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The clinical treatment of bacterial keratitis: A review of drop instillation regimes

  • John G Pearce
    Correspondence
    Corresponding author.
    Affiliations
    John Curtin School of Medical Research, Australian National University (ANU), 131 Garran Rd, Acton, ACT 2601, Australia
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  • Rohan W Essex
    Affiliations
    Academic Unit of Ophthalmology, ANU Medical School, Building 4, The Canberra Hospital, Garran, Canberra, ACT 2065, Australia

    Department of Ophthalmology, Canberra Hospital, 15 Hospital Road, Garran, Canberra, ACT 2065, Australia

    Royal Victorian Eye and Ear Hospital, 32 Gisbourne Street, East Melbourne, Melbourne, VIC 3002, Australia
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  • Ted Maddess
    Affiliations
    John Curtin School of Medical Research, Australian National University (ANU), 131 Garran Rd, Acton, ACT 2601, Australia
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      Abstract

      Bacterial keratitis (BK) presentations are often treated using the commercially available second-generation fluoroquinolones ciprofloxacin 0.3% and ofloxacin 0.3% as monotherapy. The guidelines available for instillation regimes are often not supported by data from clinical studies.
      This review examines the peer-reviewed clinical studies and compared treatment failure rates for ciprofloxacin 0.3% and ofloxacin 0.3% for BK in relation to Day-1 drop-regimes. From the statistical analysis, this review derived evidence-based clinically applicable minimum drop-regimes for the treatment of BK on Day-1.
      Lower numbers of drops of ciprofloxacin on Day-1 were significantly associated with increased treatment failure rates (p < 0.002). The derived minimum number of drops on Day for ciprofloxacin on Day-1 was 47 drops, and for ofloxacin 24 drops. The mean number of drops used in the clinical studies was significantly lower than the manufacturers’ recommended Day-1 regimes for both ciprofloxacin (p = 0.0006) and ofloxacin (p = 0.048). From Day-3 to −6 of treatment the drop rates for ciprofloxacin relative to recommended rates were higher, and for ofloxacin lower (p = 0.014).
      The findings of this review were then compared with a representative sample of published guidelines and case studies to determine the validity of applying those drop-regimes in clinical practice. Although the manufacturers’ suggested minimum drop-regimes on Day-1 were significantly different (120 drops ciprofloxacin, 34 drops ofloxacin, p < 0.0001), many of the published guidelines suggested the same drop-regime for both fluoroquinolones. The suggested drop numbers on Day-1 for ciprofloxacin in these guidelines and case studies were significantly less than those used in the clinical studies (p = 0.043).
      Increased treatment failure rates for ciprofloxacin are associated with lower drop numbers on Day-1. The Day-1 dosing rates for ciprofloxacin and ofloxacin should be considered separately, and the regimes suggested in published guidelines and case studies may need be re-considered in light of the findings of this review.

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      References

        • Constantinou M.
        • Jhanji V.
        • Tao L.W.
        • Vajpayee R.B.
        Clinical review of corneal ulcers resulting in evisceration and enucleation in elderly population.
        Graefes Arch Clin Exp Ophthalmol. 2009; 247: 1389-1393https://doi.org/10.1007/s00417-009-1111-9
        • Green M.
        • Carnt N.
        • Apel A.
        • Stapleton F.
        Queensland microbial keratitis database: 2005–2015.
        Br J Ophthalmol. 2019; 103: 1481-1486https://doi.org/10.1136/bjophthalmol-2018-312881
        • Prajna N.V.
        • George C.
        • Selvaraj S.
        • Lu K.L.
        • McDonnell P.J.
        • Srinivasan M.
        Bacteriologic and clinical efficacy of ofloxacin 0.3% versus ciprofloxacin 0.3% ophthalmic solutions in the treatment of patients with culture-positive bacterial keratitis.
        Cornea. 2001; 20: 175-178https://doi.org/10.1097/00003226-200103000-00013
        • Allan B.D.
        • Dart J.K.
        Strategies for the management of microbial keratitis.
        Br J Ophthalmol. 1995; 79: 777-786https://doi.org/10.1136/bjo.79.8.777
        • McDonald E.M.
        • Ram F.S.
        • Patel D.V.
        • McGhee C.N.
        Topical antibiotics for the management of bacterial keratitis: an evidence-based review of high quality randomised controlled trials.
        Br J Ophthalmol. 2014; 98: 1470-1477https://doi.org/10.1136/bjophthalmol-2013-304660
      1. Ciloxan Eye drops 0.3% (Ciprofloxacin hydrochloride) Consumer Medicine Information. Novartis Pharmaceuticals Australia Pty Limited. 2021.

      2. Australian Product Information. Ocuflox (Ofloxacin) eye drops (3mg/ml ofloxacin). Allergan Australia. 2021.

        • Kosrirukvongs P.
        • Buranapongs W.
        Topical ciprofloxacin for bacterial corneal ulcer.
        J Med Assoc Thai. 2000; 83: 776-782
        • Leibowitz H.M.
        Clinical evaluation of ciprofloxacin 0.3% ophthalmic solution for treatment of bacterial keratitis.
        Am J Ophthalmol. 1991; 112: 34S-47S
      3. Hyndiuk RA, Eiferman RA, Caldwell DR, Rosenwasser GO, Santos CI, Katz HR, et al. Comparison of ciprofloxacin ophthalmic solution 0.3% to fortified tobramycin-cefazolin in treating bacterial corneal ulcers. Ciprofloxacin Bacterial Keratitis Study Group. Ophthalmology 1996;103(11):1854-62; discussion 62-3. https://doi.org/10.1016/s0161-6420(96)30416-8.

        • Isenberg S.J.
        • Apt L.
        • Valenton M.
        • Sharma S.
        • Garg P.
        • Thomas P.A.
        • et al.
        Prospective, randomized clinical trial of povidone-iodine 1.25% solution versus topical antibiotics for treatment of bacterial keratitis.
        Am J Ophthalmol. 2017; 176: 244-253https://doi.org/10.1016/j.ajo.2016.10.004
        • Parmar P.
        • Salman A.
        • Kalavathy C.M.
        • Kaliamurthy J.
        • Prasanth D.A.
        • Thomas P.A.
        • et al.
        Comparison of topical gatifloxacin 0.3% and ciprofloxacin 0.3% for the treatment of bacterial keratitis.
        Am J Ophthalmol. 2006; 141: 282-286https://doi.org/10.1016/j.ajo.2005.08.081
        • Constantinou M.
        • Daniell M.
        • Snibson G.R.
        • Vu H.T.
        • Taylor H.R.
        Clinical efficacy of moxifloxacin in the treatment of bacterial keratitis: a randomized clinical trial.
        Ophthalmology. 2007; 114: 1622-1629https://doi.org/10.1016/j.ophtha.2006.12.011
        • Panda A.
        • Ahuja R.
        • Sastry S.S.
        Comparison of topical 0.3% ofloxacin with fortified tobramycin plus cefazolin in the treatment of bacterial keratitis.
        Eye (Lond). 1999; 13: 744-747https://doi.org/10.1038/eye.1999.220
      4. Ofloxacin monotherapy for the primary treatment of microbial keratitis: a double-masked, randomized, controlled trial with conventional dual therapy. The Ofloxacin Study Group. Ophthalmology 1997;104(11):1902-9, https://www.ncbi.nlm.nih.gov/pubmed/9373124.

      5. Bacterial Keratitis Preferred Practice Pattern. American Academy of Ophthalmology Preferred Practice Pattern Cornea and External Disease Panel. Ophthalmology 2019;126(1):1 - 55.

      6. Microbial keratitis Clinical Pratcice Guideline, The Royal Victorian Eye and Ear Hospital. Dr Elise Chan and the Clinical Practice Guidelines Working Party. 2021.

      7. Clinical Practice Guide for the Diagnosis, Treatment and Management of Anterior Eye Conditions. Optometry Australia 2018.

        • Diec J.
        • Carnt N.
        • Tilia D.
        • Evans V.
        • Rao V.
        • Ozkan J.
        • et al.
        Prompt diagnosis and treatment of microbial keratitis in a daily wear lens.
        Optom Vis Sci. 2009; 86: E904-E907https://doi.org/10.1097/OPX.0b013e3181ae0084
        • Meyer J.J.
        • McGhee C.N.
        Acute corneal hydrops complicated by microbial keratitis: case series reveals poor immediate and long-term prognosis.
        Cornea. 2016; 35: 1019-1022https://doi.org/10.1097/ICO.0000000000000883
        • Barker N.H.
        • Thompson J.M.
        • Mullen M.G.
        • Weekes M.A.
        • Nguyen L.N.
        • Haynes C.K.
        • et al.
        Rhizobium radiobacter: a recently recognized cause of bacterial keratitis.
        Cornea. 2016; 35: 679-682https://doi.org/10.1097/ICO.0000000000000780
        • Yip H.
        • Whiting M.
        Kingella kingae microbial keratitis in a human immunodeficiency virus patient with orthokeratology lens wear.
        Clin Exp Ophthalmol. 2017; 45: 420-421https://doi.org/10.1111/ceo.12900
      8. Gentle A. Back to school on ocular therapeutics: Considerations in the use of antimicrobials and anti-inflammatories. Southern Regional Conference, Online lecture presentation, September 2021. 2021.

      9. Corneal Guidelines, Sussex Eye Hospital.

      10. Therapeutic guidelines for the treatment of bacterial keratitis. eTG complete. Therapeutic Guidelines (Antibiotics: Bacterial keratitis). 2019.

      11. Eye Wiki (Bacterial keratitis) American Academy of Ophthalmology 2021; March.

        • Carnt N.
        • Samarawickrama C.
        • White A.
        • Stapleton F.
        The diagnosis and management of contact lens-related microbial keratitis.
        Clin Exp Optom. 2017; 100: 482-493https://doi.org/10.1111/cxo.12581
        • Pearce J.G.
        • Essex R.W.
        • Maddess T.
        Topical chloramphenicol usage in Australia pre- and post-rescheduling as a non-prescription medication.
        Clin Exp Ophthalmol. 2021; https://doi.org/10.1111/ceo.13963
        • McDerby N.
        • Watson S.L.
        • Robaei D.
        • Naunton M.
        Inappropriate use of topical chloramphenicol results in vision loss.
        Clin Exp Ophthalmol. 2015; 43: 192-193https://doi.org/10.1111/ceo.12465
        • Wilhelmus K.R.
        • Abshire R.L.
        • Schlech B.A.
        Influence of fluoroquinolone susceptibility on the therapeutic response of fluoroquinolone-treated bacterial keratitis.
        Arch Ophthalmol. 2003; 121: 1229-1233https://doi.org/10.1001/archopht.121.9.1229
        • Wilhelmus K.R.
        • Hyndiuk R.A.
        • Caldwell D.R.
        • Abshire R.L.
        • Folkens A.T.
        • Godio L.B.
        0.3% ciprofloxacin ophthalmic ointment in the treatment of bacterial keratitis. The ciprofloxacin ointment/bacterial keratitis study group.
        Arch Ophthalmol. 1993; 111: 1210-1218https://doi.org/10.1001/archopht.1993.01090090062020
        • Tsai A.C.
        • Tseng M.C.
        • Chang S.W.
        • Hu F.R.
        Clinical evaluation of ciprofloxacin ophthalmic solution in the treatment of refractory bacterial keratitis.
        J Formos Med Assoc. 1995; 94: 760-764
        • Sharma V.
        • Sharma S.
        • Garg P.
        • Rao G.N.
        Clinical resistance of Staphylococcus keratitis to ciprofloxacin monotherapy.
        Indian J Ophthalmol. 2004; 52: 287-292
        • Ly C.N.
        • Pham J.N.
        • Badenoch P.R.
        • Bell S.M.
        • Hawkins G.
        • Rafferty D.L.
        • et al.
        Bacteria commonly isolated from keratitis specimens retain antibiotic susceptibility to fluoroquinolones and gentamicin plus cephalothin.
        Clin Exp Ophthalmol. 2006; 34: 44-50https://doi.org/10.1111/j.1442-9071.2006.01143.x
        • Booranapong W.
        • Kosrirukvongs P.
        • Prabhasawat P.
        • Srivannaboon S.
        • Suttiprakarn P.
        Comparison of topical lomefloxacin 0.3 per cent versus topical ciprofloxacin 0.3 per cent for the treatment of presumed bacterial corneal ulcers.
        J Med Assoc Thai. 2004; 87: 246-254
        • Al-Shakarchi F.
        Initial therapy for suppurative microbial keratitis in Iraq.
        Br J Ophthalmol. 2007; 91: 1583-1587https://doi.org/10.1136/bjo.2007.123208
        • Parks D.J.
        • Abrams D.A.
        • Sarfarazi F.A.
        • Katz H.R.
        Comparison of topical ciprofloxacin to conventional antibiotic therapy in the treatment of ulcerative keratitis.
        Am J Ophthalmol. 1993; 115: 471-477https://doi.org/10.1016/s0002-9394(14)74449-6
        • Khokhar S.
        • Sindhu N.
        • Mirdha B.R.
        Comparison of topical 0.3% ofloxacin to fortified tobramycin-cefazolin in the therapy of bacterial keratitis.
        Infection. 2000; 28: 149-152https://doi.org/10.1007/s150100050068
      12. MIMS Australia 2021. Ciloxan Eye Drops.

      13. MIMS Australia 2021. Ocuflox eye drops.

        • O'Brien T.P.
        • Maguire M.G.
        • Fink N.E.
        • Alfonso E.
        • McDonnell P.
        Efficacy of ofloxacin vs cefazolin and tobramycin in the therapy for bacterial keratitis. Report from the Bacterial Keratitis Study Research Group.
        Arch Ophthalmol. 1995; 113: 1257-1265https://doi.org/10.1001/archopht.1995.01100100045026
        • Butler T.K.
        • Spencer N.A.
        • Chan C.C.
        • Singh Gilhotra J.
        • McClellan K.
        Infective keratitis in older patients: a 4 year review, 1998–2002.
        Br J Ophthalmol. 2005; 89: 591-596https://doi.org/10.1136/bjo.2004.049072