# Presentation: 307838

**March 5, 2003**
**Anti-Infective Drug Advisory Committee**

**John Bradley, MD**
**Children’s Hospital San Diego**

## 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***

## 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.**

## Clinicians’ Use of Data

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

## Clinicians’ Use of Data

**FDA**

**IDSA, others**

**NCCLS**

**CDC**

**Safety and efficacy analysis of submitted data**

**Recommendations for clinicians for treating patients for all infections, all abx**

**Organism ID, and interpretations of susceptibility, based on in vitro testing, and PD **

**Epidemiological evaluation of pathogens (particularly resistant ones)**

## 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**

## 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 don’t 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**

## When Can You Extrapolate Efficacy?

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

## 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 **

## When Can You Extrapolate Safety?

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

## 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**