title: Ophthalmic antibiotic use and multidrug-resistant staphylococcus epidermidis: a controlled, longitudinal study.
abstract: OBJECTIVE
  To analyze the emergence of multidrug-resistant Staphylococcus epidermidis after repeated conjunctival exposure to topical macrolide or fluoroquinolone antibiotics.
  
  
  METHODS
  Prospective, controlled, longitudinal study with 1-year follow-up.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors.affiliation: Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Sarita B
authors.initials: SB
authors.lastname: Dave
authors.forename: Hassanain S
authors.initials: HS
authors.lastname: Toma
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001372:Aza Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D017963:Azithromycin / Q000008:administration & dosage / Q000627:therapeutic use; D020256:Choroidal Neovascularization / Q000188:drug therapy*; D003228:Conjunctiva / Q000382:microbiology*; D024901:Drug Resistance, Multiple, Bacterial; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000627:therapeutic use; D005500:Follow-Up Studies; D000077734:Gatifloxacin; D006801:Humans; D058449:Intravitreal Injections; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000008:administration & dosage / Q000627:therapeutic use; D011446:Prospective Studies; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000302:isolation & purification*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D017963:Azithromycin; D015242:Ofloxacin; D000077734:Gatifloxacin; D000077266:Moxifloxacin