45Antibiotics

Key points

The Endophthalmitis Vitrectomy Study (EVS) provided ophthalmologists with evidence-based management strategies to deal with endophthalmitis for the first time. However, since the completion of the EVS, numerous unresolved issues

remain. The use of oral antibiotics has important implications for the ophthalmologist, particularly in the prophylaxis and/or management of postoperative, posttraumatic, or bleb-associated bacterial endophthalmitis. One can reasonably conclude that significant intraocular penetration of an antibiotic after oral administration may be a property unique to the newer generation of fluroquinolones. Prophylactic use of mupirocin nasal ointment resulted in significant reduction of conjunctival flora with or without preoperative topical 5% povidone-iodine prep. Ocular fungal infections have traditionally been very difficult to treat due to limited therapeutic options both systemically and intravitreally. Because of its broad spectrum of coverage, low MIC90 levels (minimum inhibitory concentration of antibiotic required to kill 90% of isolates) for the organisms of concern, good tolerability, and excellent bioavailability, voriconazole through various routes of administration may be useful to the ophthalmologist in the primary treatment of or as an adjunct in the current management of ocular fungal infections.

INTRODUCTION

In spite of significant advances in endophthalmitis management over the past two decades, numerous unresolved issues remain. There is no doubt that approximately 20 years ago, the advent of intravitreal antibiotics paved the way for notably improved visual and anatomic outcomes. In the mid-1990s, the EVS readily addressed the role of vitrectomy versus vitreous tap in the treatment of postoperative endophthalmitis, and documented that patients with hand motion or better vision fared equally well with either a complete pars plana vitrectomy or a vitreous tap.1 If the visual acuity was light perception, then outcomes were better with a complete vitrectomy. Both procedures employed intravitreal antibiotics consisting of vancomycin and amikicin. This study provided ophthalmologists with evidence-based management strategies to deal with this difficult condition for the first time.

The EVS also provided us with very important data regarding the pathogens which most commonly cause postoperative endophthalmitis (Figure 45.1). Additionally, the study determined that there was no apparent benefit from the use of intravenous (IV) antibiotics (cephalosporins and aminoglycosides).1 The chosen systemic antibiotics in the EVS were the best available at the time; however, several studies following the completion of the EVS revealed that systemically administered cephalosporins and aminoglycosides do not readily achieve therapeutic intraocular concentrations in the vitreous cavity.2,3

Unfortunately, even within the confines of a well-conceived and thought-out multicenter, prospective clinical trial like the EVS, a number of pertinent issues remain unresolved or were not fully

addressed in the original study. These include the choice of the intravitreal antibiotics (ceftazidime was not employed, and today it has virtually replaced the use of intravitreal amikacin), the management of types of endophthalmitis not specifically studied in the EVS (filtering bleb-associated, posttraumatic, indolent, and fungal endophthalmitis), the role of intravitreal corticosteroids, and inpatient versus outpatient management of infection.

Additionally, since the completion of the EVS, new antibiotics such as the fourth-generation fluoroquinolones have been developed, and these agents will most likely play a key role in the treatment of proven infection or in the prophylaxis against infection in the near future (as will be described below).

THE ENDOPHTHALMITIS

VITRECTOMY STUDY

In the mid-1990s, the EVS group set out to determine the role of vitrectomy versus vitreous tap in the treatment of postoperative endophthalmitis, and to address the role of IV antibiotics versus no IV antibiotics in treating endophthalmitis. Vitrectomy was introduced in the 1970s and many surgeons began to employ it in conjunction with intravitreal antibiotics for treating endophthalmitis. There were several theoretical advantages to vitrectomy, including the removal of infecting organisms and their toxins, better distribution of antibiotics, clearing of tractional membranes that could lead to retinal detachment, clearing of opacities in the vitreous, and providing a good volume of vitreous material for microbiologic culture. Prior to the EVS, small human studies were inconclusive to the benefits of vitrectomy and in previous studies it appeared that only the most advanced cases of endophthalmitis underwent vitrectomy. Therefore, visual outcomes were poor and it was uncertain if vitrectomy would yield superior outcomes in eyes with better presenting vision. In the early 1990s, the role of vitrectomy in the management of endophthalmitis was quite controversial. During this time, the role of systemic IV antibiotics in the management of endophthalmitis was uncertain. It was the standard of care; however, it was questioned whether the theoretical benefit outweighed the systemic side-effects of antibiotics used at the time, as well as costs associated with the drug and hospitalization for administration of these antibiotics. These unresolved issues served as the impetus for the largest prospective study on endophthalmitis management to date.4

Clinical centers in 25 US cities enrolled 420 patients over a 3 1 2-year period. Entry criteria were stringent and were limited to patients who had a clinical diagnosis of endophthalmitis within 6 weeks of cataract extraction or secondary intraocular lens placement and had vision worse than 20/50 but at least light perception. Additionally, included patients were required to have a hypopyon and clouding of anterior chamber or vitreous media sufficient to obscure clear visualization of second-order retinal arterioles. Patients were excluded that did not have a cornea and anterior chamber clear enough to visualize some part of iris. Furthermore, the cornea was to be clear enough to allow the possibility of pars plana vitrectomy.4 All eyes in the EVS underwent immediate cultures of the anterior chamber and vitreous. Intravitreal amikacin and vancomycin were administered, as were subconjunctival