Vancomycin is a widely used glycopeptide antibiotic that is effective against most Gram-positive bacteria including Streptococcus, Staphylococcus, and Bacillus species. It is commonly used for the treatment of methicillin-resistant coagulase-negative Staphylococcus and methicillin-resistant Staphylococcus aureus (MRSA) infections. Vancomycin kills bacteria by binding irreversibly to d-alanyl-d-alanine moieties of the N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) peptides. This inhibits the synthesis and cross-linking of the NAM/NAG polymers that form the backbone of the cell wall. Resistant mutants are very rare, except for vancomycin-resistant Enterococcus. The mechanism of acquiring vancomycin resistance includes conversion of d-Ala-d-Ala to the depsipeptide d-Ala-d-Lac or to d-Ala-d-Ser, leading to altered cross-linkages in the peptidoglycans of the cell wall [4].
In the Endophthalmitis Vitrectomy Study, 100% of the Gram-positive bacteria were susceptible to vancomycin [5]. However, in the current series, three acute-onset postoperative endophthalmitis patients with Gram-positive organisms (Staphylococcus epidermidis, Bacillus sp., and Enterococcus faecalis) were resistant to vancomycin. There have been reports of using vancomycin as a prophylaxis either intracamerally or in the irrigating solution during cataract surgery [6, 7] which may possibly increase the emergence of vancomycin-resistant Gram-positive bacteria. In the present series, Bacillus sp. was the most common Gram-positive bacteria resistant to vancomycin. In a previous report, resistance among Bacillus sp. to vancomycin was noted in 10 of 31 (32.3%) organisms isolated between 1991 and 1998 [8]. In another large case series reported by Miller and associates, all of the Bacillus sp. isolates were sensitive to vancomycin [9].
In the current study, most of the patients had poor visual outcomes. This can be attributed to multiple factors including initial delay in presentation, microbial resistance, and virulence of the organism, as well as concurrent trauma in some patients. It was interesting to note that these vancomycin-resistant Gram-positive organisms were most likely to be sensitive to the second-generation fluoroquinolone ciprofloxacin.
Quinupristin-dalfopristin, linezolid, daptomycin, and tigecycline have been used to treat systemic infections caused by vancomycin-resistant bacteria, though there are no formal recommendations for treatment of such endophthalmitis cases, given the paucity of these infections. Quinupristin/dalfopristin is a synthetic, parenteral, streptogramin antibiotic that acts by sequential ribosomal binding to inhibit protein synthesis and is effective in vitro against Enterococcus faecium, MRSA, Streptococcus pneumoniae, and other Gram-positive cocci. Hernandez-Da Mota reported successful treatment of endophthalmitis due to vancomycin-resistant S. aureus by administration of intravitreal 0.4 mg/0.1 ml quinupristin/dalfopristin injection [10]. Linezolid is an oxazolidinone antibiotic that inhibits protein synthesis by binding to domain V of the 235 ribosomal RNA of the 50S subunit of bacterial ribosomes and is active in vitro against vancomycin-resistant Enterococcus, MRSA, vancomycin-resistant S. aureus, and penicillin-resistant S. pneumoniae. Systemic linezolid has been reported in the successful treatment of vancomycin-resistant E. faecium endophthalmitis following penetrating keratoplasty [11]. Daptomycin is a lipopeptide that binds to the bacterial cytoplasmic membrane to effect release of intracellular ions and cell death. It demonstrates good in vitro bactericidal activity for vancomycin-resistant strains of bacteria accounting for endophthalmitis, including S. epidermidis, S. aureus, S. pneumoniae, E. faecalis, and E. faecium
[12]. Comer and colleagues demonstrated that administration of 200 μg of intravitreal daptomycin was safe and efficacious in a rabbit model of bacterial endophthalmitis [13]. Tigecycline is a glycylcycline antibiotic that binds to the 30S ribosomal subunit to inhibit protein synthesis. It is active in vitro against MRSA, other multidrug-resistant Gram-positive cocci, and many Gram-negative bacilli [14].
Limitations of this report include the fact that the isolates were vancomycin-resistant by disk diffusion method which was not confirmed by MIC and the small number of cases in this retrospective series. However, it should be noted that these vancomycin-resistant organisms have been reported to be resistant to multiple other antibiotics [15]. In the current series, six of the seven isolates showed multidrug resistance.