Antibiotic Therapy For Todays Ocular Infections 2011 - Michigan ...

Antibiotic Therapy for Today’s
Ocular Infections
Gary E. Oliver, O.D.
Associate Clinical Professor
State University of New York
State College of Optometry
goliver@sunyopt.edu
geoliver.od@att.net
Dosage Considerations
• Standard ‐ dosage required for normal
therapeutic regimen, may be increased for
more severe infection
• Loading Dose ‐ increased frequency or
concentration to rapidly build higher tissue
titers of antibiotic agent
• Combination Therapy ‐ increases spectrum
of activity, agents must have different
mechanisms of action
Oral Administration Considerations
• Ocular/Medical/Medication/Allergy Hx
• Physical characteristics ‐ age, body weight,
race, sex, etc.
• Age ‐ 12 years or older
• Body Weight
– Average Male 75‐77 kg/Female 53‐55 kg
– Pediatric Dosages
• Clark’s Formula/Augsberger’s Rule
Antibiotics General Principles
• Bactericidal Agents ‐ destroy organisms, more
effective during growth and multiplication
• Bacteriostatic Agents ‐ inhibit multiplication, do not
directly destroy organisms
• Spectrum of Activity ‐ range of organisms which are
destroyed or inhibited by agent
• Resistance ‐ organisms which are not affected by the
pharmaceutical agent
• Ideal Agent ‐ bactericidal, rapid kill rate, low dose,
low toxicity
Antibiotics
• Dosage requirements
• Loading dose
– Nonfluoroquinolones ‐ one gtt q5min for 5
doses, then q30min
– Fluoroquinolones ‐ one gtt q15‐30min for 6
hrs, the q30‐60min
– Fortified agents ‐ one gtt q30min for 24 hrs
• Maintenance dose ‐ establish as
appropriate, usually q3‐4h
Antibiotic Agents
• Bacterial resistance update
– Ocular Trust
– Ocular Microbiology & Immunology Group
• Antibiotic potency issues
• Dosage considerations
• MRSA issues

Bacterial Resistance
• Specific mechanisms
– Development of altered receptors or enzymes that
interact with the drug (production of altered penicillin
binding proteins)
– Decrease in concentration of drug that reaches the
receptors by altered rates of entry or removal of drug
(aminoglycosides may have decreased ribosomal binding
due to decreased diffusion through cell wall)
Methicillin Resistant Staphylococcus
aureus (MRSA)
• HA‐MRSA – health care associated MRSA
– Older adults
– Patients with weakened immune systems
– Hospital, nursing home, dialysis patients
• CA‐MRSA – community associated MRSA
– Affects otherwise healthy patients of any age
– Serious skin and soft tissue infections
– Pneumonia
Methicillin Resistant Staphylococcus
aureus (MRSA)
• CA‐MRSA
– Young age
– Participation in contact sports
– Sharing towels or athletic equipment
– Weakened immune system
– Crowded or unsanitary conditions
– Association with health care workers
• HA‐MRSA
– Current or recent hospitalization
– Live in long term care facility
– Use of invasive devices
– Recent antibiotic use
Bacterial Resistance
• Enhanced destruction or inactivation of drug (B‐
lactamases which catalyze the hydrolysis of
penicillins)
• Synthesis of resistant metabolic pathways
(trimethoprim resistance in Streptococcus due to
production of thymidine nucleotides by alternative
pathway)
• Failure to metabolize the drug (anaerobic bacteria
may not metabolize drug metronidazole to active
metabolites)
Methicillin Resistant Staphylococcus
aureus (MRSA)
• Risk factors
– Antibiotic resistance
– Unnecessary antibiotic use
– Antibiotics in food, water
– Bacterial mutation
Methicillin Resistant Staphylococcus
aureus (MRSA)
• Ocular infection
– Suspect MRSA in unresponsive bacterial infections
– Consider possibility of MRSA in higher risk patients
• Initial treatment options in known MRSA infections
– Conjunctivitis ‐ Trimethoprim‐Polymyxin B, Besifloxacin or
Tobramycin
– Bacterial Keratitis – Fluoroquinolone combined with
Trimethoprim‐Polymyxin B. Cosnider Besifloxacin.
Vancomycin for nonresponsive infection or hospital
acquired infection.

Antibiotic Agents
• Topical Agents
– 0.5% moxifloxacin (Vigamox, Moxeza)
– 0.3%, 0.5% gatifloxacin (Zymar, Zymaxid)
– 0.6% besifloxacin (Besivance)
– 0.5%, 1.5% levofloxacin (Quixin, Iquix)
– 0.3% ciprofloxacin (Ciloxan)
– 0.3% ofloxacin (Ocuflox)
Topical Fluoroquinolones
– Besifloxacin (Besivance) – chlorofluoroquinolone
agent, vehicle permits increased contact time
– 0.5% Moxifloxacin (Moxeza) – vehicle permits
increased contact time, less frequent dosing
– 0.5% Gatifloxacin (Zymaxid) –higher
concentration than Zymar
Topical Antibiotics
• Clinical Insights
– Most efficacious agents for Staph. aureus –
trimethoprim, besifloxacin, tobramycin
– Also are the preferred agents for MRSA
– Aminoglycosides more toxic to cornea than most
other agents
– Least corneal toxicity –trimethoprim,
moxifloxacin, bacitracin/polymyxin B and
erythromycin
Topical Fluoroquinolones
• Clinical Insights
– Concentration dependent activity
– Broad spectrum efficacy
– Possibly less efficacious against Staph. aureus
than other Gram+ organisms
– Preferred agents for corneal infection
Antibiotic Agents
• Topical Agents
– 0.3% tobramycin (Tobrex)
– 0.3% gentamicin (Genoptic)
– 1% azithromycin (AzaSite)
– Trimethoprim/polymyxin B (Polytrim)
– Bacitracin/polymyxin B (Polysporin)
– Neomycin/polysporin B/gramicidin (Neosporin)
– 0.5% erythromycin (Ilotycin)
– 10% sulfacetamide (Bleph‐10)
Topical Antibiotics
• Clinical Insights
– Preferred agents for pediatric infection
• Trimethoprim/polymyxin B
• Moxifloxacin
• Azithromycin
• Tobramycin
• Erythromycin

Antibiotic/Steroid Combinations
• Steroid first, antibiotic second
• Should have indication for steroid treatment
• Dosage dependent on steroid requirements
– Tobramycin/dexamethosone
– Tobramycin/loteprednol
– Sulfacetamide/prednisolone phosphate
– Sulfacetamide/prednisolone acetate
– Gentamicin/prednisolone acetate
Oral Antibiotics
• Penicillins ‐ Gram positive organisms, need efficacy
against penicillinase producing Staphylococcus
aureus, administer 1‐1.5 g/day in split doses
– Amoxicillin/clavulanate potassium (Augmentin)
– Dicloxacillin
– Amoxicillin
Fluoroquinolones
• Broad spectrum antibacterial activity with
greater potency than most other agents
• Efficacy against both G+ & G‐ organisms
• However, resistant strains are developing
particularly to the earlier generation drugs
Oral Antibiotic Agents
• Oral Medications
– Penicillins
• Amoxicillin/clavulanic acid
• Dicloxacillin
• Amoxicillin
– Cephalosporins
• Cephalexin
• Cefaclor
• Cefadroxil
– Fluoroquinolones
• Levofloxacin
• Moxifloxacin
• Ciprofloxacin
Oral Antibiotics
• Cephalosporins ‐ may have broader spectrum of
activity, need efficacy against penicillinase producing
Staphylococcus aureus, administer 1‐1.5 g/day in
split doses
– Cefadroxil (Duricef)
– Cephalexin (Keflex, KefTab)
– Cefaclor (Ceclor)
– Cefazolin (Ancef) –topical only as fortified agent
– Ceftazidime (Ceptaz, Fortaz) –topical only as fortified
agent
– Ceftriaxone (Rocephin) – injectable, IV only
Oral Antibiotics
• Fluoroquinolones ‐ broad spectrum G+ & G‐ activity
– Levofloxacin (Levaquin) typical dosage 500‐750
mg qd x 7 days
– Moxifloxacin (Avelox) typical dosage 400mg qd x 7
days
– Ciprofloxacin (Cipro) typical dosage 250‐500 mg
bid x 7days

Fluoroquinolones
• Fluoroquinolone agents usually not preferred over
penicillins, cephalosporins or macrolides for routine
cases.
• However, may be needed if other agents have been
ineffective or patient has risk factors, such as blood
borne viral disease or being immunocompromised
• Fluoroquinolone agents not usually preferred for
pediatric infection due to risk of adverse reactions.
• Not good choice for children ‐ cartilage damage, bone
development issues, increased risk of tendon rupture
(Achilles), can elevate theophylline levels
Oral Antibiotics
• Macrolides ‐ both G+ & G‐ activity with
efficacy against Chlamydia trachomatis
– Azithromycin (Zithromax) 500 mg first day,
followed by 250 mg x 4 days
• For Chlamydia trachomatis ‐ Initially 1,000 mg single
dose
• If not effective, give full course of drug or switch to
doxycycline
– Erythromycin EES 400 mg qid
• Achieve equivalent of erythromycin 500 mg base
Macrolides
• Erythromycin may also be contraindicated if
patient taking any of the following drugs.
– Anticoagulant agents
– Digoxin
– Statin agents
– Dilantin
– Theophylline
Oral Antibiotic Agents
• Oral Medications
– Macrolides
• Azithromycin
• Erythromycin
– Tetracyclines
• Doxycycline
• Tetracycline
• Minocycline
– Folic acid inhibitor
• Trimethoprim/Sulfamethoxazole
Macrolides
• Erythromycin is the antibiotic agent with the
highest risk of interacting with other oral
medications. If not certain, check PDR,
PubMed, MedlinePlus, etc. prior to
prescribing.
• Example ‐ Fexofenadine taken concurrently
with erythromycin may lead to a toxic
reaction in susceptible patients.
Oral Antibiotics
• Tetracyclines ‐ anti‐inflammatory effects,
collagenase inhibitor, metalloproteinase‐9
inhibitor
– Tetracycline 250 mg qid
– Doxycycline (Vibramycin) 50‐100 mg bid
– Minocycline (Cleeravue‐M) 50‐100 mg bid

Tetracyclines
• Three groups of drugs ranging from short to long
acting
• Most useful drugs:
– Tetracycline ‐ short acting
– Doxycycline ‐ long acting
– Minocycline ‐ long acting
• Some tetracyclines are incompletely absorbed in
fasting state
• Doxycycline and minocycline absorbed more
completely, more tolerant of dairy products
Tetracyclines
• Tetracyclines (including doxycycline, minocycline)
not effective against many common bacteria due to
bacterial resistance issues. In eye care, drugs mainly
utilized for their apparent anti‐inflammatory effects
and treatment of Chlamydia trachomatis.
• When treating acne rosacea (inflammation),
important to taper tetracycline agent over several
months.
Trimethoprim & Pyrimethamine
• Trimethoprim efficacious for most Gram positive and
negative organisms, not effective against
Pseudomonas aeruginosa
• Trimethoprim well absorbed from the GI tract
• Pyrimethamine initially used to treat malaria
• Both drugs used for treatment of toxoplasmosis in
combination with sulfonamides
• Sulfamethoxazole and Trimethoprim (Bactrim DS)
typical dosage for bacterial infection 800 mg of
sulfamethoxazole and 160 mg of trimethoprim q12h,
duration dependent on clinical entity
Tetracyclines
• Some antibiotic agents can interfere with oral birth
control agents, particularly tetracycline.
• Actual breast cancer risk with tetracycline or
doxycycline still uncertain. Keep up with literature
in this area.
• Optic disc edema and pseudotumor cerebrei have
been reported as adverse events with tetracycline
agents but are not common. However, monitor and
be suspicious of patients reporting headaches while
being treated with these agents.
Oral Antibiotics
Sulfonamide/Trimethoprim Combinations
• Sulfamethoxazole and Trimethoprim
(Bactrim, Bactrim DS)
• Typical dosage for bacterial infection is double
strength formulation 800 mg of
sulfamethoxazole and 160 mg of
trimethoprim q12h
• Duration dependent on clinical entity