Genetic basis, antibiotic susceptibility, and clinical outcomes of lasR mutant Pseudomonas aeruginosa keratitis isolates

Abstract

Purpose : Pseudomonas aeruginosa causes vision-threatening keratitis. Approximately 20% of P. aeruginosa keratitis isolates from the SCUT study demonstrated a colony sheen appearance, and these sheen positive isolates correlated with a worse clinical outcome. These sheen isolates were found in India between 2006 and 2010. The basis of the sheen phenotype was a build-up of 4-hydroxy-2-heptylquinoline due to mutation of the lasR gene. It is not known whether North American P. aeruginosa keratitis isolates have this sheen phenotype. In this study, we examined P. aeruginosa keratitis isolates from the Charles T. Campbell Ophthalmic Microbiology Laboratory dating from 1993-2021 for a sheen phenotype. Patient outcomes were tallied and analyzed.

Methods : 399 P. aeruginosa keratitis isolates from a 20-year period were streaked out on blood agar plates and analyzed for colony sheen phenotypes. Sequencing of the lasR gene for a subset of isolates was performed. A retrospective chart review compared outcomes of keratitis patients infected by sheen positive (n=49) and negative isolates (n=19). MICs were determined using E-strips.

Results : There was an increasing trend in the frequency of sheen positive isolates, with 0% for isolates from 1993-1997 (n=57), 11% for isolates from 1998-2002 (n=63), 15% for isolates from 2003-2007 (n=61), 16% for isolates from 2008-2012 (n=56), 26% for isolates from 2013-2017 (n=101), and 26% for isolates from 2018-2021 (n=61). The majority of tested sheen positive isolates had mutations in the lasR open reading frame that differs from those found in the SCUT study. Sheen positive isolates were more likely to be resistant to ceftazidime (p<0.01), but similarly susceptible to cefiderocol, ciprofloxacin, and tobramycin. Patients infected with sheen positive isolates had better average final vision (p=0.0106).

Conclusions : P. aeruginosa sheen isolates which were previously isolated from North American keratitis patients with a similar overall frequency to those observed in India. There is a trend for increasing sheen isolates; however, retrospective chart analysis suggests better outcomes for eyes infected with lasR mutants.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.