratt MV, Abrahamsen I, Leibowitz HM (1975) Bacteriology of normal and infected conjunctiva. J Clin Microbiol 1:147–149

    PubMed  Google Scholar 

  32. Peyman GA (1977) Antibiotic administration in the treatment of bacterial endophthalmitis: II. Intravitreal injections. Surv Ophthalmol 21:332, 339–346

    Google Scholar 

  33. Peyman GA, Vastine DW, Crouch ER, Herbst RW (1974) Clinical use of intravitreal antibiotics to treat bacterial endophthalmitis. Trans Am Acad Ophthalmol Otolaryngol 78:862–875

    Google Scholar 

  34. Peyman GA, Vastine DW, Meisels HI (1975) The experimental and clinical use of intravitreal antibiotics to treat bacterial and fungal endophthalmitis. Doc Ophthalmol 39:183–201

    PubMed  Google Scholar 

  35. Phillips I, King A, Shannon K, Warren C (1983) Cefotetan: in-vitro antibacterial activity and susceptibility toß-lactamases. J Antimicrob Chemother 11 [Suppl A]:1–9

    Google Scholar 

  36. Puliafito CA, Baker AS, Haaf J, Foster CS (1982) Infectious endophthalmitis. Review of 36 cases. Ophthalmology 89:921–929

    PubMed  Google Scholar 

  37. Ruckdeschel G (1983) Activity in vitro of cefotetan against non-sporing anaerobes: a comparative study. J Antimicrob Chemother 11 [Suppl A]: 117–124

    PubMed  Google Scholar 

  38. Rutgard JJ, Berkowitz RA, Peyman GA (1978) Intravitreal cephalothin in experimental endophthalmitis. Ann Ophthalmol 10:293–298

    PubMed  Google Scholar 

  39. Sasovetz D (1978) Ketamine hydrochloride: an effective general anesthetic for use in electroretinography. Ann Ophthalmol 10:1510–1514

    PubMed  Google Scholar 

  40. Schenk AG, Peyman GA, Paque JT (1974) The intravitreal use of carbenicillin (Geopen) for treatment ofPseudomonas endophthalmitis. Acta Ophthalmol (Cophenh) 52:707–717

    Google Scholar 

  41. Toda M, Saito T, Yano K, Suzaki K, Saito M, Mitsuhashi S (1980) In vitro and in vivo antibacterial activities of YM 09330, a new cephamycin derivative. In: (Nelson JD, Grassi CC (eds)) Current chemotherapy and infectious disease, vol. 1. American Society of Microbiology, Washington, D.C., pp 280–281

    Google Scholar 

  42. Tsacopoulos M, Baker R, Levy S (1976) Studies on retinal oxygenation. In: Grote J, Reneau D, Thews G (eds) International symposium on oxygen transport to tissue II. New York, Plenum Press, pp 413–416 (Advances in experimental biology and medicine series, vol 75.

    Google Scholar 

  43. Waring GO (1977) Antibiotic administration in the treatment of bacterial endophthalmitis. Surv Ophthalmol 21:332–346

    Google Scholar 

  44. Werner H (1983) Inhibitory activity of cefotetan and otherß-lactams against anaerobes. J Antimicrob Chemother 11 [Suppl A]:107–115

    PubMed  Google Scholar 

  45. Wise R, Andrews JM, Hancox J (1982) In vitro activity of cefotetan, a new cephamycin derivative, compared with that of otherß-lactam compounds. Antimicrob Agents Chemother 21:486–491

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Universitäts-Klinik für Augenheilkunde, Anichstrasse 35, A-6020, Innsbruck, Austria

    Wolfgang Philipp, Beata Pümpel, Hans Peter Aichberger & Wolfgang Mayer

  2. Institut für pathologische Anatomic der Universität, Müllerstrasse 44, A-6020, Innsbruck, Austria

    Kurt Schmid & Hans Jörg Steiner

  3. Institut für Hygiene der Universitat, Fritz-Pregl-Strasse 3, A-6020, Innsbruck, Austria

    Franz Allerberger

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  1. Wolfgang Philipp
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  2. Kurt Schmid
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  3. Hans Jörg Steiner
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  4. Beata Pümpel
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  5. Franz Allerberger
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  6. Hans Peter Aichberger
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  7. Wolfgang Mayer
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Philipp, W., Schmid, K., Steiner, H.J. et al. Toxicity and clearance of intravitreal cefotetan. Graefe's Arch Clin Exp Ophthalmol 228, 475–480 (1990). https://doi.org/10.1007/BF00927265

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  • DOI: https://doi.org/10.1007/BF00927265

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