Purpose
To report the successful use of topical linezolid 0.2% in the treatment of gram-positive bacterial keratitis.
Study Design
Retrospective, interventional case series.
Methods
All cases of bacterial keratitis treated at the University of Illinois Eye and Ear Infirmary with topical linezolid were identified from the Cornea and External Disease Clinic and were reviewed for culture results, prior therapy, clinical course, and visual outcome.
Results
Three patients received topical linezolid, all for cases of culture-positive or presumed gram-positive keratitis. Cases consisted of 1 patient with recalcitrant vancomycin-resistant Enterococcus faecalis (VRE) and 2 patients with infectious crystalline keratitis, 1 previously culture-positive for an uncharacterized Staphylococcus and the other for Streptococcus mitis . All 3 patients had rapid resolution of their infectious keratitis and noted no pain or discomfort attributed to the topical therapy. The patient with VRE keratitis developed a consecutive Candida keratitis elsewhere in the same cornea at the end of therapy for her VRE keratitis.
Conclusion
Topical linezolid 0.2% can be an effective ophthalmic antibiotic for the treatment of gram-positive keratitis, including VRE, and is both significantly more comfortable and less immediately toxic to the ocular surface than topical vancomycin.
The most common non–contact lens–related pathogens in infectious keratitis are gram-positive in nature. Although a number of topical antibiotics, including fourth-generation fluoroquinolones, fortified cephalosporins, and fortified vancomycin, have previously been effective in their treatment, increasing laboratory and clinical resistance of these pathogens has been reported. Methicillin-resistant Staphylococcus aureus (MRSA) is now commonly reported in all types of ocular and adnexal infections, mirroring the alarming rise seen in both hospital- and community-acquired systemic infections. Along with cephalosporin resistance, these organisms are also significantly fluoroquinolone-resistant, leaving topical vancomycin as the only remaining well-studied ophthalmic antibiotic reliably effective against these pathogens.
However, the topical use of vancomycin, even at reduced concentrations, is often exceedingly painful and can be toxic to the ocular surface with extended use. Further, vancomycin-resistant organisms remain uncommon but have been reported in both systemic and ocular infections. The need for additional alternative agents for gram-positive bacterial keratitis is compelling. A study by our group had previously demonstrated the tolerability and efficacy of topical linezolid in reducing streptococcal colony counts in an experimental rabbit model of infectious keratitis when compared with topical vancomycin (Slover CM, et al. IOVS 2007;48:ARVO E-Abstract 4744). For these reasons, we report the clinical efficacy of topical linezolid in 2 commonly recalcitrant infections, infectious crystalline keratitis and vancomycin-resistant Enterococcus faecalis (VRE) keratitis resistant to or intolerant of topical ophthalmic vancomycin.
Methods
This was a retrospective, interventional case series reviewed by the Institutional Review Board (IRB) of the University of Illinois–Chicago and determined to meet criteria for exemption from full IRB review. Patients were identified from the University of Illinois Eye and Ear Cornea and External Disease Clinic who had received topical linezolid for any reason. Patients were offered this therapy if their infection was resistant to other available antibiotics or if they were intolerant of previous therapy. All patients were consented with regard to the unknown efficacy and risks of therapy and agreed to the alternative use of the drug.
Each case was reviewed for risk factors for infection, previous use of medications, vision, and general ophthalmic examination. The patients’ clinical course, time to resolution, and final disposition were recorded. The causative pathogen and sensitivities were also noted.
Results
All 3 identified patients had successful resolution of their keratitis with the use of topical linezolid. One patient was an avid lake swimmer, whereas the other 2 patients had long-standing persistent epithelial defects after penetrating keratoplasty and were wearing bandage soft contact lenses at the time of infection. All 3 patients had previously received topical vancomycin, 2 for their current infection and 1 for a remote bout of infectious crystalline keratitis. The patient in Case 1 (VRE) was clinically resistant to topical vancomycin, while the other 2 could not tolerate the therapy because of either severe pain with administration or exacerbation of a persistent epithelial defect with prior use.
Case 1
A 63-year-old woman with a history of previous laser in situ keratomileusis (LASIK), cataract extraction, and endophthalmitis underwent an uneventful penetrating keratoplasty in the right eye for multiple failed grafts in January 2007. The patient developed a persistent epithelial defect, which was slowly healing with a bandage contact lens. Three months after surgery, the patient was noted to have hand motions vision and an asymptomatic corneal infiltrate in the peripheral superonasal aspect of the graft. At that time, the patient was using a number of topical glaucoma medications, prophylactic topical moxifloxacin 4 times daily, and topical corticosteroids. Hourly fortified topical vancomycin and tobramycin was initiated without significant improvement in the infiltrate and with progression to a complete epithelial defect over the first week. Cultures then returned VRE sensitive only to Synercid (quinupristin + dalfopristin), tetracycline, and linezolid. Hourly topical linezolid 0.2% was substituted for vancomycin, with the tobramycin reduced to 4 times daily. A significant reduction in the infiltrate was noted 1 week later with complete resolution 3 weeks later. Unfortunately, a new Candida infiltrate developed temporally, which was also successfully treated, but with significant scarring. The area of the VRE infiltrate healed without significant loss of tissue ( Figure 1 ). Final vision was limited by glaucoma at count fingers in the right eye.
Case 2
A 63-year-old woman from Wisconsin presented to the University of Illinois Eye and Ear Cornea Clinic with a history of progressive, persistent keratitis of the right eye for approximately 1 month. The patient was a non–contact lens wearer but had undergone LASIK and multiple procedures for floppy eyelid syndrome in the past and was an avid lake water swimmer. She reported a similar episode 1 year previously in the left eye, which took an extended time to resolve, leaving her with a best-corrected vision of 20/50. The right eye initially presented with a superficial superotemporal keratitis, which responded poorly to topical fluoroquinolones. A corneal culture subsequently grew a few gram-positive cocci. The patient was referred to another cornea specialist, under whose care cultures were negative but topical fortified vancomycin and gentamicin were initiated. The patient experienced severe pain on instillation of the vancomycin and required systemic hydrocodone to continue its use. The eye became severely inflamed and, despite some improvement in the peripheral infiltrate, continued progression into the visual axis and intolerance of the fortified antibiotics resulted in their discontinuation. The patient’s corrected visual acuity was 20/100 in this right eye and she was severely photophobic. Clinical examination on presentation demonstrated an area of peripheral haze and a branching anterior stromal infiltrate extending into the visual axis ( Figure 2 ). A diagnosis of chronic infectious crystalline keratitis was made at this visit and, pending cultures, hourly topical linezolid 0.2% alone was offered because of the patient’s history of intolerance of vancomycin. Cultures for typical and atypical organisms were subsequently negative, but significant resolution of pain and improvement in vision occurred within a few days of therapy, and 1 month later the patient was seen with complete resolution of the infiltrate ( Figure 3 ). One month later her vision had returned to 20/25 − .
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