Summary

This lecture outline covers different aspects of antibiotics, including bacterial overview, cell wall synthesis, and other mechanisms of action. It details various types of antibiotics and their applications.

Full Transcript

Antibiotics 1. Bacterial Overview a. Bacteria in 80-90% of eyes include i. Coagulase negative staphylococci ii. Propionibacterium acnes iii. Corynebacterium species b. Bacteria in some non-infected eyes include i. Staph aureus ii. Strep pneumoniae iii. H. flu c. Unique structure i. Chlamydia – trach...

Antibiotics 1. Bacterial Overview a. Bacteria in 80-90% of eyes include i. Coagulase negative staphylococci ii. Propionibacterium acnes iii. Corynebacterium species b. Bacteria in some non-infected eyes include i. Staph aureus ii. Strep pneumoniae iii. H. flu c. Unique structure i. Chlamydia – trachoma, inclusion conjunctivitis 1. Mimics viruses ii. Treponema pallidum – syphilis d. MBC – minimum bactericidal concentration – least amount of drug to kill 99.99% of an organism e. Bacteriostatic – inhibit bacterial growth, work with immune system i. MIC – minimum inhibitory concentration – least amount of drug to inhibit growth f. Not always a precise distinction between cidal and static, depends on concentration and microorganism g. Resistance i. Antibiotics in animal feed is the main reason h. Oral antibiotics indicated for: meibomianitis, internal hordeolum, ocular rosacea, dacryocystitis, preseptal cellulitis, chlamydial conjunctivitis, and prophylaxis in orbital fractures and sinusitis i. Probiotics i. Live, nonpathogenic microorganisms that improve microbial balance ii. Consist of yeast or lactic acid bacteria iii. Regulated as a dietary supplement and food iv. Used to tx antibiotic related diarrhea, but do not take with antibiotic, space at least 2 hours v. Lower intestinal pH, enhance mucin from gut epithelial cells, promote secretory IgA, interfere with quorum sensing, anti-inflammatory effect, decrease colonization, decrease invasion by pathogenic organisms, modify host immune response, activate opioid and cannabinoid receptors in gut vi. Sauerkraut, yogurt, pickles, kefir, kimchi j. Oral contraceptives i. May have reduced activity while on oral antibiotics due to increased liver p450 enzyme induction, diarrhea, and decreased enterohepatic circulation, increased liver degradation, contraceptive displacement from receptor site k. Antimicrobials interact with warfarin l. Topical antibiotics indicated for: anterior segment infection, conjunctivitis, corneal ulcer, blepharitis, prophylaxis 2. Cell Wall Synthesis a. Penicillins – bactericidal, G + and – i. Block the PEP side chain cross linking as the final step in peptidoglycan synthesis ii. Side chain determines antibacterial spectrum iii. Use: 1. Hordeolum 2. Preseptal cellulitis 3. Dacryocystitis 4. Dacryoadenitis iv. ADR: hypersensitivity response 1. Allergy not as common as once thought 2. Cross react with cephalosporin v. Classifications: 1. Gram + effectivity a. G, and V 2. Resistant to Penicillinase a. Dicloxacillin i. Not inactivated by penicillinase that would otherwise destroy the beta-lactam ring ii. Pregnancy safe 3. Extended spectra, good against G – a. Amoxicillin b. Amoxicillin and clavulanate (Augmentin) i. Clavulanate: B-lactamase inhibitor that protects penicillin component from inactivation by penicillinase or B-lactamase ii. Weak antimicrobial activity iii. Pregnancy safe 4. Antipseudomonal activity b. Cephalosporin – bactericidal i. Similar to penicillins in MOA, spectrum ii. Classified as 1st through 4th generations, greater gram - activity with more generations and less gram +, as well as greater effect against resistant organisms iii. ADR: hypersensitivity, cross sensitivity, Vitamin K deficiency (may cause bleeding) iv. Use 1. Preseptal cellulitis 2. Dacryocystitis 3. Dacryoadenitis 4. Orbital fracture 5. Other – fortified use v. Cephalexin (Keflex) 1. First generation 2. Oral 3. Pregnancy safe vi. Cefaclor vii. Cefazolin 1. First generation 2. Injection 3. Pregnancy safe 4. Fortified c. Vancomycin – bactericidal, gram + i. Injection, capsule, fortified ii. Less safe for pregnancy iii. ADR: highly toxic, anaphylaxis, vasculitis, nephrotoxicity, ototoxicity, neutropenia, others iv. Used for MRSA, bacterial endophthalmitis, bacterial keratitis, ruptured globe, orbital cellulitis d. Bacitracin – bactericidal, gram + i. Ointment ii. Pregnancy safe iii. Used in blepharitis iv. Can be used in combinations 3. Cytoplasmic Membrane a. Polymyxin B – bactericidal, gram i. Especially good with pseudomonas (CL) ii. Interacts with cells osmotic integrity iii. ADR rare iv. Used in combo with other antibiotics and steroids b. Gramicidin – bactericidal, gram + i. Used in combo ii. Pregnancy safe 4. Protein Synthesis a. Aminoglycosides – bactericidal, gram + and i. Bind to 30S subunit, interfering with protein synthesis, and allowing misreading of mRNA causing mutation and premature chain termination ii. Neomycin 1. Gram + and 2. Ineffective against P.aeruginosa 3. Used in combo 4. ADR: drug sensitization (contact dermatitis) iii. Gentamicin 1. Useful against pseudomonas a. 2. Ineffective against streptococcus 3. ADR: corneal and conjunctival toxicity, allergic reactions iv. Tobramycin 1. Useful for pseudomonas a. 2. Similar to gentamicin except more sensitive to some resistant pseudomonas strains and P. aeruginosa 3. Used in combination with dexamethasone – TobraDex 4. Less ADRs v. Amikacin 1. Useful for pseudomonas a. 2. No ophthalmic 3. Injection 4. Used in traumatic endophthalmitis and bacterial keratitis b. Tetracyclines – bacteriostatic, gram + and - and chlamydia i. Oral use: 1. Chlamydia – inclusion conjunctivitis or trachoma 2. Acne rosacea, meibomianitis a. Free fatty acids i. Released from sebum by bacterial lipases ii. Irritating and inflammatory iii. Tetracycline: decreases lipase production 3. Nontuberculous phlyctenular keratoconjunctivitis 4. Non Infected corneal ulcers a. Related to anti collagenolytic activity of systemic tetracycline ii. Oral – antibiotic, decrease bacterial lipase production, anti-inflammatory, anticollagenolytic iii. Topical – prophylaxis gonococcal ophthalmia neonatum, not in US iv. ADR: depress bone growth, not indicated for pregnant women or young kids, for tetracycline calcium complexes, also cause intracranial hypertension (pseudotumor cerebri) v. Absorption affected by: food (not doxycycline), iron containing tonics or antacids containing calcium, magnesium, or aluminum vi. Adverse reactions: hypersensitivity reactions, photosensitivity/toxic reactions, epigastric distress, changes in tooth development such as discoloration, dysgenesis, staining, and caries, blood dyscrasias, potentiate coumarin type anticoagulant effect, vestibular toxicity vii. Contraindications: pregnancy, may use short term while breastfeeding, theoretical risk of permanent infant bone and teeth discoloration with prolonged use, children under 8 viii. Tetracycline 1. Take on empty stomach 2. For acne rosacea, chlamydia, meibomianitis, resistant sebaceous blepharitis 3. Replaced by erythromycin for neonatal prophylaxis ix. Doxycycline (Vibramycin) 1. Chlamydia, acne rosacea, meibomianitis, and ocular surface inflammatory disease 2. May take with food 3. ORACEA must be taken on empty stomach 4. For rosacea, use ORACEA, contains 30mg immediate release and 10mg delayed release, NEVER REACHES THERAPEUTIC LEVEL x. Minocycline 1. May not have symptoms or may develop years after discontinuation, decreased cerebrospinal fluid absorption 2. May cause vestibular toxicity c. Macrolides i. Erythromycin ii. Azithromycin iii. Clarithromycin d. Chloramphenicol e. Clindamycin

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