Antibiotic Overuse

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Antibiotic Overuse Resistance

• Carolyn Bray
• April 11, 2006
• Sponsored By Dr. Craig Hoesley

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INTRODUCTION

• Antimicrobial resistance in the community.
• Penicillin-resistant Streptococcus pneumoniae
• Pediatrics Physician Parent Antibiotic
  Perceptions
• Pharmacotherapy Can we keep up with bacterial
  drug resistance?
• UAB Microbial Resistance 2005
• Combative strategies

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FACTORS CONTRIBUTING TO ANTIBIOTIC RESISTANCE

• Inappropriate antibiotic use
• Animal husbandry and agriculture
• Prolonged Hospitalization
• ICU Hospitalization
• Immunocompromised patient population
• Use of invasive devices and catheters

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AMBULATORY ANTIBIOTIC UTILIZATION

• Approximately 50 of outpatient antibiotic
  prescriptions are inappropriate.
• JAMA 1999
• In the US, acute respiratory tract infections are
  the indication for up to 75 of all antibiotics
  prescribed in an ambulatory setting.
• Approximately 50 of common colds URIs, and 80
  of bronchitis visits treated with antibiotics
  each year.
• Between 1980-1992 prescribing rates for more
  expensive, broad spectrum antibiotics (e.g.
  cephalosporins) tripled.
• Cochrane Collaboration Review 2006 Delayed
  prescriptions for infections where antibiotics
  were not immediately indicated reduces antibiotic
  use without increasing patient morbidity.

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PENICILLIN-RESISTANT STREPTOCOCCUS PNEUMONIAE

• Leading cause of CAP, meningitis, otitis media in
  the US.
• Excessive antibiotic use for ARIs is fueling an
  epidemic of community antibiotic-resistant
  bacteria.
• Major risk factor for carriage spread of
  resistant S. pneumoniae is prior antibiotic use.
• JAMA 1998
• Prior to 1980, 99 of all S. pneumoniae cases
  were susceptible to penicillin.
• In the past decade, 40 of isolates have
  intermediate to high penicillin resistance.
• Dagan 1998
• 19 of 120 children had a new pneumococcal isolate
  colonizing their nasopharynx within 3-4 days of
  treatment.
• In 16 of the 19 children, the isolate was
  resistant to the antibiotic the child was taking.

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PENICILLIN-RESISTANT STREPTOCOCCUS PNEUMONIAE

• JOI 2004
• B-lactam, Macrolide, Clindamycin, Tetracycline,
  and Bactrim resistance rates have reached
  unprecedented levels within S. pneumoniae
  isolates.
• 77 of PCN-resistant S. pneumoniae were also
  resistant to Erythromycin
• Highest rates of PCN-resistant S. pneumoniae
  (50.4) were observed in the Southeastern US.
• Fluoroquinolone resistance is beginning to emerge
  as a problem.
• CID 2004
• Of S. pneumoniae strains regarded as Levofloxacin
  susceptible, 59 possess a single-step mutation
  in the QRDR, which can easily mutate to further
  levels of fluoroquinolone nonsusceptibility.

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PEDIATRICS

• Children have the highest rates of antibiotic use
  and infection with antibiotic-resistant
  pathogens.
• JAMA 1998
• Colds, URIs, bronchitis account for over 20 of
  all antibiotic prescriptions despite lack of
  evidence that they improve outcome.
• Pediatrics 1999
• 336 Pediatricians and Family Physicians surveyed
• 97 believe antibiotic overuse contributes to
  resistance
• 86 of pediatricians and family physicians
  prescribe antibiotics for bronchitis, 42 for the
  common cold.
• Pediatrics 2004
• Physicians were 7 more likely to make a
  bacterial diagnosis and 21 more likely to
  prescribe antibiotics when they perceived parents
  expected them.

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PARENT PERCEPTION OF ANTIBIOTIC NECESSITY

• Pediatrics 1997
• 400 parents interviewed
• 58 of thought antibiotics were necessary for a
  fever
• 58 for cough
• 32 believed antibiotics were necessary for the
  common cold.
• Pediatrics 2004
• 543 parents participated
• 70 of parents believed antibiotics were
  necessary for treatment of their childs illness
  in a pre-visit survey.
• Parents expected antibiotics in 81 of cases that
  ultimately resulted in a bacterial diagnosis.
• Parents expected antibiotics in 66 of cases that
  ultimately resulted in a viral diagnosis.

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NEW IMPROVED ANTIMICROBIALS WHAT IS ON THE
HORIZON?

• The number of new antimicrobials approved has
  been steadily decreasing
• Pharmacotherapy 2004
• From 1998-2002 only 7 of 225 FDA new drug
  approvals were for antibiotics. An approval
  decrease of 56 compared with 1983-87.
• In 2002, no new antibiotics were introduced, in
  2003 only two were introduced.
• Few large pharmaceutical companies remain
  interested in developing new antimicrobial
  agents.
• The medical community is losing the fight against
  antibiotic-resistant superbugs.

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2005 UAB ANTIBIOTIC RESISTANCE HOW ARE WE
DOING?

• Streptococcus pneumoniae
• 45 resistant to PCN (55 in 2004)
• 7 to 3rd generation Cephalosporins (20 in
  2004)
• 45 to Macrolides (50 in 2004)
• 3 to Moxifloxacin (0 in 2004)
• Vancomycin-Resistant Enterococcus
• Enterococcus faecalis 5 Vancomycin resistance
  (0 in 1999)
• Entercoccus faecium 86 Vancomycin resistance
  (73 in1999)
• Pseudomonas aeruginosa
• 26 resistant to Piperacillin/Tazobactam (Zosyn)
  
• 22 to Ceftazidime
• 50 to Ciprofloxacin (30 in 2000)
• Escherichia coli
• 29 resistant to Ciprofloxacin (10 in 2003)

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REDUCING BACTERIAL DRUG RESISTANCE

• Antibiotic Restriction
• Local Regional
• Education
• Patient Physician
• Infection Control
• Vaccinations
• Haemophilis influenza

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ANTIBIOTIC RESTRICTION

• Local
• UAB Fluoroquinolone restriction
• Regional
• Finland Example 40 reduction in community
  macrolide use resulted in a 48 decrease in
  erythromycin resistance among group A
  streptococcal isolates over a 4 year time period.
• Iceland Example Penicillin resistance in S.
  pneumoniae isolates carried by children in day
  care decreased 25 with successful antibiotic
  reduction campaigns over a 3 year period.

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EDUCATION

• Physician
• JAMA 1999
• 2 Control Sites No change in prescription
  rates.
• Limited Intervention Site Office-based
  education materials only. No change.
• Full Intervention Site Received household
  office based patient education and clinician
  education.
• Antibiotic prescriptions for bronchitis
  decreased from 74 to 48 in 4 months without
  increasing return visit rates or incidence of
  pneumonia.
• Patient
• Patient antibiotic expectation increases
  physician prescription rates.
• Public and patient education on antibiotic use
  compliments physician education.
• Multi-faceted interventions involving physician,
  patient, and community education are most
  effective.

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SUMMARY

• Inappropriate use of antibiotics is a major
  public health threat in the United States.
• Bacterial drug resistance increase
  infection-associated morbidity and mortality,
  decreasing utility of antimicrobials for future
  generations, and dramatically inflates the cost
  of health care.
• We currently are not producing new antimicrobials
  fast enough to keep pace with bacterial drug
  resistance.
• Antibiotic restriction and physician/patient
  education can help to control antibiotic
  resistance.
• Full interventions with education of the public,
  patient, and physician are most effective.

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REFERENCES

• Ambrose PG, etal. CID Correspondence 2004
  Fluoroquinolone-Resistant Streptococcus
  pneumonia, an Emerging but Unrecognized Public
  Health Concern Is it Time to Resight the
  Goalposts? 1554-1555.
• Arnold SR, Straus DE. The Cochrane Collection
  2006 Interventions to improve antibiotic
  prescribing practices in ambulatory care
  (Review) 1-14
• Doern, GV, Brown SD. Journal of Infection 2004
  Antimicrobial susceptibility among
  community-acquired respiratory tract pathogens in
  the USA data from PROTEKT US 2000-01 56-65.
• Gonzales R, Steiner JF, Lum A Barrett PH. JAMA
  281(16) 1999 Decreasing Antibiotic Use in
  Ambulatory Practice 1512-1519.
• Mangione-Smith R, etal. Pediatrics, 2004
  Racial/Ethnic Variation in Parent Expectations
  for Antibiotics Implications for Public Health
  Campaigns 385-393.
• Nyquist AC, Gonzales R, etal. JAMA 279(11) 1998
  Antibiotic Prescribing for Children with Colds,
  Upper Respiratory Tract Infections, and
  Bronchitis 875-877.
• Steinman MA, Landefeld Cs, Gonzales R. JAMA
  289(6) 2003 Predictors of Broad-Spectrum
  Antibiotic Prescribing for Acute Respiratory
  Tract Infections in Adult Primary Care 719-725.
• Rybak MJ. Pharmacotherapy 2004 Update on
  Antimicrobial Resistance 203-213.
• Stephenson J. JAMA 1996 Icelandic researchers
  are showing the way to bring down rates of
  antibiotic-resistant bacteria 275175.
• Waites KB, Moser SA, Como J. 2005 University
  Hospital Report of Inpatient Antimicrobial
  Susceptibilities April-December 2004.

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QUESTIONS