Outpatient Antibiotic Therapy

1

How Clinicians Use Data For Clinical Decision
Making March 5, 2003 Anti-Infective Drug
Advisory Committee
John Bradley, MD Childrens Hospital San Diego
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Clinicians Use of Data

• Clinical information
• Patient being treated
• Infection being treated
• Organism information from cultures (ID and
  susceptibility)
• Antibiotic PK, PD, toxicity characteristics of
  the FDA-approved agents which are active in vitro

3
Clinicians Use of Data

• FDA
• Review of data on safety and efficacy, with
  approval only for the particular indications
  submitted by the sponsor (no new indications for
  ampicillin!)
• The medical literature for preferred antibiotic
  therapy
• IDSA guidelines, AAP Redbook Committee, Sanford
  Guide, published clinical trials, etc.

4
Clinicians Use of Data

• Patient information
• Immune competence
• Age
• Co-morbidities
• Etc
• Clinical exam, laboratory (organ dysfunction
  information) and imaging studies

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Clinicians Use of Data
Safety and efficacy analysis of submitted data
FDA
Organism ID, and interpretations of
susceptibility, based on in vitro testing, and PD
Recommendations for clinicians for treating
patients for all infections, all abx
IDSA, others
NCCLS
CDC
Epidemiological evaluation of pathogens
(particularly resistant ones)
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Clinicians Use of Data

• Example 1
• A 12 year old with leukemia with neutropenia and
  pneumonia, grows Pseudomonas aeruginosa
  ceftazidime-resistant, meropenem- and
  ciprofloxacin-susceptible from a bronch wash
• I will treat with meropenem based on safety and
  efficacy in pediatric meningitis, and published
  adult and pediatric data on clinical efficacy of
  carbapenems in pneumonia

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Clinicians Use of Data

• Example 2 (pre-Haemophilus vaccine)
• 18 month old with periorbital cellulitis and
  bacteremia (with H. influenzae, type b), is being
  treated with ceftriaxone
• I am asked by a resident why I dont use i.v.
  TMP-SMZ, as he frequently uses this drug for H.
  flu in otitis.
• No published series exists on bacteremic
  infections caused by H. flu, treated with
  TMP-SMZ. I feel uncomfortable extrapolating from
  otitis efficacy to sepsis and cellulitis efficacy

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When Can You Extrapolate Efficacy?

• If you can successfully treat a difficult
  infection, you should be able to treat a simple
  infection

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When Can You Extrapolate Efficacy?

• Some infections are harder to treat based on
  penetration of antibiotic to the site of
  infection
• Poor drug penetration (intra-abdominal abscess,
  meningitis) vs excellent penetration (UTI,
  pneumonia)
• Seriousness of infection, spontaneous resolution
  of infection
• Meningitis or pneumonia (Fine Class V) vs. AECB
  or AOM
• Co-morbidities of patients
• Healthy young adult vs neutropenia, old age or
  neonate

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When Can You Extrapolate Safety?

• Safety of high dose anti-infectives in situations
  demonstrating borderline drug exposure to a
  pathogen in infected tissues

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When Can You Extrapolate Efficacy?

• We use published data on safety and efficacy for
  infections caused by a certain pathogen, consider
  the host and location of the infection,
  antibiotic toxicities and in vitro
  susceptibilities, as well as the risk of failure,
  to extrapolate efficacy in using an antibiotic
  which has not been previously studied for the
  type of infection or the patient population we
  are treating