Bacterial Keratitis

Overview

Bacterial keratitis is an urgent corneal infection that requires prompt recognition, laboratory evaluation, and initiation of therapy.¹ Inflammatory corneal diseases, predominantly bacterial infections, are considered one of the leading causes of monocular blindness worldwide, with bacterial infections found in approximately 80% of patients with ulcerative keratitis.² By the time of presentation, severe visual loss from corneal ulceration and opacity may already be present, and these changes may persist despite treatment.³ Topical fortified antibiotic eyedrops constitute the mainstay of therapy.¹

Epidemiology & Risk Factors

The risk factors and bacterial isolates associated with bacterial keratitis differ significantly between high-income and low- or middle-income countries, such that general management guidelines may not be universally appropriate.³

Recognized risk factors have evolved in recent years. Contact lens wear and refractive surgery have increased in importance as risk factors according to some studies, while bacterial keratitis is observed less frequently after trauma.² The likely bacterial causes may vary among geographic regions and over time.¹ In patients with contact lens-related keratitis and post-refractive surgery infections, microorganisms such as Pseudomonas species and atypical mycobacteria are particularly detectable.²

Pathophysiology

Bacterial keratitis typically requires a breach in the corneal epithelial barrier to allow bacterial invasion of the corneal stroma. Once bacteria penetrate the cornea, they proliferate and trigger both direct microbial damage and an intense host immune response that contributes to tissue destruction.

Virulence factors of bacteria may affect pathogenicity within species and influence clinical outcomes, though these factors are not routinely assessed in clinical practice.³ The clinical course and severity can vary widely depending on the type and species of bacteria involved, ranging from small superficial infiltrates to necrotizing forms.⁴ Poor outcomes often result from corneal melting, scarring, and perforation secondary to the combined effects of bacterial virulence and immune-mediated tissue damage.⁵

Clinical Presentation

Although the diagnosis of bacterial keratitis may seem intuitive, multiple uncertainties exist regarding the diagnostic criteria used, which impacts the interpretation of investigations and recruitment to clinical studies.³

Patients typically present with acute symptoms including:

• Eye pain
• Photophobia
• Decreased vision
• Purulent discharge
• Conjunctival injection

The clinical appearance varies widely depending on the bacterial species, ranging from small superficial infiltrates to severe necrotizing forms.⁴ The concept that bacterial keratitis can only be confirmed by culture is problematic, as approximately 50% of cases that are clinically consistent with bacterial keratitis have negative microbiological investigations.³ The etiology of these culture-negative cases remains unknown.³

Exam Findings

Key examination findings in bacterial keratitis include:

• Corneal epithelial defect with underlying stromal infiltrate
• Stromal suppuration and opacity
• Anterior chamber reaction with hypopyon in severe cases
• Conjunctival injection and chemosis
• Mucopurulent discharge
• Corneal edema surrounding the infiltrate

The specific morphology and pattern of the infiltrate may vary with the causative organism. Pseudomonas aeruginosa classically presents with a rapidly progressive ulcer that may demonstrate invasive characteristics.⁵ Features such as central location, depth, and size of the ulcer have clinical and prognostic significance.⁵

Classification

Bacterial keratitis can be classified by several schemas:

By severity:

• Superficial: limited to epithelium and anterior stroma
• Deep: involving mid to posterior stroma
• Severe/necrotizing: extensive tissue destruction with potential for perforation

By location:

• Central: within the central 4mm optical zone
• Peripheral: outside the central zone

By associated risk factor:

• Contact lens-related
• Post-traumatic
• Post-surgical (including post-refractive surgery)
• Associated with ocular surface disease

By causative organism:

• Gram-positive (Staphylococcus, Streptococcus)
• Gram-negative (Pseudomonas, other)
• Atypical bacteria (Nocardia, atypical mycobacteria)

Central, deep, or large ulcers represent a distinct clinical subset with different prognostic and treatment considerations.⁵

Differential Diagnosis

• Fungal keratitis (often with worse clinical outcomes than bacterial ulcers)⁵
• Acanthamoeba keratitis (diagnosable with in vivo confocal microscopy)⁵
• Viral keratitis, particularly herpes simplex stromal keratitis⁵
• Sterile inflammatory keratitis
• Autoimmune corneal disease
• Exposure or neurotrophic keratopathy with secondary infection
• Marginal keratitis related to staphylococcal hypersensitivity

Management

Diagnosis: Culture remains the prevailing diagnostic tool for bacterial keratitis.⁵ Laboratory evaluation should be performed to identify the causative organism.¹ Possibilities for diagnostics have expanded in recent years through molecular biological techniques, though these cannot replace established methods.² Next-generation sequencing holds potential for early and accurate diagnosis, even for organisms difficult to culture by conventional methods.⁵

Antimicrobial Therapy: Topical fortified antibiotic eyedrops remain the mainstay of therapy.¹ A recent review found all commonly prescribed topical antibiotics to be equally effective for bacterial keratitis.⁵ The numerous classes of available antibiotics render the treatment scope diverse and complex, especially before the pathogen has been specified and antibiotic sensitivity has been tested.⁴

Current estimation of bacterial susceptibility to antimicrobials is based on data from systemic administration and achievable serum or tissue concentrations, rather than relevant corneal concentrations and biological activity in the cornea.³ Provision of minimum inhibitory concentrations of antimicrobials for isolated bacteria would represent an important step forward.³

Broad, often empiric use of highly effective antimicrobial agents, especially fluoroquinolones, is assumed to be a factor in transformation of the microbial spectrum.² An increase in the prevalence of antimicrobial resistance is a concern, though the effect this has on disease outcomes remains unclear.³

Adjuvant Therapies: Topical corticosteroids represent an adjuvant therapy aimed at reducing the immune response associated with keratitis.⁵ The Steroids for Corneal Ulcers Trial found that although steroids provided no significant improvement overall, they appeared beneficial for ulcers that were central, deep or large, non-Nocardia, or classically invasive Pseudomonas aeruginosa; for patients with low baseline vision; and when started early after initiation of antibiotics.⁵

Emerging Approaches: New therapeutic approaches to reduce bacterial virulence are in development.⁴ New technologies have been developed to detect and kill bacteria, with potential application to bacterial keratitis.³

Complications

Outcomes remain poor in many cases secondary to several serious complications:

• Corneal melting and tissue necrosis
• Progressive stromal scarring and permanent opacity
• Corneal perforation
• Endophthalmitis
• Permanent visual impairment or blindness^3,5

Severe visual loss from corneal ulceration and opacity may be present by the time of presentation and may persist despite appropriate treatment.³ Corneal melting, scarring, and perforation represent the major mechanisms by which bacterial keratitis leads to poor visual outcomes.⁵

Clinical Pearls

• Approximately 50% of cases clinically consistent with bacterial keratitis will be culture-negative; negative cultures do not exclude the diagnosis³
• All commonly prescribed topical antibiotics have been found equally effective in recent reviews, supporting empiric broad-spectrum coverage while awaiting culture results⁵
• Risk factors and bacterial isolates vary significantly between high-income and low- or middle-income countries; regional epidemiology should guide empiric therapy³
• Contact lens-related cases are particularly associated with Pseudomonas species and atypical mycobacteria²
• For appropriately selected cases (central, deep, large, non-Nocardia ulcers or those with low baseline vision), early addition of topical steroids after antibiotic initiation may improve outcomes⁵
• Minimum inhibitory concentration data, when available, provides more clinically relevant information than standard susceptibility reporting based on serum concentrations³

Common Pitfalls

• Assuming that negative cultures exclude bacterial keratitis; half of clinically typical cases are culture-negative³
• Delaying treatment pending culture results in an urgent, sight-threatening infection¹
• Interpreting antimicrobial susceptibility data based on systemic concentrations rather than achievable topical corneal concentrations³
• Applying general management guidelines without considering significant regional differences in bacterial isolates and resistance patterns³
• Using topical steroids in all cases; benefit appears limited to specific subgroups and should be avoided in Nocardia infections⁵
• Failing to recognize that broad empiric use of fluoroquinolones may contribute to changes in the microbial spectrum and resistance patterns²
• Overlooking atypical organisms such as atypical mycobacteria in contact lens wearers or post-refractive surgery patients²