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 • 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
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
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
Slit Lamp Photos
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
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
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.
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%
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
After 3 days of Abx Before
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
MRSA and External Ocular MRSA Infections
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
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
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
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
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%
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%
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%
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
CAMRSA
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
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
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.
