Principles of Antimicrobial Therapy

• Structural and biochemical differences exist between humans and Simplifying Systemic Antibiotics microorganisms. Antimicrobial therapy takes advantage of these Blair Lonsberry, MS, OD, MEd., FAAO differences, e.g. Professor of Optometry Pacific University College of Optometry – Bacterial cell wall [email protected] – Bacterial ribosomes

9/22/2016

Principles of Antimicrobial Therapy Principles of Antimicrobial Therapy

• Selection of an appropriate antimicrobial requires: • Bacteriostatic vs. Bactericidal – knowledge of the organisms identity, drugs: – its susceptibility, – bacteriostatic drugs “arrest” – site of infection, the growth and replication – patient factors, of bacteria thus limiting the – safety of agent and spread of infection while the – cost of therapy. body attacks. • Often, the organism is not conclusively identified, and the – bactericidal drugs kill bacteria treatment is empirical. at serum concentration – the choice of agents in the absence of confirmatory levels testing maybe guided by known association of a particular organism with an infection in a given clinical setting

Principles of Antimicrobial Therapy Principles of Antimicrobial Therapy

• Adequate levels of the antibiotic must reach the site of • many of the antibiotics are minimally toxic infection. – such as penicillins as they interfere with a site unique to – different tissues have variable permeability to the drugs. bacteria growth – natural barriers to drug delivery exist, such as prostate, • others are reserved for life-threatening infections CNS, brain and vitreous. because of potential for serious toxicity • Patient factors are crucial in drug selection. For example: – e.g. chloramphenicol – the status of patient’s immune system, • cost of therapy also needs to be considered, – kidneys, liver, circulation, – ie. if similar efficacy is achieved with a generic or less – age, sex, pregnancy, breast feeding, expensive medication (or combo of meds) that may increase compliance. – allergies, etc.

1 Antibiotic Resistance Avoiding Resistance

• Microorganism that was originally in the spectrum • Bacterial resistance is a natural result of mutation. of activity is no longer susceptible to the drug. • Antibiotics cause a faster rate of selection against these resistant bacteria if not prescribed correctly. • Mechanisms of Resistance Include: – Avoid prescribing for non‐bacterial infections. – Producing an enzyme capable of destroying or – Avoid sublethal doses (attack to kill all). inactivating the antibiotic. – Avoid intermittent use. – Altering the target site receptor for the antibiotic so as – Always complete the full dosage for an appropriate length of to reduce or block its binding. time. – NEVER TAPER AN ANTIBIOTIC below recommended dosing – Preventing the entry of the antibiotic into the bacterial schedule! cell or actively transporting the antibiotic out.

Preventing Resistance ARMOR

• The IDSA suggests five to seven days is long • Antibiotic Resistance Monitoring in Ocular enough to treat a bacterial infection without Microorganisms (ARMOR) encouraging resistance in adults, though children • Approximately 42% of isolates were determined should still get the longer course to be MRSA – this is different than previous guidelines of • Newer fluoroquinolones have better activity than treating infections from 10-14 days. earlier generations • Besivance has the lowest MIC values of all the fluoroquinolones • Vancomycin is drug of choice if MRSA present • Azithromycin had very poor activity against Staph

9/22/2016

MRSA MRSA

• Healthcare‐associated methicillin‐resistant • Risk factors for infection due to HA‐MRSA include: Staphylococcus aureus (HA‐MRSA) is – antibiotic use, associated with severe, invasive disease in – prolonged hospitalization, hospitalized patients – intensive care, • Community‐associated methicillin‐resistant S. – invasive devices, aureus (CA‐MRSA) is most often associated – hemodialysis, with skin and soft tissue infections in young, – MRSA colonization, and healthy individuals with no recent healthcare – proximity to others with MRSA colonization or exposure infection.

https://pacificu.box.com/v/OAL2016 https://pacificu.box.com/v/OAL2016

2 MRSA MRSA

• Additional risk factors for CA‐MRSA infection • Clindamycin (300 to 450 mg every six to eight include: hours) has good activity against MRSA. It has excellent tissue penetration, particularly into bone • skin trauma (eg, lacerations, abrasions, tattoos, and abscesses injection drug use), • Trimethoprim‐sulfamethoxazole (one double‐ • cosmetic body shaving, strength tablet twice daily) is a reasonable agent • incarceration, for treatment of skin and soft tissue infections due to MRSA with known susceptibility to the • HIV infection, and drug, although in general it is not advisable for • sharing equipment that is not cleaned or empiric management of soft tissue infections that laundered between users. may be due to group A streptococci

https://pacificu.box.com/v/OAL2016 https://pacificu.box.com/v/OAL2016

OPHTHALMIC MRSA INFECTIONS IN THE PARKLAND HEALTH AND HOSPITAL SYSTEM, 2000 – 2004 MRSA Blomquist, Trans Am Ophthalmol Soc 2006;104:322-345

• Monotherapy with trimethoprim‐ 1 million patients seen in the system from 2000-2004, with 3460 confirmed MRSA infections sulfamethoxazole for treatment of - of the total MRSA infections, 1.3% if them were ocular

uncomplicated skin infection may be Ophthalmic Infection Percent of Cases reasonable for relatively young patients in the Preseptal cellulitis 42% Conjunctivitis 21% absence of systemic manifestations or Corneal ulcers 10% comorbid conditions Endophthalmitis 8% Orbital cellulitis 2% Other: e.g. dacrocystitis 10%

https://pacificu.box.com/v/OAL2016

Sites of Antimicrobial Actions

Inhibitors of Cell Wall Synthesis

3 Inhibitors of Cell Wall Synthesis B‐Lactam Antibiotics

• Human cells do not possess a cell wall like • This group includes: bacteria do – penicillins, – it is a very selective way to interfere with bacterial growth. – cephalosporins, • To be maximally effective, the inhibitors – carbapenems and monobactams. require actively proliferating bacteria – they are ineffective against non-dividing bacteria. • All PCN’s have short ½ lives • The most important members of this group • B-lactamase inhibitors are sometimes added in are: combination to reduce a bacteria’s ability to – B-lactam antibiotics and – vancomycin. overcome the activity of the antibiotic – E.g potassium clavulanate (clavulanic acid)

Penicillins Penicillins

• Among the most widely effective and least toxic • This group includes the following commonly used members: – increased resistance has limited their use – Amoxicillin (250/500 tid, 875 mg bid or extended release 775mg qd) – they are bactericidal • May be taken with food • Interfere with the last step of bacterial wall • treatment of otitis media, sinusitis, and infections synthesis, resulting in cell lysis. caused by susceptible staph/strept involving upper and lower respiratory tract, skin and urinary tract; • Therapeutic application in gram (+) cocci and prophylaxis of infective endocarditis bacilli, gram (-) cocci, anaerobic, spirochetes • Pediatric dosing: (syphilis). – <3 months: oral 20-30 mg/kg/day divided q 12 hrs • The most common side effects include – >3 months: oral 20-50 mg/kg/day divided 8-12 hrs hypersensitivity and diarrhea. – >12 yrs: extended release 775 mg daily

Penicillins: Dicloxacillin Penicillins

Name Treatment for Administration – Dicloxacillin (250-500 mg) (Not Available in Canada) Penicillin G and V All stages and forms of syphilis Via IM or IV injection • penicillinase resistant, used in penicillin resistant staph Ampicillin Prophylactic use in dental Adults: • administer orally at least 1 hour before or 2 hours surgery patients - 250-500 mg every 6 hours Active against haemophilus and after meals salmonella • Dosing: – Children<40kg: 12.5-25 mg/kg daily divided – Children>40kg: 125-250 mg q 6 hours Nafcillin Osteomyelitis, septicemia, IM/IV endocarditis and CNS Adults: – Adults: 250 mg q 6 hours infections - 500 mg every 4-6 hours

4 Penicillins: Augmentin Penicillins: Augmentin

• Augmentin is amoxicillin with potassium • Augmentin is very effective for skin and skin clavulanate (clavulanic acid 125 mg). structure infections such as: • dacryocystitis, • Clavulanate is a B-Lactamase inhibitor which • internal hordeola, reduces a bacteria’s ability to negate the effect • pre-septal cellulitis. of the amoxicillin by inactivating penicillinase – Treatment of: (enzyme that inactivates the antibiotic affect). • otitis media, – Dicloxacillin can also be used in infections due to • sinusitis, • penicillinase-producing staph. lower respiratory and urinary infections. – Given prophylactically to dental surgery patients.

Penicillins: Augmentin Stevens‐Johnson Syndrome

– It has low: • Stevens‐Johnson syndrome is a rare, serious disorder of the skin and mucous • GI upset, membranes. – reaction to a medication or an • allergic reaction and anaphylaxis. infection – Serious complications include: – begins with flu‐like symptoms, followed by a painful red or purplish • anemia, rash that spreads and blisters. Then the top layer of the affected skin dies • pseudomembranous colitis and and sheds. • Stevens-Johnson syndrome.

9/22/2016

Stevens‐Johnson Syndrome Penicillins: Augmentin.

• medical emergency that usually requires hospitalization. Adults: • treatment focuses on eliminating the underlying cause, – 250-500 mg tab q 8hr (tid) (also available in chewable controlling symptoms and minimizing complications. tablets and suspension) • recovery can take weeks to months, depending on the – or 875 mg q 12hr (bid) severity. – 1000 mg XR: q12 hr and • if it was caused by a medication, the patient will need to not for use in children <16 Peds: <3 mos 30mg/kg/day permanently avoid that drug and others closely related to divided q12hrs using it. suspension • >3 mos 45-90mg/kg/day divided q12hrs (otitis media 90mg for 10 days)

9/22/2016

5 Sinusitis Treatment Penicillins: Hordeola: • The infection is likely bacterial and should be • Internal are secondary to a staph infection of the meibomian glands treated with antibiotics if: • External are an infection of the Zeis or – symptoms last for 10 days without improvement, or Moll glands – Patients present with tenderness and – include fever of 102 degrees or higher, swelling of affected area. – nasal discharge and facial pain lasting three to four days • Standard treatment includes: – good lid hygiene with warm • Because of increasing resistance to the antibiotic compresses and lid washes – Augmentin 500 mg bid-tid for 5-7 amoxicillin — the current standard of care — the days. ISDA recommends Augmentin – may consider topical AB ung on • Augmentin 250/500 TID for 5-7 days for adults, external hordeolum. 10-14 days for children

Penicillins: Dacryocystitis Penicillins: Dacryocystitis

• Dacryocystorhinostomy (DCR) • infection of the lacrimal sac – surgical procedure of usually secondary to an obstruction. choice. • in pediatric patients: – allows for the bypassing of – the obstruction usually the lacrimal duct apparatus resolves by age 9-12 months. as long as the canalicular – many pediatric apparatus is intact. ophthalmologists will wait until after this age to probe • Punctal dilation and the ducts to free the nasolacrimal irrigation is obstruction. contraindicated in the acute stage due to the increased risk of periorbital cellulitis.

Penicillins: Dacrocystitis Preseptal Cellulitis

 Infection and inflammation • Treatment includes: located anterior to the orbital – Augmentin 500/125 mg (500 septum and limited to the mg amoxicillin/125 mg superficial periorbital tissues clavulanic acid) TID and eyelids. • or 875/125 mg BID for 7  Usually follows sinus infection or days or internal hordeolum (possibly trauma)  Eyelid swelling, redness, ptosis, pain and low grade fever.

6 Preseptal Cellulitis Differentiating Orbital vs. Preseptal

 Tx: FINDING ORBITAL PRESEPTAL  Augmentin 500 mg TID or 875 Visual Acuity Decreased Normal mg BID for 5-7 days Proptosis Marked Absent  Keflex 500 mg QID 5-7 days Chemosis and Marked Rare/Mild  or if moderate to severe IV Fortaz Hyperemia (ceftazidime) 1‐2 g q8h. Pupils RAPD Normal  If MRSA possible, consider Pain and Motility Restricted and Painful Normal Bactrim/Septra IOP Normal Temperature 102 ‐ 104 Normal/mild elevation HA and Assoc. Common Absent Symptoms

Treatment: Orals for Preseptal, Often IV for Orbital

Cephalosporins Side Effects and Contraindications

• Closely related structurally and functionally to the • Hypersensitivity Reactions penicillins, are common. – have the same mode of action, – Risk of cross sensitivity with – affected by the same resistance mechanisms. PCN’s is higher for 1st – tend to be more resistant to B-lactamases. generation, but often • classified as 1st, 2nd, 3rd, 4th and now 5th generation based overestimated for later largely on their bacterial susceptibility patterns and medications. resistance to B-lactamases. – Used to state the cross • Typically administered IV or IM, poor oral absorption. sensitivity was ~10%, but now believed to be closer to 3%.

Cephalosporins Cephalosporins

• 1st generation: cefadroxil (Duricef), cefazolin • Keflex (cephalexin) 1st Generation: (Ancef)• , cephalexin (Keflex), and cephalothin – treatment of respiratory, GI, skin and skin structure, and bone • 2nd generations: cefaclor (Ceclor), cefprozil, infections as well as otitis media cefuroxime (Zinacef), cefotetan, cefoxitin – Adults: 250-1000 mg every 6 hours • 3rd generation: cefdinir (Cefzon), cefixime, • - typical dosing 500 every 6 hours cefotaxime (Claforan), ceftazidime (Fortaz), ceftibuten, ceftizoxime, ceftriaxone (Rocephin – Children: 25-100 mg/kg/day divided 6-8 hours IM/IV). – Available: • 4th generation: cefepime • 250 mg • • Duricef, Keflex, Ceclor and Cefzon (all orally 500 mg administered) are effective against most gram • 750 mg (pricey 750 mg (20): $153.80 generic, brand 750 mg positive pathogens and especially good for skin (50): $521.56) and soft tissue infections. – Typically a BID dosing – Not commonly used

7 Cephalosporins Cephalosporins

• Cefaclor (Ceclor) (2nd generation): • Cefaclor (Ceclor): – Immediate‐release: 250 to 500 mg every 8 hours – Mild preseptal cellulitis = 250‐500 mg TID in – Extended‐release: 500 mg every 12 hours adults and 20‐40 mg/kg/day in three divided doses for children Note: An extended‐release tablet dose of 500 mg twice daily is clinically equivalent to an immediate‐release capsule dose of 250 mg 3 times daily; an extended‐release tablet dose of 500 mg twice daily is NOT clinically equivalent to 500 mg 3 times daily of other cefaclor formulations.

9/22/2016 9/22/2016

Cephalosporins Cephalosporin

• Cefzon or Omnicef (cefdinir): • Cefazolin (Ancef) (1st generation): – 3rd generation – Usual dosage range: IM, IV: 1 to 1.5 g every 8 – Oral: 300 mg twice daily or 600 mg once daily for hours, depending on severity of infection; 10 days. maximum: 12 g daily – • Skin and soft tissue infection due to MSSA: IV: 1 g every 8 hours for Indicated for maxillary sinusitis and otitis media 7 to 14 days – Also indicated for soft tissue infections • Skin and soft tissue necrotizing infection due to MSSA (off‐label (uncomplicated) use): IV: 1 g every 8 hours; continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for – Pricey 48 to 72

9/22/2016 9/22/2016

Cephalosporins: Chlamydia: Treatment Hyperacute Conjunctivitis • Recommended Treatment Regimens: • Hyperacute conjunctivitis: – Azithromycin 1 g orally in a single dose – usually secondary to gonorrhea • OR or chlamydia. – Doxycycline 100 mg orally twice a day for 7 days • profuse purulent discharge, • Alternative Treatment Regimens: – Erythromycin base 500 mg orally four times a day for 7 days • pain, • OR • redness, – Erythromycin ethylsuccinate 800 mg orally four times a day for 7 days • chemosis, • OR • papillae, – Levofloxacin 500 mg orally once daily for 7 days • positive nodes • OR – Ofloxacin 300 mg orally twice a day for 7 days

9/22/2016

8 Gonorrhea Conjunctivitis Treatment Gonorrhea Conjunctivitis Treatment

• For patients with uncomplicated – Cefixime (Suprax) 400 mg oral gonorrhea conjunctivitis: in a single dose – Single 250 mg IM injection (not considered standard anymore. Ceftriaxone (Rocehphin) for No failures in treatment noted in the treatment of the gonococcal infection US but have been reported in Canada and Europe) PLUS – - Azythromycin (1g) for possible concurrent use of ocular lavage additional activity against and topical fluoroqinolone gonorrhea plus possible • e.g. chlamydia co-infection cipro/moxi/besi/gatifloxacin q1-2 hrs

Cephalosporins Cephalosporins: Dacryoadenitis

• Dacryocystitis Tx: • An inflammation or infection of • Keflex 250-500 mg po QID, the lacrimal gland. • In febrile cases: – S&S include: • IV cefazolin (Ancef) 1g q8h or • swelling of lid, •IV cefuroxime (Zinacef) 1.5g q8h. • pain in area of swelling, • Preseptal cellulitis: • excess tearing or discharge and swelling of lymph nodes. – Mild: • maybe secondary to viral or • Ceclor (cefaclor) 250-500mg q8h bacterial infection or an – Moderate to severe: inflammatory condition (e.g. • IM Rocephin (ceftriaxone) 1-2 grams/day or sarcoid or Graves disease) • IV Fortaz (ceftazidime) 1-2 g q8h.

Cephalosporins: Cephalosporins: Dacryoadenitis Orbital Cellulitis • infection and inflammation within the orbital cavity producing orbital S&S. • Tx: • most commonly secondary to ethmoid sinusitis. – Most cases are viral and self resolving (supportive measures) • Staph and Strept most common isolates. • Signs and Symptoms include: – If bacterial: – decreased VA, – pain, • Keflex (cephalexin) 250-500mg po QID, – red eye, – HA, • for more severe cases IV – diplopia, cefazolin(Ancef) 200mg/kg divided into 3 doses. – bulging eye, – APD, – If the enlargement does not subside – EOM restriction, after 2 weeks, consider lacrimal gland biopsy. – lid swelling and – fever (generally 102 degrees F or higher)

9 Cephalosporins: Orbital Cellulitis Treatment Orbital Cellulitis Vancomycin: 5 to 20 mg/kg IV per day every 8 to 12 hours • IV therapy continued until improvement PLUS: (one of the following) noticed (minimum 3‐5 days) ‐ Ceftriaxone (Rocephin): 2 g IV • Switch to oral antibiotics (2‐3 weeks): every 24 hours or – Clindamycin 300 mg every 8 hours ‐ Cefotaxime: 2 g IV every four – hours or Clindamycin or Bactrim/Septra PLUS • ‐ Ampicillin‐sulbactam: 3 g IV Augmentin 875 mg every 12 hours or every six hours • Cefpodoxime 400 mg every 12 hours or • Cefdinir 300 mg twice daily

9/22/2016

Endophthalmitis Endophthalmitis

• intraocular infection involving • Signs/symptoms typically present: anterior/posterior segments usually • Post-trauma: 12-24 hours secondary to postoperative • Post –surgery: day 2 (or later) infection (0.1% risk post-op • Post-intravitreal injection: 1-6 days cataract). (av 3.4 days) – 95% gram +ve bacteria including • staph (80%), strept (10%) with about 6% gram –ve organisms (these infections to be more virulent and have worse prognosis)

Post-operative Endophthalmitis Endophthalmitis Treatment Post-operative endophthalmitis: • Patients’ present with: • Endophthalmitis Vitrectomy Study (EVS), vitrectomy decreased the rate of severe vision loss from 47% (tap • decreased VA (95%) group) to 20% (vitrectomy group) in patients who • pain (75%), presented with the worst vision (light perception only) • red eye (80%), • Intravitreal: • hypopyon (>80%) – vancomycin 1 mg/0.1ml and ceftazidime (Fortaz) 2.25 • discharge, proptosis, mg/0.1 ml (or amikacin) • corneal edema, injection, – if no improvement after 48 hours a repeat injection of either vancomycin or Fortaz (but not amikacin secondary to retinal •KP’s, toxicity issues) • vitritis, photophobia, – Intravitreal steroids maybe considered

10 Post-traumatic Endophthalmitis Vancomycin/Bacitracin Treatment Post-traumatic endophthalmitis: (in addition to • Vancomycin and bacitracin both inhibit cell wall synthesis. intravitreal) • Vancomycin is increasingly important as it is effective • Subconjunctival: against multiple drug-resistant organisms (such as MRSA/MRSE and enterococci) – vancomycin 25mg and ceftazidime (Fortaz) 100mg (gentamicin) and dexamethasone 12-24mg, – used in patients who have penicillin allergies • Topical: – often considered the drug of last resort, though overuse has brought about resistance. – fortified vancomycin (Vancocin HCl 2.5% Ophthalmic) and ceftazidime (Fortaz) 50mg/ml/hr, topical steroid and • Bacitracin is active against a wide variety of gram (+) cycloplegic, organisms • controversial IV systemic AB. – restricted to topical use due to its potential for nephrotoxicity.

Vancomycin Vancomycin

• Vancomycin is typically administered systemically as an infusion •Treatment: due to its poor oral absorption • Orbital Cellulitis – complications are minimized when it is administered at less than 10 mg/min • Endophthalmitis • topical fortified vancomycin can be compounded (25-50 mg/ml) (Vancocin HCl 2.5% Ophthalmic Drops) • Complications include: – anaphylaxis (hypotension, wheezing, dyspnea, urticaria, pruritis), – upper body flushing, – pain secondary to muscle spasm, nausea, diarrhea, headache. – typically the most serious complication is nephrotoxicity but it is an infrequent complication.

Bacitracin • Due to nephrotoxicity, bacitracin not PROTEIN used as a systemic med. • Bacitracin useful for bacterial lid SYNTHESIS disease (staph blepharitis) INHIBITORS – has a low rate of allergy and toxicity. • Primarily gram + activity so Protein Synthesis Inhibitors usually found in combination with a gram - compound – e.g. polymixin B (Polysporin).

11 Protein Synthesis Inhibitors Tetracyclines

• These antibiotics work by targeting the • Nonresistant strains concentrate this antibiotic bacterial ribosome. intracellularly resulting in inhibition of protein synthesis. – they are structurally different from mammalian ribosomes, • Broad spectrum, bacteriostatic, – in higher concentrations many of these antibiotics – effective against gram (+) and (-) bacteria and against can cause toxic effects. non-bacterial organisms – widespread resistance has limited their use. • This group includes: • Drug of choice for Rocky Mountain Spotted Fever, – (a) tetracyclines, (b) aminoglycosides, (c) macrolides, Cholera, Lyme disease, mycoplasma pneumonia, and – (d) chloramphenicol, (e) clindamycin, (f) chlamydial infections. quinupristin/dalfopristin and (g) linezolid – Doxy can be used to treat MRSA skin infections with a known susceptibility

Side Effects of Tetracyclines Tetracyclines

• Side effects include gastric discomfort, phototoxicity, effects on calcified tissues, vestibular problems, • This group includes: pseudotumor. – Tetracycline (250mg - 500 mg cap BID-QID) needs • Pregnancy Category D. – Tetracyclines are attracted to embryonic and growing to be taken 1 hour before or 2 hours after a meal. bone tissue. • Depress growth of long bones in pregnant – Minocycline (100 mg cap BID) women/children. • Cause changes in both deciduous and permanent teeth – Doxycycline (20mg - 100 mg cap or tab BID) during the time of tooth development (Includes discoloration and increased cavities) • In Canada doxy comes in 100 mg tablets (Apo-Doxy, Novo-Doxylin and Vibra-Tabs) • Contraindicated in: – Women in the last half of pregnancy • Apprilon (30 mg doxy + 10 mg slow release doxy) – Lactating women – Children under 8 years of age

Tetracyclines Tetracyclines: Acne Rosacea

• Rules of Thumb with Doxy: • Mainstay oral Tx is Oracea (40 mg in – Do not take before lying down (>2 hours before) morning) or – doxycycline 50 mg po or minocycline 100 – Do not take with calcium and avoid antacids mg po for 4-12 wks. – Do not take with dairy – Do take with food – NOTE: Oracea is subantimicrobial therapy

12 Acne Rosacea Treatments Tetracyclines: Oral Antibiotics Topical Treatments Non-Prescription Adult Inclusion Conjunctivitis Erythromycin metronidazole (Metrogel) Rosacea-Ltd III • occurs in sexually active adults Tetracycline BenzaClin (Clindamycin 1% & ZenMed • women are more susceptible than men. benzoyl peroxide 5%) • usually transmitted through hand-to-eye Doxycycline BenzaMycin (Erythromycin 3% & Neova Therapy spread of infected genital secretions. benzoyl peroxide 5%) • incubation period is one to two weeks Minocycline tretinoin (Retin-A) Kinerase • Signs and Symptoms: – ocular irritation, watering, Clindamycin 1% lotion/gel Rosacare mucopurulent discharge and positive Plexion Cleanser/Lotion (Sulfa 10% nodes & sulfur 5%) – often a unilateral disease but can involve both eyes www.internationalrosaceafoundation.org – follicles inferior fornix, mixed papillary/follicular on upper lid, subepithelial infiltrates, SPK.

Tetracyclines: Adult Inclusion Conjunctivitis Treatment Tetracyclines: Ocular Conditions • Hordeola: • Mainstay oral treatment is: – doxycycline 50-100 mg po BID for 2-3 weeks. – may consider topical AB ung on external – Doxycycline 100 mg po BID for 7 hordeolum. days. • Meibomian Gland Dysfunction: – good lid hygiene with warm compresses and lid Or scrubs in conjunction with – Azithromycin 1 gram single dose – doxycycline 50 mg po for 2-3 months. • Recurrent Corneal Erosion – Topical AB therapy is done – treat with doxycycline 50 mg po BID for 2-3 concurrently. months • include use of topical steroid bid-tid for 6-8 weeks.

Aminoglycosides Aminoglycosides

• Previously were mainstay treatment for infections due to • This group includes: aerobic gram (-) bacilli. – due to serious associated toxicities, they have been – Gentamicin replaced by safer antibiotics such as 3rd gen – Neomycin cephalosporins, fluoroquinilones, cilastin. – Streptomycin • Effective in the treatment of infections suspected of being due to aerobic gram (-) bacilli including Pseudomonas. – Tobramycin – usually combined with B-lactam or vancomycin for – Amikacin anaerobic bacteria. They are bacteriocidal! • Can have severe adverse effects including ototoxicity, nephrotoxicity, delay in nerve conduction, and skin rash.

13 Aminoglycosides: Ocular Indications Macrolides

• Erythromycin was the first of these drugs, as an • Systemic aminoglycocides not alternative to penicillin. Bacteriostatic though at commonly indicated for ocular [higher] maybe cidal conditions • Macrolides bind to the bacterial ribosome and – amikacin has been used for inhibit protein synthesis. endophthalmitis IV and intravitreal – have same spectrum of action as penicillins so are used in those patients who are allergic to that • Topical preparations are widely used as group. single agent preparations, in • Resistance to erythromycin is becoming a serious combination with other antibiotics as clinical problem. well as in combination with steroids. • Adverse effects include: – epigastric distress, jaundice, ototoxicity and contraindicated in patients with hepatic disease.

Macrolides Clarithromycin (Biaxin)

• This group includes: • Derivative of Erythromycin that is more stable in gastric acid with a ½ life that is nearly twice that – Erythromycin (125 or 250 mg cap, enteric coated) of Erythromycin. dosing 250mg q 6h or 500 q12h – Clarithromycin • Used for respiratory and skin infections as well as – Azithromycin (Z-pak) (500mg first day, then 250 the treatment of H. Pylori ulcers, but can be used for Chlamydia if needed. mg for next 4 days) – Telithromycin • BIAXIN is available as immediate‐release tablets, extended‐release tablets, and granules for oral suspension.

Macrolides Azythromycin

• Azithromycin (Z-pak) is active against respiratory • Hyperacute conjunctivitis: infections due to H. influenzae and Moraxella. – Secondary to Chlamydia or Gonorrhea – it is a costly medication (generic now available), • Adult inclusion conjunctivitis – now a preferred therapy for urethritis by – Secondary to chlamydial infection chlamydia. – excellent for soft tissue infections. – use with caution in patients with impaired liver function and no controlled studies for use in pregnancy.

14 Macrolides: Ocular Indications Macrolides: Ocular Indications

• Erythromycin can be used as • Erythromycin available in topical alternative treatment in patient ointment form with: – Ilotycin – internal hordeola, – for treatment of superficial – pre-septal cellulitis, infections – dacrocystitis • blepharitis and prophylaxis • remember high incidence of of ophthalmia neonatorum staph resistance.

Chloramphenicol Chloramphenicol: Ocular Indications

• Active against a wide range of gram (+) and (-) • Systemic treatment rarely used for ocular organisms. conditions. – because of its toxicity, its use is restricted to life- • Available in solution 0.5% and ointment 1% threatening infections for which no alternative (Chloroptic) exists. – generally not used in the US but commonly used • Bacteriocidal and bacteriostatic depending on abroad (Europe and Australia). the organism. • Effective against most ocular bacterial infections • Adverse effects include hemolytic and aplastic but because of potentially fatal complications anemia. should only be used as a last resort.

Clindamycin Clindamycin

• Inhibits protein synthesis by • Occasionally used in the treatment of Ocular binding to a portion of the 50S Toxoplasmosis but not FDA approved. ribosome subunit. • Another option for use in the treatment of • Available IV, IM, and orally. MRSA ocular infections: – 450 mg TID for Adults • High levels of side effects such as serious pseudomembranous colitis and superinfections have – 10 –30 mg/kg/day in three doses for kids limited use. – Main use is in patients allergic to Sulfa drugs.

15 Inhibitors of Nucleic Acid Synthesis/Function. • The fluoroquinolones are the main group of antibiotics that act in this fashion. Inhibitors of Nucleic Acid – they enter the bacterium via passive diffusion and once inside the cell inhibit the replication of bacterial DNA by Synthesis/Function interfering with the action of DNA gyrase and topoisomerase IV during bacterial growth and reproduction. • unfortunately, their overuse has already led to the emergence of resistant strains.

Inhibitors of Nucleic Acid Inhibitors of Nucleic Acid Synthesis/Function. Synthesis/Function. • Rifampin is the other major member of this • All the fluoro are bactericidal, with activity group and is an inhibitor of RNA synthesis becoming more pronounced as the serum [drug] • Bactericidal increases. • Is a broad spectrum antibiotic but is used – in general, they are effective against gram(-) bacteria mostly in the treatment of TB including pseudomonas and haemophilus, and have good activity against some gram (+) organisms such as – resistance is common strept. – Rifampin is typically used in combination with other anti-TB meds • Common practice to classify the fluoro into “ ” – has a new role in treatment of MRSA in generations with nalidixic acid being 1st combination with fusidic acid. generation.

Inhibitors of Nucleic Acid Inhibitors of Nucleic Acid Synthesis/Function. Synthesis/Function. • Ciprofloxacin is the most frequently used fluoro in the US. • The fluoro are generally very well tolerated – effective against many systemic infections, with the exception of serious infections caused by MRSA, the though some of the most common adverse enterococci and pneumococci. reactions include: – it is used in treating infections caused by enterobacteria – GI upset, (ex. travelers diarrhea) and drug of choice for anthrax prophylaxis. – CNS problems (HA and dizziness), – has good activity against pseudomonas, and may have – phototoxicity, synergistic activity with B-lactams. – liver toxicity, • Resistance has developed due to mutations in both gyrase and topoisomerase. – nephrotoxicity

16 Inhibitors of Nucleic Acid Ocular Indications Synthesis/Function. – connective tissue problems: • Hyperacute conjunctivitis (gonococcal): Oral or • strongly associated with Achilles tendinopathy and IM fluoroquinolone (only indicated if unable tendon rupture to use cephalosporin) • Achilles tendinopathy was stronger among individuals • Cat Scratch Disease: ciprofloxacin 500-750 mg who were >60 years old and female po q 12h for 10-14 days. • The median duration of fluoroquinolone use before • Orbital cellulitis: IV ciprofloxacin the onset of tendon injury is eight days • Majority of the use of fluoroquinolones in – should be avoided in pregnancy, nursing mothers ocular use is in the form of topical drops and and children under age of 18 and patient >60 ointments. Used in all forms of infections and prophylaxis in ocular surgeries.

Ocular Fluoroquinolones

• Besivance (besifloxacin 0.6%) is strictly an ophthalmic preparation with no systemic counterpart Inhibitors of Metabolism – thought to possibly reduce chance of resistance development – has DuraSite as vehicle so forms a gel-like liquid on the eye increasing contact time – Indications for coverage of Pseudomonas and MRSA

Inhibitors of Metabolism Sulfonamides

• Folic acid is required for the synthesis of precursor • Sulfa drugs are seldom prescribed alone except in the molecules for RNA, DNA and other compounds developing countries, where they are used because of their low cost and efficacy in certain infections such as necessary for cellular growth. trachoma. – in the absence of folic acid, cells cannot grow or divide. • With the combination with trimethoprim, co-trioxazole • (a) Sulfonamides and (b) trimethoprim are folic there was a renewed interest in the sulfa drugs. acid antagonists and interfere with an infecting • Sulfa drugs are bacteriostatic, bacteria’s ability to divide. – active against selective enterobacteria in the urinary tract. • Compounding the two has made a synergistic – resistance exists is those bacteria that don’t synthesize compound used for effective treatment of a variety folic acid and in any PABA producing bacteria of bacterial infections. (purulent producing bacteria).

17 Sulfonamides Trimethoprim and Pyrimethamine

• Adverse effects include: • Similar antibacterial spectrum as sulfonamides, though has a 20-50 fold more potent affect than the sulfonamides. – hypersensitivity reactions such as rashes, • Trimethoprim maybe used on its own to treat acute UTI’s – angioedema, and in the treatment of bacterial prostatitis (fluor preferred – Stevens-Johnson syndrome are fairly common. though) and vaginitis – may also result in nephrotoxicity, hemolytic anemia, – been found to be an effective treatment option for MRSA • Pyrimethamine is used for prophylaxis and Tx of malaria. – drug potentiation • Resistance does exist, and adverse affects include several • Ex. increased effect of hypoglycemic effect of blood anemias which can be reversed by administering folic tolbutamide or anticoagulent of warfarin acid.

Trimethoprim: Ocular Indications Co‐Trimoxazole (Bactrim/Septra) • Combination of trimethoprim and • Combined with sulfa (Bactrim/Septra) sulfamethoxazole indicated for MRSA suspected infections – shows greater antimicrobial activity • Trimethoprim is found in combination with than equivalent quantities of either polymixin B in a topical eye drop. drug alone. • Has broader spectrum of action than – Trimethoprim has both gram +/- activity but not the sulfa’s and is effective in treating: effective against pseudomonas so Polymixin B is – UTIs and respiratory tract infections added. – often considered for treatment of • Low rate of allergic and toxic reactions, and MRSA skin infections approved for children >2 months.

Co‐Trimoxazole (Bactrim/Septra) Co-Trimoxazole (Bactrim/Septra)

• Resistance is more difficult because has to • Available: develop resistance to both drugs. – Bactrim/Septra tablets: • Adverse effects include: – contains 80 mg trimethoprim and 400 mg – severe potential for dermatologic reactions, sulfamethoxazole – GI upset, – dosing 2 tablets every 12 hours – blood disorders, and – Bactrim DS/Septra DS (Double Strenth) – drug potentiation. • contains 160 mg trimethoprim and 800 mg sulfamethoxazole • Dosing 1 tablet every 12 hours

18 Drugs Affecting the Cell Membrane

• Interact with the phospholipids of the cell membrane causing increased permeability and Inhibitors of Cell Membrane disruption of the osmotic gradient. Function • Bactericidal in nature.

• Two Main Drugs: – Polymyxin B – Gramicidin

V: Inhibitors of Cell Membrane Function • Isoniazid is the most potent of the anti-tubercular drugs and interferes with the production of mycobacterial cell walls. • Mycobacteria is a slow growing organism and Thank You!!! treatment is often required from 6 months to several years. – due to poor compliance, resistance has developed and therefore treatment is never given as a single agent. • Multi-drug therapy is given and maybe changed on a regular basis in order to effectively treat the patient.

9/22/2016

19