Pseudomonas aeruginosa is one of the major causative bacteria of bacterial keratitis. It is the most common cause of corneal infection among Gram-negative bacilli 2). It is characterized by liquefactive necrosis due to proteases and exotoxins, and can rapidly progress to corneal perforation.
The proportion of bacterial keratitis caused by Pseudomonas varies from 6.8% to 55% depending on reports. Although it differs by region and population, it is reported as the most common causative bacterium in surveys of CL wearers 2). The risk is particularly high in soft CL wearers, with some reports indicating that Pseudomonas accounts for about 55% of CL-related corneal infections 2).
Compared to other bacterial keratitis, it progresses rapidly, and delay in treatment directly affects prognosis. This article explains the clinical picture, diagnosis, treatment, and pathophysiology of Pseudomonas keratitis.
Acute-onset eye pain is the most common symptom. The pain is severe and accompanied by conjunctival injection, tearing, and mucopurulent discharge. Visual acuity decreases markedly when infiltration involves the pupillary area. Eyelid swelling and photophobia are also frequently observed.
Ring abscess (annular infiltrate): A characteristic finding of Pseudomonas keratitis, forming a ring-shaped infiltrate in the peripheral cornea3)
Ground-glass opacity: Diffuse corneal stromal opacity with blurred margins of the infiltrate 3)
Brush-shaped infiltrate: An early pattern where the infiltrate margin spreads radially 3)
Corneal epithelial defect: Accompanied by extensive epithelial loss, with surrounding edematous epithelium
Corneal thinning and perforation: Progressive stromal melting due to proteases can lead to perforation
Anterior Segment Findings
Hypopyon: Frequently observed and correlates with the severity of the abscess
Hyphema (anterior chamber hemorrhage): Reported as a rare complication 1)
Ciliary injection: Marked injection due to deep vascular dilation around the limbus
Chemosis: Edematous swelling of the bulbar conjunctiva associated with severe inflammation
Chan et al. reported a case of Pseudomonas aeruginosa keratitis with hyphema in a 45-year-old contact lens wearer. Despite pan-susceptibility on drug sensitivity testing, the infection was clinically refractory and eventually improved with intravenous piperacillin/tazobactam 1).
Pseudomonas aeruginosa is an environmental bacterium widely distributed in soil and water. The healthy corneal surface is protected from infection by the epithelial barrier, but epithelial damage or microtrauma from contact lens wear can trigger infection 2).
Risk Factor
Details
Contact lens wear
Greatest risk factor 2)
Corneal trauma
Plant injury, foreign body, etc.
Ocular surface disease
Dry eye, eyelid abnormalities
Contact lens wear is the greatest risk factor, especially continuous wear of soft contact lenses and improper care 2). Contamination of the contact lens case is often the source of infection.
Corneal trauma and epithelial defects after corneal surgery can also trigger onset. Long-term use of steroid eye drops reduces local immunity and increases infection risk.
Notably, Pseudomonas aeruginosa has been reported to have the ability to invade even normal corneal epithelium2). This is a characteristic distinct from many other bacterial keratitis pathogens.
QWill I definitely get Pseudomonas aeruginosa keratitis if I use contact lenses?
A
Not all CL wearers become infected. Proper lens care and hygiene can significantly reduce the risk. However, inappropriate use such as sleeping while wearing lenses, neglecting to clean the case, or rinsing lenses with tap water greatly increases the risk of infection. If you notice any abnormality, remove the CL and seek medical attention early.
When Pseudomonas aeruginosa keratitis is suspected based on clinical findings, microbiological examination to identify the causative organism is essential 3).
Examination Method
Purpose
Gram stain
Confirmation of gram-negative rods 3)
Culture test
Identification of causative organism and drug susceptibility 3)
Antimicrobial susceptibility testing
Guide for selecting therapeutic drugs3)
Corneal scraping is the basic technique for specimen collection, and scraping from the infiltrate margin improves the detection rate3). If Gram-negative rods are identified on Gram stain, infection with Gram-negative rods including Pseudomonas aeruginosa is strongly suspected.
For culture, use blood agar, chocolate agar, and selective media for Gram-negative rods such as Drigalski agar (BTB agar)3). Pseudomonas aeruginosa is a non-glucose-fermenting Gram-negative rod, and the production of a characteristic green pigment (pyocyanin) and a sweet odor are clues for identification.
Antimicrobial susceptibility testing is essential for determining treatment strategy3). However, even if susceptibility testing indicates sensitivity, clinical resistance to treatment may occur, requiring caution1).
Based on the guidelines for infectious keratitis, antimicrobial agents are selected considering the presumed causative organism and drug susceptibility3). Treatment initiation is urgent, and empirical therapy should be started without waiting for culture results.
Mild to Moderate Cases
First-line: Frequent instillation of fluoroquinolone (FQ) eye drops3)
Recommended drugs: Levofloxacin (LVFX) 1.5% or moxifloxacin (MFLX) 0.5%3)
Administration: Instill every hour upon waking and every 2 hours before bedtime, then taper according to improvement
Severe Cases
FQ + aminoglycoside combination: Cefmenoxime eye drops combined with aminoglycoside (tobramycin or gentamicin) eye drops3)
Intravenous therapy: Consider systemic administration of ceftazidime in cases of impending corneal perforation
Management of refractory cases: Systemic administration of piperacillin/tazobactam (Tazocin®) has been reported to be effective1)
The use of concomitant steroids for bacterial keratitis is controversial. In a subgroup analysis of the SCUT (Steroids for Corneal Ulcers Trial), steroid combination therapy for Pseudomonas aeruginosa keratitis did not contribute to improved visual outcomes and showed a trend toward harm2). Caution is required, especially in elderly patients and severe cases.
QHow long is the treatment period for Pseudomonas aeruginosa keratitis?
A
The treatment period varies depending on severity, but generally takes several weeks to over a month. Even mild cases require at least 2–3 weeks of topical treatment. Severe or treatment-resistant cases may require longer, and if corneal scarring remains, corneal transplantation may be considered for visual recovery. Do not discontinue eye drops on your own; follow your doctor’s instructions.
Adhesion stage: Pseudomonas aeruginosa adheres to ganglioside receptors on the corneal epithelial cell surface using pili. Epithelial microtrauma due to contact lens wear exposes receptors and promotes bacterial adhesion.
Biofilm formation: After adhesion, it produces glycocalyx (polysaccharide capsule) to form a biofilm. Biofilm inhibits antibiotic penetration and contributes to treatment resistance.
Pseudomonas aeruginosa injects toxins directly into host cells via the type III secretion system (T3SS).
ExoU: A potent cytotoxin with phospholipase activity that rapidly necroses corneal epithelial cells. ExoU-positive strains (cytotoxic strains) have a high risk of corneal perforation.
ExoS: Has ADP-ribosyltransferase activity and GTPase-activating activity, disrupting the cytoskeleton and causing cells to round up. ExoS-positive strains (invasive strains) are superior at intracellular invasion.
ExoT: Has similar functions to ExoS but with weaker effects.
ExoY: Has adenylyl cyclase activity, increasing cAMP levels and disrupting intercellular junctions.
Proteases produced by Pseudomonas aeruginosa are key factors causing liquefactive necrosis of the corneal stroma.
Elastase (LasB): Degrades collagen and proteoglycans, melting the corneal stroma.
Alkaline protease (AprA): Degrades host immunoglobulins and complement components, contributing to immune evasion.
The combined action of these toxins and proteases causes rapid melting of the corneal stroma, leading to descemetocele formation and corneal perforation in severe cases. Ring abscesses are formed by annular accumulation of neutrophils and deposition of immune complexes.
QWhy does Pseudomonas aeruginosa dissolve the cornea?
A
Pseudomonas aeruginosa secretes large amounts of powerful degrading enzymes such as elastase and alkaline protease. These enzymes break down collagen fibers and proteoglycans, the main components of the cornea, causing the corneal stroma to necrotize as if “melting” (liquefactive necrosis). Furthermore, it directly injects toxins into cells using a syringe-like device called the type III secretion system, destroying corneal epithelial cells. This multi-step attack is the cause of the rapid progression and severity of Pseudomonas aeruginosa keratitis.
Chan et al. reported a case of Pseudomonas aeruginosa keratitis that was pan-susceptible on drug sensitivity testing but did not respond to standard antimicrobial therapy (cefazolin, gentamicin, moxifloxacin, ciprofloxacin), and was successfully treated with systemic piperacillin/tazobactam (Tazocin®)1).
In this case, a 45-year-old male with a 15-year history of contact lens wear presented with rapidly progressive corneal infiltration and hyphema. The hyphema was presumed to be triggered by aspirin intake. After starting Tazocin®, inflammation subsided, and final visual acuity improved to corrected 0.63 (pinhole 0.83)1).
This report demonstrates that in vitro susceptibility and in vivo treatment response can diverge, suggesting the usefulness of piperacillin/tazobactam as an alternative treatment option for clinical treatment resistance.
The increase in fluoroquinolone-resistant Pseudomonas aeruginosa is a global problem 2). Resistance mechanisms involve target mutations in DNA gyrase and topoisomerase IV, as well as overexpression of efflux pumps. The development of new antimicrobial agents and novel administration routes for existing drugs (e.g., intracorneal injection) are being investigated.
Chan JY, Tan JH, Ong HS, et al. Recalcitrant Pseudomonas aeruginosa Keratitis with Hyphaema Responding to Tazocin (Piperacillin/Tazobactam): A Case Report. Case Rep Ophthalmol. 2021;12(1):292-298.
American Academy of Ophthalmology Cornea/External Disease Preferred Practice Pattern Panel. Bacterial Keratitis Preferred Practice Pattern. Ophthalmology. 2024;131(2):P1-P47.
