Nocardia Keratitis

Excerpt

Nocardia is a gram-variable, aerobic, weakly acid-fast bacterium that infrequently causes ocular disease, most often as a corneal infection (see Image. Filamentous Nocardia). Misdiagnosis or delayed recognition of Nocardia keratitis commonly stems from nonspecific clinical features that resemble those produced by more prevalent pathogens. The organism often responds poorly to standard empiric agents for bacterial keratitis, including fluoroquinolones, leading to treatment delays and avoidable visual morbidity.

A rare but potentially vision-threatening corneal infection, Nocardia keratitis typically follows direct inoculation of the epithelium by the pathogen, which is found in soil, decaying vegetation, and water (see Image. Nocardia Keratitis). While Nocardia most frequently causes pulmonary or cutaneous disease, ocular involvement may arise from systemic spread or primary infection. Corneal entry usually occurs through epithelial defects associated with trauma, contact lens wear, ocular surface disease, or prior surgery, underscoring the relevance of both environmental and iatrogenic risk factors.

Nocardia keratitis accounts for fewer than 2% of bacterial keratitis cases in temperate climates but appears more frequently in tropical and subtropical regions where agricultural exposure and humid conditions favor organism growth. The risk increases among patients with impaired ocular surface defenses, including those with dry eye, neurotrophic keratitis, prior herpetic infection, and immunodeficiency. Although systemic immunocompromise is not required for corneal involvement, chronic topical steroid use and systemic diseases such as diabetes mellitus may contribute to more severe disease courses.

Clinically, Nocardia keratitis presents insidiously, with patients reporting photophobia, foreign-body sensation, tearing, and blurred vision developing over several days to weeks. On slit-lamp examination, the hallmark feature is a multifocal, superficial stromal infiltrate with a characteristic “wreath-like” or “serpiginous” pattern and satellite lesions radiating from a central nidus. Corneal epithelial defects often appear irregular and overlay thin, yellowish stromal infiltrates. A dense perineural infiltrate—radial, bead-like accumulations along corneal nerves—is another suggestive finding, though not pathognomonic. Hypopyon formation is uncommon but, when present, may indicate deeper anterior chamber involvement.

Rapid, accurate diagnosis remains challenging. Standard smear techniques using gram, modified acid-fast (eg, Kinyoun), and Giemsa stains can reveal delicate, branching filamentous organisms. However, low organism load and atypical morphology may lead to misidentification as fungal filaments or other actinomycetes. Culture on selective media such as blood agar, Sabouraud dextrose agar (SDA), and Lowenstein-Jensen medium supports the growth of Nocardia colonies, typically chalky, matte, and white to tan over 3 to 5 days. Species-level identification may require biochemical assays, high-performance liquid chromatography, or molecular methods such as polymerase chain reaction (PCR) and 16S rRNA gene sequencing—tools that enable faster turnaround times and precise speciation to guide antimicrobial therapy.

Effective treatment depends on the timely initiation of targeted topical and, when needed, systemic antibiotics. Historically, sulfonamides, particularly topical trimethoprim-sulfamethoxazole (TMP-SMX), were used based on Nocardia’s susceptibility profile. Topical amikacin 2.5% is now widely considered first-line therapy for its potent in vitro and in vivo activity, superior corneal penetration, and favorable safety profile. A typical regimen includes hourly instillation during the acute phase, followed by tapering over 4 to 6 weeks, depending on clinical response.

Systemic TMP-SMX (160/800 mg twice daily) may be added for deep stromal involvement or scleral extension due to its complementary ocular tissue penetration. Alternative agents, such as topical linezolid, clarithromycin, or minocycline, may be used in cases of amikacin resistance, intolerance, or disseminated disease, highlighting the need for species-specific susceptibility data.

Despite targeted therapy, Nocardia keratitis may remain refractory, with prolonged healing and risk of corneal thinning, perforation, and scarring. Surgical interventions, including epithelial debridement, lamellar keratectomy, and therapeutic penetrating keratoplasty (TPK), are often required for persistent infiltrates, progressive stromal melt, or impending perforation. Adjunctive strategies such as corneal cross-linking have been evaluated in small case series to slow collagen degradation and microbial proliferation, though controlled clinical trials are lacking.

Outcomes vary widely and depend on diagnostic timing, species virulence, stromal depth of infection, host immune status, and the prompt initiation of effective antimicrobial therapy. Visual prognosis ranges from near-complete recovery with early treatment to severe impairment or globe loss in advanced or mismanaged cases. The high morbidity of Nocardia keratitis underscores the need for clinical vigilance, especially in at-risk individuals such as contact lens users, agricultural workers, and those with ocular surface disease.

From a systems perspective, Nocardia keratitis exposes key deficiencies in current ophthalmic practice, including the following:

1. Underrecognition due to clinical overlap with fungal keratitis

2. Limited access to rapid species-level diagnostics

3. Inconsistent empiric antibiotic regimens lacking Nocardia coverage

Addressing these gaps requires interprofessional collaboration among ophthalmologists, microbiologists, pharmacists, and primary care providers. Optimizing outcomes depends on streamlining diagnostic workflows, standardizing laboratory protocols, and disseminating guideline-based treatment strategies.

The expanding use of molecular diagnostics and the emergence of antimicrobial resistance demand continued surveillance and prospective studies. Comparative trials of topical agents, novel drug-delivery platforms (eg, antibiotic-loaded contact lenses or intracorneal implants), and evaluation of adjunctive therapies such as collagen cross-linking offer promising avenues for investigation. The potential utility of immunomodulators, biologics targeting inflammatory mediators, and photodynamic therapy remains largely unexplored, presenting opportunities to personalize treatment for this uncommon infection.

Nocardia keratitis presents significant diagnostic and therapeutic challenges with potentially severe visual consequences. A clear understanding of its epidemiology, clinical features, microbiology, and treatment is essential for managing corneal infections, especially in settings with high environmental exposure risk or ocular surface compromise. Improved outcomes depend on early recognition, targeted antimicrobial therapy, timely surgical intervention when warranted, and sustained interprofessional collaboration. Ongoing education, research, and quality-improvement efforts will be critical to advancing care and reducing the global burden of Nocardia keratitis.