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16 Cards in this Set
- Front
- Back
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Untoward Effects of Antibiotics
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• Antibiotic resistance
• Adverse drug events (ADEs) – Hypersensitivity/allergy – Drug side effects – Clostridium difficile infection – Antibiotic associated diarrhea/colitis • Increased health-care costs |
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Antibiotics account for 19.3% of drug related adverse events
• 78.7% for allergic events • 19.2% for adverse events (e.g. diarrhea, vomiting) – Approximately 50% due to penicillin & cephalosporin classes – 6.1% required hospital admission |
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Six Goals of Antibiotic
Stewardship Programs |
Reduce antibiotic consumption and inappropriate use
• Reduce Clostridium difficile infections • Improve patient outcomes • Increase adherence/utilization of treatment guidelines • Reduce adverse drug events • Decrease or limit antibiotic resistance – Hardest to show – Best data for health-care associated gram negative organisms |
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Nine Factors to Consider
When Selecting an Antibiotic |
1. Spectrum of coverage
2. Patterns of resistance 3. Evidence or track record for the specified infection 4. Achievable serum, tissue, or body fluid concentration (e.g. cerebrospinal fluid, urine) 5. Allergy 6. Toxicity 7. Formulation (IV vs. PO); if PO assess bioavailability 8. Adherence/convenience (e.g. 2x/day vs. 6x/day) 9. Cost |
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Empiric Therapy (85%)
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• Infection not well defined
(“best guess”) • Broad spectrum • Multiple drugs • Evidence usually only 2 randomized controlled trials • More adverse reactions • More expensive |
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Directed Therapy (15%)
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• Infection well defined
• Narrow spectrum • One, seldom two drugs • Evidence usually stronger • Less adverse reactions • Less expensive |
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Why So Much Empiric Therapy?
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Need for prompt therapy with certain infections
– Life or limb threatening infection – Mortality increases with delay in these cases • Cultures difficult to do to provide microbiologic definition (i.e. pneumonia, sinusitis, cellulitis) • Negative cultures • Provider Beliefs – Fear of error or missing something – Not believing culture data available – “Patient is really sick, they should have ‘more’ antibiotics” – Myth of “double coverage” for gram-negatives e.g. pseudomonas – “They got better on drug X, Y, and Z so I will just continue those” |
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Conclusion
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• The therapeutic benefit of antibiotics should be
balanced with their unintended adverse consequences • Inappropriate antibiotic use is associated with increased antibiotic resistance, adverse drug effects and Clostridium difficile infection • Antibiotic stewardship is important for preserving existing antibiotics and improving patient outcomes • Antibiotic prescribing should be prudent, thoughtful and rational |
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New Antibiotics decreasing
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3 principal causes of the antibiotic market
failure: |
– Scientific
– Economic – Regulatory |
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Scientific
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• The “low hanging fruit” has already been
plucked • With each of the > 100 antibacterial agents developed in the U.S. since sulfonamides, the bar has been raised as to what is to discover and develop the next generation • Discovery and development of antibiotics has become scientifically more complex, more expensive, and more time consuming over time -many drugs but few targets |
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economic
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Antibiotics represent a poor return on investment
• Antibiotics are short course therapies, and companies know that they will make much more money selling a drug you have to take very day for the rest of your life • Imbalanced drug pricing in society. – We will pay $50,000 for a course of cancer chemotherapy that prolongs life by 3 months, but we don’t want to pay more than $100 for a course of antibiotics that cures the target infection. – Pricing difference is neither rational nor data-driven; there is no cost-efficacy analysis that supports cancer drug pricing. Rather, drug pricing in the U.S. is based on public perception and fear • People are terrified of cancer, but not of infections • There is a need to educate the public and payors about the true value of antibiotics |
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Telithromycin [Ketex] Effect
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• NDA twice rejected before finally being approved in 2004
over the objection of FDA scientists • July-September 2005 there were two deaths, 35 liver adverse reactions, 44 cardiac events, and 80 visual events in Ketek patients • January 20, 2006: FDA issued a Public Health Advisory • More than a year for the FDA to finally ban Ketek for use in two of its 3 approved indications • Drug is still approved to treat pneumonia • New labeling warns of acute hepatic failure, including fatal liver injury, some requiring liver transplants, and some occurring after only a few doses |
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Economic
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At discovery, the net present value of antibiotic
to a drug company is MINUS $50 million – HIGH cost of development – Short duration of treatment – Limited patient pool • That compares to a positive $1 billion for a new musculoskeletal drug |
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Telithromycin [Ketex] Effect
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• FDA simply required demonstration the candidate drug
eliminated symptoms of infection as reliably as the approved antibiotic • FDA instead required that applicants needed to show that patients were no more likely to die — of any cause — within 28 days of treatment with a new drug • Patients with hospital-acquired pneumonia already ill, making it hard to know if candidate drug played a part in their death • Of necessity, trials have to be larger for statistical validity • Relative rarity of infections needing new antibiotics • Patients should NOT have received other antibiotics before test agent |
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GAIN Act 10/1/2012
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Incorporated in the FDA Safety and Innovation Act
that reauthorized prescription drug user fees • Provides added exclusivity for antibiotics and earmarks antibiotics for Priority Review • Mandates the creation of a pathogen-focused antibacterial drug development pathway • Provides the ability to develop drugs for emerging multi-resistant pathogens based on the bugs they kill - regardless of the site of infection • Mutually agreed upon minimum efficacy datasets can be obtained practically and rapidly • With GAIN, political pressure to limit the risk of adverse effects from antibiotics has been replaced by congressional calls to reinvigorate product development |
