ORIGINAL INVESTIGATION

Age- and Sex-Associated Trends

in Bloodstream Infection
A Population-Based Study in Olmsted County, Minnesota
Daniel Z. Uslan, MD; Sarah J. Crane, MD; James M. Steckelberg, MD; Franklin R. Cockerill III, MD;
Jennifer L. St. Sauver, PhD; Walter R. Wilson, MD; Larry M. Baddour, MD

Background: Despite increasing concerns about antimicrobial resistance and emerging pathogens among blood
culture isolates, contemporary population-based data on
the age- and sex-specific incidence of bloodstream infections (BSIs) are limited.
Methods: Retrospective, population-based, cohort study
of all residents of Olmsted County, Minnesota, with a BSI
between January 1, 2003, and December 31, 2005. The
medical record linkage system of the Rochester Epidemiology Project and microbiology records were used to
identify incident cases.

more common in males than females (23.8% vs 13.9%;

P=.002). The age-adjusted incidence rate of BSI was 156
per 100 000 person-years for females and 237 per 100 000
person-years for males (P.001), with an age- and sexadjusted rate of 189 per 100 000 person-years. Rates of
BSI due to gram-positive cocci were 64 per 100 000 person-years for females and 133 per 100 000 person-years
for males (P.001); gram-negative bacillus BSI rates (85/
100 000 person-years for females and 79/100 000 personyears for males) were not significantly different between sexes (P=.79). The rate of S aureus BSI was 23 per
100 000 person-years for females and 46 per 100 000 person-years for males (P =.005).

Results: A total of 1051 unique patients with positive

blood culture results were identified; 401 (38.2%) were

classified as contaminated. Of 650 patients with cultures deemed clinically relevant, the mean SD age was
63.123.1 years, and 52.5% were male. The most common organisms identified were Escherichia coli (in 163
patients with BSIs [25.1%]) and Staphylococcus aureus (in
108 patients with BSIs [16.6%]). Nosocomial BSIs were

Author Affiliations: Divisions

of Infectious Diseases
(Drs Uslan, Steckelberg,
Wilson, and Baddour) and
Primary Care Internal Medicine
(Dr Crane), Department of
Medicine, Division of
Microbiology, Department of
Pathology (Dr Cockerill), and
Department of Health Sciences
Research (Dr St. Sauver), Mayo
Clinic College of Medicine,
Rochester, Minn. Dr Uslan is
now with the Division of
Infectious Diseases, David
Geffen School of Medicine at
UCLA, Los Angeles, Calif.

Conclusions: There are significant differences in the age

and sex distribution of organisms among patients with
BSIs. The incidence of BSI increases sharply with increasing age and is significantly higher in males, mainly because of nosocomial organisms, including S aureus.

Arch Intern Med. 2007;167:834-839

ORTALITY FROM BLOOD-

stream infections
(BSIs) remains high,
with a case-fatality rate
as high as 20% to 30%,
despite significant advances in antimicrobial therapy and automated blood culture
techniques.1-3 Concerns about increasing antimicrobial resistance among blood isolates have been noted, especially due to organisms with limited available treatment
options, such as extended-spectrum
-lactamaseproducing gram-negative bacilli or methicillin-resistant Staphylococcus
aureus.4 Recent data suggest that rates of BSI
due to S aureus have been increasing,5,6 with
the rate of nosocomial primary S aureus BSI
more than doubling.7 Previous European
observations of BSIs from the 1980s and
1990s have estimated incidence rates of BSI
to be between 76.5 and 153 per 100 000.8,9
There has been speculation that as rates of
BSI increase, complications of BSI, such as
infective endocarditis (IE)10 and vertebral

(REPRINTED) ARCH INTERN MED/ VOL 167, APR 23, 2007

834

osteomyelitis,11 also will increase.12 However, there have been minimal recent population-based data evaluating trends in BSI,
and it is unclear which populations are at
highest risk for BSI due to different organisms. Such data are necessary for targeting
treatment and prevention efforts. We, therefore, conducted a retrospective, populationbased, cohort study to evaluate age- and sexassociated trends in the incidence of BSI in
a geographically defined population.
METHODS

STUDY SETTING
Olmsted County is located in southeastern Minnesota and has population characteristics similar to those of US non-Hispanic whites.13 The
population according to the 2000 census was
124 277. There is a low prevalence of intravenous drug abuse.14 The Rochester Epidemiology Project is a medical record linkage system
that indexes medical records from all individu-

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als seen by a health care provider and residing in Olmsted

County. A single dossier exists for each patient, into which medical diagnoses, surgical interventions, and other key information from medical records are regularly abstracted and entered into computerized indexes using the International
Classification of Diseases, Ninth Revision, Clinical Modification.13,15 The Rochester Epidemiology Project provides access
to all inpatient, outpatient, emergency department, and nursing home records of county residents, regardless of provider,
allowing for accurate population-based incidence studies of disease causes and outcomes.13

CASE ASCERTAINMENT
Cases of BSI were identified via computerized databases from both
microbiology laboratories in Olmsted County: Mayo Clinic and
Olmsted Medical Center. All positive blood culture results identified between January 1, 2003, and December 31, 2005, were included. The BSIs were classified as nosocomial, health care associated, or community acquired.16 The Mayo Clinic uses an
automated blood culture system (BACTEC 9240) and aerobic
(Plus/10 Aerobic/F) and anaerobic (Lytic/10 Anaerobic/F) culture vials, and Olmsted Medical Center also uses an automated
blood culture system (BACTEC 9050) and aerobic (Standard/10
Aerobic/F) and anaerobic (Anaerobic/F) culture vials (BD Biosciences, San Jose, Calif). Blood cultures were identified using
standard microbiology techniques according to the Clinical Laboratory Standards Institute. Both laboratories are certified by the
College of American Pathologists. There were no significant
changes in culture techniques during the study period. The medical records of all cases of BSI were manually reviewed by the primary investigator (D.Z.U.) to confirm the diagnosis and residency status. Any cases of BSI judged problematic were reviewed
with an experienced infectious diseases investigator (L.M.B.). Nonresidency in Olmsted County at the time of BSI was an exclusion
criterion. Patients were followed up from the date of BSI through
their most recent health care encounter, as documented in the
Rochester Epidemiology Project database.
Given that contaminated blood cultures may represent up
to half of all positive blood culture results,17-20 we used the definition of contamination as previously described by Bekeris et
al.21 A blood culture was considered to be contaminated if 1
or more of the following were identified in only 1 bottle: coagulase-negative staphylococcal species, Propionibacterium acnes, Micrococcus species, viridans group streptococci, Corynebacterium species, or Bacillus species.

DATA ANALYSIS
Incidence rates of BSI were derived using cases of BSI as the
numerator and assuming that the entire Olmsted County population between 2003 and 2005 was at risk of infection. The denominator was interpolated from the 2000 Olmsted County census figures, using an annual projected population growth rate
of 1.9% per year. Incidence rates were directly adjusted to the
age distribution of the US white 2000 population.22 Only initial episodes of BSI were included as incident cases. For patients with multiple events, incidence rates were calculated based
on the first event only. Deaths were confirmed via Minnesota
electronic death certificate data, and 95% confidence intervals
(CIs) around the point estimates were calculated assuming that
incident cases followed a Poisson error distribution. Differences in means between multiple groups were tested with 1-way
analysis of variance. Cox proportional hazards modeling was
used to examine the association between organism and survival while adjusting for age and sex. The level of significance
for all statistical tests was 2-sided, with .05. All analyses were
(REPRINTED) ARCH INTERN MED/ VOL 167, APR 23, 2007
835

conducted using computer software ( JMP software, version

6.0.0; SAS Institute Inc, Cary, NC). The institutional review
boards of Mayo Clinic and Olmsted Medical Center approved
the study.
RESULTS

A total of 1051 unique patients with positive blood culture results between January 1, 2003, and December 31,
2005, were identified. Of these patients, 401 (38.2%) had
positive blood culture results that met the definition of
contamination. Of the contaminants, 286 (71.3%) were
coagulase-negative staphylococci, 29 (7.2%) were Corynebacterium species, 18 (4.5%) were Micrococcus species, and 12 (3.0%) were Propionibacterium acnes. A total
of 650 patients had positive blood culture results that were
deemed clinically relevant, and were included as incident cases. Multiple BSIs were noted in 29 patients (4.5%).
The meanSD age of the cases was 63.123.1 years, and
52.5% were male. Of the cases, 64 (9.8%) were nonwhite, reflecting the general demographic characteristics of southeastern Minnesota. A total of 188 cases
(28.9%) occurred in patients older than 80 years. Causative organisms by epidemiologic category are shown in
Table 1. The 2 most common causative organisms overall were Escherichia coli (163 BSIs [25.1%]) and S aureus (108 BSIs [16.6%]).
Of the BSIs, 124 (19.1%) were nosocomial, 237 (36.5%)
were health care associated, and 289 (44.5%) were community acquired. Males were more likely to have nosocomial BSIs than females (Figure 1). Females had 43
nosocomial BSIs (13.9%), 112 health careassociated BSIs
(36.2%), and 154 community-acquired BSIs (49.8%),
compared with 81 nosocomial BSIs (23.8%), 125 health
careassociated BSIs (36.7%), and 135 communityacquired BSIs (39.6%) for males (P =.002).
Age- and sex-specific incidence rates are shown in
Table 2. The annual incidence of BSIs during the study
period, age and sex adjusted to the US white 2000 census, was 189 (95% CI, 174-204) per 100 000 person-years.
The age-adjusted incidence rates were 156 for females
(95% CI, 138-174) and 237 for males (95% CI, 211263) (P.001). The incidence rate of BSIs in the eldest
patients (80 years) was 1455 (95% CI, 1268-1691) per
100 000 person-yearsmore than 3 times greater than
the incidence rate among the next oldest age group (60-79
year olds). In addition, the incidence rate in males in this
group (rate, 2149; 95% CI, 1695-2603) was almost twice
that of females (rate, 1143; 95% CI, 922-1366) (P.001).
Incidence rates increased with age across both sexes, but
males had substantially higher incidence rates in the older
age groups (70 years) (Figure 2).
To further investigate sex-associated differences in patients with BSIs, we compared rates of BSI due to grampositive cocci vs those due to gram-negative bacilli. There
were 321 total gram-positive BSIs (49.8%), 281 gramnegative BSIs (43.6%), and 43 polymicrobial BSIs (6.7%).
The mean age among those with polymicrobial BSIs (71.5
years; 95% CI, 64.6-78.5 years) was greater than among
those with gram-positive BSIs (61.8 years; 95% CI, 59.364.4 years) or gram-negative BSIs (63.1 years; 95% CI,
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Table 1. Rank Order of Microorganisms in 650 BSIs, 2003 to 2005, in Olmsted County, Minnesota
Total
(N = 650)

Rank
1
2
3
4
5
6
7
8
9
10
11
12
13

Nosocomial
(n = 124)

Escherichia coli
Staphylococcus aureus
Coagulase-negative staphylococci
Klebsiella species
-Hemolytic streptococci
Polymicrobial (2 organisms)*
Viridans group streptococci
Streptococcus pneumoniae
Enterococcus species
Anaerobe
Pseudomonas species
Candida species
Other

S aureus
Coagulase-negative staphylococci
E coli
Enterococcus species
Klebsiella species
Pseudomonas species
Candida species
Anaerobe
Polymicrobial
-Hemolytic streptococci
Viridans group streptococci
S pneumoniae
Other

Health Care Associated

(n = 237)
E coli
S aureus
-Hemolytic streptococci
Coagulase-negative staphylococci
Klebsiella species
Polymicrobial
Enterococcus species
Viridans group streptococci
S pneumoniae
Pseudomonas species
Anaerobe
Candida species
Other

Community Acquired
(n = 289)
E coli
S aureus
Klebsiella species
-Hemolytic streptococci
Viridans group streptococci
S pneumoniae
Polymicrobial
Coagulase-negative staphylococci
Anaerobe
Enterococcus species
Pseudomonas species
Candida species
Other

Abbreviation: BSI, bloodstream infection.

*Polymicrobial BSIs are counted with their respective organisms.
Includes Citrobacter freundii, Enterobacter cloacae, Salmonella (nontyphi), Proteus species, Acinetobacter species, Haemophilus influenzae, Serratia marcescens,
Moraxella species, Stenotrophomonas maltophilia, Prevotella species, Neisseria meningitidis, and Lactobacillus species (all 5 BSIs).

CA

HCA

Nosocomial

100
90
39.6

80
49.8

% of BSIs

70
60
50
36.7

40
30

36.2

20
10

23.8
13.9

0
Female

Male

Sex

There was a similar difference in rates of BSIs due to

viridans group streptococci, 25 (of 35, or 71.4%) of
which were in males (incidence, 16/100 000 personyears for males and 5/100 000 person-years for
females; P = .01). Comparisons of incidence rates by
sex for the 6 most common organisms are shown in
Figure 4.
The median duration of follow-up after BSI was 329
days (interquartile range, 94-668 days). Eighty-eight individuals died during the initial hospitalization (crude
mortality, 13.5%). There was no overall difference in mortality by sex (hazard ratio for males, 1.07; 95% CI, 0.681.70; P =.76). The hazard ratio for death corresponding
to a 10-year increase in age was 1.18 (95% CI, 1.061.32; P =.002). The age-adjusted hazard ratio for death
due to nosocomial BSI was 4.64 (95% CI, 2.52-8.80;
P.001).

Figure 1. Distribution of the 650 bloodstream infections (BSIs) by health

care exposure category. CA indicates community acquired; and HCA, health
care associated. Percentages may not total 100 due to rounding.

60.4-65.8 years) (P=.03). The overall incidence of grampositive BSIs was 64 (95% CI, 53-75) per 100 000 personyears for females and 133 (95% CI, 112-153) per 100 000
person-years for males (P.001). Gram-negative BSI incidence was 85 (95% CI, 72-98) per 100 000 personyears for females and 79 (95% CI, 64-95) per 100 000
person-years for males (P = .79). Age- and sexassociated trends in the incidence of gram-positive vs
gram-negative BSI are shown in Figure 3. For E coli,
the age-adjusted incidence rate was 61 (95% CI,
50-72) per 100 000 person-years for females and 32
(95% CI, 22-42) per 100 000 person-years for males
(P = .002); the age- and sex-adjusted rate was 48 (95%
CI, 41-55) per 100 000. The overall age-adjusted incidence rate (per 100 000 person-years) for S aureus was
23 (95% CI, 16-30) for females and 46 (95% CI,
34-57) for males (P = .005); the age- and sex-adjusted
rate was 32 (95% CI, 26-39) per 100 000 person-years.
(REPRINTED) ARCH INTERN MED/ VOL 167, APR 23, 2007
836

COMMENT

In our geographically defined population, the incidence

of BSI increased sharply with age. Bloodstream infection due to E coli was far more common in females, likely
reflecting the propensity for urinary tract infections, including pyelonephritis, in females. There were marked
differences in the rates of S aureus BSI between males and
females, with rates in males almost double those in females in some age groups. A similar difference was noted
with viridans group streptococci.
The difference in sex-specific incidence rates is striking. Reasons for the increased frequency of BSI due to
gram-positive cocci in males seem directly related to the
increased number of nosocomial BSIs in males. Increased intravenous drug abuse among males seems an
unlikely explanation, given that most cases were in elderly persons and given the low prevalence of intravenous drug abuse in Olmsted County.14 It is tempting to
speculate that this proclivity among older males for BSIs
due to gram-positive cocci may explain, in part, the obWWW.ARCHINTERNMED.COM

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Table 2. Age- and Sex-Specific Annual Incidence Rates of BSI per 100 000, in 650 Patients in Olmsted County, Minnesota,
2003 to 2005*
Age Group, y
Type of Infection
Escherichia coli
Female
Male
Total
Staphylococcus aureus
Female
Male
Total
Gram-positive cocci
Female
Male
Total
Gram-negative bacilli
Female
Male
Total
All BSIs
Female
Male
Total

0-18

19-39

40-59

60-79

80

Total

5.4 (3)
1.7 (1)
3.5 (4)

26.2 (16)
10.0 (6)
18.2 (22)

47.5 (26)
11.6 (6)
29.9 (32)

161.4 (39)
101.4 (21)
133.7 (60)

403.6 (36)
249.9 (10)
356.0 (46)

61.5 (120)
31.1 (44)
47.7 (164)

1.8 (1)
10.3 (6)
6.1 (7)

0
5.0 (3)
2.5 (3)

18.3 (10)
30.8 (16)
24.4 (26)

78.7 (19)
111.0 (23)
93.6 (42)

145.8 (13)
424.8 (17)
232.2 (30)

22.7 (43)
45.3 (65)
32.0 (108)

14.4 (8)
29.1 (17)
21.9 (25)

21.3 (13)
23.4 (14)
22.4 (27)

40.2 (22)
100.2 (52)
69.4 (74)

169.7 (41)
318.5 (66)
238.4 (107)

470.9 (42)
1149.5 (46)
681.1 (88)

64.1 (124)
133.1 (188)
93.2 (321)

9.0 (5)
8.6 (5)
8.8 (10)

36.0 (22)
20.1 (12)
28.2 (34)

80.3 (44)
50.1 (26)
65.6 (70)

186.2 (45)
188.2 (39)
187.2 (84)

594.2 (53)
749.7 (30)
642.4 (83)

85.3 (161)
78.5 (111)
80.9 (281)

23.5 (13)
37.6 (22)
30.7 (35)

58.9 (36)
46.9 (28)
52.9 (64)

124.1 (68)
158.0 (82)
140.6 (150)

372.5 (90)
593.6 (123)
474.6 (213)

1143.7 (102)
2149.1 (86)
1455.0 (188)

156.4 (309)
237.3 (341)
188.9 (650)

Abbreviation: See Table 1.

*Data are given as incidence per 100 000 person-years. Total numbers in each age group include polymicrobial BSIs and Candida species. Numbers in
parentheses indicate the actual number of BSI cases.
Total rates by sex are age adjusted, and overall total rates are age and sex adjusted to the US white 2000 census.

(REPRINTED) ARCH INTERN MED/ VOL 167, APR 23, 2007

837

3500

Incidence Rate per 100 000 Person-Years

servation that IE predominantly affects older males.23-27

The incidence rates of IE in a population-based setting
have been previously described, with an age- and sexadjusted rate of 4.9 per 100 000 person-years.14,23 The incident rate ratio for male vs female sex was 2.5:1.0.14
Recent series of patients, from the International Collaboration on Endocarditis, with IE due to S aureus reported
that 60% to 70% were male.28,29 In our study, the rate of
S aureus BSIs in males was twice that in females. The sex
discrepancy in IE cases could be explained by differences in underlying rates of BSI. This is a novel observation that deserves further investigation.
Data derived from population-based studies for BSI in
the United States were not previously available. The incidence of BSI in our study (190 per 100 000 person-years)
exceeds that of prior estimated incidence rates of BSI from
Europe from the 1980s and 1990s (76.5 and 153 per
100 000).8,9 It is unclear if this is because of a true increase
in the rates of BSI overall, changes in blood culture techniques resulting in detection bias, or differing population
demographics in the varying regions studied.
The rank order of microorganisms defined in our study
was similar to that reported previously.20,30,31 In our population-based study, E coli remained the most common
causative organism, followed by S aureus. These trends
for organisms isolated are similar to a recent large series4 of BSIs from the United Kingdom, which also reported E coli and S aureus as the most common organisms isolated. A recent analysis32 of 24 179 cases of
nosocomial BSIs in US hospitals found that the most common organisms were coagulase-negative staphylococci,
S aureus, enterococci, and Candida species. We specu-

Male
Female

3000
2500
2000
1500
1000
500
0
0

10

20

40

50

60

70

80

90

Age, y

Figure 2. Incidence rates of bloodstream infection by age, from January 1,

2003, to December 31, 2005, in Olmsted County, Minnesota.

late that the difference in rank order of microorganisms

seen in our study is because of the inclusion of community-acquired and health careassociated BSIs.
Our study has several limitations. We used a set definition of blood culture contamination to avoid ascertainment bias in retrospectively identifying incident cases.
However, as noted by Bekeris et al,21 isolates classified
as contaminants using this study definition could still be
reflective of clinical infection. Prior studies31,33 of BSIs with
coagulase-negative staphylococci have suggested that approximately 25% to 30% of isolates were considered to
be pathogens. In our study, there were 58 clinically significant coagulase-negative staphylococcal BSIs (16.9%)
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30

of 344 positive blood culture results for this organism.

Our results may, therefore, underestimate the true incidence of BSIs due to this organism.
Another limitation is that Olmsted County is a relatively homogeneous population in regard to racial and
ethnic composition, with a low prevalence of intravenous drug abuse. Therefore, the generalizability of our

studys findings to groups underrepresented in the population could be limited. However, as previously noted,
the characteristics of the Olmsted County population are
similar to those of other US whites, with the exception
of slightly higher income and education levels, and studies in Olmsted County can be extrapolated to a large part
of the general population.13 Presumably, an increased
prevalence of intravenous drug abuse would result in an
increase in the incidence of BSI in younger age groups.
Last, it is possible that residents of the population could
have been examined and diagnosed as having BSI at an
institution outside of Olmsted County, although the geographic isolation of Olmsted County from other urban
centers makes this unlikely.13,23 Only patients with BSI
detected via positive blood culture result were included
as incident cases; therefore, patients with BSIs who did
not have blood cultures drawn (ie, did not seek medical
attention or were treated empirically without cultures)
would have been missed. Patients who received antimicrobial therapy prior to cultures being obtained may have
falsely negative cultures. Our results, then, would be an
underestimate of the true incidence of BSIs. It is difficult to know what impact, if any, this would have on ageand sex-specific incidence rates.
The primary strength of the study is that through use
of the Rochester Epidemiology Project we were able to
study incidence of BSI in a large population without the
referral bias seen with single-institution studies of BSI.14
The essentially complete ascertainment of all BSI cases
in our study for a population of known size, age, and sex
distribution allows an unbiased and accurate estimation
of incidence rates.
In conclusion, our data indicate that there are striking sex-associated differences in organism distribution
among patients with BSI. Escherichia coli BSI was more
common in females, and BSI due to S aureus and viridans group streptococci was more common in males. The
epidemiologic and pathogenic factors associated with these
sex differences deserve further investigation. In addition, sex-specific BSI trends may have implications for
empirical antimicrobial therapy in patients with pre-

Incidence Rate per 100 000 Person-Years

1600
Male
1400

Female

1200
1000
800
600
400
200
0

Incidence Rate per 100 000 Person-Years

1600
1400
1200
1000
800
600
400
200
0
0

10

20

30

40

50

60

70

80

90

Age, y

Figure 3. Incidence rates of gram-positive cocci (A) and gram-negative

bacilli (B) bloodstream infections by age, from January 1, 2003, to December
31, 2005, in Olmsted County, Minnesota.

Incidence Rate per 100 000 Person-Years

80
Male
Female

70
60
50
40
30
20
10

Escherichia
coli

Staphylococcus
aureus

CoagulaseNegative
Staphylococci

Klebsiella
Species

-Hemolytic
Streptococci

Viridans Group
Streptococci

Organism

Figure 4. Incidence rates of the 6 most commonly isolated microorganisms in 650 patients by sex, from January 1, 2003, to December 31, 2005, in Olmsted
County, Minnesota. Error bars represent 95% confidence intervals calculated around the point estimate, assuming incident cases follow a Poisson error
distribution. P values for comparisons by sex for each organism are as follows: Escherichia coli, P = .002; Staphylococcus aureus, P = .005; coagulase-negative
staphylococci, P= .10; Klebsiella species, P=.07; -hemolytic streptococci, P = .60; and viridans group streptococci, P = .01.

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838

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sumed BSI, especially as rates of antimicrobial resistance increase. Further research on specific sexassociated risk factors for BSI is needed to clarify these
trends.
Accepted for Publication: December 26, 2006.
Correspondence: Daniel Z. Uslan, MD, Division of Infectious Diseases, David Geffen School of Medicine at
UCLA, 10833 LeConte Ave, 37-121 CHS, Los Angeles,
CA 90095 (duslan@mednet.ucla.edu).
Author Contributions: Dr Uslan had full access to all of
the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Uslan, Crane, Steckelberg,
Cockerill, St. Sauver, and Baddour. Acquisition of data:
Uslan and Cockerill. Analysis and interpretation of data:
Uslan, Steckelberg, Cockerill, St. Sauver, Wilson, and
Baddour. Drafting of the manuscript: Uslan and St. Sauver.
Critical revision of the manuscript for important intellectual content: Uslan, Crane, Steckelberg, Cockerill, St.
Sauver, Wilson, and Baddour. Statistical analysis: Uslan.
Obtained funding: Steckelberg and Baddour. Administrative, technical, and material support: Crane, Steckelberg,
Wilson, and Baddour. Study supervision: Steckelberg,
Cockerill, Wilson, and Baddour. Epidemiologic expertise: St. Sauver.
Financial Disclosure: None reported.
Previous Presentation: This study was presented in part
at the Infectious Diseases Society of America Annual Meeting; October 15, 2006; Toronto, Ontario.
Acknowledgment: We thank Imad Tleyjeh, MD, for assistance with the study design; Emily Vetter and Barbara
Yawn, MD, for assistance in obtaining microbiology records; and Kathy Parsons for administrative support.
REFERENCES
1. Pedersen G, Schonheyder HC, Sorensen HT. Antibiotic therapy and outcome of
monomicrobial gram-negative bacteraemia: a 3-year population-based study. Scand
J Infect Dis. 1997;29:601-606.
2. Perl TM, Dvorak L, Hwang T, Wenzel RP. Long-term survival and function after
suspected gram-negative sepsis. JAMA. 1995;274:338-345.
3. Bates DW, Pruess KE, Lee TH. How bad are bacteremia and sepsis? outcomes
in a cohort with suspected bacteremia. Arch Intern Med. 1995;155:593-598.
4. Reacher MH, Shah A, Livermore DM, et al. Bacteraemia and antibiotic resistance of its pathogens reported in England and Wales between 1990 and 1998:
trend analysis. BMJ. 2000;320:213-216.
5. Steinberg JP, Clark CC, Hackman BO. Nosocomial and community-acquired Staphylococcus aureus bacteremias from 1980 to 1993: impact of intravascular devices and methicillin resistance. Clin Infect Dis. 1996;23:255-259.
6. Lowy FD. Staphylococcus aureus infections. N Engl J Med. 1998;339:520-532.
7. Banerjee SN, Emori TG, Culver DH, et al. Secular trends in nosocomial primary
bloodstream infections in the United States, 1980-1989: National Nosocomial
Infections Surveillance System. Am J Med. 1991;91(suppl):86S-89S.
8. Pedersen G, Schonheyder HC, Kristensen B, Sorensen HT. Communityacquired bacteraemia and antibiotic resistance: trends during a 17-year period
in a Danish county. Dan Med Bull. 2000;47:296-300.
9. Madsen KM, Schonheyder HC, Kristensen B, Sorensen HT. Secular trends in incidence and mortality of bacteraemia in a Danish county 1981-1994. APMIS. 1999;
107:346-352.

(REPRINTED) ARCH INTERN MED/ VOL 167, APR 23, 2007

839

10. Fernandez-Guerrero ML, Verdejo C, Azofra J, de Gorgolas M. Hospital-acquired

infectious endocarditis not associated with cardiac surgery: an emerging problem.
Clin Infect Dis. 1995;20:16-23.
11. Jensen AG, Espersen F, Skinhoj P, Rosdahl VT, Frimodt-Moller N. Increasing frequency of vertebral osteomyelitis following Staphylococcus aureus bacteraemia in Denmark 1980-1990. J Infect. 1997;34:113-118.
12. Fowler VG Jr, Olsen MK, Corey GR, et al. Clinical identifiers of complicated Staphylococcus aureus bacteremia. Arch Intern Med. 2003;163:2066-2072.
13. Melton LJ III. History of the Rochester Epidemiology Project. Mayo Clin Proc.
1996;71:266-274.
14. Steckelberg JM, Melton LJ III, Ilstrup DM, Rouse MS, Wilson WR. Influence of
referral bias on the apparent clinical spectrum of infective endocarditis. Am J
Med. 1990;88:582-588.
15. Bower JH, Maraganore DM, McDonnell SK, Rocca WA. Incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976-1990. Neurology. 1999;
52:1214-1220.
16. Friedman ND, Kaye KS, Stout JE, et al. Health careassociated bloodstream infections in adults: a reason to change the accepted definition of communityacquired infections. Ann Intern Med. 2002;137:791-797.
17. Bates DW, Goldman L, Lee TH. Contaminant blood cultures and resource utilization: the true consequences of false-positive results. JAMA. 1991;265:
365-369.
18. Aronson MD, Bor DH. Blood cultures. Ann Intern Med. 1987;106:246-253.
19. MacGregor RR, Beaty HN. Evaluation of positive blood cultures: guidelines for
early differentiation of contaminated from valid positive cultures. Arch Intern Med.
1972;130:84-87.
20. Weinstein MP, Murphy JR, Reller LB, Lichtenstein KA. The clinical significance
of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults, II: clinical observations, with special reference to
factors influencing prognosis. Rev Infect Dis. 1983;5:54-70.
21. Bekeris LG, Tworek JA, Walsh MK, Valenstein PN. Trends in blood culture contamination: a College of American Pathologists Q-Tracks study of 356 institutions.
Arch Pathol Lab Med. 2005;129:1222-1225.
22. US Census Bureau. Olmsted County QuickFacts. http://quickfacts.census.gov
/qfd/states/27/27109.html. Accessed December 15, 2006.
23. Tleyjeh IM, Steckelberg JM, Murad HS, et al. Temporal trends in infective endocarditis: a population-based study in Olmsted County, Minnesota. JAMA. 2005;
293:3022-3028.
24. Hoen B, Alla F, Selton-Suty C, et al; Association pour lEtude et la Prevention de
lEndocardite Infectieuse (AEPEI) Study Group. Changing profile of infective endocarditis: results of a 1-year survey in France. JAMA. 2002;288:75-81.
25. Fonager K, Lindberg J, Thulstrup AM, Pedersen L, Schonheyder HC, Sorensen
HT. Incidence and short-term prognosis of infective endocarditis in Denmark,
1980-1997. Scand J Infect Dis. 2003;35:27-30.
26. Benn M, Hagelskjaer LH, Tvede M. Infective endocarditis, 1984 through 1993: a
clinical and microbiological survey. J Intern Med. 1997;242:15-22.
27. Griffin MR, Wilson WR, Edwards WD, OFallon WM, Kurland LT. Infective endocarditis: Olmsted County, Minnesota, 1950 through 1981. JAMA. 1985;254:
1199-1202.
28. Miro JM, Anguera I, Cabell CH, et al; International Collaboration on Endocarditis
Merged Database Study Group. Staphylococcus aureus native valve infective endocarditis: report of 566 episodes from the International Collaboration on Endocarditis Merged Database. Clin Infect Dis. 2005;41:507-514.
29. Fowler VG Jr, Miro JM, Hoen B, et al; ICE Investigators. Staphylococcus aureus
endocarditis: a consequence of medical progress. JAMA. 2005;293:3012-3021.
30. Cockerill FR III, Hughes JG, Vetter EA, et al. Analysis of 281,797 consecutive blood
cultures performed over an eight-year period: trends in microorganisms isolated and the value of anaerobic culture of blood. Clin Infect Dis. 1997;24:
403-418.
31. Cockerill FR III, Wilson JW, Vetter EA, et al. Optimal testing parameters for blood
cultures. Clin Infect Dis. 2004;38:1724-1730.
32. Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB.
Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases
from a prospective nationwide surveillance study. Clin Infect Dis. 2004;39:
309-317.
33. Mirrett S, Weinstein MP, Reimer LG, Wilson ML, Reller LB. Relevance of the number of positive bottles in determining clinical significance of coagulase-negative
staphylococci in blood cultures. J Clin Microbiol. 2001;39:3279-3281.

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