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Insert Your Text Here. Antibiotic Use. Antibiotic Use. Richard W. Waguespack, MD, FACS AAOHNS Education Steering CMTE & Chair, Core Otolaryngology Practice Management Education Committee Birmingham, AL rwagmd1@aol.com. Antibiotic Use.

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  1. Insert Your Text Here Antibiotic Use

  2. Antibiotic Use Richard W. Waguespack, MD, FACS AAOHNS Education Steering CMTE & Chair, Core Otolaryngology Practice Management Education Committee Birmingham, AL rwagmd1@aol.com

  3. Antibiotic Use No conflict of interest or financial disclosures to make relating to this presentation. Any “off label” discussion regarding antibiotics or other medications adheres to widely accepted standards of clinical usage. (For example, no antibiotic has been approved for treatment of chronic sinusitis, but many are used to treat this condition on a routine basis.)

  4. Antibiotic Use In the 1950’s & 1960’s, widespread availability of antibiotics meant which of the following statements was true relating to Otolaryngology? A The specialty was predicted to involute and ultimately disappear or become marginalized. B The specialty was predicted to thrive and expand its scope of knowledge. C There would be little or no predictable change to the specialty.

  5. Academy Resources @www.entnet.org • Tonsillectomy in Children Guideline (just published January 2011) • Acute Otitis Externa Guideline • Otitis Media with Effusion Guideline • BPPV Guideline (Benign Paroxysmal Positional Vertigo) • Hoarseness Guideline • Cerumen Impaction Guideline • Clinical Otolaryngology OnLine (COOL) modules • Primary Care Otolaryngology (e-Book) • David N Fairbanks Pocket Guide to Antimicrobial Therapy in Otolaryngology-Head & Neck Surgery 2007 • www.entnet.org/EducationAndResearch/ • loader.cfm?csModule=security%2fgetfile&pageid=9878

  6. Antibiotic Use • Overview of antibiotics • On- and off-label usages • Classes of antibiotics • Method of action • Pharmacokinetics/pharmacodynamics • Allergic reactions and adverse events • Renal and hepatic considerations • Drug interactions • Pregnancy and breast feeding • “Over-prescribing” • Colonization/carrier state vs infection

  7. Antibiotic Use • Mechanisms of drug resistance development (“Dead bugs don’t mutate”) • Use of cultures • Otolaryngology specific antibiotic usage • Atypical infections • Innovative delivery • Topical • Aerosolized • Pulse therapy • Prophylactic antibiotics

  8. Overview of antibiotics • No perfect antibiotic exists or likely ever will (ie, no gorillacillin or cefakilemal) • Narrow spectrum antibiotics should be used whenever possible • Try to use standard, clinically proven drugs • Resistance or selection of resistant bacteria may develop quickly in an individual and community (“use it and lose it”) • When in doubt, culture • If still in doubt, consult Infectious Disease and other relevant (sub)specialties

  9. Overview of antibiotics • Be aware of community resistance trends • Integrate use of other medications into decision- making, including BCPs (automate whenever possible) • Account for recent antimicrobial treatment • Consider host factors, including environmental aspects • Be honest with patients and treat their disease, not their expectations “Gimme a shot, doc!” • Recognize our “public health” responsibilities • All else being equal, use the least expensive medication

  10. Penicillins • Natural penicillins Narrow • Penicillin V, G • Antistaphylococcal penicillins Narrow • Methicillin, Oxacillin, Cloxacillin, Dicloxacillin, Nafcillin • Amino-penicillins Moderately broad • Ampicillin, amoxicillin • Augmented amino-penicillins Broad • Amox/clav • Ampi/sulbac • Antipseudomonas penicillins Narrow • Ticarcillin +/- clav, Piperacillin +/- tazobactam

  11. Penicillins • Method of action • Interfere with bacterial cell wall growth • Development of resistance • β–lactamase (40% H flu, 90% M Catarrahais, anaerobes, MRSA) • Resistant cell wall penicillin binding proteins (30-40% Strep pneumo) • Pharmacokinetics/pharmacodynamics • Generally good tissue penetration except crossing blood-brain barrier in absence of inflammation • Good GI absorption, especially amoxicillin

  12. Penicillins • Allergic reactions and adverse events • Rash using amox-, ampicillin with mono- nucleosis (50-90%) • Most common class to cause drug reactions • If anaphylactic reaction, asthma, angioedema, never give a β–lactam • Most common is macular rash on trunk or limbs; stop the drug to avoid exfoliative dermatitis • If rash, usually safe to begin cephalosporin • Stevens-Johnson syndrome is rare

  13. Penicillins • Renal and hepatic considerations • Adjust dose frequency if CrCl<30 • Hepatic adjustment not defined for amox; avoid amox/clav if significant impairment • Drug interactions • Warfarin • Pregnancy and breast feeding • Class B • Substantial data suggests safe with lactation

  14. Cephalosporins (cefdujour) • First Generation Narrow • Oral cephalexin (Keflex), cephadroxil (Duricef). Excellent GI absorption. • IV cephazolin (Ancef) • Second Generation Moderately broad • Oral cefuroxime-axetil (Ceftin), cefaclor (Ceclor), cefdinir (Omnicef), cefprozil (Cefzil), cefpodoxime (Vantin). Cefditoren (Spectracef) • IV cefoxitin (Mefoxin), cefotetan, cefuroxime (Zinacef)

  15. Cephalosporins (cefdujour) • Third Generation Broad • Oral cefixime (Suprax), ceftibuten (Cedax) • IV cefotaxime (Claforan), ceftazidime (Fortaz), ceftriaxone (Rocephin) • Fourth Generation Very Broad • Cefepime • Generally 2nd and 3rd generation drugs have less activity against G+ and more against G- bacteria

  16. Cephalosporins • Method of action • Similar to penicillins • Penicillin resistance of Strep pneumo suggests resistance to the class • Pharmacokinetics/pharmacodynamics • Drug dependent • Allergic reactions and adverse events • One of the safest classes • 1-7% occurrence of drug reactions in persons with penicillin allergy • Nephrotoxicity rare; potentiates risk with aminoglycosides

  17. Cephalosporins • Renal and hepatic considerations • Drug dependent but generally minimal effect • Drug interactions • Aminoglycoside nephrotoxicity • Drug dependent • Pregnancy and breast feeding • Most commonly used oral preparations are class B and safe during lactation • Drug dependent

  18. Macrolides • Major types Narrow • Erythromycins • Azithromycin • Clarithromycin (XL) • Ketek • Method of action • Inhibit RNA-based bacterial protein synthesis • Anti-inflammatory effect • Strep pneumo resistance to penicillins usually associated with macrolide resistance also • Atypicals covered • G+ (not MRSA) and oral anaerobes covered

  19. Macrolides • Pharmacokinetics/pharmacodynamics • Azith remains intracellular for days (may enhance resistance) • Class best taken on an empty stomach; Clarith better absorbed • Good tissue levels • Allergic reactions and adverse events • Relatively safe drugs • GI symptoms most common • Transient hearing loss with high dose erythromycin • Avoid with myasthenia gravis

  20. Macrolides • Renal and hepatic considerations • Consider adjusting dose if CrCl<30 • Drug interactions • Calcium channel blockers may cause hypotension in elderly • Azith does not adversely interact with drugs metabolized via cytochrome P450; others in class do interact (antiarrhythmics, statins, warfarin, theophylline, digoxin, dopamine antagonists, methylprednisolone, benzodiazepines, Tegretol) • Clarithromycin-check for other drug interactions • Pregnancy and breast feeding • Class C; safety in lactation unknown

  21. Clindamycin • Inhibits RNA-based bacterial protein synthesis • Coverage of G+ and anaerobic bacteria • Increasing resistance to penicillin resistant Strep pneumo • Pharmacokinetics/pharmacodynamics • Well absorbed orally q 6-8hr • Good tissue levels, except blood-brain barrier • Allergic reactions and adverse events • Diarrhea in 20%; 1st associated with C. difficile colitis (Black Box warning) • Uncommon allergic reactions

  22. Clindamycin • Renal and hepatic adjustments for impairment usually not needed • Drug interactions • Few, except Botulinum toxin and neuro- muscular blockade agents • Pregnancy and breast feeding • Class B • Possibly unsafe during lactation

  23. Aminoglycosides • Major drugs Narrow • Streptomycin-mainly anti-tuberculosis drug • Neomycin-mainly used topically for G+ and G- • Gentamicin • Tobramycin • Amikacin • Inhibits bacterial protein synthesis • Genta-, tobramycin, amikacin coverage of G- bacteria and Staph, including MRSA • Concentration killing • Requires topical or parenteral administration

  24. Aminoglycosides • Allergic reactions and adverse events • Ototoxicity and nephrotoxicity which require close monitoring of serum levels and end organ function • Instillation into middle ear, novel application • Neuromuscular blockade • No known hepatic considerations • Drug interactions mainly based on potential additive ototoxicity • Pregnancy and breast feeding • Class D; unknown safety during lactation

  25. Fluoroquinolones • Generally not first-line drugs • Not approved for systemic use below age 18 (Black Box) • Inhibits 2 enzymes associated with DNA synthesis • Low occurrence of drug resistance (so far!) • Topical use • Classes of fluoroquinolones • Ciprofloxacin • “Respiratory quinolones” (eg, levofloxacin, moxifloxacin) maintain G- coverage with improved G+ coverage • Pharmacokinetics/pharmacodynamics • Excellent tissue penetration often exceeding serum levels • Good GI absorption (avoid taking with Al, Mg, Fe, Zn, Ca)

  26. Fluoroquinolones • Allergic reactions and adverse events • GI and rashes • Dizziness and CNS symptoms; lowering seizure threshold? • Renal and hepatic considerations • Dose adjust if renal impairment • Generally minimal hepatic risk with current meds (Remember trovofloxacin!) • Drug interactions • Careful use with drugs that prolong QT interval (moxifloxacin) • Theophylline • Insulin and oral hypoglycemics • Pregnancy and breast feeding

  27. Tetracyclines • Main agents Broad • Doxycycline, Minocycline • Inhibits bacterial protein synthesis and binds to ribosomes; bacteriostatic • Used for atypical infections • Lyme disease and rickettsial infections • Mycoplasma • Occasionally used on oral mucosal ulcers • Pharmacokinetics/pharmacodynamics • Well absorbed by GI tract but not with food • Doxy-, minocycline less affected by Ca, Mg antacids, milk, multivitamins

  28. Tetracyclines • Considerable resistance G+ bacteria, anaerobes, Pseudomonas • Allergic reactions and adverse events • Photosensitivity common • Discoloration of teeth; not for children < 8yo • Vertigo with minocycline • Renal and hepatic considerations • No renal impairment adjustments • Monitor LFS with prolonged use • Drug interactions minimal • Not to be used during pregnancy (Class D) or while breast feeding

  29. Sulfonamides • Trimethoprim-Sulfamethoxazole (TMP-SMX) is the most common form used today Moderately Broad • TMP is also an antibacterial • Synergistic with sulfonamides to block protein synthesis at different sites • Resistance may require combination with other agents • Very useful for treatment of MRSA • Allergic reactions and adverse events • Frequently associated with rashes, esp AIDS patients • Photosensitivity • Blood dyscrasias rare but serious (with prolonged usage)

  30. Sulfonamides • Do not use under 2 months of age • Renal and hepatic impairment require dose adjustment • Drug interactions • Adverse reactions with phenytoin, warfarin, rifampin, oral hypoglycemics, methotrexate • Care with ACE inhibitors (hypokalemia) • Pregnancy and breast feeding • Class C; avoid in 3rd trimester (neonatal jaundice) • Conditional safety during lactation

  31. Other Antibiotics • Chloramphenacol • Metronidazole • Rifampin • Vancomycin • Mupirocin

  32. Special Otolaryngology Topics • Soft tissue infections • Tonsillitis, acute and chronic • Peritonsillar cellulitis and abscess • Supraglottitis • Bronchitis and chronic cough • Laryngitis • Suppurative thyroiditis • Bites • Tick (Lyme Disease, Rocky Mountain Spotted Fever, Erlichia?) • Snake and insects • Human and other mammalian

  33. Atypical infections • Atypical mycobacterial infections • Mycoplasma-little evidence of emerging resistance • Erythro-, clarithro-, azithromycin • Tetracyclines • Quinolones • Pertussis (Bordetella Pertussis 95%) • Resurgence • Treat early (eg, Erythromycin, TMP-SMX) • Cat Scratch Disease (Bartonella) • Erythro-, clarithro-, azithromycin • Tetracyclines

  34. Antibiotic Use • Innovative delivery methods • Topical • Aerosolized • Pulse therapy • WASP (“Wait And See Prescription”)

  35. Mechanisms of drug resistance development • Day care • Multiple antibiotics usage • Prophylactic antibiotic usage • Biofilms • Immunologic compromise • Immunoglobulin deficiencies • Mucociliary dysfunction • Chronic mucosal disease • Cystic fibrosis

  36. Treating Side Effects • Candidiasis (restoration of native flora) • Topical (nystatin, clotrimazole) • Systemic (fluconazole) • Gastrointestinal (side effect or bacterial?) • Discontinuance of drug? • Colitis • Vancomycin, metronidazole • Rashes • Steroids, symptomatic therapy • Photosensitivity • Tetracyclines, sulfonamides, fluoroquinolones • Prevention

  37. Use of Prophylactic Antibiotics • Otitis media • CSF rhinorrhea • Assessment preoperatively (coordinate with PQRS reporting?) • Contaminated/infected field • Cardiac valve disease with risk of endocarditis • Artificial joints • Compromised host factors (post radiation, immune compromise, steroid use, poor nutritional status) • Intradural exposure • Length of surgery

  38. Use of Prophylactic Antibiotics • Route, type, and timing of administration • Topical • Systemic • Duration of postoperative antibiotics • Routine prophylaxis • Otologic • Head & Neck • Post-tonsillectomy +/- adenoidectomy • Rhinologic • Toxic Shock Syndrome

  39. Future Directions?

  40. OK, folks! … It’s a wrap! Gary Larson (Far Side)

  41. Questions?

  42. Antibiotic Use Richard W. Waguespack, MD, FACS AAOHNS Education Steering CMTE & Chair, Core Otolaryngology Practice Management Education Committee Birmingham, AL rwagmd1@aol.com

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