Você está na página 1de 8

REVIEW 10.1111/1469-0691.

12180

Update on blood cultures: how to obtain, process, report, and interpret

T. J. Kirn and M. P. Weinstein


Departments of Medicine (Infectious Diseases) and Pathology & Laboratory Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA

Abstract

The detection and identification of microorganisms circulating in the bloodstream of patients is arguably one of the most important
functions of the clinical microbiology laboratory. Effective implementation of this function requires careful consideration of specimen
collection and processing, culture techniques, result reporting, and, perhaps most importantly, result interpretation by the physician. The
purpose of this review is to provide a synopsis of the current state of the art for each of these areas, with the intention of providing
adequate information to enable clinical laboratory personnel and physicians to critically evaluate and, if required, improve their current
blood culture practices.

Keywords: blood culture, clinical microbiology, interpretation, rapid methods, specimen collection
Article published online: 13 March 2013
Clin Microbiol Infect 2013; 19: 513–520

Corresponding author: M. P. Weinstein, Departments of Medicine


(Infectious Diseases) and Pathology & Laboratory Medicine, UMDNJ-
Robert Wood Johnson Medical School, 1 Robert Wood Johnson
Place, New Brunswick, NJ 08903, USA
E-mail: Weinstei@umdnj.edu

Introduction therapeutic intervention, whereas the number of BSIs appears


to be increasing, especially those occurring in populations that
were previously less affected (outpatients).
Bloodstream infections (BSIs) represent an important cause of
Because BSIs remain an important cause of morbidity and
human morbidity and mortality. The evaluation of patients
mortality, and prompt targeted therapeutic intervention may
suspected of having a BSI routinely includes blood cultures,
improve patient outcomes, there has been significant interest
which optimally yield an aetiological diagnosis and provide the
in improving the speed and accuracy of blood culture methods
opportunity to perform antimicrobial susceptibility testing to
in the clinical microbiology laboratory. Despite these efforts,
guide therapeutic intervention when necessary. The clinical
little has changed since the introduction of continuous-
significance of positive blood cultures has been extensively
monitoring blood culture systems in the 1990s, but incremen-
evaluated over the past several decades [1–6]. These studies
tal advances in more rapid identification and susceptibility
have served to define the most frequent aetiological agents
prediction have occurred, especially for some particularly
responsible for BSIs and the range of agents, and have
troublesome pathogens. Moreover, greater advances appear
improved our understanding of the risks and outcomes
to be on the horizon.
associated with such infections. As the baseline characteristics
of patients have changed with advances in medicine (e.g. more
Blood Culture Collection
immunocompromised hosts, more indwelling catheters and
other intravascular devices, and changes in therapy for human
immunodeficiency virus), the epidemiology of BSIs has also The utility of blood culture for detecting BSI is directly
evolved, with more infections occurring in patients with influenced by the collection of optimal specimens only from
intravascular devices and in outpatient settings [5]. Addition- patients with clinical findings compatible with BSI; routine
ally, there appears to be a trend towards improved outcomes ‘surveillance’ blood cultures are costly and of little clinical value
in patients with BSIs, perhaps as a consequence of earlier [7–9]. Clearly, venipuncture is the preferred method for blood

ª2013 The Authors


Clinical Microbiology and Infection ª2013 European Society of Clinical Microbiology and Infectious Diseases
514 Clinical Microbiology and Infection, Volume 19 Number 6, June 2013 CMI

culture collection. Arterial blood samples do not increase Once optimal blood culture specimens are collected
diagnostic yield, and blood specimens obtained from intravas- according to the principles outlined above, they should be
cular lines have demonstrated increased rates of contamina- sent to the laboratory as promptly as possible. These
tion in some studies [10]. The American College of Physicians specimens should never be refrigerated or frozen, and should
guidelines recommend that collecting blood for culture from be held at room temperature for no more than a few hours if
intravascular devices be avoided, and the CLSI recommends necessary. Although an extended delay between blood culture
that, if one must collect a blood culture from an intravenous collection and incubation in a continuous-monitoring blood
line, it should be paired with a culture that is obtained via culture instrument is not recommended, a significant diminu-
venipuncture to assist in the interpretation of positive results tion in pathogen recovery has only been experimentally
[11,12]. The timing of blood culture collection does not appear observed when blood culture bottles have been held for
to significantly affect the recovery of clinically relevant >24 h at 4°C or room temperature and for >12 h at 37°C
microorganisms, and most authorities therefore recommend [26]. Lengthy incubation of blood culture bottles prior to
collecting multiple sets simultaneously or over a short period entering them into a continuous-monitoring blood culture
of time, except when documentation of continuous bactera- instrument may delay or impede the detection of growth by
emia is required for patients with endovascular infection the instrument, and is discouraged.
[12,13]. Whenever possible, two to four sets of blood
specimens should be collected from independent venipuncture
Laboratory Techniques for Blood Culture
sites, and, for adult patients, each set should consist of 20–
40 mL of blood [12–15]. The volume of blood drawn from
infants and children is less well prescribed, but should be based In the vast majority of institutions, most blood culture
on the child’s age and not exceed 1% of the patient’s total specimens delivered to the laboratory are entered into an
blood volume [12,16]. It is clear that the total volume of blood incubation protocol on a continuously monitored blood
cultured from adult patients is directly proportional to the culture device. There are several manufacturers of such
yield of microorganisms recovered. This is a consequence of devices, and their performance characteristics are similar [27–
the fact that most adult patients with BSIs have very low 35]. These devices incubate the blood culture bottles for a
circulating concentrations of viable microorganisms. Inade- prescribed period of time (determined by the user) and signal
quate blood volume or the collection of a single blood culture audibly and/or visually if growth is detected.
set significantly reduces the sensitivity of the test, and also Each automated blood culture system has its own associ-
makes the interpretation of results far more difficult ated medium formulations that must be selected by the user.
[13,15,17,18]. Collection of multiple sets of blood cultures The blood culture bottles typically contain proprietary
from a single venipuncture or intravascular line should also be mixtures of culture medium, an anticoagulant, and, in many
avoided. For optimal recovery of diverse BSI aetiological cases, resins or charcoal mixtures to reduce the effects of
agents, each set of blood cultures should include paired antimicrobials and other toxic compounds. Generally, combi-
aerobic and anaerobic blood culture bottles, and the aerobic nations of medium formulations that are complementary to
bottle should be filled first [12,19,20]. each other are chosen to enhance the recovery of the most
Proper skin antisepsis prior to collection of blood cultures via diverse range of microorganisms. Medium combinations typ-
peripheral venipuncture is paramount, to reduce blood culture ically include aerobic and anaerobic formulations and, in select
contamination rates and facilitate result interpretation for the circumstances, a formulation containing reagents that are ideal
clinician. A variety of skin disinfectants have been clinically for recovering mycobacteria and/or yeasts may be inoculated
evaluated, and reports comparing their relative efficacy have as well. Controlled studies comparing the performance of
been published [21–25]. On the basis of these data, current media with and without the addition of antimicrobial binding
guidance documents conclude that tincture of iodine, chlorine or absorbing agents (resins and/or charcoal compounds) have
peroxide and chlorhexidine gluconate are superior to povidine- repeatedly demonstrated that the latter formulations are
iodine preparations, and that tincture of iodine and chlorhex- clearly superior for the recovery of microorganisms, especially
idine gluconate are probably equivalent for skin antisepsis prior staphylococci and yeasts [29,34–37].
to blood culture collection [12]. Although chlorhexidine Blood cultures entered into automated, continuous-moni-
gluconate is an adequate disinfectant for older infants, children, toring protocols should routinely be incubated for 5 days.
and adults, it should not be used on infants <2 months of age, Multiple studies have shown that this incubation time is
and an alternative is therefore required in centres where this adequate for the detection of the majority of pathogens,
disinfectant is otherwise routinely employed. including fastidious bacteria that belong to the Haemophilus,

ª2013 The Authors


Clinical Microbiology and Infection ª2013 European Society of Clinical Microbiology and Infectious Diseases, CMI, 19, 513–520
CMI Kirn and Weinstein Blood cultures review 515

Actinobacillus, Cardiobacterium, Eikinella and Kingella (HACEK) often of unclear clinical significance when they are isolated
group, and that incubation beyond 5 days increases the with these methods [51]. In cases where fungaemia caused by a
number of contaminants recovered [38–43]. Longer incuba- mould is suspected, alternative blood culture methods should
tion times may be required when dimorphic fungaemia or be employed, such as the lysis centrifugation method, in which
bacteraemia caused by Legionella, Brucella, Bartonella or Nocar- the lysed and pelleted blood specimen can be plated on
dia spp. is suspected. Blood cultures for Mycobacterium spp. medium that specifically supports the growth of moulds and
should be incubated for 4 weeks. dimorphic fungi. Some fungi require highly specialized medium
The detection of some microorganisms is enhanced by supplements, the most noteworthy example being the
employing blood culture techniques in addition to or in place requirement for lipid supplementation for Malasezzia furfur,
of standard instrumented blood culture systems. The most which is often achieved by overlaying fungal medium with olive
common example of this principle is the utilization of the oil.
Isolator blood culture system (Wampole Laboratories, Cran-
bury, NJ, USA) for the enhanced detection of dimorphic fungi Mycobacterial blood cultures
and Bartonella spp. [44–46]. This system is unique in that it is Mycobacterial BSIs occur in immunocompromised patients
non-broth-based. Instead, blood samples obtained by veni- (either as a consequence of iatrogenic immunosuppression, or
puncture are collected into a tube that contains a lysing associated with an immunosuppressive condition) and patients
solution. The tubes are then transported to the laboratory, with long-term vascular access devices. Investigation tailored
where they are centrifuged. The supernatant is discarded, and to the recovery of mycobacterial blood isolates should thus
the pellet is inoculated onto solid medium, the composition of generally be limited to patients with such characteristics.
which may be tailored to recover the organisms (bacteria, As mycobacteria are commonly located intracellularly,
fungi, and/or mycobacteria) that are most likely or highly approaches to growing them in vitro often include lysis of
suspected on the basis of clinical findings. Although there are leukocytes prior to incubation in a rich medium that contains
clear advantages to using this approach in select circumstances fatty acids. Mycobacteria may be optimally recovered, with
(suspicion of BSI caused by dimorphic fungi or Bartonella spp.), extended incubation of 4 weeks, with manual methods such as
it is not routinely employed, as it is quite labour-intensive, it lysis centrifugation or the use of commercial ‘lytic’ media in
poses a greater risk of laboratory-acquired infection to manual or instrumented systems. These blood culture formu-
technologists, and it is inferior to standard blood culture lations typically contain a proprietary mixture of fatty acids
methods for the detection of anaerobes, Haemophilus spp., and that support mycobacterial growth, along with antimicrobial
pneumococci [47–50]. agents. Limited comparisons between formulations suggest
some variability in the performance of lytic culture media, but
comprehensive comparative studies of all formulations have
Special Considerations for Select Microor-
not been performed [52–56].
ganisms
Fastidious microorganisms
Fungal blood cultures Fastidious microorganisms are rarely implicated in BSI in
Fungi represent an emerging group of organisms that are clinical practice, but when they are isolated from blood
responsible for BSI with increasing frequency. The growth cultures they often represent serious infection. In some cases,
requirements for fungi often differ from those for bacteria, the observation of signal-positive Gram stain-negative blood
most notably with regard to optimal growth temperature and culture results provides a clue that a fastidious microorganism
media. For example, most yeasts grow best at 37°C, whereas might be implicated as the BSI aetiological agent. In those
filamentous fungi often grow best at lower (27–30°C) cases, collaboration between the laboratory and clinician is
temperatures. Most routine manual and automated blood essential to ensure that appropriate steps are taken to increase
culture systems are able to support the growth of yeasts such the odds of isolation of such organisms. Some organisms may
as Candida spp. However, if suspicion is high for a BSI being be small or of unusual morphology, and not readily recognized
caused by yeast, and routine blood cultures are negative, then by the technologist. In other cases, the organism may not stain
it may be reasonable to consider a request for alternative test well with standard Gram stain protocols (e.g. Mycoplasma and
methods that are optimally designed to support the growth of Campylobacter). In those cases, alternative staining techniques
most yeasts. Moulds, and especially dimorphic fungi, often may be employed, including the use of acridine orange (to stain
grow poorly in typical instrumented blood culture systems. bacterial nucleic acids) or the use of carbol fuschin as an
Furthermore, the recovery of moulds such as Aspergillus spp. is alternative to safranin as a counterstain in the Gram stain

ª2013 The Authors


Clinical Microbiology and Infection ª2013 European Society of Clinical Microbiology and Infectious Diseases, CMI, 19, 513–520
516 Clinical Microbiology and Infection, Volume 19 Number 6, June 2013 CMI

protocol to enhance the staining of Campylobacter, Helicobacter, organism identification and organism-specific susceptibility
and Brucella. testing should only be performed on clinically important
Perhaps the most frequently encountered fastidious bacte- isolates, and not on organisms that probably represent
ria are the members of the HACEK group as the aetiological contaminants [57,58]. Isolates that are probably associated
agents for subacute bacterial endocarditis. As noted above, in with true BSI (as per the laboratory protocol) should be saved
the vast majority of cases, these organisms are isolated with in the laboratory (by serial subculture) for several days to
standard blood culture techniques without the need for special allow additional testing if required, and may be retained for
protocols or procedures. This is also generally true for Brucella longer periods of time (in a frozen archive) to allow
spp., Campylobacter spp., and Francisella spp., but is not true for investigation of recurrent BSIs in appropriate patients.
all fastidious bacteria.
Abiotrophia and Granulicatella are usually detected with
Interpretation of Positive Blood Cultures
automated blood culture instruments, but do not grow well
on standard, unsupplemented solid media, as they require
pyridoxal or cysteine for growth. This can be accomplished by The interpretation of positive blood culture results is often
co-cultivation with staphylococci, by the use of pyridoxal- straightforward, but sometimes presents a significant dilemma
impregnated disks placed on the surface of standard blood agar for physicians and clinical microbiologists. For the latter
plates, or by the use of specially supplemented or enriched circumstance, a variety of laboratory data must be evaluated in
media. the context of the clinical picture to arrive at an accurate
The yield of standard blood culture media for the cultivation interpretation. The pattern of positivity of blood cultures is
of Bartonella spp. is typically low. Special techniques, including often useful; when the majority of or all blood culture sets
lysis centrifugation methods and/or serological investigations, obtained by independent venipuncture are positive for the same
are thus indicated for the diagnosis of BSI caused by Bartonella microorganism, the likelihood that this represents true BSI is
spp. exceedingly high, regardless of the organism’s identity [2].
Legionella spp. require buffered charcoal yeast extract Likewise, the identities of organisms isolated from positive blood
(BCYE) for optimal growth. Recovery of Legionella can be cultures also have value. Staphylococcus aureus, Streptococcus
achieved by subculturing standard blood culture medium that pneumoniae, Enterobacteriaceae, Pseudomonas aeruginosa and
has been incubated according to the standard protocol for Candida albicans are almost always predictive of true BSI.
5 days into BCYE, or by utilizing BCYE in conjunction with Conversely, Corynebacterium spp. and Propionibacterium spp.
lysis centrifugation methods. A detailed description of all of the almost always represent contamination. The recovery of
special techniques required for the culture of other rarely viridans group streptococci, coagulase-negative staphylococci
encountered fastidious organisms (e.g. Helicobacter and Lepto- (CoNS) and enterococci is more difficult to interpret, as some
spira) is beyond the scope of this review, and has been studies have demonstrated that they represent true BSI in 38%,
provided elsewhere [12]. 15% and 78% of cases, respectively [1]. Notably, CoNS
represent one of the most commonly encountered blood
culture contaminants, but also constitute an important cause of
Isolation, Identification, and Susceptibility
BSI in the ever-expanding population of patients with implanted
Testing
devices and indwelling catheters. Interpretation for these cases
may be aided by identifying CoNS to the species level when more
Once blood cultures become positive for growth, either by than one set of blood cultures becomes positive. If the same
manual subculture techniques or signalling from automated species of CoNS is isolated from multiple blood culture sets, the
systems, a Gram stain is performed. A positive Gram stain odds that it represents true bacteraemia as opposed to
result should be regarded as a critical value, and immediately contamination increase [3]. Without this additional information,
phoned to the ordering clinician or another responsible using the number of positive blood culture sets that are
member of the healthcare team providing care to the patient. generically positive for CoNS is a less reliable predictor. Finally,
Subcultures are performed at this point, and these allow some have suggested that the number of blood culture bottles
identification and, if indicated, susceptibility testing to be (as opposed to the number of sets) has predictive value, in that
performed, typically over the next 24–48 h. the more that are positive for CoNS, the more likely it is that the
Laboratories should have a comprehensive protocol in patient has bacteraemia caused by CoNS. However, systematic
place to guide the appropriate work-up of organisms isolated evaluations of this approach have proven it to be unreliable
from blood cultures. To optimally utilize resources, complete [18,59].

ª2013 The Authors


Clinical Microbiology and Infection ª2013 European Society of Clinical Microbiology and Infectious Diseases, CMI, 19, 513–520
CMI Kirn and Weinstein Blood cultures review 517

on newer or novel technology. Molecular methods, including


Rapid Methods for Identification and
nucleic acid amplification assays (NAATs), DNA sequencing
Susceptibility Testing of Isolates from
approaches, DNA microarrays, and probe hybridization, have
Positive Blood Cultures
emerged as useful tools for microorganism identification, and,
in some cases, the prediction of antimicrobial susceptibility
Prompt detection, identification and susceptibility testing of for select antibiotics [62–66]. Novel phenotypic approaches
the aetiological agents responsible for BSIs is critical, as it have also been shown to reduce turn-around time for the
allows clinicians to make the most informed decisions about identification and limited susceptibility testing of select
possible therapeutic interventions. Blood cultures incubated in organisms (Kirn et al., IDSA Annual Meeting, 2011). Finally,
modern instrumented systems that are ultimately positive for matrix-assisted laser desorption ionization time-of-flight mass
most bacterial pathogens typically signal positive in a median spectrometry, which has already demonstrated widespread
time of 12–36 h, whereas the time to positivity from collection utility in the routine identification of microorganisms in the
to detection is longer for some fastidious bacteria, anaerobes, clinical microbiology laboratory, appears to be a very
and fungi [28,29]. Following detection, Gram stain rapidly promising approach to the rapid identification of organisms
provides some information to the clinician that may be useful directly from signal-positive blood culture broths [67]. The
for determining the significance of the positive result and/or major drawback of this approach, like most of the others, is
determining initial antimicrobial therapy. Standard microbio- the lack of rapid susceptibility information to accompany the
logical protocols that rely on biochemical identification of organism identity. It is not yet clear when or if this capability
microorganisms plus phenotypic antimicrobial susceptibility will be possible with matrix-assisted laser desorption ioniza-
testing follow, and may take an additional 48–72 h, assuming tion time-of-flight mass spectrometry or other rapid methods,
that the results obtained are easily interpreted. It may take and the actual clinical utility of microorganism identification in
days longer to generate final results for organisms that are the absence of susceptibility information is narrow and
difficult to identify biochemically or grow slowly in vitro. Given unproven.
the usual delay of 3–5 days from the collection of blood
cultures to the time at which final identification and suscep-
tibility results are obtained, there has been keen interest in
Rapid Methods for Detection of
reducing this interval by employing a variety of rapid methods.
Microorganisms Directly in Blood Specimens
In some cases, the time to delivery of results may be reduced
by employing traditional microbiological protocols earlier in Although technological improvements have led to reductions
the work-up. For example, the coagulase test, which is in the time required for identification and (in limited cases)
traditionally used to distinguish CoNS isolates from coagu- susceptibility testing of isolates from signal-positive blood
lase-positive isolates, may be performed directly on signal- cultures, a further improvement would obviously be the ability
positive blood culture broths that show Gram-positive cocci in to rapidly and directly detect and identify microorganisms in
clusters on Gram staining [60]. This approach allows rapid blood samples from patients with a suspected BSI. Currently
distinction between CoNS and coagulase-positive staphylo- available solutions involve the use of NAATs that are designed
cocci (which are mostly S. aureus), and may influence the to detect specific microorganisms in blood samples [68].
ability of clinicians to interpret the clinical significance of a Controlled trials evaluating the performance of such solutions
positive blood culture result and their ability to begin as compared with standard blood cultures have demonstrated
appropriate antimicrobial therapy. Obviously, this is not a reasonably good performance, with the obvious limitation that
complete solution, as it does not definitively identify the NAATs will only detect a subset of possible BSI pathogens,
organism and nor does it provide susceptibility information. To and provide no susceptibility information [68,69]. As conven-
augment such an approach, some laboratories may couple tional phenotypic susceptibility testing requires isolated
direct coagulase testing with the use of chromogenic agar organisms, if the direct NAAT is positive and the correspond-
medium, which allows identification of methicillin-resistant ing culture is negative, susceptibility information may never be
S. aureus isolates within 18–24 h [61]. Clearly, this solution available. Thus, at the present time, such an approach may
represents an improvement over traditional methods, but serve only as an adjunct to standard of care protocols. As is
applies only to one specific organism and gives susceptibility the case for rapid methods for blood culture isolate identi-
results for only one drug. fication, the actual clinical impact of rapid methods for direct
More robust approaches to improving the turn-around pathogen detection in blood specimens has not been exten-
time for the laboratory diagnosis of BSIs have focused largely sively studied.

ª2013 The Authors


Clinical Microbiology and Infection ª2013 European Society of Clinical Microbiology and Infectious Diseases, CMI, 19, 513–520
518 Clinical Microbiology and Infection, Volume 19 Number 6, June 2013 CMI

Conclusions 10. Bryant JK, Strand CL. Reliability of blood cultures collected from
intravascular catheter versus venipuncture. Am J Clin Pathol 1987; 88:
113–116.
11. Aronson MD, Bor DH. Blood cultures. Ann Intern Med 1987; 106: 246–
Technological advances have resulted in the ability to more
253.
rapidly identify and, in some cases, predict the susceptibility of 12. Wilson ML, Clinical and Laboratory Standards Institute. Principles and
the aetiological agents of BSIs to a limited extent. Although procedures for blood cultures: Approved guideline. Wayne, PA: Clinical and
Laboratory Standards Institute, 2007.
these methods hold great promise for the future, conventional
13. Cockerill FR 3rd, Wilson JW, Vetter EA et al. Optimal testing
blood culture methods remain the dominant approach to parameters for blood cultures. Clin Infect Dis 2004; 38: 1724–1730.
diagnosing most patients with BSIs. Therefore, the traditional 14. Washington JA. Blood cultures: Principles and techniques. Mayo Clin
principles of patient selection, adequate and careful specimen Proc 1975; 50: 91–98.
15. Lee A, Mirrett S, Reller LB, Weinstein MP. Detection of bloodstream
collection, appropriate cultivation and accurate result inter- infections in adults: How many blood cultures are needed? J Clin
pretation remain critical to the delivery of the most effective Microbiol 2007; 45: 3546–3548.
care for our patients with suspected BSIs. 16. Gaur AH, Giannini MA, Flynn PM et al. Optimizing blood culture
practices in pediatric immunocompromised patients: Evaluation of
media types and blood culture volume. Pediatr Infect Dis J 2003; 22:
545–552.
Transparency Declaration 17. Li J, Plorde JJ, Carlson LG. Effects of volume and periodicity on blood
cultures. J Clin Microbiol 1994; 32: 2829–2831.
18. Mirrett S, Weinstein MP, Reimer LG, Wilson ML, Reller LB. Relevance
Neither of the authors of the present manuscript have a of the number of positive bottles in determining clinical significance of
commercial or other association that might pose a conflict of coagulase-negative staphylococci in blood cultures. J Clin Microbiol 2001;
interest (e.g. pharmaceutical stock ownership or consultancy). 39: 3279–3281.
19. Bartlett JG, Dick J. The controversy regarding routine anaerobic blood
cultures. Am J Med 2000; 108: 505–506.
20. Patel R, Vetter EA, Harmsen WS, Schleck CD, Fadel HJ, Cockerill FR
References 3rd. Optimized pathogen detection with 30- compared to 20-milliliter
blood culture draws. J Clin Microbiol 2011; 49: 4047–4051.
21. Strand CL, Wajsbort RR, Sturmann K. Effect of iodophor vs iodine
1. Weinstein MP, Towns ML, Quartey SM et al. The clinical significance of tincture skin preparation on blood culture contamination rate. JAMA
positive blood cultures in the 1990s: A prospective comprehensive 1993; 269: 1004–1006.
evaluation of the microbiology, epidemiology, and outcome of bacter- 22. Mimoz O, Karim A, Mercat A et al. Chlorhexidine compared with
emia and fungemia in adults. Clin Infect Dis 1997; 24: 584–602. povidone-iodine as skin preparation before blood culture. A random-
2. Weinstein MP, Murphy JR, Reller LB, Lichtenstein KA. The clinical ized, controlled trial. Ann Intern Med 1999; 131: 834–837.
significance of positive blood cultures: A comprehensive analysis of 500 23. Little JR, Murray PR, Traynor PS, Spitznagel E. A randomized trial of
episodes of bacteremia and fungemia in adults. Ii. Clinical observations, povidone-iodine compared with iodine tincture for venipuncture site
with special reference to factors influencing prognosis. Rev Infect Dis disinfection: Effects on rates of blood culture contamination. Am J Med
1983; 5: 54–70. 1999; 107: 119–125.
3. Weinstein MP, Mirrett S, Van Pelt L et al. Clinical importance of 24. King TC, Price PB. An evaluation of iodophors as skin antiseptics. Surg
identifying coagulase-negative staphylococci isolated from blood cul- Gynecol Obstet 1963; 116: 361–365.
tures: Evaluation of microscan rapid and dried overnight gram-positive 25. Barenfanger J, Drake C, Lawhorn J, Verhulst SJ. Comparison of
panels versus a conventional reference method. J Clin Microbiol 1998; chlorhexidine and tincture of iodine for skin antisepsis in preparation
36: 2089–2092. for blood sample collection. J Clin Microbiol 2004; 42: 2216–2217.
4. Weinstein MP. Clinical importance of blood cultures. Clin Lab Med 26. Sautter RL, Bills AR, Lang DL, Ruschell G, Heiter BJ, Bourbeau PP.
1994; 14: 9–16. Effects of delayed-entry conditions on the recovery and detection of
5. Pien BC, Sundaram P, Raoof N et al. The clinical and prognostic microorganisms from bact/alert and bactec blood culture bottles. J Clin
importance of positive blood cultures in adults. Am J Med 2010; 123: Microbiol 2006; 44: 1245–1249.
819–828. 27. Magadia RR, Weinstein MP. Laboratory diagnosis of bacteremia and
6. McDonald LC, Fune J, Gaido LB et al. Clinical importance of increased fungemia. Infect Dis Clin North Am 2001; 15: 1009–1024.
sensitivity of bact/alert fan aerobic and anaerobic blood culture bottles. 28. Mirrett S, Reller LB, Petti CA et al. Controlled clinical comparison of
J Clin Microbiol 1996; 34: 2180–2184. bact/alert standard aerobic medium with bactec standard aerobic
7. Nielsen J, Kolmos HJ, Rosdahl VT. Poor value of surveillance cultures medium for culturing blood. J Clin Microbiol 2003; 41: 2391–2394.
for prediction of septicaemia caused by coagulase-negative staphylo- 29. Wilson ML, Mirrett S, Meredith FT, Weinstein MP, Scotto V, Reller LB.
cocci in patients undergoing haemodialysis with central venous Controlled clinical comparison of BACTEC Plus Anaerobic/F to
catheters. Scand J Infect Dis 1998; 30: 569–572. standard Anaerobic/F as the anaerobic companion bottle to plus
8. Levin PD, Hersch M, Rudensky B, Yinnon AM. Routine surveillance Aerobic/F medium for culturing blood from adults. J Clin Microbiol 2001;
blood cultures: Their place in the management of critically ill patients. J 39: 983–989.
Infect 1997; 35: 125–128. 30. McDonald LC, Weinstein MP, Fune J, Mirrett S, Reimer LG, Reller LB.
9. Czirok E, Prinz GY, Denes R, Remenyi P, Herendi A. Value of Controlled comparison of BacT/Alert FAN aerobic medium and
surveillance cultures in a bone marrow transplantation unit. J Med BACTEC fungal blood culture medium for detection of fungemia. J Clin
Microbiol 1997; 46: 785–791. Microbiol 2001; 39: 622–624.

ª2013 The Authors


Clinical Microbiology and Infection ª2013 European Society of Clinical Microbiology and Infectious Diseases, CMI, 19, 513–520
CMI Kirn and Weinstein Blood cultures review 519

31. Wilson ML, Mirrett S, McDonald LC, Weinstein MP, Fune J, Reller LB. Isolator lysis-centrifugation blood culture tube. J Clin Microbiol 1983; 17:
Controlled clinical comparison of Biomerieux Vital and BACTEC NR- 864–869.
660 blood culture systems for detection of bacteremia and fungemia in 48. Kiehn TE, Wong B, Edwards FF, Armstrong D. Comparative recovery
adults. J Clin Microbiol 1999; 37: 1709–1713. of bacteria and yeasts from lysis-centrifugation and a conventional
32. Zaidi AK, Mirrett S, McDonald JC et al. Controlled comparison of blood culture system. J Clin Microbiol 1983; 18: 300–304.
Biomerieux Vital and BACTEC NR-660 systems for detection of 49. Henry NK, Grewell CM, Van Grevenhof PE, Ilstrup DM, Washington
bacteremia and fungemia in pediatric patients. J Clin Microbiol 1997; 35: JA 2nd. Comparison of lysis-centrifugation with a biphasic blood
2007–2012. culture medium for the recovery of aerobic and facultatively anaerobic
33. Jorgensen JH, Mirrett S, McDonald LC et al. Controlled clinical bacteria. J Clin Microbiol 1984; 20: 413–416.
laboratory comparison of BACTEC Plus Aerobic/F resin medium with 50. Washington JA 2nd, Ilstrup DM. Blood cultures: Issues and contro-
BacT/Alert aerobic FAN medium for detection of bacteremia and versies. Rev Infect Dis 1986; 8: 792–802.
fungemia. J Clin Microbiol 1997; 35: 53–58. 51. Simoneau E, Kelly M, Labbe AC, Roy J, Laverdiere M. What is the
34. Wilson ML, Weinstein MP, Mirrett S et al. Controlled evaluation of clinical significance of positive blood cultures with Aspergillus sp in
BacT/Alert standard anaerobic and FAN anaerobic blood culture hematopoietic stem cell transplant recipients? A 23 year experience.
bottles for the detection of bacteremia and fungemia. J Clin Microbiol Bone Marrow Transplant 2005; 35: 303–306.
1995; 33: 2265–2270. 52. Waite RT, Woods GL. Evaluation of BACTEC Myco/F Lytic medium
35. Weinstein MP, Mirrett S, Reimer LG et al. Controlled evaluation of for recovery of mycobacteria and fungi from blood. J Clin Microbiol
BacT/Alert standard aerobic and FAN aerobic blood culture bottles for 1998; 36: 1176–1179.
detection of bacteremia and fungemia. J Clin Microbiol 1995; 33: 978– 53. Fuller DD, Davis TE Jr, Denys GA, York MK. Evaluation of BACTEC
981. Myco/F Lytic medium for recovery of mycobacteria, fungi, and bacteria
36. Pohlman JK, Kirkley BA, Easley KA, Basille BA, Washington JA. from blood. J Clin Microbiol 2001; 39: 2933–2936.
Controlled clinical evaluation of BACTEC Plus Aerobic/F and BacT/ 54. Tortoli E, Cichero P, Chirillo MG et al. Multicenter comparison of ESP
Alert aerobic FAN bottles for detection of bloodstream infections. J culture system II with BACTEC 460TB and with Lowenstein-Jensen
Clin Microbiol 1995; 33: 2856–2858. medium for recovery of Mycobacteria from different clinical specimens,
37. Flayhart D, Borek AP, Wakefield T, Dick J, Carroll KC. Comparison of including blood. J Clin Microbiol 1998; 36: 1378–1381.
BACTEC Plus blood culture media to BacT/Alert FA blood culture 55. Archibald LK, McDonald LC, Addison RM et al. Comparison of
media for detection of bacterial pathogens in samples containing BACTEC Myco/F Lytic and Wampole Isolator 10 (lysis-centrifugation)
therapeutic levels of antibiotics. J Clin Microbiol 2007; 45: 816–821. systems for detection of bacteremia, mycobacteremia, and fungemia in
38. Petti CA, Bhally HS, Weinstein MP et al. Utility of extended blood a developing country. J Clin Microbiol 2000; 38: 2994–2997.
culture incubation for isolation of Haemophilus, Actinobacillus, Cardio- 56. Crump JA, Tanner DC, Mirrett S, McKnight CM, Reller LB. Controlled
bacterium, Eikenella, and Kingella organisms: A retrospective multicenter comparison of BACTEC 13A, Myco/F Lytic, BacT/Alert MB, and
evaluation. J Clin Microbiol 2006; 44: 257–259. Isolator 10 systems for detection of mycobacteremia. J Clin Microbiol
39. Evans MR, Truant AL, Kostman J, Locke L. The detection of positive 2003; 41: 1987–1990.
blood cultures by the BACTEC NR660. The clinical importance of 57. Richter SS, Beekmann SE, Croco JL et al. Minimizing the workup of
four-day versus seven-day testing. Diagn Microbiol Infect Dis 1991; 14: blood culture contaminants: Implementation and evaluation of a
107–110. laboratory-based algorithm. J Clin Microbiol 2002; 40: 2437–2444.
40. Masterson KC, McGowan JE Jr. Detection of positive blood cultures by 58. Weinstein MP. Blood culture contamination: Persisting problems and
the BACTEC nNR660. The clinical importance of five versus seven partial progress. J Clin Microbiol 2003; 41: 2275–2278.
days of testing. Am J Clin Pathol 1988; 90: 91–94. 59. Peacock SJ, Bowler IC, Crook DW. Positive predictive value of blood
41. Hardy DJ, Hulbert BB, Migneault PC. Time to detection of positive cultures growing coagulase-negative Staphylococci. Lancet 1995; 346:
BacT/Alert blood cultures and lack of need for routine subculture of 5- 191–192.
to 7-day negative cultures. J Clin Microbiol 1992; 30: 2743–2745. 60. Qian Q, Eichelberger K, Kirby JE. Rapid identification of Staphylococcus
42. Wilson ML, Mirrett S, Reller LB, Weinstein MP, Reimer LG. Recovery aureus in blood cultures by use of the direct tube coagulase test. J Clin
of clinically important microorganisms from the BacT/Alert blood Microbiol 2007; 45: 2267–2269.
culture system does not require testing for seven days. Diagn Microbiol 61. Pape J, Wadlin J, Nachamkin I. Use of BBL Chromagar MRSA medium
Infect Dis 1993; 16: 31–34. for identification of methicillin-resistant Staphylococcus aureus directly
43. Baron EJ, Scott JD, Tompkins LS. Prolonged incubation and extensive from blood cultures. J Clin Microbiol 2006; 44: 2575–2576.
subculturing do not increase recovery of clinically significant microor- 62. Wolk DM, Picton E, Johnson D et al. Multicenter evaluation of the
ganisms from standard automated blood cultures. Clin Infect Dis 2005; Cepheid XPERT Methicillin-Resistant Staphylococcus aureus (MRSA)
41: 1677–1680. test as a rapid screening method for detection of MRSA in nares. J Clin
44. Wilson ML, Davis TE, Mirrett S et al. Controlled comparison of the Microbiol 2009; 47: 758–764.
BACTEC high-blood-volume fungal medium, BACTEC Plus 26 aerobic 63. Tissari P, Zumla A, Tarkka E et al. Accurate and rapid identification of
blood culture bottle, and 10-milliliter Isolator blood culture system for bacterial species from positive blood cultures with a DNA-based
detection of fungemia and bacteremia. J Clin Microbiol 1993; 31: 865– microarray platform: An observational study. Lancet 2010; 375: 224–
871. 230.
45. Lyon R, Woods G. Comparison of the BacT/Alert and Isolator blood 64. Shepard JR, Addison RM, Alexander BD et al. Multicenter evaluation of
culture systems for recovery of fungi. Am J Clin Pathol 1995; 103: 660– the Candida albicans/Candida glabrata peptide nucleic acid fluorescent in
662. situ hybridization method for simultaneous dual-color identification of
46. Brenner SA, Rooney JA, Manzewitsch P, Regnery RL. Isolation of C. albicans and C. glabrata directly from blood culture bottles. J Clin
Bartonella (Rochalimaea) henselae: Effects of methods of blood collection Microbiol 2008; 46: 50–55.
and handling. J Clin Microbiol 1997; 35: 544–547. 65. Jordan JA, Jones-Laughner J, Durso MB. Utility of pyrosequencing in
47. Henry NK, McLimans CA, Wright AJ, Thompson RL, Wilson WR, identifying bacteria directly from positive blood culture bottles. J Clin
Washington JA 2nd. Microbiological and clinical evaluation of the Microbiol 2009; 47: 368–372.

ª2013 The Authors


Clinical Microbiology and Infection ª2013 European Society of Clinical Microbiology and Infectious Diseases, CMI, 19, 513–520
520 Clinical Microbiology and Infection, Volume 19 Number 6, June 2013 CMI

66. Aittakorpi A, Kuusela P, Koukila-Kahkola P et al. Accurate and rapid performance, cost, and turnaround time. J Clin Microbiol 2012; 50:
identification of Candida spp. Frequently associated with fungemia by 3324–3328.
using PCR and the microarray-based Prove-It sepsis assay. J Clin 68. Pasqualini L, Mencacci A, Leli C et al. Diagnostic performance of a
Microbiol 2012; 50: 3635–3640. multiple real-time PCR assay in patients with suspected sepsis hospi-
67. Lagace-Wiens PR, Adam HJ, Karlowsky JA et al. Identification of talized in an internal medicine ward. J Clin Microbiol 2012; 50: 1285–1288.
blood culture isolates directly from positive blood cultures by use of 69. Mencacci A, Leli C, Montagna P et al. Diagnosis of infective endocar-
matrix-assisted laser desorption ionization-time of flight mass ditis: Comparison of the Lightcycler Septifast real-time PCR with blood
spectrometry and a commercial extraction system: Analysis of culture. J Med Microbiol 2012; 61: 881–883.

ª2013 The Authors


Clinical Microbiology and Infection ª2013 European Society of Clinical Microbiology and Infectious Diseases, CMI, 19, 513–520