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The correct blood volume for paediatric blood cultures: a conundrum?
Journal Pre-proof The correct blood volume for pediatric blood cultures: a conundrum? Silke Huber, Benjamin Hetzer, Roman Crazzolara, Dorothea Orth-Höller PII:
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Clinical Microbiology and Infection
Received Date: 2 August 2019 Revised Date:
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Accepted Date: 5 October 2019
Please cite this article as: Huber S, Hetzer B, Crazzolara R, Orth-Höller D, The correct blood volume for pediatric blood cultures: a conundrum?, Clinical Microbiology and Infection, https://doi.org/10.1016/ j.cmi.2019.10.006. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.
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Intended category:
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Bloodstream Infection
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Title:
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The correct blood volume for pediatric blood cultures: a conundrum?
5 6
Authors
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Silke Huber1, Benjamin Hetzer², Roman Crazzolara², Dorothea Orth-Höller1
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Institutions
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1
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Austria
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2
Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck,
Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria
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Length of Abstract (i):
297 words
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Length of Paper (ii):
2661 words
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Running title: Blood volume for pediatric blood cultures
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Corresponding author
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Dorothea Orth-Höller, MD
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Institute of Hygiene and Medical Microbiology
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Medical University of Innsbruck
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Schöpfstrasse 41
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6020 Innsbruck, Austria
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[email protected]
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Abstract
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Background
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Bloodstream infections (BSI) are a major cause of morbidity and mortality in pediatric patients. For fast
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and accurate diagnosis, blood culture (BC) is the gold standard. However, the procedure for blood
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sampling in pediatric patients, particularly the optimal blood volume, is the subject of controversy
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stemming from a lack of knowledge on the bacterial load and because of several obstacles such as low
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intravascular volume with the risk of causing anemia.
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Objectives
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The aim of this narrative review was to summarize current knowledge on blood sampling in pediatric
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patients for BC purposes in particular on blood volume, number and type of BC bottles needed for
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reasonable future guidelines/recommendations.
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Sources
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A comprehensive literature search of PubMed including all English literature was performed in June 2019
41
using the search terms ‘blood culture’, ‘blood volume’, ‘bloodstream infection’, ‘diagnostic’, ‘pediatric’
42
and/or ‘sepsis’.
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Content
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The amount of inoculated blood determines the sensitivity, specificity and time to positivity of a BC, and
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low-level bacteremia (≤ 10 cfu/mL) in pediatric patients is presumed to be more common than reported.
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Current approaches for “adequate” blood volume for pediatric BC are mainly weight- or age-dependent.
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Of these recommendations scheme devised by Gaur and colleagues seems most appropriate and calls for a
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sample of 1-1.5 mL for children weighing less than 11 kg and 7.5 mL for a patient weight of 11-17 kg to
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be drawn into one BC bottle. Inclusion of a more detailed grading in the weight range 4-14 kg as
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published by Gonsalves and colleagues might be useful.
51
Implications
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This review could be important for future guidelines on pediatric BC collection and thus could contribute
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to improving patient management and lowering the economic and global health burden associated with
54
BSI. Furthermore, upcoming molecular-based approaches with low sample volumes might be an
55
interesting alternative.
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Background
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Bloodstream infections (BSI) are associated with substantial morbidity, mortality and a heavy economic
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burden [1,2]. The SPROUT study, a global cross-sectional study including 26 countries demonstrated a
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prevalence of 8.2% for severe sepsis in children (<18 years) in intensive care units not differing by
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age [3]. In neonates the incidence of BSI is reported to be weight-dependent with the highest incidence
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seen in the birthweight group under 499g [4]. Blood culture (BC) with a continuously monitored BC
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system is the gold standard for diagnosis of BSI. Fast and accurate identification of causative pathogens is
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known to be essential for etiological global surveillance, modification of empirical therapy and ultimately
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for patient outcome [5].The prevalence of BSI-causing pathogens very much depends on the patient’s
65
age, underlying diseases and current therapy [6] as well as the socio-economic environment. The most
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common pathogens identified in BSI in infants younger than 1 month are Escherichia coli, group B
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Streptococcus, Listeria monocytogenes and Staphylococcus aureus [2,7,8]. Above that age mainly
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Staphylococcus aureus, Streptococcus pneumoniae, Neisseria meningitidis and E. coli predominate [6]. In
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immunosuppressed patients the spectrum is different and includes more pathogens [9]. The bacterial load
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within pediatric BSI remains controversial as findings are divergent and report both high [10–15] and
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low [1,16–21] concentrations for different pathogens. For BC collection in adult patients, consistent
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recommendations for blood volume, number and type of BC bottles exist. In contrast, sampling from
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pediatric patients is controversially discussed in literature, especially the blood volume as a major factor
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for successful pathogen recovery [6,22]. The optimal blood volume might be limited due to a small
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intravascular blood, as present in neonates [6,23,24]. Furthermore, repeated blood draws in critically ill
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children increase the risk for anemia or other circulatory problems. Most importantly, blood collection in
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small children is time-consuming, associated with major distress and requires trained personnel due to
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technical challenges and in order to avoid contamination. In fact, the most frequently reported painful
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events in hospitalized children were venipuncture for lab draws or intravenous lines [25]. As the latter is
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recognized to have a negative impact on the child’s level of cooperation [26], strategies for minimizing
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unnecessary exposure of children are considered good clinical practice. The aim of this narrative review
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was to summarize the current knowledge on BC collection in pediatric patients including volume, number
83
and type of BC bottle.
84
Sources
85
A comprehensive literature search (from 1989 to 2019) of PubMed including all English literature was
86
performed in June 2019 using the search terms ‘blood culture’, ‘blood volume’, ‘bloodstream infection’,
87
‘diagnostic’, ‘pediatric’ and/or ‘sepsis’. Queries regarding diagnostic accuracy of blood volume were
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answered by study selection of clinical trials and cross-sectional studies. Two independent reviewers used
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the keywords “volume”, “blood” and “culture” and included only studies focusing on pediatric patients.
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The majority of these studies were prospective. Exclusion criteria were editorials, letters and conference
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abstracts/reports. Any disagreements between selected studies were resolved by discussion with the third
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and fourth reviewers. Additionally, guidelines stating specific volumes for pediatric patients were
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summarized.
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Results
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Blood Volume and Bacterial Load
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Blood volume is stated to be the major factor influencing successful recovery of pathogens in BC [6,22].
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In adults BC is standardized with a recommended blood volume of 8-10 mL per BC bottle [27,28],
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usually two to three sets each containing one aerobic and one anaerobic BC bottle from a single
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venipuncture are taken. This volume might not be available in pediatric patients, especially in younger
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age groups. Thus, the optimal blood volume in this patient group remains a conundrum, although several
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age- as well as weight-based recommendations exist (Table 1, Table 2). Definitely, the amount of
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inoculated blood volume determines the sensitivity, specificity and time to positivity of a BC [29]. This is
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clearly supported by studies claiming that each additional 1 mL of blood drawn increases the yield of
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bacteria by up to 4.7% [12,30–32]. In the past, it was presumed that a low blood volume of 0.5-1.0 mL is
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sufficient for detecting BSI [33] as bacteremia in pediatric patients was thought to be associated with a
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high bacterial load [10–15]. However, the incidence of low level bacteremia in pediatric patients is
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presumed to be more common than reported [1,16–21]. In fact, Kellogg and colleagues assessed 121
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pediatric patients up to 15 years of age with confirmed bacteremia for their bacterial load. Interestingly,
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60.3% of those patients had a low and even 23.1% an extremely low bacterial load, namely ≤ 10 colony-
110
forming units (cfu) per mL and ≤ 1 cfu per mL, respectively [16]. Considering these results, they
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suggested that a total blood volume up to 4.5% (2-4.5 mL), 3% (≤ 6 mL) and 2.9% (23-60 mL, aliquoted
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in several bottles) of the total blood volume for patients weighing ≤ 2 kg, ≤ 12.7 kg and ≥ 12.8 kg,
113
respectively, is imperative for successful recovery of causative pathogens (Table 1, Fig. 1) [16–18,34].
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Subsequently, the American Society for Microbiology (ASM) and the Infectious Disease Society of
115
America (IDSA) published similar recommendations for the total blood volume needed for
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BC [27,28,35]. However, the volumes recommended by Kellogg and colleagues, ASM and IDSA might
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not be feasible in the routine clinical setting, especially in patients with low body weight (≤ 2 kg), in
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particular premature and mature neonates classified as extremely preterm (23+0 gestational age),
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moderate preterm (32+0 gestational age) or term (40+0 gestational age) (Fig. 1). In general, blood
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sampling involving up to 4% of the total blood volume of a patient can be replaced by adequate blood
121
production [34]. It must be considered that in critically ill children blood production is altered, and
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furthermore this patient group is often exposed to repeated blood draws for additional laboratory tests,
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thus possibly exceeding the critical value of 4% blood loss. The Clinical and Laboratory Standards
124
Institute even recommends not exceeding 1% of a patient’s total blood volume for pediatric blood
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culture [22]. This approach was also used by Gaur and colleagues, who suggested a detailed, weight-
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dependent sampling of 1-1.5 mL for children weighing less than 11 kg and 7.5 mL for a patient weight of
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11-17 kg [36]. This grading might be more realistic in the clinical setting, especially in the case of
128
neonates. Subsequently, this study was cited in MiQ: Qualitätsstandards in der mikrobiologisch-
129
infektiologischen Diagnostik (MiQ: Quality Standards in Microbiological-infectiological Diagnostics)
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published by experts of the German Society of Hygiene and Microbiology [37]. Gonsalves and colleagues
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proposed a similar scheme with more detailed grading in the weight range 4-14 kg and he could show a
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significant higher detection rate with this weight-based volume compared to inadequate volume BC in the
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true bacteremia group [38]. Several additional studies support the weight–based approach with a different
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grading (Table 1, Fig. 1) [1,39]. There is evidence that these approaches are superior in pathogen
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detection compared to inadequate BC volumes, however there are no data comparing different weight-
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based schemes [38,39]. Most studies and guidelines recommend to sample ≥ 40 mL blood for patients
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weighing ≥ 37 kg reflecting BC recommendations for adults. Gaur and colleagues suggest a volume of
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16.5 mL only for this patient group which seems rather low.
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Another approach to determining the optimal blood volume for BC that is often used in studies
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investigating neonates and/or young children depends on the age of the patient (Table 2). The majority of
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these studies suggested a blood volume of 0.5-1 mL for neonates [40–43]. The volume of 0.5 mL was
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most probably chosen as this is the minimal volume validated by the companies offering BC
143
diagnostics [44,45]. For infants (≤ 12 months; equates to < 9.6 kg according to the 50th percentile of child
144
growth standard [46–48]) a blood volume of 1-3 mL, for toddlers (1-4 years; 8.9-16.3 kg) 3-4 mL, for
145
school children (5 to 9 years, 16.1-28.2 kg) 6-8 mL and for older children (> 10 years; > 31.2 kg) at least
146
20 mL was recommended [1]. Connell and colleagues demonstrated that the implementation of an age-
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dependent approach resulted in an increase in positive BC from 2.6% to 5.1% as compared to an
148
insufficient blood volume [40].
149
A further approach is to adapt the media volume to the amount of collected blood. This is also supported
150
by the fact that BC bottles are validated for a particular broth-to-blood ratio [45]. For this reason, the two
151
leading manufacturers of BC bottles have developed smaller BC bottles for pediatric use. Solórzano-
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Santos and colleagues investigated whether a 1:10 scale-down of a standardized BC system while
153
maintaining the same broth-to-blood ratio would affect the assay’s performance. Since sensitivity and
154
specificity for the micro-culture system were 95% and 99%, respectively, compared to a routine blood
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culture, this system was recommended for diagnosis of pediatric sepsis in laboratories with manual
156
systems [49].
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Considering the different approaches, the general consensus appears to support the basic recommendation
158
that blood draw for BC should be based on the patient’s age and/or weight, both of which are
159
interdependent variables. However, the wide range of the different recommendations for optimal blood
160
volume for the various age and weight groups is remarkable (Table 3).
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Blood Volume and Contamination
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Despite proper aseptic handling, the BC contamination rate is 1-3%, resulting in inconclusive diagnosis,
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unnecessary antimicrobial treatment [1], increased mortality of patients with suspected sepsis and a
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burden on the health system [39]. In addition to aseptic blood culture procedure and methodology,
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inadequate blood volume inoculation into culture bottles is associated with a disproportionate risk of
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culturing contaminants [43]. A recent study conducted at Batson Children’s Hospital in Jackson,
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Mississippi (USA) demonstrated a decrease in contamination rates from 2.85% to 1.54% as a result of
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introducing a standardized blood sampling method with optimized (weight-based) volume (Table 1) and
169
personnel training [39]. In general, the main aspects of such personnel training should include proper
170
handling of skin antisepsis, hand hygiene of the personnel taking blood, use of gloves and cleaning the
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tops of the BC bottles with antiseptics [50].
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Blood Volume, Number and Type of Blood Culture Bottles
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Whenever possible, blood for BC should be sampled from a new peripheral venipuncture site. To increase
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sensitivity and differentiate between contaminants and true pathogens in adult patients it is proposed that
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two or more culture sets be used, drawn from different sampling sites. However, in neonates and infants it
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is often not possible to obtain a blood volume sufficient for more than one or even only one BC bottle.
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For pediatric use smaller BC bottles were introduced to offer a good proportion of broth and a small
178
blood volume to support the growth of most common pathogens and thus increase the likelihood of
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recovering true pathogens in an acceptable time [44,45]. To our knowledge pediatric BC bottles are
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currently available only for aerobic conditions. Validated blood volumes for a single pediatric BC bottle
181
from the two leading companies for BSI diagnosis range between 0.5-4 and 5 mL [44,45] with an
182
optimum of 1-3 mL [44]. Above this volume, both companies recommend the use of adult BC
183
bottles [44,45]. The number of bottles for pediatric BC is highly associated with the collected blood
184
volume [16,27,28,45]. Thus, it seems reasonable to aliquot the blood only when the collected blood
185
volume exceeds the optimal blood volume for one BC bottle. Our statement is supported by several
186
publications suggesting that a blood volume < 10 mL should be drawn in one aerobic bottle [27–
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29,39,45]. Pathogens affecting children are mostly aerobic. Thus, collecting blood in a pediatric aerobic
188
bottle seems reasonable. The additional use of an anaerobic bottle might not be necessary as anaerobic
189
bacteremia is present in less than 1% of BSI in pediatric patients [51]. Still, some facultative anaerobic
190
pathogens may be isolated preferentially under anaerobic conditions [1,52]. Limited studies of the use of
191
pediatric BC bottles only vs. pediatric plus an adult anaerobic BC bottle have produced controversial
192
results. The decision whether to use an anaerobic BC bottle is more likely to be made by the treating
193
physician on a case-to-case basis. The main indications to do so are cellulitis, chorioamnionitis or
194
necrotizing enterocolitis.
195
Alternative Diagnostic Methods
196
Isolators:
197
An alternative to conventional BC might be a special system called isolator. With this system white and
198
red blood cells are lysed by adding blood to a chemical buffer. The specimen is then either directly spread
199
on an appropriate agar plate or first centrifuged to precipitate blood cell residues. A major advantage of
200
this system is the fact that only a small blood volume (1.5 mL) is needed to recover and quantify
201
pathogens [16]. Data on the accuracy of this approach are rare and even controversial, with either
202
comparable [53,54] or inferior [36] detection rates as compared to BC.
203
Molecular Diagnostics:
204
As time to result is an important factor in avoiding a bad outcome, molecular diagnostics, more
205
specifically PCR-based systems, for pathogen detection directly from blood samples were developed.
206
Beside the reduced time to detection, these systems also offer advantages in that they need only small
207
blood volumes (1 mL), detect intracellular or slow growing pathogens and avoid inconclusive results due
208
to antimicrobial treatment. On the other hand, pathogen detection from small blood samples harbors the
209
risk of a false-negative result due to low bacterial load [55,56]. Other disadvantages of PCR-based
210
systems include contamination-induced false-positive results, high costs, limited pathogen panel and lack
211
of resistance determination [57]. Nevertheless, Lucigano and colleagues investigated the performance of a
212
multiplex PCR-based system (LightCycler® SeptiFast Test) using over 1,600 samples from pediatric
213
patients. In comparison to BC, SeptiFast results showed a specificity of 93.5% and a sensitivity of 85%
214
with a 4.3% increased rate of positive results [58]. In conclusion, the molecular diagnosis of bacterial BSI
215
is a good alternative for some occasions, for example in neonates with previous maternal antibiotic
216
treatment, but is not yet a substitute for BC.
217
Conclusions
218
This review aims to summarize the current literature regarding the optimal volume of blood draw for BC
219
and provides recommendations for treating physicians in daily practice. It is important for critically ill
220
children with suspected BSI to obtain a rapid and reliable diagnosis. However, the management of BSI
221
patients calls for repeated and possibly painful blood draws for various laboratory tests. Such blood draws
222
often exceed physiological replacement and can cause a negative impact on the level of cooperation of
223
pediatric patients. For all these reasons it seems most reasonable and realistic to follow the scheme
224
devised by Gaur and colleagues, namely a weight-dependent sampling of 1 mL for children weighing less
225
than 2 kg, 1.5 mL for patients with a weight under 11 kg and 7.5 mL for a patient weight of 11-
226
17 kg [36]. As the recommended blood volume for the latter patient group is often difficult to obtain, it
227
might be valuable to include the scheme developed by Gonsalves and colleagues, providing a more
228
detailed grading for a patient weight of 4-14 kg [38]. For a patient weight of ≥ 37 kg a blood volume
229
≥ 40 mL should be considered. Beside this weight-based approach, we recommend to use the age-
230
dependent approach of Revell and Doern as an alternative [1]. Definitely, it is recommended to collect a
231
weight- or age-dependent blood volume and inoculate this sample into one pediatric or adult aerobic BC
232
bottle if the total volume sampled does not exceed 4-5 mL or 10 mL, respectively [27–29,39,45]. For
233
quality management reasons it is strongly recommended that monitoring be performed frequently and that
234
all personnel involved in drawing blood be trained regarding sampling volume and processing [39,40,43].
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Besides BC, molecular-based diagnostics may be an interesting alternative in future with the advantage of
236
requiring a small blood volume. For BSI fast and accurate diagnosis is mandatory and this review could
237
be important for future guidelines on pediatric BC collection to improve patient management and lower
238
the economic and global health burden associated with BSI.
239
Transparency Declaration
240
The authors declare no conflict of interests.
241
Funding Statement
242
No funds were received from the current work.
243
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Gonsalves WI, Cornish N, Moore M, Chen A, Varman M. Effects of volume and site of blood
335 336
draw on blood culture results. J Clin Microbiol 2009;47:3482–5. [39]
El Feghaly RE, Chatterjee J, Dowdy K, Stempak LM, Morgan S, Needham W, et al. A Quality
337
Improvement Initiative: Reducing Blood Culture Contamination in a Children’s Hospital.
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Pediatrics 2018;142:e20180244.
339
[40]
Connell TG, Rele M, Cowley D, Buttery JP, Curtis N. How Reliable Is a Negative Blood Culture
340
Result? Volume of Blood Submitted for Culture in Routine Practice in a Children’s Hospital.
341
Pediatrics 2007;119:891–6.
342
[41]
343 344
Volume for Neonatal Blood Cultures. Pediatr Infect Dis J 2015;34:351–4. [42]
345 346
Yaacobi N, Bar-Meir M, Shchors I, Bromiker R. A Prospective Controlled Trial of the Optimal
Sarkar S, Bhagat I, DeCristofaro JD, Wiswell TE, Spitzer AR. A study of the role of multiple site blood cultures in the evaluation of neonatal sepsis. J Perinatol 2006;26:18–22.
[43]
Harewood FC, Curtis N, Daley AJ, Bryant PA, Gwee A, Connell TG. Adequate or Inadequate?
347
The Volume of Blood Submitted for Blood Culture at a Tertiary Children’s Hospital. Clin Pediatr
348
2018;57:1310–7.
349
[44]
350 351
uk/products/diagnostics-systems/blood-culture-systems/bactec-media (accessed July 10, 2019). [45]
352 353
[46]
World
Health
Organisation
(WHO).
The
WHO
Child
Growth
Standards
2016.
https://www.who.int/childgrowth/en/ (accessed July 30, 2019). [47]
356 357
Novak-Weekley SM, Dunne WMD. Blood Culture: A key investigation for diagnosis of bloodstream infections 2018. https://www.biomerieux-usa.com (accessed July 8, 2019).
354 355
BD Diagnostics Europe. BD BACTECTM Media Broschure 2009. https://www.bd.com/en-
Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr 2013;13:59.
[48]
Voigt M, Rochow N, Straube S, Briese V, Olbertz D, Jorch G. Birth weight percentile charts based
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on daily measurements for very preterm male and female infants at the age of 154–223 days. J
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Perinat Med 2010;38:289–95.
360
[49]
Solorzano-Santos F, Miranda-Novales MG, Leanos-Miranda B, Diaz-Ponce H, Palacios-Saucedo
361
G. A Blood Micro-Culture System for the Diagnosis of Bacteremia in Pediatric Patients. Scand J
362
Infect Dis 1998;30:481–3.
363
[50]
364 365
Gesundheitsforsch - Gesundheitsschutz 2017;60:216–30. doi:10.1007/s00103-016-2485-6. [51]
366 367
Zaidi AK, Knaut AL, Mirrett S, Reller LB. Value of routine anaerobic blood cultures for pediatric patients. J Pediatr 1995;127:263–8.
[52]
368 369
Prävention von Infektionen, die von Gefäßkathetern ausgehen. Bundesgesundheitsblatt -
Martin WJ. Routine anaerobic blood cultures: Reasons for continued use. Clin Microbiol Newsl 1992;14:133–4.
[53]
Campos JM, Spainhour JR. Comparison of the Isolator 1.5 Microbial Tube with a conventional
370
blood culture broth system for detection of bacteremia in children. Diagn Microbiol Infect Dis
371
1985;3:167–74.
372
[54]
373 374
system for detection of bacteremia in children. J Clin Microbiol 1984;19:634–8. [55]
375 376
Afshari A, Schrenzel J, Ieven M, Harbarth S. Bench-to-bedside review: Rapid molecular diagnostics for bloodstream infection - a new frontier? Crit Care 2012;16:222.
[56]
377 378
Carey RB. Clinical comparison of the Isolator 1.5 microbial tube and the BACTEC radiometric
Reimer LG, Wilson ML, Weinstein MP. Update on detection of bacteremia and fungemia. Clin Microbiol Rev 1997;10:444–65.
[57]
van de Groep K, Bos MP, Savelkoul PHM, Rubenjan A, Gazenbeek C, Melchers WJG, et al.
379
Development and first evaluation of a novel multiplex real-time PCR on whole blood samples for
380
rapid pathogen identification in critically ill patients with sepsis. Eur J Clin Microbiol Infect Dis
381
2018;37:1333–44.
382
[58]
Lucignano B, Ranno S, Liesenfeld O, Pizzorno B, Putignani L, Bernaschi P, et al. Multiplex PCR
383
Allows Rapid and Accurate Diagnosis of Bloodstream Infections in Newborns and Children with
384
Suspected Sepsis. J Clin Microbiol 2011;49:2252–8.
385 386 387 388 389 390
391
Legend to Figure
392
Figure 1. Loss of intravascular blood volume associated with sample collection for blood culture. The y
393
axis shows the total blood volume loss (in %) when collecting blood according to different
394
guidelines [1,16,27,28,35,36,38]. The x axis demonstrates this scenario at different patient ages
395
(extremely preterm, 23+0 gestational weeks; moderate preterm, 32+0 gestational weeks; term, 40+0
396
gestational weeks; 3 months; 1 year; 2 years; 10 years). The total blood volume was calculated according
397
to Howie [24] (85ml/kg in neonates and 75ml/kg in children) and using the 50th female weight
398
percentile [46–48]. Blood loss of 4% due to blood sampling (indicated with a dashed line) can be replaced
399
by adequate blood production and is considered safe for the patient [34]. However, it should be
400
considered that critically ill children often have a lower intravascular blood volume than calculated here
401
for healthy children and are exposed to repeated blood draws for additional laboratory tests. The Clinical
402
and Laboratory Standards Institute recommends a blood draw for pediatric BC of less than 1% of a
403
patient’s total blood volume (indicated with a dotted line) [22]. It is noteworthy that adherence to the
404
recommendations of Kellogg and colleagues and the guidelines of the American Society for Microbiology
405
(ASM) and the Infectious Disease Society of America (IDSA) might result in excessive blood loss in
406
neonates.
407
Table 1 Overview of studies and guidelines with weight-dependent approaches for blood volume for pediatric blood culture. Total Blood Study/Guidelines
Weight [kg]
Volume† [mL]
Number of Bottles‡/Isolators
Studies
Kellogg et al. (2000) [16]
Gaur et al. (2003) [36]
≤ 1.0
2.0
2
1.1-2.0
4.5
2
2.1-12.7
6.0
2
12.8-36.3
23.0
4
> 36.3 1.5-2.1
60.0 1.0
4 1
2.2-11.1
1.5
1
11.2-17.1
7.5
3
17.2-37.2
11,5
3
> 37.3 < 3.9
16.5
3
1.0
2
4.0-7.9
3.0
2
8.0-13.9
6.0
2
Gonsalves et al.
14.0-18.9
12.0
4
(2009) [38]
19.0-25.9
16.0
4
26.0-39.9
20.0
4
40.0-53.9
4
> 54.0 ≤ 3.0
32.0 40.0 2.0
4 1
> 3.0-5.0
3.0
1
> 5.0-7.0
5.0
1
> 7.0-12.0
10.0
2
> 12.0-20.0
15.0
3
> 20.0-30.0
30.0
3
> 30.0-45.0 > 45.0 < 5.0
40.0 60.0 1.0
6 1
≤ 5.0-10.0
2.0
1
> 10.0-20.0
6.0
2
> 20.0-40.0
10.0
2
> 40.0
20.0
2
Revell & Doern (2017) [1]
El Feghaly et al. (2018) [39]
4
Guidelines ≤ 1.0
2.0
N/A
ASM (2005) [35] & IDSA
1.1-2.0
4.0
N/A
(2013, updated
2.1-12.7
6.0
N/A
2018)*[27,28]
12.8-36.3
20.0
N/A
> 36.3
40.0-60.0
N/A
N/A: not available ASM: American Society for Microbiology; IDSA: Infectious Disease Society of America *blood volumes <10 mL should be aliquoted in one bottle (pediatric or aerobic) †
recommended total blood volume to be drawn and divided into stated number of bottles/isolator
‡
including aerobic, anaerobic or pediatric bottles
Table 2 Overview of studies with age-dependent approaches to blood volume for pediatric blood culture. Total Blood Study
Patient Age
Volume† [mL]
Sarkar et al. (2006) [42]
Connell et al. (2007) [40]
Bottles‡/Isolators
< 1 mo
≥ 1.0
1
< 1 mo
1.0
2
< 1 mo
> 0.5
1
Yaacobi et al. (2015) [41]
Number of
& Harewood et al.
≥ 1-36 mos
≥ 1.0
1
(2018) [43]
> 36 mos < 12 mos
≥ 4.0 1.0-3.0
1-2*
Revell & Doern
12-48 mos
3.0-4.0
1-2*
(2017) [1]
5-9 yrs
6.0-8.0
1-2*
≥ 10 yrs
20.0
2
1-2
mo: month; mos: months; yrs: years *for critically ill patients †
recommended total blood volume to be drawn and divided into stated number of bottles/isolators
‡
including aerobic, anaerobic or pediatric bottles
Table 3 Summary of recommendations for optimal blood volume based on self-defined age or weight classes.
Patient Weight [kg]
Total Blood Volume† [mL]
≤ 2.0
1.0-4.5
> 2.0-5.0
1.0-6.0
> 5.0-10.0
1.5-10.0
> 10.0-20.0
6.0-23.0
> 20.0-30.0
≥ 10.0
Patient Age
Total Blood Volume† [mL]
< 1 yr
> 0.5-3.0
≥ 1-3 yrs
1.0-4.0
> 3-10 yrs
3.0- 8.0
≥ 10 yrs
20.0
References
[1,16,27,28,35,36,38,39]
References
[1,40-43]
yr: year; yrs: years †
min. and max. recommended total blood volume to be drawn for pediatric blood culture
Figure 1
S1198-743X(19)30533-6
DOI:
https://doi.org/10.1016/j.cmi.2019.10.006
Reference:
CMI 1803
To appear in:
Clinical Microbiology and Infection
Received Date: 2 August 2019 Revised Date:
4 October 2019
Accepted Date: 5 October 2019
Please cite this article as: Huber S, Hetzer B, Crazzolara R, Orth-Höller D, The correct blood volume for pediatric blood cultures: a conundrum?, Clinical Microbiology and Infection, https://doi.org/10.1016/ j.cmi.2019.10.006. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.
1
Intended category:
2
Bloodstream Infection
3
Title:
4
The correct blood volume for pediatric blood cultures: a conundrum?
5 6
Authors
7
Silke Huber1, Benjamin Hetzer², Roman Crazzolara², Dorothea Orth-Höller1
8 9
Institutions
10
1
11
Austria
12
2
Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck,
Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria
13 14 15
Length of Abstract (i):
297 words
16
Length of Paper (ii):
2661 words
17 18
Running title: Blood volume for pediatric blood cultures
19 20 21
Corresponding author
22
Dorothea Orth-Höller, MD
23
Institute of Hygiene and Medical Microbiology
24
Medical University of Innsbruck
25
Schöpfstrasse 41
26
6020 Innsbruck, Austria
27
[email protected]
28
Abstract
29
Background
30
Bloodstream infections (BSI) are a major cause of morbidity and mortality in pediatric patients. For fast
31
and accurate diagnosis, blood culture (BC) is the gold standard. However, the procedure for blood
32
sampling in pediatric patients, particularly the optimal blood volume, is the subject of controversy
33
stemming from a lack of knowledge on the bacterial load and because of several obstacles such as low
34
intravascular volume with the risk of causing anemia.
35
Objectives
36
The aim of this narrative review was to summarize current knowledge on blood sampling in pediatric
37
patients for BC purposes in particular on blood volume, number and type of BC bottles needed for
38
reasonable future guidelines/recommendations.
39
Sources
40
A comprehensive literature search of PubMed including all English literature was performed in June 2019
41
using the search terms ‘blood culture’, ‘blood volume’, ‘bloodstream infection’, ‘diagnostic’, ‘pediatric’
42
and/or ‘sepsis’.
43
Content
44
The amount of inoculated blood determines the sensitivity, specificity and time to positivity of a BC, and
45
low-level bacteremia (≤ 10 cfu/mL) in pediatric patients is presumed to be more common than reported.
46
Current approaches for “adequate” blood volume for pediatric BC are mainly weight- or age-dependent.
47
Of these recommendations scheme devised by Gaur and colleagues seems most appropriate and calls for a
48
sample of 1-1.5 mL for children weighing less than 11 kg and 7.5 mL for a patient weight of 11-17 kg to
49
be drawn into one BC bottle. Inclusion of a more detailed grading in the weight range 4-14 kg as
50
published by Gonsalves and colleagues might be useful.
51
Implications
52
This review could be important for future guidelines on pediatric BC collection and thus could contribute
53
to improving patient management and lowering the economic and global health burden associated with
54
BSI. Furthermore, upcoming molecular-based approaches with low sample volumes might be an
55
interesting alternative.
56
Background
57
Bloodstream infections (BSI) are associated with substantial morbidity, mortality and a heavy economic
58
burden [1,2]. The SPROUT study, a global cross-sectional study including 26 countries demonstrated a
59
prevalence of 8.2% for severe sepsis in children (<18 years) in intensive care units not differing by
60
age [3]. In neonates the incidence of BSI is reported to be weight-dependent with the highest incidence
61
seen in the birthweight group under 499g [4]. Blood culture (BC) with a continuously monitored BC
62
system is the gold standard for diagnosis of BSI. Fast and accurate identification of causative pathogens is
63
known to be essential for etiological global surveillance, modification of empirical therapy and ultimately
64
for patient outcome [5].The prevalence of BSI-causing pathogens very much depends on the patient’s
65
age, underlying diseases and current therapy [6] as well as the socio-economic environment. The most
66
common pathogens identified in BSI in infants younger than 1 month are Escherichia coli, group B
67
Streptococcus, Listeria monocytogenes and Staphylococcus aureus [2,7,8]. Above that age mainly
68
Staphylococcus aureus, Streptococcus pneumoniae, Neisseria meningitidis and E. coli predominate [6]. In
69
immunosuppressed patients the spectrum is different and includes more pathogens [9]. The bacterial load
70
within pediatric BSI remains controversial as findings are divergent and report both high [10–15] and
71
low [1,16–21] concentrations for different pathogens. For BC collection in adult patients, consistent
72
recommendations for blood volume, number and type of BC bottles exist. In contrast, sampling from
73
pediatric patients is controversially discussed in literature, especially the blood volume as a major factor
74
for successful pathogen recovery [6,22]. The optimal blood volume might be limited due to a small
75
intravascular blood, as present in neonates [6,23,24]. Furthermore, repeated blood draws in critically ill
76
children increase the risk for anemia or other circulatory problems. Most importantly, blood collection in
77
small children is time-consuming, associated with major distress and requires trained personnel due to
78
technical challenges and in order to avoid contamination. In fact, the most frequently reported painful
79
events in hospitalized children were venipuncture for lab draws or intravenous lines [25]. As the latter is
80
recognized to have a negative impact on the child’s level of cooperation [26], strategies for minimizing
81
unnecessary exposure of children are considered good clinical practice. The aim of this narrative review
82
was to summarize the current knowledge on BC collection in pediatric patients including volume, number
83
and type of BC bottle.
84
Sources
85
A comprehensive literature search (from 1989 to 2019) of PubMed including all English literature was
86
performed in June 2019 using the search terms ‘blood culture’, ‘blood volume’, ‘bloodstream infection’,
87
‘diagnostic’, ‘pediatric’ and/or ‘sepsis’. Queries regarding diagnostic accuracy of blood volume were
88
answered by study selection of clinical trials and cross-sectional studies. Two independent reviewers used
89
the keywords “volume”, “blood” and “culture” and included only studies focusing on pediatric patients.
90
The majority of these studies were prospective. Exclusion criteria were editorials, letters and conference
91
abstracts/reports. Any disagreements between selected studies were resolved by discussion with the third
92
and fourth reviewers. Additionally, guidelines stating specific volumes for pediatric patients were
93
summarized.
94
Results
95
Blood Volume and Bacterial Load
96
Blood volume is stated to be the major factor influencing successful recovery of pathogens in BC [6,22].
97
In adults BC is standardized with a recommended blood volume of 8-10 mL per BC bottle [27,28],
98
usually two to three sets each containing one aerobic and one anaerobic BC bottle from a single
99
venipuncture are taken. This volume might not be available in pediatric patients, especially in younger
100
age groups. Thus, the optimal blood volume in this patient group remains a conundrum, although several
101
age- as well as weight-based recommendations exist (Table 1, Table 2). Definitely, the amount of
102
inoculated blood volume determines the sensitivity, specificity and time to positivity of a BC [29]. This is
103
clearly supported by studies claiming that each additional 1 mL of blood drawn increases the yield of
104
bacteria by up to 4.7% [12,30–32]. In the past, it was presumed that a low blood volume of 0.5-1.0 mL is
105
sufficient for detecting BSI [33] as bacteremia in pediatric patients was thought to be associated with a
106
high bacterial load [10–15]. However, the incidence of low level bacteremia in pediatric patients is
107
presumed to be more common than reported [1,16–21]. In fact, Kellogg and colleagues assessed 121
108
pediatric patients up to 15 years of age with confirmed bacteremia for their bacterial load. Interestingly,
109
60.3% of those patients had a low and even 23.1% an extremely low bacterial load, namely ≤ 10 colony-
110
forming units (cfu) per mL and ≤ 1 cfu per mL, respectively [16]. Considering these results, they
111
suggested that a total blood volume up to 4.5% (2-4.5 mL), 3% (≤ 6 mL) and 2.9% (23-60 mL, aliquoted
112
in several bottles) of the total blood volume for patients weighing ≤ 2 kg, ≤ 12.7 kg and ≥ 12.8 kg,
113
respectively, is imperative for successful recovery of causative pathogens (Table 1, Fig. 1) [16–18,34].
114
Subsequently, the American Society for Microbiology (ASM) and the Infectious Disease Society of
115
America (IDSA) published similar recommendations for the total blood volume needed for
116
BC [27,28,35]. However, the volumes recommended by Kellogg and colleagues, ASM and IDSA might
117
not be feasible in the routine clinical setting, especially in patients with low body weight (≤ 2 kg), in
118
particular premature and mature neonates classified as extremely preterm (23+0 gestational age),
119
moderate preterm (32+0 gestational age) or term (40+0 gestational age) (Fig. 1). In general, blood
120
sampling involving up to 4% of the total blood volume of a patient can be replaced by adequate blood
121
production [34]. It must be considered that in critically ill children blood production is altered, and
122
furthermore this patient group is often exposed to repeated blood draws for additional laboratory tests,
123
thus possibly exceeding the critical value of 4% blood loss. The Clinical and Laboratory Standards
124
Institute even recommends not exceeding 1% of a patient’s total blood volume for pediatric blood
125
culture [22]. This approach was also used by Gaur and colleagues, who suggested a detailed, weight-
126
dependent sampling of 1-1.5 mL for children weighing less than 11 kg and 7.5 mL for a patient weight of
127
11-17 kg [36]. This grading might be more realistic in the clinical setting, especially in the case of
128
neonates. Subsequently, this study was cited in MiQ: Qualitätsstandards in der mikrobiologisch-
129
infektiologischen Diagnostik (MiQ: Quality Standards in Microbiological-infectiological Diagnostics)
130
published by experts of the German Society of Hygiene and Microbiology [37]. Gonsalves and colleagues
131
proposed a similar scheme with more detailed grading in the weight range 4-14 kg and he could show a
132
significant higher detection rate with this weight-based volume compared to inadequate volume BC in the
133
true bacteremia group [38]. Several additional studies support the weight–based approach with a different
134
grading (Table 1, Fig. 1) [1,39]. There is evidence that these approaches are superior in pathogen
135
detection compared to inadequate BC volumes, however there are no data comparing different weight-
136
based schemes [38,39]. Most studies and guidelines recommend to sample ≥ 40 mL blood for patients
137
weighing ≥ 37 kg reflecting BC recommendations for adults. Gaur and colleagues suggest a volume of
138
16.5 mL only for this patient group which seems rather low.
139
Another approach to determining the optimal blood volume for BC that is often used in studies
140
investigating neonates and/or young children depends on the age of the patient (Table 2). The majority of
141
these studies suggested a blood volume of 0.5-1 mL for neonates [40–43]. The volume of 0.5 mL was
142
most probably chosen as this is the minimal volume validated by the companies offering BC
143
diagnostics [44,45]. For infants (≤ 12 months; equates to < 9.6 kg according to the 50th percentile of child
144
growth standard [46–48]) a blood volume of 1-3 mL, for toddlers (1-4 years; 8.9-16.3 kg) 3-4 mL, for
145
school children (5 to 9 years, 16.1-28.2 kg) 6-8 mL and for older children (> 10 years; > 31.2 kg) at least
146
20 mL was recommended [1]. Connell and colleagues demonstrated that the implementation of an age-
147
dependent approach resulted in an increase in positive BC from 2.6% to 5.1% as compared to an
148
insufficient blood volume [40].
149
A further approach is to adapt the media volume to the amount of collected blood. This is also supported
150
by the fact that BC bottles are validated for a particular broth-to-blood ratio [45]. For this reason, the two
151
leading manufacturers of BC bottles have developed smaller BC bottles for pediatric use. Solórzano-
152
Santos and colleagues investigated whether a 1:10 scale-down of a standardized BC system while
153
maintaining the same broth-to-blood ratio would affect the assay’s performance. Since sensitivity and
154
specificity for the micro-culture system were 95% and 99%, respectively, compared to a routine blood
155
culture, this system was recommended for diagnosis of pediatric sepsis in laboratories with manual
156
systems [49].
157
Considering the different approaches, the general consensus appears to support the basic recommendation
158
that blood draw for BC should be based on the patient’s age and/or weight, both of which are
159
interdependent variables. However, the wide range of the different recommendations for optimal blood
160
volume for the various age and weight groups is remarkable (Table 3).
161
Blood Volume and Contamination
162
Despite proper aseptic handling, the BC contamination rate is 1-3%, resulting in inconclusive diagnosis,
163
unnecessary antimicrobial treatment [1], increased mortality of patients with suspected sepsis and a
164
burden on the health system [39]. In addition to aseptic blood culture procedure and methodology,
165
inadequate blood volume inoculation into culture bottles is associated with a disproportionate risk of
166
culturing contaminants [43]. A recent study conducted at Batson Children’s Hospital in Jackson,
167
Mississippi (USA) demonstrated a decrease in contamination rates from 2.85% to 1.54% as a result of
168
introducing a standardized blood sampling method with optimized (weight-based) volume (Table 1) and
169
personnel training [39]. In general, the main aspects of such personnel training should include proper
170
handling of skin antisepsis, hand hygiene of the personnel taking blood, use of gloves and cleaning the
171
tops of the BC bottles with antiseptics [50].
172
Blood Volume, Number and Type of Blood Culture Bottles
173
Whenever possible, blood for BC should be sampled from a new peripheral venipuncture site. To increase
174
sensitivity and differentiate between contaminants and true pathogens in adult patients it is proposed that
175
two or more culture sets be used, drawn from different sampling sites. However, in neonates and infants it
176
is often not possible to obtain a blood volume sufficient for more than one or even only one BC bottle.
177
For pediatric use smaller BC bottles were introduced to offer a good proportion of broth and a small
178
blood volume to support the growth of most common pathogens and thus increase the likelihood of
179
recovering true pathogens in an acceptable time [44,45]. To our knowledge pediatric BC bottles are
180
currently available only for aerobic conditions. Validated blood volumes for a single pediatric BC bottle
181
from the two leading companies for BSI diagnosis range between 0.5-4 and 5 mL [44,45] with an
182
optimum of 1-3 mL [44]. Above this volume, both companies recommend the use of adult BC
183
bottles [44,45]. The number of bottles for pediatric BC is highly associated with the collected blood
184
volume [16,27,28,45]. Thus, it seems reasonable to aliquot the blood only when the collected blood
185
volume exceeds the optimal blood volume for one BC bottle. Our statement is supported by several
186
publications suggesting that a blood volume < 10 mL should be drawn in one aerobic bottle [27–
187
29,39,45]. Pathogens affecting children are mostly aerobic. Thus, collecting blood in a pediatric aerobic
188
bottle seems reasonable. The additional use of an anaerobic bottle might not be necessary as anaerobic
189
bacteremia is present in less than 1% of BSI in pediatric patients [51]. Still, some facultative anaerobic
190
pathogens may be isolated preferentially under anaerobic conditions [1,52]. Limited studies of the use of
191
pediatric BC bottles only vs. pediatric plus an adult anaerobic BC bottle have produced controversial
192
results. The decision whether to use an anaerobic BC bottle is more likely to be made by the treating
193
physician on a case-to-case basis. The main indications to do so are cellulitis, chorioamnionitis or
194
necrotizing enterocolitis.
195
Alternative Diagnostic Methods
196
Isolators:
197
An alternative to conventional BC might be a special system called isolator. With this system white and
198
red blood cells are lysed by adding blood to a chemical buffer. The specimen is then either directly spread
199
on an appropriate agar plate or first centrifuged to precipitate blood cell residues. A major advantage of
200
this system is the fact that only a small blood volume (1.5 mL) is needed to recover and quantify
201
pathogens [16]. Data on the accuracy of this approach are rare and even controversial, with either
202
comparable [53,54] or inferior [36] detection rates as compared to BC.
203
Molecular Diagnostics:
204
As time to result is an important factor in avoiding a bad outcome, molecular diagnostics, more
205
specifically PCR-based systems, for pathogen detection directly from blood samples were developed.
206
Beside the reduced time to detection, these systems also offer advantages in that they need only small
207
blood volumes (1 mL), detect intracellular or slow growing pathogens and avoid inconclusive results due
208
to antimicrobial treatment. On the other hand, pathogen detection from small blood samples harbors the
209
risk of a false-negative result due to low bacterial load [55,56]. Other disadvantages of PCR-based
210
systems include contamination-induced false-positive results, high costs, limited pathogen panel and lack
211
of resistance determination [57]. Nevertheless, Lucigano and colleagues investigated the performance of a
212
multiplex PCR-based system (LightCycler® SeptiFast Test) using over 1,600 samples from pediatric
213
patients. In comparison to BC, SeptiFast results showed a specificity of 93.5% and a sensitivity of 85%
214
with a 4.3% increased rate of positive results [58]. In conclusion, the molecular diagnosis of bacterial BSI
215
is a good alternative for some occasions, for example in neonates with previous maternal antibiotic
216
treatment, but is not yet a substitute for BC.
217
Conclusions
218
This review aims to summarize the current literature regarding the optimal volume of blood draw for BC
219
and provides recommendations for treating physicians in daily practice. It is important for critically ill
220
children with suspected BSI to obtain a rapid and reliable diagnosis. However, the management of BSI
221
patients calls for repeated and possibly painful blood draws for various laboratory tests. Such blood draws
222
often exceed physiological replacement and can cause a negative impact on the level of cooperation of
223
pediatric patients. For all these reasons it seems most reasonable and realistic to follow the scheme
224
devised by Gaur and colleagues, namely a weight-dependent sampling of 1 mL for children weighing less
225
than 2 kg, 1.5 mL for patients with a weight under 11 kg and 7.5 mL for a patient weight of 11-
226
17 kg [36]. As the recommended blood volume for the latter patient group is often difficult to obtain, it
227
might be valuable to include the scheme developed by Gonsalves and colleagues, providing a more
228
detailed grading for a patient weight of 4-14 kg [38]. For a patient weight of ≥ 37 kg a blood volume
229
≥ 40 mL should be considered. Beside this weight-based approach, we recommend to use the age-
230
dependent approach of Revell and Doern as an alternative [1]. Definitely, it is recommended to collect a
231
weight- or age-dependent blood volume and inoculate this sample into one pediatric or adult aerobic BC
232
bottle if the total volume sampled does not exceed 4-5 mL or 10 mL, respectively [27–29,39,45]. For
233
quality management reasons it is strongly recommended that monitoring be performed frequently and that
234
all personnel involved in drawing blood be trained regarding sampling volume and processing [39,40,43].
235
Besides BC, molecular-based diagnostics may be an interesting alternative in future with the advantage of
236
requiring a small blood volume. For BSI fast and accurate diagnosis is mandatory and this review could
237
be important for future guidelines on pediatric BC collection to improve patient management and lower
238
the economic and global health burden associated with BSI.
239
Transparency Declaration
240
The authors declare no conflict of interests.
241
Funding Statement
242
No funds were received from the current work.
243
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244
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391
Legend to Figure
392
Figure 1. Loss of intravascular blood volume associated with sample collection for blood culture. The y
393
axis shows the total blood volume loss (in %) when collecting blood according to different
394
guidelines [1,16,27,28,35,36,38]. The x axis demonstrates this scenario at different patient ages
395
(extremely preterm, 23+0 gestational weeks; moderate preterm, 32+0 gestational weeks; term, 40+0
396
gestational weeks; 3 months; 1 year; 2 years; 10 years). The total blood volume was calculated according
397
to Howie [24] (85ml/kg in neonates and 75ml/kg in children) and using the 50th female weight
398
percentile [46–48]. Blood loss of 4% due to blood sampling (indicated with a dashed line) can be replaced
399
by adequate blood production and is considered safe for the patient [34]. However, it should be
400
considered that critically ill children often have a lower intravascular blood volume than calculated here
401
for healthy children and are exposed to repeated blood draws for additional laboratory tests. The Clinical
402
and Laboratory Standards Institute recommends a blood draw for pediatric BC of less than 1% of a
403
patient’s total blood volume (indicated with a dotted line) [22]. It is noteworthy that adherence to the
404
recommendations of Kellogg and colleagues and the guidelines of the American Society for Microbiology
405
(ASM) and the Infectious Disease Society of America (IDSA) might result in excessive blood loss in
406
neonates.
407
Table 1 Overview of studies and guidelines with weight-dependent approaches for blood volume for pediatric blood culture. Total Blood Study/Guidelines
Weight [kg]
Volume† [mL]
Number of Bottles‡/Isolators
Studies
Kellogg et al. (2000) [16]
Gaur et al. (2003) [36]
≤ 1.0
2.0
2
1.1-2.0
4.5
2
2.1-12.7
6.0
2
12.8-36.3
23.0
4
> 36.3 1.5-2.1
60.0 1.0
4 1
2.2-11.1
1.5
1
11.2-17.1
7.5
3
17.2-37.2
11,5
3
> 37.3 < 3.9
16.5
3
1.0
2
4.0-7.9
3.0
2
8.0-13.9
6.0
2
Gonsalves et al.
14.0-18.9
12.0
4
(2009) [38]
19.0-25.9
16.0
4
26.0-39.9
20.0
4
40.0-53.9
4
> 54.0 ≤ 3.0
32.0 40.0 2.0
4 1
> 3.0-5.0
3.0
1
> 5.0-7.0
5.0
1
> 7.0-12.0
10.0
2
> 12.0-20.0
15.0
3
> 20.0-30.0
30.0
3
> 30.0-45.0 > 45.0 < 5.0
40.0 60.0 1.0
6 1
≤ 5.0-10.0
2.0
1
> 10.0-20.0
6.0
2
> 20.0-40.0
10.0
2
> 40.0
20.0
2
Revell & Doern (2017) [1]
El Feghaly et al. (2018) [39]
4
Guidelines ≤ 1.0
2.0
N/A
ASM (2005) [35] & IDSA
1.1-2.0
4.0
N/A
(2013, updated
2.1-12.7
6.0
N/A
2018)*[27,28]
12.8-36.3
20.0
N/A
> 36.3
40.0-60.0
N/A
N/A: not available ASM: American Society for Microbiology; IDSA: Infectious Disease Society of America *blood volumes <10 mL should be aliquoted in one bottle (pediatric or aerobic) †
recommended total blood volume to be drawn and divided into stated number of bottles/isolator
‡
including aerobic, anaerobic or pediatric bottles
Table 2 Overview of studies with age-dependent approaches to blood volume for pediatric blood culture. Total Blood Study
Patient Age
Volume† [mL]
Sarkar et al. (2006) [42]
Connell et al. (2007) [40]
Bottles‡/Isolators
< 1 mo
≥ 1.0
1
< 1 mo
1.0
2
< 1 mo
> 0.5
1
Yaacobi et al. (2015) [41]
Number of
& Harewood et al.
≥ 1-36 mos
≥ 1.0
1
(2018) [43]
> 36 mos < 12 mos
≥ 4.0 1.0-3.0
1-2*
Revell & Doern
12-48 mos
3.0-4.0
1-2*
(2017) [1]
5-9 yrs
6.0-8.0
1-2*
≥ 10 yrs
20.0
2
1-2
mo: month; mos: months; yrs: years *for critically ill patients †
recommended total blood volume to be drawn and divided into stated number of bottles/isolators
‡
including aerobic, anaerobic or pediatric bottles
Table 3 Summary of recommendations for optimal blood volume based on self-defined age or weight classes.
Patient Weight [kg]
Total Blood Volume† [mL]
≤ 2.0
1.0-4.5
> 2.0-5.0
1.0-6.0
> 5.0-10.0
1.5-10.0
> 10.0-20.0
6.0-23.0
> 20.0-30.0
≥ 10.0
Patient Age
Total Blood Volume† [mL]
< 1 yr
> 0.5-3.0
≥ 1-3 yrs
1.0-4.0
> 3-10 yrs
3.0- 8.0
≥ 10 yrs
20.0
References
[1,16,27,28,35,36,38,39]
References
[1,40-43]
yr: year; yrs: years †
min. and max. recommended total blood volume to be drawn for pediatric blood culture
Figure 1