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Clinical Sciences |

Association Between Cytotoxic and Invasive Pseudomonas aeruginosa and Clinical Outcomes in Bacterial Keratitis

Durga S. Borkar, BA; Suzanne M. J. Fleiszig, OD, PhD; Chelsia Leong, OD; Prajna Lalitha, MD; Muthiah Srinivasan, MD; Avanti A. Ghanekar, OD; Connie Tam, PhD; Wing Y. Li, OD; Michael E. Zegans, MD; Stephen D. McLeod, MD; Thomas M. Lietman, MD; Nisha R. Acharya, MD, MS
JAMA Ophthalmol. 2013;131(2):147-153. doi:10.1001/jamaophthalmol.2013.778.
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Objectives  To determine whether cytotoxic and invasive Pseudomonas aeruginosa strains differentially influence clinical presentation, outcomes, or therapeutic response in bacterial keratitis.

Methods  Pseudomonas aeruginosa isolates from the National Eye Institute–funded Steroids for Corneal Ulcers Trial were subtyped as cytotoxic or invasive strains. The main outcome measure compared between the 2 subtypes was change in visual acuity at 3 months using Huber robust regression, adjusting for topical corticosteroid treatment.

Results  Of 101 confirmed P aeruginosa isolates from the Steroids for Corneal Ulcers Trial, 74 had a classically cytotoxic or invasive genotype. While corneal ulcers caused by genotypically invasive P aeruginosa strains were associated at presentation with significantly better visual acuity than corneal ulcers caused by genotypically cytotoxic P aeruginosa strains when adjusting for the effect of ulcer location (P = .008), invasive ulcers had improved significantly less than cytotoxic ulcers at 3 months (0.35; 95% CI, 0.04-0.66 logMAR; P = .03 [3.5-line difference]). Compared with topical moxifloxacin alone, adjunctive treatment with topical corticosteroids was associated with significantly more improvement in visual acuity in the invasive subgroup (P = .04) but was associated with less improvement in visual acuity in the cytotoxic subgroup (P = .07).

Conclusions  Rational profiling of differentially expressed virulence determinants (eg, cytotoxicity and invasiveness for P aeruginosa) could be used as a tool for decision making in the management of infections to optimize outcomes.

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Grahic Jump Location

Figure 1. Percentage invasiveness and percentage cytotoxicity by strain type for genotypically classically invasive and cytotoxic Pseudomonas aeruginosa strains. A, The spread and the mean value of percentage invasiveness for genotypically invasive and cytotoxic strains. Three of the genotypically cytotoxic strains were gentamicin and amikacin resistant; therefore, percentage invasiveness was not measured for these 3 strains. B, The spread and the mean value of percentage cytotoxicity for genotypically invasive and cytotoxic strains. The median for each group is represented by the line in the middle of each box. The interquartile range (the span of the 25th to 75th percentiles) is denoted by the lower to upper bounds of each box. The whiskers extend from the smallest percentage invasiveness or percentage cytotoxicity within 1.5 times the interquartile range below the 25th percentile to the largest percentage invasiveness or percentage cytotoxicity within 1.5 times the interquartile range above the 75th percentile. Individual data points denote values outside this range. P values shown were obtained by 2-group mean comparison t test.

Place holder to copy figure label and caption
Grahic Jump Location

Figure 2. Change in logMAR best spectacle–corrected visual acuity at 3 months by treatment arm (placebo vs corticosteroid) for each Pseudomonas aeruginosa strain type. The median for each group is represented by the line in the middle of each box. The interquartile range (the span of the 25th to 75th percentiles) is denoted by the lower to upper bounds of each box. The whiskers extend from the smallest visual acuity change within 1.5 times the interquartile range below the 25th percentile to the largest visual acuity change within 1.5 times the interquartile range above the 75th percentile. Individual data points denote values outside this range. P values shown were obtained by 2-group mean comparison t test. The P value for the interaction term between treatment arm and strain genotype was .005 and was obtained using Huber robust regression.

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