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Regis Kowalski, Tyler Kowalski, Eric Romanowski, Robert Shanks, Leela Raju; The In Vitro Activity of Tigecycline for Clinically Relevant Ocular Pathogens. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4288.
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Tigecycline is a glycylcycline antibiotic that is FDA approved for the treatment of skin and soft tissue infections, community-acquired pneumonia, and intra-abdominal infections. Previous studies of clinical isolates from these body sites demonstrated that tigecycline is active in vitro against isolates of a number of Gram-positive and Gram-negative pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), but lacks significant potency against Pseudomonas aeruginosa to be useful for treatment of systemic infections A topical ophthalmic formulation (RPX-978) is in development. The goal of the current study was to determine the in vitro activity of tigecycline against multiple clinically relevant ocular pathogens.
Minimum Inhibitory Concentrations (MIC) using CLSI reference methods for broth dilution were determined for 110 clinical conjunctivitis isolates based on incidence at the Campbell Lab: Staphylococcus aureus (SA) (n=36), coagulase-negative Staphylococcus (CNS) (14), Streptococcus pneumoniae (SP) (22), other Gram-positive bacteria (GP) (8) (2 Streptococcus viridans group and 6 beta-hemolytic Streptococcus species), Haemophilus species (HS) (20), and other Gram-negative bacteria (10) (2 Serratia marcescens, 2 Proteus mirablis, 3 Pseudomonas aeruginosa, 1 Enterobacter aerogenes, 1 Pseudomonas fluorescens, and 1 Klebsiella species). In addition, MICs were performed on 26 keratitis isolates of Pseudomonas aeruginosa (PA) and 10 endophthalmitis isolates each of MRSA, MSSA, MRCNS, and MSCNS. A total of 176 isolates were tested.
: Data is expressed as (MIC50, MIC90 and Range of MICs) in μg/ml respectively. Conjunctivitis: SA (0.25, 0.5, 0.125-0.5); CNS (0.25, 0.5, 0.05-1.0); SP (<0.03, 0.125, <0.03-0.25); GP (0.125, 0.5, <0.03-1.0); HS (2.0, 4.0, 2.0-4.0); GN (1.0, 4.0, 0.5-8.0). Keratitis: PA (4.0, 8.0, 0.5-8.0). Endophthalmitis: MRSA (0.5, 0.5, 0.25-0.5); MSSA (0.125, 0.5, 0.125-8.0); MRCNS (0.25, 0.25, 0.125-0.25); MSCNS (0.25, 0.5, 0.125-0.5).
Tigecycline demonstrated broad spectrum in vitro activity against clinically relevant ocular pathogens. Potent activity was demonstrated against MRSA isolates, and lower than expected MICs were demonstrated for PA. Further development of topical tigecycline to treat eye infections is warranted.
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