Antibiotics: Principles and Illustrative Cases

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Antibiotics Principles and Illustrative Cases

• Jake Nania, M.D.
• Pediatric Infectious Diseases
• February 2, 2006

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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
• READ UP and SEE MORE PATIENTS
• Adjust Rx based on info from the Micro Lab
• Gram Stain should never narrow, only broaden Rx
• Culture and susceptibilities

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Making wise antibiotic choices

• 2 Pathogen-specific factors
• Know (or look up) susceptibility patterns for
  suspected organisms
• Best Hospital Antibiogram, Pts previous
  cultures
• 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

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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

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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

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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
  organism
• 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.

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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

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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

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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
  infiltrate.
• What empiric antibiotics and why?

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Case 2

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

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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
  230-237.
• Add a macrolide?
• For empiric mycoplasma/chlamydophila coverage
• For dual therapy for pneumococcus?
• If serious ß-lactam allergy
• Clindamycin, vancomycin, or newer FQs

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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

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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
  pending.
• What empiric antibiotics?

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Case 3

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

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Case 3

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

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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

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Case 3

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

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Case 3

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

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Meningitis Case Key points

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

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Take-home Points

• Prophylaxis consider carefully if benefits
  outweigh risks and look for evidence
• Selection of an appropriate agent is multi-step
  process
• 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
http//home.mdconsult.com/das/book/54675379-2/view
/1259
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
DRUGS www.idsociety.org