the leading cause of posttraumatic and postoperative endophthalmitis is the colonization with exogenous gram - positive bacteria that usually dominate the normal ocular surface , with a significant percentage of the causative organisms being staphylococcus aureus [ 2 , 3 ] . postoperative endophthalmitis is fairly rare , but the incidence has increased over the last decade . increase in drug - resistant organisms is one of the more serious aspects contributing to this increased risk to patients . traditional management of endophthalmitis includes performing either vitreous tap / biopsy or vitrectomy and delivering appropriate intravitreal antibiotic therapy . since the endophthalmitis vitrectomy study ( evs ) published in 1995 however , recent reports of vancomycin resistance in gram - positive bacteria associated with endophthalmitis and increasing extra - ocular vancomycin resistance have both pointed to the need for alternative treatment tools for gram - positive intraocular infections . newer antibiotics designated for vancomycin - resistant infections are commercially available . the preclinical study by comer et al .   uses rabbit models to demonstrate that of these antimicrobials , daptomycin ( dap ) appears to offer the greatest solution of providing both a viable treatment alternative and final outcome improvements . there has been one case report on methicillin - resistant s. aureus ( mrsa ) endogenous endophthalmitis treated with intravitreal dap ( 200 g/0.1 ml ) . however , this is the first report to our knowledge of intravitreal dap used to successfully treat culture - negative recalcitrant exogenous endophthalmitis . our current report illustrates the multidimensional strategy and flexible approaches required to find the optimal management of postoperative endophthalmitis . a 63-year - old caucasian male who had a history of retinal tear in the left eye after successful laser retinopexy 2 years before , subsequently developed an epiretinal membrane that was being monitored . on routine follow - up , he reported increasing metamorphopsia and blurred vision in the left eye that was now interfering with his ability to perform daily occupational tasks . his visual acuity at that visit was 20/30 in the right eye and 20/150 in the left eye . examination revealed a significant macular pucker in the left eye with macular edema ( central macular thickness = 632 m ) . given his significant decrease in vision , the significant progression and contraction of the epiretinal membrane , and the impact on his life , he was offered epiretinal membrane surgery . after a full discussion of risks , benefits , and alternatives , he elected to proceed . he underwent routine epiretinal membrane peeling under standard sterile precautions without any complications with a 23-guage pars plana sutureless vitrectomy technique . on postoperative day 1 , he was healing well with only trace anterior chamber cell and flare . on postoperative day 3 , he presented with hand motions vision , significant eye pain , a 3-mm hypopyon with 4 + cell / flare , and 3 + corneal edema with no view to the posterior segment . b - scan revealed no retinal detachment . a vitreous tap and injection of intravitreal 0.1 ml vancomycin/0.1 ml ceftazidime / and 0.1 ml of dexamethasone he was started on oral avelox 400 mg / day , topical atropine , and topical prednisolone . the gram stain revealed rare gram - positive cocci , but the culture was negative . the decision was made to proceed with anterior chamber washout and core vitrectomy with repeat antibiotics ( vancomycin and ceftazidime ) and culture . on postoperative day 1 following this surgery , his anterior segment was clear of hypopyon with 1 + cell / flare , and there was some residual peripheral vitreous debris . on postoperative day 3 , he redeveloped a 3-mm hypopyon and underwent repeat intravitreal injections of vancomycin and ceftazidime . on postoperative day 4 , his hypopyon height progressed , pain increased , and corneal edema worsened . the decision was made to undergo repeat pars plana vitrectomy , and anterior chamber washout with injections of intravitreal dap ( 200 g/0.1 ml ) . this time postoperatively his eye was quiet with only trace cell / flare and no hypopyon . his ultimate vision was counting fingers , attributed to the recalcitrance of his initial infection . his topical prednisolone drops were gradually tapered over 8 weeks with no recurrence of intraocular inflammation or infection . the patient 's history and course suggest that he developed gram - positive bacterial endophthalmitis that was fastidious to grow on culture and was likely resistant to vancomycin . only the intravitreal dap succeeded in treating his recalcitrant infection . this case study suggests that vancomycin resistance should be considered in culture - negative endophthalmitis , and dap should be considered as an important treatment alternative . vancomycin is a widely used glycopeptide antibiotic that clinicians have traditionally used intravitreously against gram - positive organisms because of its broad - spectrum activity , minimal resistance , acceptable rates of intraocular sterilization , and lack of toxicity . vancomycin resistant mutants are very rare , but several recent publications have reported increasing resistance to vancomycin in extraocular infections caused by common gram - positive endophthalmitis isolates such as staphylococcus , streptococcus , and enterococcus sp . . although vancomycin - resistant endophthalmitis is limited to a few case reports [ 5 , 6 , 7 , 8 , 9 ] , the appearance of endophthalmitis caused by vancomycin - resistant enterococci ( vre ) and vancomycin - resistant s. aureus ( vrsa ) accelerated shortly after the mrsa endemic emerged in medical centers in the 1990s . vre endophthalmitis has been described in 4 patients to date : a hospitalized immunocompromised patient with bacteremia , an immunocompetent patient after keratoplasty with infected donor tissue , an immunocompetent patient 20 years following trabeculectomy , and an immunocompetent patient following cataracts surgery . the current case report suggests that vancomycin resistance is not only confined to gram - positive or culture - positive endophthalmitis , but that vancomycin resistance should be considered in culture - negative endophthalmitis . in the evs , culture - negative or culture - equivocal cases were common at 17.9 and 12.9% , respectively , totaling 30.8% of cases . further confirmed that studies of endophthalmitis must presume a 2530% rate of culture - negative endophthalmitis . this case proposes that we ought to consider vancomycin resistance as a possibility in these 30% of endophthalmitis cases . fine - tuning our clinical roadmap in these cases will find increasing importance in the setting of rising resistance rates , particularly since cases of vancomycin - resistant endophthalmitis are often associated with worse visual outcomes . dap is a lipopeptide antibiotic that is approved to treat skin and soft tissue infections , bacteremia , endocarditis , and osteomyelitis [ 2 , 5 ] . although dap is not formally recom mended for endophthalmitis treatment , it has shown to have a significantly longer half - life than vancomycin , and to be just as effective as vancomycin . a 1-mg dose of dap ensures noninferiority from the bactericidal efficacy of a 1-mg dose of vancomycin . dap also demonstrates superior in vitro activity for vancomycin - resistant bacteria strains typically accounting for endophthalmitis . these strains include : s. epidermidis , s. aureus , s. pneumoniae , e. faecalis , and e. faecium . dap kills 99.9% of gram - positive bacteria within 68 h compared to 1224 h or simple bacteriostasis with vancomycin . in a rabbit ventriculitis model , dap achieved superior bactericidal activity and more rapid kill - times ; antibacterial activity of dap is rapid and concentration dependent , while antibacterial activity of vancomycin is slow and time dependent [ 2 , 4 ] . .   also demonstrated that administration of 200 g of intravitreal dap was safe and efficacious in a rabbit model of bacterial endophthalmitis . higher concentrations lead to a dose - dependent increase in cataract formation , erg suppression , and photoreceptor damage . the therapeutic window may seem narrow , but 200 g of intravitreal dap resulted in near complete vitreous sterilization 24 h after treatment , and complete vitreous sterilization by 48 h . moreover , clinical and histopathologic examinations confirmed preservation of the retina , photoreceptor layers , ocular structure architecture , and limited ocular inflammation after sterilization of the treated eye [ 2 , 4 ] . in conclusion , vancomycin resistance among gram - positive isolates is an uncommon , but emerging challenge . vancomycin resistance should be considered in culture - negative endophthalmitis recalcitrant to treatment , and dap should be considered as an alternative in these cases , though further studies will be needed to better determine its therapeutic utility in human clinical trials . the patient gave informed consent and the study protocol adhered to the ethical guidelines of the institute 's committee on human research .
purposeto report the first case to our knowledge of intravitreal daptomycin used to successfully treat culture - negative vancomycin resistant to exogenous endophthalmitis.methodscase report with preoperative , intraoperative , and postoperative findings.resultsa 63-year - old caucasian male underwent routine pars plana vitrectomy with epiretinal membrane peeling . 
 he developed acute postoperative endophthalmitis , and underwent vitreous tap and injection of intravitreal vancomycin / ceftazidime / dexamethasone . 
 gram stain showed gram - positive cocci , but cultures were negative . 
 his infection subsequently proved very recalcitrant and his treatment course involved pars plana vitrectomy with anterior chamber washout and repeat injection of antibiotics , followed by repeat intravitreal vancomycin and ceftazidime . 
 ultimately , a second vitrectomy with intravitreal daptomycin controlled his intraocular infection . on each occasion 
 , cultures were negative.conclusionthis case suggests that vancomycin resistance should be considered in culture - negative postoperative endophthalmitis , and intravitreal daptomycin should be considered as an important treatment alternative . 
 although vancomycin resistance is fairly rare in endophthalmitis , acknowledgment of its increasing occurrence rate is critical for optimal management .