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Letter
Measuring Impact of Antimicrobial
Resistance
Mary-Claire Roghmann,*
Douglas D. Bradham,† Min Zhan,* Scott K. Fridkin,‡ and Trish M. Perl§
*University of Maryland School of Medicine, Baltimore, Maryland, USA:
†VA Maryland Health Care System, Baltimore, Maryland, USA; ‡Centers for
Disease Control and Prevention, Atlanta, Georgia, USA; and §Johns Hopkins
Medical Institutions, Baltimore, Maryland, USA
Suggested
citation for this article
To the Editor: Staphylococcus aureus and Enterococcus
faecium commonly cause healthcare-associated bloodstream infections
(BSI) in the intensive care unit (ICU). Antimicrobial resistance is increasing
in both organisms. The impact of antimicrobial resistance on dying of
BSI has been studied extensively (1,2). Many studies
have concluded that BSI caused by an antimicrobial-resistant organism
results in higher death rates (1,3–8). However, as discussed
in a recent report by Kaye et al., "outcome studies of antimicrobial
drug resistance are notoriously hard to perform because of confounding
variables related to coexisting conditions" (9).
Indeed, almost all studies have shown that infections with antimicrobial-resistant
organisms occur later in hospitalization than infections with antimicrobial-susceptible
organisms, which suggests that differences in death rates may be, at least
in part, caused by a difference in the patients' underlying illnesses
and protracted hospital course. We report 2 additional methodologic issues
that can affect estimates of the impact of antimicrobial resistance: combining
different organisms and combining populations from different types of
ICUs.
The original objective of our multicenter observational study was to
quantify the clinical impact of antimicrobial resistance in S. aureus
and E. faecium infections when these bacteria cause a specific
type of infection: a monomicrobial, ICU-attributable, central vascular
catheter–associated bloodstream infection (CVC-BSI). We studied 187 adult
ICU patients with BSI caused by S. aureus and E. faecium
at 3 tertiary care institutions from 1994 to 1999. The institutional review
boards of each institution and the Centers for Disease Control and Prevention
approved this study. Severity of illness was measured with an APACHE II
score at ICU admission and on day 7 in the ICU (if applicable). The score
would indicate the patient's risk of dying in the hospital before a BSI
developed by using a measure validated for predicting in-hospital deaths
in ICU patients (10).
The study population stratified by organism is shown in the Table.
Fifty-eight percent of patients had CVC-BSI with S. aureus, and
42% had CVC-BSI with E. faecium. Overall, 58% of the organisms
causing CVC-BSI were resistant to oxacillin if S. aureus or to
vancomycin if E. faecium. However, patients with E. faecium
CVC-BSI were more likely to be infected with antimicrobial-resistant bacteria
(69% versus 50%, p<0.01), and had a higher mortality rate (54% versus
34%, p<0.01) than patients with S. aureus CVC-BSI. This finding
indicates that the type of organism (E. faecium versus S. aureus)
confounds the association between resistance and death. In addition, the
distribution of ICU type by organism varies, which suggests that patient
populations infected with these 2 different organisms were different in
other ways. Thus, confounding factors for the association between resistance
and death may differ for E. faecium and S. aureus, and analysis
of the 2 organisms should be conducted separately. This is consistent
with the results of Kaye et al. who showed that the effect of resistance
was higher for S. aureus (odds ratio [OR] 3.4) than for E. faecium
(OR 2.5) by using separate analyses to show death rates (9).
Furthermore, these researchers found different confounding factors in
the adjusted analysis of S. aureus than in the adjusted analysis
of E. faecium. Because of the need to conduct separate analyses,
which reduced our statistical power, our study was ultimately unable to
show a difference in death rates if it existed.
In summary, future studies measuring the impact of antimicrobial resistance
on death rates should be restricted to a specific type of infection cause
by a single organism in a uniform setting using a validated system to
predict mortality in that setting. As such, future studies should involve
multiple study sites.
This project was
supported by cooperative agreements (U50/CCU316578-01 and UR8/CCU315092-03)
from the Centers for Disease Control and Prevention. Mary-Claire Roghmann
was supported by a VA Career Development Award during the time this
work was performed.
References
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MJ, Karchmer AW, Carmeli Y. Comparison
of mortality associated with methicillin-resistant and methicillin-susceptible
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- Niederman MS. Impact
of antibiotic resistance on clinical outcomes and the cost of care.
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methicillin-resistant Staphylococcus aureus bacteremia: Is it
any worse than nosocomial methicillin-sensitive Staphylococcus aureus
bacteremia? Infect Control Hosp Epidemiol. 2000;21:645–8.
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factors for mortality in Staphylococcus aureus bacteremia.
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DJ, et al. Staphylococcus
aureus bacteremia among elderly vs younger adult patients: comparison
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- Kaye KS, Engemann JJ, Mozaffari E, Carmeli Y. Reference
group choice and antibiotic resistance outcomes. Emerg Infect Dis.
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Table. Description of
187 adult patients with central vascular catheter-associated bloodstream
infections with Staphylococcus aureus or Enterococcus
faecium attributable to the intensive care unit*
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Characteristics
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S. aureus (n = 109)
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E. faecium (n = 78)
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p value
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Patient demographics
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Male (%)
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74
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56
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0.02
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Mean age, y (SD)
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58 (17)
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56 (16)
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0.32
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Type of ICU
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<0.01
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Cardiac (%)
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20
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10
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Cardiothoracic surgery (%)
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6
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6
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Medical (%)
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20
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40
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Neurologic/neurosurgical (%)
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6
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0
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Surgical (%)
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20
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37
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Trauma (%)
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28
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6
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Severity of illness
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Mean APACHE II score at ICU admission
(SD)
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19 (8)
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21 (9)
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0.12
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Mean APACHE II score within 7
days of BSI (SD)
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17 (8)
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20 (8)
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0.05
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Resistant infections (%)
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50
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69
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0.01
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In-hospital death rate (%)
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34
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54
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<0.01
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*SD, standard deviation; ICU, intensive care unit.
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Suggested citation
for this article:
Roghmann M-C, Bradham
DD, Zhan M, Fridkin SK, Perl TM. Measuring impact of antimicrobial resistance
[letter]. Emerg Infect Dis [serial on the Internet]. 2005 Jun [date
cited]. Available from http://www.cdc.gov/ncidod/EID/vol11no06/04-1220.htm
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