Methicillin-Resistant Staphylococcus⁎

Ophthalmology Volume 114, Number 7, July 2007 Adverse Event Reporting Dear Editor: Accurate adverse event reporting in clinical trials is critical in assisting the medical community to evaluate the safety of pharmaceutical products. However, adverse event collection methods may influence the incidence of reported side effects. Bent et al recently evaluated differences in reported systemic side effects when asking patients a general query such as “How are you doing?” versus giving them a specific symptom checklist.1 The authors found that with a general question adverse events were reported in 11% of patients, but in 77% when using a specific checklist. A similar difference might exist for ocular symptoms using general and specific queries for adverse events. Unfortunately, little information is available regarding response rate variation for adverse events in ophthalmic clinical trials based on general or specific queries. We performed a meta-analysis of clinical trials managed by Pharmaceutical Research Corporation during the past 10 years that included a solicited ophthalmic symptom query checklist and also a general query, “How are you doing since your last visit?” All the included studies were conducted as double-masked, randomized, crossover comparisons of glaucoma medicines timolol, carteolol, dorzolamide, brinzolamide, bimatoprost, and dorzolamide/timolol or pilocarpine/timolol fixed combinations. One study included a placebo arm.2 The meta-analysis included data from 4 studies including 223 patients.2–5 The results are shown in Table 1 (available at http://aaojournal.org). For 13 of 14 questions, there was a statistically greater positive response rate to a specific query than to a nonspecific one (chi-square or Fisher exact test, as appropriate). Only for photophobia, which had a low rate of positive responses generally, was a statistical difference not found. This meta-analysis showed that a specific question about an ocular symptom more often provides a positive response than does a general query. Our findings helped confirm for ophthalmic symptoms what Bent et al found for systemic symptoms.1 However, the prior trial differed from ours in that it was prospective, treatment was with a placebo, and patients were evaluated with a checklist of 53 symptoms. Our report represented a retrospective meta-analysis of comparative studies evaluating a variety of glaucoma medicines. Nonetheless, statistical differences were found between general and specific ophthalmic queries in our analysis that may have importance to a physician in the following ways: (1) to assist in evaluating differences of adverse event rates between published studies, (2) to help to clarify why a published rate for a side effect might differ from that in their own clinical practice, and (3) to understand in clinical trial design that the chance of eliciting a specific symptom may differ based on the manner of query. This study suggests that a specific ophthalmic symptom query will more often elicit a positive response than a general query. This study did not evaluate differences in adverse event response rates in a prospective manner using the same

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glaucoma medications. Further research might further clarify differences in response rates between specific and general adverse event queries for ophthalmic products. BONNIE KRUFT LINDSAY A. NELSON, BS JEANETTE A. STEWART, RN WILLIAM C. STEWART, MD Charleston, South Carolina References 1. Bent S, Padula A, Avins AL. Better ways to question patients about adverse medical events: a randomized, controlled trial. Ann Intern Med 2006;144:257– 61. 2. Stewart WC, Day DG, Stewart JA, et al. Short-term ocular tolerability of dorzolamide 2% and brinzolamide 1% versus placebo in primary open-angle glaucoma and ocular hypertension subjects. Eye 2004;18:905–10. 3. Stewart WC, Cohen JS, Netland PA, et al. Efficacy of carteolol 1% versus timolol maleate 0.5% in patients with increased intraocular pressure. Am J Ophthalmol 1997;124:498 –505. 4. Kaluzny JJ, Szaflik J, Czechowicz-Janicka K, et al. Timolol 0.5%/dorzolamide 2% fixed combination versus timolol 0.5%/ pilocarpine 2% fixed combination in primary open-angle glaucoma or ocular hypertensive patients. Acta Ophthalmol Scand 2003;81:349 –54. 5. Day DG, Sharpe ED, Beischel CJ, et al. Safety and efficacy of bimatoprost 0.03% versus timolol maleate 0.5%/dorzolamide 2% fixed combination. Eur J Ophthalmol 2005;15:336 – 42.

Methicillin-Resistant Staphylococcus* Dear Editor: Methicillin-resistant Staphylococcus aureus (MRSA) infection constitutes a significant health care problem. Although the prevalence of MRSA increased in hospitals worldwide, the absence of antibiotic selective pressure favoring their survival and attenuated virulence were thought to make resistant organisms unable to compete in the community. However, in the mid-1990s reports began to appear in the United States of community-acquired MRSA infections, with the most common manifestations being skin and soft-tissue infections.1 Because of the prevalence of S. aureus in preseptal and orbital cellulitis in past reports, we wondered if MRSA is a significant cause of periorbital cellulitis. A retrospective study was approved by the institutional review boards of the University of Texas Southwestern Medical Center and Parkland Memorial Hospital. Chart review of all eyes of patients with a diagnosis-related group code for preseptal cellulitis, eyelid abscess, or orbital cellulitis seen at Parkland Memorial Hospital between January 1, 1999 and June 30, 2005 was conducted. Methicillinresistant S. aureus isolates were categorized as nosocomial if the patient had been hospitalized for 48 hours before obtaining the culture or if the patient had been hospitalized

*Presented in part at: Association for Research in Vision and Ophthalmology Annual Meeting, May 3, 2006, Fort Lauderdale, Florida. Supported in part by an unrestricted research grant from Research to Prevent Blindness, Inc., New York, New York.

Letters to the Editor at Parkland Memorial Hospital in the 6 months before the date of the culture. Thirty patients with culture-positive preseptal cellulitis were identified. Average age was 40.3 years (range, 17–70). Although Parkland Memorial Hospital does have neonatal units, adults are predominantly seen at the hospital, as children are treated at nearby Children’s Medical Center. Staphylococcus aureus was cultured in 22 cases (73%), other gram-positive bacteria in 5 (17%), and gram-negative bacteria in 3 (10%), and one culture grew Fusarium species in addition to gram-positive bacteria. Twenty (91%) S. aureus isolates were methicillin resistant, and 17 (85%) of the MRSA isolates were categorized as community acquired. Eleven (55%) of the MRSA cases had abscess formation, compared with only 4 cases (40%) without MRSA; the difference was not significant. Nineteen patients with culture-positive orbital cellulitis were identified, with an average age of 40.7 years (range, 17– 65). Staphylococcus aureus was isolated in 5 cases (26%), other gram-positive bacteria were identified in 12 (63%), and gram-negative bacteria in 4 (21%), and one culture grew Fusarium species. All patients had either subperiosteal or orbital abscesses, except for one patient with Pseudomonas aeruginosa. Four of the S. aureus isolates were methicillin resistant, with 3 isolates considered community acquired. Overall, 20 (83%) of the 24 preseptal and orbital MRSA infections in this study were community acquired, not nosocomial. We found that most preseptal cellulitis was due to S. aureus, and most of the S. aureus isolates were community-acquired MRSA. Community-acquired MRSA should be considered a possibility for skin and soft-tissue infections with the appearance of a spider or insect bite, if there is a history of contact with a correctional facility (as either a prisoner or a visitor), if there is a history of playing contact sports or association with a sports facility, or if the infection is recurrent.2 Community-acquired MRSA orbital cellulitis has only rarely been reported.3 Unlike nosocomial MRSA isolates, which are more likely to be resistant to multiple other antibiotics, communityacquired MRSA isolates are more likely to be sensitive to antibiotics other than ␤-lactams.4 However, there is not much of a track record for the use of oral antibiotics to which isolates show in vitro susceptibility to communityacquired MRSA infections, and it is uncertain whether initial therapy with an antibiotic active against MRSA even affects the outcome of skin and soft-tissue infections. Lee et al5 found that children presenting with MRSA skin and soft-tissue abscesses ⬍5 cm in diameter were managed effectively with incision and drainage despite receiving ineffective antibiotic coverage. Microbial culture and sensitivity studies, however, are needed to guide antibiotic therapy for severe ophthalmic infections. A prospective study comparing outcomes of community-acquired preseptal cellulitis with the patient treated as an outpatient with alternate antibiotics (such as sulfamethoxazole/trimethoprim with or without rifampin) with the ␤-lactams traditionally used would be useful to guide empiric therapy in MRSA-endemic areas like Dallas. For hospitalized patients at our institution with se-

vere cellulitis, we tend to cover empirically for MRSA with intravenous vancomycin in addition to a broadspectrum antibiotic. SCOTT ROBERT WITHERSPOON, MD PRESTON H. BLOMQUIST, MD Dallas, Texas References 1. Herold BC, Immergluck LC, Maranan MC, et al. Communityacquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA 1998;279: 593– 8. 2. Fridkin SK, Hageman JC, Morrison M, et al, Active Bacterial Core Surveillance Program of the Emerging Infections Program Network. Methicillin-resistant Staphylococcus aureus disease in three communities. N Engl J Med 2005;352:1436 – 44. 3. Rutar T, Zwick OM, Cockerham KP, Horton JC. Bilateral blindness from orbital cellulitis caused by community-acquired methicillin-resistant Staphylococcus aureus. Am J Ophthalmol 2005;140:740 –2. 4. Naimi TS, LeDell KH, Como-Sabetti K, et al. Comparison of community- and health care-associated methicillin-resistant Staphyloccus aureus infection. JAMA 2003;290:2976 – 84. 5. Lee MC, Rios AM, Aten MF, et al. Management and outcome of children with skin and soft tissue abscesses caused by community-acquired methicillin-resistant Staphylococcus aureus. Pediatr Infect Dis J 2004;23:123–7.

Epithelioid Trophoblastic Tumor Dear Editor: Epithelioid trophoblastic tumor (ETT) belongs to the complex entity of gestational trophoblastic disease, which also comprises the hydatidiform mole, choriocarcinoma, and placental site trophoblastic tumor. Epithelioid, an unusual type of trophoblastic tumor, has features resembling those of carcinoma.1 We describe the clinical and histopathological findings of a choroidal lesion as the initial manifestation of metastasis from an ETT of an unknown primary site. A 37-year-old white woman complained of a superior visual field defect in her left eye for a month. On examination, her visual acuities (VAs) were 20/20 (right eye) and 20/80 (left). The right fundus appeared normal. The left fundus revealed the presence of a mass inferonasal to the optic disc covered with blood (Fig 1A [all figures available at http://aaojournal.org]). Ultrasonography identified a solid tumor of low and medium internal reflectivity (Fig 1B). In the affected area, fluorescein angiography revealed hypofluorescence, and scattered hypoperfused spots covered the inferior fundus (Fig 2A). Indocyanine green angiography depicted engorgement of a large choroidal vessel (Fig 2B). The macular area appeared normal. Observation was advised, and 1 month later, the patient complained of vaginal spotting and pain located in the right-side adnexa. Ultrasonography revealed a probable extrauterine pregnancy with a serum level of ␤– human chorionic gonadotropin (␤-hCG) of 120 mIU/ml, and she underwent a laparotomy. The laparotomy was nondiagnostic but did not confirm either an extrauterine pregnancy or an ETT in the

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