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THE JUDICIOUS USE OF ANTIBIOTICS. “New medicines, and new methods of cure, always work miracles for a while ” - William Heberden, 1802. INCREASING RESISTANCE IN THE US.

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THE JUDICIOUS USE OF ANTIBIOTICS


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    1. THE JUDICIOUS USE OF ANTIBIOTICS “New medicines, and new methods of cure, always work miracles for a while” - William Heberden, 1802 AIM Infectious Diseases Workshop

    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. AIM Infectious Diseases Workshop

    3. INFECTIOUS DISEASES • Syndrome • Host • Likely pathogens • Antibiotic options AIM Infectious Diseases Workshop

    4. SYNDROME • First distinguish infectious from non-infectious • Allergy • Malignancy • Autoimmune • Drugs AIM Infectious Diseases Workshop

    5. SYNDROMEANATOMY/ORGAN SYSTEM • Site of infection influences • Likely pathogens • ABX activity - penetration, pH, foreign body • Need for ‘cidal’ vs ‘static’ therapy AIM Infectious Diseases Workshop

    6. SYNDROMEANATOMY/ORGAN SYSTEM • General - FUO, adenopathy • Skin/soft tissue - cellulitis, wound infection, necrotizing fasciitis • CNS - meningitis, encephalitis, brain abscess • HEENT - sinusitis, otitis, pharyngitis, abscess • Respiratory - bronchitis, pneumonia • CV - endocarditis, phlebitis, bacteremia, catheter-related AIM Infectious Diseases Workshop

    7. SYNDROMEANATOMY/ORGAN SYSTEM • Abdominal - peritonitis, abscess, cholecystitis/cholangitis, appendicitis • Urinary tract - cystitis, pyelonephritis, perinephric abscess • Genital tract - urethritis, cervicitis, PID, prostatitis • Musculoskeletal - pyomyositis, osteomyelitis, septic arthritis AIM Infectious Diseases Workshop

    8. HOST • Demographics - age, habits • Exposure - sick contacts, residence/travel, hospitalization/institutionalization • Co-morbidities - immunosuppression, organ dysfunction, surgery, foreign bodies • Prior antibiotic use AIM Infectious Diseases Workshop

    9. LIKELY PATHOGENS • Based on syndrome and host AIM Infectious Diseases Workshop

    10. ISOLATION/IDENTIFICATION • Real vs contaminant • Possible presence of others AIM Infectious Diseases Workshop

    11. SUSCEPTIBILITY • Testing may not take into account: • Inoculum effect • ABX concentrations at site of infection • Subpopulations • Repressed but inducible genes AIM Infectious Diseases Workshop

    12. ANTIBIOTIC USAGE PRINCIPLES • Use narrow spectrum when possible • Use older agent when feasible • Use combination therapy only when indicated AIM Infectious Diseases Workshop

    13. ANTIBIOTIC OPTIONS • Staphylococcus aureus • MSSA - antistaphylococcal PCN, 1st or 3rd generation ceph, clindamycin, macrolide, carbapenem • MRSA - vancomycin, linezolid, daptomycin AIM Infectious Diseases Workshop

    14. ANTIBIOTIC OPTIONS • Streptococcus pyogenes • PCN, 1st or 3rd generation ceph, clindamycin, macrolide • Streptococcus pneumoniae • PSSP - PCN, 1st or 3rd generation ceph, clindamycin, macrolide, doxy • PRSP - newer quinolone, 3rd generation ceph, vancomycin AIM Infectious Diseases Workshop

    15. ANTIBIOTIC OPTIONS • Enterococci • PCN-susceptible - PCN/amp ± AGC • PCN-resistant - vancomycin or daptomycin ± AGC • VRE - linezolid, quinopristin/dalfopristin, teicoplanin, daptomycin • AGC-resistant - high-dose continuous infusion PCN/amp AIM Infectious Diseases Workshop

    16. ANTIBIOTIC OPTIONS • Gram-negative rods • Older quinolones, TMP/SMX, 2nd and 3rd generation ceph, beta-lactam/beta-lactamase inhibitor combinations, carbapenem • SPACEY - inducible extended spectrum beta-lactamase production AIM Infectious Diseases Workshop

    17. ANTIBIOTIC OPTIONS • Anaerobes • Metronidazole, clindamycin, beta-lactam/beta-lactamase inhibitor combinations, carbapenem AIM Infectious Diseases Workshop

    18. ABECB • Annual treatment costs in U.S. - inpatient ~$1.6 billion, outpatient ~$40 million (Niederman et al, 1999) • Almost 7 million prescriptions written annually for ABX related to bronchitis = 11% of total ABX prescriptions (Gonzalez et al, 1997) AIM Infectious Diseases Workshop

    19. ABECBCommon Pathogens Fredrick, AM, et al. Clin Ther 2001; 23: 1683-1706. AIM Infectious Diseases Workshop

    20. ABECBTREATMENT STRATEGIES • Simple • Increased dyspnea, sputum, sputum purulence • 1st line: Amox, Doxy, TMP-SMX • Alternatives: Amox-Clav, FQ, macrolide, 2nd generation Ceph • Complicated • Above Sx plus 1 of: frequent exacerbations, co-morbidity, age >65, chronic bronchitis >10 yr • 1st line: FQ • Alternative: Amox-Clav, 2nd-3rd generation Ceph, newer macrolide; consider hospitalization and iv Rx • Chronic • Above plus continuous year-round production of purulent sputum • 1st line: Cipro + Amox-Clav • Alternative: consider hospitalization and iv Rx AIM Infectious Diseases Workshop

    21. OTITIS MEDIACOMMON PATHOGENS AIM Infectious Diseases Workshop

    22. ACUTE OTITIS MEDIADIAGNOSIS • Acute onset • Signs of middle ear effusion • Signs and symptoms of middle-ear inflammation AAP. Pediatrics 2004;113:1451-54. AIM Infectious Diseases Workshop

    23. ACUTE OTITIS MEDIAMANAGEMENT • Pain management • Observation if: • >2 y old • Non-severe illness • Ready means of communication • Able to re-evaluate within 48-72 h if not improved • Ability to obtain medications in timely manner • Antibacterial therapy • Amoxicillin 80-90 mg/kg/d • Alternatives include cephalosporins or newer macrolides • Amoxicillin-clavulanate 90 mg/kg/d for treatment failures AAP. Pediatrics 2004;113:1451-54. AIM Infectious Diseases Workshop

    24. SINUSITISCOMMON PATHOGENS Pfaller et al. AJM 2001; 111: 4S. AIM Infectious Diseases Workshop

    25. SINUSITISDIAGNOSIS • Most important criterion is persistence of nasal purulence for >14 days, associated with daytime cough • Sinus pressure and tenderness are nonspecific markers AIM Infectious Diseases Workshop

    26. SINUSITISTREATMENT Systematic review of 32 trials involving >7000 patients acute maxillary sinusitis => • Penicillin and amoxicillin better than placebo • No significant difference in cure rate between classes of antibiotics for the following comparisons: • Newer non-penicillin antibiotics versus penicillins • Newer non-penicillin antibiotics versus amoxicillin-clavulanate Tang. Ann EM 2003. AIM Infectious Diseases Workshop

    27. PNEUMONIACOMMON PATHOGENS • Streptococcus pneumoniae • Haemophilus influenzae • Moraxella catarrhalis • Legionella pneumophila • Mycoplasma pneumoniae • Chlamydia pneumoniae AIM Infectious Diseases Workshop

    28. PNEUMONIALIKELY PATHOGENS • Alcoholism - S. pneumoniae, anaerobes • COPD and/or smoking - S. pneumoniae, H. influenzae, M. catarrhalis, Legionella species • Poor dental hygiene - anaerobes • Elderly - S. pneumoniae, Legionella spp. • HIV infection (early stage) - S. pneumoniae, H. influenzae, M. tuberculosis, S. aureus, P. aeruginosa • HIV infection (late stage) - above plus P. jerovici (carinii), Cryptococcus, Histoplasma spp. • Corticosteroid therapy - S. pneumoniae, L. pneumophila ,P. aeruginosa AIM Infectious Diseases Workshop

    29. PNEUMONIALIKELY PATHOGENS • Suspected large-volume aspiration - anaerobes (chemical pneumonitis, obstruction) • Structural disease of lung (bronchiectasis, cystic fibrosis, etc.) - P. aeruginosa, Burkholderia cepacia, S. aureus • Injection drug use - S. aureus, anaerobes, M. tuberculosis, S. pneumoniae • Airway obstruction - anaerobes, S. pneumoniae H. influenzae, S. aureus • Recent hospitalization - S. aureus, P. aeruginosa, enteric Gram-negative bacilli AIM Infectious Diseases Workshop

    30. PNEUMONIALIKELY PATHOGENS • Nursing home residency - S. pneumoniae, gram-negative bacilli, H. influenzae, S. aureus, anaerobes, C. pneumoniae • Influenza active in community - influenza, S. pneumoniae, S. aureus, S. pyogenes, H. influenzae • Epidemic legionnaires' disease - Legionella spp. • Exposure to bats or soil enriched with bird droppings - H. capsulatum, C. neoformans • Exposure to birds - Chlamydia psittaci • Exposure to rabbits - Francisella tularensis • Travel to southwestern US - Coccidioides spp. • Exposure to farm animals or parturient cats - Coxiella burnetii (Q fever) AIM Infectious Diseases Workshop

    31. PNEUMONIAMANAGEMENT AIM Infectious Diseases Workshop

    32. UTIDIAGNOSIS • Leukocyte esterase test ~80-90% sensitive, nitrite test ~50% sensitive compared with quantitative culture with greater than or equal to 105 cfu • False-negative nitrite test results may occur with: • low levels of bacteriuria • patients taking diuretics • patients on a low-nitrate diet • infections with bacteria that do not reduce nitrates • Combining both tests improves sensitivity => 85-90% • Specificity ~ 95% for both AIM Infectious Diseases Workshop

    33. UTICOMMON PATHOGENS AIM Infectious Diseases Workshop

    34. UTITREATMENT • Acute uncomplicated cystitis • 3-day treatment with TMP/SMX, FQ • Recurrent cystitis • Treat relapse with 7-day course of FQ, otherwise treat as acute uncomplicated • Acute pyelonephritis • 2-week course AIM Infectious Diseases Workshop

    35. ANTIBIOTIC OVERUSE • Of 6.5 million ABX prescriptions written in 1992 for children younger than 18 (Nyquist AC et al. JAMA 1998;279:875-877.): • 12% for colds • 9% for URI or nasopharyngitis • 9% for bronchitis • In Kentucky study (Mainous AG et al. J Fam Pract 1996;42:357-61): • 60% of patients with common cold received ABXs • Estimated $37.5 million spent for ABX prescriptions in U.S. annually for common cold AIM Infectious Diseases Workshop

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    38. PATIENT • 43 year old male presents with cough x 3 days AIM Infectious Diseases Workshop

    39. PATIENT AIM Infectious Diseases Workshop

    40. PATIENT AIM Infectious Diseases Workshop

    41. ANTIBIOTIC FAILURE • Persistent or new fever or other signs of infection • Persistent laboratory abnormalities • Development of sepsis or other organ involvement • Persistent isolation of organism from culture AIM Infectious Diseases Workshop

    42. ANTIBIOTIC FAILURE • Antibiotic-related • Compliance • Wrong agent • Wrong dose • Drug interactions • Poor tissue penetration AIM Infectious Diseases Workshop

    43. ANTIBIOTIC FAILURE • Host-related • Immunologic defect • Anatomic defect • Foreign body AIM Infectious Diseases Workshop

    44. ANTIBIOTIC FAILURE • Organism-related • Emergence of resistance • Pre-existing co-infection • Superinfection AIM Infectious Diseases Workshop

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    50. CONTROLLING OUTPATIENT RESISTANCE • Explain that unnecessary antibiotics may be harmful • Share the facts • Build cooperation and trust • Encourage active management of the illness • Be confident with recommendations to use alternative treatments • Start the educational process in the waiting room (www.cdc.gov/ncidod/dbmd/antibioticresistance) • Involve office personnel in the process AIM Infectious Diseases Workshop