JOURNAL OF CLINICAL MICROBIOLOGY, July 2002, p. 2437–2444 Vol. 40, No.

7
0095-1137/02/$04.00⫹0 DOI: 10.1128/JCM.40.7.2437–2444.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Minimizing the Workup of Blood Culture Contaminants:

Implementation and Evaluation of a
Laboratory-Based Algorithm
S. S. Richter,* S. E. Beekmann, J. L. Croco, D. J. Diekema, F. P. Koontz,
M. A. Pfaller, and G. V. Doern
Medical Microbiology Division, Department of Pathology, University of Iowa College of Medicine,
Iowa City, Iowa
Received 5 November 2001/Returned for modification 4 December 2001/Accepted 16 April 2002

An algorithm was implemented in the clinical microbiology laboratory to assess the clinical significance of
organisms that are often considered contaminants (coagulase-negative staphylococci, aerobic and anaerobic
diphtheroids, Micrococcus spp., Bacillus spp., and viridans group streptococci) when isolated from blood
cultures. From 25 August 1999 through 30 April 2000, 12,374 blood cultures were submitted to the University
of Iowa Clinical Microbiology Laboratory. Potential contaminants were recovered from 495 of 1,040 positive
blood cultures. If one or more additional blood cultures were obtained within ⴞ48 h and all were negative, the
isolate was considered a contaminant. Antimicrobial susceptibility testing (AST) of these probable contami-
nants was not performed unless requested. If no additional blood cultures were submitted or there were
additional positive blood cultures (within ⴞ48 h), a pathology resident gathered patient clinical information
and made a judgment regarding the isolate’s significance. To evaluate the accuracy of these algorithm-based
assignments, a nurse epidemiologist in approximately 60% of the cases performed a retrospective chart review.
Agreement between the findings of the retrospective chart review and the automatic classification of the isolates
with additional negative blood cultures as probable contaminants occurred among 85.8% of 225 isolates. In
response to physician requests, AST had been performed on 15 of the 32 isolates with additional negative
cultures considered significant by retrospective chart review. Agreement of pathology resident assignment with
the retrospective chart review occurred among 74.6% of 71 isolates. The laboratory-based algorithm provided
an acceptably accurate means for assessing the clinical significance of potential contaminants recovered from
blood cultures.

False-positive blood cultures lead to additional laboratory
tests, unnecessary antibiotic use, and longer hospitalizations
that increase patient care costs (2, 16). Assessing the clinical
significance of blood culture isolates can be difficult, but ac-
tions based on the accurate identification of contaminants may
minimize the associated costs and lower future contaminant
rates. An algorithm was implemented in the University of Iowa
Clinical Microbiology Laboratory to assess the clinical signifi-
cance of organisms that are often considered contaminants
when isolated from blood cultures. An independent retrospec-
tive chart review was used to assess the accuracy of automatic
assignments made by the algorithm, determinations of clinical
significance by pathology residents, and the reclassification of
probable contaminant isolates as pathogens after physicians
requested antimicrobial susceptibility testing (AST).
(This report was presented in part at the 101st General
Meeting of the American Society for Microbiology, 21 May
2001 [abstr. C-65].)
MATERIALS AND METHODS
From 25 August 1999 through 30 April 2000, 12,374 blood culture sets were
submitted to the University of Iowa Clinical Microbiology Laboratory. The
* Corresponding author. Mailing address: Department of Pathology,
C606 GH, University of Iowa College of Medicine, Iowa City, IA
52242. Phone: (319) 356-2990. Fax: (319) 356-4916. E-mail: sandra
-richter@uiowa.edu.
majority of blood culture sets consisted of an aerobic and anaerobic bottle
(Organon Teknika, Durham, N.C.) inoculated by phlebotomists, nurses, resi-
dents, and medical students. Each bottle within a blood culture set was inocu-
lated with blood obtained from the same venipuncture site or line. The blood
culture bottles were incubated at 37°C in a continuous monitoring system (BacT/
Alert; Organon Teknika) for up to 5 days. When a blood culture was signaled
positive, a gram stain was performed and the results were reported to the floor.
The blood culture broth was plated on solid medium, and the organism was
identified by conventional methods when growth was observed (11).
Organisms considered to be potential contaminants (coagulase-negative staph-
ylococci [CNS], aerobic diphtheroids, anaerobic diphtheroids, Micrococcus spp.,
Bacillus spp., and viridans group streptococci [VGS]) were further evaluated with
an algorithm (Fig. 1) based on the number of positive blood cultures as follows.
(i) When one or more additional blood cultures were obtained from a patient
within ⫾48 h and all were negative (no growth detected at that time), the
technologist automatically reported the isolate as a probable contaminant and
AST was not performed unless the patient’s physician contacted the laboratory.
When a physician requested AST, the original classification as a probable con-
taminant was removed from the hospital information system and replaced with
the phrase “susceptibility test results to follow.” (ii) When no additional blood
cultures were obtained from a patient within ⫾48 h, a pathology resident gath-
ered clinical data from the hospital’s computerized information system and often
discussed the potential significance of the isolate with a physician caring for the
patient. On the basis of the judgment of the resident, the isolate was classified as
a pathogen, indeterminate, or a contaminant. AST was performed only for
pathogens and indeterminate isolates. (iii) When additional positive blood cul-
tures (with the same organism) were obtained from a patient within ⫾48 h, with
one exception, isolates were assessed by a pathology resident to determine their
clinical significance as described for condition ii above. Isolates of VGS with
additional positive blood cultures were automatically considered to be patho-
gens.
The number of bottles positive within a set was not considered in the algo-

2437
2438 RICHTER ET AL.
FIG. 1. Overview of the laboratory-based algorithm used in this
study.
rithm—each blood culture set was treated as a single entity. The 48-h time period
specified in the algorithm was based on collection times and considered an
absolute cutoff. No consideration was given to the amount of time for which an
additional negative culture had been incubated. If an additional negative blood
culture later turned positive, the pathology resident would be consulted as
outlined for condition iii (isolates with additional positive blood cultures) and
asked to evaluate the significance of the isolate obtained from the newly positive
culture. The classification of an isolate originally as a probable contaminant was
not altered unless a physician requested AST as described for condition i above.
Pathology residents were given a reference that discusses the clinical signifi-
cance of positive blood cultures (17) and instructed to consider each patient’s
clinical history, leukocyte count, body temperature, number of positive blood
cultures, results from other sites, radiographic data, histopathologic findings, and
current status to arrive at a judgment of an isolate’s significance. In addition,
conversations with physicians caring for patients were encouraged, especially
prior to classification of an isolate as a contaminant.
To assess the accuracy of the assignments, a retrospective chart review was
performed in approximately 60% of the cases by a nurse epidemiologist with the
J. CLIN. MICROBIOL.
assistance of an infectious disease physician. Determination of whether the blood
culture isolate was clinically significant was based on this chart review, which
included the patient’s clinical signs and symptoms, leukocyte count, other culture
results, imaging studies, and overall clinical course.
Isolates with additional negative cultures that were initially classified as con-
taminants but for which AST was performed because of a request by the patient’s
physician were subsequently reclassified as pathogens for the purpose of this
evaluation. Error rates were determined for individual steps (isolates with addi-
tional negative cultures automatically considered contaminants, isolates reclas-
sified as pathogens after a physician’s request for AST, pathology residents’
evaluation of isolates, and VGS isolates automatically considered pathogens
because of additional positive blood cultures), as well as for the overall perfor-
mance of the combined steps. A very major (VM) error was defined as classifi-
cation of an isolate as a contaminant that was determined to be clinically signif-
icant by the retrospective chart review. A major (M) error was defined as
classification of an isolate as indeterminate or a pathogen that was not consid-
ered clinically significant by the retrospective chart review. For assessment of the
overall performance of the automatic steps of the algorithm and evaluations by
individuals, isolates that were reclassified as pathogens because a physician called
and requested AST were only considered on the basis of their final classification
as pathogens and considered to represent M errors if not found to be clinically
significant by the retrospective chart review.
RESULTS
Organisms considered to be potential contaminants (CNS,
aerobic diphtheroids, anaerobic diphtheroids, Micrococcus
spp., Bacillus spp., and VGS) were isolated from 495 of 1,040
positive blood cultures during the study period (Table 1). Of
these 495 isolates, 286 (57.8%) were automatically classified as
probable contaminants because of additional negative blood
cultures (26 of these isolates were reclassified as pathogens
after a physician-requested AST), 171 (34.5%) required inves-
tigation by a pathology resident, and 15 (3.0%) were automat-
ically classified as pathogens (VGS with additional positive
cultures). The algorithm was not applied to 4.6% of the 495
isolates: 17 isolates from deceased patients and 6 CNS isolates
from babies (for reasons detailed below). The percentages of
the organism groups determined to be contaminants according
to the final assignments were as follows: CNS, 61.7%; VGS,
42.5%; aerobic diphtheroids, 75.8%; Bacillus spp., 28.6%; Mi-
crococcus spp., 80%; anaerobic diphtheroids, 77.8%.
The only opposition from clinicians to implementation of
the algorithm was from neonatologists approximately halfway
through the study period. At their request, the algorithm was
modified so that isolates of CNS from the neonatal intensive
care unit (NICU) and intermediate care nursery (INS) would
always be considered significant. The six subsequent CNS iso-
lates from these areas were reviewed retrospectively, and four
(67%) were not considered significant. The NICU/INS iso-
lates, as well as those collected from patients who were de-
ceased, were not included in the evaluation of the algorithm.
The final assignment of 301 isolates on the basis of the
automatic steps of the algorithm, evaluations by pathology
residents, and the reclassification of probable contaminant iso-
lates as pathogens after physicians requested AST was com-
pared to the significance determined by the retrospective chart
review (Table 2). Only the significance of the first blood culture
isolate from a patient was determined by the retrospective
chart review. Of the 301 isolates, 225 (74.7%) were automati-
cally classified as probable contaminants because of additional
negative blood cultures (19 of these isolates were reclassified
as pathogens after a physician requested AST), 71 (23.6%)
required investigation by a pathology resident, and 5 (1.7%)
VOL. 40, 2002 MINIMIZING THE WORKUP OF BLOOD CULTURE CONTAMINANTS 2439

TABLE 1. Assignments of clinical significance for 495 blood culture isolates

No. of No. (%) of isolates

Organism group
isolates Contaminant Indeterminate Pathogen Deceased patienta NICU/INSb

CNS 389 240 (61.7) 49 (12.6) 82 (21.1) 12 (3.1) 6 (1.5)

Additional negative within ⫾48 h 232 211 (90.9)c 18 (7.7)d 2 (0.9) 1 (0.4)
Only blood culture within ⫾48 h 57 20 (35.7)e 20 (35.1)e 8 (14.3)e 5 (8.9) 4 (7.1)
Additional positive within ⫾48 h 100 9 (8.8)e 29 (29.0)e 56 (54.9)e 5 (4.9) 1 (1.0)

VGS 40 17 (42.5) 2 (5.0) 18 (45.0) 3 (7.5)

Additional negative within ⫾48 h 16 13 (81.3)c 3 (18.8)d
Only blood culture within ⫾48 h 9 4 (44.4)e 2 (22.2) e
3 (33.3)
Additional positive within ⫾48 h 15 15 (100)f

Aerobic diphtheroids 33 25 (75.8) 3 (9.1) 5 (15.1)

Additional negative within ⫾48 h 20 20 (100)c
Only blood culture within ⫾48 h 6 3 (50.0)e 3 (50.0)e
Additional positive within ⫾48 h 7 2 (28.6)e 5 (71.4)e

Bacillus spp. 14 4 (28.6) 1 (7.1) 7 (50.0) 2 (14.3)

Additional negative within ⫾48 h 6 3 (50.0)c 3 (50.0)d
Only blood culture within ⫾48 h 2 1 (50.0)e 1 (50.0)e
Additional positive within ⫾48 h 6 4 (66.7)e 2 (33.3)

Micrococcus spp. 10 8 (80.0) 2 (20.0)

Additional negative within ⫾48 h 9 7 (77.8)c 2 (22.2)d
Only blood culture within ⫾48 h 1 1 (100)e
Additional positive within ⫾48 h

Anaerobic diphtheroids 9 7 (77.8) 2 (22.2)

Additional negative within ⫾48 h 6 6 (100)c
Only blood culture within ⫾48 h 1 1 (100)e
Additional positive within ⫾48 h 2 2 (100)e

Total 495 301 (60.8) 57 (11.5) 114 (23.0) 17 (3.4) 6 (1.2)

Positive blood cultures (all organisms) 1,040 301 (28.9) 57 (5.5) 114 (11.0) 17 (1.6) 6 (0.6)

Total blood cultures drawn 12,374 301 (2.4) 57 (0.5) 114 (0.9)
a
The significance of isolates belonging to deceased patients was not determined.
b
Isolates from the NICU and INS during the latter half of the study period, when neonatologists requested all CNS isolates to be considered significant.
c
Isolates considered contaminants because of additional negative blood cultures.
d
Isolates initially classified as contaminants because of additional negative cultures but subsequently considered to be pathogens after a physician called and
requested AST.
e
Isolates evaluated by pathology residents.
f
VGS with additional positive blood cultures were automatically considered pathogens.

were automatically classified as pathogens (VGS with addi-
tional positive cultures). Agreement between the final assign-
ment and the retrospective chart review occurred among
87.1% of 233 CNS, 91.3% of 23 VGS, 81.8% of 22 aerobic
diphtheroids, 100% of 7 Bacillus sp., 77.8% of 9 Micrococcus
sp., and 85.7% of 7 anaerobic diphtheroid isolates. Overall,
VM errors occurred in 6.3% of the cases and M errors oc-
curred in 6.6% of the cases.
Agreement between the findings of the retrospective chart
review and the automatic classification by the algorithm of the
225 isolates with additional negative blood cultures as probable
contaminants occurred among 85.8% of those isolates (14.2%
VM error rate; Table 3). In response to physician requests,
AST had been performed on 15 of the 32 isolates with addi-
tional negative cultures considered significant by a retrospec-
tive chart review. The agreement of the reclassification of the
19 isolates as pathogens (because of AST requests) with the
retrospective chart review was 78.9% (21.1% M error rate;
Table 4). The VM error rate for the overall algorithm would
have been 11.3% (34 of 301) and the M error rate would have
been 5.3% (16 of 301) if the 19 isolates had not been reclas-
sified as pathogens.
Agreement of pathology resident assignments with retrospec-
tive chart reviews occurred among 74.6% of 71 isolates (2.8% VM
error rate, 22.5% M error rate; Table 5). The five VGS isolates
with additional positive cultures that were automatically classified
as pathogens by the algorithm were all considered significant by
the retrospective chart review (Table 2).
DISCUSSION
Previous studies suggest that more than 40% of all positive
blood cultures may represent contaminants (9, 17). The prob-
lem of false-positive blood cultures and the associated costs
has been discussed for many years. In 1984, John and Bannister
estimated the annual cost of false-positive blood cultures in the
United States as possibly exceeding 22 million dollars (7).
Multivariate analyses have shown contaminants to be indepen-
2440 RICHTER ET AL. J. CLIN. MICROBIOL.

TABLE 2. Agreement of assignment with retrospective chart review for 301 isolates
Retrospective chart review No. (%) of isolates
Assignment
No. significant No. not significant Agreement VM errora M errorb

CNS (n ⫽ 233) 203 (87.1) 14 (6.0) 16 (6.9)

Contaminant (n ⫽ 179)
Additional negative blood culturesc
Only blood culture obtainedd
Additional positive blood culturesd
Indeterminate (n ⫽ 24)
Only blood culture obtainedd
Additional positive blood culturesd
Pathogen (n ⫽ 30)
Additional negative blood culturese
Only blood culture obtainedd
Additional positive blood culturesd
13 151
1 11
3
7 7
8 2
9 3
3 4
11

VGS (n ⫽ 23) 21 (91.3) 1 (4.3) 1 (4.3)

Contaminant (n ⫽ 14)
Additional negative blood culturesc 1 10
Only blood culture obtainedd 3
Additional positive blood culturesd
Indeterminate (n ⫽ 1)
Only blood culture obtainedd 1
Additional positive blood culturesd
Pathogen (n ⫽ 8)
Additional negative blood culturese 3
Only blood culture obtainedd
Additional positive blood culturesf 5

Aerobic diphtheroids (n ⫽ 22) 18 (81.8) 3 (13.6) 1 (4.5)

Contaminant (n ⫽ 18)
Additional negative blood culturesc 2 14
Only blood culture obtainedd 1
Additional positive blood culturesd 1

Indeterminate (n ⫽ 3)
Only blood culture obtainedd 2 1
Additional positive blood culturesd
Pathogen (n ⫽ 1)
Additional negative blood culturese
Only blood culture obtainedd
Additional positive blood culturesd 1

Bacillus spp. (n ⫽ 7) 7 (100) 0 (0) 0 (0)

Contaminant (n ⫽ 4)
Additional negative blood culturesc 3
Only blood culture obtainedd 1
Additional positive blood culturesd

Indeterminate (n ⫽ 1)
Only blood culture obtainedd 1
Additional positive blood culturesd
Pathogen (n ⫽ 2)
Additional negative blood culturese 2
Only blood culture obtainedd
Additional positive blood culturesd

Micrococcus spp. (n ⫽ 9) 7 (77.8) 1 (11.1) 1 (11.1)

Contaminant (n ⫽ 7)
Additional negative blood culturesc 1 6
Only blood culture obtainedd
Additional positive blood culturesd

Continued on following page

VOL. 40, 2002 MINIMIZING THE WORKUP OF BLOOD CULTURE CONTAMINANTS 2441

TABLE 2. Continued
Retrospective chart review No. (%) of isolates
Assignment
No. significant No. not significant Agreement VM errora M errorb

Indeterminate (n ⫽ 0)
Only blood culture obtainedd
Additional positive blood culturesd
Pathogen (n ⫽ 2)
Additional negative blood culturese 1 1
Only blood culture obtainedd
Additional positive blood culturesd

Anaerobic diphtheroids (n ⫽ 7) 6 (85.7) 0 (0) 1 (14.3)

Contaminant (n ⫽ 6)
Additional negative blood culturesc 5
Only blood culture obtainedd 1
Additional positive blood culturesd
Indeterminate (n ⫽ 1)
Only blood culture obtainedd
Additional positive blood culturesd 1
Pathogen (n ⫽ 0)
Additional negative blood culturese
Only blood culture obtainedd
Additional positive blood culturesd

All organisms (n ⫽ 301) 262 (87.0) 19 (6.3) 20 (6.6)

a
Isolate classified as contaminant by the algorithm but determined to be clinically significant by retrospective chart review.
b
Isolate classified as indeterminant or a pathogen by the algorithm but not considered significant by retrospective chart review.
c
Isolates considered contaminants because of additional negative blood cultures.
d
Isolates evaluated by pathology residents.
e
Isolates initially classified as contaminants because of additional negative cultures but subsequently considered to be pathogens after a physician called and requested AST.
f
VGS with additional positive blood cultures were automatically considered pathogens.

dently correlated with a 20% increase in subsequent laboratory tures on the basis of the organism identification and the number
costs and 39% higher antimicrobial charges (2). Souvenir et al. of positive cultures after noting that only 11% of contaminated
reported the use of antibiotics to treat 41% of 59 patients with cultures had additional positive cultures while 69% of significant
false-positive blood cultures, with vancomycin used for 83% of isolates had more than one positive culture (9). CNS, diphthe-
the treated pseudobacteremic patients (16). The cost for inap- roids, bacilli, and alpha- or nonhemolytic streptococci were often
propriate therapy was approximately $1,000/patient (16). contaminants (9). Although contamination may occur at any
Thirty years ago, MacGregor proposed guidelines for the dif- stage of blood culture processing, the continued predominance of
ferentiation of contaminated from significant positive blood cul- skin flora organisms in false-positive cultures points to insufficient
skin disinfection and poor phlebotomy technique as primary
causes of pseudobacteremia (4).
TABLE 3. Agreement of automatic classification of isolates with
additional negative blood cultures as probable contaminants with
retrospective chart review TABLE 4. Agreement of reclassification of isolates with additional
negative blood cultures as pathogens after physician requested AST
Retrospective chart
review with retrospective chart review
Isolates with additional % % VM
negative blood cultures No. No. not Agreement errorsa Retrospective chart
significant significant Isolates with additional review % %M
negative blood cultures
No. No. not Agreement errorsa
CNS (n ⫽ 176) 22 154 87.5 12.5 reclassified as pathogens
significant significant
VGS (n ⫽ 14) 4 10 71.4 28.6
Aerobic diphtheroids 2 14 87.5 12.5 CNS (n ⫽ 12) 9 3 75 25
(n ⫽ 16) VGS (n ⫽ 3) 3 100 0
Bacillus spp. (n ⫽ 5) 2 3 60 40 Aerobic diphtheroids
Micrococcus spp. (n ⫽ 9) 2 7 77.8 22.2 (n ⫽ 0)
Anaerobic diphtheroids 5 100 0 Bacillus spp. (n ⫽ 2) 2 100 0
(n ⫽ 5) Micrococcus spp. (n ⫽ 2) 1 1 50 50
Anaerobic diphtheroids
All organisms 32 193 85.8 14.2 (n ⫽ 0)
(n ⫽ 225)
All organisms (n ⫽ 19) 15 4 78.9 21.1
a
Isolate initially classified as contaminant by the algorithm but determined to
a
be clinically significant by retrospective chart review. Nineteen isolates were later Isolate reclassified as a pathogen because of physician request to perform
considered pathogens after a physician called requesting AST. AST but not considered significant by retrospective chart review.
2442 RICHTER ET AL. J. CLIN. MICROBIOL.

TABLE 5. Agreement of pathology resident assignment with retrospective chart review

Retrospective chart review No. (%)
Pathology resident assignment
No. significant No. not significant Agreement VM errorsa M errorsb

CNS (n ⫽ 57) 43 (75.4) 1 (1.8) 13 (22.8)

Contaminant (n ⫽ 15) 1 14
Indeterminate (n ⫽ 24) 15 9
Pathogen (n ⫽ 18) 14 4
VGS (n ⫽ 4) 3 (75.0) 0 1 (25.0)
Contaminant (n ⫽ 3) 3
Indeterminate (n ⫽ 1) 1
Pathogen (n ⫽ 0)
Aerobic diphtheroids (n ⫽ 6) 4 (66.6) 1 (16.7) 1 (16.7)
Contaminant (n ⫽ 2) 1 1
Indeterminate (n ⫽ 3) 2 1
Pathogen (n ⫽ 0) 1
Bacillus spp. (n ⫽ 2) 2 (100) 0 (0) 0 (0)
Contaminant (n ⫽ 1) 1
Indeterminate (n ⫽ 1) 1
Pathogen (n ⫽ 0)
Micrococcus spp. (n ⫽ 0)
Anaerobic diphtheroids (n ⫽ 2) 1 (50.0) 0 (0) 1 (50.0)
Contaminant (n ⫽ 1) 1
Indeterminate (n ⫽ 1) 1
Pathogen (n ⫽ 0)

All organisms (n ⫽ 71) 35 36 53 (74.6) 2 (2.8) 16 (22.5)

a
Isolate classified as a contaminant by a pathology resident but determined to be clinically significant by the retrospective chart review.
b
Isolate classified as indeterminate or a pathogen by a pathology resident but not considered significant by the retrospective chart review.

Bates and Lee developed a model based on four factors (time
to positivity, additional positive blood cultures, organism cate-
gory, and clinical risk class) to help clinicians determine the sig-
nificance of a blood culture isolate at the time of the initial report
by the laboratory (3). Ram et al. validated Bates’ model and also
found that a modified version, with elimination of the clinical risk
class, performed as well as the original algorithm (13). Bates’
statement that “the most significant limitation” of his study was
“the lack of an independent gold standard for the diagnosis of
bacteremia” continues to be true today (3). Although subjective
and cumbersome, the optimal approach to distinguishing between
true bacteremia and a contaminant is a comprehensive assess-
ment of the patient’s clinical and microbiologic data by an infec-
tious disease expert (15). This is not a feasible option for a mi-
crobiology laboratory to employ when deciding whether to
perform AST on a positive blood culture isolate. The algorithm
we implemented was based on MacGregor’s early observation of
the importance of the number of positive cultures (9) and was
limited to organisms that colonize skin.
Because of data that suggest that the number of bottles
positive within a set (typically an aerobic and anaerobic bottle
filled from a single venipuncture sample) is not useful in pre-
dicting true bacteremia, this information was not incorporated
into our algorithm (10, 14). A frequently referenced paper
urges caution before calling a single positive blood culture a
contaminant after no difference in hypothermia, fever, leuko-
cytosis, or mortality was found in patients with CNS in one
bottle versus two or more bottles (12). That study used the
number of positive single bottles rather than culture sets as the
basis for comparison, and the exact number of patients with a
single bottle positive was not reported but was less than 16
(12). The study design and small patient sample make it diffi-
cult to use the data (12) as an argument against our algorithm’s
automatic classification of a single positive blood culture with
additional negative cultures as a contaminant. Some of the
patients with one bottle positive only had one set of cultures
drawn (12). The significance of these cultures would be eval-
uated by a pathology resident according to our algorithm.
Another report found no difference in the frequency of
septicemia among 36 patients with CNS in a single bottle
compared to 38 patients with two or more bottles positive (5).
Again, the small sample size and criteria based on the number
of bottles (rather than sets) positive limit the strength of these
data (5) as evidence to refute our algorithm design. A recent
analysis found that more than half of the reported bloodstream
infections due to CNS in the Evaluation of Processes and
Indicators in Infection Control study were single positive blood
cultures and suggested that bloodstream infection rates may be
overestimated when using the Centers for Disease Control and
Prevention surveillance definition (L. C. McDonald, R. Car-
rico, B. Simmons, et al., 11th Annu. Sci. Meet. Soc. Healthcare
Epidemiol. Am., Toronto, Ontario, Canada, abstr. 105, 2001).
The Centers for Disease Control and Prevention definition of
nosocomial bloodstream infection when a skin flora organism
is isolated from a single blood culture only requires an intra-
venous line and antimicrobial therapy to have been instituted
in addition to fever, chills, or hypotension (6). At least one of
these nonspecific signs or symptoms of infection is present in
almost all patients from whom blood cultures are obtained.
At the University of Michigan, Kirchhoff and Sheagren
VOL. 40, 2002 MINIMIZING THE WORKUP OF BLOOD CULTURE CONTAMINANTS
judged 85% of 694 CNS isolates to be contaminants but auto-
matically considered isolates from patients with single positive
CNS cultures to be contaminants and only reviewed the charts
of patients with multiple positive cultures done ⱕ10 days apart
(70 patients with 221 positive cultures) (8). More than half
(52.9%) of the 221 isolates were determined to be contami-
nants, and the authors suggested that microbiology laborato-
ries should limit AST of CNS to significant isolates (8). Further
support for a laboratory-based algorithm came from Archer,
who proposed that the laboratory should implement methods
to identify high-probability contaminants (i.e., single positive
blood cultures with additional negative cultures) and not pro-
ceed with AST unless it is requested by a clinician (1).
During our study period, the percentage of CNS isolates clas-
sified as contaminants (61.7%; Table 1) was lower than that re-
ported by Weinstein (81.9%) (17). The remaining percentages of
isolates classified as indeterminate and pathogens (12.6 and
21.1%) were consequently higher than those of Weinstein et al.
(5.8 and 12.4%) (17). We believe that these differences are evi-
dence of an appropriate tendency of our pathology residents
(compared to infectious disease experts utilized in other studies)
to err on the side of overcalling significance. Of the 20 M errors
revealed by the retrospective chart review, 16 were attributed to
pathology residents and 4 were attributed to clinicians calling and
requesting AST of isolates with additional negative cultures. A
negative impact from the M errors was not apparent. AST was
performed on the isolates, and the results reported as would have
been done if we had not implemented the algorithm.
Only two VM errors were a result of a pathology resident
calling a significant isolate a contaminant. The other VM er-
rors involved isolates automatically classified as contaminants
because of additional negative cultures. The alternative of as-
sessing every positive blood culture (an additional 289 isolates
during our 8-month study period) would overly burden pathol-
ogy residents and result in too many phone calls to clinicians.
All of the patients associated with the VM errors received
appropriate antimicrobial therapy despite the laboratory’s re-
port that the isolate was a probable contaminant.
The microbiology laboratory avoided performing AST on
301 isolates classified as contaminants during the 8-month pe-
riod. With $46.25 billed for each AST, $13,921.25 in microbi-
ology charges was deferred. At our institution, continued use
of the algorithm should result in an annual reduction of un-
necessary patient charges by $20,881.88.
It is hoped that reporting of a nonsignificant isolate as a
probable contaminant decreases the likelihood that a patient
will receive therapy. Of the 165 patients with CNS isolates
deemed nonsignificant by a retrospective chart review and re-
ported as probable contaminants by the laboratory, only 35
(21%) were receiving vancomycin more than 30 h after the
report. Without a control group, it is difficult to ascribe mean-
ing to this information. Souvenir reported that 34% of 59
false-positive blood culture isolates were treated with vanco-
mycin (16), while a smaller percentage of pseudobacteremic
patients in our study received a full course of vancomycin
(21%; P ⫽ 0.04 by the Fisher exact test). This difference may
reflect an effect of our laboratory reporting on clinicians’ be-
havior; however, other factors (i.e., physician and patient char-
acteristics) must also be considered.
Despite the inherent difficulty of discerning bacteremia from
2443
pseudobacteremia, the algorithm provided an acceptably accu-
rate means for assessing the clinical significance of potential
contaminants recovered from blood cultures. We believe it is
important for clinical microbiology laboratories to attempt to
identify false-positive blood cultures in order to limit further
microbiology testing of the isolate and suggest to the clinician
that therapy may not be warranted. The act of reporting a
susceptibility profile may increase the chance that a patient will
be treated. Avoidance of unnecessary antimicrobial therapy
should lower costs and minimize pressure for the emergence of
resistance. A further benefit of implementing our algorithm
was the ability to determine a contamination rate that was
incorporated into a quality assurance monitor with interven-
tions aimed at optimizing the specimen collection procedure.
Finally, the algorithm has provided opportunities to educate
pathology residents about the significance of particular organ-
isms when they are isolated from blood cultures and has in-
creased residents’ involvement in clinical microbiology labora-
tory activities. Laboratories that do not have pathology
residents could utilize other qualified individuals to evaluate
the significance of selected blood culture isolates.
ACKNOWLEDGMENTS
This project received financial support from Organon Teknika.
We thank the following University of Iowa pathology residents for
determining the clinical significance of blood culture isolates: Michelle
Barry, Michele Cooley, Marc Dvoracek, Avina Kolareth, Julie
Meredith, Paul Murray, Sanjai Nagendra, Charles Nicholson, Stephen
Plumb, Rostislav Ranguelov, Daniel Schraith, Eric Stevens, Sergei
Syrbu, Manaf Ubaidat, and Michael Woltman. We are indebted to the
following technologists of the University of Iowa Clinical Microbiology
Laboratory for incorporating the algorithm into their daily work: Linda
Aker, Barry Buschelman, Tony Chavez, Carmen Clark, Sen Dinh,
Carol Hayward, Jean Jennings, Mary Lindsey, Nancy Paulsen, Connie
Quee, Lissa Sanford, Dennis Troy, and Carol Yang.
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