THE JUDICIOUS USE OF ANTIBIOTICS

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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. 199393
(suppl)15-24. Barry AL. AAC. 1994382419-25.
Washington JA. DMID. 199625183-190. Thornsberry
C. DMID 199729249-57 Doern GV. AAC.
1996401208-13. Thornsberry C. JAC
199944749-59.
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PRINCIPLES OFINFECTIOUS DISEASES

• Make the correct Dx
• Use ABX only when it is anticipated that they
  will substantially improve health outcomes
• Use the appropriate ABX for the likely or proven
  organisms
• Know your local ABX resistance patterns
• Recognize when ABX must be used immediately vs
  when they may be delayed
• Know the limitations of the microbiology lab
• Recognize when special treatment is needed and
  when it is not (e.g., cidal therapy, double
  coverage, surgery)
• Know the natural and ABX-modified Hx of
  infectious diseases
• Anticipate reasons for perceived or real failure
  of ABX

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INFECTIOUS DISEASES

• Syndrome
• Host
• Likely pathogens
• Antibiotic options

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CASE 1

• Patient presents with fever, MS change, diarrhea
  x 1 day
• What is fever?
• Mackowiak (1992)
• Oral temps 35.6-38.2, with diurnal variation (low
  at 6 a.m., high at 4-6 p.m.)
• 99th percentile 37.2 in a.m., 37.7 in p.m.

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CASE 1

• Evaluate host
• 62 yo male, COPD (steroid-dependent),
  bronchiectasis, DM (poorly controlled), hep C
• Admitted 12 weeks ago with GI bleed, ascites
  encephalopathy, D/C'd to NH on lactulose,
  H2-blocker, Cipro in addition to baseline meds
• Diarrheal illness in NH

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CASE 1

• DDx
• Empiric Rx?
• Recognize when ABX must be used immediately vs
  when they may be delayed

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WHEN IS EMERGENT ABX RX NEEDED?

• Bacterial meningitis
• Sepsis
• Meningococcemia
• Neutropenic fever ()
• Toxic shock/strep
• Necrotizing fasciitis

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CASE 1

• Exam
• Not toxic-appearing, confused
• Fundi benign
• Coarse rhonchi
• Hyperactive bowel sounds
• Stiff neck, no focal neurologic findings
• What next?
• LP WBC 85 (90 lymphs), protein 35, glucose
  48/84, lactic acid 1.2, gram stain negative
• Empiric Rx?
• Use ABX only when it is anticipated that they
  will substantially improve health outcomes

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CASE 2

• Patient returns 2 months later with fever, pain,
  redness, swelling behind left knee
• DDx
• Exam
• Not toxic-appearing, cellulitis
• Likely pathogens?
• Staphylococcus aureus
• Streptococcus pyogenes
• Gram-negatives
• Anaerobes

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CASE 2
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CASE 2

• ABX Rx?
• Started on Amox-Clav
• Continued fever, worsening extent and severity of
  erythema after 24 hours
• Know the natural and ABX-modified Hx of
  infectious diseases
• Changed to Cipro/Clinda
• Defervesced after 24 hours on Cipro/Clinda
• Recrudescence of fever 4 days later
• What we have here is a failure to eradicate?
• Anticipate reasons for perceived or real failure
  of ABX

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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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CASE 3

• Admitted for C. difficile colitis
• D/Cd after 1 week stay
• Returns to ED 3 days later with cough
• History?
• Exam
• Coarse rhonchi

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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 gt65, chronic bronchitis gt10 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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CASE 3
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CASE 3
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PNEUMONIAMANAGEMENT
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CASE 3

• Sputum Cx ? Pseudomonas aeruginosa
• Know the limitations of the microbiology lab

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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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CASE 3

• Double-coverage?
• Enterococcal endocarditis
• TB and other mycobacterial infections
• HIV
• Pseudomonas bacteremia/PNA
• ? Enterobacter
• S. aureus prosthesis infection
• Hep C
• Cryptococcal meningitis in AIDS