Nocardia keratitis presenting as an anterior chamber ball of exudates and its management
- 1 Cornea and Anterior Segment, LV Prasad Eye Institute GMR Varalakshmi Campus, Visakhapatnam, India
- 2 Cornea, LV Prasad Eye Institute, Hyderabad, India
- 3 Ocular Microbiology Service, LV Prasad Eye Institute GMR Varalakshmi Campus, Visakhapatnam, India
- Correspondence to Dr Maneesha Mohan Bellala; maneeshabellala@gmail.com
Abstract
A man in late 40s presented with corneal ulcer of the right eye of 1 month duration. He had a central corneal epithelial defect measuring 4.6×4.2 mm with an underlying 3.6×3.5 mm anterior to mid stromal patchy infiltrate and 1.4 mm hypopyon. Gram stain of the colonies on chocolate agar showed presence of confluent thin branching, gram-positive beaded filaments, which were positive after 1% acid fast stain. This confirmed our organism to be Nocardia sp. Topical amikacin was started but continued worsening of the infiltrate and presence of a ball of exudates in the anterior chamber, prompted the use of systemic trimethoprim-sulfamethoxazole. There was a dramatic improvement in the signs and symptoms, with complete resolution of infection over a period of 1 month.
Background
Nocardia are oblique aerobic, branching, beaded, gram-positive, weakly acid-fast, filamentous bacteria, of the family Actinomycetaceae frequently encountered in soil and decaying vegetable matter.1 2 Nocardia keratitis is often misdiagnosed because it is not commonly encountered in day to day practice and the clinical picture may resemble fungal or acanthamoeba keratitis.3 N. infections do not respond to regularly used first-line medications for bacterial keratitis, such as fluoroquinolones.
Hence, early scraping of infiltrate and prompt diagnosis of organisms becomes essential for appropriate treatment. With the initiation of therapy, N. keratitis carries a good prognosis. We report a case of a rare presentation of N. keratitis and also discuss the use of combination of treatment modality (topical and systemic) for best possible outcomes.
Case presentation
An immunocompetent man in his 40s presented with a 1-month report of a red, painful, photophobic right eye. He recalled an incident a few days prior to the complaints; fall of dust while doing agriculture work. He had no previous medical history. He was diagnosed elsewhere clinically as a case of fungal keratitis and started on topical natamycin 5%, tobramycin (0.3%) and homatropine(2% w/v) and oral ketoconazole 200 mg . He had been using these medications for the past 20 days but failed to respond to treatment and was referred to our hospital for further management. Presenting uncorrected visual acuity in the right eye was counting fingers at 1 m. The right eye had lid oedema and anterior segment examination was significant for circumciliary congestion, a central corneal epithelial defect of 4.6×4.2 mm with an underlying 3.6×3.5 mm anterior to mid stromal patchy infiltrate having a hypopyon of 1.4 mm (figure 1A). On B-Scan, the vitreous was echo free and retina attached. The left eye examination was unremarkable. Corneal scrapings were obtained and stained for microscopic evaluation with 10% potassium hydroxide and Gram’s stain. Smear examination showed Gram-positive thin beaded filaments which were positive after 1% acid fast stain (figure 1C,D) and grew on chocolate agar. This confirmed our organism to be Nocardia sp. Treatment with hourly amikacin eye drops 2% (2 per cent amikacin was prepared by diluting 2 mL (100 mg/1 mL) of parental amikacin injection in 8 mL of Tears plus eye drops (polyvinyl alcohol 14 mg+povidone 6 mg, Allergan, Irvine, California) and homatropine 0.5% eye drops was initiated. Worsening was observed in the form of increase in infiltrate size to 6×5.5 mm, developing the characteristic wreath-like pattern and increasing AC exudation at 1-week follow-up(figure 2A). The patient was asked to continue the same medication and the importance of compliance was stressed as he was not using medications as prescribed. In the next visit, patient presented with further detoriation(figure 2B) and repeatscraping was done to rule out any mixed infection, but smear examination demonstrated only Nocardia. Topical fortified cefuroxime was added based on sensitivity report. The patient reviewed at the clinic after 1 week. On examination, we noted lid oedema, corneal epithelial defect of 4 mmV×4.5 mmH×5.5 mm (diagonally) overlying a resolving mid stromal infiltrate and endoexudates organised into a well-defined lesion with rounded margins; occupying an area of 8 mmH×6mmV×7.5mm touching the lens capsule along with a hypopyon of 2 mm and deep vascularisation at 6–7’0 clock(figure 2C).
(A) Slit-lamp image of right eye showing a central corneal epithelial defect of 4.6×4.2 mm with an underlying 3.6×3.5 mm anterior to mid stromal patchy infiltrate having a hypopyon of 1.4 mm, (B) fluorescein stained image of the same observed under blue filter, (C) Gram’s stain (×100) revealing Gram positive thin beaded filaments and also depicting, (D) acid fast positive nature of the organism.
Clinical deterioration—slit lamp photographs 7 (A), 15 (B) and 21 (C) days after first presentation. Note the small pinhead-like gray-white infiltrates initially appearing as satellites at the edge of the superficial lesion, and subsequently spreading over the affected area while increasing in size and also the increase in retrocorneal exudates eventually forming an anterior chamber (AC) ball.
Differential diagnosis
Nocardia sp. keratitis often mimics fungal keratitis clinically as both can present as patchy stromal infiltrates and could mislead clinicians to begin empirical treatment with antifungal therapy as done in this case initially. Acanthamoeba keratitis is included in the differential diagnosis of N. keratitis, as both present with marked blepharospasm, photophobia and wreath-like infiltrates.
N. keratitis can sometimes present as pseudo-dendritic epithelial defect mimicking viral epithelial keratitis or superior limbic keratoconjunctivitis if involving superior part of the cornea.4 Also its benign course and presence of vascularisation can lead to assumption of recurrence of herpetic interstitial keratitis.
Treatment
We considered an AC wash initially in view of increasing exudates (figure 3A), but instead; the decision to add oral antibiotics was made and so; a fixed combination of sulfamethoxazole/trimethoprim (800 mg/160 mg) was administered every 12 hourly. Patient reviewed after 3 days and there was reduction in the size of epithelial defect (4.5 mmV × 6 mmH) (figure 3B) and endoexudates (measuring 6.5 mmV × 8 mmH). He was asked to continue same medications. After 10 days, there was significant reduction in the AC exudation measuring 4×4.5 mm and <1 mm hypopyon (figure 3C). Eventually complete healing of epithelial defect occurred with a residual deep seated infiltrate in subsequent follow-up (figure 3D).
(A,B,C,D) Slit lamp photographs of resolution of nocardia keratitis after adding oral sulfamethoxazole/trimethoprim.
Outcome and follow-up
Oral treatment with sulfamethoxazole/trimethoprim (800 mg/160 mg) two times per day was continued upto 2 weeks after resolution of stromal infiltrate—a total of 6 weeks of the drug. After which patient was asked to continue topical fortified amikacin eye drops for another 4 weeks, eventually resulting in a macular corneal scar with an early cataractous lens (figure 4A,B).
(A, B) At the final review; right eye showed a nebulo-macular corneal scar involving the visual axis and no anterior chamber activity was noted.
Discussion
Among the different species of Nocardia responsible for ocular infection, N. asteroides has been identified to be the most common causative agent for keratitis.5 Predisposing factors are trauma with vegetative material, dirt, stone, prior surgery, corticosteroid use and inappropriate contact lens wear.6 N keratitis typically presents as patchy anterior stromal infiltrate, occasionally with feathery borders, stromal hyphae and wreath-like infiltrates.5 Other associated findings like moderate AC reaction, hypopyon, satellite lesions, Descemet folds and diffuse keratic precipitates have too been documented.5 7–9 The presentation of this case was consistent with these reports but was unusual as it developed an organised AC ball. The inadvertent use of topical corticosteroids may also have been a predisposing factor. A rabbit model of topical corticosteroid use in N. keratitis observed the development of large granulomatous lesions with extension into the AC in those treated with topical steroids, whereas no extension was noted in those not treated with steroids.10
Very often diagnostic intraocular surgery is needed to determine causative organism.11–14
N. keratitis has a good prognosis if treated promptly. Lalitha et al demonstrated that the best visual outcomes will be attained if treatment starts within 15 days of ulcer onset.9 Sensitivity testing of potential antibiotics is prudent before initiating treatment especially in atypical clinical presentations.
Sulphacetamide, sulpha-methoxazole and trimethoprim were viewed to be the treatment of choice in the early years,15 until it was observed that the minimum inhibitory concentrations (MIC) of amikacin was much lower than the sulphonamides when used to treat n. keratitis.16 Ever since, amikacin in the concentration of 2%–2.5% is the drug of choice for ocular Nocardiosis.6 17–19 Despite its high reported sensitivity, amikacin resistant cases have been described.2 19 20
Topical trimethoprim–sulphamethoxazole is also an effective primary therapy for superficial N. keratitis.21 In vitro studies have shown that when given together, the two compounds are synergistic because of their sequential inhibition of bacterial folic acid synthesis, an essential pathway for DNA replication. As a result, MICs for the two drugs are lowered when given together.22 Sulfonamides with or without trimethoprim have been the main stay of antimicrobial therapy for human nocardiosis.23–25
Orally administered sulfamethoxazole/trimethoprim is known to attain therapeutic levels in the aqueous and vitreous cavity in a non-inflamed human eye.26 Although systemic antibiotics have been used in treatment of N. endophthalmitis,27–29 its role in keratitis is not very clear.6 In this patient, however, the resolution of exudates in the AC only occurred after commencement of sulfamethoxazole/trimethoprim (800 mg/160 mg).
Burdová et al reported a similar case of post-traumatic exogenous endophthalmitis caused by N. farcinica that required systemic drugs for a prolonged amount of time (12 months) due to the involvement of iris tissue and the anterior lens capsule. Only after a later microbiological sample yielded a negative result; was the oral sulfamethoxazole/trimethoprim combination discontinued.12 While some cases required more than 3 months of systemic medication,13 other authors have reported favourable outcomes for N. endophthalmitis after 6–10 weeks of oral therapy.14 30 According to Sharma and O’Hagan,31 the infection resurfaced following the application of topical steroids, requiring reintroduction of oral sulfamethoxazole/trimethoprim. Therefore, we suggest that the duration of systemic therapy be determined based on the severity of the infection and the immune status of the patient.
The high ocular penetration and minimal side effect profile of sulfamethoxazole/trimethoprim make it beneficial as an adjunct to topical treatment in Nocardia sp. keratitis, and we recommend considering its use in cases presenting with exuberant AC exudates, based on cultured drug sensitivities.
Written consent was obtained from the patient for publication of this case report and any accompanying images, provided no identifying features were released.
Patient’s perspective
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At first, I did not expect to be admitted to the hospital. However, I am very pleased with the dramatic response I received after starting the treatment.
Learning points
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Nocardia keratitis is often misdiagnosed. Routine smear examination with use of 1% acid fast staining can help differentiate this uncommon organism.
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The high ocular penetration and minimal side effect profile of oral sulfamethoxazole/trimethoprim make it beneficial as an adjunct treatment in Nocardia keratitis with intraocular extension.
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We recommend considering its use in cases presenting with exuberant anterior chamber exudates in place of surgical intervention provided the iris and lens are uninvolved.
Ethics statements
Patient consent for publication
Acknowledgments
Dr Joveeta Joseph (Head of Microbiology, Jhaveri Microbiology Centre, L V Prasad Eye Institute, Hyderabad) for her expert opinion. Mr.Vinod Kumar Uttaravalli for the slit lamp photography.
Footnotes
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Contributors MMB was involved in pt care from intial presentation to last follow-up. BB for providing valuable inputs during the treatment. PST was involved in drafting of the manuscript. BB and BM were involved in critical revision of the manuscript for important intellectual content.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.
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