Nocardia is an aerobic, Gram-positive, non-motile, branching filamentous bacterium belonging to the order Actinomycetales. Originally classified as a fungus, it is now recognized as a true bacterium. Its diameter is less than 1.5 μm, and there are at least 12 recognized species. The most common cause of corneal infection is N. asteroides3).
Nocardia is commonly found in soil, mud, dust, and decaying vegetation, and is distributed worldwide. It is not part of the normal flora of the eye or respiratory tract. N. asteroides is more common in temperate regions, while N. brasiliensis is more common in tropical and subtropical regions.
Nocardia ocular infections include keratitis, scleritis, conjunctivitis, canaliculitis, dacryocystitis, orbital cellulitis, and endophthalmitis, with corneal infection being the most common. The prevalence among all microbial keratitis is less than 2%1). In a large multicenter prospective treatment study (SCUT), Nocardia species accounted for 11.5% of cases in a patient population primarily from South India6).
Clinically important is that Nocardia does not respond to common first-line antibiotics for bacterial keratitis, such as fluoroquinolones.
Nocardia is a branching filamentous bacterium originally classified as a fungus, and the clinical presentation of keratitis—patchy infiltrates, satellite lesions, and indolent course—also resembles fungal keratitis. However, it can be differentiated from fungi by Gram stain showing positive branching filaments and weak acid-fastness. KOH preparation does not detect fungal elements1)2).
Nocardia ocular infection usually follows a protracted course.
Typical Findings
Wreath-like infiltration: Yellow-white, pinhead-sized superficial infiltrates arranged in a ring. A characteristic pattern indicating pathogenicity1).
Satellite lesions: Small infiltrates scattered around the main lesion.
Hypopyon: Accompanied by anterior chamber reaction, usually with hypopyon.
Epithelial defect: Corneal epithelium over the infiltrate is damaged, becoming fluorescein-positive.
Atypical Findings
Pseudodendritic epithelial defect: Mimics herpes keratitis3).
Superior corneal localized type: May be misdiagnosed as superior limbic keratoconjunctivitis (SLK)3).
Anterior chamber exudate ball (AC ball): A rare finding in severe cases4).
Corneal neovascularization: Appears in the periphery in chronic cases.
Infiltration is mainly in the anterior stroma, involving the epithelium and subepithelial tissue. The surrounding stroma is usually clear. Corneal sensation may be reduced.
Typically, yellow-white pinhead-sized superficial infiltrates are arranged in a wreath-like pattern with satellite lesions. However, atypical clinical presentations such as pseudodendritic defects or SLK-like superior localized forms may occur, making differentiation from fungal keratitis and herpes keratitis difficult in some cases 3).
Nocardia is an actinomycete that inhabits soil and causes keratitis associated with CL wear or trauma 5). The guidelines also note that it produces poorly demarcated pale infiltrates 5).
The gold standard for diagnosis is scraping of the corneal lesion.
Nocardia is not sensitive to growth inhibitors and grows aerobically as small, white, dry colonies on blood agar, chocolate agar, and Sabouraud dextrose agar. Growth usually occurs within 48–72 hours, but a 7-day incubation period may be necessary 1). The appearance of white colonies with calcification on the medium may be mistaken for contaminants, but since Nocardia is not a common contaminant, its isolation is always considered significant.
MALDI-TOF mass spectrometry, PCR-based assays, and 16S rRNA gene sequencing enable rapid species-level identification and detection of resistant strains.
Main differential diagnoses of Nocardia keratitis:
Nocardia is a slow-growing bacterium; although it can usually be cultured within 48–72 hours, isolation from clinical specimens may require 7 days or more1). This slow growth rate contributes to diagnostic delays. Modern diagnostic techniques such as MALDI-TOF and PCR are enabling rapid identification.
Claudia et al. (2025) reported a case of Nocardia keratitis in a 41-year-old man with a wreath-like infiltrate and hypopyon, treated with subconjunctival amikacin and topical tobramycin. The hypopyon completely resolved after one month, but corneal scarring and neovascularization remained, requiring consideration of corneal transplantation1).
Chang et al. (2021) reported Nocardia keratitis in a 41-year-old male contact lens user. It was misdiagnosed as SLK or herpes simplex keratitis, leading to multiple incorrect treatments over three months. Culture identified N. asteroides, which was resistant to amikacin, so topical trimethoprim-sulfamethoxazole (SEPTRA) 80 mg/mL was administered, resulting in clinical improvement within 3 days. Final visual acuity was 20/303).
Bellala et al. (2023) reported a case of Nocardia keratitis in a man in his 40s that did not respond to topical amikacin and formed an exudative ball in the anterior chamber (AC ball). Addition of oral sulfamethoxazole-trimethoprim (800/160 mg bid) led to dramatic improvement, with complete healing in one month. Oral TMP-SMX reaches therapeutic concentrations in the aqueous humor and vitreous even in non-inflamed eyes, making it useful for cases with anterior chamber involvement4).
For initial treatment before identification of the causative organism, in severe cases, combine two drugs from fluoroquinolones, cephalosporins, and aminoglycosides 5). If Nocardia is suspected, include amikacin in the combination.
In bacterial keratitis, if Acanthamoeba, Nocardia, or fungi are suspected, corticosteroids should be avoided 6).
In a subgroup analysis of SCUT, steroid use for Nocardia keratitis was associated with worse visual outcomes, and similar results were observed at 12 months of follow-up 6). On the other hand, in non-Nocardia bacterial keratitis, adding steroids within 2–3 days after starting antibiotics led to one line better visual acuity at 3 months 6).
Nocardia keratitis is usually managed adequately with medical treatment. Surgical treatment is considered in the following cases:
Surgical options: therapeutic lamellar keratectomy, penetrating keratoplasty, conjunctival flap.
For amikacin-resistant Nocardia keratitis, trimethoprim-sulfamethoxazole (TMP-SMX) is an effective alternative. The injectable formulation (80 mg/mL sulfamethoxazole + 16 mg/mL trimethoprim) can be used directly as eye drops3). The synergistic effect of both drugs lowers the MIC compared to either agent alone. Oral administration also achieves therapeutic concentrations in the aqueous humor and vitreous body4).
Nocardia grows and proliferates slowly and does not cause fulminant infection immediately after invasion. Since this bacterium can infect healthy individuals, its virulence factors are thought to be involved.
In a rabbit model of Nocardia keratitis, large granulomatous lesions extending into the anterior chamber were observed in the group treated with topical steroids. This extension was not observed in the group without steroids. Steroids are thought to suppress the host immune response and promote the extension of Nocardia into the anterior chamber4).
Molecular biological techniques such as MALDI-TOF mass spectrometry, PCR-based assays, and next-generation sequencing (NGS) enable rapid identification of Nocardia at the species level. These technologies can significantly shorten the identification time compared to conventional culture methods, which require several days to a week.
Reports of amikacin-resistant Nocardia are increasing, highlighting the growing importance of drug susceptibility testing3).
Rahman et al. (2025) reported a case of Nocardia keratitis following agricultural trauma. After one month of incorrect initial treatment with antifungal agents, switching to targeted therapy centered on amikacin 2% led to dramatic improvement within 5 days. The ulcer healed in 3 weeks, and final visual acuity was 6/182).
In the future, establishment of evidence-based standardized treatment protocols for Nocardia ocular infections is needed1).
