BioMed Research International
Volume 2018 (2018), Article ID 7013470, 6 pages
https://doi.org/10.1155/2018/7013470

Research Article

Comparison of the Fully Automated FilmArray BCID Assay to a 4-Hour Culture Test Coupled to Mass Spectrometry for Day 0 Identification of Microorganisms in Positive Blood Cultures

Paul O. Verhoeven,1,2 Cyrille H. Haddar,1,2 Josselin Rigaill,1,2 Nathalie Fonsale,² Anne Carricajo,1,2 Florence Grattard,1,2 and Bruno Pozzetto1,2

¹GIMAP EA 3064 (Groupe Immunité des Muqueuses et Agents Pathogènes), University of Lyon, Faculty of Medicine of Saint-Etienne, Saint-Etienne, France
²Laboratory of Infectious Agents and Hygiene, University Hospital of Saint-Etienne, Saint-Etienne, France

Correspondence should be addressed to Bruno Pozzetto; bruno.pozzetto@univ-st-etienne.fr

Received 9 September 2018; Accepted 8 November 2018; Published 21 November 2018

Academic Editor: Frederick D. Quinn

Copyright © 2018 Paul O. Verhoeven et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

Rapid bacterial identification of positive blood culture is important for adapting the antimicrobial therapy in patients with blood stream infection. The aim of this study was to evaluate the performance of the multiplex FilmArray Blood Culture Identification (BCID) assay by comparison to an in-house protocol based on MALDI-TOF MS identification of microcolonies after a 4-hour culture, for identifying on the same day the microorganisms present in positive blood culture bottles. One hundred and fifty-three positive bottles from 123 patients were tested prospectively by the 3 techniques of bacterial identification: 11 bottles yielding negative results by the 3 tests were considered false positive (7.2%). The reference MALDI-TOF MS technique identified 134 monomicrobial (87.6%) and 8 double infections (5.2%), which resulted in a total of 150 microorganisms. Globally, 137 (91.3%) of these 150 pathogens were correctly identified by the fully automated multiplex FilmArray BCID system at the species or genus level on day of growth detection, versus 117 (78.8%) by MALDI-TOF MS identification on nascent microcolonies after a 4-hour culture (P < 0.01). By combining the two approaches, 140 (93.5%) of the positive bottles were identified successfully at day 0. These results confirm the excellent sensitivity of the FilmArray BCID assay, notably in case of multimicrobial infection. Due to the limited number of targets included into the test, it must be coupled to another identification strategy, as that presented in this study relying on MALDI-TOF MS identification of microcolonies obtained after a very short culture period.

1. Introduction

Rapid bacterial identification of positive blood culture is important for adapting the antimicrobial therapy in patients with blood stream infection [1]. Matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has considerably shortened the time for identifying bacteria recovered from positive blood cultures [2]. In order to perform the identification of pathogens on the same day after detection of growth, different strategies have been proposed relying on lysis/filtration method coupled to MALDI-TOF MS [3–8], on rapid identification by MALDI-TOF MS of nascent colonies obtained after plating blood cultures for a short-incubation period [9–11], or on direct identification of pathogens present in blood cultures using fully automated PCR assays [12–21].

The aim of this study was to evaluate the performance of the multiplex FilmArray Blood Culture Identification (BCID) assay by comparison to an in-house protocol based on the MALDI-TOF MS identification after a 4-hour culture (termed “fast MALDI-TOF MS”) [9] for identifying on the same day the microorganisms present in positive blood culture bottles.

2. Material and Methods

2.1. Design of the Study

Blood cultures detected positive during the laboratory operating hours by the BD BACTEC 9240 system (Plus Aerobic/F and Plus Anaerobic/F bottles) (Becton Dickinson, Meylan, France) in patients hospitalized at the University Hospital of Saint-Etienne on a period of 10 months were included into the study with the limitation of a single aerobic or anaerobic vial per puncture site, per patient, and per day to increase the range of microorganisms responsible for blood stream infection.

2.2. Techniques

For the reference technique, medium from positive bottles was gram-stained and inoculated onto agar plates with incubation under aerobic and anaerobic atmosphere until a growth was observed (average time of 21 hours). Resulting colonies were identified by MALDI-TOF MS (Microflex LT, Bruker Daltonik GmbH, Bremen, Germany) using MALDI Biotyper v3.0 software. MALDI Biotyper scores greater than or equal to 1.7 and 1.9 were used for identification at genus and species levels, respectively, according to the thresholds previously described [22].

For the fast MALDI-TOF MS assay, microcolonies recovered from agar plates after 4 hours of incubation under appropriate conditions (Figure 1) were recovered and submitted to MALDI-TOF MS analysis. MALDI Biotyper scores greater than or equal to 1.5 were used for bacterial identification; this threshold was deduced from a previous study that we performed to validate the use of MALDI-TOF MS for bacterial identification from positive blood cultures after short-time culture [9].

Figure 1: Pictures of microcolonies of Staphylococcus aureus (upper panel) and Escherichia coli (lower panel) on blood agar after four hours of incubation at 37°C under 5% of CO₂.

The FilmArray BCID assay (BioFire Diagnostics, Salt Lake City, UT, USA, and bioMérieux, Marcy l’Etoile, France) was performed following manufacturer’s recommendations. Briefly, a 200 µl-volume of positive blood culture bottle was added to the red buffer and vortexed shortly. Then, blue and red buffers were transferred into the cartridge using the provided syringes. Extraction, amplification, and reading steps were fully automated into the Biofire instrument. Results that were analyzed by the software were available within 1 hour of time through a report indicating the detected microorganism(s).

2.3. Statistical Analyses

Descriptive variables were reported with their 95% confidence interval (CI). The Chi-square test was used for the comparison of qualitative variables; the two-tailed Fisher exact test was preferred in case of small effectives. P values under 5% were considered to be statistically significant.

3. Results

One hundred and fifty-three (153) positive blood culture bottles from 123 patients were tested prospectively by the 3 techniques of bacterial identification. Eleven bottles yielded negative results by the 3 tests and were considered false positive (7.2%). The reference MALDI-TOF MS technique identified 134 monomicrobial (87.6%) and 8 double infections (5.2%), which resulted in the identification of a total of 150 microorganisms listed in Table 1.

Table 1: Number of pathogens detected in the 153 blood specimen bottles by the three techniques that were compared in this study. The MALDI-TOF MS technique was taken as the gold standard.

Reference technique (MALDI-TOF MS)
MALDI-TOF
MS at day 0
(% according to reference)
FilmArray
BCID assay (% according to reference)
P value¹

All pathogens
150
117 (78.0)
137 (91.3)
< 0.01

Gram positive bacteria detected by the FilmArray BCID panel
85
70 (82.4)
82 (96.5)
< 0.01

    (i) Staphylococcus aureus
23
22 (95.7)
22 (95.7)²

     (ii) Coagulase negative staphylococci³
42
36 (85.7)
41 (97.6)⁴

     (iii) Streptococcus pneumoniae
3
2 (66.7)
3 (100)

     (iv) Streptococcus agalactiae
0
0
0

     (v) Streptococcus pyogenes
0
0
0

     (vi) Streptococcus spp.⁵
5
4 (80.0)
4 (80.0)

     (vii) Enterococcus spp.⁶
11
5 (45.5)
11 (100)

     (viii) Listeria monocytogenes
1
1 (100)
1 (100)

Gram negative bacteria detected by the FilmArray BCID panel
52
45 (86.5)
52 (100)
<0.05

     (i) Acinetobacter baumannii
0
0
0

     (ii) Haemophilus influenzae
1
0
1 (100)

     (iii) Neisseria meningitidis
0
0
0

     (iv) Pseudomonas aeruginosa
0
0
0

     (v) Enterobacteriaceae
51
45 (88.2)
51 (100)

          (a) Enterobacter cloacae complex
3
3 (100)
3 (100)

          (b) Escherichia coli
34
31 (91.2)
34 (100)

          (c) Klebsiella oxytoca
2
0
2 (100)

          (d) Klebsiella pneumoniae
9
8 (88.9)
9 (100)

          (e) Proteus spp.
1
1 (100)
1 (100)

          (f) Serratia marcescens
2
2 (100)
2 (100)

Yeasts detected by the FilmArray BCID panel
3
0
3 (100)
NS

     (i) Candida albicans
2
0
2 (100)

     (ii) Candida glabrata
0
0
0

     (iii) Candida krusei
1
0
1 (100)

     (iv) Candida parapsilosis
0
0
0

     (v) Candida tropicalis
0
0
0

Microorganisms absent from the FilmArray BCID panel but detected by MALDI-TOF MS
10
2 (20.0)
0
NS

     (i) Gemella haemolysans
1
0
0

     (ii) Gemella spp.
1
0
0

     (iii) Corynebacterium amycolatum
2
0
0

     (iv) Acinetobacter ursingii
1
0
0

     (v) Clostridium perfringens
1
0
0

     (vi) Clostridium ramosum
1
1 (100)
0

     (vii) Bacteroides ovatum
1
1 (100)
0

     (viii) Propionibacterium spp.
1
0
0

     (ix) Fusarium spp.
1
0
0

two-tailed Fisher exact test was used. NS: not significant at the level of 5%.

²Four strains of S. aureus were positive for the mecA gene.

³The 42 strains of coagulase negative staphylococci included 35 strains of S. epidermidis, 3 strains of S. capitis, 2 strains of S. hominis, and 1 strain of S. caprae, S. haemolyticus, and S. warneri, each.

⁴Thirty-five strains of coagulase negative staphylococci were positive for the mecA gene.

⁵The 5 strains of Streptococcus spp. included 2 strains of S. gallolyticus, 2 strains of S. mitis/oralis, and 1 strain of S. parasanguinis.

⁶The 11 strains of Enterococcus spp. included 6 strains of E. faecalis, 3 strains of E. faecium, 1 strain of E. gallinarum, and 1 strain of E. hirae.

The fast MALDI-TOF MS technique missed 33 microorganisms that gave either no significant growth in 4 hours (10 cases) or a score under 1.5 (13 cases), including 6 of the 11 Enterococcus spp. and the 3 yeasts (Table 1). Concerning the 8 double infections, 10 of 16 germs were missed (62.5%): 1 germ in 6 cases and 2 germs in 2 cases (Table 2).

Table 2: Pathogens identified in the 8 blood culture bottles exhibiting coinfection.

Reference technique (MALDI-TOF MS)
MALDI-TOF
MS at day 0
FilmArray
BCID assay

E. coli / K. oxytoca
K. oxytoca
E. coli / K. oxytoca

E. coli / K. oxytoca
K. oxytoca
E. coli / K. oxytoca

E. coli / K. pneumoniae
E. coli
E. coli / K. pneumoniae

E. coli / K. pneumoniae
E. coli
E. coli / K. pneumoniae

E. coli / E. faecalis
E. faecalis
E. coli / E. faecalis

E. coli / E. hirae
-
E. coli / E. hirae / Streptococcus spp.

S. epidermidis / S. hominis
S. hominis
Staphylococcus spp. (+ mecA gene)

C. albicans / C. krusei
-
C. albicans / C. krusei

The FilmArray BCID test missed 13 microorganisms, including 10 agents that were off-panel (Table 1), one strain of S. warneri (this species was mentioned as ill-recognized in the booklet of the test), one strain of S. gallolyticus, and one strain of S. aureus (identified as Staphylococcus spp.). Extraction control or amplification control included in the cartridge was not amplified in 3 cases (2.0%) but a correct identification was obtained after the second run. In 6 bottles, an additional germ was identified by comparison to the reference technique (2 strains of Staphylococcus spp., 1 strain of S. aureus, 1 strain of Streptococcus spp., 1 strain of E. coli, and 1 strain of K. pneumoniae). The 8 coinfections detected by the reference technique were also detected by the FilmArray BCID assay; by comparison to the reference technique, an additional strain of Staphylococcus spp. was identified in one bottle whereas a strain of Streptococcus spp. was missed in another bottle (Table 2).

Concerning antimicrobial resistances detected by FilmArray BCID, no isolate was found to harbor vanA/vanB or KPC genes. Four of the 22 isolates of S. aureus (18.2%) and 35 of the 41 coagulase negative staphylococci (85.4%) were detected positive for the mecA gene by FilmArray BCID. Resistance to oxacillin was confirmed by standard antimicrobial susceptibility testing for all isolates (MIC greater than or equal to 4 mg/l) but 5 coagulase negative staphylococci that were not tested.

Table 3 depicts the performances of the two rapid tests by comparison to the reference method for the 153 positive blood specimen bottles. The global agreement of the FilmArray BCID with the reference technique was 91.5% [95% CI: 87.1-95.9], significantly higher than that with the fast MALDI-TOF MS assay (79.7% [95% CI: 73.4-86.0], P < 0.01 by Chi-square test). The sensitivity of the FilmArray BCID assay was 90.9% [95% CI: 86.1-95.6], significantly higher than that of the fast MALDI-TOF method (78.2% [95% CI: 71.4-85.0], P < 0.01 by Chi-square test). By combining the two approaches, 93.5% of the bottles were identified correctly at day 0.

Table 3: Comparative results of the two rapid techniques on the 153 blood culture bottles of the study. Success was defined by the capacity to obtain the same result (absence or presence of one or two microorganisms) as that of the reference method (MALDI-TOF MS).

MALDI-TOF MS at day 0 after a 4-hour culture

success
failure

FilmArray BCID assay
success
119
21

failure
3
10

4. Discussion

These results confirm the excellent sensitivity of the FilmArray BCID assay reported in previous studies [13, 14, 20, 21, 23–27], notably in case of multimicrobial infection. Although no sequencing was performed in this study, it was previously shown that microorganisms identified only by FilmArray BCID could be detected by sequencing, showing that they were true positives [13]. By contrast to other rapid techniques coupled to MALDI-TOF MS, the hands-on time is only of 3-5 minutes and the test does not require trained personnel. The ability to detect resistance genes to some antimicrobial agents is a further advantage.

Due to the limited number of targets included into the test, it must be coupled to another identification strategy. Its high cost and the need to test each sample individually may represent further limitation in laboratories with high test volume [14]. Although less sensitive, notably for slow-growing microorganisms, the 4-hour incubation MALDI-TOF MS method used as comparator in this study represents a much cheaper alternative.

As suggested by Fiori et al. [28], it could be interesting to reserve the FilmArray BCID approach to those bottles that failed identification by the fast MALDI-TOF MS method (≈20% of the bottles tested in this study). The study of Pardo et al. [29] demonstrated that the FilmArray BCID assay, when coupled with antimicrobial stewardship intervention, was a cost-effective tool to improve patient care. In a recent meta-analysis including 31 studies and 5920 patients, Timbrook et al. [30] showed that molecular rapid diagnostic tests in bloodstream infections were associated with significant decrease in mortality risk if associated with an antimicrobial stewardship program. Similar conclusions were drawn from previous reviews on the same topic [31, 32]. Consequently, it could be interesting to target this identification approach to patients considered as the more critical and for whom the rapid adaptation of the antimicrobial therapy represents a key issue in terms of prognosis.

5. Conclusions

This study confirms the excellent analytical performances of the FilmArray BCID assay for microorganism identification at day 0 in positive blood cultures, notably in case of polymicrobial infections (including yeasts). When combined with a 4-hour culture test coupled to mass spectrometry, it was able to give a correct result in more than 93% of the tested cases. Due to high cost and limited targets, the FilmArray BCID could be dedicated to the more severe patients with suspected sepsis who need a quick adjustment of their antimicrobial treatment. In these patients, the analysis of the literature indicates that the implementation of the test must be combined with an antimicrobial stewardship program to provide significant clinical results.

Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this article.

Acknowledgments

Laurie Sahuc, Camille Laroa, and the whole staff of the laboratory of Infectious Agents and Hygiene of the University Hospital of Saint-Etienne are acknowledged for their skillful technical assistance. The authors thank Denis Fortier and William Caule from the Eurobio Company, France, for providing the FilmArray BCID kits free of charge.

References

L. Leibovici, I. Shraga, M. Drucker, H. Konigsberger, Z. Samra, and S. D. Pitlik, “The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection,” Journal of Internal Medicine, vol. 244, no. 5, pp. 379–386, 1998.

D. Martiny, F. Debaugnies, D. Gateff et al., “Impact of rapid microbial identification directly from positive blood cultures using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry on patient management,” Clinical Microbiology and Infection, vol. 19, no. 12, pp. E568–E581, 2013.

B. La Scola and D. Raoult, “Direct identification of bacteria in positive blood culture bottles by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry,” PLoS ONE, vol. 4, no. 11, Article ID e8041, 2009.

A. Ferroni, S. Suarez, J.-L. Beretti et al., “Real-time identification of bacteria and Candida species in positive blood culture broths by matrix-assisted laser desorption ionization-time of flight mass spectrometry,” Journal of Clinical Microbiology, vol. 48, no. 5, pp. 1542–1548, 2010.

G. Prod'Hom, A. Bizzini, C. Durussel, J. Bille, and G. Greub, “Matrix-assisted laser desorption ionization-time of flight mass spectrometry for direct bacterial identification from positive blood culture pellets,” Journal of Clinical Microbiology, vol. 48, no. 4, pp. 1481–1483, 2010.

J. Rychert, C.-A. D. Burnham, M. Bythrow et al., “Multicenter evaluation of the vitek MS matrix-assisted laser desorption ionization-time of flight mass spectrometry system for identification of gram-positive aerobic bacteria,” Journal of Clinical Microbiology, vol. 51, no. 7, pp. 2225–2231, 2013.

A. Fothergill, V. Kasinathan, J. Hyman, J. Walsh, T. Drake, and Y. F. Wayne Wang, “Rapid identification of bacteria and yeasts from positive-blood-culture bottles by using a lysis-filtration method and matrix- assisted laser desorption ionization-time of flight mass spectrum analysis with the SARAMIS database,” Journal of Clinical Microbiology, vol. 51, no. 3, pp. 805–809, 2013.

W. Jamal, R. Saleem, and V. O. Rotimi, “Rapid identification of pathogens directly from blood culture bottles by Bruker matrix-assisted laser desorption laser ionization-time of flight mass spectrometry versus routine methods,” Diagnostic Microbiology and Infectious Disease, vol. 76, no. 4, pp. 404–408, 2013.

P. O. Verhoeven, F. Grattard, A. Carricajo et al., New protocol for accurate bacterial identification from positive blood cultures by matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF MS), Abstr 23rd ECCMID, Berlin, Germany, 2013.

E. A. Idelevich, I. Schüle, B. Grünastel, J. Wüllenweber, G. Peters, and K. Becker, “Rapid identification of microorganisms from positive blood cultures by MALDI-TOF mass spectrometry subsequent to very short-term incubation on solid medium,” Clinical Microbiology and Infection, vol. 20, no. 10, pp. 1001–1006, 2014.

E. A. Idelevich and K. Becker, “Identification and susceptibility testing from shortly incubated cultures accelerate blood culture diagnostics at no cost,” Clinical Infectious Diseases, vol. 62, no. 2, pp. 268-269, 2016.

N. Mancini, S. Carletti, N. Ghidoli, P. Cichero, R. Burioni, and M. Clementi, “The era of molecular and other non-culture-based methods in diagnosis of sepsis,” Clinical Microbiology Reviews, vol. 23, no. 1, pp. 235–251, 2010.

A. J. Blaschke, C. Heyrend, C. L. Byington et al., “Rapid identification of pathogens from positive blood cultures by multiplex polymerase chain reaction using the FilmArray system,” Diagnostic Microbiology and Infectious Disease, vol. 74, no. 4, pp. 349–355, 2012.

O. Altun, M. Almuhayawi, M. Ullberg, and V. Ozenci, “Clinical evaluation of the FilmArray blood culture identification panel in identification of bacteria and yeasts from positive blood culture bottles,” Journal of Clinical Microbiology, vol. 51, no. 12, pp. 4130–4136, 2013.

L. P. Samuel, R. J. Tibbetts, A. Agotesku, M. Fey, R. Hensley, and F. A. Meier, “Evaluation of a microarray-based assay for rapid identification of Gram positive organisms and resistance markers in positive blood cultures,” Journal of Clinical Microbiology, vol. 51, no. 4, pp. 1188–1192, 2013.

C. M. Wojewoda, L. Sercia, M. Navas et al., “Evaluation of the verigene gram-positive blood culture nucleic acid test for rapid detection of bacteria and resistance determinants,” Journal of Clinical Microbiology, vol. 51, no. 7, pp. 2072–2076, 2013.

K. V. Sullivan, N. N. Turner, S. S. Roundtree et al., “Rapid detection of gram-positive organisms by use of the verigene gram-positive blood culture nucleic acid test and the bact/alert pediatric fan system in a multicenter pediatric evaluation,” Journal of Clinical Microbiology, vol. 51, no. 11, pp. 3579–3584, 2013.

B. W. Buchan, C. C. Ginocchio, R. Manii et al., “Multiplex identification of gram-positive bacteria and resistance determinants directly from positive blood culture broths: evaluation of an automated microarray-based nucleic acid test,” PLoS Medicine, vol. 10, Article ID e1001478, 2013.

J. Mestas, C. M. Polanco, S. Felsenstein, and J. D. Bard, “Performance of the verigene gram-positive blood culture assay for direct detection of gram-positive organisms and resistance markers in a pediatric hospital,” Journal of Clinical Microbiology, vol. 52, no. 1, pp. 283–287, 2014.

M. M. Bhatti, S. Boonlayangoor, K. G. Beavis, and V. Tesic, “Evaluation of filmarray and verigene systems for rapid identification of positive blood cultures,” Journal of Clinical Microbiology, vol. 52, no. 9, pp. 3433–3436, 2014.

C. Ward, K. Stocker, J. Begum, P. Wade, U. Ebrahimsa, and S. D. Goldenberg, “Performance evaluation of the Verigene® (Nanosphere) and FilmArray® (BioFire®) molecular assays for identification of causative organisms in bacterial bloodstream infections,” European Journal of Clinical Microbiology & Infectious Diseases, vol. 34, no. 3, pp. 487–496, 2015.

P. Seng, M. Drancourt, F. Gouriet et al., “Ongoing revolution in bacteriology: routine identification of bacteria by matrix-assisted laser desorption ionization time-of-flight mass spectrometry,” Clinical Infectious Diseases, vol. 49, no. 4, pp. 543–551, 2009.

M. Almuhayawi, O. Altun, K. Strålin, and V. Özenci, “Identification of microorganisms by filmarray and matrix-assisted laser desorption ionization-time of flight mass spectrometry prior to positivity in the blood culture system,” Journal of Clinical Microbiology, vol. 52, no. 9, pp. 3230–3236, 2014.

M. Paolucci, C. Foschi, M. V. Tamburini, S. Ambretti, T. Lazzarotto, and M. P. Landini, “Comparison between MALDI-TOF MS and FilmArray blood culture identification panel for rapid identification of yeast from positive blood culture,” Journal of Microbiological Methods, vol. 104, pp. 92-93, 2014.

K. H. Rand and J. P. Delano, “Direct identification of bacteria in positive blood cultures: Comparison of two rapid methods, FilmArray and mass spectrometry,” Diagnostic Microbiology and Infectious Disease, vol. 79, no. 3, pp. 293–297, 2014.

H. Salimnia, M. R. Fairfax, P. R. Lephart et al., “Evaluation of the FilmArray blood culture identification panel: results of a multicenter controlled trial,” Journal of Clinical Microbiology, vol. 54, no. 3, pp. 687–698, 2016.

T. R. Southern, T. C. VanSchooneveld, D. L. Bannister et al., “Implementation and performance of the BioFire FilmArray® Blood Culture Identification panel with antimicrobial treatment recommendations for bloodstream infections at a midwestern academic tertiary hospital,” Diagnostic Microbiology and Infectious Disease, vol. 81, no. 2, pp. 96–101, 2015.

B. Fiori, T. D'Inzeo, A. Giaquinto et al., “Optimized Use of the MALDI BioTyper System and the FilmArray BCID Panel for Direct Identification of Microbial Pathogens from Positive Blood Cultures,” Journal of Clinical Microbiology, vol. 54, no. 3, pp. 576–584, 2016.

J. Pardo, K. P. Klinker, S. J. Borgert, B. M. Butler, P. G. Giglio, and K. H. Rand, “Clinical and economic impact of antimicrobial stewardship interventions with the FilmArray blood culture identification panel,” Diagnostic Microbiology and Infectious Disease, vol. 84, no. 2, pp. 159–164, 2016.

T. T. Timbrook, J. B. Morton, K. W. Mcconeghy, A. R. Caffrey, E. Mylonakis, and K. L. LaPlante, “The effect of molecular rapid diagnostic testing on clinical outcomes in bloodstream infections: A systematic review and meta-analysis,” Clinical Infectious Diseases, vol. 64, no. 1, pp. 15–23, 2017.

K. Z. Vardakas, F. I. Anifantaki, K. K. Trigkidis, and M. E. Falagas, “Rapid molecular diagnostic tests in patients with bacteremia: evaluation of their impact on decision making and clinical outcomes,” European Journal of Clinical Microbiology & Infectious Diseases, vol. 34, no. 11, pp. 2149–2160, 2015.

E. Minejima and A. Wong-Beringer, “Implementation of rapid diagnostics with antimicrobial stewardship,” Expert Review of Anti-infective Therapy, vol. 14, no. 11, pp. 1065–1075, 2016.