Grand Rounds Marc Moore, M.D. PGY-21/12/07. CC: Red eyes OU CC: Red eyes OU HPI: 71 year-old Caucasian female who presents with redness and “gritty, scratchy”

Grand RoundsGrand Rounds

Marc Moore, M.D.Marc Moore, M.D.

PGY-2PGY-2

1/12/071/12/07

CC: Red eyes OUCC: Red eyes OU HPI: 71 year-old Caucasian HPI: 71 year-old Caucasian

female who presents with female who presents with redness and “gritty, scratchy” redness and “gritty, scratchy” feeling in both eyes.feeling in both eyes.

What else do you want to know?What else do you want to know?

HPIHPI Symptoms present for two weeksSymptoms present for two weeks Blurry visionBlurry vision Mild photophobiaMild photophobia Started in left eye first, then moved to Started in left eye first, then moved to

right eyeright eye Occasional watery dischargeOccasional watery discharge Some matting, especially in the Some matting, especially in the

morningmorning No known exposure or recent URINo known exposure or recent URI

HistoryHistory MedHx: Recurrent Colon CA s/p sigmoid MedHx: Recurrent Colon CA s/p sigmoid

resection, COPD, Arthritis, Stress resection, COPD, Arthritis, Stress incontinenceincontinence

OcHx: noneOcHx: none Meds: Erbitux & Celecoxib (part of study), Meds: Erbitux & Celecoxib (part of study),

Phenergan, Requip, Prilosec, Coumadin, Phenergan, Requip, Prilosec, Coumadin, SynthroidSynthroid

All: IV dyeAll: IV dye SocHx: smokes ½ ppd, no alcoholSocHx: smokes ½ ppd, no alcohol FamHx: father with prostate CAFamHx: father with prostate CA ROS: nausea due to chemoROS: nausea due to chemo

ExamExam

VA: 20/50 VA: 20/50 20/40 OD 20/40 OD

20/70 20/70 20/30 OS 20/30 OS Motility: full OUMotility: full OU CVF: full OUCVF: full OU Pupils: no RAPDPupils: no RAPD Tp: 15 OD, 17 OSTp: 15 OD, 17 OS

Slit Lamp PhotosSlit Lamp Photos

ExamExam External: no preauricular LADExternal: no preauricular LAD Lids & lashes: wnlLids & lashes: wnl Conj: 1-2+ injection OU; No follicles; Conj: 1-2+ injection OU; No follicles;

(+) blanching with phenylephrine (+) blanching with phenylephrine Cornea: scattered PEE OU; No Cornea: scattered PEE OU; No

subepithelial infiltratessubepithelial infiltrates AC: D&Q OUAC: D&Q OU Lens: 1+ NSC OULens: 1+ NSC OU DFE: C/D 0.1 OU; wnl OUDFE: C/D 0.1 OU; wnl OU

Differential of Red Eye in the Differential of Red Eye in the ImmunosuppressedImmunosuppressed

Herpes Zoster Herpes Zoster OphthalmicusOphthalmicus

ConjunctivitisConjunctivitis BacterialBacterial ViralViral MicrosporidiaMicrosporidia Molluscum contagiosumMolluscum contagiosum Drug-relatedDrug-related

KeratitisKeratitis HSVHSV CMVCMV

UveitisUveitis CMVCMV SyphilisSyphilis ToxoplasmosisToxoplasmosis Drug-InducedDrug-Induced Pseudohypopyon Pseudohypopyon

secondary to lymphomasecondary to lymphoma Masquerade Masquerade

syndromessyndromes Intraepithelial neoplasmIntraepithelial neoplasm Malignant melanomaMalignant melanoma Sebaceous cell CASebaceous cell CA

EpiscleritisEpiscleritis ScleritisScleritis

Patient coursePatient course Pt placed on Bacitracin ointment TID OU Pt placed on Bacitracin ointment TID OU

and PF Art Tears QID for presumed and PF Art Tears QID for presumed bacterial conjunctivitis. bacterial conjunctivitis.

3 days later, pt sent to clinic again by her 3 days later, pt sent to clinic again by her oncologist after no improvement. oncologist after no improvement. Oncologist wanted pt checked for corneal Oncologist wanted pt checked for corneal abrasions or ulcers.abrasions or ulcers.

Consideration being given to Consideration being given to discontinuing the pt from the study discontinuing the pt from the study medication (Erbitux) if ocular symptoms medication (Erbitux) if ocular symptoms persisted.persisted.

Erbitux (Cetuximab)Erbitux (Cetuximab) Recombinant human/mouse chimeric Recombinant human/mouse chimeric

epidermal growth factor receptor epidermal growth factor receptor (EGFR) monoclonal antibody(EGFR) monoclonal antibody

Approved as single agent in Approved as single agent in treatment of patients with EGFR-treatment of patients with EGFR-expressing, metastatic colon CAexpressing, metastatic colon CA

Most common adverse events Most common adverse events reported are hypersensitivity and reported are hypersensitivity and acne-like rashacne-like rash

Package insert quotes conjunctivitis Package insert quotes conjunctivitis rate of 7%rate of 7%

Patient CoursePatient Course Pt exam (3 days after initial exam) Pt exam (3 days after initial exam)

essentially unchangedessentially unchanged Bacterial and viral cultures obtained Bacterial and viral cultures obtained

from right inferior fornixfrom right inferior fornix Viral culture: negativeViral culture: negative Bacterial culture: MRSA (sensitive to Bacterial culture: MRSA (sensitive to

Gentamicin, Minocycline, Rifampin, Gentamicin, Minocycline, Rifampin, Vancomycin, Sulfa Trimethoprim)Vancomycin, Sulfa Trimethoprim)

Pt initiated on fortified Tobramycin Pt initiated on fortified Tobramycin drops q 2 hrs OU while awakedrops q 2 hrs OU while awake

BeforeBefore After 3 days of After 3 days of AbxAbx

Patient CoursePatient Course

Drops gradually tapered until D/C after Drops gradually tapered until D/C after 10 days.10 days.

Pt ocular symptoms completely subsidedPt ocular symptoms completely subsided Pt discontinued Erbitux one week later Pt discontinued Erbitux one week later

due to insufficient benefit from due to insufficient benefit from treatmenttreatment

Celecoxib discontinued due to truncal Celecoxib discontinued due to truncal rashrash

MRSAMRSAandand

External Ocular MRSA External Ocular MRSA InfectionsInfections

Methicillin-Resistant Methicillin-Resistant S. S. AureusAureus

Recent population-based study in Recent population-based study in Annals Annals of Internal Medicineof Internal Medicine

9622 patients analyzed with nasal swabs9622 patients analyzed with nasal swabs Prevalence of colonization with MRSA in Prevalence of colonization with MRSA in

the noninstitutionalized was 0.84%the noninstitutionalized was 0.84% More likely to find colonization with:More likely to find colonization with:

Age > 65Age > 65 FemalesFemales DiabetesDiabetes Long-term care in the past yearLong-term care in the past year

External Ocular MRSA External Ocular MRSA InfectionsInfections

Study published 2005 from the UK Study published 2005 from the UK looked at 544 documented MRSA looked at 544 documented MRSA infectionsinfections

17 of 544 were external ocular infections17 of 544 were external ocular infections Six (35%) with conjunctivitisSix (35%) with conjunctivitis Four (24%) with keratitisFour (24%) with keratitis Three (18%) with dacryocystitisThree (18%) with dacryocystitis Three (18%) with socket infectionThree (18%) with socket infection One (6%) with infected draining device One (6%) with infected draining device

after RD repairafter RD repair

External Ocular MRSA External Ocular MRSA InfectionsInfections

All patients had one or more of the All patients had one or more of the following risk factors:following risk factors: MalignancyMalignancy Debilitating systemic diseaseDebilitating systemic disease History of ocular surface disorderHistory of ocular surface disorder

Conclusion: External MRSA infections Conclusion: External MRSA infections are uncommon in the UK, are uncommon in the UK, representing only 3% of external representing only 3% of external S. S. aureus aureus infectionsinfections

MRSA Conjunctivitis in Long-MRSA Conjunctivitis in Long-Term-Care FacilityTerm-Care Facility

Study from 1990 followed 20 Study from 1990 followed 20 episodes (in 19 pts) of MRSA episodes (in 19 pts) of MRSA conjunctivitis over 3 yearsconjunctivitis over 3 years

17 of 19 pts had severe neurological 17 of 19 pts had severe neurological impairmentimpairment

Oral ciprofloxacin and topical Oral ciprofloxacin and topical vancomycin associated with clinical vancomycin associated with clinical resolutionresolution

Antibiotic Resistance of Antibiotic Resistance of MRSAMRSA

Marangon, et al (2004) looked at Marangon, et al (2004) looked at 1230 1230 S. aureusS. aureus isolates from keratitis isolates from keratitis and conjunctivitis over 12 year and conjunctivitis over 12 year period (1990-2001)period (1990-2001)

Corneal MRSA isolates increased Corneal MRSA isolates increased from 12% to 39.5%from 12% to 39.5%

Conjunctival MRSA isolates increased Conjunctival MRSA isolates increased from 7.2% to 18.9%from 7.2% to 18.9%

Overall, MRSA isolates increased Overall, MRSA isolates increased from 8.5% to 27.9%from 8.5% to 27.9%

Antibiotic Resistance of Antibiotic Resistance of MRSAMRSA

Ciprofloxacin resistance increased Ciprofloxacin resistance increased from 55.8% to 83.7%from 55.8% to 83.7%

Levofloxacin resistance increased Levofloxacin resistance increased in MRSA corneal isolates from 4.7% in MRSA corneal isolates from 4.7% in Jan 2000 to 82.1% in Dec 2001in Jan 2000 to 82.1% in Dec 2001

No resistance to Vancomycin was No resistance to Vancomycin was detecteddetected

Gentamicin sensitivities were 86%Gentamicin sensitivities were 86%

Antibiotic Resistance of Antibiotic Resistance of MRSAMRSA

Kotlus, et al (2006) studied in vitro Kotlus, et al (2006) studied in vitro resistance of MRSA ocular isolates against resistance of MRSA ocular isolates against fluoroquinolones, vancomycin and fluoroquinolones, vancomycin and gentamicingentamicin

Culture specimens obtained from 21 pts Culture specimens obtained from 21 pts treated by the cornea servicetreated by the cornea service

Resistance ratesResistance rates Gatifloxacin 71%Gatifloxacin 71% Moxifloxacin 68%Moxifloxacin 68% Ciprofloxacin 94%Ciprofloxacin 94% Ofloxacin 94%Ofloxacin 94% Vancomycin 0%Vancomycin 0% Gentamicin 3%Gentamicin 3%

Community-associated MRSA Community-associated MRSA (CAMRSA)(CAMRSA)

Often sensitive to TMP-sulfa, Often sensitive to TMP-sulfa, tetracycline, rifampin and tetracycline, rifampin and clindamycinclindamycin

Can cause necrotizing pneumonias, Can cause necrotizing pneumonias, large soft-tissue abscesses, and large soft-tissue abscesses, and necrotizing fasciitisnecrotizing fasciitis

Six month prospective case series Six month prospective case series (Rutar et al, 2006) identified 9 pts (Rutar et al, 2006) identified 9 pts with CAMRSA ophthalmic infectionswith CAMRSA ophthalmic infections

8 of 9 pts had no h/o hospitalization8 of 9 pts had no h/o hospitalization

CAMRSACAMRSA

CAMRSACAMRSA Most ophthalmic infections (9 of 11) Most ophthalmic infections (9 of 11)

caused by USA300 clonecaused by USA300 clone Infections includedInfections included

orbital cellulitisorbital cellulitis endogenous endophthalmitisendogenous endophthalmitis panuveitispanuveitis lid abscesseslid abscesses septic venous thrombosisseptic venous thrombosis

Treatment of infections often Treatment of infections often required debridement of necrotic required debridement of necrotic tissues in addition to non-beta-tissues in addition to non-beta-lactam class antibiotics lactam class antibiotics

ConclusionsConclusions MRSA must be a consideration in any MRSA must be a consideration in any

external ocular infection unresponsive to external ocular infection unresponsive to standard antibiotic therapy over 2 weeksstandard antibiotic therapy over 2 weeks

Suspicion for ocular MRSA must increase Suspicion for ocular MRSA must increase with:with: MalignancyMalignancy Debilitating systemic diseaseDebilitating systemic disease History of ocular surface disorderHistory of ocular surface disorder

Resistance to fluoroquinolones is Resistance to fluoroquinolones is increasing, even with 4increasing, even with 4thth generation generation

Vancomycin and gentamicin remain Vancomycin and gentamicin remain effective treatmentseffective treatments

Community-associated MRSA is an Community-associated MRSA is an evolving ocular pathogen most often found evolving ocular pathogen most often found in “hospital-naive” patientsin “hospital-naive” patients

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