Antibiotic Resistance and the Antibiotic Crisis Daniel Z. Uslan, MD Director, Antimicrobial Stewardship Program Assistant Clinical Professor Division of Infectious Diseases, UCLA
Learning Objectives Understand the present crisis of resistant microorganisms and declining antibiotic development Identify the reasons for physician misuse and overuse of antibiotics Describe antibiotic stewardship programs and understand their role in decreasing utilization Systematically apply specific strategies to improve antibiotic utilization Cite cultural considerations in the prevalence of this topic
Cultural Considerations CA Assembly Bill 1995 requires each CME activity to have a component on Cultural Diversity No studies on antibiotic prescribing differences or resistance among different races/ethnicities
The Dark Ages In December 1942, a 4 yo girl in excellent health developed facial cellulitis after trauma Spread relentlessly, fever to 104 F, could not sleep because her face and neck so swollen she could not swallow her own saliva Began gasping for breath Herrell 43 Proc Staff Meetings Mayo Clinic 18:65-76
On arrival to the hospital Moribund dead within 2 days After 14 days of penicillin Totally fine for >65 years
Why Is This Important? For most of the infectious diseases on the wards of Boston City Hospital in 1937, there was nothing that could be done beyond bed rest and good nursing care. Then came the explosive news of sulfanilamide, and the start of the real revolution in medicine. Lewis Thomas, MD Albert Lasker Award winner Member of the National Academies of Science National Book Award Lewis Thomas. Notes of a Medicine Watcher. 83. Viking Press
Why Is This Important? Lewis Thomas. Notes of a Medicine Watcher. 83. Viking Press I remember the astonishment when the first cases of pneumococcal and streptococcal septicemia were treated in Boston in 1937. The phenomenon was almost beyond belief. Here were moribund patients, who would surely have died without treatment, improving within a matter of hours and feeling entirely well within the next day we became convinced, overnight, that nothing lay beyond reach for the future. Medicine was off and running.
The Power of Antibiotics Disease Pre-Antibiotic Death Rate Death Rate with Antibiotics Change in Death Rate Community 35% 10% -25% Pneumonia 1 Hospital 60% 30% -30% Pneumonia 2 Endocarditis 3 100% 25% -75% Meningitis 4 80% 20% -60% Cellulitis 5 11% <0.5% -10% By comparison, treatment of acute MI with aspirin 6-3% 1IDSA Position Paper 08 Clin Infect Dis 47(S3):S249-65; 2IDSA/ACCP/ATS/SCCM Position Paper 10 Clin Infect Dis In Press; 3Kerr AJ. Subacute Bacterial Endocarditis. Springfield IL: Charles C. Thomas, 1955 & Lancet 1935 226:383-4; 4Lancet 38 231:733-4 & Waring et al. 48 Am J Med 5:402-18; 5Spellberg et al. 09 Clin Infect Dis 49:383-91 & Madsen 73 Infection 1:76-81; 6 88 Lancet 2:349-60
Why Is This Important? with today s [antibiotics] it is possible to place in the hands of a barefoot, nonliterate villager more real power to affect the outcome of a critically ill [patient] than could have been exerted by the most highly trained urban physician of 25 years ago. (Dr. Walsh McDermott 1960 Science 131:197-205) Walsh McDermott, MD Cornell University 1 st President of Medical Board of National Academy of Sciences (precursor to IOM) Albert Lasker Award winner for early work on isoniazid
In just 75 years RIP Antibiotics: 1937-2012
Antibiotic-Resistance Is Skyrocketing (CDC Data) % of isolates
US hospital discharges with diagnosis of infection with drug-resistant microorganisms 1993-2005 Rate per 100,000 hospital discharges 1200 1000 800 600 400 200 0 Courtesy John Rex 1993-2005: A dramatic increase 0.3% 0.6% 1% 1993 1995 1997 1999 2001 2003 2005 Data from US Healthcare Cost and Utilization Network 2010-02-23 IOM Countermeasures, Big Pharma Commercial Perspectives - Rex
Courtesy J.G. Bartlett No New Classes to Treat Gram Negative Bacilli For 4 Decades For Gram positives, we need better drugs. For Gram negatives, we need ANY drugs. John Bartlett, MD
Geographical distribution of extremedrug resistant KPC Klebsiella bacteria Nov, 2006
Geographical distribution of extremedrug resistant KPC Klebsiella bacteria Current
NDM-1 E. coli & Klebsiella In 2010, reports of new resistant mechanism spread from India to UK/US All strains resistant to all antibiotics except tigecycline or colistin 10% strains resistant to both of those drugs also truly pan-resistant This is our worst nightmare Kumarasamy 10 Lancet Infectious Diseases 10:597-602; MMWR 10 59:750
Pan Resistant Superbugs 11/6/10, New York Times, report on antibiotic resistant infections For these infections, we're back to dancing around a bubbling cauldron while rubbing two chicken bones together. --Brad Spellberg, MD Page A1 (front page) Quote of the Day
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Health Care Costs of Resistance Resistant infections prolong length of hospital stay by 24% and increase costs by 29% vs. susceptible infections (Maudlin et al. AAC 10 54:109-115) Cost to US of antibiotic resistance is 8 million additional hospital days and $21-34 billion/yr (Roberts et al. CID 09 49:1175-84; & PRN Newswire Antibiotic-Resistant Infections Cost the U.S. Healthcare System in Excess of $20 Billion Annually 10-19-09)
2 million people acquire healthcare-associated infections per year
100,000 people die as a result More than AIDS, breast cancer, traffic accidents combined
Microbes vs. Humans Microbes Humans Factor Number on Earth 5x10 31 6x10 9 10 22 Mass (metric tons) 5x10 16 3x10 8 10 8 Generation Time 30 min 30 yr 5x10 5 Time on Earth (yrs) 3.5x10 9 4x10 6 10 3 Microbiology in the 21st century, ASM, 2004; Spellberg et al 2008 Clin Infect Dis
Microbes vs. Humans Genetic Promiscuity Microbes Humans* Diversity/Adaptability Cross-phylum Intra-species *genus/species Homo sapiens, family Hominidae, order Primate, class Mammalia, phylum Chordata
Microbes vs. Humans Equivalent promiscuity would require capability to exchange DNA with: chimpanzee (family Hominidae) orangutan (order Primate) Pretty cool grizzly bear / tiger / walrus / killer whale (class Mammalia) falcon / frog / crocodile (phylum Chordata)
Microbes have been creating and defeating antibiotics for 20 million times longer than Homo sapiens have even known antibiotics existed.
The future of humanity and microbes will likely evolve as episodes of our wits versus their genes. Nobel Laureate Joshua Lederberg Science 2000 288:287-93
How Do We Combat Resistance? Two Options
1. New Antibiotics
New Drug Research and Development A short section
New Antibacterial Agents Approved 1983-2012 18 16 14 12 10 8 6 4 2 0 1983-1987 1988-1992 1993-1997 1998-2002 2003-2007 2008-2012
Timeline for Development of a New Antibiotic
In contrast 67 new drugs for cancer 33 for inflammation and pain 34 for metabolic/endocrine disorders 32 for pulmonary disease