Consequences of inaction: importance of infection control practices.
(17/7957)
The increasing prevalence of antimicrobial-resistant pathogens in health care facilities is due in large part to overuse of antibiotics and poor compliance with recommended infection control practices. To control the spread of such pathogens, health care facilities must reduce overuse and abuse of antibiotics, and they must implement new multidisciplinary programs to improve hand hygiene practices among health care workers and improve compliance with recommended barrier precautions. (+info)
Minimizing potential resistance: the molecular view.
(18/7957)
The major contribution of molecular biology to the study of antibiotic resistance has been the elucidation of nearly all biochemical mechanisms of resistance and the routes for dissemination of genetic information among bacteria. In this review, we consider the potential contribution of molecular biology to counteracting the evolution of resistant bacteria. In particular, we emphasize the fact that fundamental approaches have had direct practical effects on minimizing potential resistance: by improving interpretation of resistance phenotypes, by providing more adequate human therapy, by fostering more prudent use of antibiotics, and by allowing the rational design of new drugs that evade existing resistance mechanisms or address unexploited targets. (+info)
Restricting the selection of antibiotic-resistant mutants: a general strategy derived from fluoroquinolone studies.
(19/7957)
Studies with fluoroquinolones have led to a general method for restricting the selection of antibiotic-resistant mutants. The strategy is based on the use of antibiotic concentrations that require cells to obtain 2 concurrent resistance mutations for growth. That concentration has been called the "mutant prevention concentration" (MPC) because no resistant colony is recovered even when >10(10) cells are plated. Resistant mutants are selected exclusively within a concentration range (mutant selection window) that extends from the point where growth inhibition begins, approximated by the minimal inhibitory concentration, up to the MPC. The dimensions of the mutant selection window can be reduced in a variety of ways, including adjustment of antibiotic structure and dosage regimens. The window can be closed to prevent mutant selection through combination therapy with > or =2 antimicrobial agents if their normalized pharmacokinetic profiles superimpose at concentrations that inhibit growth. Application of these principles could drastically restrict the selection of drug-resistant pathogens. (+info)
Minimizing potential resistance: the molecular view--a comment on Courvalin and Trieu-Cuot.
(20/7957)
The complexity of bacterial resistance to antimicrobial agents is driven by the interplay of many mechanistic and epidemiologic factors. Mechanistically, resistance by target alteration, reduced permeation, and drug inactivation can occur by both chromosomal mutation and acquisition of new genetic elements. Epidemiologically, exposure to antimicrobial agents provides a growth or persistence advantage for any existing resistant bacteria, generally irrespective of the mechanism. When a single chromosomal mutation is sufficient to cause resistance, any such exposure provides a risk of selection, as long as a sufficiently large bacterial population is exposed. Transmission of resistant bacteria can also amplify resistance of any type, but it is particularly important for complex resistance mechanisms that have evolved over time and for mechanisms that depend on infrequent biological events in nature. Because true biological barriers to the development of resistance are likely to be elusive, multiple approaches that address both the use of antimicrobial agents and transmission are necessary to slow the advance of resistance. (+info)
Minimizing potential resistance: a population dynamics view.
(21/7957)
I examine the results of studies that used mathematical models of the epidemiology and population genetics of antibiotic treatment and resistance in open communities and in hospitals to explore the following issues: the relationship between antibiotic consumption and the frequency of antibiotic resistance in bacterial populations in communities and in hospitals; methods of controlling the growth, dissemination, and persistence of antibiotic resistance in these settings; the extent to which resistance can be controlled; and the speed with which the effects of control measures will be realized. In open communities, it will take years or even decades to see substantial reductions in the frequency of antibiotic resistance solely as a result of more prudent (reduced) use of antibiotics. However, if we can restrict the input of resistant bacteria into hospitals, through the application of infection control and other measures, it should be possible to reduce the frequency of resistance and even eliminate resistant bacteria from these institutions in short order. (+info)
Mathematical models as tools for evaluating the effectiveness of interventions: a comment on Levin.
(22/7957)
Possible interventions to minimize resistance rates are numerous and can involve reduction and/or change in antimicrobial use, infection control, and vaccinations. As mathematical models are becoming more realistic they can be useful to quantitatively evaluate the relative contribution of individual risk factors and for the planning of future intervention strategies. The fitness cost associated with resistance is an important parameter and small differences can have a profound effect on the results. The mathematical models presented for communities predicted that even with cessation of antibiotic use, the decline in resistance frequency would be slow. This contrasts with successful interventions in Finland and Iceland. Future models have to include important variables such as herd immunity and take into account the heterogeneity of open communities. Provision of susceptible strains from areas with low resistance rates to areas with high resistance rates can have a profound effect on the success of interventions to minimize resistance. (+info)
Antimicrobial use and the emergence of antimicrobial resistance with Streptococcus pneumoniae in the United States.
(23/7957)
The rapid emergence of resistance to antimicrobial agents by Streptococcus pneumoniae in the United States has been influenced by various factors, including the clonal nature of most resistant strains and the fact that organisms with a multiresistant phenotype have become stably endemic. The ease with which transmission occurs and the fact that humans, especially children, are often colonized asymptomatically in the upper respiratory tract have contributed to the problem. Clearly, the most important factor in the emergence of antimicrobial resistance with S. pneumoniae, however, is the selective pressure of antimicrobial agents. Potency, defined as a product of both antibacterial effect and drug delivery, is a key factor. Generally speaking, the more potent an antimicrobial agent, the less likely it is to select for resistance. This is germane to comparisons of oral agents within specific antimicrobial classes (e.g., beta-lactams, macrolides, and fluoroquinolones). Within each class, potencies differ. In view of the existence of stably endemic multidrug-resistant S. pneumoniae, given comparable cost, side-effect profile, palatability, convenience of dosing, and accessibility, use of the most potent agent(s) within a particular class is advocated. (+info)
Association between antibiotic resistance and community prescribing: a critical review of bias and confounding in published studies.
(24/7957)
The reported association between antibiotic prescribing and resistance may be subject to bias or confounding. Bias describes any effect at any stage of investigation or inference tending to produce results that depart systematically from the true value. A confounding variable is one that is associated independently with both exposure and outcome. Confounding variables may create an apparent association or mask a real association. Pharmacoepidemiology is the study of the use and the effects of drugs in large numbers of people. We have used standard pharmacoepidemiological methods to investigate sources of bias and confounding in the association between prescribing and resistance. We conclude that the association is statistically valid and that the consistency of evidence supports a cause-effect relationship. Nonetheless, several important sources of bias and confounding must be taken into account in future studies that analyze the impact of prescribing policies on resistance. (+info)