Emergence of Multi-Antibiotic Resistance of Conjunctival Flora: A Prospective, Controlled, Longitudinal Study of Patients Undergoing Intravitreal Injections

Abstract

Purpose: : Intravitreal (IVT) injection is an increasingly prevalent cause of endophthalmitis. Antibiotics are frequently used to prevent infection. This study’s intent was to determine changes in antibiotic susceptibility and emergence of multi-antibiotic resistance of Staphylococcus epidermidis from individuals undergoing serial IVT injections for choroidal neovascularization (CNV).

Methods: : This was a prospective, controlled, longitudinal study of 48 eyes of 24 patients undergoing serial IVT injections for CNV. All subjects received 4 consecutive monthly unilateral IVT injections and then were treated as needed. Subjects were randomly assigned 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 cultures of the treated and untreated (control) fellow eye were taken at baseline and after each injection for 1 year. Bacterial isolates were tested for susceptibility against 16 antibiotics.

Results: : After 4 consecutive injections, a total of 58 isolates of S. epidermidis were each isolated from control and treated eyes. Resistance to ≥ 3 antibiotics was present in 69% of S. epidermidis isolated from control eyes compared to 90% from treated eyes (P = 0.01). A total of 46 and 38 isolates of S. epidermidis were cultured from control and treated eyes respectively from their 5^th until final injection. Resistance to ≥ 5 antibiotics was present in 48% of control eyes compared to 71% of treated eyes (P < 0.05). A significant number of fluoroquinolone-treated eyes developed S. epidermidis resistant to 3^rd (P < 0.01) and 4^th (P < 0.01) generation fluoroquinolones compared to control eyes and also developed resistance to trimethoprim/sulfamethoxazole (P < 0.01), gentamicin (P = 0.04), and clindamycin (P = 0.03). Similarly, a significant number of azithromycin-treated eyes developed S. epidermidis resistant to macrolides (P < 0.01) in addition to trimethoprim/sulfamethoxazole (P < 0.01) and doxycycline (P < 0.01).

Conclusions: : Conjunctival S. epidermidis repeatedly exposed to fluoroquinolone or azithromycin antibiotics rapidly developed fluoroquinolone or macrolide resistance, respectively. Resistance to other antibiotics and emergence of multi-antibiotic resistance was also observed.

Clinical Trial: : http://www.clinicaltrials.gov 00831961

Keywords: endophthalmitis • antibiotics/antifungals/antiparasitics • age-related macular degeneration