Ophthalmic Infections PDF

Ophthalmic Infections Taryn A. Eubank, PharmD, BCIDP Research Assistant Professor [email protected] Recommended readings & references • American Academy of Ophthalmology (https://www.aao.org/guidelines-browse) ‘ American Academy of Ophthalmology. Preferred Practice Pattern Guidelines: Conj...

Ophthalmic Infections Taryn A. Eubank, PharmD, BCIDP Research Assistant Professor [email protected] Recommended readings & references • American Academy of Ophthalmology (https://www.aao.org/guidelines-browse) ‘ American Academy of Ophthalmology. Preferred Practice Pattern Guidelines: Conjunctivitis. (2018). Accessed from: https://www.aao.org/preferred-practicepattern/conjunctivitis-ppp-2018 ‘ American Academy of Ophthalmology. Preferred Practice Pattern Guidelines: Bacterial Keratitis. (2018). Accessed from: https://www.aao.org/preferred-practice-pattern/bacterialkeratitis-ppp-2018 ‘ American Academy of Ophthalmology. Herpes Simplex Virus Keratitis: A Treatment Guideline. (2014). Accessed from: https://www.aao.org/clinical-statement/herpes-simplexvirus-keratitis-treatment-guideline • Infectious Diseases Society of America (https://www.idsociety.org/practiceguideline/practice-guidelines) ‘ Infectious Diseases Society of America. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. (2016) Accessed from: https://www.idsociety.org/practice-guideline/candidiasis/ • Mandell, Douglas, And Bennett's Infectious Disease Essentials. 2017. 2 Objectives 1. Describe the epidemiologic and clinical features of the common types of ophthalmic infections 2. Identify the need for pharmacotherapy among patients presenting with suspected ophthalmic infection 3. Design appropriate pharmacotherapeutic plans for patients with ophthalmic infections 3 Eye anatomy Conjunctivitis = infection of thin, transparent membrane covering front of eye and inner surface of eyelids (conjunctivitis) Endophthalmitis = infection of interior of the eye (vitreous and/or aqueous humor) Keratitis = infection of clear, front part of eye (cornea) 4 Conjunctivitis epidemiology • Affects 6 million people annually in the United States • Affects all ages  bacterial causes more common in children vs. viral more common in adults • Rarely causes permanent visual loss/structural damage, but large economic impact due to lost work or school time, cost of medical visits, testing and treatment 5 Conjunctivitis (“pink eye”) differential Bacterial Allergic Viral Redness  (mod-severe)   (mild-mod) Edema   Discharge  (purulent)  (watery)  (watery) Laterality Unilateral, 2nd eye involvement 1-2 days Bilateral Unilateral > bilateral  (severe)  (mild) Itching Example 6 Conjunctivitis microbiology • Viral (**most common causes**): • Adenovirus (most common), herpes simplex virus (HSV), picornavirus, varicella (herpes) zoster virus (VZV), Molluscum contagiosum • Bacteria (both Gram-positive and Gram-negative causes common): ‘ Skin flora & oral/respiratory flora (S. aureus, Corynebacterium diptheriae, S. pneumoniae, Haemophilus spp., Moraxella spp., Neisseria spp., enteric Gram-negative rods) ‘ Neonatal conjunctivitis: sexually transmitted bacteria passed during birthing (Chlamydia trachomatis, Neisseria gonorrhoeae) 7 Conjunctivitis treatment principles • Diagnosis: routine lab evaluation not usually required (except for neonatal conjunctivitis (ophthalmia neonatorum) ‘ Bacterial cultures and staining may be helpful for recurrent, severe, or chronic purulent conjunctivitis in any age group and in cases where the conjunctivitis has not responded to medication • Indiscriminate use of topical antibiotics or corticosteroids should be avoided • Viral conjunctivitis will not respond to anti-bacterial agents, and mild bacterial conjunctivitis is likely to be self-limited • **No evidence exists demonstrating the superiority of any topical antibiotic agent** 8 Viral conjunctivitis differential Causative Pathogen Risk Factors Natural History Adenovirus Exposure to infected individual (especially in school setting), recent ocular testing, concurrent upper respiratory infection Self-limited, with improvement of symptoms & signs within 5–14 days HSV Primary HSV infection: exposure to infected individual Prior infection with HSV: trigger for reactivation (e.g. stress, acute viral or febrile illnesses, UV exposure, surgery, trauma) Usually subsides without treatment within 4–7 days unless complications occur VZV Acute chicken pox, exposure to an individual with active chicken pox or recurrent VZV (shingles) Primary infection (chicken pox) & conjunctivitis from recurrent infection usually subsides in a few days Vesicles can form at the limbus, especially in primary infection 9 Viral conjunctivitis treatment • General principles: ‘ Typically self-resolving within days to weeks without adverse sequelae (unless concomitant keratitis) ‘ Avoid antibiotics ‘ Avoid corticosteroids, may worsen infection and prolong viral shedding ‘ Cold compresses to reduce irritation ‘ May consider artificial tears, topical antihistamines, topical steroids, or oral analgesics to mitigate symptoms • Adenovirus (most common): no evidence of effective antiviral, use non-pharmacological treatment • VZV: topical antivirals not shown to help; vaccination for prevention (recombinant > live) 10 Bacterial conjunctivitis differential Causative Pathogen Risk Factors Natural History Nongonococcal Contact with infected individual; concomitant bacterial otitis media, sinusitis, or pharyngitis; nasopharyngeal bacterial colonization; unhygienic living conditions; contact lens wear, contaminated ocular meds Mild: self-limited in adults. May progress to complications in children Severe: may persist without treatment, rarely hyperacute Gonococcal Oculogenital spread Neonatal: Vaginal delivery by infected mother; inadequate prenatal care Neonate: onset 1–7 days after birth, (later if a topical antibiotic was used), rapid evolution to severe, purulent conjunctivitis Adult: rapid development of severe hyperpurulent conjunctivitis Chlamydial “Inclusion” - C. trachomatis serotypes D-K, sexually transmitted, vaginal delivery (neonate) “Trachoma” - C. trachomatis serotypes A-C; seen in developing world without access to clean water/sanitation; spread by direct/indirect contact with secretions from infected eyes, nose, or throat Neonate: onset 5–19 days after birth, may persist for 3–12 mo if untreated 11 Bacterial conjunctivitis treatment • Nongonoccocal: ‘ Typically self-resolving, but more rapid recovery and reduced morbidity with topical antibiotics ‘ Choice of antibiotic is usually empiric; no clinical evidence suggesting the superiority of any particular topical antibiotic ‘ Most convenient/least expensive topical, broad-spectrum option can be selected; duration 5-7 days • Gonococcal/Chlamydial: ‘ Systemic antibiotic therapy REQURIED to treat conjunctivitis due to Neisseria gonorrhoeae and Chlamydia trachomatis ‘ No data to support addition of topical therapy ‘ Patients and sexual contacts should be informed about the possibility of concomitant disease and referred appropriately 12 Topical ophthalmic antibiotics Brand Generic Preparation(s) Dosing Notes Protect from light FLUOROQUINOLONES Ciloxan ciprofloxacin 0.3 % sol. 0.3% oint. 1-2 drops Q2H x 2 days, then Q4H x 5 days ½ in. ribbon TID x 2 days, then BID x 5 days Quixin levofloxacin 0.5% sol. 1-2 drops Q2H x 2 days (max 8x/day), then Q4H x 5 days (max 4x/day) Vigamox Moxeza moxifloxacin moxifloxacin 0.5 % sol. 0.5 % sol. 1 drop TID x 7 days 1 drop BID x 7 days Ocuflox ofloxacin 0.3 % sol. 1-2 drops Q2-4H x 2 days, then QID x 5 days Zymaxid gatifloxacin 0.5 % sol. 1 drop Q2H x 2 days (max 8x/day), then BID-QID x 5 days Besivance besifloxacin 0.6 % susp. 1 drop TID x 7 days Shake before use Refrigerate before opening, keep at room temp. after opening, discard >14 days MACROLIDES AzaSite azithromycin 1% sol. 1 drop BID x 2 days, then daily x 5 days Ilotycin erythromycin 5 mg/g oint. ~1 cm ribbon up to 6x/day 13 Topical ophthalmic antibiotics Brand Generic Preparation(s) Dosing* Notes 0.3% sol. 0.3% oint. 0.3/0.1% susp. 0.3/0.1% oint. 1-2 drops Q2-4H x 5-7 days 0.5 in ribbon BID-TID x 5-7 days 1-2 drops Q4-6H x 5-7 days 0.5 in ribbon TID-QID x 5-7 days Taper dose (increase time interval) as condition responds 0.3% sol. 0.3% oint. 1-2 drops Q2-4H x 5-7 days 0.5 in ribbon BID-TID x 5-7 days AMINOGLYCOSIDES Tobrex tobramycin Tobradex tobramycin + dexamethsone Garamycin, Gentak gentamicin MISCELLANEOUS Bleph-10 sulfacetamide 10% sol. 10% oint. 1-2 drops Q2-3H x 7-10 days 0.5 in ribbon Q3-4H x 7-10 days Polycin, Polycin B bacitracin + polymyxin B 500 units/ 10,000 units/g oint. Apply Q3-4H x 7-10 days Polytrim polymyxin B + trimethoprim 10,000 units/mL / 0.1% sol. 1 drop Q3H (max 6x/day) x 7-10 days Maxitrol neomycin + polymyxin B + dexamethasone (3.5 mg/10,000 units/0.1%) / g oint. Apply Q3-4H x 7-10 days Taper dose (increase time interval) as cond. responds 14 Counseling points: conjunctivitis • Good hygiene is important to break transmission chain of adenoviral conjunctivitis • Counseling patient and family can prevent further infections and recurrences: ‘ Wash hands frequently with soap and water ‘ Use separate towels ‘ Avoid close contact with others during the period of contagion (especially health care workers and childcare providers!) ‘ Contagious period variable, but generally considered to be 7 days from symptom onset 15 Ophthalmia neonatorum prophylaxis 16 Patient case #1 • TC is a 5 year‐old male • Brought to pediatrician by mother who reports TC has been from constantly rubbing right eye the past two days and began rubbing left eye this morning • Mother also reports purulent, yellow discharge from right eye for 2 days and left eye this morning • TC has no PMH, is up to date on vaccinations, has not been sick recently, and has no known drug allergies, attends day care while parents are at work • Physical exam: ‘ No preauricular lymphadenopathy ‘ PERRLA ‘ Visual acuity at baseline 17 Patient case #1 Which of the following is most appropriate treatment recommendation for TC? A. moxifloxacin 0.3% ophthalmic solution B. tobramycin 0.3% + dexamethasone 0.1% ophthalmic solution C. trifluridine 1% ophthalmic solution D. cool compress alone 18 Eye anatomy Conjunctivitis = infection of thin, transparent membrane covering front of eye and inner surface of eyelids (conjunctivitis) Endophthalmitis = infection of interior of the eye (vitreous and/or aqueous humor) Keratitis = infection of clear, front part of eye (cornea) 19 Keratitis epidemiology & overview • ~71,000 cases in US annually, increasing incidence in recent years • Higher disease burden in developing countries • Rapid progression (as quickly as within 24 hours!) ‘ Vision loss 2/2 corneal scarring ‘ Corneal perforation if untreated or severe • Clinical presentation: Rapid‐onset severe pain, discomfort, and photophobia, blepharospasm, and hyperemia (redness) ‘ Decreased visual acuity common ‘ Discharge uncommon unless concomitant conjunctivitis ‘ Corneal infiltrate, epithelial defect and/or ulceration, corneal edema on physical exam 20 Keratitis risk factors • Rarely occurs in the normal eye  cornea's natural resistance to infection • Risk factors include anything that may alter the ocular surface defense mechanism, allowing bacteria to invade cornea ‘ **Contact lens wear** ‘ Trauma (surgical or non-surgical) ‘ Contaminated ocular medications ‘ Ocular surface diseases (altered corneal structure) ‘ Systemic diseases ‘ Immunosuppression 21 Keratitis microbiology • Majority of community-acquired cases resolve with empiric therapy and are managed without smears or cultures ‘ Cultures, corneal scrapings, corneal biopsies may be helpful following poor clinical response to empiric treatment • Bacteria may be Gram-positive or Gram-negative ‘ Staphyloccus and Streptococcus spp. and Gram-negative rods (Pseudomonas spp.) most common overall causes ‘ Polymicrobial infection not uncommon (trauma as risk factor) • Viral pathogens: HSV, VZV, adenovirus • Contact lens wearers: outbreaks with Acanthamoeba (2007, 2011) and Fusarium (2005-06) 22 Counseling points: contact lens care 23 Keratitis treatment principles • Topical antibiotic eye drops preferred over ocular ointments ‘ Ointments lack solubility, unable to penetrate cornea significantly ‘ Subconjunctival antibiotics may be helpful for imminent scleral spread or corneal perforation ‘ Begin empiric, broad-spectrum antibiotics ASAP • May consider corticosteroids after 24-48 hours when the causative organism is identified and/or infection is responding to therapy. ‘ AVOID in cases of infection involving Acanthamoeba, Nocardia, and fungus • Preferred treatment regimens: duration 7-14 days following improvement of symptoms and ulcer(s) ‘ Mild/moderate: 4th generation fluoroquinolone (moxifloxacin, gatifloxacin) ‘ Q1H until symptom and ulcer improvement, then taper ‘ Central/severe: fortified cefazolin (or vanc if MRSA suspected) and aminoglycoside solution ‘ Loading dose – Q5‐15min x 1H, then Q1H until improvement, then taper • Modification of antibiotics, concentration, or frequency if no improvement in 48H or microbiology results available 24 Bacterial keratitis treatment Organism Antibiotic Topical concentration Notes No organism identified OR multiple types of organisms -Cefazolin -OR- vancomycin -PLUS-Tobramycin or gentamicin -OR-Fluoroquinolones* 25-50 mg/mL Gatifloxacin and moxifloxacin with better Gram-positive coverage -Cefazolin -OR-Fluoroquinolones* -OR-Resistant Enterococcus or Staphylococcus spp, or PCN all: Vancomycin or bacitracin 50 mg/mL Various** Gram-negative rods Tobramycin or gentamicin -ORCeftazidime -ORFluoroquinolones* 9-14 mg/L 50 mg/mL Various** Gram-negative cocci (gonococcal) Ceftriaxone -ORCeftazidime -ORFluoroquinolones* 50 mg/mL 50 mg/mL Various** Gram-positive cocci 9-14 mg/mL Various** Vancomycin/bacitracin not to be used for empiric monotherapy unless confirmed Gram-positive 10-50 mg/mL or 10,000 IU Systemic therapy necessary for suspected gonococcal infection. *Gatifloxacin, moxifloxacin, and besifloxacin preferred due to less Gram-positive resistance **Besifloxacin 6 mg/ml; ciprofloxacin 3 mg/ml; gatifloxacin 3 mg/ml; levofloxacin 15 mg/ml; moxifloxacin 5 mg/ml; ofloxacin 3 mg/ml, all commercially available 25 HSV keratitis treatment Depends on penetration of infection: • Epithelial HSV keratitis: topical or oral antivirals; avoid corticosteroids • Stromal HSV keratitis: oral antiviral + tapered topical corticosteroid ‘ Duration ≥10 weeks • Endothelial HSV keratitis: oral antiviral + topical corticosteroid ‘ Duration based on response; average 21-25 days 26 Topical ophthalmic antivirals • Oral options: (off-label use) ‘ Acyclovir 400 mg PO TID x 14-21 day ‘ Valacyclovir 1000 mg PO BID x 14-21 days ‘ Famciclovir 500 mg PO BID x 14-21 days • Topical options: 2 products with FDA-indication Brand Generic Preparation(s) Dosing* Notes Viroptic trifluridine 1% solution 1 drop Q2H while awake (max 9/day), until re‐epithelialization of corneal ulcer, then Q4h (max 5x/day) x 7 days, max 21 days treatment Store in refrigerator. Do not exceed maximum dose. Zirgan ganciclovir 0.15% gel 1 drop 3-5x/day until corneal ulcer heals, then TID x 7 days Avoid contact lenses 27 Patient case 2 • TB is a 25 year‐old male presenting to the emergency room with a 5 day history of right eye irritation with clear discharge • Today, it became extremely painful, his vision began to blur, and he could not keep his eye open in the light • TB has a history of herpes labialis (cold sores), and is currently having an outbreak 28 Patient case 2 2. Which of the following pharmacotherapeutic regimens is most appropriate to treat TB? A. ganciclovir 0.15% gel B. acyclovir 400 mg PO TID C. trifluridine 1% ophthalmic solution + dexamethasone 0.1% ophthalmic solution D. valacyclovir 1000 mg PO BID + dexamethasone 0.1% ophthalmic solution 29 Eye anatomy Conjunctivitis = infection of thin, transparent membrane covering front of eye and inner surface of eyelids (conjunctivitis) Endophthalmitis = infection of interior of the eye (vitreous and/or aqueous humor) Keratitis = infection of clear, front part of eye (cornea) 30 Endophthalmitis epidemiology • Very rare condition but usually with poor outcomes (potentially permanent vision loss) ‘ Incidence < 0.01‐0.37 % post‐ocular surgery ‘ 10‐25% post‐penetrating trauma (rare event) • Clinical presentation: Reduced or blurred vision, floaters, pain, redness, eyelid swelling ‘ Hypopyon on eye exam ‘ Systemic signs of infection (fever, elevated WBC) may be present if endogenous or if spread outside eye globe (panophthalmitis) 31 Endophthalmitis etiologies Two classifications: 1. Exogenous (>90% of all cases) – microorganism introduced directly from the environment ‘ Risk factors: ophthalmic surgery, intravitreal medication injection, vitrectomy, trauma ‘ Mainly BACTERIAL 2. Endogenous (2‐8% of all cases) – microorganism spread from metastatic infection ‘ Risk factors: immunosuppression, intravenous drug use, indwelling catheterization, dental procedure ‘ Mainly FUNGAL (rare overall) 32 Common endophthalmitis pathogens Category Pathogen Acute post cataract Coagulase-negative staphylococci (70% of all cases) Chronic post cataract Propionibacterium acnes Post injection (macular degeneration treatments) Viridans streptococci, coagulase-negative staphylococci Bleb-related Streptococcus pneumoniae, Haemophilus influenzae Post-traumatic Bacillus cereus Endogenous Staphylococcus aureus, Streptococcus spp., Gram-negative bacilli, Candida Fungal Candida spp., Aspergillus spp., Fusarium 33 Endophthalmitis treatment Exogenous Endogenous Intravitreal antibiotics Intravitreal + systemic antibiotics Broad-spectrum unless pathogen known Usually pathogen directed from systemic cultures; broad spectrum if not known Vitrectomy improves visual outcome in very severe cases Vitrectomy benefit unclear Adjunctive corticosteroids often used (intravitreal dexamethasone better than systemic) *Intravitreal antibiotics and often vitreal debridement required; systemic antibiotics are not adequate* • Broad‐spectrum (Gram‐positive & Gram‐negative) unless organism identified • vancomycin + ceftazidime -OR- amikacin -OR- fluoroquinolone 34 Candida endophthalmitis • All patients with candidemia should have a dilated retinal examination, preferably performed by an ophthalmologist, within the first week of therapy to establish if endophthalmitis is present • Chorioretinitis alone: systemic antifungal sufficient • Endophthalmitis: intravitreal + systemic antifungal required ‘ Intravitreal treatment: injection of either: ‘ Amphotericin B deoxycholate, 5–10 µg/0.1 mL sterile water, or ‘ Voriconazole, 100 µg/0.1 mL sterile water or normal saline ‘ Systemic treatment: fluconazole treatment of choice for susceptible Candida spp. ‘ Echinocandins not preferred due to limited vitreous penetration ‘ Duration of treatment should be at least 4–6 weeks • Consider vitrectomy  decrease organism burden and allows removal of fungal abscesses that are inaccessible to systemic antifungal agents 35 Patient case 3 • ES is a 46 year old female with a PMH of intravenous drug use and Staphylococcus aureus infective endocarditis who completed treatment for her IE 3 weeks ago • She presents to ER with a 1 week history worsening fatigue and fever • She sought care today because her vision has become blurry, she is seeing dark spots, and her eyelid is swollen 36 Patient case 3 3. Which of the following courses of action is most appropriate to treat ES? A. IV vancomycin B. IV & intravitreal vancomycin C. IV vancomycin + IV ceftazidime D. IV & intravitreal vancomycin + IV & intravitreal ceftazidime 37 Key take home points • Conjunctivitis (COMMON) – viral more common that bacterial ‘ Viral (more watery)  No role for topical antivirals ‘ Bacterial (more purulent)  no specific topical antibacterial preferred; but use helps shorten duration ‘ Gonococcal or chlamydial  treat underlying infection too ‘ Very contagious  counseling on good hygiene important • Keratitis (less common) – CONTACT LENSES ‘ Eye drops >> ointments (corneal penetration) • Endophthalmitis (rare but the most serious) – could be exogenous (usually bacterial) or endogenous (usually fungal) ‘ Intravitreal antibiotics and often vitreal debridement required for treatment ‘ If endogenous source, will also need systemic antibiotics 38 Eye infections in the news 39 Questions? [email protected] 40