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

Department of Ocular Microbiology, Aravind Eye Care System, Madurai, India.
Clinical Infectious Diseases (Impact Factor: 8.89). 03/2012; 54(10):1381-7. DOI: 10.1093/cid/cis189
Source: PubMed


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.
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.
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).
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.

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    • "Analysis of moxifloxacin resistance of bacterial keratitis isolates (including P, aeruginosa) from the SCUT study showed that increased resistance to this fluoroquinolone in vitro (i.e. increased minimum inhibitory concentration) was associated with poorer clinical outcomes, including reduced visual acuity at 3 weeks, a larger ulcer, and slower corneal re-epithelialization [27]. Here, we analyzed P. aeruginosa strains isolated from the SCUT study, and two laboratory isolates and their T3SS mutants, for their in vitro susceptibility to fluoroquinolones and other antimicrobials including cephalosporins and aminoglycosides. "
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    ABSTRACT: To determine the relationship between type three secretion genotype and fluoroquinolone resistance for P. aeruginosa strains isolated from microbial keratitis during the Steroids for Corneal Ulcers Trial (SCUT) and for two laboratory strains, PA103 and PAO1. Confirmed P. aeruginosa isolates from the SCUT were divided into exoU(+) or exoU(-). The exoU(+) strains contained the gene encoding ExoU, a powerful phospholipase toxin delivered into host cells by the type three secretion system. Isolates were then assessed for susceptibility to fluoroquinolone, cephalosporin, and aminoglycoside antibiotics using disk diffusion assays. Etest was used to determine the MIC of moxifloxacin and other fluoroquinolones. Laboratory isolates in which the exoU gene was added or deleted were also tested. A significantly higher proportion of exoU(+) strains were resistant to ciprofloxacin (p = 0.001), gatifloxacin (p = 0.003), and ofloxacin (p = 0.002) compared to exoU(-) isolates. There was no significant difference between exoU(+) or exoU(-) negative isolates with respect to susceptibility to other antibiotics except gentamicin. Infections involving resistant exoU(+) strains trended towards worse clinical outcome. Deletion or acquisition of exoU in laboratory isolates did not affect fluoroquinolone susceptibility. Fluoroquinolone susceptibility of P. aeruginosa isolated from the SCUT is consistent with previous studies showing elevated resistance involving exoU encoding (cytotoxic) strains, and suggest worse clinical outcome from infections involving resistant isolates. Determination of exoU expression in clinical isolates of P. aeruginosa may be helpful in directing clinical management of patients with microbial keratitis.
    Full-text · Article · Apr 2014 · BMC Ophthalmology
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    • "Some epidemiologic studies identify the pneumococcus as the top cause of bacterial keratitis [32] [33] [34] [35] [36] [37] [38] [39]. Most other reports show this bacterium and other Streptococcus species to be the causative agents most commonly encountered aer P. aeruginosa and/or S. aureus [40] [41] [42] [43] [44] [45] [46] [47] [48] [49]. Pneumococcal keratitis is not typically contact lens associated like P. aeruginosa, but predisposing conditions such as ocular trauma or surgery are factors in this disease [32, 33, 36, 39, 41, 48, 50–54]. "
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    ABSTRACT: Ocular bacterial infections are universally treated with antibiotics, which can eliminate the organism but cannot reverse the damage caused by bacterial products already present. The three very common causes of bacterial keratitis-Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae-all produce proteins that directly or indirectly cause damage to the cornea that can result in reduced vision despite antibiotic treatment. Most, but not all, of these proteins are secreted toxins and enzymes that mediate host cell death, degradation of stromal collagen, cleavage of host cell surface molecules, or induction of a damaging inflammatory response. Studies of these bacterial pathogens have determined the proteins of interest that could be targets for future therapeutic options for decreasing corneal damage.
    Full-text · Article · Jan 2013 · Journal of Ophthalmology
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    ABSTRACT: PURPOSE: To compare the clinical course of Nocardia species keratitis with keratitis resulting from other bacterial organisms and to assess the effect of corticosteroids as adjunctive therapy using data collected from the Steroids for Corneal Ulcers Trial. DESIGN: Subgroup analysis of a randomized controlled trial. METHODS: Setting: Multicenter randomized controlled trial. Study population: Five hundred patients with bacterial keratitis randomized 1:1 to topical corticosteroid or placebo who had received at least 48 hours of topical moxifloxacin. Intervention/observation procedure: Topical prednisolone phosphate 1% or placebo and clinical course of Nocardia keratitis. Main outcome measures: Best spectacle-corrected visual acuity and infiltrate or scar size at 3 months from enrollment. RESULTS: Of 500 patients enrolled in the trial, 55 (11%) had a Nocardia corneal ulcer. Patients with Nocardia ulcers had better presentation visual acuity compared with non-Nocardia ulcers (median Snellen visual acuity, 20/45, compared with 20/145; P < .001) and comparable 3-month visual acuity (median, 20/25, vs 20/40; P = .25). Nocardia ulcers had approximately 2 lines less of improvement in visual acuity compared with non-Nocardia ulcers (0.21 logarithm of the minimal angle of resolution; 95% confidence interval, 0.09 to 0.33 logarithm of the minimal angle of resolution; P = .001). This difference may reflect the better starting visual acuity in patients with Nocardia ulcers. In Nocardia ulcers, corticosteroids were associated with an average 0.4-mm increase in 3-month infiltrate or scar size (95% confidence interval, 0.03 to 0.77 mm; P = .03). CONCLUSIONS: Nocardia ulcers responded well to treatment. They showed less overall improvement in visual acuity than non-Nocardia ulcers, but had better presentation acuity. Corticosteroids may be associated with worse outcomes.
    No preview · Article · Sep 2012 · American Journal of Ophthalmology
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