Antibiotic resistance

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Antibiotic resistance

  1. 1. THE JUDICIOUS USE OF ANTIBIOTICS <ul><li>“ New medicines, and new methods of cure, always work miracles for a while ” - William Heberden, 1802 </li></ul>
  2. 2. INCREASING RESISTANCE IN THE US Thornsberry C. Infect Med . 1993;93 (suppl):15-24. Barry AL. AAC . 1994;38:2419-25. Washington JA. DMID . 1996;25:183-190. Thornsberry C. DMID 1997;29:249-57; Doern GV. AAC . 1996;40:1208-13. Thornsberry C. JAC 1999;44:749-59.
  3. 3. INFECTIOUS DISEASES <ul><li>Syndrome </li></ul><ul><li>Host </li></ul><ul><li>Likely pathogens </li></ul><ul><li>Antibiotic options </li></ul>
  4. 4. SYNDROME <ul><li>First distinguish infectious from non-infectious </li></ul><ul><ul><li>Allergy </li></ul></ul><ul><ul><li>Malignancy </li></ul></ul><ul><ul><li>Autoimmune </li></ul></ul><ul><ul><li>Drugs </li></ul></ul>
  5. 5. SYNDROME ANATOMY/ORGAN SYSTEM <ul><li>Site of infection influences </li></ul><ul><ul><li>Likely pathogens </li></ul></ul><ul><ul><li>ABX activity - penetration, pH, foreign body </li></ul></ul><ul><ul><li>Need for ‘cidal’ vs ‘static’ therapy </li></ul></ul>
  6. 6. SYNDROME ANATOMY/ORGAN SYSTEM <ul><li>General - FUO, adenopathy </li></ul><ul><li>Skin/soft tissue - cellulitis, wound infection, necrotizing fasciitis </li></ul><ul><li>CNS - meningitis, encephalitis, brain abscess </li></ul><ul><li>HEENT - sinusitis, otitis, pharyngitis, abscess </li></ul><ul><li>Respiratory - bronchitis, pneumonia </li></ul><ul><li>CV - endocarditis, phlebitis, bacteremia, catheter-related </li></ul>
  7. 7. SYNDROME ANATOMY/ORGAN SYSTEM <ul><li>Abdominal - peritonitis, abscess, cholecystitis/cholangitis, appendicitis </li></ul><ul><li>Urinary tract - cystitis, pyelonephritis, perinephric abscess </li></ul><ul><li>Genital tract - urethritis, cervicitis, PID, prostatitis </li></ul><ul><li>Musculoskeletal - pyomyositis, osteomyelitis, septic arthritis </li></ul>
  8. 8. HOST <ul><li>Demographics - age, habits </li></ul><ul><li>Exposure - sick contacts, residence/travel, hospitalization/institutionalization </li></ul><ul><li>Co-morbidities - immunosuppression, organ dysfunction, surgery, foreign bodies </li></ul><ul><li>Prior antibiotic use </li></ul>
  9. 9. LIKELY PATHOGENS <ul><li>Based on syndrome and host </li></ul>
  10. 10. ISOLATION/IDENTIFICATION <ul><li>Real vs contaminant </li></ul><ul><li>Possible presence of others </li></ul>
  11. 11. SUSCEPTIBILITY <ul><li>Testing may not take into account: </li></ul><ul><ul><li>Inoculum effect </li></ul></ul><ul><ul><li>ABX concentrations at site of infection </li></ul></ul><ul><ul><li>Subpopulations </li></ul></ul><ul><ul><li>Repressed but inducible genes </li></ul></ul>
  12. 12. ANTIBIOTIC USAGE PRINCIPLES <ul><li>Use narrow spectrum when possible </li></ul><ul><li>Use older agent when feasible </li></ul><ul><li>Use combination therapy only when indicated </li></ul>
  13. 13. ANTIBIOTIC OPTIONS <ul><li>Staphylococcus aureus </li></ul><ul><ul><li>MSSA - antistaphylococcal PCN, 1st or 3rd generation ceph, clindamycin, macrolide, carbapenem </li></ul></ul><ul><ul><li>MRSA - vancomycin, linezolid, daptomycin </li></ul></ul>
  14. 14. ANTIBIOTIC OPTIONS <ul><li>Streptococcus pyogenes </li></ul><ul><ul><li>PCN, 1st or 3rd generation ceph, clindamycin, macrolide </li></ul></ul><ul><li>Streptococcus pneumoniae </li></ul><ul><ul><li>PSSP - PCN, 1st or 3rd generation ceph, clindamycin, macrolide, doxy </li></ul></ul><ul><ul><li>PRSP - newer quinolone, 3rd generation ceph, vancomycin </li></ul></ul>
  15. 15. ANTIBIOTIC OPTIONS <ul><li>Enterococci </li></ul><ul><ul><li>PCN-susceptible - PCN/amp ± AGC </li></ul></ul><ul><ul><li>PCN-resistant - vancomycin or daptomycin ± AGC </li></ul></ul><ul><ul><li>VRE - linezolid, quinopristin/dalfopristin, teicoplanin, daptomycin </li></ul></ul><ul><ul><li>AGC-resistant - high-dose continuous infusion PCN/amp </li></ul></ul>
  16. 16. ANTIBIOTIC OPTIONS <ul><li>Gram-negative rods </li></ul><ul><ul><li>Older quinolones, TMP/SMX, 2nd and 3rd generation ceph, beta-lactam/beta-lactamase inhibitor combinations, carbapenem </li></ul></ul><ul><ul><li>SPACEY - inducible extended spectrum beta-lactamase production </li></ul></ul>
  17. 17. ANTIBIOTIC OPTIONS <ul><li>Anaerobes </li></ul><ul><ul><li>Metronidazole, clindamycin, beta-lactam/beta-lactamase inhibitor combinations, carbapenem </li></ul></ul>
  18. 18. ABECB <ul><li>Annual treatment costs in U.S. - inpatient ~$1.6 billion, outpatient ~$40 million (Niederman et al, 1999) </li></ul><ul><li>Almost 7 million prescriptions written annually for ABX related to bronchitis = 11% of total ABX prescriptions (Gonzalez et al, 1997) </li></ul>
  19. 19. ABECB Common Pathogens Fredrick, AM, et al. Clin Ther 2001; 23: 1683-1706.
  20. 20. ABECB TREATMENT STRATEGIES <ul><li>Simple </li></ul><ul><ul><li>Increased dyspnea, sputum, sputum purulence </li></ul></ul><ul><ul><li>1st line: Amox, Doxy, TMP-SMX </li></ul></ul><ul><ul><li>Alternatives: Amox-Clav, FQ, macrolide, 2nd generation Ceph </li></ul></ul><ul><li>Complicated </li></ul><ul><ul><li>Above Sx plus 1 of: frequent exacerbations, co-morbidity, age >65, chronic bronchitis >10 yr </li></ul></ul><ul><ul><li>1st line: FQ </li></ul></ul><ul><ul><li>Alternative: Amox-Clav, 2nd-3rd generation Ceph, newer macrolide; consider hospitalization and iv Rx </li></ul></ul><ul><li>Chronic </li></ul><ul><ul><li>Above plus continuous year-round production of purulent sputum </li></ul></ul><ul><ul><li>1st line: Cipro + Amox-Clav </li></ul></ul><ul><ul><li>Alternative: consider hospitalization and iv Rx </li></ul></ul>
  21. 21. OTITIS MEDIA COMMON PATHOGENS
  22. 22. ACUTE OTITIS MEDIA DIAGNOSIS <ul><li>Acute onset </li></ul><ul><li>Signs of middle ear effusion </li></ul><ul><li>Signs and symptoms of middle-ear inflammation </li></ul>AAP. Pediatrics 2004;113:1451-54.
  23. 23. ACUTE OTITIS MEDIA MANAGEMENT <ul><li>Pain management </li></ul><ul><li>Observation if: </li></ul><ul><ul><li>>2 y old </li></ul></ul><ul><ul><li>Non-severe illness </li></ul></ul><ul><ul><li>Ready means of communication </li></ul></ul><ul><ul><li>Able to re-evaluate within 48-72 h if not improved </li></ul></ul><ul><ul><li>Ability to obtain medications in timely manner </li></ul></ul><ul><li>Antibacterial therapy </li></ul><ul><ul><li>Amoxicillin 80-90 mg/kg/d </li></ul></ul><ul><ul><ul><li>Alternatives include cephalosporins or newer macrolides </li></ul></ul></ul><ul><ul><li>Amoxicillin-clavulanate 90 mg/kg/d for treatment failures </li></ul></ul>AAP. Pediatrics 2004;113:1451-54.
  24. 24. SINUSITIS COMMON PATHOGENS Pfaller et al. AJM 2001; 111: 4S.
  25. 25. SINUSITIS DIAGNOSIS <ul><li>Most important criterion is persistence of nasal purulence for >14 days, associated with daytime cough </li></ul><ul><li>Sinus pressure and tenderness are nonspecific markers </li></ul>
  26. 26. SINUSITIS TREATMENT <ul><li>Systematic review of 32 trials involving >7000 patients acute maxillary sinusitis => </li></ul><ul><li>Penicillin and amoxicillin better than placebo </li></ul><ul><li>No significant difference in cure rate between classes of antibiotics for the following comparisons: </li></ul><ul><ul><li>Newer non-penicillin antibiotics versus penicillins </li></ul></ul><ul><ul><li>Newer non-penicillin antibiotics versus amoxicillin-clavulanate </li></ul></ul>Tang. Ann EM 2003.
  27. 27. PNEUMONIA COMMON PATHOGENS <ul><li>Streptococcus pneumoniae </li></ul><ul><li>Haemophilus influenzae </li></ul><ul><li>Moraxella catarrhalis </li></ul><ul><li>Legionella pneumophila </li></ul><ul><li>Mycoplasma pneumoniae </li></ul><ul><li>Chlamydia pneumoniae </li></ul>
  28. 28. PNEUMONIA LIKELY PATHOGENS <ul><li>Alcoholism - S. pneumoniae, anaerobes </li></ul><ul><li>COPD and/or smoking - S. pneumoniae, H. influenzae, M. catarrhalis, Legionella species </li></ul><ul><li>Poor dental hygiene - anaerobes </li></ul><ul><li>Elderly - S. pneumoniae, Legionella spp. </li></ul><ul><li>HIV infection (early stage) - S. pneumoniae, H. influenzae, M. tuberculosis, S. aureus, P. aeruginosa </li></ul><ul><li>HIV infection (late stage) - above plus P. jerovici (carinii), Cryptococcus, Histoplasma spp. </li></ul><ul><li>Corticosteroid therapy - S. pneumoniae , L. pneumophila , P. aeruginosa </li></ul>
  29. 29. PNEUMONIA LIKELY PATHOGENS <ul><li>Suspected large-volume aspiration - anaerobes (chemical pneumonitis, obstruction) </li></ul><ul><li>Structural disease of lung (bronchiectasis, cystic fibrosis, etc.) - P. aeruginosa, Burkholderia cepacia, S. aureus </li></ul><ul><li>Injection drug use - S. aureus, anaerobes, M. tuberculosis, S. pneumoniae </li></ul><ul><li>Airway obstruction - anaerobes, S. pneumoniae H. influenzae, S. aureus </li></ul><ul><li>Recent hospitalization - S . aureus , P. aeruginosa , enteric Gram-negative bacilli </li></ul>
  30. 30. PNEUMONIA LIKELY PATHOGENS <ul><li>Nursing home residency - S. pneumoniae , gram-negative bacilli, H. influenzae, S. aureus, anaerobes, C. pneumoniae </li></ul><ul><li>Influenza active in community - influenza, S. pneumoniae, S. aureus, S. pyogenes, H. influenzae </li></ul><ul><li>Epidemic legionnaires' disease - Legionella spp. </li></ul><ul><li>Exposure to bats or soil enriched with bird droppings - H. capsulatum, C. neoformans </li></ul><ul><li>Exposure to birds - Chlamydia psittaci </li></ul><ul><li>Exposure to rabbits - Francisella tularensis </li></ul><ul><li>Travel to southwestern US - Coccidioides spp. </li></ul><ul><li>Exposure to farm animals or parturient cats - Coxiella burnetii (Q fever) </li></ul>
  31. 31. PNEUMONIA MANAGEMENT
  32. 32. UTI DIAGNOSIS <ul><li>Leukocyte esterase test ~80-90% sensitive, nitrite test ~50% sensitive compared with quantitative culture with greater than or equal to 10 5 cfu </li></ul><ul><ul><li>False-negative nitrite test results may occur with: </li></ul></ul><ul><ul><ul><li>low levels of bacteriuria </li></ul></ul></ul><ul><ul><ul><li>patients taking diuretics </li></ul></ul></ul><ul><ul><ul><li>patients on a low-nitrate diet </li></ul></ul></ul><ul><ul><ul><li>infections with bacteria that do not reduce nitrates </li></ul></ul></ul><ul><ul><li>Combining both tests improves sensitivity => 85-90% </li></ul></ul><ul><li>Specificity ~ 95% for both </li></ul>
  33. 33. UTI COMMON PATHOGENS
  34. 34. UTI TREATMENT <ul><li>Acute uncomplicated cystitis </li></ul><ul><ul><li>3-day treatment with TMP/SMX, FQ </li></ul></ul><ul><li>Recurrent cystitis </li></ul><ul><ul><li>Treat relapse with 7-day course of FQ, otherwise treat as acute uncomplicated </li></ul></ul><ul><li>Acute pyelonephritis </li></ul><ul><ul><li>2-week course </li></ul></ul>
  35. 35. ANTIBIOTIC OVERUSE <ul><li>Of 6.5 million ABX prescriptions written in 1992 for children younger than 18 (Nyquist AC et al. JAMA 1998;279:875-877.): </li></ul><ul><ul><li>12% for colds </li></ul></ul><ul><ul><li>9% for URI or nasopharyngitis </li></ul></ul><ul><ul><li>9% for bronchitis </li></ul></ul><ul><li>In Kentucky study (Mainous AG et al. J Fam Pract 1996;42:357-61): </li></ul><ul><ul><li>60% of patients with common cold received ABXs </li></ul></ul><ul><ul><li>Estimated $37.5 million spent for ABX prescriptions in U.S. annually for common cold </li></ul></ul>
  36. 38. PATIENT <ul><li>43 year old male presents with cough x 3 days </li></ul>
  37. 39. PATIENT
  38. 40. PATIENT
  39. 41. ANTIBIOTIC FAILURE <ul><li>Persistent or new fever or other signs of infection </li></ul><ul><li>Persistent laboratory abnormalities </li></ul><ul><li>Development of sepsis or other organ involvement </li></ul><ul><li>Persistent isolation of organism from culture </li></ul>
  40. 42. ANTIBIOTIC FAILURE <ul><li>Antibiotic-related </li></ul><ul><ul><li>Compliance </li></ul></ul><ul><ul><li>Wrong agent </li></ul></ul><ul><ul><li>Wrong dose </li></ul></ul><ul><ul><li>Drug interactions </li></ul></ul><ul><ul><li>Poor tissue penetration </li></ul></ul>
  41. 43. ANTIBIOTIC FAILURE <ul><li>Host-related </li></ul><ul><ul><li>Immunologic defect </li></ul></ul><ul><ul><li>Anatomic defect </li></ul></ul><ul><ul><li>Foreign body </li></ul></ul>
  42. 44. ANTIBIOTIC FAILURE <ul><li>Organism-related </li></ul><ul><ul><li>Emergence of resistance </li></ul></ul><ul><ul><li>Pre-existing co-infection </li></ul></ul><ul><ul><li>Superinfection </li></ul></ul>
  43. 50. CONTROLLING OUTPATIENT RESISTANCE <ul><li>Explain that unnecessary antibiotics may be harmful </li></ul><ul><li>Share the facts </li></ul><ul><li>Build cooperation and trust </li></ul><ul><li>Encourage active management of the illness </li></ul><ul><li>Be confident with recommendations to use alternative treatments </li></ul><ul><li>Start the educational process in the waiting room ( www.cdc.gov/ncidod/dbmd/antibioticresistance ) </li></ul><ul><li>Involve office personnel in the process </li></ul>
  44. 51. VIRAL PRESCRIPTION PAD http://www.cdc.gov/drugresistance/technical/prevention_tools.htm
  45. 52. CONTROLLING INPATIENT RESISTANCE <ul><li>Alcohol hand rubs </li></ul><ul><li>Isolation procedures </li></ul><ul><li>Prescription restrictions </li></ul><ul><li>Computer-assisted prescribing </li></ul><ul><li>Cycling antibiotics? </li></ul>
  46. 53. ANTIBIOTIC RESISTANCE

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