Ophthalmic antibiotic use and multidrug-resistant staphylococcus epidermidis: a controlled, longitudinal study

Ophthalmology. 2011 Oct;118(10):2035-40. doi: 10.1016/j.ophtha.2011.03.017.


Purpose: To analyze the emergence of multidrug-resistant Staphylococcus epidermidis after repeated conjunctival exposure to topical macrolide or fluoroquinolone antibiotics.

Design: Prospective, controlled, longitudinal study with 1-year follow-up.

Participants: Forty-eight eyes of 24 patients undergoing serial unilateral intravitreal (IVT) injections for choroidal neovascularization.

Methods: Subjects received 4 consecutive monthly unilateral IVT injections and then were treated as needed. Each subject was assigned randomly to 1 of 4 antibiotics (azithromycin 1%, gatifloxacin 0.3%, moxifloxacin 0.5%, ofloxacin 0.3%) and used only their assigned antibiotic after each injection. Conjunctival culture specimens of the treated and untreated fellow eye (control) were obtained at baseline and after each injection. All bacterial isolates were tested for antibiotic susceptibility to 16 different antibiotics using the Kirby-Bauer disc diffusion technique.

Main outcome measures: Antibiotic susceptibility patterns and multidrug resistance of S. epidermidis.

Results: After 4 consecutive treatments, a total of 58 isolates of S. epidermidis each were isolated from control and treated eyes. Resistance to 3 or more antibiotics was present in 69% of S. epidermidis isolated from control eyes compared with 90% from treated eyes (P<0.02). A total of 46 and 38 isolates of S. epidermidis were cultured from control and treated eyes, respectively, from the fifth until the final injection. Resistance to 5 or more antibiotics was present in 48% of control eyes compared with 71% of treated eyes (P<0.05). In a significant number of fluoroquinolone-treated eyes, S. epidermidis developed resistance to third-generation (P<0.01) and fourth-generation (P<0.01) fluoroquinolones compared with control eyes. In addition, these organisms developed resistance to trimethoprim/sulfamethoxazole (P<0.01), gentamicin (P<0.03), and clindamycin (P<0.05). Similarly, a significant number of azithromycin-treated eyes developed S. epidermidis resistant to macrolides (P<0.01) compared with control eyes and also developed increased resistance to trimethoprim/sulfamethoxazole (P<0.02) and doxycycline (P<0.01).

Conclusions: Conjunctival S. epidermidis repeatedly exposed to fluoroquinolone or azithromycin antibiotics rapidly develop resistance. Coresistance to other antibiotics also was observed.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / therapeutic use*
  • Aza Compounds / administration & dosage
  • Aza Compounds / therapeutic use
  • Azithromycin / administration & dosage
  • Azithromycin / therapeutic use
  • Choroidal Neovascularization / drug therapy*
  • Conjunctiva / microbiology*
  • Drug Resistance, Multiple, Bacterial*
  • Fluoroquinolones / administration & dosage
  • Fluoroquinolones / therapeutic use
  • Follow-Up Studies
  • Gatifloxacin
  • Humans
  • Intravitreal Injections
  • Microbial Sensitivity Tests
  • Moxifloxacin
  • Ofloxacin / administration & dosage
  • Ofloxacin / therapeutic use
  • Prospective Studies
  • Quinolines / administration & dosage
  • Quinolines / therapeutic use
  • Staphylococcus epidermidis / drug effects
  • Staphylococcus epidermidis / isolation & purification*
  • Young Adult


  • Anti-Bacterial Agents
  • Aza Compounds
  • Fluoroquinolones
  • Quinolines
  • Azithromycin
  • Ofloxacin
  • Gatifloxacin
  • Moxifloxacin