Ocular Bacterial and Viral Infectionscurrent management of

BUSTBUGS

the

Based on a CE Symposium held inSan Francisco, California, November 2010.

This continuing education activity is supportedthrough an unrestricted educational grant from

A supplement to

COPE Course ID: 31574-AS

Expiration Date: April 1, 2014

This course is COPE approved for 2 credits

Sponsored by

Administrator:

2

LEARNING METHOD AND MEDIUMThis educational activity consists of a supplement and 20 study questions. The participantshould, in order, read the learning objectives contained at the beginning of this supplement,read the supplement, answer all questions in the post test, and complete the evaluation form.To receive credit for this activity, please follow the instructions provided on the post test andevaluation form. This educational activity should take a maximum of 2.0 hours to complete.

CONTENT SOURCEThis continuing education (CE) activity is based on a CE symposium held on Thursday, Novem-ber 18, 2010, during the American Academy of Optometry 2010 Meeting in San Francisco,California.

TARGET AUDIENCEThis educational activity intends to educate optometrists.

OVERVIEWOptometrists routinely encounter ocular infections; therefore, it is critical they receive educa-tion and updates on when and what to treat, and when to refer and co-manage with a subspe-cialist. Common ocular infections such as bacterial and viral conjunctivitis, bacterial and viralkeratitis, are diagnosed and treated by the optometrist. Additionally, optometrists see patientswho have undergone cataract surgery or other procedures which put them at risk for endoph-thalmitis. This infection also needs to be recognized and promptly co-managed with the oph-thalmic surgeon to avoid vision loss. Recent and growing reports of antibiotic resistance topathogens have elevated concerns about which antibiotics to use, when to use them, and howto recognize signs of resistance. Current issues and developments in infection managementneed to be communicated to optometrists so they may incorporate these developments intothe everyday care for their patients.

LEARNING OBJECTIVESUpon completion of this activity, optometrists will be better able to:• Distinguish bacterial from viral ocular infections• Discuss latest findings in anti-infective resistance as it relates to managing bacterialconjunctivitis, bacterial keratitis, and endophthalmitis

• Compare and contrast the currently available topical antibiotics and antivirals for efficacyand safety• Discuss best-practice regimens for infection management in conditions such as bacterialand viral conjunctivitis, and bacterial and herpetic keratitis

ACCREDITATION DESIGNATION STATEMENTThis course is COPE approved for 2 Credits for Optometrists. COPE Course ID: 31574-AS

DISCLOSURESMichael D. DePaolis, OD, FAAO, has had a financial agreement or affiliation during the pastyear with the following commercial interests in the form of Clinical Investigator, Advisory Panel,Consultant: Abbott Medical Optics; Alcon, Inc; Allergan, Inc; Bausch + Lomb Incorporated; CIBAVISION; CooperVision, Inc; Paragon Vision Sciences; SynergEyes; and Vistakon; OptometricEditor, Primary Care Optometric News; Independent Board of Directors: RevitalVision, LLC.

Paul M. Karpecki, OD, FAAO, has had a financial agreement or affiliation during the past yearwith the following commercial interests in the form of Consultant/Advisory Board: Alcon, Inc;Allergan, Inc; Bausch + Lomb Incorporated; ISTA Pharmaceuticals, Inc; and Rapid PathogenScreening, Inc.

Louise A. Sclafani, OD, FAAO, has had a financial agreement or affiliation during the past yearwith the following commercial interests in the form of Consultant/Advisory Board: Abbott MedicalOptics; Alcon, Inc; Allergan, Inc; Bausch + Lomb Incorporated; CIBA VISION; CooperVision, Inc;and Inspire Pharmaceuticals; Salary (Spouse):Optos North America;Owner: University Contacts.

Joseph P. Shovlin, OD, FAAO, has had a financial agreement or affiliation during the past yearwith the following commercial interests in the form of Consultant/Advisory Board: Abbott MedicalOptics; Alcon, Inc; Bausch + Lomb Incorporated; CIBA VISION; and Genzyme Corporation.

OFF-LABEL DISCUSSIONThis activity includes off-label discussion of ganciclovir and topical anti-inflammatory agentsfor epidemic keratoconjunctivitis.

EDITORIAL SUPPORT DISCLOSURESDerek Dore, PharmD; Cynthia Tornallyay, RD, MBA; and Barbara Lyon have no relevantcommercial relationships to disclose.

DISCLOSURE ATTESTATIONEach of the contributing physicians listed above has attested to the following:1) that the relationships/affiliations noted will not bias or otherwise influence his or herinvolvement in this activity;

2) that practice recommendations given relevant to the companies with whom he or she hasrelationships/affiliations will be supported by the best available evidence or, absent evi-dence, will be consistent with generally accepted medical practice; and

3) that all reasonable clinical alternatives will be discussed when making practicerecommendations.

GRANTOR STATEMENTThis continuing education activity is supported through an unrestricted educational grant fromBausch + Lomb Incorporated.

TO OBTAIN CE CREDITSTo obtain CE credit for this activity, read the material in its entirety and consult the referencedsources as necessary, and complete the post test. You must score a 70% or better. Please returnthe completed evaluation form along with the completed post test answer box located withinthis supplement and return via SCAN and EMAIL to Forms@MedEdicus.com OR FAX to 203-404-7767. Your certificate will be emailed to the address that you provide on the evaluationform. Please allow 4 weeks for CE Request forms to process.

The views and opinions expressed in this educational activity are those of the faculty and donot necessarily represent the views of State University of New York College of Optometry,MedEdicus LLC, Bausch + Lomb Incorporated, or Optometry Times. Please refer to the officialprescribing information for each product for discussion of approved indications, contraindi-cations, and warnings. The CE symposium on which this CE monograph is based was not affil-iated with the official program of the American Academy of Optometry.

Copyright 2011 MedEdicus LLC

Louise A. Sclafani, OD, FAAOOphthalmology and Visual ScienceAssociate Professor of SurgeryDirector, Optometry Clinics, Section of SurgeryCenter for Advanced MedicineChicago, Illinois

Joseph P. Shovlin, OD, FAAONortheastern Eye InstituteScranton, PennsylvaniaAdjunct FacultyPennsylvania College of OptometryPhiladelphia, Pennsylvania

Program Chair and ModeratorPaul M. Karpecki, OD, FAAOCorneal Services and Ocular Disease Research Clinical DirectorKoffler Vision GroupLexington, Kentucky

FacultyMichael D. DePaolis, OD, FAAOVisionary Eye AssociatesAdjunct FacultyUniversity of Rochester Medical CenterRochester, New York

Ocular Bacterial and Viral Infections

BUSTBUGS

current management of

the

3

DIFFERENTIAL DIAGNOSIS OF“PINK EYE”Louise A. Sclafani, OD, FAAO

EtiologyPink eye, or conjunctivitis, is one of the most common reasons patients presentto optometrists. Conjunctivitis is most often caused by a virus, with adenovirusaccounting for 35% to 40% of all acute conjunctivitis cases and 80% to 90%of viral cases. More than 50 adenovirus serotypes have been identified. Subtypesof adenoviral conjunctivitis include epidemic keratoconjunctivitis (EKC), whichhas traditionally been synonymous with the term “pink eye”, and pharyngocon-junctival fever, which is accompanied by fever and pharyngitis. Herpes simplexvirus (HSV) conjunctivitis and herpes zoster ophthalmicus (HZO) tend to bemost problematic, causing corneal scars and leading to recurrent outbreaks.

Bacterial conjunctivitis is most commonly caused by Staphylococcus aureus,Staphylococcus epidermidis, Streptococcus pneumoniae, and Haemophilus influen-zae. Neisseria gonorrhoeae is another possible bacterial source. Chlamydia tra-chomatis, which presents like a viral infection—causing longer-lasting andrecurrent infections—may be found in sexually active patients, neonates, andin underdeveloped countries.

Conjunctivitis can also develop from allergic and inflammatory sources.

Initial AssessmentPatients with conjunctivitis present with redness ranging from mild to severe,but typically diffuse, with congested bulbar and palpebral vessels and petechialto large subconjunctival hemorrhages. Clinicians should consider the patient’sbaseline color when assessing redness.

Viral conjunctivitis is characterized by sudden onset, bilateral presentation (fel-low eye is usually less affected), foreign body sensation (FBS), pain, photopho-bia, concurrent gastrointestinal symptoms, and upper respiratory tractinfection. Patients often can identify the viral exposure. The infection can lastfrom weeks to months. Skin lesions are representative of both HSV and HZO.

Bacterial conjunctivitis is characterized by an acute onset, FBS, pain, and uni-lateral presentation. The infection may worsen without treatment.

Allergic conjunctivitis is typically a seasonal occurrence, with itching being themost common symptom. Presentation is typically bilateral, unless the conditionis foreign body-induced.

Lid ReactionsFollicular reactions, which present as smooth dome-shaped nodules under theconjunctival epithelium, represent lymphoblastic proliferation. Usually found onthe lower lid, their apex is avascular; fine vessels are seen at the base (Figure 1).Inflammatory papillae, which present as a mosaic pattern of dilated telangiectaticvessels, have a propensity for the upper lid. Papillae are best seen with a fluo-rescein-cobalt filter (Figure 2).

Follicles are more characteristic of viral conjunctivitis, although they are oftenseen with Chlamydia infection. Papillae are an indication of allergic conjunctivitis.Mixed reaction—follicles and papillae—is commonly observed with all causes.

Corneal ReactionsCorneal punctate epithelial keratitis, which can range from very fine to dense,often causes FBS and photophobia. Keratopathy associated with viral conjunc-tivitis should not be confused with Thygeson superficial punctate keratitis,

INTRODUCTIONOptimizing outcomes in patients with ocular infections involves determining the infection etiology, appreciating ocular pathogen resistance, and under-standing the benefits and risks of anti-infective agents. Determining the cause of an ocular infection can be difficult. And, distinguishing betweenviral and bacterial etiology is important for the selection of effective and safe therapy, appropriately educating patients, and reducing spread of thecondition. Ocular pathogens are becoming increasingly resistant to the available anti-infective agents, leading to poor outcomes in conditions suchas conjunctivitis, keratitis, and even endophthalmitis—particularly when resistance patterns are not recognized and appropriate therapy is not pre-scribed. To our benefit, recent innovations have provided the eye care clinician with effective additions to the anti-infective armamentarium.

Recently, 4 leading optometrists convened at a continuing education (CE) symposium held during the 2010 American Academy of Optometryannual meeting. This CE monograph presents highlights from their presentations and case discussions. It will share their expertise in differentiatingviral from bacterial ocular infections, enhance understanding of the latest trends in ocular pathogen resistance, compare and contrast the currentlyavailable topical antiviral and antibacterial agents for efficacy and safety, and present best-practice regimens in managing ocular infections.

Figure 1. Follicles

Figure 2. Papillae Photos Courtesy Louise A. Sclafani, OD

4

which is a bilateral, intraepithelial condition with pearly lesions that do notstain profusely. Mechanical abrasion, from a large follicle or eye rubbing, shouldbe considered when making a differential diagnosis when a corneal reaction ispresent. There is usually an evolution to corneal signs with HSV infection,beginning with a discrete punctate epithelial lesion. It is at this stage of thecorneal reaction that approximately 5% of cases are mistaken for EKC. WithHSV infection, however, the lesion will typically coalesce within days to form abranching lesion (dendrite).

Infiltrates are from immune-mediated reactions, caused by infectious or nonin-fectious conditions; they are subepithelial and thus do not stain. More commonwith viral conjunctivitis, infiltrates may coalesce—typically as the patient’s con-dition is improving—and affect visual acuity (VA). Treatment with topicalsteroids may be needed. Infiltrates associated with viral conjunctivitis shouldnot be confused with infiltrates resulting from hypersensitivity to staphylococcalexotoxins, which present along the limbus—between 4 and 8 o’clock.

DischargeA common manifestation, discharge is usually watery with viral conjunctivitis.Stringy discharge is typical of allergic conjunctivitis. Purulent discharge is rep-resentative of bacterial etiology, particularly gonococcal infection.

MembranesMembranes are inflammatory discharge of fibrin with polymorphonuclear neu-trophils and fibrin coagulation on the conjunctiva. A true membrane incorporatesinto the epithelium and bleeds when removed, whereas a pseudomembrane,being superficial, can be more easily removed by peeling or scraping.

Decreased corneal sensitivity occurs with HSV infection and neurotrophic HZO,whereas bacterial conjunctivitis is not often associated with reduced sensitivity.Use of dental floss, which is firmer and more uniform than the traditional cottonwisp used for testing, can easily detect corneal sensitivity.

Lymphadenopathy, with an enlarged, tender preauricular node (PAN), is likelydiagnostic for viral infection, although the node may be inflamed with Chlamydiainfection.

Laboratory testing is diagnostically sensitive in cases of conjunctivitis; cultures,however, are expensive, time-consuming, and necessitate access to a laboratory.Polymerase chain reaction (PCR) testing is extremely sensitive and specific indetermining the ocular pathogen, but PCR is expensive and generally reservedfor hospital use or following an infectious outbreak. The RPS Adeno Detector™is an inexpensive, in-office device that easily and rapidly obtains a sample oftears. The test is highly sensitive in determining the presence of adenovirus.This allows for an accurate diagnosis, appropriate prescribing, and improvedpatient education—particularly regarding the condition’s contagious nature.Indeed, viral conjunctivitis is extremely contagious—patients can spread thecondition at least 8 days before they experience symptoms and for approxi-mately 10 to 14 days after symptoms initially occur.

HERPETIC EYE DISEASE: THE BESTMASQUERADER OF THEM ALLJoseph P. Shovlin, OD, FAAOThere are at least 8 distinct DNA viruses in the human Herpesviridae family,including HSV and herpes zoster virus (HZV). HSV-1 is the more common ocu-lar pathogen—HSV-2 more often causes genital disease and is transmitted atbirth.1 Twenty-five percent of people are seropositive for HSV at age 4; nearly100% are HSV seropositive by age 60.

HSV infections are often asymptomatic; HSV conjunctivitis, however, must bepart of the differential diagnosis, especially with presentation of unilateral fol-licular conjunctivitis. Multiple lesions can occur along the lash margins; oozinglesions are highly contagious (Figure 3). Viral skin eruptions can occur—mostlywith primary disease. In children, primary ocular disease can manifest with a

high fever and cutaneous outbreak around the lids, which results in a prolonged,serious illness that is less responsive to therapy (Figure 4). Particularly concern-ing in the young is eczema herpeticum, which can be life-threatening.

Anterior corneal involvement occurs in approximately 50% of ocular HSV infec-tion cases, and stromal disease is observed in approximately 6% of cases.2When HSV infection affects the cornea, many clinical presentations are possi-ble. Infectious epithelial keratitis can occur in the form of corneal vesicles, den-dritic ulcers, geographic ulcers, and marginal ulcers. Specifically, small raisedcorneal vesicles may develop and coalesce into a branching pattern to form adendritic ulcer (Figure 5). HSV produces the only dendriform lesion that istruly ulcerative; all other dendritic lesions are infiltrated. Marginal ulcers canoccur in areas where infiltrates move in; these ulcers may be misinterpreted asa staphylococcal-related infection. HSV-induced ulcers are typically positionednear the limbus, the bed of hypersensitivity reactions. Stromal keratitis is amanifestation of an immune stromal reaction, with vascularization, infiltration,and scarring visible; necrotizing keratitis, which is extremely difficult to manage,may also occur. Endotheliitis, which can have an infective and also an inflamma-tory component, may call for oral antivirals and topical/oral steroids. Neu-rotrophic keratopathy, a condition secondary to impaired corneal innervationand decreased tear production, can be associated with very poor outcomes.

Various conditions must be considered in the differential diagnosis for herpeticeye disease (Table 1). Early and accurate recognition of herpes as the causativepathogen is vital to optimizing outcomes in patients afflicted with active her-petic ocular infection.

Figure 3. Oozing HSV Lesions

Figure 4. Cutaneous HSV Lesions

Figure 5. Dendritic Ulcer From HSV InfectionPhotos Courtesy Joseph P. Shovlin, OD

5

THE IMPLICATIONS OF ANTIBIOTICRESISTANCEMichael D. DePaolis, OD, FAAO

Is Antibiotic Monotherapy Acceptable?Historically, antibiotic monotherapy for ocular infections was supported bysound evidence. In the mid 1990s, the fluoroquinolones ciprofloxacin andofloxacin, as monotherapy, were found to provide similar clinical success in thetreatment of bacterial keratitis when compared with the standard of care—dual therapy with a fortified aminoglycoside and a cephalosporin.3,4 These flu-oroquinolones were effectively treating gram-negative organisms. However, overthe course of the 1990s, gram-positive organisms became increasingly resistantto the fluoroquinolones.

Gram-Positive ResistanceFrom 1990 to 1998, in a study conducted at Bascom Palmer Eye Institute at theUniversity of Miami Miller School of Medicine, a gradual increase in the numberof S aureus isolates was found in bacterial keratitis cultures (29% of gram-positiveorganisms in 1990 vs 48% in 1998, P=.01; total cultures=1468). These organ-isms became increasingly resistant to ciprofloxacin and ofloxacin (11% resistantin 1990 vs 28% resistant in 1998).5 Likewise, during this time, S aureus isolatesfrom bacterial keratitis cases (n=1053) at The Charles T. Campbell OphthalmicMicrobiology Laboratory at the University of Pittsburgh Medical Center becameincreasingly resistant to ciprofloxacin (5.8% resistant in 1993 to 35% resistantin 1997) and to ofloxacin (4.7% resistant in 1993 to 35% resistant in 1997).6These trends led to the development of the advanced-generation, 8-methoxyfluoroquinolones gatifloxacin and moxifloxacin, which were designed to providebroader coverage against the resistant strains of gram-positive organisms.

Sadly, resistance to the advanced-generation fluoroquinolones eventually devel-oped. For example, gram-positive organisms, which accounted for 80.5%(124/154) of culture-positive isolates in a review of consecutive cases of endoph-thalmitis between 1999 and 2008, demonstrated a high rate of in vitro resistanceto the fluoroquinolones, with 47.1%, 43.4%, 36.8%, and 29% of isolates resist-ant to moxifloxacin, ciprofloxacin, gatifloxacin, and levofloxacin, respectively.7 Jhanjiand colleagues recently reported on a case in which coagulase-negative S epider-midis-keratitis could not be contained by topical cefazolin and gatifloxacin, withthe organism also demonstrating resistance to ciprofloxacin and moxifloxacin.Treatment with fortified vancomycin, 5%, and tobramycin, 1.3%, eventuallyresolved the infection.8 In 2006, Moshirfar and colleagues published a report on2 cases of bacterial keratitis resistant to advanced-generation fluoroquinolones:1) Pseudomonas aeruginosa-keratitis after photorefractive keratectomy despitepostoperative moxifloxacin administration; and 2) methicillin-resistant S aureus(MRSA)-keratitis following LASIK (laser-assisted in situ keratomileusis) despiteprophylactic gatifloxacin. In both cases, the isolates were found to be resistant toboth gatifloxacin and moxifloxacin. Treatment with topical aminoglycosides andsurgical intervention was needed to cure the infections.9

MRSA on the RiseA report from The Surveillance Network, involving more than 580,000 culturedocular isolates of S aureus, revealed that MRSA increased from 29.5% in 2000

to 41.6% in 2005, with the majority of the MRSA isolates found to be mul-tidrug-resistant, including resistance to traditional and advanced-generationfluoroquinolones (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin).10 Like-wise, data from the Ocular Tracking Resistance in U.S. Today (TRUST) showedthat only 15.2% of MRSA ocular isolates are susceptible to the fluoro-quinolones ciprofloxacin, gatifloxacin, levofloxacin, and moxifloxacin. Trimetho-prim was the sole agent with high activity against MRSA.11 These trends areparticularly concerning because 2.5% of the general population and 20% ofhealth care workers harbor MRSA.

P aeruginosa, a gram-negative organism that has a great predilection for thecornea, has shown significant resistance to the fluoroquinolones, includingciprofloxacin,12 gatifloxacin,13 and moxifloxacin.13 Happily, this ocular pathogenhas shown susceptibility to fortified aminoglycosides.13

There are a few therapeutic strategies that can be utilized to battle theseincreasingly resistant organisms (Table 2). Interestingly, some of our conven-tional antibiotic options, such as fortified aminoglycosides and trimethoprim,are highly effective against several resistant pathogens.10,11 Innovation is pro-viding greater options in the fight against resistant organisms.

THE NEWEST DRUGS TO COMBATBAD BUGSPaul M. Karpecki, OD, FAAO

Antiviral TherapyFor the past 3 decades, the landscape of topical antiviral therapy had notchanged. Trifluridine ophthalmic solution, 1%, the predominant topical therapyused, is dosed up to 9 times daily and has nonselective activity on the host celland the virus. This nonselectivity can cause corneal toxicity, necessitatingdecreased dosing and subsequent delayed corneal healing—or the need toadminister oral antiviral therapy.1,14,15 Vidarabine ophthalmic ointment, 3%, isoften effective for strains resistant to trifluridine,14 though clinical resistanceto the agent has been emerging. Vidarabine can induce host toxicity16 and is notalways readily available when prescribed.

Ganciclovir ophthalmic gel, 0.15%, is the first topical antiviral agent to becomeavailable in 30 years. Indicated for the treatment of acute herpetic keratitis(dendritic ulcers), the agent is dosed 1 drop 5 times daily until corneal ulcerhealing, then 3 times daily for 7 days.17 Ganciclovir is unique in its specificityfor targeting cells infected by HSV. As a prodrug, ganciclovir remains inactiveand inhibits DNA replication by HSV only after it is phosphorylated by viralthymidine kinases.17

Ganciclovir has been shown to provide clinical efficacy similar to that of thestandard topical antiviral in Europe, acyclovir ointment, 3%, in resolving dendritic

Table 2. Therapeutic Strategies to Combat Resistant Bacterial Organisms

What therapeutic strategies are indicated to battle resistant organisms?• Should you treat or refer?• When in doubt… culture• Prescribe aggressively

o Besifloxacin, gatifloxacin, or moxifloxacin,o Loading dose with frequent dosing

• Consider adjunct agentso Fortified tobramycino Polymyxin B/Trimethoprimo Vancomycin

• Minimize collateral tissue damageo Oral doxycyclineo Topical azithromycino Topical corticosteroids

Table 1. Differential Diagnosis for Herpetic Eye Disease

• Acanthamoeba keratitis, Lyme keratitis, Darier disease, Tyrosinemia• Contact lens-related pathology: infiltrates, pseudodendrites,edematous corneal formations and staining• Marginal infiltrates; antigen hypersensitivity• Other viral diseases: HZV, Epstein-Barr, adenovirus• Other noninfectious conditions: healing abrasions, drug toxicity,Thygeson disease, Fabry disease, stromal dystrophies, superficialhypertrophic dendriform epitheliopathy

6

ulcers in patients with herpetic keratitis, as demonstrated in 4 clinical trials(Tables 3 and 4),17 but because it is a gel, it is less debilitating to patients thanacyclovir ointment. Typically, clinical resolution of the dendrite will be observedafter 5 to 7 days of ganciclovir therapy—with variation depending on the sever-ity of the ulcer.

Although not approved for the treatment of EKC, ganciclovir is active againstadenoviruses in vitro; thus, I often prescribe the agent for cases of viral conjunc-tivitis—to expedite the patient’s recovery time and to reduce the risk ofspreading the highly contagious virus. A small study (n=18) showed ganciclovirto be effective in the treatment of adenoviral keratoconjunctivitis. Patients whoreceived ganciclovir had a mean recovery time of 7.7 days compared with an18.5-day recovery for patients treated with preservative-free artificial tears.1Additional studies may confirm the benefits of ganciclovir in EKC. In my expe-rience, several drops of povidone-iodine, 5%, following proparacaine topicalanesthesia, with subsequent irrigation, along with a 2-week course of topicalanti-inflammatory agents (eg, loteprednol), is an effective second-line, lessexpensive (off-label) treatment for EKC.

Antibacterial TherapyThere are a variety of antibacterial options that have been available for ocularinfections (Table 5). The advanced-generation fluoroquinolones gatifloxacin,0.3%, and moxifloxacin, 0.5%, both approved in 2003, have been effective forbacterial conjunctivitis.18,19 Ocular pathogen resistance, however, to the avail-able antimicrobials has led to the development of new antibacterial agents.

A higher concentration formulation of gatifloxacin, gatifloxacin ophthalmic solu-tion, 0.5%, was recently approved by the US Food and Drug Administration(FDA) for the treatment of bacterial conjunctivitis. The formulation has aunique dosing regimen—1 drop every 2 hours (up to 8 doses) on day 1, fol-lowed by 1 drop 2 to 4 times daily for a total of 7 days. Gatifloxacin, 0.5%,after 5 days of therapy, was shown to be clinically superior to its vehicle in the

treatment of bacterial conjunctivitis in 2 randomized, double-masked, multi-center clinical trials. In these trials, resolution of conjunctival hyperemia andconjunctival discharge was observed in 58% (193/333) of patients treatedwith gatifloxacin, 0.5%, versus 45% (148/325) receiving vehicle. Gatifloxacin,0.5%, led to an ocular pathogen eradication rate of 90% (301/333) versus70% (228/325) for its vehicle.20

A new formulation of moxifloxacin was approved by the FDA recently. The for-mulation contains a xanthan gum-based delivery system, which is designed toprolong the antimicrobial’s contact with the ocular surface.21 We expect addi-tional information to be available soon.

Recently, an advanced-generation fluoroquinolone, besifloxacin ophthalmic sus-pension, 0.6%, was added to our options. The first chlorofluoroquinolone, besi-floxacin has no systemic counterpart, which may potentially provide for minimalresistance.22,23 Besifloxacin has potent and more balanced inhibitory actionagainst bacterial DNA gyrase and topoisomerase IV enzymes compared withother fluoroquinolones.23-26 Indeed, the agent has demonstrated greaterpotency, based on minimum inhibitory concentration (MIC), against resistantgram-positive pathogens—including methicillin-resistant and fluoroquinolone-resistant S aureus and S epidermidis—compared with the advanced-generationfluoroquinolones gatifloxacin and moxifloxacin.25,26 Besifloxacin achieves goodcontact time on the ocular surface and attains high concentrations in the pre-ocular tear film, likely because of its polycarbophil-based vehicle.27 This char-acteristic of the agent allows for its flexible dosing schedule of 1 drop 3 timesa day (4-12 hours apart).28 Such dosing flexibility is particularly advantageousin a pediatric population—wherein the full daily dose can be completed with-out the need to dose during the school day.

CASE 1: BACTERIAL CONJUNCTIVITISIN A CHILDPaul M. Karpecki, OD, FAAOA 5-year-old patient presented with a red eye and significant mucopurulentdischarge, which began 2 days prior and worsened with progressive mattering.The patient was diagnosed with bacterial conjunctivitis.

Although relatively self-limiting, childhood bacterial conjunctivitis should betreated pharmacologically, to prevent comorbidities, such as keratitis, and toreduce the spread of the infection. Thus, besifloxacin ophthalmic suspension,0.6%, 1 drop 3 times a day for 7 days, was prescribed. Besifloxacin was chosenbecause of its dosing flexibility and the agent’s vehicle, DuraSite, which, basedon my clinical experience, prevents the child from tearing the medication out.

Is Care Complete?For a case of adult bacterial conjunctivitis, care may be complete with topicalmedications. However, common eye disorders in young children can be quite dif-ferent from adult ocular disorders. That is, the most common pathogens thatcause bacterial conjunctivitis/keratitis in children—S pneumoniae andH influenzae,along with other causative pathogens—Moraxella catarrhalis and adenovirus—can lead to systemic complications. Moreover, the strains of H influenzae thatcause ocular conditions in children are nontypeable and thus are not accountedfor by the H influenzae vaccine.

Therefore, effectively managing childhood conjunctivitis necessitates both theuse of an anti-infective agent and assessment of the patient’s complete clinicalpresentation. Indeed, this child also had preseptal cellulitis (Figure 6), which isone of the most common complications associated with acute bacterial con-junctivitis in children. In children, it is important for clinicians to rule out trauma,which can increase the risk for MRSA- or streptococcal-cellulitis. Cliniciansshould also examine the skin and adnexa around the orbit for a discrete reddishsheen, and assess orbital tenderness, which may indicate the ethmoidal or max-illary sinus involvement often observed with preseptal cellulitis.

Table 3. Ganciclovir Clinical Efficacy Results (1, Open-Label Trial)17

Table 4. Ganciclovir Clinical Efficacy Results (3, Single-Masked Trials)17

Ganciclovir, 0.15%N=71

Acyclovir, 3%N=67

Clinical Resolution by Day 7 55 (77%) 48 (72%)

Results from an open-label, randomized, controlled, multicenterclinical trial evaluating ganciclovir ophthalmic gel, 0.15%, compared withacyclovir ophthalmic ointment, 3%, in patients with dendritic ulcers.

Ganciclovir, 0.15%N=57

Acyclovir, 3%N=49

Clinical Resolution by Day 7 41 (72%) 34 (69%)

Results from 3 randomized, single-masked, controlled multicenter clinicaltrials evaluating ganciclovir ophthalmic gel, 0.15%, compared withacyclovir ophthalmic ointment, 3%, in 213 patients with dendritic ulcers.

Table 5. Ocular Antibacterial Therapies

• azithromycin gtts• bacitracin ung• gentamycin ung• erythromycin ung• ocufloxacin, ciprofloxacin, levofloxacin gtts• polymyxin B and trimethoprim• advanced-generation fluoroquinolone gtts

7

In pediatric ocular care, there are certain presentations that warrant a referral toa pediatrician or pediatric ophthalmologist (Table 6)—because some condi-tions, such as otitis-conjunctivitis syndrome, may require a rocephin injection.

CASE 2: MICROBIAL KERATITISMichael D. DePaolis, OD, FAAOThe patient is a 33-year-old female with a history of daily soft contact lenswear with use of various multipurpose solutions. She has no history of extendedcontact lens wear. She complains of redness, pain, tearing, and blurriness in herright eye for the last 2 days. A day earlier, her primary care physician prescribedgentamicin to the right eye 4 times daily, but she was ultimately referred to theuniversity medical clinic.

The patient is a social worker at a long-term health care facility—she statesthat she “works in an ocean of MRSA.” Upon questioning, she reports a history(since childhood) of frequent cold sores in and around the mouth, occasionallyin the nasal passage, but never in the eye.

Objective: (Figure 7)• VA OD cc reduced to hand motion at 1 foot• + vesicular lesion on her upper lid• Decreased corneal sensation OD• Slit lamp examination (SLX): central corneal ulcer, peripheral satellitelesions, anterior chamber (AC) reaction• No preauricular adenopathy

Plan:• Laboratory tests for bacteria, fungal, viral, and acanthamoeba• Moxifloxacin, 0.5%, to the right eye every 1 hour with reduction toevery 3 hours• Valacyclovir 1000 mg by mouth 3 times daily• Eventual addition of prednisolone acetate to the right eye 4 times daily

Two-week follow-up:• Dramatic improvement (Figure 8)• VA OD cc 20/80• No culture growth• SLX: corneal ulcer reepithelialized, stromal scar, AC deep and quiet• Plan:

o Moxifloxacin, 0.5%, to the right eye 4 times daily with eventualdiscontinuation

o Prednisolone acetate to the right eye 4 times a day with eventualdiscontinuation

o Valacyclovir decreased to 1000 mg by mouth daily until 1 weekbefore the 3-month follow-up

Three-month follow-up:• Patient presents with iritis• Plan:

o Reinitiate oral valacyclovir

The patient’s iritis eventually resolved.

Discussion:With negative cultures, no definitive etiology was determined. Initially, thispatient’s history (MRSA exposure at work) and clinical picture (bacteria-likeulcer) suggested bacterial keratitis. However, with a history of cold sores andthe AC reaction, HSV is also a suspected pathogen. Bacterial HSV co-infectionis also likely, which underscores the importance of dual antibacterial-antiviraltherapy when facing this type of clinical presentation.

CASE 3: EPIDEMIC KERATOCONJUNCTIVITISLouise A. Sclafani, OD, FAAOAn ophthalmology resident presents with painful, injected red eye for the past24 hours.

Day 1• C/O FBS, watery discharge, photophobia• SLX: follicles, 2+ injection, 1+ punctate epithelial erosions (PEE) + palpa-ble preauricular node, non-febrile, + malaise• Diagnosis: viral conjunctivitis• Plan: cultures/PCR (at patient’s request), preservative-free artificial tears,cool compresses and instruction not to work in the clinic for 1 week

Day 7• Symptoms worse, fellow eye slightly irritated, severe subconjunctivalhemorrhages• C/O 102°F fever and severe nausea, vomiting, and diarrhea

Figure 6. Case 1 Patient: Preseptal CellulitisPhoto used with permission: P. Karpecki

Table 6. When to Refer to a Pediatrician/Pediatric Ophthalmologist

• Fever or general malaiseo Purchase a tympanic or forehead thermometer

• Acute earache or ear infectiono Approximately one-third of all childhood cases are otitis-conjunctivitis syndrome

• A notable red sheen around the eyelidso Preseptal cellulitis or cellulitis

• Significant purulent rhinorrhea or an upper respiratory infectionassociated with any fussiness or sleeplessness

Figure 7. Case 2 Patient: Initial Presentation at University Medical ClinicPhotos Courtesy Michael D. DePaolis, OD

Figure 8. Case 2 Patient: 2-week Follow-upPhotos Courtesy Michael D. DePaolis, OD

8

• SLX: follicles, 3+ injection/chemosis, 2+ PEE• Cultures: + Adenovirus 19 (HAdV type 19)• Diagnosis: viral conjunctivitis• Plan: Continue preservative-free artificial tears, cool compresses, isolation

Days 10 to 14• C/O injection, chemosis, FBS, photophobia, reduction in vision (blurriness),no gastrointestinal symptoms• VA: 20/40, 20/20-• SLX (Figure 9): subepithelial infiltrates 3+/1+, pseudomembrane rightlower lid 3 mm• Plan: Peel pseudomembrane, topical steroids 4 times daily with tapering(every 5 days) over 1 month

The patient’s symptoms gradually improved and he returned to working in clin-ical care at 3 weeks.

Approximately 1 month after his initial presentation, a second ophthalmologiststaff member was affected with the same viral strain (HAdV type 19). In addition,an unusual increase in the number of conjunctivitis cases occurred in the neonatalintensive care unit (NICU). Infectious disease (ID) was consulted to investigate.ID determined the dates, vector, and location of transmission. All affectedneonates had undergone an eye examination in the clinic and cultures/PCR foundthe neonates to have the same strain (HAdV type 19) as the 2 clinicians. An iso-lation process was initiated—cohorting neonates into 3 pods (affected, exposed,new admissions). No cross-transmission ever occurred. A sterilization processwas begun and eye examinations were not performed until the process was com-plete (2 weeks). Eight days (6 weeks from initial case) after eye equipment was“cleaned” with standard 30-minute soak in 70% isopropyl alcohol, HAdV type 19was isolated on numerous pieces of equipment, confirmed with PCR.

This case highlights the contagious nature of viral conjunctivitis and stressesthe importance of early correct identification of the infection etiology, whichmay limit the spread of disease, minimize time loss from work, and reduce toxicity

and drug resistance from excessive empirical use of antibiotics. This outbreakprompted improvement of the ophthalmology sterilization practice—disposableequipment is now used in the NICU. Due to the excellent standard proceduresalready in place at the institution, no cross-transmission after the outbreak wasrecognized and the unit was able to swiftly reopen to transfers.

CASE 4: HERPES SIMPLEX KERATITISJoseph P. Shovlin, OD, FAAOThe patient is a 68-year-old white male who was recently released from thehospital after ventilation therapy for acute respiratory distress. He was treated1 week earlier for presumed marginal keratitis with topical tobramycin/dexa-methasone ophthalmic suspension, 0.3/0.05%, to the left eye every 2 hours.At presentation, SLX showed multiple geographic lesions (circumferential) atthe limbal sulcus of the left eye (Figure 10).

The tobramycin/dexamethasone ophthalmic suspension was discontinued and thepatient began therapy with ganciclovir ophthalmic gel, 0.15%, to the left eye 5times daily, valacyclovir 500mg bymouth 3 times daily, and antibiotic prophylaxis.

The patient’s lesions responded exquisitely to the topical ganciclovir and oralvalacyclovir, with no adverse events. The choice of using dual antiviral therapyin this case deviated from the current evidence. The National Institutes ofHealth-sponsored Herpes Simplex Virus Epithelial Keratitis Trial (HEDS-EKT)found that there was no benefit from the addition of an oral antiviral agent(acyclovir) to treatment with a topical antiviral (trifluridine) in preventing thedevelopment of stromal keratitis or iritis in patients with acute HSV epithelialkeratitis. In addition, the study found that the risk of stromal keratitis or irido-cyclitis was low in the year following an episode of epithelial keratitis whentreated with a topical antiviral (trifluridine) alone.29 In this case, however, dualantiviral therapy was warranted based on the patient’s compromised health.His ocular condition was likely induced or enhanced by his recent respiratoryillness and subsequent hospitalization, and exacerbated by the aggressive dos-ing of the topical corticosteroid.

Figure 9. Case 3 Patient: Subepithelial Infiltrates at 2-week Follow-upPhoto Courtesy Louise A. Sclafani, OD

Figure 10. Case 4 Patient: Geographic LesionsPhoto Courtesy Joseph P. Shovlin, OD

CONCLUSIONTo accurately diagnose ocular infections, optometrists should thoroughly assess a patient’s complete clinical presentation. This involves evaluatingpatient history, closely examining the lids and the cornea, and considering all signs and symptoms that may be caused by pathogens such as ade-novirus, Staphylococcus, and importantly, the greatest masquerader of them all—herpes. Conjunctivitis-causing and keratitis-causing organisms,particularly MRSA, have become increasingly resistant to many of the available anti-infectives, namely the fluoroquinolones ciprofloxacin, gati-floxacin, levofloxacin, moxifloxacin, and ofloxacin. Fortunately, traditional agents such as the aminoglycosides and trimethoprim are effectivelytreating some of these resistant pathogens. Newer additions to the fluoroquinolone antibiotic class, besifloxacin ophthalmic suspension, 0.6%,and gatifloxacin ophthalmic solution, 0.5%, have shown effectiveness in treating bacterial ocular infections. Besifloxacin’s balanced and potentaction against bacteria DNA synthesis sets the stage for low resistance and high activity against virulent, resistant bacteria. A recent addition tothe antiviral armamentarium, ganciclovir ophthalmic gel, 0.15%, is an effective, safe, and convenient option for patients with herpetic keratitis, hold-ing promise for the treatment of viral conjunctivitis. Optimizing outcomes for patients with ocular infections is achieved with the use of best-practiceregimens that are based on pathogen resistance patterns and safe and effective anti-infective therapy.

9

1. Colin J. Ganciclovir ophthalmic gel, 0.15%: a valuable tool for treating ocular herpes.Clin Ophthalmol. 2007;1(4):441-453.

2. Liesegang TJ, Melton LJ 3rd, Daly PJ, Ilstrup DM. Epidemiology of ocular herpes simplex.Incidence in Rochester, Minn, 1950 through 1982. Arch Ophthalmol. 1989;107(8):1155-1159.

3. Hyndiuk RA, Eiferman RA, Caldwell DR, et al. Comparison of ciprofloxacin ophthalmicsolution 0.3% to fortified tobramycin-cefazolin in treating bacterial corneal ulcers.Ciprofloxacin Bacterial Keratitis Study Group. Ophthalmology. 1996;103(11):1854-1862.

4. Ofloxacin monotherapy for the primary treatment of microbial keratitis: a double-masked, randomized, controlled trial with conventional dual therapy. The Ofloxacin StudyGroup. Ophthalmology. 1997;104(11):1902-1909.

5. Alexandrakis G, Alfonso EC, Miller D. Shifting trends in bacterial keratitis in south Floridaand emerging resistance to fluoroquinolones. Ophthalmology. 2000;107(8):1497-1502.

6. Goldstein MH, Kowalski RP, Gordon YJ. Emerging fluoroquinolone resistance in bacterialkeratitis: a 5-year review. Ophthalmology. 1999;106(7):1313-1318.

7. Almeida DR, Miller D, Alfonso EC. Anterior chamber and vitreous concordance inendophthalmitis: implications for prophylaxis. Arch Ophthalmol. 2010;128(9):1136-1139.

8. Jhanji V, Sharma N, Satpathy G, Titiyal J. Fourth-generation fluoroquinolone-resistantbacterial keratitis. J Cataract Refract Surg. 2007;33(8):1488-1489.

9. Moshirfar M, Mirzaian G, Feiz V, Kang PC. Fourth-generation fluoroquinolone-resistantbacterial keratitis after refractive surgery. J Cataract Refract Surg. 2006;32(3):515-518.

10. Asbell PA, Sahm DF, Shaw M, Draghi DC, Brown NP. Increasing prevalence of methicillinresistance in serious ocular infections caused by Staphylococcus aureus in the UnitedStates: 2000 to 2005. J Cataract Refract Surg. 2008;34(5):814-818.

11. Asbell PA, Colby KA, Deng S, et al. Ocular TRUST: nationwide antimicrobial susceptibilitypatterns in ocular isolates. Am J Ophthalmol. 2008;145(6):951-958.

12. Zagans ME, Romen F, O’Toole G. Antibiotic resistance of ciprofloxacin is associated withbiofilm formation in ocular isolates of Pseudomonas Aeruginosa. Abstract presented at:35th Annual Ocular Microbiology and Immunology Group Meeting; November 10, 2001;New Orleans, LA.

13. Kowalski RP, Karenchak LM, Romanowski EG, Mah FS, Ritterband DC, Gordon JS. In Vitroantibiotic susceptibility testing of second generation fluoroquinolone resistantPseudomonas Aeruginosa. Abstract presented at: 35th Annual Ocular Microbiology andImmunology Group Meeting; November 10, 2001; New Orleans, LA.

14. Wang JC, Ritterband DC. Keratitis, Herpes Simplex. emedicine from WebMD.http://emedicine.medscape.com/article/1194268-print. Updated November 18, 2010.Accessed January 19, 2011.

15. Gasset AR, Katzin D. Antiviral drugs and corneal wound healing. Invest Ophthalmol.1975;14(8):628-630.

16. Lee SY. Herpes simplex virus ocular infections. Drugs Today (Barc). 1998;34(3):241-249.17. Zirgan [package insert]. Tampa FL: Bausch & Lomb Incorporated; 2010.18. ZYMAR [package insert]. Irvine, CA: Allergan, Inc; 2010.19. Vigamox [package insert]. Fort Worth, TX: Alcon Laboratories, Inc; 2008.20. Zymaxid [package insert]. Irvine, CA: Allergan, Inc.; 2010.21. Lindstrom R, Lane S, Cottingham A, et al. Conjunctival concentrations of a new oph-

thalmic solution formulation of moxifloxacin 0.5% in cataract surgery patients. J OculPharmacol Ther. 2010;26(6):591-595.

22. Carter NJ, Scott LJ. Besifloxacin ophthalmic suspension 0.6%. Drugs. 2010;70(1):83-97.23. Cambau E, Matrat S, Pan XS, et al. Target specificity of the new fluoroquinolone besi-

floxacin in Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli. J Antimi-crob Chemother. 2009;63(3):443-450.

24. Blondeau JM. Fluoroquinolones: mechanism of action, classification, and development ofresistance. Surv Ophthalmol. 2004;49 suppl 2:S73-S78.

25. Haas W, Pillar CM, Hesje CK, Sanfilippo CM, Morris TW. Bactericidal activity of besi-floxacin against staphylococci, Streptococcus pneumoniae and Haemophilus influenzae.J Antimicrob Chemother. 2010;65(7):1441-1447.

26. Torkildsen G, Proksch JW, Shapiro A, Lynch SK, Comstock TL. Concentrations of besi-floxacin, gatifloxacin, and moxifloxacin in human conjunctiva after topical ocular adminis-tration. Clin Ophthalmol. 2010;4:331-341.

27. Proksch JW, Granvil CP, Siou-Mermet R, Comstock TL, Paterno MR, Ward KW. Ocularpharmacokinetics of besifloxacin following topical administration to rabbits, monkeys,and humans. J Ocul Pharmacol Ther. 2009;25(4):335-344.

28. Besivance [package insert]. Tampa, FL: Bausch & Lomb Incorporated; 2009.29. A controlled trial of oral acyclovir for the prevention of stromal keratitis or iritis in

patients with herpes simplex virus epithelial keratitis. The Epithelial Keratitis Trial.The Herpetic Eye Disease Study Group. Arch Ophthalmol. 1997;115(6):703-712.

To obtain COPE credit for this activity, you must complete the CE Post Test bywriting the best answer to each question in the Answer Box located on the ActivityEvaluation/Credit Request form on page 11.

1. The most common cause of conjunctivitis is:A. S aureusB. AdenovirusC. Herpes simplex virusD. C trachomatisE. S epidermidis

2. Bacterial conjunctivitis may be caused by:A. S aureusB. S pneumoniaeC. H influenzaeD. N gonorrhoeaeE. All the above

3. Which of the following statements regarding lid reactions with conjunctivitis is true?A. Follicles are more characteristic of bacterial conjunctivitisB. Papillae are always an indication of conjunctivitis caused by a foreign body substanceC. Mixed lid reaction (follicles and papillae) is commonly observed with all causes ofconjunctivitis

D. Mixed lid reaction (follicles and papillae) is rarely observed with cases ofconjunctivitis

E. Papillae are often seen with Chlamydia infection

4. Which of the following statements is/are true regarding methods used to identify theocular pathogen in conjunctivitis?A. Polymerase chain reaction (PCR) testing is very sensitive and specific in determiningthe ocular pathogen; however, it is expensive and is typically reserved for hospital useor following an infectious outbreak

B. Laboratory testing is an insensitive method in determining the ocular pathogenC. The RPS Adeno Detector™ is a highly sensitive, in-office device that is used to deter-mine the presence of adenovirus in tears

D. A and CE. All the above

5. Which presentation most closely characterizes viral conjunctivitis?A. Patient complains of red, painful itchy eyes. Both eyes are producing purulent dis-charge. Patient has a painful rash on face.

B. Patient complains of red, itchy eyes. Both eyes producing stringy discharge, andpapillae are present on the upper lids.

C. Patient complains of red, painful right eye. Patient has an unexplained skin lesion,decreased corneal sensitivity determined by dental floss test, and a corneal dendriticlesion.

D. Patient complains of red, painful right eye, with FBS, photophobia, and nausea andvomiting. Left eye has less discomfort. Both eyes producing watery discharge, and fol-licles are present on the lower lids. Patient has enlarged, tender preauricular node.

E. Patient complains of red, painful right eye with FBS, and photophobia. Left eye isunaffected. Right eye producing purulent discharge and follicles are present on thelower right lid. Preauricular nodes are normal.

BUST THE BUGS: Current Management of Ocular Bacterial And Viral InfectionsCE POST TEST

REFERENCES

CE Post Test continued on page 10.

10

6. Which of the following is true?A. HSV-1 is the most common ocular pathogen among the viruses in the human

Herpesviridae familyB. HSV-2 is the most common ocular pathogen among the viruses in the human

Herpesviridae familyC. HSV ocular infections always lead to symptoms immediately following exposureD. In children, HSV ocular infections are self-limiting and are never associated withsignificant systemic symptoms

E. None of the above is true

7. Anterior corneal involvement occurs in approximately ____ of ocular HSV infection cases.A. 10%B. 25%C. 50%D. 75%E. 100%

8. Corneal involvement with herpetic eye disease may manifest clinically as:A. Epithelial keratitisB. Stromal keratitisC. EndotheliitisD. Neurotrophic keratopathyE. All the above

9. Which of the following must be considered in the differential diagnosis for herpeticeye disease?A. Lyme keratitisB. Contact lens-related pathologyC. AdenovirusD. Drug toxicityE. All the above

10. In the mid 1990s, the fluoroquinolones ciprofloxacin and ofloxacin, when used asmonotherapy:A. Were highly resistant to gram-positive ocular organismsB. Were highly resistant to gram-negative ocular organismsC. Provided similar clinical success in the treatment of bacterial keratitis, when comparedwith the standard of care (dual therapy with a fortified aminoglycoside and acephalosporin)

D. Were more effective in the treatment of bacterial keratitis compared with thestandard of care (dual therapy with a fortified aminoglycoside and a cephalosporin)

E. Were less effective in the treatment of bacterial keratitis compared with the standardof care (dual therapy with a fortified aminoglycoside and a cephalosporin)

11. Which of the following is/are true regarding resistance of ocular pathogens toantibacterial therapy?A. S aureus isolates from cases of bacterial keratitis have become increasingly resistant tociprofloxacin and ofloxacin

B. In a review of consecutive cases of endophthalmitis between 1999 and 2008,gram-positive organisms showed a high rate of resistance to the fluoroquinolonesciprofloxacin, gatifloxacin, levofloxacin, and moxifloxacin

C. Recent publications have reported on therapeutic failures with the fluoroquinolonesgatifloxacin and moxifloxacin for the treatment of bacterial keratitis

D. Some traditional antibiotic agents, such as the aminoglycosides and trimethoprim,have demonstrated good activity against some of the resistant ocular pathogens

E. All the above

12. Data from the The Surveillance Network and the Ocular TRUST show that the majority ofMRSA ocular isolates are resistant to:A. trimethoprim, vancomycin, cefazolin, gatifloxacinB. trimethoprim, vancomycin, cefazolin, moxifloxacinC. besifloxacin, tobramycin, gatifloxacin, moxifloxacinD. besifloxacin, ciprofloxacin, gatifloxacin, levofloxacinE. ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin

13. Approximately ___ of the general population and ___ of health care workersharbor MRSA.A. 0%; 10%B. 2.5%; 20%C. 25%; 50%D. 50%; 75%E. 75%; 100%

14. The ocular pathogen P aeruginosa has shown significant resistance to:A. besifloxacin, ciprofloxacin, gatifloxacinB. gatifloxacin, moxifloxacin, fortified aminoglycosidesC. besifloxacin, moxifloxacin, fortified aminoglycosidesD. ciprofloxacin, gatifloxacin, moxifloxacinE. None of the above

15. Therapeutic strategies to combat resistant bacterial organisms include:A. Prescribe aggressively (loading dose with frequent dosing)B. Prescribe low-dose oral macrolidesC. Consider using adjunct agents, such as fortified tobramycin, polymyxin B/trimethoprim, or vancomycin

D. Prescribe monotherapyE. A and C

16. Which of the following anti-infectives is used as antiviral therapy?A. vidarabineB. azithromycinC. bacitracinD. gentamicinE. erythromycin

17. Which of the following antiviral agents has/have recently become available inthe United States?A. trifluridine ophthalmic solution, 1%B. ganciclovir ophthalmic gel, 0.15%C. acyclovir ointment, 3%D. vidarabine ophthalmic ointment, 3%E. A and C

18. Which of the following statements regarding topical antiviral agents is/are true?A. Vidarabine ophthalmic ointment, 3%, is often effective for strains resistant totrifluridine

B. Trifluridine ophthalmic solution, 1%, is associated with no corneal toxicityC. Ganciclovir ophthalmic gel, 0.15%, is unique in its specificity for targeting cellsinfected by HSV

D. The Herpes Simplex Virus Epithelial Keratitis Trial (HEDS-EKT) found that theaddition of an oral antiviral agent (acyclovir) to treatment with a topical antiviral(trifluridine) provided significant benefit in preventing the development of stromalkeratitis and iritis in patients with acute HSV epithelial keratitis, compared withtrifluridine monotherapy

E. A and C

19. Which of the following statements regarding topical antibacterial agents is/are true?A. Gatifloxacin ophthalmic solution, 0.5%, has shown clinical superiority over its vehiclein resolving conjunctival hyperemia and conjunctival discharge in patients withbacterial conjunctivitis

B. A new formulation of moxifloxacin is availableC. Besifloxacin ophthalmic suspension, 0.6%, has potent and balanced inhibitory actionagainst bacterial DNA gyrase and topoisomerase IV enzymes

D. Besifloxacin ophthalmic suspension, 0.6%, has shown greater potency againstmethicillin-resistant and fluoroquinolone-resistant S aureus and S epidermidiscompared with gatifloxacin and moxifloxacin

E. All the above

20. Which of the following statements regarding the treatment of viral conjunctivitis is/are true?A. Viral conjunctivitis is rarely contagious; thus, affected patients can typically beinstructed to return to work/school immediately following an accurate diagnosis

B. A small study showed that patients treated with cool compresses experienced ashorter mean recovery time compared with patients treated with preservative-freeartificial tears

C. A small study showed that patients treated with povidone-iodine, 5%, experienceda shorter mean recovery time compared with patients treated with preservative-freeartificial tears

D. A small study showed that patients treated with ganciclovir experienced ashorter mean recovery time compared with patients treated with preservative-freeartificial tears

E. All the above

11

Participant Information (Please Print) ___ Home ___ Office

OE Tracker Number:______________________________________________________ (for ODs)

Last Name _________________________________________________ First Name __________________________________ Specialty __________________________________

Degree �OD �PharmD �RPh �NP �RN �PA �Other_____________________

EMAIL: ___________________________________________________________________________________________________________________________________________Please note: We do not sell or share email addresses. This will be used strictly to return your certificate.

Institution _________________________________________________________________________________________________________________________________________

Street Address ____________________________________________________________________________________________________________________________________

City _____________________________________________________ State _____________ ZIP Code _________________ Country __________________________________

Phone ____________________________________________________________________ Fax _____________________________________________________________________

Post Test Answer Box (please circle the letter for your answer)

Activity EvaluationActivity Rating: 5 = Strongly Agree 4 = Agree 3 = Neutral 2 = Disagree 1 = Strongly DisagreeCircle the number that best reflects your opinion on the degree to which the following learning objectives were met:

Program ObjectivesUpon completion of this activity, I am better able to:1. Distinguish bacterial from viral ocular infections 5 4 3 2 12. Discuss latest findings in anti-infective resistance as it relates to managingbacterial conjunctivitis, bacterial keratitis, and endophthalmitis 5 4 3 2 1

3. Compare and contrast the currently available topical antibiotics andantivirals for efficacy and safety 5 4 3 2 1

4. Discuss best-practice regimens for infection management in conditions suchas bacterial and viral conjunctivitis, and bacterial and herpetic keratitis 5 4 3 2 1

Did you perceive any commercial bias in any part of this activity? �No �Yes

(please describe) _________________________________________________________________________________________________________________________________

1. Please list one or more things, if any, you learned from participating in this educational activity that you did not already know.

__________________________________________________________________________________________________________________________________________________

__________________________________________________________________________________________________________________________________________________

2. I plan to make the following changes in my practice: _______________________________________________________________________________________________

__________________________________________________________________________________________________________________________________________________

Additional Comments ______________________________________________________________________________________________________________________________

__________________________________________________________________________________________________________________________________________________

Ocular Bacterial and Viral Infections

BUSTBUGS

current management of

the

1 2 3 4 5 6 7 8 9 10

A B C D E A B C D E A B C D E A B C D E A B C D E A B C D E A B C D E A B C D E A B C D E A B C D E

11 12 13 14 15 16 17 18 19 20

A B C D E A B C D E A B C D E A B C D E A B C D E A B C D E A B C D E A B C D E A B C D E A B C D E

COPE Course ID: 31574-AS

CREDIT REQUESTTo receive CE credit, please complete this Evaluation form and the Post Test. Record your answers to thePost Test in the Answer Box located below. Return via one of the following methods: SCAN and EMAIL toForms@MedEdicus.com OR FAX to 203-404-7767. Your comments help us to determine the extent towhich this educational activity has met its stated objectives, assess future educational needs, and createtimely and pertinent future activities. Please provide all the requested information below. This ensures thatyour certificate is filled out correctly and is emailed to the proper address. It also enables us to contactyou about future CE activities. Please print clearly or type. Illegible submissions cannot be processed.

Expiration Date: April 1, 2014

Ocular Bacterial and Viral Infections

BUSTBUGS

current management of

the