Ocular TRUST 3: Ongoing Longitudinal Surveillance of Antimicrobial Susceptibility in Ocular Isolates

1. Ocular TRUST 3: Ongoing Longitudinal Surveillance of Antimicrobial Susceptibility in Ocular Isolates • Financial Disclosures • Dr. Asbell has served as a consultant to Inspire Pharmaceuticals and Vistakon Pharmaceuticals; has received lecture fees from Alcon Laboratories, Allergan Pharmaceuticals, Inspire Pharmaceuticals, Santen Pharmaceuticals, and Vistakon Pharmaceuticals; and has received grant support from Allergan Pharmaceuticals and Inspire Pharmaceuticals • Dr. Sahm has nothing to disclose • Dr. Shedden is an employee of Vistakon Pharmaceuticals, LLC Penny A. Asbell, MD, FACS, MBA1; Daniel F. Sahm, PhD2; and Arthur Shedden, MD3 for the Ocular TRUST Study Group 1Mount Sinai School of Medicine; 2Eurofins Medinet Anti-Infective Services; 3Vistakon Pharmaceuticals, LLC Supported by an unrestricted grant from Vistakon Pharmaceuticals, LLC

2. Background Ocular TRUST is an ongoing annual survey of nationwide antimicrobial susceptibility patterns of common ocular pathogens. To date, more than 1,000 isolates from ocular infections have been submitted to an independent, central laboratory for in vitro testing. Ocular TRUST, now in its third year, remains the only longitudinal nationwide susceptibility surveillance program specific to ocular isolates. Purpose To report on the third annual survey from Ocular TRUST and to evaluate longitudinal antimicrobial susceptibility patterns across Ocular TRUST surveys.

3. Methods The Ocular TRUST network, comprising 104 institutions and including 10 eye centers, collected more than 350 staphylococci and streptococci isolates from ocular infections from September 2007 through May 2008. Isolates were submitted to a centralized independent laboratory for susceptibility testing by broth microdilution according to Clinical and Laboratory Standards Institute (CLSI) methodology. Participating Sites

4. Methods (continued) Antimicrobials tested represent six classes of drugs: fluoroquinolones (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin); dihydrofolate reductase inhibitors (trimethoprim); macrolides (azithromycin); aminoglycosides (tobramycin); polypeptides (polymyxin B); and β-lactams (penicillin). Minimum inhibitory concentrations (MICs) were interpreted as Susceptible, Intermediate, or Resistant according to CLSI 2008 published interpretive criteria (M100-S18), where available. Other interpretive criteria were used for staphylococci susceptibility to polymyxin B (CLSI breakpoints for P. aeruginosa) and for S. pneumoniae susceptibility to ciprofloxacin (FDA breakpoints), polymyxin B (CLSI P. aeruginosa breakpoints), tobramycin (package insert), and trimethoprim (CLSI Staphylococcus spp. breakpoints). Staphylococci were classified as methicillin-resistant or methicillin-susceptible based on susceptibility to oxacillin.

6. Results Staphylococcus aureus In Vitro Susceptibility Methicillin-Resistant S. aureus Methicillin-Susceptible S. aureus Key CIP, ciprofloxacin; GAT, gatifloxacin; LEV, levofloxacin; MOX, moxifloxacin; AZTH, azithromycin; PEN, penicillin; PLX, polymyxin B; TOB, tobramycin; TMP, trimethoprim

7. In Ocular TRUST 3, most antimicrobials, except penicillin and polymyxin B, continue to be highly active against MSSA (azithromycin shows only moderate activity) • With the exception of trimethoprim and tobramycin, less than one-third of MRSA strains are susceptible to ophthalmic antimicrobials • Susceptibility profiles remain virtually identical for the fluoroquinolones, regardless of methicillin phenotype • S. aureus is more susceptible to the fluoroquinolones than to macrolides, as represented by azithromycin

8. Coagulase-Negative Staphylococci (CNS) In Vitro Susceptibility Methicillin-Resistant CNS Methicillin-Susceptible CNS Key CIP, ciprofloxacin; GAT, gatifloxacin; LEV, levofloxacin; MOX, moxifloxacin; AZTH, azithromycin; PEN, penicillin; PLX, polymyxin B; TOB, tobramycin; TMP, trimethoprim

9. Of the antimicrobials tested, only azithromycin,penicillin, and polymyxin B were not highly activeagainst methicillin-susceptible CNS • Less than 50% of methicillin-resistant CNS isolatesare susceptible to ophthalmic antimicrobials,except for tobramycin and trimethoprim, which are somewhat more active • CNS susceptibility profiles are the same forfluoroquinolones regardless of methicillinphenotype

10. Streptococcus pneumoniae In Vitro Susceptibility S. pneumoniae Key CIP, ciprofloxacin; GAT, gatifloxacin; LEV, levofloxacin; MOX, moxifloxacin; AZTH, azithromycin; PEN, penicillin; PLX, polymyxin B; TOB, tobramycin; TMP, trimethoprim • In Ocular TRUST 3, S. pneumoniae susceptibilityprofiles for fluoroquinolones are virtually identical, except for modestly lower susceptibility rates for ciprofloxacin • Polymyxin B and tobramycin are not active against S. pneumoniae isolates • S. pneumoniae isolates are less susceptible to azithromycin, penicillin, and trimethoprim than to fluoroquinolones

11. Longitudinal Patterns • Across 3 years of surveillance in the Ocular TRUST program, antimicrobial susceptibility rates have fluctuated from year to year but have remained relatively stable • Trimethoprim continues to be the most active agent in staphylococcal isolates, regardless of methicillin status • Methicillin resistance in staphylococci is a marker of diminished susceptibility, ie, multi-drug resistance, to ophthalmic antimicrobials • Polymyxin B and penicillin have the most limited spectra of activity of all antimicrobials tested • Additional longitudinal data are needed to determine whether a change in S. pneumoniae susceptibility from 2006 to 2008 represents a true decline in azithromycin susceptibility or year-to-year fluctuation • Fluoroquinolones continue to be the most consistently active agents against all pathogens tested in Ocular TRUST • Susceptibility patterns for 3-year period (2006-2008) are virtually identical for all fluoroquinolones and do not show a decline