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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
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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.