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

  • John G Pearce
    Corresponding author.
    John Curtin School of Medical Research, Australian National University (ANU), 131 Garran Rd, Acton, ACT 2601, Australia
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  • Rohan W Essex
    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
    John Curtin School of Medical Research, Australian National University (ANU), 131 Garran Rd, Acton, ACT 2601, Australia
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      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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