CLINICAL THERAPEUTICS

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Comparison of Pharmacist-Directed Management of Multiplex

PCR Blood Culture Results with Conventional Microbiology
Methods on Effective and Optimal Therapy within a
Community Hospital

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Allison M. Porter,a,b Christopher M. Bland,a,b Henry N. Young,b David R. Allen,a* Sabrina R. Croft,a,b R. Ellen Gayheart,c
Parks W. Miller,a* Rachel J. Musgrove,a Emilee M. Robertson,a Geneen M. Gibsona,b

a Department of Pharmacy, St. Joseph’s/Candler Health System, Savannah, Georgia, USA

b University of Georgia College of Pharmacy, Athens, Georgia, USA
c
Department of Microbiology, St. Joseph’s/Candler Health System, Savannah, Georgia, USA

ABSTRACT Multiplex PCR combined with a pharmacist-driven reporting protocol

was compared to the standard of care within a community hospital to evaluate ini-
tial changes after notification of a positive blood culture. The intervention group
demonstrated decreased times to changes in antimicrobial therapy (P ⫽ 0.0081), in-
creased changes to optimal antimicrobial therapy (P ⫽ 0.013), and decreased vanco-
mycin use for coagulase-negative staphylococcus contaminants (P ⬍ 0.01) with mul-
tiplex PCR implementation and pharmacist intervention.

KEYWORDS community, pharmacy, rapid diagnostic test, stewardship, mRDT

I t is critical to quickly identify pathogens and to provide effective antimicrobial

therapy for bloodstream infections, to limit morbidity and deaths (1–3). Rapid
optimization of therapy should limit the use of broad-spectrum antimicrobials and
maximize clinical cures (4). Conventional microorganism identification typically
takes 48 to 72 h. However, recent advancements in diagnostic technology have led
Citation Porter AM, Bland CM, Young HN, Allen
to the availability of rapid microorganism identification from blood cultures. Early DR, Croft SR, Gayheart RE, Miller PW, Musgrove
studies, primarily performed in academic centers, involving molecular rapid diag- RJ, Robertson EM, Gibson GM. 2019.
nostic tests (mRDTs) demonstrated improved outcomes, especially in conjunction Comparison of pharmacist-directed
management of multiplex PCR blood culture
with antimicrobial stewardship programs (ASPs) (2, 5). We report findings regarding results with conventional microbiology
effective and optimal therapies with the use of mRDTs with a pharmacist-driven methods on effective and optimal therapy
model within a community hospital, compared to standard microbiology reporting within a community hospital. Antimicrob
Agents Chemother 63:e01575-18. https://doi
methodology. .org/10.1128/AAC.01575-18.
St. Joseph’s Hospital, an anchor hospital in St. Joseph’s/Candler Health System, Copyright © 2018 American Society for
is a 330-bed community hospital in Savannah, Georgia. All admitted nonpregnant Microbiology. All Rights Reserved.
adult patients who had a positive blood culture with an organism that was Address correspondence to Allison M. Porter,
alliporter236@gmail.com.
identifiable by multiplex PCR (BioFire FilmArray blood culture identification panel),
* Present address: David R. Allen, Department
with results reported between 7:00 a.m. and 3:30 p.m. on Monday through Friday, of Pharmacy, Inova Fairfax Medical Campus,
were included. Patients were excluded if they were receiving palliative or hospice Falls Church, Virginia, USA; Parks W. Miller,
care, had been transferred from an outside hospital with an already positive blood Department of Pharmacy, Saint Thomas
Rutherford, Murfreesboro, Tennessee, USA.
culture, or had positive blood culture results reported after discharge or death. The
Received 30 July 2018
St. Joseph’s/Candler Health System institutional review board approved this inves- Returned for modification 12 September
tigation. 2018
This single-center, retrospective, before-and-after study was conducted over two Accepted 10 October 2018
Accepted manuscript posted online 15
12-month periods. The control group consisted of patients with positive blood
October 2018
cultures between December 2014 and November 2015, who were treated under the Published 21 December 2018
conventional microorganism identification protocol, in which the initial Gram stain

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Porter et al. Antimicrobial Agents and Chemotherapy

TABLE 1 Antimicrobial recommendation algorithm utilized by pharmacists after reported positive multiplex PCR result
No. of casesb
Control group Intervention
Organisma Antibiotic(s) (n ⴝ 123) group (n ⴝ 85)
Gram-positive organisms
Enterococcus
VSE (VanA/B negative) Ampicillin i.v., 2 g q4h 5 6
PCN allergy Vancomycin i.v.
VRE (VanA/B positive) Linezolid i.v., 600 mg q12 1
Alternative Daptomycin i.v., ⱖ8 mg/kg q24h
Listeria Ampicillin i.v., 2 g q4h
PCN allergy Sulfamethoxazole-trimethoprim i.v., 10–15 mg/kg/day divided q6–12h
Staphylococcus
MSSA (MecA negative) Cefazolin i.v., 2 g q8h 6 5
Alternative Nafcillin i.v., 2 g q4h
PCN allergy Vancomycin i.v.

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MRSA (MecA positive) Vancomycin i.v. 11 6
CoNS 58c 41
MSCoNS (MecA negative) 10
1/2 BC sets Cefazolin, 2 g q8h, or consider discontinuing antibiotics
2/2 BC sets Cefazolin, 2 g q8h, or consider discontinuing antibiotics
MRCoNS (MecA positive) 31
1/2 BC sets Vancomycin i.v. or consider discontinuing antibiotics
2/2 BC sets Vancomycin i.v.
Streptococcus agalactiae (group B) Penicillin G i.v., 3 million units q4h 3 2
Alternative Ceftriaxone i.v., 1–2 g q24h
PCN allergy Vancomycin i.v.
Streptococcus pyogenes (group A) Penicillin G i.v., 3 million units q4h 1
Alternative Ceftriaxone i.v., 1–2 g q24h
PCN allergy Vancomycin i.v.
Streptococcus pneumoniae/Streptococcus mitis 5 2
CNS source Ceftriaxone i.v., 2 g q12h, ⫹ vancomycin i.v.
Non-CNS source Ceftriaxone i.v., 1–2 g q24h
PCN allergy Levofloxacin i.v., 500 mg q24h, for lung source or vancomycin otherwise
Streptococcus species Ceftriaxone i.v., 1–2 g q24h 8 3
PCN allergy Vancomycin i.v.

Gram-negative organisms
Acinetobacter baumannii Piperacillin-tazobactam i.v., 4.5 g q8h, ⫹ tobramycin i.v. 1
Alternative Meropenem i.v., 2 g q8h, ⫹ tobramycin i.v.
Haemophilus influenzae Ceftriaxone i.v., 1–2 g q24h 2
Alternative Ampicillin-sulbactam i.v., 3 g q6h
PCN allergy Levofloxacin i.v., 750 mg q24h
Neisseria meningitidis Ceftriaxone i.v., 2 g q24h
Alternative Penicillin G i.v., 4 million units q4h
PCN allergy Levofloxacin i.v., 750 mg q24h
Pseudomonas aeruginosa Piperacillin-tazobactam i.v., 4.5 g q8h, ⫹ tobramycin i.v. 3 2
PCN allergy Meropenem i.v., 2 g q8h, ⫹ tobramycin i.v.

Enterobacteriaceae
Enterobacter cloacae complex Cefepime i.v., 2 g q8h or 2 g q12h for non-CNS 5
PCN allergy Meropenem i.v., 1 g q8h
Escherichia coli Piperacillin-tazobactam i.v., 3.375 g q8h 9 8
PCN allergy Meropenem i.v., 1 g q8h
Klebsiella oxytoca Cefepime i.v., 2 g q8h
Meropenem i.v., 1 g q8h
Klebsiella pneumoniae Meropenem i.v., 1 g q8h 6 2
Proteus species Ceftriaxone i.v., 1–2 g q24h 4 2
PCN allergy Meropenem i.v., 1 g q8h
Serratia marcescens Ceftriaxone i.v., 1–2 g q24h 1
PCN allergy Meropenem i.v., 1 g q8h
Enterobacteriaceae species Cefepime i.v., 2 g q8h
PCN allergy Meropenem i.v., 1 g q8h
KPC resistance gene positive Consider ID consult
aBC, blood culture; VSE, vancomycin-susceptible enterococcus; i.v., intravenously; q, every; PCN, penicillin; VRE, vancomycin-resistant enterococcus; MSSA, methicillin-
sensitive Staphylococcus aureus; MRSA, methicillin-resistant Staphylococcus aureus; MSCoNS, methicillin-sensitive CoNS; MRCoNS, methicillin-resistant CoNS; CNS,
central nervous system; KPC, Klebsiella pneumoniae carbapenemase.
bValues indicate the total number of organisms identified, because some patients grew multiple organisms.
cUnable to determine whether the case was MecA positive.

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TABLE 2 Demographic characteristics

Characteristica Control group (n ⴝ 118) Intervention group (n ⴝ 77) P
Age (mean ⫾ SD) (y) 68.78 ⫾ 15.26 62.69 ⫾ 16.01 0.0082b

Gender (no. [%]) 0.70

Male 58 (49.15) 40 (51.95)
Female 60 (50.85) 37 (48.05)

CCI (mean ⫾ SD) 5.67 ⫾ 2.58 4.62 ⫾ 2.77 0.0078b

aSD, standard deviation; CCI, Charlson comorbidity index.
bBy t test.

results were communicated to a nurse, who then notified the provider. The inter-

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vention group consisted of patients with multiplex PCR identification in conjunction with a
pharmacist-driven reporting protocol; patients were identified through records from mi-
crobiology calls received between April 2016 and March 2017. The microbiology
laboratory called the pharmacist with a positive multiplex PCR result; the pharmacist
notified the provider and nurse, gave recommendations, and entered accepted orders
for antimicrobial changes directly into the electronic health record (Meditech 6.15).
Pharmacists utilized an algorithm approved by the antimicrobial subcommittee (con-
sisting of antimicrobial stewardship pharmacists and infectious diseases [ID] physicians)
to make recommendations in response to positive multiplex PCR results (Table 1).
The following data were collected: age, gender, drug allergies, comorbidities, all
blood and other-source cultures and susceptibilities from that admission, and all
antimicrobials, with the time of initiation and/or discontinuation, from that admission.
Progress notes for each patient were read to determine whether antimicrobials were
being used for anything aside from the specified cultures and to obtain additional
treatment information.
The primary outcome was the time to change in antimicrobial therapy, measured
from the time of the call from the microbiology laboratory to the time at which the
antimicrobial change was verified in the electronic health record. If the change was
made ⱖ24 h after the phone call or after a subsequent call, then the patient was
categorized as “no change,” so that only initial changes were captured. Secondary
outcomes further delineated the primary outcome as the time to change from subop-
timal to optimal antimicrobial therapy or from ineffective to effective antimicrobial
therapy. Optimal antimicrobial therapy was defined by the treatment algorithm de-
scribed previously. Effective antimicrobial therapy was defined as the organism being
susceptible to the antimicrobial regimen prescribed but with further modification being
necessary to obtain optimal classification. Other secondary outcomes included the
number of patients changed to optimal or effective antimicrobial therapy, the presence

TABLE 3 Results
Multivariate logistic regression
analysisa
Intervention
Outcome Control group group P OR (95% CI) P
Patients with change in therapyb
Time to change (median) (min) 160 50 0.0081 0.28 (0.10–0.77) 0.014
Time to optimal therapy (median) (min) 178 76.5 0.083 0.19 (0.22–1.55) 0.12
Time to effective therapy (median) (min) 152 50 0.015 Outcome predicted perfectly
No. (%) changed to optimal therapy 7 (15.6) 12 (41.4) 0.013 4.28 (1.38–13.31) 0.012
No. (%) changed to effective therapy 11 (24.4) 5 (17.2) 0.462 0.53 (0.15–1.83) 0.318

Patients with CoNS contaminantsc

No. (%) with vancomycin use for CoNS contaminants after call 27 (69.23) 3 (10) ⬍0.01
aOR, odds ratio; CI, confidence interval.
bControl group, n ⫽ 45; intervention group, n ⫽ 29.

cCoNS contaminants all had 1/4 blood culture sets positive or 1/2 blood culture sets positive with adjudication by an ID pharmacist or ID physician. Control group,

n ⫽ 39; intervention group, n ⫽ 30.

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TABLE 4 Optimal therapy interventions

Change to optimal therapy in intervention
group (n ⴝ 12) Organism(s)a
Escalation (n ⫽ 5)
No treatment to vancomycin MRSA (n ⫽ 2), CoNS (n ⫽ 2)
No treatment to cefazolin MSSA (n ⫽ 1)

De-escalation (n ⫽ 7)
Discontinuation of vancomycin CoNS contaminant (n ⫽ 2),b Gram-negative organism (n ⫽ 2), Streptococcus species (n ⫽ 1)
Piperacillin-tazobactam to cefepime KPC-negative Enterobacter (n ⫽ 1)
Meropenem to cefazolin MSSA (n ⫽ 1)
aMRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus; KPC, Klebsiella pneumoniae carbapenemase.
bCoNS contaminants all had 1/4 blood culture sets positive or 1/2 blood culture sets positive with adjudication by an ID pharmacist or ID physician.

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of effective antimicrobial therapy, and vancomycin use for coagulase-negative staph-
ylococcus (CoNS)-contaminated cultures.
Descriptive statistics were calculated to characterize patients in the two groups and
the study outcomes. Nonparametric statistics were used to examine differences be-
tween the groups, due to the nonnormal distributions of the outcome variables.
Bivariate analyses, including chi-square, Fisher’s exact, and Wilcoxon rank-sum tests,
were conducted to examine differences in outcomes between the two groups. Out-
come variables were dichotomized at the median scores. Multivariate logistic regres-
sion analyses were used to examine differences in outcomes between the two groups,
with adjustment for potentially confounding variables. Stata MP 13.1 was used to
analyze the data.
A total of 118 patients were identified for the control group and 77 for the
intervention group, based on inclusion and exclusion criteria (Table 2). The inter-
vention group demonstrated decreased median time-to-change values for effective
therapy, as well as increased numbers of patients changed to optimal therapy
(Table 3). Multivariate logistic regression analyses indicated that the intervention
group was less likely to have a greater time-to-change value (P ⬍ 0.01) and more
likely to be changed to optimal therapy (P ⬍ 0.01), in comparison to the control
group, after accounting for differences between the groups. Changes to optimal
therapy were split between escalation and de-escalation. The most common
changes in the intervention group included the addition of vancomycin for
methicillin-resistant Staphylococcus aureus and the discontinuation of vancomycin
when it was determined to be clinically unnecessary (Table 4). Five patients, all in
the control group, continued to receive ineffective antimicrobial therapy after the
initial microbiology call; all others ultimately received either effective or optimal
therapy, with or without a change. Vancomycin use for CoNS contaminants de-
creased considerably in the intervention group (p ⬍ 0.01).
The majority of studies demonstrating benefits with mRDT and ASPs have been
conducted in academic medical centers, with significantly more resources than
community hospitals (2–5). One study found that mRDT in the absence of an ASP
did not improve clinical outcomes, demonstrating the necessity of ASP resources
(6). Our study focused on combining multiplex PCR results with pharmacist-driven
management within a community hospital that employed 10 clinical pharmacists, 7
of whom participated in this study. Four clinical pharmacists providing recommen-
dations had no formal specialty ID postgraduate training but had access to formally
trained ID pharmacists if needed. Additionally, non-ID pharmacy residents were
involved in the communications and recommendations, supervised directly by the
clinical pharmacist. The outcome data were encouraging, as this study best repre-
sents most clinical practice settings in the United States where mRDT and ASPs
could potentially be implemented. Our study design also differs from that of many
published studies, because we evaluated only immediate changes after identifica-
tion, rather than evaluating the final regimen. Limitations of our study included

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mRDT and Pharmacist Intervention in a Community Hospital Antimicrobial Agents and Chemotherapy

communication issues, prescriber unfamiliarity with the new technology, documen-

tation inconsistencies, and the implementation of two interventions at once.
In conclusion, integration of multiplex PCR with pharmacist-directed management
of blood culture results resulted in shorter times to effective therapy and increased
numbers of patients receiving optimal therapy after initial interventions within a
community hospital. More studies are needed to further delineate the role of mRDT and
pharmacists in these settings.

ACKNOWLEDGMENTS
This research received no specific grant from any funding agency in the public,
commercial, or not-for-profit sectors.
C.M.B. reports consulting for bioMérieux. All other authors report no conflicts of
interest relevant to this article.

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