VIROLOGY

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Impact of Rapid Molecular Diagnostic Testing of Respiratory

Viruses on Outcomes of Adults Hospitalized with Respiratory
Illness: a Multicenter Quasi-experimental Study
Nasir Wabe,a Ling Li,a Robert Lindeman,b Ruth Yimsung,b Maria R. Dahm,a Susan McLennan,b,c Kate Clezy,d
Johanna I. Westbrook,a Andrew Georgioua

a Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Macquarie University, North Ryde, NSW, Australia
b NSW Health Pathology, Chatswood, NSW, Australia
c
Sydney Medical School, University of Sydney, Sydney, NSW, Australia
d Infectious Diseases Department, Prince of Wales Hospital, Randwick, NSW, Australia

ABSTRACT A standard multiplex PCR offers comprehensive testing for respiratory

viruses. However, it has traditionally been performed in a referral laboratory with a
lengthy turnaround time, which can reduce patient flow through the hospital. We
aimed to determine whether the introduction of a rapid PCR, but with limited tar-
gets (Cepheid Xpert Flu/RSV XC), was associated with improved outcomes for adults
hospitalized with respiratory illness. A controlled quasi-experimental study was con-
ducted across three hospitals in New South Wales, Australia. Intervention groups re-
ceived standard multiplex PCR during the preimplementation, July to December
2016 (n ⫽ 953), and rapid PCR during the postimplementation, July to December
2017 (n ⫽ 1,209). Control groups (preimplementation, n ⫽ 937, and postimplemen-
tation, n ⫽ 1,102) were randomly selected from adults hospitalized with respiratory
illness during the same periods. The outcomes were hospital length of stay (LOS)
and microbiology test utilization (blood culture, urine culture, sputum culture, and
respiratory bacterial and virus serologies). The introduction of rapid PCR was associ-
ated with a nonsignificant 8.9-h reduction in median LOS (95% confidence interval
[CI], ⫺21.5 h to 3.7 h; P ⫽ 0.17) for all patients and a significant 21.5-h reduction in
median LOS (95% CI, ⫺36.8 h to ⫺6.2 h; P ⬍ 0.01) among patients with positive test
results in an adjusted difference-in-differences analysis. For patients receiving test re-
Citation Wabe N, Li L, Lindeman R, Yimsung R,
sults before disposition, rapid PCR use was associated with a significant reduction in Dahm MR, McLennan S, Clezy K, Westbrook JI,
LOS, irrespective of test results. Compared with standard PCR testing, rapid PCR use Georgiou A. 2019. Impact of rapid molecular
diagnostic testing of respiratory viruses on
was significantly associated with fewer blood culture (adjusted odds ratio [aOR],
outcomes of adults hospitalized with
0.67; 95% CI, 0.5 to 0.82; P ⬍ 0.001), sputum culture (aOR, 0.56; 95% CI, 0.47 to 0.68, respiratory illness: a multicenter quasi-
P ⬍ 0.001), bacterial serology (aOR, 0.44; 95% CI, 0.35 to 0.55, P ⬍ 0.001) and viral experimental study. J Clin Microbiol
57:e01727-18. https://doi.org/10.1128/JCM
serology (aOR, 0.42; 95% CI, 0.33 to 0.53, P ⬍ 0.001) tests, but not with fewer urine
.01727-18.
culture tests (aOR, 0.94; 95% CI, 0.78 to 1.12, P ⫽ 0.48). Rapid PCR testing of adults Editor Michael J. Loeffelholz, Cepheid
hospitalized with respiratory illnesses can deliver benefits to patients and reduce Copyright © 2019 American Society for
resource utilization. Future research should consider a formal economic analysis and Microbiology. All Rights Reserved.
assess its potential impacts on clinical decision making. Address correspondence to Nasir Wabe,
nasir.wabe@mq.edu.au.
For a commentary on this article, see https://
KEYWORDS influenza, molecular diagnostic, rapid PCR, respiratory viruses doi.org/10.1128/JCM.01890-18.
Received 26 October 2018
Returned for modification 18 November

I nfluenza and other respiratory viruses, such as a respiratory syncytial virus (RSV),
rhinovirus, coronavirus, human metapneumovirus, and parainfluenza viruses, cause
significant morbidity and mortality in Australia and worldwide (1–3). Acute respiratory
2018
Accepted 29 November 2018
Accepted manuscript posted online 12
December 2018
viral infections are estimated to cause 5.8 million deaths worldwide (4), and each year, Published 28 March 2019
up to 650, 000 deaths are related to respiratory diseases from seasonal influenza (5). In

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Wabe et al. Journal of Clinical Microbiology

Australia, influenza-like illness is a common presentation among working-age adults

and is responsible for decreased productivity and lost working days (3).
The laboratory diagnosis of respiratory viruses has evolved considerably in recent
years with the development of novel molecular methods (6). Molecular methods use
nucleic acid amplification techniques, such as reverse transcription PCR (PCR), and are
considered effective diagnostic tests to confirm respiratory viral infections (7). A stan-
dard multiplex PCR test can detect several respiratory viruses with very high sensitivity
and specificity in a single test (8). While it offers comprehensive testing for respiratory
viruses, multiplex PCR requires specialized laboratory facilities and expertise (9), and it
has traditionally been performed in a referral laboratory with a lengthy test turnaround
time (TAT), which can reduce patient flow through the hospital.
New rapid PCR-based tests have recently been developed, including the Cepheid
Xpert assays (Cepheid, Sunnyvale, CA) (10). Rapid viral diagnosis at hospital-based
laboratories can improve the timeliness of care in hospital and has the potential for
reducing resource utilization (11). The use of rapid PCR was introduced across hospitals
in New South Wales (NSW), Australia, in July 2017 (N. Wabe, L. Li, R. Lindeman, R.
Yimsung, M.R. Dahm, S. McLennan, K. Clezy, J.I Westbrook, and A. Georgiou, submitted
for publication). It is an easy-to-use diagnostic test for accurate detection and differ-
entiation of influenza A/B and RSV. Existing international evidence has shown an
association between the implementation of rapid viral diagnosis and reductions in
hospital length of stay (LOS) (12) and other laboratory test ordering practices (13–15).
However, the impact of the introduction of a rapid PCR has not yet been investigated
in Australia.
In this study, we compared outcomes of patients tested for influenza A/B and RSV
using a rapid PCR (Cepheid Xpert Flu/RSV XC) at the local hospital laboratory during the
first six months following its introduction (July to December 2017), with patients tested
at a referral laboratory using a standard multiplex PCR (Allplex respiratory panels;
Seegene) during the corresponding period in 2016. The objective was to determine
whether the introduction of a rapid PCR testing for influenza A/B and RSV for adults
hospitalized with respiratory illness was associated with a reduction in hospital LOS and
a change in microbiology test utilization compared with those associated with standard
multiplex PCR testing.

MATERIALS AND METHODS

Study setting. The study was conducted across three major tertiary teaching hospitals in New South
Wales, Australia, each offering a comprehensive range of inpatient and community services, hospital A
(⬎65,000 admissions per year), hospital B (⬎50,000 admissions per year), and hospital C (⬎28,000
admissions per year). Ethics approval was granted by the Human Research Ethics Committee of the South
Eastern Sydney Local Health District (approval HREC/16/POWH/412).
Study design and population. We conducted a controlled, nonrandomized, quasi-experimental
study. A patient selection flow chart is presented in Fig. 1. The study periods were between July and
December 2016 (preimplementation) and between July and December 2017 (postimplementation).
The inclusion criteria were patients (aged ⬎18 years) admitted with a respiratory illness [International
Classification of Diseases version 10 Australian Modification (ICD-10-AM), J00-J99] during the study
period and having at least one laboratory test result.
The intervention groups included patients tested for respiratory viruses using the standard multiplex
PCR during the preimplementation (standard PCR group) and patients tested for influenza or RSV using
the rapid PCR during the postimplementation (rapid PCR group). The standard PCR used in this study
consisted of Allplex respiratory panels 1, 2, and 3 (Seegene Inc., Seoul, Republic of Korea) (16). It was
available as a referral test at a large referral laboratory located at hospital B. All three hospitals sent
samples to this laboratory to conduct a standard multiplex PCR. Standard multiplex PCR testing was
generally batched. During the influenza season, it was performed 1 to 2 times a day (per demand) on
weekdays and once a day on weekends. Outside the influenza season, the test was performed once every
day. The multiplex PCR assay was offered as three panels that can detect up to 16 viruses with influenza
A subtyping. Panel 1 includes influenza A (subtypes H1, H1pdm09, and H3), influenza B, and RSV (types
A and B); panel 2 includes adenovirus, metapneumovirus, enterovirus, and parainfluenza virus (types 1,
2, 3, and 4); and panel 3 includes bocavirus (types 1, 2, 3, and 4), coronavirus (types OC43, 229E, and
NL63), and rhinovirus (types A, B, and C) (16). In this study, all patients in the standard PCR group received
panel 1 and, depending on whether a specific request for other viruses was made, panels 2 and or 3 were
also ordered.
The rapid PCR used in this study was a Cepheid Xpert Flu/RSV XC assay (Cepheid, Sunnyvale, CA). The
Cepheid Xpert Flu/RSV XC assay demonstrated a high sensitivity and specificity for detection of influenza

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Rapid PCR Testing of Adults with Respiratory Illness Journal of Clinical Microbiology

Intervention group Control group

Pre-implementation (July-December 2016)

Adult patients hospitalised with respiratory illnesses who had at least

one laboratory test ordered during pre-implementation period (n=2,769)

Standard PCR ordered Standard PCR not ordered

(n=953) (n=1,816)

Excluded unmatched patients

(n=879)

Standard PCR Group Control Group 2016

(n=953) (n=937)
Post-implementation (July-December 2017)

Adult patients hospitalised with respiratory illnesses who had at least

one laboratory test ordered during post-implementation period (n=2,791)

Rapid PCR ordered Rapid PCR not ordered

(n=1,209) (n= 1,582)

Excluded unmatched patients

(n=480)

Rapid PCR Group Control Group 2017

(n=1,209) (n=1,102)

FIG 1 Patient selection flow chart.

A, influenza B, and RSV (17). However, unlike the standard multiplex PCR, Cepheid Xpert Flu/RSV XC
cannot discriminate among influenza A virus subtypes. It is a hospital laboratory-based test. Hospitals A
and B had an onsite laboratory to perform the rapid testing. Hospital C sent samples to hospital A
because of its proximity to this hospital. During the influenza season, rapid PCR testing was available 24
h a day, 7 days a week, and outside the influenza season, the test was available on demand with approval
from the pathologist or registrar on duty.
The control groups were selected from the population that fulfilled the above inclusion criteria but
were not tested with standard PCR or rapid PCR. They were selected randomly from the population after
matching during the respective study periods on study hospital, age quartile, mode of separation from
the hospital, and gender. The purpose of matching was to balance the distribution of baseline
characteristics across groups. The diagnosis of influenza among patients in the control groups was based
on clinical assessment. Relevant demographic, clinical characteristics, and laboratory test data were
obtained by linking the admitted patient and laboratory information system data sets. Detailed infor-
mation on the linkage process has been described elsewhere (18).
Outcome measures. The primary outcome was hospital LOS. Hospital LOS was calculated by
subtracting the admission date/time from the hospital separation date/time. As secondary outcomes, we
compared utilization of commonly ordered microbiology tests, including blood culture; urine micros-
copy, culture, and sensitivity (urine MC&S); sputum culture; respiratory bacterial serology (e.g., Myco-
plasma pneumoniae IgM Antibody [Ab], Bordetella pertussis toxin IgA Ab and Pneumocystis jirovecii
immunofluorescence assay [IF], and Hemophilus influenzae B Ab), and respiratory virus serology (e.g.,
Parainfluenza Ab complement fixation test [CFT], Adenovirus CFT and RSV Ab CFT).
Statistical analysis. Descriptive statistics, including medians with interquartile ranges (IQR), were
calculated. Demographic and clinical characteristics of the groups were compared using Pearson’s
chi-square test for categorical variables and Mann-Whitney tests for continuous variables.
The impact of a rapid PCR on hospital LOS was assessed using a median regression. As LOS data were
highly positively skewed, commonly used approaches such as ordinary least-squares regression, which
models the conditional mean of the outcome variable, were not appropriate (19). Median regression is
robust to extreme values and therefore well suited for modeling LOS (20). A difference-in-differences
(DID) analysis was conducted to estimate the effect of a rapid PCR on the LOS by comparing the median
change over time in the LOS for the intervention group, compared to the median change over time for
the control group.
Comparison of other microbiology test utilization (e.g., blood culture, yes/no) between intervention
and control groups was performed using binary logistic regression. Analyses were adjusted for relevant
demographic and clinical characteristics.
For both primary and secondary outcomes, a subgroup analysis was conducted by test results. For
the primary outcome, a further subgroup analysis was conducted by limiting the analysis to patients

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Wabe et al. Journal of Clinical Microbiology

whose test results were returned during their stay in the hospital (i.e., excluding patients discharged
before test results became available). All P values were 2-tailed, and a P value of ⬍0.05 was considered
statistically significant. Analyses were conducted using Stata version 15 (StataCorp LP, College
Station, TX).

RESULTS
Demographic and clinical characteristics. The intervention group included 2,162
patients (953 preimplementation [standard PCR group] and 1,209 postimplementation
[rapid PCR group]). The control group consisted of 2,039 patients (937 preimplemen-
tation [control group 2016] and 1,102 postimplementation [control group 2017]) (Fig.
1). All patients in the standard PCR group received panel 1 with or without other panels;
64.1% (n ⫽ 611) received panel 1 only; 32.2% (n ⫽ 307) received all 3 panels; 2.3% (n ⫽
22) received panels 1 and 3; and 1.4% (n ⫽ 13) received panels 1 and 2. Postimple-
mentation, 20.2% (n ⫽ 244) of patients in the rapid PCR group were ordered at least
one standard multiplex PCR panel in addition to the rapid PCR itself. Of the 244
patients, 40.9% (n ⫽ 100) received all 3 panels; 43.4% (n ⫽ 106) received panels 2 and
3; 12.3% (n ⫽ 30) received panel 1; and 3.3% (n ⫽ 8) received panels 1 and 3 (n ⫽ 3),
panels 1 and 2 (n ⫽ 2), panel 2 (n ⫽ 2), or panel 3 (n ⫽ 1).
The distributions of patient demographic and clinical characteristics in the interven-
tion and control groups were similar in terms of gender, age, study hospital, weekday
of admission, and mode of separation from the hospital. However, the distributions of
the source of referral, intensive care admission status, and principal diagnosis were
different across groups (Table 1).
Influenza and pneumonia were the most common principal diagnosis in all groups.
However, intervention groups had higher proportions of admissions due to influenza
and pneumonia compared to those of the control groups (P ⬍ 0.01). Similarly, intensive
care unit (ICU) admissions were higher in intervention groups than those in the control
groups. Over 80% of patients were subsequently discharged home, and in-hospital
death occurred in 3.6 to 7.7% of patients (Table 1).
For all intervention patients admitted to hospital through emergency departments
(ED), respiratory virus testing (both standard and rapid PCR) was ordered while patients
were in the ED. The tests were ordered a median of 3.8 h and 3.2 h before separation
from the ED for standard PCR and rapid PCR groups, respectively. The median ED LOS
of the two groups (prior to hospital admission) were roughly comparable, namely, 6.8
h for standard PCR and 7.2 h for the rapid PCR.
Twenty-two percent of patients receiving the standard PCR and 36.4% in the rapid
PCR group were positive for at least one respiratory virus. The overall median TAT was
significantly shorter for rapid PCR compared to standard multiplex PCR (2.3 h versus
27.4 h, P ⬍ 0.01). Significantly more patients were discharged from the hospital before
test results became available in the standard PCR group than in the rapid PCR group
(18.9% versus 2.2%; P ⬍ 0.01) (Table 2). Of these discharged patients, the results of
19.4% (n ⫽ 35) in the standard PCR and 11.1% (n ⫽ 3) in the rapid PCR groups
eventually came back positive for at least one respiratory virus.
Primary outcome. Table 3 presents the results of median regression for the main
and subgroup analyses. In the adjusted analyses, we controlled for multiple factors
potentially affecting LOS (Table S1). For the control group, there was no significant
difference in the median LOS between controls 2016 and 2017 (75.3 h versus 78.9 h,
P ⫽ 0.68). For the intervention group, an analysis that included all patients, regardless
of test result outcome, showed no significant difference in the median LOS. Similarly,
for patients with negative results, there was no significant difference in the median LOS.
However, for patients with positive results, the median LOS decreased significantly, by
21.2 h (95% CI, ⫺38.0 to ⫺4.5; P ⬍ 0.01) in the within-intervention-groups analysis and
by 21.5 h (95% CI, ⫺36.8 to ⫺6.2; P ⬍ 0.01) in the DID analysis following the introduc-
tion of rapid PCR.
When the analysis was limited to patients whose test results were returned during
their stay in the hospital, rapid PCR was associated with a significant decrease in the
median LOS, irrespective of test result. Adjusted analysis showed a significant reduction

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TABLE 1 Comparison of demographic and clinical characteristics of intervention and control groups
Data for:
Intervention vs control groups
Intervention group Control group (P value)e
Standard PCR Rapid PCR 2017 Standard PCR vs Rapid PCR vs
Variable (n ⴝ 953) (n ⴝ 1,209) 2016 (n ⴝ 937) (n ⴝ 1,102) control 2016 control 2017
Female, n (%) 480 (50.4) 619 (51.2) 473 (50.5) 565 (51.3) 0.96 0.97
Age (yrs), median (IQR) 75 (62–84) 77 (65–86) 75 (62–84) 76 (64–84) 0.97 0.11

Hospital, n (%) 0.94 0.58

A 434 (45.5) 672 (55.6) 431 (46.0) 589 (53.5)
B 340 (35.7) 205 (17.0) 327 (34.9) 198 (18.0)
C 179 (18.8) 332 (27.5) 179 (19.1) 315 (28.6)

Time of day of hospital admission, n (%) ⬍0.01 0.95

7 a.m.–7 p.m. 598 (62.8) 866 (71.6) 657 (70.1) 788 (71.5)
7 p.m.–7 a.m. 355 (37.2) 343 (28.4) 280 (29.9) 314 (28.5)

Day of week of admission, n (%) 0.99 0.24

Weekdays 700 (73.5) 920 (76.1) 688 (73.4) 815 (74.0)
Weekends 253 (26.5) 289 (23.9) 249 (26.6) 287 (26.0)

Source of referral, n (%)

Emergency department 926 (97.2) 1,196 (98.9) 874 (93.3) 1,007 (91.4) ⬍0.01 ⬍0.01
Othera 27 (2.8) 13 (1.1) 63 (6.7) 95 (8.6)

Intensive care admission, n (%) 110 (11.5) 113 (11.0) 41 (4.4) 52 (4.7) ⬍0.01 ⬍0.01

Mode of separation, n (%) 0.68 0.09

Discharged by hospital 805 (84.5) 972 (80.4) 805 (85.9) 924 (83.9)
Transferred/discharged at own risk 110 (11.5) 171 (14.1) 98 (10.5) 125 (11.3)
Died in hospital 38 (4.0) 66 (5.5) 34 (3.6) 53 (4.8)

Charlson comorbidity index, median (IQR) 1 (0–2) 1 (0–2) 1 (0–2) 1 (0–2) 0.01 0.13

Principal diagnosis, n (%) ⬍0.01 ⬍0.01

Influenza and pneumonia 527 (55.3) 758 (62.7) 276 (29.5) 358 (32.5)
Chronic lower respiratory diseases 229 (24.0) 258 (21.3) 293 (31.3) 307 (27.9)
Acute upper respiratory infections 53 (5.6) 45 (3.7) 75 (8.0) 95 (8.6)
Other acute lower respiratory infectionsb 70 (7.4) 51 (4.2) 64 (6.8) 62 (5.6)
Lung diseases due to external agentsc 36 (3.8) 43 (3.6) 97 (10.4) 91 (8.3)
Other respiratory diseasesd 38 (4.0) 54 (4.5) 132 (14.1) 189 (17.2)
aMedical practitioner, outpatient, day procedure center, community health.
bICD-10-AM: J20 to J22.
cICD-10-AM: J60 to J70.

dICD-10-AM: J30 to J39; J85 to J84; J85 to J86; J90 to J94, and J95 to J99.

eComparisons were made using Pearson’s chi-square test for categorical variables and the Mann-Whitney test for continuous variables, and the P value shows the

distribution of a given variable across groups.

in the LOS both in the within-intervention-groups analysis (median, ⫺22.8 h; 95% CI,
⫺33.1 to ⫺12.5; P ⬍ 0.01) and in the DID analysis (median, ⫺25.5 h; 95% CI, ⫺38.1 to
⫺12.9; P ⬍ 0.01) following the introduction of rapid PCR. For patients with positive test
results, the median LOS decreased by 27.9 h (95% CI, ⫺45.2 to ⫺10.5; P ⬍ 0.01) in the
within-intervention-groups analysis and by 33.4 h (95% CI, ⫺49.5 to ⫺17.3; P ⬍ 0.01) in
the DID analysis following the introduction of rapid PCR (Table 3). Of patients in the
rapid PCR group, the median LOS of patients who received an additional standard
multiplex PCR panel was almost 1 day longer than that of those not requiring the
multiplex PCR.
Secondary outcome. Figure 2 compares utilization of five common microbiology
tests by intervention and control groups during the postimplementation versus base-
line. Overall, after adjusting for confounding variables, patients in the rapid PCR group
had significantly fewer blood culture, sputum culture, and respiratory bacterial and viral
serology tests compared to standard PCR (Fig. 2A). For positive test results, patients in
the rapid PCR group had significantly fewer sputum culture, and respiratory bacterial

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TABLE 2 Test results and timeliness of care among intervention groups

Results for:
Standard PCR Rapid PCR
Variable (n ⴝ 953) (n ⴝ 1,209)
Positive test result to at least one virus, n (%) 210 (22.0) 440 (36.4)

Virus detected, n (%)

Influenza A/B 24 (1.3) 405 (17.7)
Respiratory syncytial virus 38 (2.0) 36 (1.6)
Rhinovirus 70 (7.4)
Coronavirus 36 (3.8)
Human metapneumovirus 26 (2.7)
Parainfluenza virus 22 (2.3)
Adenovirus/enterovirus/bocavirusa 7 (0.4)

Test TAT (h), median (IQR)b

Hospital A 29.8 (25.2–40.6) 1.7 (1.4–2.4)
Hospital B 23.9 (17.4–28.5) 2.6 (1.9–3.9)
Hospital C 29.2 (24.7–41.4) 3.7 (2.9–5.8)
Overall 27.4 (23.0–36.8) 2.3 (1.6–3.7)

Time to sample (h) received at the 5.7 (3.2–17.4) 3.9 (2.1–7.3)

lab from admission, median (IQR)
Time to test result from admission, median (IQR) 40.3 (28.3–52.6) 7.5 (4.5–16.7)
Discharged before a test result became 180 (18.9) 27 (2.2)
available, n (%)
aAdenovirus ⫽ 3, bocavirus ⫽ 3, and enterovirus ⫽ 1.
bTAT, turnaround time; IQR, interquartile range.

and viral serology tests but not fewer blood culture and urine MC&S tests compared to
those in the standard PCR group (Fig. 2B). For negative test results, with the exception
of urine MC&S, there were significantly fewer other tests ordered for the rapid PCR
group compared to those in the standard PCR group (Fig. 2C). In the control group, with
the exception of blood culture, there was no difference in ordering practices over time
(Fig. 2C).

DISCUSSION
In this controlled, quasi-experimental study, we investigated the impact of rapid PCR
testing of influenza A/B and RSV across three hospitals on hospital LOS and related
microbiology test utilization. We found that the introduction of rapid PCR was associ-
ated with significant reductions in the hospital LOS among patients with positive test
results and in the use of other common microbiology tests, including blood culture,
sputum culture, and respiratory bacterial and viral serology tests, compared with those
for patients in the preimplementation period who received standard multiplex PCR
testing.
In our study, the impact of rapid PCR on hospital LOS was statistically significant
among patients with positive test results. This finding is unsurprising, given that
patients can leave the hospital earlier if a bacterial infection has been ruled out. For
patients requiring antiviral therapy, treatment can be started more quickly in patients
with positive results, which may expedite their discharge (21), whereas patients with
negative results are more likely to stay in the hospital, as they may require further
investigation and management. This was consistent with results of a previous U.S. study
(11). Rappo et al. retrospectively assessed the impact of early diagnosis of respiratory
infections using rapid PCR (FilmArray) on the outcomes of over 337 adult patients over
two flu seasons at a tertiary care center in New York, NY, USA, and found a significant
reduction in hospital LOS among influenza-positive patients with rapid PCR (11).
In the analysis that included all patients regardless of test results, there was no
significant difference in LOS between rapid PCR and standard PCR groups. This was
because more patients in the standard PCR group (18.9% versus 2.2%) were discharged
from the hospital even before the test results were available. These patients had a

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 TABLE 3 Median regression analysis showing changes in the median LOS following the introduction of rapid PCR
Change in LOS within the intervention groups (pre to post)a
Unadjusted Adjustedb Adjusted DID analysisb
No. of Median LOS
Variable patients (h [95% CI]) Coefficient (95% CI) P value Coefficient (95% CI) P value Coefficient (95% CI) P value
Intervention group
Regardless of test results
Standard PCR 953 100.9 (96.2 to 109.9) Reference group Reference group Reference group
Rapid PCR 1,209 101.8 (97.1 to 112.8) 0.9 (⫺7.9 to 9.6) 0.85 ⫺6.5 (⫺16.0 to 2.9) 0.18 ⫺8.9 (⫺21.5 to 3.7) 0.17
Positive test results
Standard PCR 210 98.6 (94.5 to 116.9) Reference group Reference group Reference group
Rapid PCR 440 92.9 (81.5 to 98.6) ⫺5.5 (⫺19.9 to 8.8) 0.45 ⫺21.2 (⫺38.0 to ⫺4.5) 0.01 ⫺21.5 (⫺36.8 to ⫺6.2) ⬍0.01
Negative test results

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Standard PCR 743 101.4 (96.0 to 113.0) Reference group Reference group Reference group
Rapid PCR 769 116.2 (103.4 to 122.6) 14.8 (2.4 to 27.1) 0.02 1.4 (⫺10.8 to 13.5) 0.83 ⫺1.2 (⫺14.9 to 12.4) 0.86
Rapid PCR Testing of Adults with Respiratory Illness

Subgroup analysis including only patients

whose test results were returned
during their stay in the hospital
Regardless of test results
Standard PCR 773 126.0 (117.9 to 139.0) Reference group Reference group Reference group
Rapid PCR 1,182 104.0 (98.3 to 114.8) ⫺22.2 (⫺32.5 to ⫺11.9) ⬍0.01 ⫺22.8 (⫺33.1 to ⫺12.5) ⬍0.01 ⫺25.5 (⫺38.1 to ⫺12.9) ⬍0.01
Positive test results
Standard PCR 175 117.5 (100.5 to 142.8) Reference group Reference group Reference group
Rapid PCR 437 93.2 (82.2 to 98.6) ⫺24.3 (⫺42.0 to ⫺6.6) ⬍0.01 ⫺27.9 (⫺45.2 to ⫺10.5) ⬍0.01 ⫺33.4 (⫺49.5 to ⫺17.3) ⬍0.01
Negative test results
Standard PCR 598 129.7 (121.2 to 142.7) Reference group Reference group Reference group
Rapid PCR 745 117.9 (109.6 to 125.2) ⫺11.9 (⫺25.9 to 2.2) 0.09 ⫺17.3 (⫺30.4 to ⫺4.3) ⬍0.01 ⫺19.6 (⫺33.7 to ⫺5.5) ⬍0.01

Control group
2016 937 75.3 (71.0 to 80.5) Reference group Reference group
2017 1,102 78.9 (73.0 to 87.3) 3.2 (⫺5.6 to 12.1) 0.47 1.6 (⫺6.0 to 9.2) 0.68 Not applicable
aA negative coefficient indicates a median decrease in the LOS compared to the reference group.
bAdjusted for age, study hospital, the source of referral, intensive care admission status, mode of separation, Charlson comorbidity index and type of principal diagnosis. DID (difference-in-difference) ⫽ ΔLOS (h) in

intervention group ⫺ ΔLOS (h) in control group.

jcm.asm.org 7
Journal of Clinical Microbiology
Wabe et al. Journal of Clinical Microbiology

FIG 2 Common microbiology test utilization. (A) Regardless of test results, (B) positive test results, (C) negative test results, and (D) control
groups. The middle square shows the odds ratio (OR), and the horizontal line shows the 95% confidence interval (CI) of the OR. The
inclusion of “1” in the 95% CI indicates a nonsignificant difference in the ordering practices between groups. All analyses were adjusted
for baseline variables, including age, study hospital, the source of referral, intensive care admission status, mode of separation, Charlson
comorbidity index, and type of principal diagnosis. MC&S, microscopy, culture, and sensitivity.

shorter LOS compared with that of patients who were discharged after test results were
available, confounding the effect of rapid PCR on hospital LOS. When the analysis was
limited to patients whose test results were returned during their stay in the hospital,
rapid PCR use was associated with a significant reduction in the median LOS, irrespec-
tive of test results.
In a recent large UK study, the use of a molecular point-of-care-test (POCT) resulted
in a reduction in hospital LOS regardless of test results, although the effect was more
noticeable among patients with positive test results (22). Brendish et al. conducted a
pragmatic randomized controlled trial enrolling 720 adult patients (aged ⱖ18 years) at
a large teaching hospital in the United Kingdom (the ResPOC trial). That study assessed
the impact of molecular POCT testing for respiratory viruses compared with referral
laboratory testing and found a significant reduction in hospital LOS by 1.1 days in the
patients receiving POCT. In a subgroup analysis, patients with positive rapid PCR results
had a hospital stay that was an average of 1.7 days shorter than that of patients with
negative results (22).
In contrast to our findings and the results of the ResPOC trial (22) and Rappo et al.
(11), the use of rapid PCR did not decrease hospital LOS in a study by Andrews et al.
(21). The authors conducted a quasi-randomized trial to assess the impact of the
FilmArray respiratory panel as a POCT compared to laboratory-based PCR, serology, or
culture testing on a range of outcomes, including hospital LOS. The study enrolled 545
patients aged ⱖ16 years and presenting with influenza-like illness or other respiratory
tract infections at an Acute NHS Hospital Trust in London, United Kingdom. Interest-
ingly, the authors found an 11% increase in hospital LOS in the rapid PCR group,
although it was not statistically significant. The authors attributed the lack of impact on
LOS to a delay in initiating FilmArray testing. The median time to test result from
admission was 19 h in their study. This was substantially longer than ours (the median
time to test result from admission was 7.5 h), and this may explain the differences
between our findings and those of Andrews et al. (21).

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Rapid PCR Testing of Adults with Respiratory Illness Journal of Clinical Microbiology

The limitation of the rapid PCR (Cepheid Xpert Flu/RSV XC) used in our study is its
inability to diagnose other respiratory viruses. While it can accurately detect influenza
A/B and RSV, other clinically relevant respiratory viruses, such as rhinovirus, coronavirus,
metapneumovirus, and parainfluenza viruses, cannot be detected by our current rapid
PCR method. This means that patients can still be ordered standard multiplex PCR
following the results of rapid PCR if other respiratory viruses are suspected. Our analysis
showed that 20% of the patients in the rapid PCR group also received multiplex PCR,
and their median LOS was almost 1 day longer than that of those not requiring the
multiplex PCR. Other studies implemented multiplex PCR respiratory panel (i.e., our
version of the referral laboratory-based standard PCR) as a POCT test (11, 21, 22),
avoiding the need for further respiratory viral investigations. The introduction of a
broader multiplex PCR as a POCT in the future may offer better outcomes for patients.
Our results show that the utilization of blood culture, sputum culture, and respira-
tory bacterial and virus serology tests was significantly lower among patients tested
with rapid PCR. To the best of our knowledge, no previous studies have studied the
impact of PCR-based rapid tests on other laboratory test utilization in hospitalized
adults. Previous studies that assessed other test ordering practices were conducted
using antigen-based POCT in ED (23). Poehling et al. (13) and Blaschke et al. (14)
reported significantly fewer blood culture tests when POCT was used, similar to our
findings. Other studies have reported fewer biochemistry tests, including full blood
count (14, 15), C-reactive protein (15), and urinalysis (14, 15), when POCT was used.
Our findings have some important implications. Reducing hospital LOS has large
economic benefits. Cost savings for hospitals can be achieved through avoidance of
unnecessary hospital resource utilization, including that of supplementary laboratory
and imaging testing (24, 25). In a Spanish study by Soto et al., rapid PCR decreased the
isolation time of hospitalized patients by 23.7 h, which resulted in a cost reduction of
$70 per hospitalized patient (24). A half-day reduction in hospital LOS in one U.S. study
was associated with an estimated annual savings of $500 to 900 million (26). Rapid
diagnostic testing can have safety implications too. Reducing LOS in hospital leads to
a reduction in hospital-acquired infections, including the disruption of Clostridium
difficile transmission (27). According to a large U.S. study, reducing LOS by about 1 day
lowers the risk of 30-day readmission through a reduction in infection risk (28).
The strengths of this study include its relatively large sample size, its utilization of
real-world routinely collected clinical practice data, and multiple-center inclusion of
three teaching hospitals, which enhances the generalizability of our findings. Unlike
several prior studies (11, 12, 14, 29), we applied a quasi-experimental, controlled study
design that allowed us to account for secular trends or sudden changes over time (30).
Moreover, we used a number of strategies to reduce the potential impact of confound-
ing variables. We used matching on key baseline variables to identify comparable
control groups. To reduce seasonal effects, a similar time frame for both groups (i.e.,
July to December) was selected. To decrease the potential for selection bias, all
hospitalized adults tested for influenza and RSV during the study period were included.
Finally, we conducted within-intervention-groups and DID analyses, adjusting for dif-
ferences in several baseline patient and clinical characteristics.
There are some limitations to consider when interpreting the findings of the current
study. Given that this study was not a randomized controlled trial, our findings should
not be interpreted as a cause and effect relationship. Due to a lack of randomization,
there is always a risk of unidentified or hidden confounders in a quasi-experimental
study (31). While our results indicated that the use of rapid PCR was associated with
fewer other microbiology test utilizations, because of lack of data on regarding the time
when the clinicians ordered the tests, our study did not examine whether the larger
number of tests ordered with the standard PCR was associated with orders after results
were returned to the patient. As we did not have access to treatment data, we were
unable to assess the potential impact of rapid PCR testing on clinical decision making,
including whether it influenced the decision to initiate antiviral therapy following
positive results or to deescalate its use if patients were already using the medication

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Wabe et al. Journal of Clinical Microbiology

and the test result returned negative. Although our current study result suggests
economic benefits of rapid PCR testing, a formal health economic study is required.
Conclusion. The introduction of rapid PCR testing of influenza and RSV viruses for
hospitalized adults was associated with a significant reduction in hospital LOS for
patients with positive results and a significant reduction in microbiology test use
compared with those for patients who received standard multiplex PCR testing. These
findings suggest there may be economic and patient outcome benefits from this
intervention that should be tested in a future cost-effectiveness study.

SUPPLEMENTAL MATERIAL
Supplemental material for this article may be found at https://doi.org/10.1128/JCM
.01727-18.
SUPPLEMENTAL FILE 1, PDF file, 0.1 MB.

ACKNOWLEDGMENTS
The study was part of a partnership project funded by the National Health and
Medical Research Council (NHMRC) of Australia (project grant APP1111925).

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