Transcript 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
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
Differential of Red Eye in the
Immunosuppressed


Herpes Zoster
Ophthalmicus
Conjunctivitis






Bacterial
Viral
Microsporidia
Molluscum contagiosum
Drug-related







Keratitis


Uveitis
Masquerade syndromes


HSV
CMV



CMV
Syphilis
Toxoplasmosis
Drug-Induced
Pseudohypopyon secondary
to lymphoma
Intraepithelial neoplasm
Malignant melanoma
Sebaceous cell CA
Episcleritis
Scleritis
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
Before
After 3 days of Abx
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-TermCare 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 (19902001)
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 “hospitalnaive” 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):14N17N.
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. LexiComp 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.