1 Endophalmitis: Prävention und Therapie

1.1 Combined Meropenem and Linezolid as a Systemic Treatment for Postoperative Endophthalmitis

Systemische Kombinationstherapie mit Meropenem und Linezolid zur Behandlung von postoperativen Endophthalmitiden

C. Tappeiner¹, K. Schuerch¹, D. Goldblum¹², S. Zimmerli³, J. C. Fleischhauer¹, B. E. Frueh¹

¹ Department of Ophthalmology, Inselspital, University Hospital, Bern, Switzerland

² Department of Ophthalmology, University Hospital, Basel, Switzerland

³ Institute for Infectious Diseases, University of Bern, Bern, Switzerland

1.1.1 Introduction

Endophthalmitis is a severe infection of intraocular tissues with an incidence of 0.05 to 0.082% after cataract surgery ▶ [1], ▶ [2]. It is most commonly caused by bacteria of the conjunctival flora: coagulase negative Staphylococcus spp. (84%), Staphylococcus aureus (50%), Streptococcus spp. (30%), Enterococcus spp. (14%), and Gram-negative organisms (56%) ▶ [3], ▶ [4]. The visual prognosis after endophthalmitis depends mainly on the causative pathogen and the time interval between onset of endophthalmitis and initiation of treatment ▶ [4]. Symptoms normally develop within six weeks after cataract surgery including pain, blurred vision, and a decrease in visual acuity due to inflammation of the aqueous, vitreous humor, and retinal structures ▶ [5]. Treatment of choice for early onset endophthalmitis according to the multicentre, prospective endophthalmitis vitrectomy study (EVS) is pars plana vitrectomy for eyes with poor vision such as light perception, intravitreal injection of antibiotics (e.g., vancomycin and amikacin), and possibly additional subconjunctival antibiotic injections ▶ [5]. The EVS found no significant benefit of an additional systemic antibiotic treatment with amikacin and ceftazidime with respect to visual acuity outcome and concluded that omission of systemic antibiotic treatment may reduce toxic effects, costs, and length of hospitalization. The conclusions of the EVS have not been universally accepted because the combination of amikacin and ceftazidime may not be an efficient treatment for endophthalmitis ▶ [6], ▶ [7]. Furthermore, amikacin was shown to poorly penetrate through the blood-retina barrier ▶ [8].

Meanwhile, newer generations of systemic antibiotics with an improved antibacterial spectrum are available: meropenem, a carbapenem with high in vitro activity against Pseudomonas aeruginosa, Haemophilus influenzae, Streptococcus pneumoniae, and methicillin-susceptible strains of Staphylococcus aureus and S. epidermidis ▶ [9] and linezolid, an oxazolidinone, which is active against the majority of Gram-positive organisms including methicillin-resistant Staphylococcus spp., penicillin-resistant Pneumococcus and vancomycin-resistant Enterococcus spp. ▶ [10]. Furthermore, both antibiotics penetrate well through the blood-retina barrier ▶ [11], ▶ [12]. In contrast to systemic amikacin, which did not reach therapeutic vitreous concentrations for methicillin-sensitive S. epidermidis and P. aeruginosa, meropenem was shown to reach therapeutic levels for both organisms in the vitreous ▶ [8], ▶ [12]. Ceftazidime, used in the EVS, offers a good penetration into the vitreous and may be useful in the treatment of endophthalmitis due to Gram-negative organisms including P. aeruginosa. However, only 4% of EVS cases were caused by Gram-negative bacteria ▶ [5], ▶ [13], ▶ [14].

The goal of this retrospective study was to evaluate outcome and adverse effects of a systemic combination treatment with meropenem and linezolid (group 1) in comparison to a treatment with conventional antibiotics (group 2) in patients with endophthalmitis occurring after cataract surgery.

1.1.2 Patients and Methods

In this retrospective single centre study we reviewed data from 71 patients treated between April 1998 and November 2007 at the Department of Ophthalmology, Inselspital, Bern, Switzerland due to endophthalmitis occurring within 6 weeks after cataract surgery. The inclusion criteria of the endophthalmitis vitrectomy study (EVS) were applied in all patients (symptoms of bacterial endophthalmitis within 6 weeks after cataract surgery, visual acuity of light perception or better and worse than 20/50; hypopyon or sufficient clouding of the anterior chamber or vitreous to obscure a view of retinal arterioles). Exclusion criteria as in the EVS were eye diseases limiting visual acuity to 20/100 or worse before the development of cataract, penetrating ocular trauma, retinal or choroidal detachment, intolerance to any study drug, strong suspicion of fungal endophthalmitis, age younger than 18 years and unsuitability for surgery ▶ [5].

Medical history including topical and systemic treatment, previous eye surgeries, best-corrected visual acuity (BCVA), and findings of slit lamp examination, applanation tonometry, fundoscopy and ocular sonography were reviewed and evaluated retrospectively.