This document discusses the judicious use of antibiotics and increasing antibiotic resistance. It provides information on common infectious disease syndromes, likely pathogens, and antibiotic treatment options. It emphasizes using narrow-spectrum antibiotics when possible, older agents when feasible, and combination therapy only when necessary to help reduce antibiotic overuse and resistance.

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

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. INFECTIOUS DISEASES Syndrome Host Likely pathogens Antibiotic options

4. SYNDROME First distinguish infectious from non-infectious Allergy Malignancy Autoimmune Drugs

5. SYNDROME ANATOMY/ORGAN SYSTEM Site of infection influences Likely pathogens ABX activity - penetration, pH, foreign body Need for ‘cidal’ vs ‘static’ therapy

6. SYNDROME ANATOMY/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

7. SYNDROME ANATOMY/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

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

9. LIKELY PATHOGENS Based on syndrome and host

10. ISOLATION/IDENTIFICATION Real vs contaminant Possible presence of others

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

12. ANTIBIOTIC USAGE PRINCIPLES Use narrow spectrum when possible Use older agent when feasible Use combination therapy only when indicated

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

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

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

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

17. ANTIBIOTIC OPTIONS Anaerobes Metronidazole, clindamycin, beta-lactam/beta-lactamase inhibitor combinations, carbapenem

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)

19. ABECB Common Pathogens Fredrick, AM, et al. Clin Ther 2001; 23: 1683-1706.

20. ABECB TREATMENT 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

21. OTITIS MEDIA COMMON PATHOGENS

22. ACUTE OTITIS MEDIA DIAGNOSIS Acute onset Signs of middle ear effusion Signs and symptoms of middle-ear inflammation AAP. Pediatrics 2004;113:1451-54.

23. ACUTE OTITIS MEDIA MANAGEMENT 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.

24. SINUSITIS COMMON PATHOGENS Pfaller et al. AJM 2001; 111: 4S.

25. SINUSITIS DIAGNOSIS Most important criterion is persistence of nasal purulence for >14 days, associated with daytime cough Sinus pressure and tenderness are nonspecific markers

26. SINUSITIS TREATMENT 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.

27. PNEUMONIA COMMON PATHOGENS Streptococcus pneumoniae Haemophilus influenzae Moraxella catarrhalis Legionella pneumophila Mycoplasma pneumoniae Chlamydia pneumoniae

28. PNEUMONIA LIKELY 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

29. PNEUMONIA LIKELY 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

30. PNEUMONIA LIKELY 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)

31. PNEUMONIA MANAGEMENT

32. UTI DIAGNOSIS Leukocyte esterase test ~80-90% sensitive, nitrite test ~50% sensitive compared with quantitative culture with greater than or equal to 10 5 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

33. UTI COMMON PATHOGENS

34. UTI TREATMENT 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

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

38. PATIENT 43 year old male presents with cough x 3 days

39. PATIENT

40. PATIENT

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

42. ANTIBIOTIC FAILURE Antibiotic-related Compliance Wrong agent Wrong dose Drug interactions Poor tissue penetration

43. ANTIBIOTIC FAILURE Host-related Immunologic defect Anatomic defect Foreign body

44. ANTIBIOTIC FAILURE Organism-related Emergence of resistance Pre-existing co-infection Superinfection

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

51. VIRAL PRESCRIPTION PAD http://www.cdc.gov/drugresistance/technical/prevention_tools.htm

52. CONTROLLING INPATIENT RESISTANCE Alcohol hand rubs Isolation procedures Prescription restrictions Computer-assisted prescribing Cycling antibiotics?

53. ANTIBIOTIC RESISTANCE