Hassanain S. Toma

Antibiotic resistance of conjunctiva and nasopharynx evaluation study: a prospective study of patients undergoing intravitreal injections.

PURPOSE To determine the baseline antibiotic susceptibility patterns of conjunctival and nasopharyngeal flora isolated from patients undergoing intravitreal (IVT) injections for choroidal neovascularization (CNV). DESIGN Prospective, observational study. PARTICIPANTS Forty-eight eyes of 24 patients undergoing unilateral IVT injections for CNV. METHODS Bilateral conjunctival and unilateral nasopharyngeal cultures on the treatment side were taken before application of any topical medications. MAIN OUTCOME MEASURES Bacterial isolates were identified and tested for antibiotic susceptibility to 16 different antibiotics using the Kirby-Bauer disc diffusion technique. RESULTS A total of 57 bacterial isolates were obtained from the conjunctiva of 48 eyes. Coagulase-negative staphylococci (CNS) accounted for 37 of the 57 isolates (65%). The most common CNS organisms were Staphylococcus epidermidis and Staphylococcus lugdunensis accounting for 73% and 11% of CNS isolates, respectively. More than half of S. epidermidis isolates demonstrated some level of resistance to ofloxacin and levofloxacin, and 33% and 37% of isolates showed some level of resistance against gatifloxacin and moxifloxacin, respectively. Some 60% and 30% of CNS isolates were resistant to ≥ 3 and ≥ 5 antibiotics, respectively. Among the 24 nasopharyngeal cultures, 8 (33%) grew Staphylococcus aureus, and 1 of the 8 isolates (13%) was resistant to all penicillin, cephalosporin, macrolide, and fluoroquinolone antibiotics tested. CONCLUSIONS Our results demonstrate subtantial levels of resistance to third- and fourth-generation fluoroquinolones and multiresistance among ocular CNS isolated from patients undergoing IVT injections for CNV.

Ophthalmic antibiotics and antimicrobial resistance a randomized, controlled study of patients undergoing intravitreal injections.

PURPOSE To determine whether repeated exposure of ocular and nasopharyngeal flora to ophthalmic antibiotics promotes antimicrobial resistance in patients undergoing intravitreal injections for choroidal neovascularization (CNV). DESIGN Prospective, randomized, controlled, clinical trial. PARTICIPANTS Forty-eight eyes of 24 patients undergoing unilateral intravitreal injections for CNV. METHODS Patients were assigned randomly to 1 of 4 ophthalmic antibiotics (azithromycin 1%, ofloxacin 0.3%, gatifloxacin 0.3%, moxifloxacin 0.5%) to be used after each injection in the treatment eye only. Bilateral conjunctival and unilateral nasopharyngeal cultures on the treatment side were obtained at baseline and were repeated at each subsequent visit for 1 year. All bacterial isolates were tested for antibiotic susceptibility to 16 different antibiotics using the Kirby-Bauer disc diffusion technique. Genetic analysis of bacteria strains was performed using pulse-field gel electrophoresis. MAIN OUTCOME MEASURES Changes in antibiotic susceptibility patterns of conjunctival and nasopharyngeal flora over time and emergence of resistant strains. RESULTS Eight subjects (33%) grew Staphylococcus aureus from the nasopharynx and 1 subject (13%) showed emergence of a resistant strain. Coagulase-negative staphylococci (CNS) cultured from eyes repeatedly exposed to fluoroquinolone antibiotics demonstrated significantly increased rates of resistance to third- and fourth-generation fluoroquinolones compared with untreated eyes. Resistance to ofloxacin and levofloxacin was roughly 85% (P = 0.003), and resistance to gatifloxacin and moxifloxacin approached 67% (P = 0.009) and 77% (P<0.001), respectively. In contrast, CNS isolated from eyes repeatedly exposed to azithromycin demonstrated significantly increased resistance (94%) to erythromycin and azithromycin when compared with control eyes (P = 0.009) and decreased resistance to third-generation (P<0.03) and fourth-generation (P<0.001) fluoroquinolones when compared with eyes exposed to fluoroquinolones. CONCLUSIONS Repeated exposure of ocular and nasopharyngeal flora to ophthalmic antibiotics selects for resistant strains.

Ophthalmic Antibiotic Use and Multidrug-Resistant Staphylococcus epidermidis: A Controlled, Longitudinal Study

PURPOSE To analyze the emergence of multidrug-resistant Staphylococcus epidermidis after repeated conjunctival exposure to topical macrolide or fluoroquinolone antibiotics. DESIGN Prospective, controlled, longitudinal study with 1-year follow-up. PARTICIPANTS Forty-eight eyes of 24 patients undergoing serial unilateral intravitreal (IVT) injections for choroidal neovascularization. METHODS Subjects received 4 consecutive monthly unilateral IVT injections and then were treated as needed. Each subject was assigned randomly to 1 of 4 antibiotics (azithromycin 1%, gatifloxacin 0.3%, moxifloxacin 0.5%, ofloxacin 0.3%) and used only their assigned antibiotic after each injection. Conjunctival culture specimens of the treated and untreated fellow eye (control) were obtained at baseline and after each injection. All bacterial isolates were tested for antibiotic susceptibility to 16 different antibiotics using the Kirby-Bauer disc diffusion technique. MAIN OUTCOME MEASURES Antibiotic susceptibility patterns and multidrug resistance of S. epidermidis. RESULTS After 4 consecutive treatments, a total of 58 isolates of S. epidermidis each were isolated from control and treated eyes. Resistance to 3 or more antibiotics was present in 69% of S. epidermidis isolated from control eyes compared with 90% from treated eyes (P<0.02). A total of 46 and 38 isolates of S. epidermidis were cultured from control and treated eyes, respectively, from the fifth until the final injection. Resistance to 5 or more antibiotics was present in 48% of control eyes compared with 71% of treated eyes (P<0.05). In a significant number of fluoroquinolone-treated eyes, S. epidermidis developed resistance to third-generation (P<0.01) and fourth-generation (P<0.01) fluoroquinolones compared with control eyes. In addition, these organisms developed resistance to trimethoprim/sulfamethoxazole (P<0.01), gentamicin (P<0.03), and clindamycin (P<0.05). Similarly, a significant number of azithromycin-treated eyes developed S. epidermidis resistant to macrolides (P<0.01) compared with control eyes and also developed increased resistance to trimethoprim/sulfamethoxazole (P<0.02) and doxycycline (P<0.01). CONCLUSIONS Conjunctival S. epidermidis repeatedly exposed to fluoroquinolone or azithromycin antibiotics rapidly develop resistance. Coresistance to other antibiotics also was observed. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Changes in Ocular Flora in Eyes Exposed to Ophthalmic Antibiotics

PURPOSE To determine changes in ocular flora in individuals repeatedly exposed to topical macrolide or fluoroquinolone antibiotics. DESIGN Prospective, controlled, longitudinal study with 1-year follow-up. PARTICIPANTS Forty-eight eyes of 24 patients undergoing serial unilateral intravitreal injection for choroidal neovascularization. METHODS Patients received 4 consecutive monthly unilateral intravitreal injections and were then treated as needed. Each patient was randomized to 1 of 4 antibiotics (azithromycin 1%, gatifloxacin 0.3%, moxifloxacin 0.5%, ofloxacin 0.3%) and used only their assigned antibiotic for 4 days after each injection. Conjunctival cultures of the treated eye and untreated fellow eye (control) were taken at baseline and before each injection. All bacterial isolates were tested for antibiotic susceptibility to 16 different antibiotics using the Kirby-Bauer disc diffusion technique. MAIN OUTCOME MEASURES Changes in bacteria composition of the conjunctiva over time. RESULTS In azithromycin-treated eyes, Staphylococcus epidermidis and Staphylococcus aureus accounted for 54.5% and 18.2% of cultured isolates, respectively, at baseline and 90.9% (P<0.01) and 4.5% (P<0.01), respectively, after azithromycin exposure. In fluoroquinolone-treated eyes, 45.7% and 6.5% of cultured isolates at baseline were S epidermidis and S aureus, respectively, but these percentages increased to 63.4% (P<0.03) and 13% (P = 0.24), respectively, after fluoroquinolone exposure. In contrast, the percentage of gram-negative species decreased from 8.7% at baseline to 1.6% (P<0.05) in fluoroquinolone-treated eyes. The percentage of S epidermidis isolated from azithromycin-treated eyes was significantly greater when compared with fellow control eyes (P<0.01) or fluoroquinolone-treated eyes (P<0.01). CONCLUSIONS The percentage of S epidermidis isolated from the conjunctival surface significantly increases after repeated exposure to azithromycin and to a lesser degree fluoroquinolone antibiotics at the expense of other commensal flora. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Cancer-associated Retinopathy with Retinal Periphlebitis in a Patient with Ovarian Cancer

Purpose: To describe a case of cancer-associated retinopathy (CAR) due to ovarian cancer presenting with retinal periphlebitis and a negative-type pattern electroretinogram (ERG). Design: Case report. Methods: Retrospective chart review. Results: A negative-type ERG in the setting of progressive vision loss and retinal periphlebitis led to the discovery of metastatic ovarian cancer and ultimately the diagnosis of CAR. Conclusions: CAR can present with periphlebitis and a negative-type ERG. Greater awareness of these associations may allow for earlier detection of future cases.

The Safety, Pharmacokinetics, and Efficacy of Intraocular Celecoxib

PURPOSE To determine safety, pharmacokinetics, and anti-inflammatory effects of intraocular celecoxib. METHODS The right eye of animals was injected with 1.5, 3, or 6 mg celecoxib prepared in dimethyl sulfoxide (DMSO). Left eyes served as controls and received 0.1 mL DMSO. Electroretinograms (ERG) were obtained at baseline and at 1, 4, and 12 weeks, and eyes were enucleated afterward for histopathologic analysis. For pharmacokinetics, 3 mg celecoxib was injected, and vitreous and retina/choroid drug levels were then analyzed at specific time points. For efficacy, 1 μg lipopolysaccharide was injected to induce inflammation; the right eye was then injected with 3 mg celecoxib (six eyes) or 2 mg triamcinolone acetonide (six eyes) and the left eye with saline. Twenty-four hours later, aqueous fluid was removed, and total leukocyte concentration and prostaglandin E2 (PGE2) concentration were determined. RESULTS Histologic and ERG studies demonstrated no signs of retinal or optic nerve toxicity. After a single 3-mg injection, vitreous (0.06 μg/mL) and retina/choroid (132.31 μg/g) celecoxib concentrations at 8 weeks exceeded median inhibitory concentration. Treatment with celecoxib and triamcinolone significantly reduced total leukocyte count by 40% (P = 0.02) and 31% (P = 0.01), respectively. Reduction in PGE2 levels paralleled reduction in leukocyte counts (P < 0.05). There was no increase in intraocular pressure, but cataract formation was observed at higher concentrations. CONCLUSIONS Intraocular injection of celecoxib appeared to be nontoxic and demonstrated excellent penetration into the retina/choroid and sustained drug levels out to 8 weeks. Celecoxib demonstrated potent anti-inflammatory effects, but there was an association with cataract formation at higher doses.