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Grand Rounds

Grand Rounds. Marc Moore, M.D. PGY-2 1/12/07. CC: Red eyes OU HPI: 71 year-old Caucasian female who presents with redness and “gritty, scratchy” feeling in both eyes. What else do you want to know?. HPI. Symptoms present for two weeks Blurry vision Mild photophobia

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Grand Rounds

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  1. Grand Rounds Marc Moore, M.D. PGY-2 1/12/07

  2. CC: Red eyes OU • HPI: 71 year-old Caucasian female who presents with redness and “gritty, scratchy” feeling in both eyes. What else do you want to know?

  3. HPI • Symptoms present for two weeks • Blurry vision • Mild photophobia • Started in left eye first, then moved to right eye • Occasional watery discharge • Some matting, especially in the morning • No known exposure or recent URI

  4. History • MedHx: Recurrent Colon CA s/p sigmoid resection, COPD, Arthritis, Stress incontinence • OcHx: none • Meds: Erbitux & Celecoxib (part of study), Phenergan, Requip, Prilosec, Coumadin, Synthroid • All: IV dye • SocHx: smokes ½ ppd, no alcohol • FamHx: father with prostate CA • ROS: nausea due to chemo

  5. Exam • VA: 20/50  20/40 OD 20/70  20/30 OS • Motility: full OU • CVF: full OU • Pupils: no RAPD • Tp: 15 OD, 17 OS

  6. Slit Lamp Photos

  7. Exam • External: no preauricular LAD • Lids & lashes: wnl • Conj: 1-2+ injection OU; No follicles; (+) blanching with phenylephrine • Cornea: scattered PEE OU; No subepithelial infiltrates • AC: D&Q OU • Lens: 1+ NSC OU • DFE: C/D 0.1 OU; wnl OU

  8. Herpes Zoster Ophthalmicus Conjunctivitis Bacterial Viral Microsporidia Molluscum contagiosum Drug-related Keratitis HSV CMV Uveitis CMV Syphilis Toxoplasmosis Drug-Induced Pseudohypopyon secondary to lymphoma Masquerade syndromes Intraepithelial neoplasm Malignant melanoma Sebaceous cell CA Episcleritis Scleritis Differential of Red Eye in the Immunosuppressed

  9. Patient course • Pt placed on Bacitracin ointment TID OU and PF Art Tears QID for presumed bacterial conjunctivitis. • 3 days later, pt sent to clinic again by her oncologist after no improvement. Oncologist wanted pt checked for corneal abrasions or ulcers. • Consideration being given to discontinuing the pt from the study medication (Erbitux) if ocular symptoms persisted.

  10. Erbitux (Cetuximab) • Recombinant human/mouse chimeric epidermal growth factor receptor (EGFR) monoclonal antibody • Approved as single agent in treatment of patients with EGFR-expressing, metastatic colon CA • Most common adverse events reported are hypersensitivity and acne-like rash • Package insert quotes conjunctivitis rate of 7%

  11. Patient Course • Pt exam (3 days after initial exam) essentially unchanged • Bacterial and viral cultures obtained from right inferior fornix • Viral culture: negative • Bacterial culture: MRSA (sensitive to Gentamicin, Minocycline, Rifampin, Vancomycin, Sulfa Trimethoprim) • Pt initiated on fortified Tobramycin drops q 2 hrs OU while awake

  12. After 3 days of Abx Before

  13. Patient Course • Drops gradually tapered until D/C after 10 days. • Pt ocular symptoms completely subsided • Pt discontinued Erbitux one week later due to insufficient benefit from treatment • Celecoxib discontinued due to truncal rash

  14. MRSA and External Ocular MRSA Infections

  15. Methicillin-Resistant S. Aureus • Recent population-based study in Annals of Internal Medicine • 9622 patients analyzed with nasal swabs • Prevalence of colonization with MRSA in the noninstitutionalized was 0.84% • More likely to find colonization with: • Age > 65 • Females • Diabetes • Long-term care in the past year

  16. External Ocular MRSA Infections • Study published 2005 from the UK looked at 544 documented MRSA infections • 17 of 544 were external ocular infections • Six (35%) with conjunctivitis • Four (24%) with keratitis • Three (18%) with dacryocystitis • Three (18%) with socket infection • One (6%) with infected draining device after RD repair

  17. External Ocular MRSA Infections • All patients had one or more of the following risk factors: • Malignancy • Debilitating systemic disease • History of ocular surface disorder • Conclusion: External MRSA infections are uncommon in the UK, representing only 3% of external S. aureus infections

  18. MRSA Conjunctivitis in Long-Term-Care Facility • Study from 1990 followed 20 episodes (in 19 pts) of MRSA conjunctivitis over 3 years • 17 of 19 pts had severe neurological impairment • Oral ciprofloxacin and topical vancomycin associated with clinical resolution

  19. Antibiotic Resistance of MRSA • Marangon, et al (2004) looked at 1230 S. aureus isolates from keratitis and conjunctivitis over 12 year period (1990-2001) • Corneal MRSA isolates increased from 12% to 39.5% • Conjunctival MRSA isolates increased from 7.2% to 18.9% • Overall, MRSA isolates increased from 8.5% to 27.9%

  20. Antibiotic Resistance of MRSA • Ciprofloxacin resistance increased from 55.8% to 83.7% • Levofloxacin resistance increased in MRSA corneal isolates from 4.7% in Jan 2000 to 82.1% in Dec 2001 • No resistance to Vancomycin was detected • Gentamicin sensitivities were 86%

  21. Antibiotic Resistance of MRSA • Kotlus, et al (2006) studied in vitro resistance of MRSA ocular isolates against fluoroquinolones, vancomycin and gentamicin • Culture specimens obtained from 21 pts treated by the cornea service • Resistance rates • Gatifloxacin 71% • Moxifloxacin 68% • Ciprofloxacin 94% • Ofloxacin 94% • Vancomycin 0% • Gentamicin 3%

  22. Community-associated MRSA (CAMRSA) • Often sensitive to TMP-sulfa, tetracycline, rifampin and clindamycin • Can cause necrotizing pneumonias, large soft-tissue abscesses, and necrotizing fasciitis • Six month prospective case series (Rutar et al, 2006) identified 9 pts with CAMRSA ophthalmic infections • 8 of 9 pts had no h/o hospitalization

  23. CAMRSA

  24. CAMRSA • Most ophthalmic infections (9 of 11) caused by USA300 clone • Infections included • orbital cellulitis • endogenous endophthalmitis • panuveitis • lid abscesses • septic venous thrombosis • Treatment of infections often required debridement of necrotic tissues in addition to non-beta-lactam class antibiotics

  25. Conclusions • MRSA must be a consideration in any external ocular infection unresponsive to standard antibiotic therapy over 2 weeks • Suspicion for ocular MRSA must increase with: • Malignancy • Debilitating systemic disease • History of ocular surface disorder • Resistance to fluoroquinolones is increasing, even with 4th generation • Vancomycin and gentamicin remain effective treatments • Community-associated MRSA is an evolving ocular pathogen most often found in “hospital-naive” patients

  26. References • Brennen C, Muder RR. Conjunctivitis associated with methicillin-resistant Staphylococcus aureus in a long-term-care facility. Am J Med. 1990 May;88(5N):14N-17N. • Graham PL, Lin SX, Larson EL. A U.S. population-based survey of Staphylococcus aureus colonization. Ann Intern Med. 2006 Mar 7;144(5):318-25. • Kotlus BS, Wymbs RA, Vellozzi EM, Udell IJ. In vitro activity of fluoroquinolones, vancomycin, and gentamicin against methicillin-resistant Staphylococcus aureus ocular isolates. Am J Ophthalmol. 2006 Nov;142(5):726-9. • Krachmer JH, Mannis MJ, Holland EJ. Cornea and External Disease: Clinical Diagnosis and Management. 1997 Mosby 745-777. • Marangon FB, Miller D, Muallem MS, Romano AC, Alfonso EC. Ciprofloxacin and levofloxacin resistance among methicillin-sensitive Staphylococcus aureus isolates from keratitis and conjunctivitis. Am J Ophthalmol. 2004 Mar;137(3):453-8. • Rose BD, Rush JM, ed. Cetuximab: Drug Information. UpToDate Online 14.3. Lexi-Comp Inc. 2006. • Rutar T, Chambers HF, Crawford JB, Perdreau-Remington F, Zwick OM, Karr M, Diehn JJ, Cockerham KP. Ophthalmic manifestations of infections caused by the USA300 clone of community-associated methicillin-resistant Staphylococcus aureus.Ophthalmology. 2006 Aug;113(8):1455-62. • Shanmuganathan VA, Armstrong M, Buller A, Tullo AB. External ocular infections due to methicillin-resistant Staphylococcus aureus (MRSA). Eye. 2005 Mar;19(3):284-91. • Wong SF. Cetuximab: An Epidermal Growth Factor Receptor Monoclonal Antibody for the Treatment of Colorectal Cancer. Clinical Therapeutics. 2005 Nov;12(6):684-694.

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