Bacterial keratitis, sampling and treatment

Infectious keratitis represents one of the most critical visual emergencies in anterior segment ophthalmology. The human cornea possesses an extraordinary anatomic and immunological defense system: an intact non-keratinised stratified squamous epithelium secured by tight junctions (zonula occludens), a basement membrane, an acellular Bowman layer, an avascular stroma populated by quiescent keratocytes and uniformly spaced collagen fibrils, Descemet membrane, and a single monolayer of metabolic endothelium. Disruption of the epithelial barrier permits microbial adhesion, invasion, and inflammatory destruction.

Only a select group of virulent microorganisms can penetrate an intact, healthy corneal epithelium:

1. Neisseria gonorrhoeae
2. Neisseria meningitidis
3. Corynebacterium diphtheriae
4. Listeria monocytogenes
5. Haemophilus aegyptius (Koch-Weeks bacillus)

All other pathogens require an epithelial breach—induced by contact lens wear, mechanical microtrauma, foreign bodies, bullous keratopathy, dry eye disease, trichiasis, or neurotrophic hypoesthesia—to establish stromal infection.

1. Bacterial Keratitis: Pathogen Profiles & Biomicroscopic Morphology

Bacterial keratitis progresses with alarming speed. Bacteria liberate endotoxins, exotoxins, and proteases, inciting an intense host polymorphonuclear neutrophil (PMN) infiltration that degrades stromal collagen and proteoglycans, precipitating stromal melting and corneal perforation.

Major Pathogen Profiles

• Pseudomonas aeruginosa: The most devastating pathogen associated with soft contact lenses (especially extended/overnight wear). A Gram-negative, aerobic, motile rod that elaborates Exotoxin A (inhibiting host protein synthesis via elongation factor 2 ADP-ribosylation), elastase, and a Type III secretion system (ExoU cytotoxin causing rapid cellular lysis). Slit-lamp biomicroscopy reveals a dense "ground-glass" stromal haze, copious yellowish-green mucopurulent discharge (pyocyanin pigment), rapid liquefactive stromal necrosis capable of complete corneal melting and perforation within 24 to 48 hours, and an immune ring infiltrate (Wessely ring) formed by antigen-antibody complex precipitation.
• Staphylococcus aureus (including MRSA): Gram-positive cocci in clusters. Characteristically produces a distinct, round, focal white-yellow stromal infiltrate with distinct, well-demarcated margins, minimal surrounding stromal spread, and microabscesses.
• Streptococcus pneumoniae: Gram-positive lancet-shaped diplococci. Typically produces a creeping, serpiginous ulcer with an undermined, advancing necrotic border and extensive deep stromal necrosis accompanied by an early, massive sterile hypopyon in the anterior chamber.
• Moraxella lacunata: Gram-negative diplobacilli. Tends to cause an indolent, oval, paracentral or inferior stromal ulcer with slow progression, seen predominantly in elderly, malnourished, alcoholic, or immunosuppressed patients.

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2. Corneal Diagnostic Workup: Scraping Protocol & Culture Media

Every corneal ulcer that is central, large ($> 1.5–2.0\text{ mm}$), deep ($> 50\%$ stromal depth), vision-threatening, or recalcitrant to initial therapy requires immediate corneal scraping for microscopy and culture prior to initiating antimicrobial drops.

Scraping Protocol

1. Instil preservative-free topical anaesthetic (proxymetacaine 0.5% or proparacaine 0.5%). Avoid anaesthetics with bacteriostatic preservatives such as benzalkonium chloride (BAK), which inhibit microbial growth on agar.
2. Under direct slit-lamp visualisation, use a sterilised platinum Kimura spatula, a 21-gauge sterile needle, or a sterile surgical blade (#15) to scrape the advancing border and base of the ulcer. Avoid necrotic slough, which contains dead neutrophils rather than viable organisms.
3. Inoculate solid media using gentle "C-streaks" without breaking the agar surface. Inoculate liquid broths directly.

Primary Diagnostic Stains and Culture Media

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3. Antimicrobial Pharmacotherapy for Bacterial Keratitis

Fortified Topical Antibiotics

For severe, central, deep or rapidly progressive bacterial keratitis, obtain appropriate microbiological samples promptly and start intensive treatment without waiting for culture results. Empirical treatment may use a suitable fluoroquinolone or fortified combination according to severity, local susceptibility, prior treatment and specialist protocol. Fortified vancomycin and ceftazidime are useful options in selected cases, not a mandatory universal pair for every ulcer. Review response closely and adjust to the organism and sensitivity results.

• Gram-Positive Coverage: Fortified Vancomycin 50 mg/mL (5%) or Cefuroxime/Cefazolin 50 mg/mL. Vancomycin provides bactericidal coverage against Methicillin-Resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci, and penicillin-resistant Streptococcus pneumoniae.
• Gram-Negative Coverage: Fortified Ceftazidime 50 mg/mL (5%) or Amikacin/Tobramycin 14 mg/mL (1.4%). Ceftazidime provides excellent coverage against Pseudomonas aeruginosa without the epithelial toxicity seen with prolonged aminoglycoside administration.

Intensive Dosing Schedule

• Loading Phase: One drop every 5 minutes for the first 30 minutes.
• Induction Phase: One drop alternating every 15 to 30 minutes round-the-clock for the initial 24 to 48 hours.
• Consolidation Phase: Gradual tapering according to objective clinical response: re-epithelialisation, blunting of infiltrate borders, reduction in stromal oedema, and clearance of anterior chamber hypopyon.

Monotherapy with Fluoroquinolones

Fluoroquinolone monotherapy can be appropriate in selected bacterial ulcers, including some more substantial lesions, according to susceptibility and local protocol. Severity, location, progression and clinical response determine escalation; there is no universal peripheral-size-only rule.

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