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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
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
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
INFECTIOUS DISEASES
  • Syndrome
  • Host
  • Likely pathogens
  • Antibiotic options

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syndrome
SYNDROME
  • First distinguish infectious from non-infectious
    • Allergy
    • Malignancy
    • Autoimmune
    • Drugs

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syndrome anatomy organ system
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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syndrome anatomy organ system6
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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syndrome anatomy organ system7
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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slide8
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
LIKELY PATHOGENS
  • Based on syndrome and host

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isolation identification
ISOLATION/IDENTIFICATION
  • Real vs contaminant
  • Possible presence of others

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

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antibiotic options14
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 options15
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 options16
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 options17
ANTIBIOTIC OPTIONS
  • Anaerobes
    • Metronidazole, clindamycin, beta-lactam/beta-lactamase inhibitor combinations, carbapenem

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abecb
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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abecb common pathogens
ABECBCommon Pathogens

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

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abecb treatment strategies
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 media common pathogens
OTITIS MEDIACOMMON PATHOGENS

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acute otitis media diagnosis
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 media management
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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sinusitis common pathogens
SINUSITISCOMMON PATHOGENS

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

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sinusitis diagnosis
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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sinusitis treatment
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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pneumonia common pathogens
PNEUMONIACOMMON PATHOGENS
  • Streptococcus pneumoniae
  • Haemophilus influenzae
  • Moraxella catarrhalis
  • Legionella pneumophila
  • Mycoplasma pneumoniae
  • Chlamydia pneumoniae

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pneumonia likely pathogens
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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pneumonia likely pathogens29
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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pneumonia likely pathogens30
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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pneumonia management
PNEUMONIAMANAGEMENT

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uti diagnosis
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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uti common pathogens
UTICOMMON PATHOGENS

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uti treatment
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
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
PATIENT
  • 43 year old male presents with cough x 3 days

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patient39
PATIENT

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patient40
PATIENT

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antibiotic failure
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 failure42
ANTIBIOTIC FAILURE
  • Antibiotic-related
    • Compliance
    • Wrong agent
    • Wrong dose
    • Drug interactions
    • Poor tissue penetration

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antibiotic failure43
ANTIBIOTIC FAILURE
  • Host-related
    • Immunologic defect
    • Anatomic defect
    • Foreign body

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antibiotic failure44
ANTIBIOTIC FAILURE
  • Organism-related
    • Emergence of resistance
    • Pre-existing co-infection
    • Superinfection

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controlling outpatient resistance
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
VIRAL PRESCRIPTION PAD

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

controlling inpatient resistance
CONTROLLING INPATIENT RESISTANCE
  • Alcohol hand rubs
  • Isolation procedures
  • Prescription restrictions
  • Computer-assisted prescribing
  • Cycling antibiotics?

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antibiotic resistance
ANTIBIOTIC RESISTANCE

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