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Antibiotics: Principles and Illustrative Cases. Jake Nania, M.D. Pediatric Infectious Diseases February 2, 2006. Making wise antibiotic choices. #1 Know what you’re targeting! Send appropriate diagnostic studies before antibiotics are started

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Antibiotics principles and illustrative cases

Antibiotics: Principles and Illustrative Cases

Jake Nania, M.D.

Pediatric Infectious Diseases

February 2, 2006


Making wise antibiotic choices
Making wise antibiotic choices

#1 Know what you’re 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


Making wise antibiotic choices1
Making wise antibiotic choices

#2 Pathogen-specific factors

Know (or look up) susceptibility patterns for suspected organisms:

  • Best: Hospital Antibiogram, Pt’s 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…


Making wise antibiotic choices2
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 <18 years

      • Erythromycin, if < 2 weeks


Making wise antibiotic choices3
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 >PCNs, Ceph, Vanc > AG

      • Bloodstream: Azithromycin tissue >> blood levels


Making wise antibiotic choices4
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


Case 1 prophylaxis
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 soapthe 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
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
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
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 RR=40, T=102, 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?


Case 2
Case 2

  • Treatable Pathogens of concern:

    • Pneumococcus

    • Mycoplasma pneumoniae

    • S.aureus (including CA-MRSA)

    • Chlamydophila pneumoniae

    • GAS

    • H.flu, M.catarrhalis


Case 21
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 β-lactam allergy:

      • Clindamycin, vancomycin, or newer FQs


Empiric pneumonia therapy key points
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:

    • β-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
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”. HR=140, RR=30, BP=85/39, T=100.2. 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?


Case 3
Case 3

  • Pathogens of Concern:

    • Pneumococcus

    • Meningococcus

    • Also…

      • H.flu (undervaccinated?)

      • S.aureus

      • GAS

      • Rickettsial – R.rickettsii, Ehrlichia

      • Salmonella


Case 31
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


Case 32
Case 3

  • Work-up of note:

    • WBC=20.8 (80%N, 14%L, 5%M),Plt=585

    • CSF WBC=504 (94%N, 4%M), RBC=135

    • CSF Prot=67, Gluc=6

    • CSF Gram Stain: 2+PMNs, 2+ GPCs

    • CSF and Blood Cx: S.pneumoniae


Case 33
Case 3

  • Susceptibility panel of our patient’s S.pneumoniae isolate:

    Penicillin R

    Ceftriaxone I

    Clindamycin S

    Erythromycin S

    Vancomycin S

    Rifampin S


Case 34
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 β-lactam allergy:

      • Vancomycin plus Rifampin

      • ID consult!


Meningitis case key points
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 β-lactam allergy


Take home points
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


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


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