Anti-infectives Flashcards
What do different types of eye mucus mean
- Yellow mucus
- White/yellow balls of mucus
- Thick crusty mucus
- Stringy, white mucus
- Watery mucus
- Small,dry particles of mucus
- Can be caused by a stye if accompanied by a small lump
- Common signs of dacryocystitis or tear drainage infection
- May be caused by blepharitis
- May represent allergic conjunctivitis
- Can be caused by viral conjunctivitis
- Often a sign of dry eye syndrome
When to use opthalmic antibiotics
Most acute red eyes do NOT involve a bacterial infection
Mucopurulent discharge
• No discharge = No infection
• Putrid smelling discharge = anaerobic infection
Diffuse conjunctival injection
• Sectoral injection = No infection
Corneal compromise
• Significant corneal damage renders it increasingly susceptible to infection
Differential diagnosis of conjunctivitis
Bacteriostatic antibiotics
Bactericidal antibiotics
Gram sensitivity of penicillins
+>-
gm + especially strep, syphillis, semi syn for S. aureus cellulitis
Gram sensitivity of cephalosporins
+ > -
1 & 2 gm +, 3 gm- , 4 pseudomonas
Gram sensitivity of Bacitracin
gm +
Bacterial conjunctivitis
Gram sensitivity of vancomycin
gram +
MRSA, C. diff
Which antibiotics are only used against gram +
Bacitracin
Vancomycin
Gramicidin
Macrolides
Which antibiotic only has activity against gram -
Polymyxin B
Gram + bacteria
Gram - bacteria
Antibiotics that are only sensitive to gram + organisms
Bacitracin
Vancomycin
Gramicidin
Macrolides
(Penicillins and cephalosporins are more effective against + than -, but effective against both)
Which antibiotic is effective only against gram -
Polymyxin B
(Aminoglycosides and fluoroquinolones are effective against + and - but more effective against -)
Sexually transmitted eye infx
Penicillins are useful for treating…
Are there topical penicillins?
No, allergy risk is too high
Cephalosporins
Cephalosporins are cross-reactive regardung allergies to which other antibiotic class
Penicillins
Cephalosporin generations
Bacitracin is available in which forms
Only topical- profound nephrotoxicity
Bacitracin (AK-tracin ointment) has coverage against…
Gram + organisms
Bacitracin + Polymyxin B (Polysporin) has coverage against…
Gram + and - , including pseudomonas
(Bacitracin- gram+ and polymyxin- gram-)
Polymyxin B available formulations
Only topical due to systemic toxicity
Cationic detergent/surfactant
Topical only, never used alone (Polysporin - polymyxin + bacitracin)
Gramicidin - same mechanism as polymyxin, also found in combination
Polymyxin B opthalmic combinations
Polytrim solution
- Polymyxin + trimethoprim
- Used for most common pediatric ocular infx: H influenza & S pneumoniae
- Excellent option for restistant S epidermidis & MRSA infx
Polysporin ointment
- Polymyxin + bacitracin
Neosporin Ointment
- Polymyxin + neomycin + Bacitracin
Neosporin Solution
- Polymyxin + Neomycin + Gramicidin
Aminoglycosides - neomycin, gentamycin , tobramycin
Neomycin - Topical, never stand-alone
Broad spectrum except pseudomonas
Gentamycin- severe infx
Tobramycin - Severe infx
Safe in penicillin allergy
Adverse reactions of aminoglycosides (neomycin,gentamycin,tobramycin)
Corneal epithelial toxicity is most pronounced with which antibiotic
Gentamycin
Which antibiotic is very useful in treating mybomian gland infections
Tetracyclines - they are anti-inflammatory and inhibit bacterial lipases, neovascularization and MMPs
Tetracycline indications (doxycycline and minocycline)
Minocycline
- Acne rosacea
Doxycycline (50mg qd x 1-6 months)
- Meibomiantis/meibomian gland stasis
- recurrent corneal erosions (doxy inhibits MMP)
- Acne rosacea
- Clamydia +/- ocular involvement eg trachoma (100mg bid x 14d)
- Syphilis ( vs 1st choice PCN intramuscularly)
Adverese reactions of Tetracyclines
• Photosensitivity
• Impaired absorption w/ food due to divalent cation binding;
doxycycline ⇩ 20% vs tetracycline ⇩ 50% w/ milk; avoid lying
down for 2 hrs following administration
• Blood dyscrasias
• “Idiopathic” Intracranial Hypertension [IIH]
• Impaired bone growth, tooth development
• Fanconi’s Syndrome: renal toxicity from expired tetracyclines
Distinct adverse reactions of
- Minocycline
- Doxycycline
Minocycline
- Vestibular toxicity within 2-3d of therapy in up to 70%
Doxycycline (Vibramycin)
- Exhibits least divalent chelation (20% w/ milk)
- Risk of erosive esophagitis*
- No azotemia due to fecal (vs renal) elimination pathway
- Excellent option for resistant S epidermidis infection (MRSE)
Contraindications of Tetracycline
- Pregnancy
- Nursing mothers
- Children under 8 yrs of age
- Renal failure (except Doxycycline)
Erythromycin (Macrolide)
- Full oral dosing negates need for topical use
- Replaced AgNO3 for neonatal gonorrhea
- Unstable in gastric acid
Azithromycin (Macrolide)
(Oral and topical)
(Eyedrop- AzaSite solution with Durasite)
- The ONLY macrolide available in a drop formulation
- Extended half-life* permits minimal dosing
- Bacterial Conjunctivitis: 1 gt bid x 2d; 1 gt qd x 5d
- Chlamydia Inclusion Conjunctivitis: 1 tab 1000 mg x 1 dose
Clarithromycin (Macrolide)
(Oral formulation - Biaxin)(BD)
- Reduced dosing compared to Erythromycin due to greater stability in GIT
Sulphonamides vs non-sulphonamides
Sulphonamides
- Folic acid inhibitors
- Inhibition of Dihydropteroate Synthase (Step 1)
- Sulfamethoxazole, Sulfacetamide, Sulfadiazine
- Commonly combined with trimethoprim
Non-sulpha
- Inhibition of Dihydrofolate Reductase (Step 2)
- Pyrimethamine, Trimethoprim
Polytrim Solution
- Polymyxin + trimethoprim
- Drug of choice for pediatric conjunctivitis
Sulfadiazine + Pyrimethamine
- These two drugs are used together to treat toxoplasmosis
- Sulphadiazine (sulphonamide) Inhibition of Dihydropteroate Synthase
- Pyrimethamine (Non-sulpha) Inhibition of Dihydrofolate Reductase
- (folic acid inhibitors)
*
Sulfamethoxaxole + Trimethoprim (Bactrim®)
- Oral drug of choice for MRSA
- (Folic acid inhibitors)
Adverse effects of Sulphonamides
- Hypersensitivity - especially sulphonamides
- Ocular effects of sulphonamides
- myopia +/- astigmatism (reversible)
Contra-indications
- Pregnancy
Fluoroquinolones
- The most commonly used class of antibiotics
- Newer generations provide greater gm + coverage over and above the excellent gm - coverage
- Nalidixic acid is the original, 1st gen fluoroquinolone; not used in eyecare
- Ciprofloxacin is available as an ointment also; the solution has no
age restrictions - Bactericidal; inhibit DNA gyrase and topoisomerase IV
Generations of fluoroquines
2nd Generation
• Norfloxacin, Ciprofloxacin, Ofloxacin
3rd Generation
• Gemifloxacin, Levofloxacin
4th Generation [2003] (“Respiratory Quinolones”)
• Moxifloxacin(eyedrops=unpreserved), Gatifloxacin, Delafloxacin
“5th” Generation: Chloro-Fluoroquinolone
• Besifloxacin w/ Durasite®
Adverse reactions of fluoroquinolones
- CNS disturbances: insomnia, confusion, impaired memory, delirium…
- White corneal precipitates w/ ciprofloxacin
Oral more than topical
Contra-indications of fluoroquinolones
- MG
- QT prolongation, arrhythmias, cardiopathies
Black Box Warnings
• Tendonitis, tendon rupture
• Peripheral neuropathy, CNS effects
• Avoid in myasthenia gravis (exacerbation of muscle weakness)
Mitomycin
- Isolated from one of two forms of Streptomyces bacteria
- A, B, and C forms exist; C (MMC) is most common
- Like ionizing radiation, it acts as a potent DNA crosslinker
- Used in medicine intravenously to treat various cancers
- Used topically in ophthalmology to treat ocular surface neoplasia;
scar formation following glaucoma filtering surgery; to prevent
haze following PRK or LASIK; toprevent fibrosis following
strabismus surgery; and to prevent recurrence following pterygium
surgery
What is topical mitomycin used for
- ocular surface neoplasia;
- scar formation following glaucoma filtering surgery;
- to prevent haze following PRK or LASIK;
- to prevent fibrosis following strabismus surgery;
- and to prevent recurrence following pterygium
Adverse reactions of mitomycin
- Ocular: Blebitis, corneal reaction, endophthalmitis, hypotony, iritis
Severe:
- Ocular: Cataracts, retinal detachment, vision loss
Which ocular antibiotics can be given to babies from 2months old?
- Tobramycin - Tobrex
- Polymyxin/trimethoprim - Polytrim
- Erythromycin - Ilotycin
From what age can you give moxifloxacin eye drops to a child
4 months
Best ocular antibiotic for treating acute bacterial infections in kids
- Polytrim® soln (Trimethoprim/Polymyxin B)
- Besifloxacin soln
- AzaSite soln
- Polysporin® ung (Bacitracin/Polymyxin B)
- Erythromycin ung
Best ocular antibiotics for treating acute bacterial infections in adults
- Mild-mod: Neosporin® ung/soln (Gramicidin/Polymyxin B/Neomycin)
- Tobramycin
- Severe: Besifloxacin or Levofloxacin 1.5%
General-purpose ophthalmic ointment*
• Polysporin®
The dilemma to combine an antimicrobial agent & steroid depends on:
- Extent of inflammation: oval-shaped processes at or near the limbus
are inflammatory (herpetic infections are more linear)* - Severity of infection relative to conjunctival injection
- Is the corneal epithelium intact?
- Does the patient test positive for lymphadenopathy?(associated with viral infx)
It’s been suggested that treatment of acute red eyes is estimated to employ
combination drugs in 45% of cases, vs steroids in 40%, and stand-alone
antibiotics in only 15%
While steroids reduce the risk of corneal scarring, they also slow the rate of
healing, increase the risk of corneal melting, and increase the risk of elevated
IOP
Antibiotic/steroid combos
Lid pathology & hygiene
- When uncontrolled, these infections can lead to painful lid infections, lid ulceration and scarring, tear debris, eyelash matting or breaking, foreign body sensation, reduced VA, itchy, dry, irritated, red eyes and contact lens wearing complications
- Demodex mites are part of the human microbiome
- Demodex folliculorum: lash follicles and meibomian glands
- Demodex brevis: sebaceous glands
- Staphylococcal bacteria are the most common
- Collarettes around the lashes are common signs of S. aureus
Lid hygiene topical products
- Lid hygiene towelettes- Active antimicrobial ingredients include preservatives, chamomile, and
tea tree oil - Active antimicrobial ingredients include tea tree oil, hypochlorous acid, PAPB and hyaluronic acid
Lid care products
OcuSoft® Lid Scrubs & Foams
• Antimicrobial: PHMB/PAPB
• Regular strength (rinsing required)
• Extra strength and Baby (leave on formula)
Systane® Lid Wipes
• Antimicrobial: Benzyl Alcohol
Blink® Lid Wipes
• Antimicrobial: Lauryl Glycoside + Polysorbate 20 surfactants +
Chamomile
• Preservative-free (leave on formula)
Cliradex® Towelettes
• Tea tree oil (Terpineol)
Sterilid® Foam
• Tea tree oil; sodium perborate preservative(dissapearing preservative)
Avenova® Lid and Lash Cleanser Rx
• Hypochlorous acid 0.01% soln; self-preserved
HypoChlor®
• Hypochlorous acid 0.02% soln or gel; self-preserved
Ilast Clean®
• Hyaluronic acid 0.2% soln + Polysorbate surfactants; self-preserved
Antivirals
- In contrast to viricides and many antibiotics, antiviral agents are designed to inhibit viral replication or proliferation
- Because viruses replicate only upon entering cells, they are “hidden” and “protected” within cells
- Cells that host viral particles may experience collateral damage when antiviral agents are used
- Viral mutation affects antiviral drug therapy efficacy; like antibiotics, antiviral resistance is a common concern
- DNA viruses, which are much more abundant that RNA viruses, live with us for a lifetime
- RNA viruses have simple structures, mutate rapidly, and are responsible for many historic epidemics: measles, Ebola, Zika, influenza, and Corona virus
Common ocular virus- Adenovirus
- Adenovirus is a cold virus that is the most common cause of
eye infection
- It results in a highly infectious conjunctivitis and/or keratitis
commonly called pinkeye
- There is currently no FDA-approved treatment for ocular
adenovirus infections which are normally self-resolving
- Palliative care and proper hygiene precautions are advised
What virus causes “pinkeye”
Adenovirus
HSV and HZV
- Herpes Simplex Virus (HSV) is the most common virus of the human body: like Herpes (Varicella) Zoster Virus (HZV), it resides in the ganglia of nerves for life
- By the 4th decade of life, approximately 65% of the US population is seropositive for HSV-1 and 25% for HSV-2; women are infected with HSV-2 more often than men
- Unlike HSV, HZV is responsible for a common childhood infection
- HZV: Chicken Pox (children); Shingles (adults)
- HSV: Type I (orofacial & genital); Type II (genital)
- HZV and HSV can infect both the anterior and posterior segments of the eye
- Human Immunodeficiency Virus (HIV), a retrovirus, has RNA in its genome but behaves like DNA in the host
- Patients with HIV have an increased risk of 2° infection by cytomegalovirus (CMV) with AIDS
Oral Antiviral prescribing
Antiviral agents for herpes
- Purines are the two-carbon nitrogen ring bases that are used to produce the DNA/RNA nucleotides adenine and guanine
- Pyrimidines are the one-carbon nitrogen ring bases that are used to produce the DNA/RNA nucleotides thymine and cytosine
- Commonly antiviral agents for herpes (simplex and keratitis) are analogs of pyrimidines (topical ophthalmic formulas only) or purines
PYRIMIDINE ANALOGS
Trifluridine
Trifluridine (Viroptic®) 1% topical solution
- 1 gt q2h-q4h x 7d
- Uniquely preserved w/ Thimerosal 0.001%(mercury based)
- More affordable than ganciclovir as a topical therapy for HSV keratitis
Adverse Effects
• Keratopathy and stromal edema; max 21 days
- Elevated IOP
- Lid edema
- Pregnancy category C
PURINE ANALOGS
Acyclovir
Ganciclovir
Famciclovir
Valcyclovir
Acyclovir (Zovirax®) 200/400/800 mg pO (now in liquid)
- Poorest GI absorption vs Valacyclovir and Famciclovir
- Contains gluten
- HSK Therapy: 400 mg pO 5x/d x 7d vs 5% ointment
- HZK Therapy: 800 mg pO 5x/d x 7-10d Oral risk of anaphylaxis, renal/liver toxicity, blood dyscrasias
Ganciclovir (Zirgan®) 0.15% topical gel
- 1 gt 5x/d until healing for acute HSV keratitis ulcers then 1 gt tid x 7d
- Preferred over trifluridine for HSV keratitis; less corneal toxicity
- X-resistance seen w/ Acyclovir
- Oral and IV formulation indicated for CMV infection
- Oral risk of blood dyscrasias, rash, sepsis; see black box FX
Famciclovir (Famvir®) 125/250/500 mg pO
• Penciclovir prodrug w/ extended plasma life
- HSK Therapy: 250 mg tid x 7-10d
- HZK Therapy: 500 mg tid x 7-10d
Valcyclovir (Valtrex®) 500/1000 mg pO
- HSK Therapy: 500 mg tid x 7-10d
- HZK Therapy: 1000 mg tid x 7-10d
- Acyclovir prodrug w/ very long plasma half-life
- Better-suited for deeper infections such as stromal keratitis
• X-sensitivity seen w/ Acyclovir
Acanthamoeba
- One of the most common soil/H2O borne protozoa
- Infection of the eye can cause a sight threatening keratitis
- Several bacterial species* can infect and replicate within acanthamoeba species
- Responsible for the most virulent form of infectious keratitis having the worst prognosis
- 85-92% of acanthamoeba keratitis cases are associated with contact lens wear > trauma
- Life cycle: Trophozoites Double-walled Cysts • Found in fresh water, soil, and airborne cysts
- Homemade saline solution is a common source
- Characterized by prominent, out of proportion pain
- A dense stromal ring infiltrate at mid-periphery of the cornea, sparing the pupillary area, is considered as the diagnostic clinical sign of acanthamoeba keratitis
Toxoplasmosis
- Toxoplasma gondii infection is commonly acquired by consumption of poorly cooked food, unwashed vegetables or exposure to cat feces
- Healthy individuals can be be infected and remain asymptomatic while harboring latent intracellular cysts that evade immune detection
- Inflammatory retinal infections can occur, especially in immunocompromised individuals
Treatment is tailored to acute vs latent infections
• Acute: Pyrimethamine (antimalarial), Sulfadiazine, Clindamycin, Spiramycin • Latent: Atovaquone, Clindamycin
What is the most common way to get a acanthamoeba infection?
Through contact lens wear
ACANTHAMOEBA THERAPY
- Medical therapy is not well-established
- Early culturing and aggressive surgical/medical therapy is crucial to a successful outcome
- Corneal Epithelial Debridement
- Topical Biguanides qh-q3h x 3-4 wks
- Polyhexamethylene biguanide 0.02% (PHMB)
- Bis-guanide 0.02% (Chlorhexidine)
Other therapies include the use of azole antifungal agents or topicals
CULTURE COLLECTION
- Culture collection can mean the difference between a rapid cure or severe morbidity
- Deciding/knowing when to culture is a critically important first step
- With corneal epithelial defects, use the : 1 mm from the axis, 2 or more infiltrates, 3 mm or larger -> -> -> CULTURE!
- Remember to avoid the use of topical agents that contain preservatives or are themselves antimicrobial prior to collection
