Is the Presence of Actinomyces spp. in Blood Culture Always Significant?

Abstract

The isolation of
Actinomyces spp
. from sterile clinical samples is traditionally regarded as significant. We reviewed the demographics, clinical risk factors and outcomes of patients with
Actinomyces spp
. isolated from blood culture in our NHS Hospital Trust and found that this is not necessarily the case.

Full text

Is the Presence of Actinomyces spp. in Blood Culture Always
Significant?
Anna Jeffery-Smith, Caoimhe Nic-Fhogartaigh, Michael Millar
Department of Infection, Barts Health NHS Trust, London, United Kingdom
The isolation of Actinomyces spp. from sterile clinical samples is traditionally regarded as significant. We reviewed the demo-
graphic characteristics, clinical risk factors, and outcomes of patients with Actinomyces spp. isolated from blood cultures in our
NHS Trust and found that this is not necessarily the case.
Actinomyces spp. are Gram-positive anaerobic bacilli found col-
onizing the human oropharynx, gastrointestinal tract, and
urogenital tract (1). Immunosuppression and local tissue damage,
allowing entry of Actinomyces spp., are recognized risk factors for
the development of actinomycosis. Actinomycosis is more com-
mon in men, except for pelvic disease associated with contracep-
tive intrauterine devices (IUDs) (2).
Orocervicofacial actinomycosis related to dental procedures
and chronic dental infections represents 50% of cases, with tho-
racic and abdominal actinomycosis accounting for approximately
40% (3). Central nervous system, bone, and cutaneous infections
have been reported (4), but hematogenous spread is rare (1,5).
Treatment of actinomycosis involves the combination of surgical
drainage and prolonged courses of antibiotic therapy. Actinomyces
spp. are susceptible in vitro to several antimicrobials, including
penicillins, macrolides, and tetracyclines; penicillins are the drugs
of choice (2). Recent studies have suggested that, with effective
debridement, the course of antibiotic therapy can be reduced
without complications (6).
Traditionally, isolation of Actinomyces spp. from sterile clinical
specimens is always viewed as significant (7). Since the introduc-
tion of 16S rRNA gene sequencing and matrix-assisted laser de-
sorption ionization–time of flight mass spectrometry (MALDI-
TOF MS) in our laboratory, we have noted an increase in the
identification of Actinomyces spp. from blood cultures. Although
16S rRNA gene sequencing was used selectively from 2004, it was
with the introduction of MALDI-TOF MS in 2009 that all isolates
were routinely identified. There was a crossover period in which
the results of the technologies were compared. Currently, we use
16S rRNA gene sequencing when MALDI-TOF MS does not pro-
vide an answer and there are clinical indications for making an
accurate identification. In the current review, only 10 of the 60
patients from whom Actinomyces spp. were isolated were consid-
ered by the attending physicians to have clinical evidence of acti-
nomycosis requiring treatment. This finding raises questions
about the significance of such isolates.
Isolates of Actinomyces spp. from blood cultures from patients
in our NHS Trust were reviewed. Our NHS Trust is an organiza-
tion comprising five secondary and tertiary care hospitals provid-
ing care to a region of East London. Demographic and outcome
information was collected from electronic patient records. Specif-
ically, we looked for evidence of disease attributable to actinomy-
cosis, as well as details of risk factors, investigations, and treat-
ments. Outcomes were reviewed, with particular attention to
hospital readmission and death.
The records were reviewed for recognized clinical risk factors
for Actinomyces infection, i.e., IUD use, diabetes mellitus, immu-
nosuppression, local tissue damage related to trauma (including
people who inject drugs [PWID]), inflammatory conditions, sur-
gery, or irradiation (2). Age between 20 and 60 years and male sex
are also risk factors; these nonclinical risk factors were not in-
cluded in the statistical analysis because of the small size of the
group and the strong covariance of these risk factors with clinical
risk factors.
Fisher’s exact test and the Mann-Whitney Utest were used in
the statistical analysis of differences between the groups (treated
versus untreated patients). The project was endorsed by the Clin-
ical Effectiveness Department at Barts Health NHS Trust. Ethical
approval was not required.
Actinomyces spp. were isolated from 61 blood cultures from 60
patients between October 2009 and December 2014. During this
period, 154,573 blood cultures were submitted to the laboratory
for processing. A total of 18,984 organisms were isolated, with a
number of cultures containing multiple organisms. Patients were
separated into two groups on the basis of whether they received
treatment as a result of the identification of Actinomyces spp.
Treatment was defined as documentation of the isolate and rec-
ommendation of a prolonged course of appropriate antibiotic
therapy and/or surgical intervention.
Patients were between 1 day and 95 years of age. Ten patients,
with ages between 35 and 89 years, fulfilled the case definition for
treatment of Actinomyces spp. There were 33 male patients, 5 of
whom received treatment, and 27 female patients, 5 of whom
received treatment.
Patients were under the care of a wide range of specialties at the
time of blood culture sampling. Eighteen of the positive blood
cultures were sent from accident and emergency, 11 from pediat-
rics and neonatology, 6 from intensive care, 20 from a range of
Received 1 December 2015 Returned for modification 17 December 2015
Accepted 19 January 2016
Accepted manuscript posted online 27 January 2016
Citation Jeffery-Smith A, Nic-Fhogartaigh C, Millar M. 2016. Is the presence of
Actinomyces spp. in blood culture always significant? J Clin Microbiol
54:1137–1139. doi:10.1128/JCM.03074-15.
Editor: P. Bourbeau
Address correspondence to Anna Jeffery-Smith,
anna.jeffery-smith@bartshealth.nhs.uk.
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
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April 2016 Volume 54 Number 4 jcm.asm.org 1137Journal of Clinical Microbiology

medical specialties, including elderly care, hematology, and renal
medicine, and 6 from surgical specialties, including maxillofacial
surgery, obstetrics, and orthopedics. A broad range of comorbidi-
ties, including cognitive impairment, hypertension, hepatitis C,
and stroke, were documented. It was clear for all except one pa-
tient that blood cultures were taken at a time of acute changes that
could be attributed to infection.
A total of 87% of isolates (53/61 isolates) were identified to the
species level. Eight of those identifications were made by 16S
rRNA PCR. All of those samples were also subjected to MALDI-
TOF MS, which confirmed the 16S rRNA PCR results for all ex-
cept two samples, for which there was no reliable identification
from MALDI-TOF MS. The remaining samples were identified by
MALDI-TOF MS alone. Four isolates gave two possible Actinomy-
ces sp. identifications, i.e., one Actinomyces viscosus or Actinomyces
naeslundii, one A. naeslundii or Actinomyces oris, and two A. vis-
cosus or A. oris. The MALDI-TOF MS scores are no longer avail-
able for analysis. No particular distribution of species between the
groups was identified (Table 1).
There was a difference in the median time to positivity in the
treated and untreated groups (36.5 h [range, 18 to 72 h] and 46 h
[range, 26 to 120 h], respectively), but this difference did not reach
statistical significance (two-tailed Mann-Whitney Utest, P⫽
0.11).
A second isolate was identified in 4 of the 10 cultures (40%) in
the treated group that were positive for Actinomyces spp., com-
pared with 15 of the 51 cultures (29%) from the 50 patients in the
untreated group. A wide range of organisms were identified, in-
cluding Corynebacterium spp., oral Streptococcus spp., and coagu-
lase-negative staphylococci. In addition to those organisms, which
are classically seen as contaminants in blood cultures, Staphylococ-
cus aureus,Enterococcus faecalis, and Escherichia coli were identi-
fied with the Actinomyces isolates; in all of those cases, the patients
were treated for those organisms even if no action was taken with
respect to the Actinomyces spp.
Seven of the 10 patients who received treatment had recog-
nized clinical risk factors (Table 2). Two patients had two risk
factors, i.e., HIV and PWID. In the untreated group, 14 patients
had risk factors and 4 patients had more than one risk factor, i.e.,
PWID with alcohol excess, leukemia and chemotherapy with a
transplant and an inflammatory condition, a renal transplant with
leukemia and chemotherapy, and an inflammatory condition and
surgery. Statistical analysis using Fisher’s exact test demonstrated
a significant difference in the presence of risk factors between the
two groups (two-tailed P⫽0.0116).
The 10 patients who received treatment had their disease cat-
egorized as follows: pulmonary actinomycosis, 3; abdominal acti-
nomycosis, 1; dental actinomycosis, 1; multiple sites, 1; soft tissue
disease, 3; not categorized, 1. One patient was not investigated for
a source of infection because of the life-limiting nature of his co-
morbidities and prioritization of palliative care input. Six patients
received a combination of antibiotic therapy and drainage/de-
bridement, and the remaining four received antibiotic therapy
alone.
In the treated group, five patients were discharged either dur-
ing or following a prolonged antibiotic course. One patient de-
clined long-term antibiotic therapy, having received 10 days of
therapy following debridement of a dental abscess. She did not
re-present with any complications. Three patients were readmit-
ted, one within 30 days and two within 6 months. Two of those
readmissions were due to ongoing infection issues attributable to
actinomycosis. One patient died as a result of chest sepsis during
admission. Another patient died as a result of complications re-
lated to a different underlying condition.
In the untreated group, 43 patients were discharged following
the positive blood culture results, without apparent complications
related to actinomycosis. Two patients were recalled and two had
their admissions prolonged for assessment. Following clinical re-
view, those patients were deemed to have no evidence of actino-
mycosis and were discharged without treatment.
Four patients from the untreated group had another hospital
admission within 30 days and an additional nine patients in the
subsequent 6 months. None of those admissions could be clearly
attributed to untreated actinomycosis. Seven deaths occurred in
the untreated group. Five patients died during the same episode as
the positive blood culture results, as a result of progression of an
underlying disease, and one died 11 months later as a result of
urosepsis, having been well in the interim. For one patient, there
was no documentation related to the death.
In this retrospective analysis of clinical correlates associated
with the isolation of Actinomyces spp. from blood cultures, the
majority of patients were not treated for actinomycosis, with no
apparent negative impact on clinical outcomes. We hypothesize
that, prior to the introduction of MALDI-TOF MS and 16S rRNA
TABLE 1 Actinomyces spp. isolated, by group
Species
No.
Total
cohort
Treated
group
Untreated
group
Actinomyces odontolyticus 14 2 12
Actinomyces oris 8
a,b
17
a,b
Actinomyces naeslundii 8
a,c
1
c
7
a
Actinomyces sp. undifferentiated 8 1 7
Actinomyces neuii 71 6
Actinomyces turicensis 62 4
d
Actinomyces viscosus 6
b,c
3
c
3
b
Actinomyces europaeus 21 1
a
One isolate was identified to a high percentage as either A. oris or A. naeslundii.
b
One isolate was identified to a high percentage as either A. oris or A. viscosus.
c
One isolate was identified to a high percentage as either A. naeslundii or A. viscosus.
d
Includes two separate isolates from the same patient.
TABLE 2 Clinical risk factors, by group
Risk factor
No.
Treated group Untreated group
Diabetes mellitus 0 3
Local tissue trauma (including PWID) 3 2
Recent surgery 1 1
Inflammatory condition 1 6
Chronic infection 1 1
Immunosuppression
HIV 2 0
Leukemia and chemotherapy 1 2
Transplant 0 2
Alcohol excess 0 2
More than one risk factor 2 4
Jeffery-Smith et al.
1138 jcm.asm.org April 2016 Volume 54 Number 4Journal of Clinical Microbiology

PCR techniques for identifying organisms to the species level di-
rectly from cultures, such organisms would have been dismissed
as contaminants such as Corynebacterium spp. or Propionibacte-
rium spp. MALDI-TOF MS has been shown to perform well for
identification to the genus level, providing reassurance that these
results accurately represent the organisms present (8).
The isolation of Actinomyces spp. from blood cultures from
patients for whom there is no evidence of clinical disease raises the
question of whether these organisms are blood culture contami-
nants or represent transitory bacteremia caused by translocation
from commensal sites. Blood culture collection procedures are
standardized in our NHS Trust, which has seen a decrease in the
number of blood cultures growing organisms that are classically
viewed as skin contaminants (9). Historically, Actinomyces spp.
have not been considered part of the human cutaneous flora.
However, the application of recent molecular methods suggests
that the flora may be more diverse than previously recognized and
Actinomyces spp. may be components at sites such as the antecu-
bital fossa in some individuals (10). The susceptibility of these
potential cutaneous Actinomyces spp. to topical antibacterial
washes used prior to procedures remains undetermined.
Alternatively, we may be detecting transient bacteremia asso-
ciated with periods of translocation from the oropharyngeal or
bowel mucosa. This phenomenon is seen with multiple mucosal
organisms in teething children and is associated with procedures
such as colonoscopy (11). Such bacteremia, although transient,
can cause significant morbidity through the sepsis response and
seeding. Classically, Actinomyces spp. cause infection at sites of
local tissue invasion; hematogenous spread and disseminated dis-
ease are rare (1,2).
In our study of 60 patients from whom Actinomyces spp. were
isolated, only 10 received treatment for actinomycosis. The main
difference between the patients who received treatment and those
who did not was the presence of clinically recognized risk factors.
This finding supports the use of such risk factors as part of the
clinical assessment to establish the significance of Actinomyces
spp. isolated from blood cultures. It also highlights the impor-
tance of interpreting results in the context of the patient’s clinical
situation and background.
One of the strengths of our study is the fact that our laboratory
performs unbiased identification of isolates, as the system to iden-
tify organisms grown from cultures is not influenced by clinical
findings. A weakness is the fact that our data on the progress of the
patients during and after hospital admission are based on infor-
mation in the electronic health records, which may not be com-
plete. In addition, only repeat attendances within the NHS Trust
could be recorded, unless admission to another NHS Trust was
documented in the records. Studies related to the analysis of blood
culture isolates suffer from an inherent sampling bias; blood cul-
tures are, and should be, performed only for patients for whom
there are concerns regarding systemic infection.
In this era of rapid development and application of diagnostic
techniques, we are identifying a multitude of organisms from a
variety of patient sample types (12). This expansion in diagnostics
needs to be matched with an understanding of the clinical signif-
icance, to ensure appropriate therapy for patients. Further re-
search to look more closely at Actinomyces spp. isolated from other
culture types will help to elucidate the true significance of these
isolates.
ACKNOWLEDGMENT
We thank David Ball for help with data collection.
FUNDING INFORMATION
This research received no specific grant from any funding agency in the
public, commercial, or not-for-profit sectors.
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Significance of Actinomyces spp. in Blood Culture
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