Clinical Infectious Diseases

REVIEW ARTICLE

Does This Patient Need Blood Cultures? A Scoping Review

of Indications for Blood Cultures in Adult Nonneutropenic
Inpatients
Valeria Fabre,1 Sima L. Sharara,1 Alejandra B. Salinas,1 Karen C. Carroll,2 Sanjay Desai,3 and Sara E. Cosgrove1
1
Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, 2Department of Pathology, Division of Medical Microbiology,
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, and 3Department of Medicine, Division of Pulmonary and Critical Care, Johns Hopkins University School of Medicine,
Baltimore, Maryland, USA

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Guidance regarding indications for initial or follow-up blood cultures is limited. We conducted a scoping review of articles published
between January 2004 and June 2019 that reported the yield of blood cultures and/or their impact in the clinical management of fever
and common infectious syndromes in nonneutropenic adult inpatients. A total of 2893 articles were screened; 50 were included.
Based on the reported incidence of bacteremia, syndromes were categorized into low, moderate, and high pretest probability of bac-
teremia. Routine blood cultures are recommended in syndromes with a high likelihood of bacteremia (eg, endovascular infections)
and those with moderate likelihood when cultures from the primary source of infection are unavailable or when prompt initiation
of antibiotics is needed prior to obtaining primary source cultures. In syndromes where blood cultures are low-yield, blood cultures
can be considered for patients at risk of adverse events if a bacteremia is missed (eg, patient with pacemaker and severe purulent cel-
lulitis). If a patient has adequate source control and risk factors or concern for endovascular infection are not present, most strepto-
cocci or Enterobacterales bacteremias do not require routine follow-up blood cultures.
Keywords. bacteremia; blood cultures; indications.

While guidance on appropriate volume of blood and number for nonneutropenic adult inpatients and developed an algo-
of blood cultures (BCx) to be collected exist [1–3], guidance rithm to promote wise use of BCx.
regarding indications for drawing BCx is limited. In clinical
practice, a large proportion of BCx are ordered to evaluate ei- METHODS
ther new or persistent fever, or leukocytosis [4, 5]; however,
Data Search and Study Selection
several studies have shown a lack of correlation between these
The review was conducted in accordance with PRISMA-ScR
clinical parameters and bacteremia [5–7]. Unnecessary BCx
(Preferred Reporting Items for Systematic Reviews and Meta-
are associated with increases in hospital length of stay, antibi-
Analyses Extension for Scoping Reviews) guidelines [11]. A sys-
otic use, and other laboratory testing [8, 9]. They may also lead
tematic search was constructed on PubMed (Supplementary Table
to anemia, patient discomfort, and adverse events associated
1) for English-language articles published between 1 January 2004
with antibiotics started for contaminants. A survey of medicine
and 1 June 2019. Two reviewers (V. F., S. L. S.) independently
residents and attending physicians reported that major factors
screened titles and abstracts for eligibility and evaluated the full
influencing BCx ordering decisions were lack of clinical guid-
text of studies assessed as relevant or unclear. Disagreements were
ance and the expectation that BCx are standard components of
resolved by consensus with a third reviewer (S. E. C.). Studies were
a fever workup [10].
included if they reported either the yield or the utility of BCx in
To develop guidance, we performed a scoping review of the
patients with fever and/or select infectious syndromes. Exclusion
literature to highlight existing evidence on indications for BCx
criteria were outpatients, children, neutropenic and bone marrow
transplant recipients, sample size < 50 patients, candidemia (as
we wanted to focus on immunocompetent hosts), uncommon
Received 28 October 2019; editorial decision 7 January 2020; accepted 13 January 2020;
infections in developed countries (eg, dengue), tuberculosis, or
published online January 14, 2020. transient bacteremia after a procedure (eg, dental extraction),
Correspondence: V. Fabre, Johns Hopkins University School of Medicine, Department of
as the focus was on common scenarios in the inpatient setting.
Medicine, Division of Infectious Diseases, 600 N Wolfe St, Osler 425, Baltimore, MD 21287
(mfabre1@jhmi.edu). Bibliographic references found in articles reviewed were also
Clinical Infectious Diseases®  2020;71(5):1339–7 examined to identify pertinent primary literature.
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society
Studies were grouped in 2 categories: initial (BCx obtained for
of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
DOI: 10.1093/cid/ciaa039 the workup of new onset of signs and symptoms) or follow-up

Scoping Review of Blood Culture Indications • cid 2020:71 (1 September) • 1339

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Figure 1. Algorithm for bacterial blood cultures recommendations in nonneutropenic patients. The algorithm is not a substitute for clinical judgment. *Blood culture (BCx)
required by US Centers for Medicare and Medicaid Services severe sepsis criteria of the Severe Sepsis and Septic Shock Early Management Bundle. †BCx positive for Candida
species require routine follow-up blood culture (FUBCx). ‡Septic thrombophlebitis, infected endovascular thrombi, implantable cardioverter defibrillator (ICD)/pacemaker lead
infections, intravascular catheter infections, and vascular graft infections. §Consider > 2 sets for suspected endocarditis. ||Patients at risk of endovascular infection: ICD/
pacemaker, vascular graft, prosthetic valves and prosthetic material used for cardiac valve repair, history of infective endocarditis, valvulopathy in heart transplant recipient,
unrepaired congenital heart disease, repaired congenital heart disease with residual shunt or valvular regurgitation, or within the first 6 months postrepair. ¶Before ordering
BCx, assess the patient’s clinical history and perform a physical examination to identify infectious and noninfectious sources for the isolated fever episode and review the po-
tential benefit added by BCx. £Prosthesis: joint or intravascular prosthesis. **Routine additional FUBCx for a single BCx with skin flora (eg, coagulase-negative staphylococci)
in an immunocompetent patient are not necessary unless bacteremia is suspected or a prosthesis is present. ††Cellulitis in patients with comorbidities: immunocompromised
hosts or those at risk of poor outcomes from sequelae from missed Staphylococcus aureus bacteremia. Abbreviations: BCx, blood culture; CAP, community-acquired pneu-
monia; HCAP, healthcare-associated pneumonia; PSI, Pneumonia Severity Index; S. aureus, Staphylococcus aureus; S. lugdunensis, Staphylococcus lugdunensis; UTI, urinary
tract infection; VAP, ventilator-associated pneumonia; VO, vertebral osteomyelitis.

(BCx ordered after a positive BCx to document clearance of
bacteremia). Among initial BCx, we recorded the reported pro-
portion of positive BCx and impact on clinical management.
Development of a BCx Order Clinical Decision Support Tool
Two authors (V. F., S. E. C.) developed an algorithm with indi-
cations for initial and follow-up blood cultures (FUBCx) based
on the available evidence. Subsequently, an internal multidis-
ciplinary group at the Johns Hopkins Hospital, with partici-
pation from antimicrobial stewardship, clinical microbiology,
infectious diseases, hospital epidemiology, critical care, surgery
and hospital medicine, reviewed and modified the algorithm,
resulting in the flowchart presented in Figure 1.
RESULTS
Of 2893 studies screened, 50 met inclusion criteria (Figure 2).
Herein, we describe the incidence of bacteremia in different
clinical scenarios, the additive value of BCx to yield from cul-
tures obtained from the primary source of infection, the impact
of BCx on clinical management and patient outcomes, and the
utility of repeating BCx after initial bacteremia with gram-posi-
tive (GP) and gram-negative (GN) organisms. Finally, we incor-
porate this knowledge into an algorithm to promote rationale
use of BCx.
Incidence of Bacteremia in Select Clinical Scenarios
Yield of Blood Cultures in Selected Infectious Syndromes
Based on the reported incidence of bacteremia, studies were
categorized into 5 groups according to the pretest probability
of bacteremia (Table 1). Very low (< 5%) probability includes
general medicine patients with isolated fever [5, 6] and fever
within the first 48 hours after a surgery [12–14]. Low (< 10%)
probability included cellulitis [15–18], cystitis/prostatitis [19,
20], nonsevere community-acquired pneumonia (CAP), and
healthcare-associated pneumonia (HCAP) [21–24]. Low to
moderate (10%–20%) includes ventilator-associated pneumonia
(VAP) [25, 26] and cellulitis in patients with severe comorbidities
[18, 27, 28]. Moderate (20% to < 50%) probability includes

1340 • cid 2020:71 (1 September) • Fabre et al

 infections, 33% of those with bacteremia had normal body temper-
ature, 52% had a normal white blood cell count, and 17% had nei-
ther fever nor an abnormal white blood cell count [7].
Among 746 patients who had BCx collected within 10 days
of a surgical procedure [12], BCx obtained within the first 48
hours postsurgery were associated with negative BCx. When
temperature was ≥ 38.6°F, postoperative day > 2 and hypoten-
sion were present, the chance of having bacteremia was 17%,
and when none of these variables were present, the probability
of negative BCx was 99% [42]. In 150 cases with BCx drawn
within 30 days of surgery, most bacteremias occurred after
Figure 2. Flow diagram of study selection. postoperative day 4 [13].

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acute pyelonephritis [29, 30], severe CAP [23, 31], cholangitis
32, 33], pyogenic liver abscess [34], and nonvascular shunt (eg,
ventriculoperitoneal shunt) infections [35]. High (≥ 50%) proba-
bility includes septic shock [6], meningitis [36], endovascular in-
fections (eg, infective endocarditis [IE], septic thrombophlebitis,
vascular graft infection) [37], ventriculoatrial shunt infections
[35], discitis, native vertebral osteomyelitis [38–40], epidural
abscess [40, 41] and nontraumatic native septic joints [39].
Role of Blood Cultures in the Evaluation of Fever and/or
Leukocytosis
In a retrospective review of 4566 bacteremias and 25 946 nega-
tive BCx episodes in immunocompetent hosts, neither leukocy-
tosis nor fever (≥ 38°C) alone reliably predicted bacteremia [6]
( Supplementary Table 2); however, shaking chills had a high likeli-
hood ratio of predicting bacteremia (4.7 [95% confidence interval,
3.0–7.2]). In a prospective study, fever alone, fever with leukocy-
tosis or leukocytosis alone were all not significantly associated with
bacteremia [5]; however, BCx ordered for suspected IE as well as
absence of antibiotic exposure within 72 hours of BCx were more
likely to yield a positive result. Among 3565 patients with suspected
Impact of Detecting Bacteremia on Clinical Management
Additive Microbiologic Information From BCx Compared to
Cultures From Primary Source
The additional utility of BCx to cultures from the primary
source of infection in identifying the causative pathogen varies
by clinical syndrome (Supplementary Table 2). The yield of in-
itial BCx is higher than that of the primary source in epidural
abscess (70% and 46%, respectively [40]) and discitis/vertebral
osteomyelitis (46% and 36%, respectively [38]). Blood and pri-
mary source of infection culture concordance is high for epi-
dural abscesses (approximately 60%–100%) [40, 41] and native
joint infections (> 86%) [48].
The yield of BCx is lower than that of the primary site in
cholangitis, acute pyelonephritis, purulent cellulitis, and se-
vere CAP. Among patients with acute ascending cholangitis,
the yield of BCx and bile culture was 26%–32% and 92%–97%,
respectively [32, 33], with high (> 85% of cases) blood and bile
culture concordance [32, 33]. In pyogenic liver abscess, the
yield of BCx and abscess culture was 25% and 81%, respectively
[34]. In patients without recent antibiotic exposure, the yield of
urine culture (UCx) in acute pyelonephritis is > 95% [29]. BCx
and UCx concordance is high (≥93%) regardless of whether

Table 1. Pretest Probability of Bacteremia in Common Clinical Scenarios (Percentages as Reported in the Studies)

Between 10% and < 20% Between 20% and < 50%
< 5% (Very Low) < 10% (Low) (Low-moderate) (Moderate) ≥ 50% (High)

Fever within first Uncomplicated cellulitis Cellulitis in patients with severe Severer sepsis Discitis and VO [39, 40, 47]
48 h of surgery [6, 15–17, 43, 44], including comorbidities [18, 27, 28] Epidural abscesses [40, 41]
[12–14, 42, 55] periorbital cellulitis [45, 46] Acute nontraumatic native septic
joints [48]
Isolated fever [5, 6] Lower urinary tract infection … Acute pyelonephritis Meningitis [6]
[19, 20] [29, 30, 49, 50]
… … … Cholangitis [32, 33] …
Pyogenic liver abscess [34]
… CAP [6, 22, 23, 51–53] VAP [25, 26] Severe CAP [31] …
HCAP [21, 22, 52, 56]
… … … Nonvascular shunt Ventriculoatrial shunt infections
infections [35] [35]
… … … Severe sepsis [54, 57] Septic shock [6]
Shaking chills in febrile pa- Catheter-related bloodstream
tient [6] infections
Abbreviations: CAP, community-acquired pneumonia; HCAP, healthcare-associated pneumonia; VAP, ventilator-associated pneumonia; VO, vertebral osteomyelitis.

Scoping Review of Blood Culture Indications • cid 2020:71 (1 September) • 1341

acute pyelonephritis cases are complicated (the former defined
as pyelonephritis in a patient with structural or anatomical ab-
normalities) [29, 30, 49, 58]. In patients with purulent cellulitis,
the yield of purulent wound drainage culture was 30%–69% [15,
27] while the yield of BCx was 7%–18% depending on patients’
comorbidities. Sputum cultures in severe CAP have a higher
yield than in nonsevere CAP (67% and 23%, respectively) and
is higher than the yield of BCx (overall, approximately 10% for
severe and nonsevere CAP) [31].
Impact of BCx on Antibiotic Decision Making
Bacteremia detection did not change antibiotic decisions
made based on UCx results for women presenting with un-
complicated [29] or complicated [49] acute pyelonephritis
(Supplementary Table 2). The impact of bacteremia in cellulitis
management was reported as no change for nonpurulent cel-
lulitis (empiric regimen was co-amoxicillin) [43] and minimal
(2% of changes based on BCx results) for complicated cellulitis
[17] (defined as cellulitis in a patient with human immunodefi-
ciency virus, solid organ transplantation [SOT], active chemo-
therapy, diabetes, peripheral vascular disease, dialysis, or other
immunocompromising condition). Another study reported an-
tibiotic changes in 12% of cellulitis cases (half of the changes
were de-escalation and half were broadening antibiotics) [28];
however, the authors did not report antibiotic regimens or cat-
egorize cases into purulent and nonpurulent cellulitis, and 25%
of bacteremias were due to GN organisms. No studies specifi-
cally reported on the risk of Staphylococcus aureus bacteremia
in patients with severe purulent cellulitis or stratified bacte-
remia risk by host comorbidities.
Multiple studies have examined the impact of BCx in CAP
management. A systematic review of articles published be-
tween 1996 and 2007 concluded that bacteremia was in-
frequent in CAP, and its detection had minimal impact in
antibiotic decisions (narrowing and escalation of antibiotics
in 0–3% and 0–1%, respectively) [59]. However, the authors
did not specifically evaluate severe CAP. An older study that
focused on the utility of BCx and CAP severity [60] reported
antibiotic changes based on BCx results in 6% of patients, all
with a Pneumonia Severity Index grade IV and V (it is un-
known if these changes were appropriate or not). Additional
studies report minimal benefit of BCx in severe CAP [22,
51]. One of these studies reported that most changes were
de-escalations [22].
Impact of Bacteremia on Clinical Outcomes
Few studies reported on whether the presence of concomi-
tant bacteremia was associated with worse clinical outcomes
(Supplementary Table 2). Bacteremia was not associated with
worse clinical outcomes in women with complicated urinary
tract infection (UTI) or women presenting with urosepsis or
septic shock (similar mortality and length of stay between those
1342 • cid 2020:71 (1 September) • Fabre et al
with and without bacteremia) [61], nor did it affect clinical cure
or recurrence of infection (independent of whether or not BCx
and UCx results were discordant) in women presenting with
uncomplicated acute pyelonephritis [29]. Bacteremia was not
associated with treatment failure or recurrence of infection
within 30 days of hospital discharge in 606 patients with cel-
lulitis (10% were immunocompromised and 10% had sepsis)
[27]. In another study, bacteremic cellulitis was associated with
longer hospital stay but not increased risk of mortality [16].
Among 1972 patients with CAP (125 with S. pneumoniae bac-
teremia and 1847 with no bacteremia), length of stay, time to
clinical stability, all-cause mortality, and CAP-related mortality
were similar between the bacteremic and nonbacteremic CAP
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groups [23]. This is in agreement with previous data reporting
similar mortality in patients with bacteremic severe CAP and
nonbacteremic severe CAP [31]. In contrast, bacteremia was as-
sociated with ICU mortality in patients with VAP [25, 26].
Role of Follow-up Blood Cultures After Initial Positive Blood Cultures
Role of Follow-up Blood Cultures in Gram-positive Bacteremia
Clinical practice guidelines by the Infectious Diseases Society
of America for the treatment of methicillin-resistant S. aureus
(MRSA) infections in adults recommend repeating BCx to doc-
ument clearance of infection 2–4 days after initial positive BCx
[62], as duration of bacteremia impacts duration of therapy
(Table 2). A study reported that following initial positive BCx
for MRSA, 14-day survival was 100% for those with negative
FUBCx, but approximately 50% for those with positive FUBCx
or no FUBCx [63]. Another study reported that S. aureus was
independently associated with positive FUBCx after 24 hours
of appropriate therapy [64] and that these patients had a slightly
higher risk of death than patients with negative FUBCx (16%
vs 12%, respectively; P < .05). In 2 studies, overall FUBCx pos-
itivity was reported in approximately 15% of cases and > 75% of
these were due to GP cocci, mostly S. aureus [65, 66]. In 1 study,
positive FUBCx after initial GP bacteremia were more likely to
be obtained in patients with a central venous catheter, those re-
ceiving hemodialysis, patients with diabetes mellitus, and patients
with fever at the time of culture [65]. In another study, persistent
bacteremia was associated with lack of source control (more com-
monly seen with spine/joint and thoracoabdominal infections)
[66]. Viridans group streptococci, β-hemolytic streptococci, and
Streptococcus pneumoniae were associated with negative FUBCx
[64, 66]. Positive FUBCx in Streptococcus anginosus bacteremia
were uncommon, but the sample size was small [66].
Role of Follow-up Blood Cultures in Gram-negative Bacteremia
Persistent bacteremia due to GN organisms was reported in
only 2% of cases in 1 study [65], and the only variable associ-
ated with positive FUBCx compared to those with a negative
FUBCx was fever when the BCx was obtained. In another study
[66], bacteremia due to Escherichia coli was associated with
 Table 2. Studies Addressing the Utility of Follow-up Blood Cultures

Major Limi-
Study Details Inclusion Criteria Exclusion Criteria No. Analyzed Results Conclusions tations

Shi et al [67], 2019, Age ≥ 18 y admitted with UTI Patients without 306 patients • Clinical characteristics: 72% women, median age 70 y, 33% malig- Routine FUBCx in UTI are not needed, Retrospec-
single hospital, and had > 1 BCx drawn bacteremia or nancy, 30% complicated UTI, 18% admission to ICU consider in those without clinical tive
Korea other source of • Positive FUBCx: 18% (55/306) response
bacteremia • Factors associated with positive FUBCx:
Staphylococcus aureus, malignancy, ICU admission, time to
defervescence > 48 h
Canzoneri et al [65], Age ≥ 18 y; repeat BCx ≥ 24 h Fungemi, false- 383 patients • Clinical characteristics: 43% in ICU; 43% had a CVC; 24% on he- To obtain 1 positive FUBCx in GN Low inci-
2017, retrospec- after an initial true-positive positive BCx modialysis; 9% neutropenic bacteremia, 17 FUBCx were needed dence of
tive observa- BCx between January and • Positive FUBCx: overall 14% (55/383); GN bac-
tional, tertiary December 2015 78% (43/55) GP; 15% (8/53) GN teremia;
care hospital, • Factors associated with positive FUBCx with GP: diabetes mellitus; source
United States ESRD on hemodialysis; fever when cultures drawn, presence of a control
CVC was not
• Factors associated with positive FUBCx with GN: fever when cul- reported
tures drawn
• Mortality and need for ICU care were similar among 3 groups: bac-
teremia cleared, persistent BCx with either GP or with GN
Miyamoto et al [63], Adult patients with ≥ 2 BCx None 64 patients • Clinical characteristics: 43% diabetes, 26% kidney disease Lack of documentation of MRSA Small
2017, retrospec- positive for MRSA within • Probability of survival at 14 d of initial positive BCx: 100% for those bacteremia clearance is associ- sample
tive, academic 2–4 d of initial BCx col- who had a negative FUBCx; 57% for those who had only positive ated with a 3-fold increased risk of size
hospital, United lection between 2011 and FUBCx; 41% for those who had no FUBCx mortality
States 2016
Wiggers et al [66], Age ≥ 17 y with a FUBCx Subsequent 701 patients • Clinical characteristics: 18% admitted to hematology/oncology FUBCx useful in patients with S. au-
2016, retrospec- between 2010 and 2014. bacteremias for • Positive FUBCx: overall 16.8% (118/701); 76.3% (90/118) GP; reus bacteremia, endovascular or
tive and a nested Case: positive FUBCx with a single patient 22.9% (27/118) GN; 1.7% (2/118) anaerobes; 7.6% (9/118) spinal infections, lack of source
case-control anal- the same bacteria 2–7 d polymicrobial control
ysis, academic after initial positive BCx; • Factors associated with positive FUBCx: S. aureus, endovascular
hospital, Canada control: negative FUBCx sources of infection (catheter-associated/device/graft infection);
epidural abscess/discitis; lack of source control within 48 h of initial
positive BCx
• Factors associated with negative FUBCx: UTI source; Escherichia
coli, Streptococcus pneumoniae, Viridans group streptococci,
β-hemolytic streptococci
• Clinical variables at time of FUBCx collection with no impact on
FUBCx results: SIRS; leukocytosis; fever; physician concern for
instability
• Positive FUBCx increased risk of 7- and 30-d mortality
Kang et al [68], Age ≥ 18 y with a first Recurrent 862 patients • Positive FUBCx: 7.2% (62/862) Routine FUBCx are not recom-
2013, 1:3 case- episode of Klebsiella Klebsiella or (186 con- • Factors associated with positive FUBCx: IAI; high CCI; SOT; unfa- mended for most K. pneumoniae
control study pneumoniae polymicrobial trols, 62 vorable treatment response on day 2 following initial BCx (fever, bacteremias; consider in those with
according to age between 2007 and 2011 infections positive leukocytosis and lack of CRP decrease constituted “unfavorable high CCI score, SOT, and/or unfavor-
and sex, 2 tertiary FUBCx treatment response”) able treatment response on day 2
care hospitals, cases) • A scoring system was created (IAI: 1 point; nosocomial after initial BCx
Korea K. pneumoniae: 2 points; fever: 3 points; lack of CRP decrease: 2
points): positive FUBCx: > 50% when score > 5 and < 5% when
score was 0–1

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 negative FUBCx; other GN bacteria were not associated with

Abbreviations: BCx, blood culture; CCI, Charlson Comorbidity Index; CRP, C-reactive protein; CVC, central venous catheter; ESRD, end-stage renal disease; FUBCx, follow-up blood culture; GN, gram-negative; GP, gram-positive; IAI, intra-abdominal infection;
were not

occurred
Major Limi-

reported

or whether

control
source
status
by im-
mune
either positive or negative FUBCx (likely due to small sample

Results
tations
size). Persistent bacteremia was observed in 7% of patients
with Klebsiella pneumoniae bacteremia and was associated with

endovascular infection due to S. au-

Persistent leukocytosis and fever are

intra-abdominal infection (presence of source control was not
reported), higher Charlson Comorbidity Index, SOT, and lack

poor predictors of bacteremia

reus or lack of source control
FUBCx useful in patients with

of clinical response to treatment [67]. In 1 study, Pseudomonas

bacteremia was an independent risk factor for positive
FUBCx in addition to IE, endovascular/articular source, and
immunocompromise (neutropenia, SOT, bone marrow trans-
Conclusions

plantation) [64]. A study of bacteremic UTI reported that pos-

itive FUBCx were associated with fever > 48 hours, admission
to the ICU, and malignancy [67]. Escherichia coli was the most

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common pathogen causing bacteremic UTI and was negatively
• Factors associated with positive FUBCx: endocarditis/endovascular

• Most common reasons to repeat BCx were fever, follow-up of pos-

source; S. aureus or Pseudomonas aeruginosa; polymicrobial bac-

associated with persistent bacteremia [67]. See Table 2 for de-

chemotherapy, 14% liver disease, 7% kidney disease, 11% leu-
• Clinical characteristics: 22% on steroids, 18% diabetic, 15% on

• Repeat BCx after a negative BCx grew an organism in 1.7% of

ICU, intensive care unit; MRSA, methicillin-resistant Staphylococcus aureus; SIRS, systemic inflammatory response syndrome; SOT, solid organ transplant; UTI, urinary tract infection.
teremia; transplant recipient; neutropenia; nosocomial origin

tails on these studies.

Clinical Decision Tool to Assist Providers in Appropriate Ordering of Blood

Cultures
Figure 1 shows the clinical pathways ordering providers can
• Positive FUBCx: overall 6.1% (392/6324)

follow to ensure more appropriate use of BCx. These recom-

itive BCx, and persistent leukocytosis

mendations are not generalizable to immunocompromised

hosts due to their overall underrepresentation in the studies
reviewed.

DISCUSSION
cases (2 BCx)

Specific guidance on when to draw BCx in clinical practice is

limited. The goal of this scoping review is to summarize know-
kemia
Results

ledge on the utility of BCx based on clinical scenario and to

incorporate this knowledge into an algorithm to help increase
their appropriate use.
No. Analyzed
392 patients

(199 BCx)

The studies included are observational of either prospectively

96 patients

or retrospectively collected data conducted mostly at single cen-

ters in the United States or Europe. No studies found a corre-
lation between bacteremia and fever or leukocytosis (both in
Exclusion Criteria

isolation or combined) in immunocompetent hosts [4–7]. Thus,

Not reported

Not reported

fever in a hospitalized patient should prompt a review of the

clinical history and physical examination to assess for possible
infection, and a decision to obtain BCx should be made based
on the pretest probability of bacteremia or the potential benefit
antibiotic therapy between
Age > 14 y with positive BCx
after ≥ 24 h of appropriate

cember 2001 from adults

added by BCx (either additional microbiologic data or impact

of BCx results in management).
Tabriz et al [4], 2004, All BCx obtained in De-

Based on the evidence, routine BCx would be indicated in

and with FUBCx
1997 and 2002
Inclusion Criteria

syndromes with high pretest probability of bacteremia such as

septic shock [6], meningitis [36], endovascular infections [37],
ventriculoatrial shunt infections [35], native vertebral osteo-
myelitis [38, 40], epidural abscess [41], and nontraumatic na-
Continued

tive septic joints [39]. When the primary site of infection is

tertiary care hos-
retrospective, 2

single hospital,
López Dupla et al

inaccessible or when it is desired to give antibiotics before ac-

United States
pitals, Spain
[64], 2005,
Study Details

cessing the primary site for cultures, BCx may be considered

Table 2.

even if the yield is moderate (eg, acute pyelonephritis and re-

cent outpatient antibiotic exposure or inability to provide a

1344 • cid 2020:71 (1 September) • Fabre et al

urine sample, and acute cholangitis when antibiotics are ap-
propriately initiated promptly before endoscopic retrograde
cholangiopancreatography).
We found sufficient data to support not drawing BCx rou-
tinely for fever developed in the first 48 hours after surgery
[12–14, 42], nonsevere CAP [6, 22, 23, 51–53], HCAP [21, 22],
and cystitis/prostatitis [19, 20], not only due to a low incidence
of bacteremia but also due to lack of additional microbiologic
information or impact in clinical management. Bacteremia is
uncommon in patients with nonsevere purulent or nonpurulent
cellulitis [6, 15–17, 43, 44], a finding supported by recent trials
evaluating efficacy of new antibiotics for skin and soft tissue in-
fections (SSTIs) [69–72]. In these trials, most patients presented
with SSTIs and systemic inflammatory response syndrome cri-
teria (patients with severe sepsis or shock, immunocompro-
mised hosts, and patients with end-stage liver disease [ESLD]
or end-stage renal disease [ESRD] were excluded), and bacte-
remia was detected in < 5% of patients. In these syndromes with
low pretest probability of bacteremia, BCx may be of value if
bacteremia has significant clinical consequences. For example, a
patient with severe purulent cellulitis and host risk factors such
as diabetes, ESLD, or ESRD is at higher risk for S. aureus bac-
teremia, which, if present, can lead to worse outcomes [73–75].
Other examples include concern for resistant GN or MRSA
infections in which optimal antibiotic treatment depends on
knowing culture and susceptibility data and concern for risk of
development of an endovascular infection in patients at risk (eg,
patient with prosthetic valve and Enterococcus bacteremia from
urinary or biliary source). The clinician must always use clinical
judgment when evaluating the need for BCx.
Although BCx yield in severe sepsis is moderate (~25%) [8,
55], BCx are mandated by the US Centers for Medicare and
Medicaid Services (CMS) severe sepsis criteria of the Severe
Sepsis and Septic Shock Early Management Bundle (SEP-1)
[76]. If CMS rules were to change, a decision to obtain BCx
could be made based on proven benefit (eg, in an otherwise
healthy patient with severe sepsis due to purulent cellulitis, cul-
ture from pus is far more likely to give a microbiologic diagnosis
than BCx).
Staphylococcus aureus is by far the most common pathogen
causing persistent bacteremia independent of source of infec-
tion; thus, FUBCx are always appropriate when this organism is
found in BCx. Staphylococcus lugdunensis can be similarly viru-
lent and is associated with IE [77]; thus, the authors recommend
FUBCx when it is found in blood. In bacteremia due to strepto-
cocci and Enterobacterales, FUBCx are unlikely to grow unless
the source of infection is endovascular or there is inadequate
source control [65, 66, 68]. Studies assessing persistent bacte-
remia associated with Pseudomonas have small numbers; how-
ever, most patients have negative FUBCx when source control
is adequate [78]. The median duration of bacteremia in a cohort
of patients with Pseudomonas including immunocompromised
Scoping Review of Blood Culture Indications • cid 2020:71 (1 September) • 1345
hosts was 1 day with < 10% of patients having positive BCx after
48 hours; persistent bacteremia was associated with absence of
source control [78]. The role of FUBCx in bacteremias due to
other less common GNs (eg, Stenotrophomonas, Acinetobacter)
needs further elucidation.
No studies specifically addressed the need to repeat BCx be-
fore placement of new intravascular catheters in cases of cath-
eter associated-bacteremia; however, the authors recommend
FUBCx in this setting to avoid seeding of new lines.
This review has limitations. The majority of studies evaluating
the impact of BCx results in antibiotic management did not
report whether longer durations of antibiotics were used or
needed in patients with bacteremia. Patients with immunosup-
Downloaded from https://academic.oup.com/cid/article/71/5/1339/5703622 by guest on 28 November 2023
pression or certain medical conditions (eg, ESLD or ESRD) are
generally poorly represented in studies, and the recommenda-
tions outlined in this report should not be applied to immuno-
compromised hosts. We did not include candidemia; however,
we addressed the most common infections and previously iden-
tified triggers of BCx in clinical practice.
In summary, our scoping review highlights scenarios where
BCx are indicated and scenarios where BCx are of no benefit
for most patients due to low yield, provision of limited addi-
tional microbiologic data, or minimal impact on antibiotic
decisions. Most patients with bacteremia do not need FUBCx
if source control is achieved, there is not known or suspected
endovascular infection, or the causative organism is not
S. aureus or S. lugdunensis.
Supplementary Data
Supplementary materials are available at Clinical Infectious Diseases online.
Consisting of data provided by the authors to benefit the reader, the posted
materials are not copyedited and are the sole responsibility of the authors,
so questions or comments should be addressed to the corresponding author.
Notes
Acknowledgments. The authors gratefully acknowledge Jaime Blanck,
MLIS, MPA, for her assistance in developing the scoping review search
strategy.
Potential conflicts of interest. S. E. C. reports personal fees from
Theravance, Novartis, and Basilea, outside the submitted work. All other
authors report no potential conflicts of interest. All authors have submitted
the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts
that the editors consider relevant to the content of the manuscript have been
disclosed.
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