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Antibiotics: Principles and Illustrative Cases


Biliary tract: PCNs, doxycycline, ceftriaxone, FQs have high excretion ... therapy: High-dose oral amoxicillin, possibly azithromycin or doxycycline ... – PowerPoint PPT presentation

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Title: Antibiotics: Principles and Illustrative Cases

Antibiotics Principles and Illustrative Cases
  • Jake Nania, M.D.
  • Pediatric Infectious Diseases
  • February 2, 2006

Making wise antibiotic choices
  • 1 Know what youre targeting!
  • Send appropriate diagnostic studies before
    antibiotics are started
  • Empiric Rx based on likely organisms at suspected
    site of infection
  • e.g. Bacterial Meningitis
  • Adjust Rx based on info from the Micro Lab
  • Gram Stain should never narrow, only broaden Rx
  • Culture and susceptibilities

Making wise antibiotic choices
  • 2 Pathogen-specific factors
  • Know (or look up) susceptibility patterns for
    suspected organisms
  • Best Hospital Antibiogram, Pts previous
  • Good Regional Data (e.g.CDC)
  • Okay Published Series of Susceptibility Data
    (including the Sanford Guide)
  • Least Helpful The guy bringing breakfast to
    morning report
  • Know agents likely active against bacteria for
    which susceptibilities are not usually done
  • e.g. oral anaerobes
  • e.g. Mycoplasma pneumoniae

Making wise antibiotic choices
  • 3 Host-specific factors
  • How sick or vulnerable how aggressive
  • Previous antibiotic history and other risk
    factors for resistant organisms
  • Renal and Hepatic Function, GI absorption
  • Ensuring therapeutic levels
  • Avoiding toxicity
  • Previous Allergy or other adverse reactions
  • Age
  • Fluoroquinolones (FQ), if lt18 years
  • Erythromycin, if lt 2 weeks

Making wise antibiotic choices
  • 3 Host-specific factors (continued)
  • Site of infection
  • Meningitis clindamycin, macrolides, 1st/2nd gen
    ceph, aminoglycosides (AG) not good choices
  • Endocarditis bacteriocidal agent(s) needed
  • Abscesses AG less active
  • Biliary tract PCNs, doxycycline, ceftriaxone,
    FQs have high excretion
  • Bone FQ, Clinda gtPCNs, Ceph, Vanc gt AG
  • Bloodstream Azithromycin tissue gtgt blood levels

Making wise antibiotic choices
  • Other important factors
  • Toxicity (e.g. AG ? oto- and nephrotoxicity)
  • Cost (someone is paying for it!)
  • Ease of administration (frequency, palatability,
    parenteral vs. oral)
  • Avoiding selection of resistance
  • Narrowest spectrum agent to cover suspected
  • Having an endpoint in mind
  • Knowing when to stop

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Case 1 Prophylaxis
  • The patient is a 59 year old male scheduled to
    have CABG for advanced coronary disease. He is
    given mupirocin ointment to apply to his anterior
    nares for the 5 days leading up to surgery and
    asked to shower with chlorhexidine soap the night
    before surgery. As the first incision is made in
    the OR, a dose of cefazolin is started. After
    successful surgery, the patient is cared for in
    the SICU. Cefazolin is continued for 3 days
    while thoracostomy tubes are in place to prevent
    infection near the site of the tubes. The
    patient is eventually discharged from the
    hospital without an infection related to his stay.

Which are best practice and proven?
  • Nasal Mupirocin
  • Reduction in SSI shown for S.aureus carriers only
    (effect diluted out for entire group in study)
  • Chlorhexidine Shower
  • Most studies show no effect
  • Cefazolin in the OR
  • The timing was suboptimal. Clear benefit when
    given in the 30 minutes BEFORE incision
  • Cefazolin while chest tubes in place
  • Not supported by available data

Antibiotic Prophylaxis Key Points
  • Intuition is not a trustworthy guide
  • Guidelines often published, evidence-based
  • Surgical Site Infection Prevention
  • SBE Prophylaxis
  • PCP prevention in compromised hosts
  • Question standard practices
  • Risk-Benefit
  • Unaffected patient prophylaxis must be
    justified to outweigh cost and risks of toxicity,
    induction of resistance

Case 2 Empiric Therapy
  • A previously healthy 4 year old girl presents
    with 2 days of fever (102), wet cough and new
    onset of right pleuritic chest pain. Exam is
    significant for RR40, T102, O2 sat of 91, lack
    of upper resp findings and focal rales in the
    right base. CXR reveals a streaky RLL
  • What empiric antibiotics and why?

Case 2
  • Treatable Pathogens of concern
  • Pneumococcus
  • Mycoplasma pneumoniae
  • S.aureus (including CA-MRSA)
  • Chlamydophila pneumoniae
  • GAS
  • H.flu, M.catarrhalis

Case 2
  • Reasonable choices
  • cefuroxime (200-240mg/kg/day)
  • ceftriaxone or cefotaxime
  • Kaplan, SL et al. Pediatr Infect Dis J. 2001 Apr
    20(4) 392-6.
  • Yu, VL et al. Clinical ID. 2003 15 July 37
  • Add a macrolide?
  • For empiric mycoplasma/chlamydophila coverage
  • For dual therapy for pneumococcus?
  • If serious ß-lactam allergy
  • Clindamycin, vancomycin, or newer FQs

Empiric Pneumonia Therapy Key Points
  • Initial Rx based on likely pathogen how ill
  • Outpatient therapy High-dose oral amoxicillin,
    possibly azithromycin or doxycycline
  • Moderately Ill Inpatient
  • ß-lactams remain effective for pneumococcal
    infections outside CNS combo therapy?
  • In adults
  • Dual therapy for community-acquired pneumonia
  • FQs play much larger role
  • Severely Ill Inpatient Include MRSA coverage

Case 3 Empiric and Definitive Rx
  • Hx and Exam A 9 month old, previously healthy
    boy presents to the ER with a 12 hour history of
    poor PO intake, fever to 103, fussiness
    alternating with sleepiness. He has had a runny
    nose for 3 days prior to onset of presenting sx.
    Other family members have cold sx. No significant
    PMHx, but mom notes that he is behind on his
    shots. HR140, RR30, BP85/39, T100.2. Exam
    reveals a somnolent but responsive infant. Ant
    fontanelle is full. His peripheral capillary
    refill is about 3 seconds. The rest of the exam
    is normal.
  • You obtain Blood, CSF and Urine for evaluations.
    CSF is non-bloody and straw colored. Other info
  • What empiric antibiotics?

Case 3
  • Pathogens of Concern
  • Pneumococcus
  • Meningococcus
  • Also
  • H.flu (undervaccinated?)
  • S.aureus
  • GAS
  • Rickettsial R.rickettsii, Ehrlichia
  • Salmonella

Case 3
  • What to give first?
  • ceftriaxone/cefotaxime
  • How much?
  • A LOT
  • Dose 100 mg/kg/dose (q24 ceftriaxone/q8
  • When?
  • NOW!
  • After the cephalosporin?
  • Vancomycin Dose 60mg/kg/day

Case 3
  • Work-up of note
  • WBC20.8 (80N, 14L, 5M),Plt585
  • CSF WBC504 (94N, 4M), RBC135
  • CSF Prot67, Gluc6
  • CSF Gram Stain 2PMNs, 2 GPCs
  • CSF and Blood Cx S.pneumoniae

Case 3
  • Susceptibility panel of our patients
    S.pneumoniae isolate
  • Penicillin R
  • Ceftriaxone I
  • Clindamycin S
  • Erythromycin S
  • Vancomycin S
  • Rifampin S

Case 3
  • Definitive Rx
  • Ceph3 plus Vancomycin
  • Plus Rifampin?
  • If response to Rx is slow over first days
  • If steroids given (penetrates even uninflamed
  • If serious ß-lactam allergy
  • Vancomycin plus Rifampin
  • ID consult!

Meningitis Case Key points
  • In suspected bacterial meningitis/sepsis, treat
    ASAP (even before LP if it will be delayed
  • Vancomycin for suspected bacterial meningitis
  • Know antibiotic penetration for the tissue
  • The dose does matter!
  • Even though killing by Vanc and Cephalosporins is
    time-dependent, high doses needed for CSF
  • Ask for help with resistant organisms or serious
    ß-lactam allergy

Take-home Points
  • Prophylaxis consider carefully if benefits
    outweigh risks and look for evidence
  • Selection of an appropriate agent is multi-step
  • Identify possible site(s) of infection
  • DDx of organisms at that site
  • Local/Hospital susceptibility patterns
  • Penetration of agent into site
  • Misuse of Antibiotics has Societal Impact

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Mandell, Bennett, Dolin Principles and
Practice of Infectious Diseases, 6th ed.,2005
Churchill Livingstone Chapter 16 - Principles of
Anti-infective Therapy
Update of Practice Guidelines for the Management
of Community-Acquired Pneumonia in
Immunocompetent Adults Lionel A. Mandell,1
John G. Bartlett,2 Scott F. Dowell,3
Thomas M. File, Jr.,4 Daniel M. Musher,5 and
Cynthia Whitney3,a
As Antibiotic Discovery Stagnates ... A Public
Health Crisis Brews BAD BUGS, NO
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