The role of oral co-trimoxazole in treating Nocardia farcinica keratitis—a case report
© The Author(s). 2016
Received: 13 May 2015
Accepted: 8 June 2016
Published: 21 June 2016
The Correction to this article has been published in Journal of Ophthalmic Inflammation and Infection 2018 8:1
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.
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.
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.
Nocardia species (sp.) are a rare cause of human ocular infections [1–8]. Advances in laboratory techniques have resulted in further speciation of the genus [2, 3]. Nocardia farcinica is a newer species and has been implicated in keratitis, endophthalmitis, and chorioretinitis [1–6]. Eight cases of Nocardia farcinica keratitis have been reported in the literature, and only one has been associated with contact lens wear (semi-permeable rigid contact lenses) . We report the first case of extended wear soft contact-lens-related Nocardia farcinica keratitis and recommend a new treatment regime.
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.
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.
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 . 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 co-trimoxazole 160/800 mg BD and atropine 1 % eye drops were 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 co-trimoxazole 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.
Nocardia sp. are Gram-positive, partially acid-fast, aerobic rod-shaped bacteria that rarely cause systemic disease due to low virulence [1–8, 10]. Advances in laboratory speciation techniques have lead to the discovery of newer species, with identification of several other Nocardia sp. capable of infiltrating the cornea [2, 3]. The discovery of Nocardia farcinica is important because of its resistance to several common topical ophthalmic antibiotics [1, 10–13].
Most reported cases of intraocular Nocardia farcinica infection have occurred secondary to haematogenous spread from a primary pulmonary infectious focus in immunocompromised individuals [3–6, 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 [1–8, 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 . The remaining case of Nocardia farcinica keratitis was contact-lens-related, occurring after semi-permeable rigid contact lenses were cleaned in unchlorinated rainwater . 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 well-documented major risk factor for microbial keratitis, due to their interference with the natural defence properties of the ocular surface . 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 . 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 wreath-like 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 . This patient was empirically treated with ciprofloxacin eye drops, and then tobramycin eye drops, another agent commonly used to treat contact lens keratitis . 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 .
Previous reports have found a high level of resistance in Nocardia farcinica to both chloramphenicol and gentamicin [1, 16, 19, 20]. This highlights the importance of testing sensitivities to all potential ophthalmic antibiotics, especially in atypical clinical presentations. This is particularly relevant with Nocardia farcinica, which is resistant to many common topical ophthalmic antibiotic preparations [1, 10, 11, 15–20]. There have been no reports of amikacin resistance in Nocardia farcinica [1, 2, 11, 12, 19, 21, 22]. There have been a few reported cases in the general medical literature of Nocardia farcinica resistance to co-trimoxazole [4, 10, 16, 17].
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 .
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-lens-related 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.
Sp, species; BCVA, best-corrected visual acuity
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
- Eggink CA, Wesseling P, Boiron P, Meis JFGM (1997) Severe keratitis due to Nocardia farcinica. J Clin Microbiol 35:999–1001PubMedPubMed CentralGoogle Scholar
- Prajna L (2009) Nocardia keratitis. Curr Opin Ophthalmol 20:1–6View ArticleGoogle Scholar
- Lakosha H, Pavlin CJ, Lipton J (2000) Subretinal abscess due to Nocardia farcinica infection. Retina 20(3):269–274View ArticlePubMedGoogle Scholar
- Dodds EM, Echandi LV, Puente SI, Kaufman S (2006) Subretinal abscess due to Norcardia farcinica resistant to trimethoprim-sulfamethoxazole in a patient with systemic lupus erythematosus. Oc Immunol Inflam 14:249–51View ArticleGoogle Scholar
- Kawakami H, Sawada A, Mochizuki K, Takahashi K, Muto T (2010) Endogenous Nocardia farcinica endophthalmitis. Jpn J Ophthalmol 54(2):164–6View ArticlePubMedGoogle Scholar
- Tsui I, Uslan DZ, Hubschman JP, Deng SX (2010) Nocardia farcinica infection of a Baerveldt implant and endophthalmitis in a patient with a Boston type 1 keratoprosthesis. J Glaucoma 19(5):339–340PubMedGoogle Scholar
- Haripriya A, Lalitha P, Mathen M, Prajna NV, Kim R, Shukla D, Natchiar G, Srinivasan M (2005) Nocardia endophthalmitis after cataract surgery: clinicomicrobiological study. Am J Ophthalmol 139:837–846View ArticlePubMedGoogle Scholar
- Hudson JD, Danis RP, Chaluvadi U, Allen SD (2003) Posttraumatic exogenous Nocardia endophthalmitis. Am J Ophthalmol 135(6):915–7View ArticlePubMedGoogle Scholar
- Feiz V, Nijm L, Glickman RD, Morse LS, Telander DG, Park SS, Polage CR, Christiansen SM, Moshifar M (2013) Vitreous and aqueous penetration of orally administered trimethoprim-sulfamethoxazole combination in humans. Cornea [Epub ahead of print]Google Scholar
- De La Iglesia P, Viejo G, Gomez B, De Miguel D, Del Valle A, Otero L (2002) Fatal pulmonary Nocardia farcinica infection. J Clin Microbiol 40(3):1098–9View ArticleGoogle Scholar
- Wallace RJ, Tsukamura M, Brown BA, Brown J, Steingrube VA, Zhang Y, Nash DR (1990) Cefotaxime-resistant Nocardia asteroides strains are isolates of the controversial species Nocardia farcinica. J Clin Microbiol 28(12):2726–32PubMedPubMed CentralGoogle Scholar
- Larruskain J, Idigoras P, Marimon JM, Perez-Trallero E (2011) Susceptibility of 186 Nocardia sp. isolates to 20 antimicrobial agents. Antimicrob Agents Chemother 55(6):2995–8View ArticlePubMedPubMed CentralGoogle Scholar
- Glupczynski Y, Berhin C, Janssens M, Wauters G (2006) Determination of antimicrobial susceptibility patterns of Nocardia spp. from clinical specimens by Etest. Clin Microbio Infect 12(9):905–12View ArticleGoogle Scholar
- Eltis M (2011) Contact-lens-related microbial keratitis: case report and review. J Optom 4(4):122–7View ArticleGoogle Scholar
- Lin JC, Ward TP, Belyea DA, McEvoy P, Kramer KK (1997) Treatment of Nocardia asteroides keratitis with polyhexamethylene biguanide. Ophthalmology 104(8):1306–11View ArticlePubMedGoogle Scholar
- Prajna L, Tiwari M, Prajna NV, Gilpin C, Prakash K, Srinivasan M (2007) Nocardia keratitis species, drug sensitivities, and clinical correlation. Cornea 26(3):255–9View ArticlePubMedGoogle Scholar
- Sharma S, Sridhar MS (1999) Diagnosis and management of Nocardia keratitis. J Clin Microbiol 37(7):2389PubMedPubMed CentralGoogle Scholar
- Sridhar MR, Sharma S, Garg P, Rao GN (2001) Treatment and outcome of Nocardia keratitis. Cornea 20(5):458–62View ArticlePubMedGoogle Scholar
- Hitti W, Wolff M (2005) Two cases of multidrug-resistant Nocardia farcinica infection in immunosuppressed patients and implications for empiric therapy. Eur J Clin Microbiol Infect Dis 24(2):142–4View ArticlePubMedGoogle Scholar
- Gowrinath K, Baig WW, Prabhu AR, Chawla K, Biary I (2009) Pulmonary Nocardiosis due to Nocardia farcinica in a renal transplant recipient. Indian J Chest Dis Allied Sci 51:237–9PubMedGoogle Scholar
- Pandya VB, Petsoglou C (2008) Nocardia transvalensis resistant to amikacin: an unusual cause of microbial keratitis. Cornea 27(9):1082–85View ArticlePubMedGoogle Scholar
- Ezeoke I, Klenk HP, Potter G, Schumann P, Moser BD, Lasker BA, Nicholson A, Brown JM (2013) Nocardia amikacinitolerans sp: an amikacin-resistant human pathogen. Int J Syst Evol Microbiol 63(3):1056–61View ArticlePubMedGoogle Scholar