Antibiotic Overuse & Resistance

1. Antibiotic Overuse & Resistance Carolyn Bray April 11, 2006 Sponsored By: Dr. Craig Hoesley

2. 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

3. 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

4. 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.

5. 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.

6. 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.

7. 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.

8. 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 child’s 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.

9. 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’.

10. 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)

11. REDUCING BACTERIAL DRUG RESISTANCE • Antibiotic Restriction Local & Regional • Education Patient & Physician • Infection Control • Vaccinations Haemophilis influenza

12. 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.

13. 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.

14. 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.

15. 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; 275:175. • Waites KB, Moser SA, Como J. 2005 University Hospital Report of Inpatient Antimicrobial Susceptibilities April-December 2004.

16. QUESTIONS