Antibiotic Overuse & Resistance

Carolyn BrayApril 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 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.

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 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’.

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)

REDUCING BACTERIAL DRUG RESISTANCE

• Antibiotic RestrictionLocal & Regional

• EducationPatient & Physician

• Infection Control

• VaccinationsHaemophilis influenza

ANTIBIOTIC RESTRICTION

• LocalUAB 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?; 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.

QUESTIONS