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

Abstract

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 cyto-toxic 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.

Distinct Susceptibilities of Corneal Pseudomonas aeruginosa Clinical Isolates to Neutrophil Extracellular Trap-Mediated Immunity

“…These differences translate into various severities of disease; in mouse keratitis studies where infection is induced by cytotoxic strains, disease pathology is worse than that caused by invasive strains (3). Consistent with these findings, patients infected with cytotoxic strains have experienced more severe pathology and, consequently, suffered from greater visual impairment after recovery from infection (4). The immune response to both invasive and cytotoxic strains is dominated by dense neutrophil infiltrates, yet the infiltration pattern and responses of polymorphonuclear neutrophils (PMNs) differ depending on the type of strain.…”

Relationship of Virulence Factors and Clinical Features in Keratitis Caused byPseudomonas aeruginosa

“…13,16 Angus et al 38 reported a role for ExoS of P. aeruginosa in survival of the corneal epithelium. In clinical cases, Borkar et al 39 investigated 101 clinical cases of P. aeruginosa keratitis from the Steroids for Corneal Ulcers Trial, involving subtyping invasive or cytotoxic strains. They reported that infiltrate sizes in cases caused by invasive strains were larger than cases caused by cytotoxic strains.…”

Management of Psuedomonas Keratitis: a review article

“…It was suggested thatpseudomonas keratitis caused by invasive strains had better visual acuity than ones caused by cytotoxic strains. On the other hand, invasive ulcers are less significantly improved compared to cytotoxic ones at three months [27].…”

“…In some resistant cases, a combination of piperacillin/tazobactam may be useful [27]. The use of topical steroids (prednisone phosphate) combined with moxifloxacin did not improve the overall clinical outcome as showed in a multi-center clinical study that enrolled patients from India and USA [42].…”

“…The size of scar at 3 months in the invasive strains was smaller when steroids and moxifloxacin were used compared to moxifloxacin alone. Less improvement was noted in the cytotoxic group (p=0.07) [7,27].…”