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Measuring the impact of drug resistance is an important step in understanding the scope of the problem and
formulating policies to limit the emergence and spread of resistant organisms. Studies have focused on
measuring the increased costs, morbidity, and mortality in patients with infections due to resistant versus
susceptible organisms. These have generally found that resistance worsens outcomes. By focusing only on
infected patients, however, they may understate the impact of resistance. It is important to recognize that
resistance also affects the treatment of individuals with nonresistant organisms. In areas with high rates of
resistance, physicians and governments have changed empiric therapy for malaria, tuberculosis, acute respi-
ratory infections, and other diseases, increasing overall treatment costs. In some instances, these costs may
exceed those attributable to treatment failure.
Estimates of the impact of antimicrobial resistance can coccus aureus strains causing infections in hospitalized
help policy makers formulate policies that encourage patients [2]. Emergence of resistance in these organisms
appropriate use of antimicrobial drugs and prevent the is a worrisome trend in developed countries, but de-
emergence and spread of resistant organisms. In this veloping nations face a much greater threat from the
article, we describe a framework for measuring the im- growth of resistance in pathogens causing community-
pact of resistance, and we review previous research on acquired diseases such as malaria.
this topic. The term “impact” here refers to the in-
creased treatment costs, prevention costs, and morbid-
FRAMEWORK FOR MEASURING THE
ity and mortality that result from resistance.
BURDEN OF RESISTANCE
Many microorganisms have displayed antimicrobial
resistance, but we focus mainly on the pathogens re- For most diseases, the burden of the illness consists
sponsible for malaria, tuberculosis (TB), diarrheal dis- entirely of treatment costs, morbidity and mortality
eases, and lower respiratory tract infections. According among the ill, and the costs of public prevention efforts.
to the World Health Organization (WHO), these are 4 Infectious diseases are different. Because they often are
of the top 5 infectious diseases in terms of years of life communicable, fear of contagion may induce even un-
lost (the fifth being AIDS) [1]. To date, most studies infected individuals (and their physicians) to alter their
on the impact of antimicrobial resistance have focused behavior [3]. The financial and psychological costs as-
narrowly on resistance to antibacterials and, more spe- sociated with these behavioral changes add to the bur-
cifically, resistance among enterococcal and Staphylo- den of infectious diseases. Philipson and Posner [4]
argue that in the case of AIDS, for example, some in-
dividuals living in areas with a high prevalence of in-
Financial support: AstraZeneca. fection will avoid risky sexual activities. They contend
Reprints or correspondence: Dr. David H. Howard, Rollins School of Public
that the forgone welfare from these activities is a com-
Health, Emory University, 1518 Clifton Rd. NE, Room 610, Atlanta, GA 30322 ponent of the burden of disease. These costs are ex-
(dhhowar@emory.edu).
cluded from standard measures of the cost of AIDS.
Clinical Infectious Diseases 2003; 36(Suppl 1):S4–10
2003 by the Infectious Diseases Society of America. All rights reserved.
Most studies of the impact of antimicrobial resistance
1058-4838/2003/3602S1-0003$15.00 measure costs, morbidity, and mortality in patients
NOTE. IDRO, infections due to resistant organisms; IDSO, infections due to susceptible organisms.
identified as having an infection due to a resistant organism. itial therapy. Practices such as susceptibility testing, which pro-
For the reasons stated above, however, simply adding up the vides more information about patients’ infections, will diminish
incremental costs of persons with infections due to resistant the impact of community characteristics on physicians’ choice
organisms understates the burden of resistance. Just as the of therapy. In the absence of susceptibility testing, however,
number of individuals infected with HIV in a given area may physicians have few clues to help them predict whether or not
affect individuals’ sexual behavior [3], local susceptibility pat- a patient is infected with a resistant pathogen, and therapy will
terns may influence even physicians’ empirical treatment of be selected on the basis of the prevailing levels of resistance in
patients with infections due to susceptible organisms [5–7]. the community. In such instances, the costs of substitution of
Before the identification of the infecting agent and its resistance empiric therapies may account for a large portion of the total
pattern, patients often are given empiric therapy. In areas where burden of resistance [5].
resistant organisms are prevalent, physicians use alternative Another factor to consider in measuring resistance-induced
drugs rather than the medication that, in the absence of resis- drug substitution is the income and wealth of patients and
tance, would be preferred on the basis of cost, dosing schedule, countries. Physicians in developed countries may be quicker to
or side effect profile [5–7]. This substitution occurs for most switch empiric therapies in response to increasing resistance
newly diagnosed patients, not just those with infections due to levels, whereas patients in developing countries may have to
resistant organisms. The excess drug costs, inconvenience, and make do with older drugs and the high rate of treatment failure
side effects experienced by patients in areas where physicians with which they are associated. Consequently, for the same
have switched empiric therapies is a seldom-measured com- underlying rate of resistance, the burden will be larger in de-
ponent of the burden of resistance. Other components of the veloping countries.
burden of resistance include the cost of expanded prevention Table 1 characterizes the costs of resistance according to
and drug-administration efforts (e.g., directly observed therapy whether or not susceptibility testing is performed at diagnosis
[DOT] for TB) that result from concerns about resistance, and and whether or not empiric therapy is effective against resistant
the cost of the increase in disease incidence that results from organisms (where resistance is defined relative to older drugs).
the transmission of infection from individuals whose infections When empiric therapy is ineffective against resistant organisms
due to resistant organisms are not treated in a timely manner. and physicians do not perform susceptibility testing, only pa-
In some instances, use of antimicrobials will reduce disease tients with infections due to resistant organisms will incur costs
prevalence [8]. Because effective treatment for susceptible path- due to resistance. The magnitude of these costs will depend on
ogens reduces their transmission, drug-resistant strains will be the length of time that patients with infections due to suscep-
responsible for a larger proportion of total cases [9]. Ultimately, tible organisms receive ineffective therapy. If physicians per-
the impact of treatment on transmission will be negated, and form susceptibility testing immediately, then the cost of resis-
prevalence may return to pretreatment levels [10]. tance will consist only of the incremental cost of second-line
For reasons outlined above, studies that examine only the therapy and the costs of susceptibility testing. If the prevalence
costs of treatment failure in patients with infections due to of resistance is high, then physicians will begin using second-
resistant organisms may understate the impact of resistance. line drugs as empiric therapy [5, 7]. As stated above, the in-
The degree to which the cost of treatment differs from the cremental cost of these drugs comprises the burden of resistance
actual burden will depend on how heavily physicians weigh because patients with infections due to resistant organisms are
individual versus community characteristics when choosing in- treated with effective therapy initially. Obviously, there are