P. aeruginosa-Different strains, different therapeutic responses

April 1, 2012

Recent results from analyses performed by investigators in the Steroids for Corneal Ulcers Trial focusing on patients with Pseudomonas aeruginosa infection showed that, just as in overall study population, adjunctive corticosteroid use did not affect treatment outcomes or safety.

This latter ancillary study is a clinical extension of basic science research initiated nearly 2 decades ago by Suzanne M. J. Fleiszig, OD, PhD, FAAO, FARVO, and colleagues at the School of Optometry, University of California (UC), Berkeley. Reporting for the group at the annual meeting of the American Academy of Optometry, Chelsia Leong presented findings from genotyping and phenotyping of the SCUT study P. aeruginosa isolates.

"We know from clinical experience treating bacterial corneal ulcers that sometimes steroids are helpful and sometimes steroids make things worse, and we know from research we have conducted in animals that P. aeruginosa subtype impacts therapeutic response. The SCUT study analyses are being performed to determine whether the subtype of P. aeruginosa may have a role on the treatment effect," said Dr. Fleiszig, professor of optometry, UC Berkeley School of Optometry.

Characterizing isolates

Dr. Fleiszig and colleagues originally reported that P. aeruginosa isolates from corneal infections can be divided into two broad categories, the invasive strains which enter and replicate within corneal epithelial cells and cytotoxic strains which destroy corneal epithelial cells via injection of toxins. They are divided into these categories by analysis of their genotype, whether the strains encode for specific virulence factors, or phenotypically, which describes the behavior of the strains in vitro.

A subsequent study in a mouse model showed that in animals with experimentally induced corneal infections, the response to therapy differed depending on whether the inciting pathogen was a cytotoxic or invasive strain of P. aeruginosa.

"Our animal experiments were designed to test hypotheses we developed based on our initial basic science research. We only performed a single animal study, however, and it was unclear whether the findings would translate clinically from mice to humans," Dr. Fleiszig told Optometry Times.

"Therefore, we were very excited when we were asked to classify the P. aeruginosa isolates from the SCUT study because of the opportunity it presented for testing our hypotheses in a human population," she said.