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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5. Factors Contributing to the Emergence of Resistance
5. Factors Contributing to the Emergence of Resistance
Pages 130-158
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From page 130... ...
In many developing countries, problems typically arise because antimicrobial agents are readily available and can be purchased as a commodity without the advice or prescription of a physician or other trained health care provider. Some common types of human behavior also play a role in promoting resistance.
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Transmission of drug-resistant organisms among patients may be airborne, from a point source (such as contaminated equipment) , or by direct or indirect contact with a contaminated environment or the contaminated hands of staff.
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For example, mortality in recent cholera and dysentery epidemics has been significantly increased by antibiotic resistance (Goma Epidemiology Group, 1995; Sengupta et al., 2000; Okeke et al., 20011. Other cases in point include tuberculosis, respiratory tract infections, infectious diarrhea, sexually transmitted diseases, and malaria.
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From page 133... ...
Examples are taken from different countries, but the principal focus here is on sub-Saharan Africa where the burden of infectious disease is highest and antibiotic use is commonly under-regulated (Djimde et al., 1998; Siringi, 20011. Emergence of Resistance Studies conducted in industrialized countries have correlated antibiotic consumption with the prevalence of antibiotic resistance.
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From page 134... ...
In addition, the rising number of HIV-positive people increases selective pressure for resistant organisms by increasing the need for prophylactic and curative antimicrobial use. As in industrialized countries, prescribers are subjected to pressure from patients (Paredes et al., 1996~.
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The situation is similar in many other developing countries, and pharmacy premises, although sanctioned, often serve as an outlet for unprescribed antibiotics because of the competitive pressure from unsanctioned providers (Chuc and Tomson, 1999; Okeke et al., 1999~. Unsanctioned providers tend to have shabbier premises and a smaller range of medicines but they flourish because they are often cheaper due to lower overheads.
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From page 136... ...
If traditional practitioners are using Western medicines, there is a need to ensure that they receive appropriate training in diagnosis, treatment, and undesirable effects, including antibiotic resistance. In some developing countries, patients prefer to seek care from sanctioned providers, even though it is available from other sources (O'Connor et al., 2001~.
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S? ~b-Standard Medicines Even when antibiotic prescription and use is optimal, sub-therapeutic dosing and consequent resistant selection can arise from poor quality antibiotic preparations.
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Global Strategy for Containment of Antimicrobial Resistance will potentially address all of these issues (WHO, 2001~. Priority should be given to education, directed at distributors and consumers as well as prescribers of antibiotics, infection control to prevent the dissemination of resistant strains, quality assurance of antibiotics and other medicines, and the insti
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From page 139... ...
This association of acute care hospitalization with antimicrobial resistance was recognized soon after the introduction of antimicrobial therapy (McGowan et al., 1975~. Widespread outbreaks of penicillin-resistant Staphylococcus aureus in the late 1950s reinforced this observation (LaForce, 1993~.
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TABLE 5-2 Variables Which Promote the Emergence and High Prevalence of Resistant Organisms in Acute Care Facilities Patient variables Intense antimicrobial use Institutionalization Inherent immunocompromised status e.g., neonate, very old Acquired immunocompromised status e.g., transplant patients, profound neutropenia, extensive burns Therapeutic interventions which compromise normal defenses e.g., indwelling urethral catheters, central lines, endotracheal tubes, surgical procedures Systemic: 30-50% of patients · Therapeutic · Prophylactic Topical use Increased opportunities for transmission · Shared equipment · Shared staff · Airborne
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From page 141... ...
The likelihood of a patient acquiring a resistant organism 1 · 1 1 1 - - correlates with the prevalence of resistant organisms In other patients In the unit or facility (Bonten et al., 1998~. The frequency of antimicrobial resistance is highest in special care units such as intensive care units, burn units, or transplant units where severely ill patients, multiple invasive devices, intense antimicrobial use, and close spatial clustering combine.
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From page 142... ...
These include increased mortality, increased morbidity, increased length of stay, and increased costs due, at least partly, to the need for more costly alternative antimicrobial therapy and infection control interventions. While the conclusion that antimicrobial resistance in acute care facilities has negative impacts is valid, there are some methodologic concerns with studies measuring outcomes.
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Hospital infection control activity should also decrease antimicrobial resistant infections and colonization. Perhaps the evidence most strongly supporting efficacy of infection control in controlling antimicrobial resistance is found in reports of control of outbreaks of antimicrobial resistant strains.
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Use of prophylactic antimicrobials, even when appropriate, contributes to the larger problem of antimicrobial resistant organisms within acute care facilities. Finally, despite development of multifaceted national guidelines for control of selected high profile resistant organisms, the prevalence of these antimicrobial resistant organisms has continued to increase.
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From page 145... ...
The continuing approach to management of antimicrobial resistant organisms within acute care facilities is, in fact, ever-intensified use of broad-spectrum antimicrobials to "cover" ever-expanding antimicrobial resistance. One study relevant to antimicrobial use and restriction described an outbreak of Klebsiel~ aerogenes in a neurosurgical unit in Britain from
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The initial response to controlling this outbreak was intensification of infection control interventions including cohorting or placing patients in private rooms, and high dose colistin therapy to prevent and eradicate colonization. These strategies had minimal impact, and deaths from K
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Development of additional antimicrobials, however, is unlikely to alter the paradigm of antimicrobial resistance in acute care facilities. This will remain a spiral of ever increasing resistance and empiric antimicrobial use until alternative effective approaches to prevention and management of nosocomial infections are developed.
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From page 148... ...
Antimicrobial agents are used in food animal production to prevent disease in high-risk animals and to control or treat disease; or to improve the ability of the animal to convert feed to muscle. Unlike the situation in human medicine where individual patients can be treated, food animal medicine is often practiced on a population basis for reasons of animal welfare, logistics, and efficiency since it is impractical to individually treat each animal in a group that consists of hundreds to tens of thousands.
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The antimicrobial agents that are used in food animal production are similar to those used in human medicine, but with several key exceptions (GAO, 1999~. The Food and Drug Administration (FDA)
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Some of the antimicrobial agents used in food animals are approved for delivery by both a parenteral and an oral route, but in many cases only a feed administration route is approved and/or feasible for a variety of reasons. A detailed compendium of the technical aspects of feed additives is available (Muirhead, 2001~.
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From page 151... ...
The antimicrobial agents involved primarily include tetracyclines, beta-lactams, sulfonamides, macrolides, lincosamides, streptogramins, and bacitracin. The European Union Commission has legislatively removed the efficiency claim authorizations of several antimicrobial agents, and plans to remove the authorizations for the remaining agents in a few years.
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From page 152... ...
Thus the central issue is not whether antibiotic use in food animals can select for resistance in particular types of bacteria which can then cause foodborne disease in people that is more difficult to treat. The real issue is what is the frequency at which this occurs and to what extent should resources be used to intervene?
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From page 153... ...
Monitoring of the quantities of drug usage to assess reduction in antibiotice use is done in several small countries, and is being done on a self-reporting basis by the veterinary pharmaceutical industry in the United States and the European Union. In conclusion, the use of antibiotics in food animals is essential to maintain a consistent supply of healthy animals entering the food chain.
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Infection Control and Hospital Epidemiology 19:333-336. Calva J
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1988. Guidelines for improving the use of antimicrobial agents in hospitals: a statement by the Infectious Diseases Society of America.
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2001. Infection Control Programmes to Control Antimicrobial Resistance.
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2000. Role of infection control measures in limiting morbidity associated with multi-resistant organisms in critically ill patients.
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From page 158... ...
TI7e Lancet Infectious Diseases 1:242-250.
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