REVIEW

C URRENT
OPINION Follow-up blood culture in Gram-negative bacilli
bacteraemia: for whom is follow-up blood
culture useful?
Maddalena Giannella a,b, Renato Pascale a,b and Pierluigi Viale a,b

Purpose of review
The aim of this narrative review is to examine available evidence about the diagnostic yielding of the
follow-up blood cultures (FU-BCs) in patients with Gram-negative bloodstream infection (GN-BSI), the
predictors of persistent GN-BSI, and the impact of the performance of FU-BCs on patient management and
clinical outcome.
Recent findings
The rate of persistent GN-BSI varies from 2.6% to 38.5%, with higher percentages in studies where FU-BCs
were obtained from selected patients. Risk factors for persistent GN-BSI were analysed and prediction tools
were proposed to guide physicians in the selection of patients. The impact of FU-BCs on patient
management is still controversial as several authors have shown that this practice was associated with
prolonged treatment duration and longer hospital stay. However, when adjusted for indication and survival
bias, the performance of FU-BCs was a strong predictor of survival in large cohorts of hospitalized patients
with GN-BSI. Favourable outcome seemed to be associated with higher rate of source control in GN-BSI
patients managed with FU-BCs.
Summary
The practice of FU-BCs in patients with GN-BSI should be individualised balancing cost/benefit ratio. The
use of risk scores could be useful in selecting patients for whom FU-BCs are appropriate.
Keywords
bloodstream infection, follow-up blood-cultures, Gram-negative bacteraemia, Gram-negative bacteria

INTRODUCTION develop a consensus definition of uncomplicated GN-

Gram-negative bloodstream infection (GN-BSI) is a BSI to assist clinicians with some key management
significant public health threat affecting both decisions including treatment duration, switch to
healthy individuals and those with underlying oral therapy, and performance of follow-up blood
&&

comorbidities [1]. In hospitalized patients, GN-BSI
is associated with high rates of morbidity and mortal-
ity [2,3], especially in vulnerable populations like the
elderly and the immunocompromised patients [4,5].
The management of patients with GN-BSI is chal-
lenging due to the broad range of scenarios that
physicians may encounter in the clinical practice
depending on host factors, infection sources, and
aetiology characteristics including the complex
resistance pattern varying across species and coun-
tries [4,6–8]. These issues may partially explain the
lack of international guidelines on the management
of GN-BSI and the wide heterogeneity in clinical
practice revealed by a survey [9]. Recently, some
attempts of filing this gap have been done. A group
of 13 infectious diseases specialists from across the
United States used a modified Delphi technique to
cultures (FU-BCs) [10 ]. Concomitantly, in order to
build a bundle for the management of Enterobacter-
ales BSI (E-BSI) and, eventually, to identify areas for
future research, our group systematically reviewed
the available evidence about the efficacy of selected
interventions, including the performance of FU-BCs,
a
Department of Medical and Surgical Sciences, University of Bologna
and bInfectious Diseases Unit, IRCCS Azienda Ospedaliero-Universi-
taria di Bologna, Bologna, Italy
Correspondence to Renato Pascale, MD, Infectious Diseases Unit,
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Department of
Medical and Surgical Sciences, University of Bologna, Via Massarenti
11, 40138 Bologna, Italy. Tel: +39 051 2143199;
e-mail: renato.pascale2@unibo.it
Curr Opin Infect Dis 2022, 35:552–560
DOI:10.1097/QCO.0000000000000865

www.co-infectiousdiseases.com Volume 35
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December 2022

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 Follow-up blood culture in Gram-negative bacilli bacteraemia Giannella et al.
KEY POINTS

Diagnostic yielding, impact on patient management
and on clinical outcome of follow-up blood cultures are
the key issues to consider in defining the approach to
the performance of such practice in patients with Gram-
negative bloodstream infection.

The most common observed predictors of persistent
Gram-negative bloodstream infection include end-stage
renal disease with need of haemodialysis,
endovascular source, extended-spectrum
betalactamases or carbapenemases producing
bacteria, inactive empirical treatment and
unfavourable course.

Although some studies observed that the performance
of follow-up blood cultures in patients with Gram-
negative bloodstream infection was associated with
prolonged treatment duration and hospital stay, other
studies showed that this practice was a strong predictor
of survival, thus a selected use balancing risk/benefit
ration could be suggested.
on the outcome of patients with E-BSI [11]. Both docu-
ments underlined that a firm conclusion in favour or
against the performance of FU-BCs in patients with
GN-BSI cannot be reached on the basis of current
evidence, suggesting the need of a targeted approach.
Indeed, if the role of FU-BCs is well established
in the management of patients with Staphylococcus
aureus bacteremia (SAB) as well as in those with
candidemia, to exclude complicated BSI and to
define the optimal treatment duration [12,13], the
performance of FU-BCs remains questioned. Routi-
nary use in the management of GN-BSI has been
discouraged by some experts who raised concerns
about the low rate of diagnostic yielding, the poten-
tial of false positive results, and the negative impact
on treatment duration and length of hospital stay
[14,15]. On the other hand, large studies addressing
potential confounders such as indication and
immortal bias have shown that FU-BCs are strongly
& &
associated with improved outcome [16 –18 ].
Therefore, the aim of this narrative review is to
examine and update available evidence about the
diagnostic yielding of the FU-BCs in patients with
GN-BSI, the predictors of persistent GN-BSI, and the
impact of FU-BCs on patient management and clinical
outcome, in order to define patients with GN-BSI for
whom the use of FU-BCs could be more cost-effective.
METHODS
We searched for randomized controlled trials
(RCTs) and observational studies published from
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January 2012 to May 2022 on PUBMED using the
following keywords
‘‘Gram negative bacteraemia’’ or ‘‘Gram negative
bloodstream infection’’ and ‘‘follow-up blood
cultures’’ or ‘‘repeat blood cultures’’. Title and
abstract screening was performed in order to check
for consistency with the selected topic. Only studies
published as full-text documents were reviewed.
PERSISTENT GRAM-NEGATIVE
BLOODSTREAM INFECTION
The majority of studies investigating the role of FU-
BCs in patients with GN-BSI referred to the rate of
persistent GN-BSI as primary endpoint. This was
defined as repeated BCs positive for the same organ-
ism isolated from the index BCs, when obtained
between 24 or 48 h up to 3–7 days after the index
blood cultures (BCs) or antibiotic onset. Thus, there
was heterogeneity in the time window considered
for obtaining FU-BCs, probably influencing the
diagnostic yielding found in the different studies.
As shown in Table 1, the rate of persistent GN-
BSI varied from 2.6% to 38.5%. In the majority of
studies, the setting was that of hospitalized adult
patients diagnosed with GN-BSI; one study included
only children, showing a rate of persistent GN-BSI of
21.2% [19], whereas another one involved only
critically ill adult patients, showing a 35.9% rate
of persistent GN-BSI [20]. Two small studies, enroll-
ing 139 and 52 patients respectively, were focused
on immunocompromised patients with GN-BSI,
showing a low rate of persistent bacteraemia,
2.6% and 9% [21,22]. Finally, in two studies the
analysis was limited to community onset GN-BSI
and to urinary tract source bacteraemia with persis-
&
tence rates of 6.8% and 17.9%, respectively [18 ,23].
Other than the definition used, and the patient
setting studied, different criteria used for drawing
FU-BCs could have influenced the rate of persistent
GN-BSI. Indeed, in studies based on a universal-like
approach, that is >80% of GN-BSI patients managed
by FU-BCs, the rate of persistent GN-BSI was usually
lower than 10%, with the already mentioned excep-
tions of children and critically ill patients. Con-
versely, in studies showing a selected approach
where only percentages of FU-BCs were between
17.6% and 30%, the rate of persistent GN-BSI was
usually higher than 10%. In particular, in our cohort
of 1576 adult hospitalized patients with GN-BSI,
held by a selected approach, FU-BCs were obtained
in 278 (17.6%) patients, where a positivity rate of
&
38.5% was detected [16 ]. The comparison of
patients with and without FU-BCs showed several
significant differences between the two groups.
Patients with FU-BCs were younger, more frequently
www.co-infectiousdiseases.com 553
 554
Table 1. Summary of the studies focused on follow-up blood cultures (FU-BCs) in patients with Gram-negative bacteraemia
Rate of FU-BCs Rate of patients
Number of GN-BSI drawn from with persistent
patients analysed and GN-BSI GN-BSI Risk factors for persistent Impact of FU-BCs on Impact of FU-BCs on
Study Definition of FU-BCs type of setting patients GN-BSI patient management clinical outcome

Kang 2013 Persistent BSI: positive 1068 hospitalized adult 862 (80.7%) 62 (7.2%) Multivariable analysis: NA NA
BMC Inf Dis result in more than one patients with Klebsiella
Intra-abdominal infection
separate BCs for > 2- pneumoniae BSI (aOR, 2.99; 95% CI,
day period in a single 1.07--8.31)
infection episode
Higher Charlson’s
Gram-negative infections

comorbidity index score

(aOR, 1.18 per each point;
95% CI, 1.01--1.36

SOT (aOR, 92.23; 95%
CI, 1.27--6689.96;

Un-favorable treatment
response (aOR4.79; 95%
CI, 1.89--12.14)

www.co-infectiousdiseases.com
Wiggers 2016 Repeat BC set drawn 2--7 901 adult hospitalized
BMC Inf Dis day after the index
BCs
Canzoneri 2017 Persistent BSI: 500 adult hospitalized
Clin Inf Dis positive BCs for the same
original organism in a
sample drawn at least
24 h after index BCs
Shi 2019 Repeat BCs taken more 333 adult hospitalized
Eur J Clin than 24 h after index
Microbiol Infect BCs
Dis.
247 (35.2%) 27 (10.9%) Multivariable analysis: - Longer treatment duration in In the overall cohort
patients with GN-BSI
Male sex (aOR: 2.59; patients with FU-BCs (GPþGN) LOS was longer
out of 1081 overall BSI 95CI, 1.28--5.25) - Higher rate of source for those with repeat

Admission to a medical control cultures compared to those
service (aOR 2.80; 95CI - High costs associated with without (26 vs. 12 days,
1.34--5.84) FU-BCs P < 0.001)

Endovascular source (aOR
7.66; 95CI 2.30--25.48)

Epidural focus of infection
(aOR 26.99; 95CI 1.91--
391.08)

Multivariable analysis was
performed on the entire
cohort of BSI (GPþGN)
140/GN-BSI 8 (5.7%) Univariable analysis: NA NA
patients with BSI (GP þ denominator
Fever when cultures drawn
GN þ polymicrobial) size was not
specified
306 (91.8%) 55 (17.9%) Multivariable analysis: No differences in duration of No differences in in-hospital
patients with urinary
Malignancy (OR 4.72, antibiotics (days) between death between patients
source bacteremia 95% CI 1.815--12.28) patients with and without with and without FU-BC

Initial ICU admission (OR FU-BC
4.95, 1.482--11.05)

CRP >16 mg/dl (OR 4.14,
1.631--10.53)

Time to defervescence >48
h (OR 3. 57, 1.37--9.25)

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Uehara 2019 Persistent bacteraemia: 99 children hospitalized 99 (100%) 21 (21.2%) Multivariable analysis:
Change in choice and/ NA
J Inf Chem isolation of the same with GNBSI
Presence of CVC OR or dose of antibiotics
organism from BCs 117.33 (95% CI 3.04--
Removal of medical
drawn at least 24 h 98.62) devices such as catheters
apart during the same
Resistance to empirical
episode antibiotics OR 9.09 (1.07-
77.30)

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December 2022

 Table 1 (Continued)
Rate of FU-BCs Rate of patients
Number of GN-BSI drawn from with persistent
patients analysed and GN-BSI GN-BSI Risk factors for persistent Impact of FU-BCs on Impact of FU-BCs on
Study Definition of FU-BCs type of setting patients GN-BSI patient management clinical outcome
Giannella 2020 Repeat BCs drawn 1576 adult hospitalized 278 (17.6%) 107 (38.5%) NA Source control and ID The performance of FU-BC
Clin Microbiol Infect between patients with GN-BSI consultation were was a protective factor at
24 h and 7 days after performed more frequently multivariable analysis for
index BCs among patients with FU- all-cause 30-day mortality
BCs after adjustment for
clinical severity and time
at risk
Maskarinec 2020 Repeat BCs drawn from 1702 adult hospitalized 1164 (65.4%) 228 (20%) Endovascular source of BSI was NA A propensity score weighted
Clin Microbiol Infect 24 h to 7 days after patients GN-BSI the main risk factor for Cox proportional hazards
the index BCs persistent GN-BSI regression model showed
reduced hospital and
attributable mortality in
patients with vs. without
FU-BCs
Spaziante 2020 Repeat BCs drawn within 78 adult critically ill 78 (100%) 28 (35.9%) Univariable analysis: NA NA
Minerva Anestesiol. 48 h from the patients with GN-BSI
Duration of fever (6 [0--12]
beginning of vs. 3 days [1--5],
antimicrobial therapy respectively, P ¼ 0.04
Mitaka 2020 Repeat BCs obtained at 442 adult hospitalized 306 (69%) 28 (9%) Multivariable analysis: NA NA
Open Forum least 24 h after the patients with GN-BSI
ESRD on hemodialysis
Infect Dis. index BCs aOR, 2.95 (95% CI, 1.14--
7.61)

intravascular device aOR
2.52 (1.02--6.28)

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ESBL or carbapenem
producing organism aOR
3.07 (1.22--7.76)
Jung 2020 Repeat BCs drawn 2--7 1481 adult hospitalized 1276 (86%) 122 (9.5%) Multivariable analysis: NA NA
BMC Infect Dis days after the initial patients with GNBSI Eradicable source of infection:
blood culture
ESBL-producing
microorganism OR 2.72
(95% CI, 1.18--6.27)

CVC-BSI OR 3.95 (1.52--
10.25)

Unfavourable treatment
response OR 2.23 (1.26--
3.94)

qSOFA score  2 on the
day of FU-BC OR 2.37
(1.03--5.44)

Effective antibiotics OR
0.36 (0.16--0.81)

Adequate source control

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OR 0.14 (0.06--0.29)
Noneradicable source of
infection

ESRD on HD OR 4.08

www.co-infectiousdiseases.com
(1.33--12.51)

Unfavourable treatment
response OR 2.23 (1.26--
3.94)

Effective antibiotics OR

555
Follow-up blood culture in Gram-negative bacilli bacteraemia Giannella et al.

0.13 (0.07--0.25)
 556
Table 1 (Continued)
Rate of FU-BCs Rate of patients
Number of GN-BSI drawn from with persistent
patients analysed and GN-BSI GN-BSI Risk factors for persistent Impact of FU-BCs on Impact of FU-BCs on
Study Definition of FU-BCs type of setting patients GN-BSI patient management clinical outcome
Amipara 2021 Repeat BCs obtained 766 adult hospitalized 219 (28.6%) 15 (6.8%) NA NA Obtaining FU-BC was
eClinMed between 24 and 96 h patients with independently associated
from index BCs community onset GN- with reduced mortality
BSI
Gram-negative infections

Clemmons 2021 Repeat BC obtained 52 adult patients with 35 (65%) 9% NA No difference in ID LOS was significantly longer
Diagn Microbiol within 72 h from index underlying solid or consultation and CVC in FU-BC vs. no FU-BC
Infect Dis. BCs haematological removal between patients group patients
malignancy and with and without FU-BC.
GN-BSI Longer treatment duration
among patients with FU-
BC
Kim 2022 Positive FU-BC was 2216 adult hospitalized 645 (29%) 89 (13.8%) Multivariable analysis: NA NA

www.co-infectiousdiseases.com
Infection defined as isolation of
the same organism in
repeated BCs 48--72 h
after index BCs
Mitaka 2022 Repeat BC drawn 376 adult hospitalized
Infect Control Hosp between 24 h and
Epidemiol. 7 days after index BCs
Buzzalino 2022 Repeat BCs drawn 139 adult patients with
Open Forum Infect Dis. between 24 h and
7 days from index BCs
patients with GNBSI
Haemodialysis aOR 2.62
(95% CI 1.22--5.63)

Fever on the day of FU-BC
aOR 3.57 (1.98--6.46)

Intravascular device aOR
2.38 (1.37--4.12)

No in vitro active antibiotic
use within 24 h aOR 2.45
(1.38--4.34)

Nonfermenter aOR 4.68
(2.59--8.45)

Multidrug resistance aOR
5.35 (2.76--10.37)
271 (72%) 27 (10%) NA After PS matching 87 pairs After PS matching 87 pairs
patients with GNBSI of patients with and of patients with and
without FU-BC were without FU-BC were
analysed: analysed:
Antibiotic treatment - LOS was longer among
duration was longer FU-BC patients
among FU-BC patients - In-hospital mortality was
4.6% vs. 11.4% among
patients with vs. without
FU-BC (P ¼ 0.16)
117 (84.2%) 3 (2.6%) NA Patients with FU-BCs more Patients with FU-BCs had
underlying solid or frequently had antibiotic longer median LOS.
haematological durations extended Inpatient all-cause mortality
malignancy and beyond the original was not different between
GN-BSI planned duration patients with and without
FU-BCs.

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aOR, adjusted odd ratio; CI, confidence interval; CVC, central venous catheter; ESBL, extended spectrum beta-lactamase; ESRD, end-stage renal disease; FU-BCs, follow-up blood cultures; GN, Gram-negative; GN-BSI,
Gram-negative bloodstream infection; GP, Gram-positive; HD, haemodialysis; ID, infectious disease; LOS, length of stay; NA, not available; PS, propensity score; SOT, solid organ transplant.

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 Follow-up blood culture in Gram-negative bacilli bacteraemia Giannella et al.
male and showed lower Charlson comorbidity
index. However, they were more frequently immu-
nocompromised, admitted to ICU, and had hospital
acquired BSI. Clinical severity at BSI onset, accord-
ing to SOFA and septic shock criteria, and nonuri-
nary sources rates were higher in patients with FU-
BCs, as well as the isolation of carbapenem resistant
strains. Finally, FU-BCs were more frequently drawn
in patients receiving an inappropriate empirical
therapy. In other studies, some of these factors have
been associated with higher probability of persistent
GN-BSI as described in the following section.
PREDICTORS OF PERSISTENT GRAM-
NEGATIVE BLOODSTREAM INFECTION
Several studies have analysed the risk factors for
persistent GN-BSI deriving prediction models in
order to select patients in which the performance
&
of FU-BCs should be recommended [17 ,24–26].
Kang et al. [27] derived a score to estimate the
likelihood of persistent Klebsiella spp. bacteraemia
considering four risk factors: intra-abdominal infec-
tion, nosocomial acquisition of infection, fever
and lack of C-reactive protein decrease, with a value
of 1, 2, 3, and 2, respectively. The frequency of
persistent bacteraemia exceeded 50% when the
score was greater than five; conversely, it was only
4.9% when the score was zero to one [27].
&
Maskarinec et al. [17 ] developed the Antibiotics –
Infection source – Medical comorbidities – Species of
bacteria (AIMS) risk scoring system. Variables
included were time to active treatment (1 day),
infection source (endovascular, gastrointestinal, uri-
nary, other), medical comorbidities (cardiac device,
haemodialysis and corticosteroids) and the Serratia
spp. aetiology. A point from 1 to 3 was assigned to
each variable, obtaining an individual score between
0 and 9. The predicted rate of persistent Gram Neg-
ative Bacteraemia (GNB) was 8.6% for patients with
AIMS score of 0, and increased with the presence of
each additional risk factor. The authors performed
also a classification and regression tree analysis to
identify breakpoints separating high and low rates
of positive FU-BCs in GNB. The only identified break-
point was source of bacteraemia. Patients with endo-
vascular vs. other sources had positive FU-BC rates of
32% vs. 17% (P < 0.001) [17 ].
&
Mitaka et al. [26] showed that factors independ-
ently associated with positive FU-BC were patients
with end-stage renal disease (ESRD) on haemodial-
ysis, intravascular device, and extended spectrum
beta-lactamase (ESBL) or carbapenemase producing
organism. The yield of FU-BCs in patients with 1 of
such factors was 23 of 155 episodes (14.8%; 95%
confidence interval [CI] 9.7–21.4). In contrast, the
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yield of FU-BCs in patients without any of the risk
factors was 5 of 151 episodes (3.3%; 95% CI 1.1–7.6).
According to these findings, approximately seven FU-
BCs were needed to yield one positive result in patients
with at least one risk factor, while 30 FU-BCs were
needed in patients without the risk factors [26].
Jung et al. [24], proposed two scores to predict
the probability of positive FU-BC in patients with
eradicable and not eradicable source of GN-BSI,
respectively. Noneradicable infections were defined
as those with a primary source impossible to remove.
In patients with eradicable source of GN-BSI the
model included: isolation of ESBL producing bacteria
(point þ1), catheter-related BSI (point þ1), unfavour-
able treatment response (point þ1), qSOFA score 2
(point þ1), administration of effective antibiotics
(point 1), and adequate source control (point 2).
The model for patients with noneradicable source of
infection included: ESRD on haemodialysis (point
þ1), unfavourable treatment response (point þ1and
the administration of effective antibiotics (point 2).
An individual total score of 1 or 2 was associated with
40% and 70% of positive FU-BCs in patients’ non-
eradicable and eradicable BSI source, respectively [24].
Kim et al. [28] identified haemodialysis, immu-
nosuppressive treatment, fever on the day of FU-BC,
and intravascular device as independent risk factors for
positive FU-BCs and assigned 1 point to each of them.
The yield of FU-BCs increased from 3% (95% CI 1–7%)
to 63.6% (95% CI 25.6–100) as the number of risk
factors increased from 0 to 4. According to this model,
the authors showed that 1.5 FU-BCs were needed to
yield one positive FU-BC in patients with four risk
factors, whereas 34 FU-BCs were needed for one pos-
itive result in patients with no risk factors. In addition,
30-day mortality rates increased as the number of
bedside risk factors for positive FU-BCs increased,
especially in patients with positive FU-BCs [28].
Positive FU-BCs is a potential indicator of com-
plicated GN-BSI (uncontrolled source, metastases to
distant sites, resistance to currently used antibiotics,
etc.), which requires a careful revision of diagnostic
and therapeutic management. In addition, persis-
tent GN-BSI has been associated with a risk of dying
nearly twice than that found in patients with neg-
&
ative FU-BCs [17 ,28]. Therefore, the use of risk
scores to select patients for whom FU-BCs are
needed may be useful in improving clinical course
and outcome of patients with GN-BSI. According to
the above data, an algorithm to identify patients for
whom FU-BC should be drawn is depicted in Fig. 1.
IMPACT ON MANAGEMENT AND OUTCOME
The main arguments used against the routine per-
formance of FU-BCs in patients with GN-BSI include
www.co-infectiousdiseases.com 557
Gram-negative infections
FIGURE 1. Algorithm to identify patients for whom FU-BC should be drawn. Proposed algorithm to identify patients for whom
FU-BC should be drawn according to risk factors from literature review. FU-BC, follow-up blood culture.
the risk of false positive results and the negative
impact on treatment duration and length of stay.
The rate of false positive FU-BCs has been
reported in a limited number of studies ranging
& &
from 0 to 4% [16 ,17 ,24]. A figure similar or even
lower than that usually associated to the practice of
drawing blood cultures.
Regarding the other arguments, several authors
showed that antibiotic course and hospital stay were
longer in patients with FU-BCs than in those with-
&&
out FU-BCs [21,22,29,30 ]. However, given the
observational design of all studies, the indication
bias should be considered. In other terms, FU-BCs
could have been ordered in patients at risk for, or
with evidence of, a complicated course of GN-BSI
more frequently than in those with uncomplicated
bacteraemia. Thus, in some studies, the prolonged
antibiotic therapy and the longer hospital stay could
have been due to a more difficult clinical scenario
without a clear role of FU-BCs. To take into account
&&
this bias, Mitaka et al. [30 ] performed a propensity
score matching obtaining 87 pairs of patients (with
and without FU-BC) with well balanced distribution
of covariates. In the propensity score-matched
cohort, the median duration of antibiotic therapy
(8 vs. 4 days, P ¼ 0.007) and the median length of
stay (9 vs. 7 days, P ¼ 0.017) were still longer in
patients with FU-BCs than in those without FU-
BCs. In the discussion, the authors hypothesized
that one plausible explanation for their findings
558 www.co-infectiousdiseases.com
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was that the treating physicians could have deferred
antibiotic withdrawal and hospital discharge while
waiting for the FU-BC results. In this respect a better
definition of the timing of and a FU-BCs sampling
should be shared. Finally, they recognised that
although propensity score matching reduces the risk
of selection bias due to known matched variables, it
cannot eliminate the risk of selection bias due to
unmatched variables or unmeasured confounders.
Other management issues associated with the
performance of FU-BCs, less underlined from pre-
vious authors, but that can have a huge impact on
patient outcome, are source control and ID consul-
tation. In particular for source control, this was
associated with the performance of FU-BCs as well
&
as with an improved patient outcome [16 ].
Finally, few authors have properly investigated
the impact of the performance of FU-BCs, irrespec-
tive of the diagnostic yielding, on patients’ outcome
& & &&
[16 –18 ,30 ]. To address this research question,
along with the already mentioned indication bias,
also survival bias could play a role. Longer survival
means more chance of performing FU-BCs. To over-
come this issue, we performed 1:1 matched analysis
based on exact SOFA scores of patients with and
without FU-BCs, and the time at risk (patients with-
out FU-BCs had survived at least up to the time
when FU-BCs were obtained). When the analysis
was adjusted for covariates previously associated
with outcome as Charlson comorbidity index, septic
Volume 35
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 Follow-up blood culture in Gram-negative bacilli bacteraemia Giannella et al.
shock, urinary tract source, central venous catheter-
related infection, complicated BSI, carbapenem
resistance, active empiric therapy and source con-
trol, the effect of FU-BCs on 30-day mortality was
strongly protective (hazard ratio [HR] 0.45, 95% CI
0.22–0.92, P ¼ 0.03). It is worth remarking that sur-
vival was highest among patients underwent both
&
FU-BCs and source control [16 ]. Also Maskarinec
& && of outstanding interest
et al. [17 ] reported that patients with FU-BCs had
significantly lower risk of all-cause (HR ¼ 0.629; 95%
CI, 0.511–0.772; P < 0.0001) and attributable in-
hospital mortality (HR ¼ 0.628; 95% CI 0.480–
0.820; P ¼ 0.0007) compared to patients without
FU-BC by a propensity score-weighted Cox regres-
sion model. Interestingly, also in a low-risk setting
such as that of community onset GN-BSI, Amipara
&
et al. [18 ], showed that after adjustments for the
propensity to obtain FU-BC and other potential con-
founders in the multivariate Cox model, obtaining
FU-BC was independently associated with reduced
mortality (HR 0.47, 95% CI 0.23–0.87; P ¼ 0.02).
To conclude this section, the potential of pro-
longing antibiotic course and length of hospital stay
associated with the implementation of FU-BCs
should be balanced with its potential favourable
impact on patient outcome mainly driven by a
higher rate of source control. It is worth mentioning
that, in clinical practice, source control other than
favours a better clinical outcome, usually allows for
shortening antibiotic treatment.
CONCLUSION
The role of FU-BCs in GNBSI is still a matter of debate
due to the contradictory literature evidence. Studies
focused on the low diagnostic yield concluded that
FU-BCs could not be cost-effective and even a coun-
terproductive practice due to unnecessary use of
healthcare resources and inappropriate use of anti-
microbials in the general population. However, stud-
ies focused on the clinical outcome have shown a
strong favourable impact of FU-BCs on the survival of
patients with GNBSI. Therefore, the selection of
patients in which to maximize the diagnostic yield
of FU-BC could be a goal of GNBSI management. To
this purpose, several scores have been developed
based on individual characteristics predisposing to
persistent bacteraemia.
Acknowledgements
All authors made a substantial contribution to the
article.
Financial support and sponsorship
None.
0951-7375 Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Conflicts of interest
There are no conflicts of interest.
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Volume 35
Number 6
December 2022