Community Acquired Pneumonia: Is Penicillin Resistance Relevant?

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Community Acquired Pneumonia Is Penicillin
Resistance Relevant?

• Edward L. Goodman, MD, FACP, FIDSA, FSHEA
• June 30, 2008

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Outline of Presentation

• Complexities of treating CAP
• Microbial Spectrum of CAP
• IDSA Guidelines
• Rationale for Guidelines
• Questions to CMS
• Responses from CMS
• Implications of CMS Responses

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Basic Diagnostic Criteria

• History
• Cough
• Fever
• Sputum production
• Pleurisy
• Physical Exam
• Altered breath sounds/percussion
• Rales
• Imaging CXR (PA/Lat if possible) CT not usually
  required
• Pulse Oximetry

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Need For ICU Admission1 major or 3 minor
criteriaMandell LA et al.IDSA/ATS Consensus
Guidelines. Clin Inf Dis 200744S27-72
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ID Society/ATS Practice GuidelinesCID 200744S45

• Recommended empirical antibiotics for community
  acquired pneumonia
• Inpatients, non ICU treatment
• A respiratory FQ (level 1)
• A beta lactam plus a macrolide (level 1)
• Inpatients, ICU treatment
• A beta lactam (cefotaxime, ceftriaxone, amp/sulb)
  plus either azithromycin (level 2) or respiratory
  FQ (level 1)
• For pen allergic, aztreonam and respiratory FQ
• These Guidelines are the basis for CMS Scorecards
• Failure to comply leads to diminished hospital
  reimbursement
• Public reporting of compliance has started in
  2008

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Rationale for IDSA/ATS Guidelines

• Increasing Penicillin resistance
• Need for atypical coverage
• Availability of FQs which
• Are highly bioavailable
• Cover atypicals
• Are rapidly bactericidal

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Why Add Macrolide to Beta Lactam?

• To cover atypical pathogens which Beta Lactams
  dont cover
• Chlamydophilia
• Mycoplasma
• Legionella

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Why Add Macrolides?

• Added benefit beyond antimicrobial effects?
• Several retrospective studies suggested better
  outcomes when macrolide added to beta lactam for
  bacteremic Pneumococcal pneumonia
• Etiology not in doubt
• Postulated immunomodulatory effect
• Recent prospective study partially confirmed
• Baddour, Yu et al 2004

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Am J Respir Crit Care Med 2004170440
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Baddour L, Yu V et al. Combination Antibiotic
Therapy Lower Mortality among Severely Ill
Patients with Pneumococcal Bacteremia. Am J Resp
Crit Care Med 2004 170440
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What About Increasing Resistance to Penicillin?

• In 1968 we used Procaine Pen G 600,000 IM BID for
  CAP (presumed pneumococcal pneumonia)
• Much data on rising MICs for Strep pneumoniae
• FQs activity not related to Pen non
  susceptibility

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Distribution of Streptococcus pneumoniaeAntimicro
bial Resistance Across the US
Doern G et al. J Infect 200448(1)56-65.
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Net Effect

• Every febrile patient in ED with the slightest
  abnormal CXR gets Levaquin or Avelox!
• Heavily promoted by drug makers
• IDSA Guidelines indirectly encourage it
• Resistance to FQ rising at an alarming rate among
  E coli and Pseudomonas
• Rising rates of C diff and MRSA can be
  attributed, in part, to FQ pressure

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2004 Antibiogram PHD
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2007 PHD
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Is Penicillin Resistance Relevant in Treating CAP?

• Clearly in Pneumococcal meningitis resistance is
  critical
• Poor penetration into CSF by penicillin
• Immunologically privileged sanctuary
• No complement
• Minimal immunoglobulin
• Not relevant in pneumonia or bacteremia

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Clinical Infectious Disease 200337230
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To Recap

• IDSA/ATS Guidelines are basis for scorecards
  judging adequacy of therapy for CAP
• These Guidelines favor monotherapy with
  Fluoroquinolones
• FQ resistance and collateral damage rising
• Penicillin resistance redefined irrelevant
  for CAP and bacteremia

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Solution?

• Amoxicillin/clav (Augmentin XR) 2 gm po BID (with
  macrolide on admission)
• ampicillin/sulbactam IV is included in IDSA/ATS
  guidelines
• Amox/clav microbiologically equivalent for
  respiratory pathogens
• Serum levels of 2 gm amox well above MIC for
  Strep pneumo
• Therefore, less pressure to use FQ

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Query to Dale Bratzler, DOCMS consultant 5/14/08

• For empiric Rx of non-ICU CAP, why not use po
  Amoxicillin/clavulanate XR (plus an oral
  macrolide) for those patients who could take an
  oral regimen?
• For non-ICU CAP where the etiology is known with
  reasonable certainty, will specific therapy be a
  fallout if it is not in the IDSA/ATS Guidelines?

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Responses from Dr. Bratzler

• With the exception of oral fluoroquinolones,
  oral antibiotics are not recommended for the
  treatment of hospitalized patients with pneumonia
  at least not initial therapy.
• I am not sure of the exact bioavailability of
  Augmentin, but it is not recommended in the
  Guidelines and will not be in the pneumonia
  performance measure.
• I think this is a fine choice for an outpatient.
  I am not aware of studies of treatment of
  inpatient pneumonia with .Augmentin.

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Bratzler - continued

• if a patient has a positive test for a pathogen
  (and the test result is available to the
  physician within the first 24 hours of
  admission), the case is excluded from the
  antibiotic selection performance measure.

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Can We Refute Bratzler?

• I think this is a fine choice for an outpatient.
  I am not aware of studies of treatment of
  inpatient pneumonia with .Augmentin

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Augmentin XR Package Insert

• Four randomized, controlled, double blind and one
  non comparative studies in adults with CAP
• In comparative studies 904 patients
• In non-comparative study 1122 patients
• Dose Amoxicillin 2 gm/clavulanate 125 mg po BID
• Results
• Comparative 86.3 - 94.7 clinical success
• Non comparative 85.6 clinical success

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Augmentin XR Package InsertClinically Evaluable
with Reduced Susceptibility to Penicillin
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Should I Appeal to CMS?Gustave Dore 1863 Don
Quixote Tilting at Windmills
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Rapid Detection of Etiology

• if a patient has a positive test for a pathogen
  (and the test result is available to the
  physician within the first 24 hours of
  admission), the case is excluded from the
  antibiotic selection performance measure.
• Excluded from report cards!
• Less need for broad spectrum, empiric therapy
  e.g., fluoroquinolones
• Only two current rapid diagnostic tests exist
• Sputum gram stain
• Urine Pneumococcal Antigen test

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Musher DM et al. Diagnostic Value of Microscopic
Examination of Gram-stained Sputum and Sputum
Cultures in Patients with Bacteremia Pneumococcal
Pneumonia. Clin Inf Dis 200439165-9
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Musher. CID 200439165-9
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Pneumococcal Urine Antigen

• Sensitivity 70-80
• Specifitygt90
• False positives
• In children
• Recently vaccinated
• Remains positive for several weeks

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Conclusions

• Urine Antigen on all cases of CAP
• If positive
• consider treatment with amoxicillin 1 gm po TID
  or IV ampicillin 1 gm Q6H
• Not included in calculation of score cards
• If negative
• Follow IDSA Practice Guidelines
• Obtain induced sputum for gram stain and culture
• Lower sensitivity requires initial adherence to
  IDSA/ATS Guidelines
• Allows potential for pathogen identification
• allows sensitivity tests
• Allows switch to narrow spectrum therapy i.e.,
  amoxicillin

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ID Society/ATS Practice GuidelinesCID 200744S45
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ID Society/ATS Practice GuidelinesCID 200744S45

• Recommended empirical antibiotics for community
  acquired pneumonia
• Inpatients, non ICU treatment
• A respiratory FQ (level 1)
• A beta lactam plus a macrolide (level 1)
• Inpatients, ICU treatment
• A beta lactam (cefotaxime, ceftriaxone, amp/sulb)
  plus either azithromycin (level 2) or respiratory
  FQ (level 1)
• For pen allergic, aztreonam and respiratory FQ

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Bibliography

• Baddour LM, Yu VL et al. Combination Antibiotic
  Therapy Lowers Mortality among Severely Ill
  Patients with Pneumococcal Bacteremia. Am J Resp
  Crit Med 2004170440.
• Mandell LA, Wunderlink RG et al. Infectious
  Diseases Society of America/American Thoracic
  Society Consensus Guidelines on the Management of
  Community Acquired Pneumonia in Adults. Clin
  Infect Dis 200744S27-42.

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Bibliography

• Musher DM, Montoya R, Wanahita,A. Diagnostic
  Value of Microscopic Examination of Gram-Stained
  Sputum and Sputum Cultures in Patients with
  Bacteremia Pneumococcal Pneumonia. Clin Infect
  Dis 200439165.
• Werno AM, Murdoch Dr. Laboratory Diagnosis of
  Invasive Pneumococcal Disease. Clin Infect Dis
  200846926.
• Woodhead M. Community-Acquired Pneumonia
  Guidelines an International Comparison A View
  from Europe. Chest 1998113183.

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Bibliography

• Williamson, S (Personal Communication May 15,
  2008).
• Bratzler, D (Personal Communication May 15, 2008)