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

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

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

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 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.

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.

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.

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.

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.

NEW & IMPROVED ANTIMICROBIALS: WHAT IS ON THE HORIZON? The number of new antimicrobials approved has been steadily decreasing: Pharmacotherapy 2004: From only 7 of 225 FDA new drug approvals were for antibiotics. An approval decrease of 56% compared with 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’.

2005 UAB ANTIBIOTIC RESISTANCE: HOW ARE WE DOING? Streptococcus pneumoniae 45% resistant to PCN (55% in 2004) 7% to 3 rd 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)

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

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.

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.

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.

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?; 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 ; Gonzales R, Steiner JF, Lum A; Barrett PH. JAMA 281(16) 1999: Decreasing Antibiotic Use in Ambulatory Practice; Mangione-Smith R, etal. Pediatrics, 2004: Racial/Ethnic Variation in Parent Expectations for Antibiotics: Implications for Public Health Campaigns; Nyquist AC, Gonzales R, etal. JAMA 279(11) 1998: Antibiotic Prescribing for Children with Colds, Upper Respiratory Tract Infections, and Bronchitis; 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; Rybak MJ. Pharmacotherapy 2004: Update on Antimicrobial Resistance; 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 University Hospital Report of Inpatient Antimicrobial Susceptibilities April-December 2004.

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