The role of oral co-trimoxazole in treating Nocardia farcinica keratitis—a case report

Background Nocardia farcinica is one of the more recently identified species of the Nocardia genus. Nocardia farcinica keratitis is a rare occurrence, with only eight previously reported cases. Semi-permeable rigid contact lens use was associated with one of these reported cases. We report the first case of extended wear soft contact-lens-related Nocardia farcinica keratitis and recommend a new treatment regime. Findings A 47-year-old lady presented with a right eye keratitis after wearing her extended wear soft contact lenses for five continuous weeks. There was no history of trauma or swimming with contact lenses in. Empirical ciprofloxacin and tobramycin eye drops were not tolerated due to ocular surface irritation on application; and instead, empirical treatment was with chloramphenicol and fortified gentamicin 1.5 % eye drops. Corneal scrapings grew Nocardia farcinica after 3 weeks—sensitive to amikacin and co-trimoxazole. Treatment was changed to amikacin 2.5 % eye drops, resulting in partial resolution of the corneal infiltrates. Oral co-trimoxazole 160/800 mg BD was added, due to cultured drug sensitivity and its high ocular penetration, with good results and a final right eye best-corrected visual acuity of 6/5. Conclusion Nocardia farcinica keratitis should be considered in the differential diagnosis of contact-lens-related keratitis. We report the first case occurring in association with extended wear soft contact lenses. Nocardia species can mimic fungal and Acanthamoeba keratitis. Treatment with oral co-trimoxazole has not been previously reported. This case demonstrates a role for co-trimoxazole in treating Nocardia farcinica keratitis based on cultured drug sensitivities.


Report
A 47-year-old Caucasian woman presented with a 2-day history of a red, painful, photophobic right eye and marked blepharospasm on a background of contact lens wear. She wore her monthly disposable soft contact lenses for five continuous weeks. There was a history of recent gardening but no trauma, travel to remote areas, or swimming whilst wearing contact lenses. Her only medication was irbesartan for well-controlled hypertension.
On examination, unaided visual acuity in the right eye at presentation was 6/18, improving to 6/9 with pinhole correction. Best-corrected visual acuity (BCVA) in the left eye was 6/9. The right eye was injected, with four central satellite lesions (Fig. 1) and moderate anterior chamber reaction (cells 3+; flare 1+; no hypopyon). The vitreous was quiet and intraocular pressure was 14 mmHg on the right eye. Ocular examination of the left eye was unremarkable. Corneal scrapings were taken and her contact lenses sent for microscopy, culture, and sensitivities.
Treatment with ciprofloxacin 0.3 % eye drops hourly and homatropine 2 % eye drops TDS right eye was commenced. The patient was non-compliant due to ocular surface irritation from the drops. Antibiotic therapy was changed to tobramycin 0.3 % eye drops hourly right eye 2 days post-presentation to improve compliance but was again unsuccessful due to irritation from tobramycin. Four days after presentation, the treatment was changed to chloramphenicol minims hourly, fortified gentamicin 1.5 % eye drops hourly, and atropine 1 % minims TDS right eye. Ocular surface discomfort settled on this treatment regime. Further right eye corneal scraping was performed.
After 1 week of treatment, the right eye's unaided visual acuity reduced to light perception, improving to 6/18 with pinhole correction. Corneal oedema and inferior keratitic precipitates had developed, and the satellite lesions had coalesced into a 4.7 × 3.8 mm wreath-like infiltrate with surrounding stromal hyphae and a central corneal epithelial defect. The posterior segment remained uninvolved. The initial corneal scraping and contact lens cultures revealed no pathogens. The second corneal scraping identified a Gram-positive aerobic Actinomyces only. Treatment on hourly chloramphenicol 0.3 % minims and gentamicin 1.5 % eye drops right eye continued until drug sensitivities were available.
Following 3 weeks of culture, the second corneal scraping grew Nocardia farcinica (Fig. 2)-sensitive to cotrimoxazole and amikacin, and resistant to cephalothin, tobramycin, and ciprofloxacin. Sensitivities to chloramphenicol and gentamicin were not available from the laboratory.
Treatment with prednisolone acetate eye drops six times per day right eye was commenced after fungal pathogens were not cultured. The patient remained on hourly chloramphenicol 0.3 % minims and gentamicin 1.5 % eye drops right eye for another 2 weeks. The keratitis remained stable in this period, and the right eye pinhole vision fluctuated between 6/36 and 6/18. The wreath-like infiltrate and central epithelial defect did not change in size, and the anterior chamber reaction reduced slightly.
The antibiotic regime was subsequently changed to amikacin 2.5 % eye drops hourly right eye based on drug sensitivities. The patient remained on atropine 1 % minims QID and prednisolone acetate eye drops six times per day right eye. Within 1 week on this regime, an improvement occurred, with less conjunctival injection and decreased density of the wreath-like infiltrate. However, the size of the infiltrate and central epithelial defect showed no change. In consultation with the Infectious Diseases Unit, oral co-trimoxazole 160/800 mg BD (trimethoprim-sulfamethoxazole) was added based on the cultured drug sensitivities and its high ocular penetration [9]. Unfortunately, given the regional location of the treating hospital, polymyxin B and trimethoprim ophthalmic solution was not available from the pharmacy. The wreath-like infiltrate  and epithelial defect resolved leaving a dense central corneal scar over the subsequent 3 weeks. The right eye BCVA was now hand movements at 3 m. The amikacin 2.5 % eye drops was tapered weekly, prednisolone acetate eye drops was increased to two hourly, and oral cotrimoxazole 160/800 mg BD and atropine 1 % eye drops were ceased. Clinical improvement occurred over the next month, and the right eye pinhole vision was now 6/18. However, the patient reported 2 days of redness, ocular surface discomfort, and photophobia whilst on amikacin 2.5 % eye drops TDS and prednisolone acetate eye drops six times per day. The right eye pinhole vision reduced to 6/60. A new epithelial defect and satellite lesion had developed superior to the corneal scar (Fig. 3). Subsequently, amikacin 2.5 % eye drops was increased to hourly, oral cotrimoxazole 160/800 mg BD was restarted, and prednisolone acetate eye drops was ceased.
The new satellite lesion did not form a wreath-like infiltrate as had occurred previously. The epithelial defect required 3 weeks of amikacin 2.5 % eye drops hourly right eye and oral co-trimoxazole 160/800 mg BD before healing. Prednisolone acetate eye drops was continued by the patient to relieve ocular discomfort against advice. Once the epithelial defect had healed, oral cotrimoxazole was ceased and amikacin eye drops was tapered.
Prednisolone acetate eye drops had been successfully ceased, and there were no signs of relapse on the tapering dose of amikacin eye drops over the course of the next 8 weeks. At final review, the right eye BCVA was 6/ 5 with a faint central wreath-like anterior stromal scar and no anterior chamber activity.
Most reported cases of intraocular Nocardia farcinica infection have occurred secondary to haematogenous spread from a primary pulmonary infectious focus in immunocompromised individuals [3][4][5][6]10]. There have been two reported cases of post-operative and post-traumatic endophthalmitis caused from Nocardia farcinica [5,6].
The genus Nocardia is saprophytes [1][2][3][4][5][6][7][8]10]. There have been eight documented cases of Nocardia farcinica keratitis [1,2]. Seven of these cases were reported in a South Indian study, and all occurred secondary to trauma with organic matter [2]. The remaining case of Nocardia farcinica keratitis was contact-lens-related, occurring after semi-permeable rigid contact lenses were cleaned in unchlorinated rainwater [1]. We report the first case of Nocardia farcinica keratitis occurring with the use of extended wear soft contact lenses.
Extended wear soft contact lenses are a welldocumented major risk factor for microbial keratitis, due to their interference with the natural defence properties of the ocular surface [14]. It has not commonly been reported as a cause of Nocardia sp. keratitis [1,2,15,16]. However, the larger studies on Nocardia sp. keratitis have been conducted in less urbanised areas, leaving the potential for population bias [2,16]. Our case adds to the small number of Nocardia sp. keratitis cases where contact lens wear was the most likely predisposing factor [1,15].
Nocardia sp. keratitis has been reported as presenting with patchy anterior stromal infiltrates-occasionally with feathery borders, stromal hyphae, and wreath-like infiltrates [1,2,6,15,16]. Keratitic precipitates and endothelial ring deposits have also been documented [2]. The presentation of this case was consistent with these reports but was unusual as there was no history of contamination with plant matter as has been described in other cases of Nocardia farcinica keratitis [1,2]. Nocardia sp. keratitis mimics the presentation of fungal keratitis and could mislead clinicians to commence empirical treatment with antifungal therapy [1,2,15,17].
Acanthamoeba keratitis is included in the differential diagnosis of Nocardia farcinica keratitis, as both present with marked blepharospasm, photophobia, and wreathlike infiltrates [1,2]. There has previously been one report of Nocardia asteroides keratitis being successfully treated with polyhexamethylene biguanide, demonstrating that this pool disinfectant could be used as empirical treatment in Nocardia sp. keratitis [2,15]. Ciprofloxacin 0.3 % eye drops are widely regarded as an empirical treatment for contact-lens-related keratitis due to its efficacy against common causative pathogens [14]. This patient was empirically treated with ciprofloxacin eye drops, and then tobramycin eye drops, another agent commonly used to treat contact lens keratitis [14]. The strain of Nocardia farcinica grown from this patient's corneal scrapings was resistant to ciprofloxacin and tobramycin. A South Indian study looking at the antibiotic sensitivities of four different Nocardia sp. (N. asteroides, N. farcinica, N. cyriageorgica, and N. otitidiscaviarum) found that Nocardia farcinica was the only species to display complete resistance to gentamicin, tobramycin, and cefotaxime but found that all seven cases were sensitive to ciprofloxacin [18].
The role of systemic antibiotics in Nocardia sp. keratitis has not been documented [2,16]. In this patient, resolution of the epithelial defect and clearing of the corneal infiltrates only occurred after the commencement of oral co-trimoxazole. The high ocular penetration and minimal side effect profile of co-trimoxazole make it beneficial as an adjunct to topical treatment in Nocardia sp. keratitis, based on cultured drug sensitivities [9].
Clinical reactivation of infection occurred with topical steroid use after the epithelial defect had commenced scarring. Reactivation with steroid use in Nocardia sp. has been highlighted before, and they should be used cautiously in Nocardia sp. infections [1,2].
Nocardia farcinica is a rare cause of keratitis and should be considered as differential diagnoses of contact-lensrelated keratitis, post-traumatic keratitis, and clinical pictures suggestive of fungal and Acanthamoeba keratitis. This is the first reported case of Nocardia farcinica keratitis occurring secondary to extended wear soft contact lenses. Nocardia sp. keratitis is a challenge to treat empirically due to high levels of resistance to common topical ophthalmic antibiotics. Despite delayed treatment in this case, the keratitis responded well to a combination of amikacin 2.5 % eye drops and oral co-trimoxazole 160/800 mg BD and long duration of therapy, with a final right eye BCVA of 6/5. This case demonstrates the effectiveness of oral co-trimoxazole160/800 mg BD in treating Nocardia farcinica keratitis, and we recommend considering it as an adjunct treatment based on cultured drug sensitivities.

Competing interests
The authors declare that they have no competing interests.