The Resistance Phenomenon in Microbes and Infectious Disease Vectors Implications for Human Health and Strategies for Containment: Workshop Summary (2003) / Chapter Skim
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1. Introduction
1. Introduction
Pages 19-43
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From page 19... ...
Higher costs that result from antimicrobial resistance are particularly burdensome for developing nations, and in some cases effective therapies are now priced out of practical reach. One major factor contributing to the emergence of drug-resistant microbes is the increase in the sheer volume of antimicrobial agents, particularly antibiotics, being used today.
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From page 20... ...
These findings are encouraging laboratories, both public and private, to step up efforts to define new resistance genes and investigate their biochemical activity. Evolutionary science has grown in sophistication and predictive power, and a body of theory and practical observation now exists that suggests possible strategies for helping to solve some of the problems that arise from the continued "arms races" between humans and microbes.
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From page 21... ...
The result of this arms race is a steady escalation of running ability, until both players challenge the maximum performance their basic construction will allow. Escalation caused by predator-prey arms races is a normal expectation of evolutionary models.
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From page 22... ...
. Rapid Escalation of HIV Probably one of the worId's fastest evolving human diseases is also one of the clearest examples of arms races in health care and the escalation that results.
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Mere weeks after the start of the immune response, amino acid evolution in the coat proteins that cover the viral shell has begun (see Figure 1-1~. The cycle of immune targeting and viral escape repeats many times, each cycle representing a turning of the arms race wheel.
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Not only is this an excellent, experimental demonstration of convergent evolution, but it also shows the ability of selection and mutation to combine to produce rapid HIV evolution within each infected individual. HIV also evolves quickly in the presence of other drugs to become resistant.
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From page 25... ...
AZT is relatively cheap to produce, and if not for evolution of resistance, we would have substantially overcome HIV years ago by deploying this and other anti-retrovirals. Instead, HIV evolution prevents us from using simple drug treatment strategies, and HIV sufferers in North America and Europe rely on triple-drug therapy to stall the progress of the disease.
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From page 26... ...
All these outcomes result from the same basic evolutionary mechanism of arms races and escalation. Antibiotic resistance and other evolutionary responses to medical treatment parallel the evolution of resistance in insect pests, agricultural weeds, and fisheries populations under strong selective mortality (Palumbi, 2001b)
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From page 27... ...
This means that our current drug strategy is best viewed as a temporary measure to slow down the HIV rampage while a more permanent solution is found. Direct Observation Therapy Hidden within the success of drug overkill strategies lies the reason for the failure of many less powerful antimicrobial approaches.
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The graph and subsequent discussion assume wide, genetically based variation in susceptibility in the original population, and no heterogeneity in drug exposure. The increase in survival time among infectious cells after a drug treatment is called the "response to selection," and it increases with the severity of the selection and the heritability of the trait in question.
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From page 29... ...
The basic principle applies to any infectious disease for which a partial antibiotic dose would generate a strong evolutionary response to selection. The strategy slows arms races because it breaks the evolutionary cycle.
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. In cases in which flight was no longer adaptive like predator-free oceanic islands these fitness costs of flight are reversed, and birds have TABLE 1-2 Responses to Antibiotic Cycling in Hospitals Trying to Reduce Costs of Treating Resistant Infections Target Response Study Gentamicin resistance Improvement Gerding et al., 1991 Ceftazidime resistance Reduced infection Kollef et al., 1997 Ceftazidime resistance Reduced drug use Kollef et al., 2000 Multi-drug resistance No improvement Dominguez et al., 2000 Ciprofloxacin resistance Reduced infection Gruson et al., 2000
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From page 31... ...
Current examples of successful deceleration of evolution include drug overkill strategies, direct observation therapy, integrated pest management, and antibiotic cycling. Use of these tactics follows from the realization that fighting infectious disease is only 1 1 1 1 1 · 1
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It is no surprise now that these are actual events but what else has happened over the past decade? While there are many factors involved in the emergence of antibiotic resistance, the two major ones still operate today: the antibiotic, which encourages selection and evolution of resistant strains, and the resistance genes which are acquired by bacteria or appear by mutation.
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Therefore, a considerable amount of pressure is being exerted on the natural microbial environment by the antibiotics provided to humans, animals, and plants, including the spraying of antibiotics on fruit trees. One area in which antibiotic usage has decreased is in aquaculture.
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This finding raises grave concerns that ciprofloxacin may not remain effective as a drug of last resort in those parts of the world where resistance to other antibiotics, namely ampicillin, chloramphenicol, and co-trimoxazole, has eliminated these drugs as effective treatment for typhoid fever. In the United States, the CDC described four patients in Minnesota and North Dakota who died from a methicillin-resistant S
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lust recently, the CDC reported an 11-month-old air! from a community in Georgia with refractory otitis media caused by a pneumococcus resistant to six different antibiotics (CDC, 2002c)
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This opinion does not help our cause against antibiotic misuse and the emergence of resistance. Secondly, bacteria emerging with resistance to these chemicals can show decreased susceptibility to antibiotics.
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Recently, the organization synthesized the efforts of various expert groups 25 reports over the past 15 years as a background and foundation for WHO's Global Strategy for Containment of Antimicrobial Resistance (WHO, 2001~. The APUA document was published along with the WHO report in 2001 (APUA, 2001~.
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From page 38... ...
APUA was able to catalyze an agreement between the companies funding these projects to meet periodically and discuss and share the data. The project provides antibiotic susceptibility surveillance information on large numbers of clinical isolates and allows early changes in susceptibility to be revealed, such as the decreased susceptibility of Haemophi~s infInenzue to fluoroquinolones detected at 0.1 percent (Travers et al., 2001~.
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From page 39... ...
pyogenes, but, rather, by replacement with other susceptible strains. In addition to the various scientific challenges that must be met, we also need to devise new public policies and procedures that will help minimize the emergence of antimicrobial resistance.
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Emerging Infectious Diseases 8: 713-716. ASM (American Society for Microbiology)
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Antimicrobial Agents and CI7emotI7erapy 337:414-418. House of Lords Select Committee on Science and Technology.
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From page 42... ...
1997. Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: Guidelines for the Prevention of Antimicrobial Resistance in Hospitals.
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From page 43... ...
2001. Global Strategy for the Containment of Antimicrobial Resistance.
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