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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

“New medicines, and new methods of cure, always work miracles for a while” - William Heberden, 1802

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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.

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INFECTIOUS DISEASES

  • Syndrome

  • Host

  • Likely pathogens

  • Antibiotic options

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SYNDROME

  • First distinguish infectious from non-infectious

    • Allergy

    • Malignancy

    • Autoimmune

    • Drugs

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SYNDROMEANATOMY/ORGAN SYSTEM

  • Site of infection influences

    • Likely pathogens

    • ABX activity - penetration, pH, foreign body

    • Need for ‘cidal’ vs ‘static’ therapy

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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

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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

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HOST

  • Demographics - age, habits

  • Exposure - sick contacts, residence/travel, hospitalization/institutionalization

  • Co-morbidities - immunosuppression, organ dysfunction, surgery, foreign bodies

  • Prior antibiotic use

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LIKELY PATHOGENS

  • Based on syndrome and host

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ISOLATION/IDENTIFICATION

  • Real vs contaminant

  • Possible presence of others

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SUSCEPTIBILITY

  • Testing may not take into account:

    • Inoculum effect

    • ABX concentrations at site of infection

    • Subpopulations

    • Repressed but inducible genes

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ANTIBIOTIC USAGE PRINCIPLES

  • Use narrow spectrum when possible

  • Use older agent when feasible

  • Use combination therapy only when indicated

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ANTIBIOTIC OPTIONS

  • Staphylococcus aureus

    • MSSA - antistaphylococcal PCN, 1st or 3rd generation ceph, clindamycin, macrolide, carbapenem

    • MRSA - vancomycin, linezolid, daptomycin

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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

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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

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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

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ANTIBIOTIC OPTIONS

  • Anaerobes

    • Metronidazole, clindamycin, beta-lactam/beta-lactamase inhibitor combinations, carbapenem

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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)

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ABECBCommon Pathogens

Fredrick, AM, et al. Clin Ther 2001; 23: 1683-1706.

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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

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OTITIS MEDIACOMMON PATHOGENS

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ACUTE OTITIS MEDIADIAGNOSIS

  • Acute onset

  • Signs of middle ear effusion

  • Signs and symptoms of middle-ear inflammation

AAP. Pediatrics 2004;113:1451-54.

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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.

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SINUSITISCOMMON PATHOGENS

Pfaller et al. AJM 2001; 111: 4S.

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SINUSITISDIAGNOSIS

  • Most important criterion is persistence of nasal purulence for >14 days, associated with daytime cough

  • Sinus pressure and tenderness are nonspecific markers

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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.

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PNEUMONIACOMMON PATHOGENS

  • Streptococcus pneumoniae

  • Haemophilus influenzae

  • Moraxella catarrhalis

  • Legionella pneumophila

  • Mycoplasma pneumoniae

  • Chlamydia pneumoniae

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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

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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

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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)

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PNEUMONIAMANAGEMENT

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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

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UTICOMMON PATHOGENS

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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

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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

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PATIENT

  • 43 year old male presents with cough x 3 days

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PATIENT

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PATIENT

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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

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ANTIBIOTIC FAILURE

  • Antibiotic-related

    • Compliance

    • Wrong agent

    • Wrong dose

    • Drug interactions

    • Poor tissue penetration

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ANTIBIOTIC FAILURE

  • Host-related

    • Immunologic defect

    • Anatomic defect

    • Foreign body

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ANTIBIOTIC FAILURE

  • Organism-related

    • Emergence of resistance

    • Pre-existing co-infection

    • Superinfection

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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

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VIRAL PRESCRIPTION PAD

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http://www.cdc.gov/drugresistance/technical/prevention_tools.htm


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CONTROLLING INPATIENT RESISTANCE

  • Alcohol hand rubs

  • Isolation procedures

  • Prescription restrictions

  • Computer-assisted prescribing

  • Cycling antibiotics?

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ANTIBIOTIC RESISTANCE

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