Revenge of Microbes Notes - Chapter 9

MICROBES: Chapter 9
The Looming Crisis in Antibiotic Availability

*3 obvious solutions to antibiotic resistance problem:
1. Educate physicians and patients about appropriate use of antibiotics
-Change behavior patterns
2. Limit a physician’s freedom to prescribe antibiotics by placing veto power in the hands of a pharmacist or infectious disease specialist
-Misprescribing or overprescribing antibiotics may receive an admonitory letter (I.C.A.)
-Infection control agent also watches for bad hygienic practices
3. Step up the discovery of new antibiotics
-Not being aggressively pursued
-Pharmaceutical companies are shutting down or cutting back on their antibiotic discovery programs

*The Profitability Calculation: Inescapable Feature of Modern Markets
-Net present value (NPV) and is a measure of the likely profitability of a drug
EX: Musculoskeletal drugs, neurological drugs NPV = 1050 and 720
Injectable antibiotics NPV = 100
~Proposed increases in FDA requirements would increase number of people in clinical trials of antibiotics and could reduce NPV to 35
-Antibiotic to market is cost of clinical trials necessary for safety and efficacy
~$800 million to take a new antibiotic through testing and approval
~New antibiotics are becoming more and more difficult to find
-New discovery methods have not produced flood of new antibiotics
~New method not likely to be a quick fix
-Consumers are convinced that drug prices are too high and are trying various tactics (buying drugs in other countries) to reduce costs
~Would not consider a few hundred dollars too great to pay
-How are drug discovery and development to be financed?
~People in developed countries are paying these costs
~Should it spread over a larger base?
-A large part of what is called “development” by some drug companies is not just the clinical trials, but advertising the drug

*Do we really need new antibiotics?
-At present, vast majority of patients who need to be treated with antibiotics have an infection that can be controlled with some antibiotic
-Looking to the future (example)…
~MRSA now resistant to Vancomycin emerges
~Future evolution of a strain is resistant to all available antibiotics
~Expect many bacteria to become resistant to trusted antibiotic
-“Pan-resistant” bacteria: resistant to all commonly used antibiotics
~EX: Pseudomonas aeruginosa (postsurgical infections); Acinetobacter baumanii (intensive care wounds)
~Now resorting to antibiotics originally too toxic for human use
-1960s: IF stopped discovering antibiotics…
~Facing a treatment crisis if the decision to stop with the first-generation antibiotics had been made
-Antibiotics take 10 years to go from discovery to market
~Amount of time needed for assessment of efficacy and safety of antibiotics that covers different age groups and people with different genetic backgrounds
~Bacteria evolve – DO NOT ignore it
*Attitudes in Medical Community
-Blasé attitude of medical community towards bacterial infections
-Complacent attitude, in initial elation over success of antibiotics
*Back to antibiotics
-Turn to bacteriologists (i.e. cancer; heart disease) in hope that chronic diseases might actually be caused by bacteria
~Antibiotics might be able to cure or prevent these diseases
-Discovery that ulcers – caused by bacteria
~Development of antibiotic regimen (1-2 weeks; $200)
~Less than $1000s and long-term therapy
-Helicobacter pylori: resistant to antibiotics for treatment
~Other intractable diseases caused by bacteria (potential)→ use of antibiotics will become more widespread and higher level of resistance

*Hospital Administrators and Lawyers Weigh In
-Hospital administrators have begun to note the increased cost of treating a patient with an antibiotic-resistant bacterial infection
~Need to use more expensive antibiotics
~Increased number of days spent in the hospital
~Disrupt family life for patients who suffer infections that keep them hospitalized longer than expected are a serious social concern
-Given infectious disease control specialists increased status/power
~Initiated new efforts to reinforce the use of simple but effective hygienic measures such as hand washing
~Isolate patients with antibiotic-resistant bacterial infections
~Postsurgical infection can be spread to other patients (crowded)
-Number of lawsuits against hospitals by patients (nosocomial infections)
~Settled out of court
~EX: Scotland 2003: 77-year-old woman with ‘minor’ kidney infection = developed septicemia and almost died (potential leg amputation) → MRSA infection
~Treat of lawsuits = spur makes physicians take antibiotic-resistance seriously
*Beyond Hospitals
-Use of antibiotics in community (outside hospitals) actually heavier in aggregate than use of antibiotics in hospitals
~MRSA: hospital-specific originally; reports of community infections
~Lead some hospitals to screen patients before for MRSA
~Four cases of juvenile deaths caused by MRSA (1997-1999)
-Bacteria resistant to multiple antibiotics are a community problem
-Antibiotic: Vancomycin
~Main defense against MRSA and S. pneumoniae
~2003: Fully Vancomycin-resistant strain of MRSA
-Face possibility of emergence of first fully antibiotic-resistant strain (ALL)
*How safe is ‘safe’?
-The effect of increase in number of subjects tested would be to increase the cost of clinical trials substantially, making antibiotics even less attractive to the pharmaceutical companies
-FDA’s decision to require that a new antibiotic must be demonstrated to be
clearly superior to existing antibiotics
-An antibiotic that is equally effective or even slightly less effective than those currently on the market for treating a certain type of infectious disease can suddenly become resistant to antibiotics already on the market
~EX: Vancomycin → Initially = less effective than existing antibiotics because it targeted gram-positive bacteria
~When gram-positive bacteria became serious resistance problem, its attractiveness improved significantly

*What is to be done?
-Government-National Institutes of Health = bigger role antibiotic discovery
-Stop demonizing the industry as profit-hungry predators
-Pharmaceutical reentry = make antibiotics ‘orphan drugs’
~Orphan drugs → important but have too small market for profit
-Extend patent protection for companies that develop new antibiotic
-Study of bacteria has become somewhat unfashionable in academic circles and number of scientist being trained had declined (alarmingly)
~Number of students steadily increasing = eventually critical mass

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