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517 Consequences of Bacterial Resistance to Antibiotics in Medical Practice Jacques F. Acar The rate of bacterial resistance to antibiotics is significant epidemiologically and ecologically. The consequences of resistance must be considered medically and economically in terms of the patients who are infected with antibiotic-resistant microorganisms. However, before the so-called "disease consequences of resistance" can be considered, it should be noted that positive changes in prescribing behavior occur when information on resistant organisms is released to practitioners and to the public. The impact of such information has not been investigated and measured. However, it is likely that knowledge about bacterial resistance increases the use of new antibiotics and additional diagnostic tests. The disease consequences of resistance should be assessed according to the morbidity and mortality rate due to antibioticresistant organisms. It can be assumed that resistant microorganisms lead to an increase in morbidity and mortality since resistance increases the risk of inappropriate therapy. There is an increased risk that patients who do not receive appropriate treatment will have a longer course of disease or a fatal outcome; moreover, as these patients remain infectious for a longer period, morbidity and transmission of the microorganism are increased. Such increased morbidity was documented in outbreaks of diseases such as shigellosis, typhoid fever, and pneumococcal infections. In hospital infections, resistant microorganisms and antibiotic therapy increased the risk of colonization, infection, and spread of the resistance [1-3]. The increased mortality during outbreaks of infections caused by resistant bacteria was evaluated for patients with nosocomially acquired infections. It was at least twice as high for patients infected with resistant organisms than for those who were not infected with resistant organisms [1]. However, most studies were biased because of problems with confounding variables (e.g., underlying conditions, levels of exposure), and often no data were available on the confounding variables [4]. The consequences of resistance in common infections have been investigated in only a few studies. Patients who are treated with an inadequate antibiotic are at risk for a poor outcome. This risk is higher if there is an underlying impairment of the host defenses [5]; the risk of transmitting the resistant microorganism is increased since the treatment is not able to eradicate it. Reprints or correspondence: Dr. Jacques F. Acar, Laboratoire de Microbiologie Medicale, Fondation HOpital Saint-Joseph, 185 rue Raymond Losserand, 75674 Paris Cedex 14, France. Clinical Infectious Diseases 1997; 24(Suppl 1):S17-8 © 1997 by The University of Chicago. All rights reserved. 1058-4838/97/2401-0034$02.00 From Laboratoire de Microbiologie Medicale, Fondation HOpital SaintJoseph, Paris, France In terms of cost-benefit, it is important to determine the rate of resistance at which the number of therapeutic failures, the use of other antibiotics, the mortality rate, the longer period of disease, and the increased transmission of resistant microorganisms decrease the benefit of antibiotic therapy and dramatically increase the cost [6]. To my knowledge, such a study has never been done for community-acquired infections. Multidrug-resistant bacteria (e.g., pneumococci) will make it even more difficult to perform such studies. The cost of the consequences of resistance has been studied during outbreaks of disease and in patients with hospitalacquired infections [1, 4, 7-9]. The consequences of resistance that are easily measured and expressed in financial terms include extra days of hospitalization and additional costs of diagnostic testing. The cost of antibiotic therapy depends on the number and type of available antibiotics (there are fewer antibiotics available for treatment of multidrug-resistant bacteria, and these antibiotics are often new and expensive) and the duration of treatment and its periodic evaluation. In addition to these costs, there are the costs associated with the campaign to eradicate resistant microorganisms from the unit and the hospital. The cost of morbidity, which has indirect effects, and the cost of mortality are not easy to measure and evaluate economically [3, 10]. A number of problems related to the ecological effects of resistant bacteria and/or genes (e.g., extension of resistant genes between different strains and species, subsequent development of high-level resistance in bacteria with a preexisting low level of resistance, and linkage between resistance and virulence determinants) and its impact in hospitals and nursing homes cannot at present be integrated in the cost of resistance. Patients who are infected with a resistant pathogen should be isolated and treated as quickly as possible to control the spread of infection. To control resistance, physicians must have access to isolation facilities and to laboratory facilities to properly test and rapidly identify the causative microorganisms; in addition, physicians must have easy access to the appropriate antibiotics [5, 11]. Table 1 summarizes some problems related to prescribing appropriate antibiotic treatment. Many more studies are needed to determine the economic benefits of the use of antibiotics and the costs of bacterial resistance [10]. The relative importance of resistance as a cause of mortality and morbidity due to bacterial infections should be assessed in outbreaks of disease, in community-acquired infections, and in hospital infections. In addition, the relationship between resistance and the consumption of antibiotics should be reexamined [5, 12, 13]. Careful evaluation of anti- Acar S18 CID 1997;24 (Suppl 1) Table 1. Problems related to prescribing appropriate antibiotic treatment. Requirements for prescribing appropriate antibiotic treatment • Evaluation of the effect of the empirical or firstline therapy • Access to bacteriologic information Individual patient During an epidemic, extrapolation of data from a few investigated cases From a database in a particular setting • Access to indicated antibiotics • Evaluation after a new antibiotic is prescribed biotic policies and new strategies of antibiotic usage that are designed to influence the use of antibiotics and to minimize the development of resistance should provide data for future research on bacterial resistance and for the development of new antibiotics. References 1. Cohen ML, Fontaine RE, Pollard RA, VonAllmen SD, Vernon TM, Gangarosa EJ. An assessment of patient-related economic costs in an outbreak of salmonellosis. N Engl J Med 1978; 299:459-60. 2. Detsky AS, Naglie IG. A clinician's guide to cost-effectiveness analysis. Ann Intern Med 1990;113:147-54. 3. Freeman J, Goldmann DA, McGowan JE Jr. Confounding and the analysis of multiple variables in hospital epidemiology. Infection Control 1987; 8:465-73. 4. Hogerzeil HV, Sallami AO, Walker GJA, Fernando G. Impact of an essential drugs programme on availability and rational use of drugs. Lancet 1989; 141 –2. 5. Holmberg SD, Solomon SL, Blake PA. Health and economic impacts of antimicrobial resistance. Rev Infect Dis 1987;9:1065-78. Causes of delay in prescribing appropriate antibiotic treatment • No recognition of the resistance problem; the results of the standard treatment are not evaluated • No laboratory facilities • No epidemiological information • Delay in investigating cases in an epidemic • Restricted or delayed access to antibiotics The use of certain antibiotics is restricted by the local formulary The antibiotic is not available in the country in question There are breaks in the system for delivering antibiotics • No follow-up after treatment is given 6. Kereselidze T, Maglacas AM. Nosocomial infections—what WHO is doing. J Hosp Infect 1984; 5(suppl A):7-11. 7. Liss RH, Batchelor FR. Economic evaluations of antibiotic use and resistance—a perspective: report of task force 6. Rev Infect Dis 1987; 9(suppl 3):S297–S312. 8. McGowan JE Jr. Antimicrobial resistance in hospital organisms and its relation to antibiotic use. Rev Infect Dis 1983; 5:1033-48. 9. McGowan JE Jr. Antibiotic resistance in hospital bacteria: current patterns, modes for appearance or spread, and economic impact. Rev Med Microbiol 1991;2:161-9. 10. McGowan JE Jr. Do intensive hospital antibiotic control programs prevent the spread of antibiotic resistance? Infect Control Hosp Epidemiol 1994; 15:478-83. 11. Quintiliani R, Nightingale CH, Crowe HM, Cooper BW, Bartlett RC, Gousse G. Strategic antibiotic decision-making at the formulary level. Rev Infect Dis 1991; 13(suppl 9):S770–S7. 12. Stratton CW IV. In vitro testing: correlations between bacterial susceptibility, body fluid levels and effectiveness of antibacterial therapy. In: Lorian V, ed. Antibiotics in laboratory medicine. 3rd ed. Baltimore: Williams & Wilkins, 1991:849-79. 13. Sturm AW. Effects of a restrictive antibiotic policy on clinical efficacy of antibiotics and susceptibility patterns of organisms. Eur J Clin Microbiol Infect Dis 1990;9:381-9.