Relationship of In Vitro Susceptibility to Moxifloxacin and In Vivo Clinical Outcome in Bacterial Keratitis

Background. For bacterial infections, the susceptibility to antibiotics in vitro has been associated with clinical outcomes in vivo, although the importance of minimum inhibitory concentration (MIC) has been debated. In this study, we analyzed the association of MIC on clinical outcomes in bacterial...

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Published in:Clinical infectious diseases 2012-05, Vol.54 (10), p.1381-1387
Main Authors: Lalitha, Prajna, Srinivasan, Muthiah, Manikandan, P., Bharathi, M. Jayahar, Rajaraman, Revathi, Ravindran, Meenakshi, Cevallos, Vicky, Oldenburg, Catherine E., Ray, Kathryn J., Toutain-Kidd, Christine M., Glidden, David V., Zegans, Michael E., McLeod, Stephen D., Acharya, Nisha R., Lietman, Thomas M.
Format: Article
Language:English
Subjects:
Acuity
and Commentaries
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
Antibacterial agents
Antibiotics
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimicrobial agents
ARTICLES AND COMMENTARIES
Aza Compounds - pharmacology
Aza Compounds - therapeutic use
Bacteria
Bacteria - classification
Bacteria - drug effects
Bacteria - isolation & purification
Bacterial infections
Bacterial Infections - drug therapy
Bacterial Infections - microbiology
Biological and medical sciences
Clinical outcomes
Clinical trials
Cornea
Corneal ulcer
Corneal Ulcer - drug therapy
Corneal Ulcer - microbiology
Corticosteroids
Data processing
Diseases of cornea, anterior segment and sclera
Etiology
Experimentation
Eye
Eye diseases
Fluoroquinolones
Health outcomes
Humans
Infection
Infectious diseases
Keratitis
Medical sciences
Microbial Sensitivity Tests
Minimum inhibitory concentration
Moxifloxacin
Ophthalmology
Pharmacology. Drug treatments
Placebos
Pseudomonas aeruginosa
Quinolines - pharmacology
Quinolines - therapeutic use
Steroid hormones
Streptococcus pneumoniae
Treatment Outcome
Ulcers
Vision
Visual acuity
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Summary:Background. For bacterial infections, the susceptibility to antibiotics in vitro has been associated with clinical outcomes in vivo, although the importance of minimum inhibitory concentration (MIC) has been debated. In this study, we analyzed the association of MIC on clinical outcomes in bacterial corneal ulcers, while controlling for organism and severity of disease at presentation. Methods. Data were collected as part of a National Eye Institute—funded, randomized, controlled trial (the Steroids for Corneal Ulcers Trial [SCUT]). All cases enrolled in SCUT had a culture-positive bacterial corneal ulcer and received moxifloxacin. The MIC to moxifloxacin was measured by E test. Outcomes included best spectacle-corrected visual acuity, infiltrate/scar size, time to re-epithelialization, and corneal perforation. Results. Five hundred patients with corneal ulcers were enrolled in the trial, and 480 were included in this analysis. The most commonly isolated organisms were Streptococcus pneumoniae and Pseudomonas aeruginosa. A 2-fold increase in MIC was associated with an approximately 0.02 logMAR decrease in visual acuity at 3 weeks, approximately 1 letter of vision loss on a Snellen chart (0.019 logMAR; 95% confidence interval [CI], .0040—.033; P = .01). A 2-fold increase in MIC was associated with an approximately 0.04-mm larger infiltrate/scar size at 3 weeks (0.036 mm; 95% CI, .010—.061; P = .006). After controlling for organism, a higher MIC was associated with slower time to re-epithelialization (hazards ratio, 0.92; 95% CI, .86—.97; P = .005). Conclusions. In bacterial keratitis, a higher MIC to the treating antibiotic is significantly associated with worse clinical outcomes, with approximately 1 line of vision loss per 32-fold increase in MIC. Clinical Trials Registration: NCT00324168.
ISSN:1058-4838
1537-6591
DOI:10.1093/cid/cis189