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C A S E R E P O R T Open Access
Actinomyces neuii: a case report of a rare
cause of acute infective endocarditis and
literature review
Wei-Teng Yang
1*
and Matthew Grant
2
Abstract
Background: Infective endocarditis caused by Actinomyces spp. is extremely rare. However, cases by new species of
Actinomyces have been increasingly reported due to advances in laboratory techniques, and many of these species
do not cause classic presentations of actinomycosis. Actinomyces neuii is reported to have a tendency to cause
endovascular infection. The course of infective endocarditis caused by Actinomyces spp. is usually indolent.
Case presentation: A 61-year-old man with history of infective endocarditis, end stage renal disease, and
monoclonal gammopathy was admitted for an abrupt fever, confusion, dysarthria, and facial droop after
hemodialysis. Echocardiogram showed vegetations on both the aortic and mitral valves. Two sets of blood culture
grew A. neuii. Brain MRI showed multiple bilateral cerebral infarcts consistent with septic emboli. The patient
recovered after valvular surgery and prolonged intravenous and oral antibiotic therapy.
Conclusions: This case illustrates an unusually acute presentation of A. neuii infective endocarditis. As with other
Gram-positive bacilli, Actinomyces spp. isolates are often regarded as a result of contamination. One should keep it
in mind as a cause of infective endocarditis in vulnerable patient populations.
Keywords: Actinomyces neuii,Actinomyces, Infective endocarditis
Background
Actinomyces spp. classically cause human actinomycosis,
an indolent granulomatous infectious disease character-
ized by orocervicofacial, thoracic, abdominopelvic, or
central nervous system abscess formation and draining
sinuses [1]. Many novel Actinomyces species have been
reported in recent decades with the advance in labora-
tory identification methods, and are associated with a
wide range of infection at many body sites [2]. However,
infective endocarditis by Actinomyces spp. is still
extremely rare. We report a patient who presented with
an acute Actinomyces neuii (A. neuii) aortic and mitral
valve endocarditis complicated by aortic root abscess
and septic cerebral emboli. He was treated successfully
with surgery and prolonged antibiotics. We then present
a review of published Actinomyces spp. endocarditis
cases following a systematic literature search.
Case presentation
Clinical presentation and diagnostic findings
A 61 year-old man was admitted with a 103 ° F fever, con-
fusion, weakness and slurred speech after hemodialysis.
He had a history of viridans streptococcal mitral valve
endocarditis, end stage renal disease on hemodialysis,
atrial fibrillation not on anticoagulation due to GI bleed-
ing, and monoclonal gammopathy of undetermined sig-
nificance. He had a productive cough for a week without
any identifiable sick contact. Physical examination was
notable for an agitated edentulous man with a left central
facial palsy, severe dysarthria, and a systolic murmur at
the left lower sternal border. His lungs were clear to aus-
cultation and there was no stigmata of endocarditis.
The patient was initially treated empirically for pneu-
monia and worked up for stroke. However, the treat-
ment plan was quickly modified when a transthoracic
echocardiogram on day two of admission revealed two
echogenic structures consistent with vegetations: 0.4 ×
0.4 cm on the anterior leaflet of the mitral valve, and the
other 0.7 × 1.8 cm attached to left coronary cusp of the
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reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
* Correspondence: Wei-Teng.Yang@ynhh.org
1
Department of Internal Medicine, Yale New Haven Health Bridgeport
Hospital, 267 Grant Street, Bridgeport, CT 06610, USA
Full list of author information is available at the end of the article
Yang and Grant BMC Infectious Diseases (2019) 19:511
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aortic valve (Fig. 1). There was also thickening of the
aortic root suggestive of abscess formation. Two sets of
blood culture grew Gram-positive rods after 37.5 h incu-
bating in anaerobic bottles (Fig. 2), and after 86 h in aer-
obic bottles. The organism was identified as A. neuii by
MALDI-TOF MS on day five of admission. Serial brain
MRI scans revealed multiple bilateral infarcts on day
two with increased number of infarcts and a small focus
of hemorrhage on day five. The patient was diagnosed
with infective endocarditis by A. neuii complicated by
aortic root abscess and presumed cerebral septic emboli.
Treatment and outcome
The patient was initially treated with vancomyin and pi-
peracillin/tazobactam until A. neuii was identified. Subse-
quently, he was treated with ampicillin and gentamicin for
two days, followed by ampicillin for the rest of his
hospitalization. The choice of ampicillin was based on a
large series that studied susceptibility to antibiotics of Ac-
tinomyces species [3], and a previously successfully treated
A. neuii endocarditis case [4]. Antibiotic susceptibility was
not tested for our patient because he responded to the
treatment well, and repeat blood cultures were all nega-
tive. A CT angiography of the brain and neck on day six
ruled out mycotic aneurysm. It was concluded that the
risk of further septic embolization outweighed the risk of
intracranial hemorrhage, and the patient underwent aortic
valve replacement, debridement of aortic root subannular
abscess, mitral valve repair, and repair of a fistula between
the aorta and left atrium on hospital day fourteen. A 2.5 ×
0.6 cm vegetation on the aortic valve and a vegetation on
the mitral chordae tendineae were removed. There was no
microscopic evidence of bacterial elements on the aortic
valve based on histopathology with Gram stain, and cul-
ture did not grow any organisms. The patient’spost-
operative course was complicated by shock requiring
intraaortic balloon pump, and a cardiac arrest from ven-
tricular fibrillation 10 days after surgery. He recovered
without further neurological deterioration, and was dis-
charged to a nursing facility two months after heart sur-
gery. He received 12 weeks of IV ampicillin followed by
11 months of oral doxycycline.
One year after the diagnosis of A. neuii endocarditis,
while on chronic doxycycline, the patient had a fever
and a bacteremia with coagulase negative Staphylococcus
and group B Streptococcus. The bacteremia was sterilized
after the initiation of antibiotic therapy and there was no
growth from subsequent blood cultures. Transthoracic
echocardiogram showed a small, mobile echogenic dens-
ity on the non-coronary cusp of the bioprosthetic aortic
valve. The patient refused to undergo transesophageal
echocardiogram to further evaluate the prosthetic valve,
so he was treated empirically for possible prosthetic
valve endocarditis. The patient was cured from infection
after two weeks of IV vancomycin and gentamicin,
followed by four weeks of IV vancomycin. He had been
taking oral doxycycline in addition to his IV antibiotics.
The patient eventually died of a sudden cardiac arrest
after hemodialysis. This was 15 months after the diagno-
sis of A. neuii infective endocarditis, and four weeks
after discontinuation of oral doxycycline. The family de-
clined autopsy.
Literature review
Primary infective endocarditis caused by Actinomyces
spp. is rare. After PubMed (search term ((actinomyces
spp) OR actinomyces) AND ((infective endocarditis) OR
endocarditis)) and additional bibliographical search, we
found 26 human cases dating back to 1939 (Table 1),
after excluding four reports, two with bacteria that have
been subsequently reclassified to different genera [29,
30], one report with possible direct extension of pul-
monary actinomycosis to the endocardium [31], and one
with primary IUD-associated actinomyosis and second-
ary endocarditis [32]. Cases were reported at all ages (6–
87 years old). Two thirds of patients were men. The
AB
Fig. 1 Transthoracic echocardiogram showed two vegetations on the aortic and mitral valves. Legend: Vegetations on the aortic valve (panel a)
and the mitral valve (panel b) were pointed by arrows
Yang and Grant BMC Infectious Diseases (2019) 19:511 Page 2 of 7
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most commonly identified species were A. israelii (19%)
and A. viscosus (15%). Twenty-two cases involved left-
sided valves (mitral 9; aortic 5; prosthetic aortic 3; both
mitral and aortic 4; undetermined 1). Risk factors in-
cluded valvular disease (41%), poor dental hygiene or
dental procedure (36%), and prosthesis (14%). All four
right-sided cases were associated with intravenous drug
use [17,19,22,25].
Most left-sided endocarditis patients had indolent
courses. This did not seem to vary over time. However,
the mortality and complications have improved signifi-
cantly over time. Five of eight patients reported before
1990 died and five had embolic events (brain, spleen,
kidneys, small bowel and skin), whereas only two of 14
cases reported after 1990 died, and only one had emboli
to skin. Despite temporal courses of a subacute endocar-
ditis, where stigmata of endocarditis are more common,
only one report described Roth’s spots [27]. It is unclear
whether this was related to virulence factors from Acti-
nomyces spp., or simply the rarity of these complications
[33]. Right-sided endocarditis cases had more acute and
fulminant courses, and were all complicated by septic
emboli to the lungs. Two (50%) of them had polymicro-
bial endocarditis [19,25], which might have contributed
to more complicated clinical courses. All four right-
sides cases survived and all were reported after the
year of 2000. Irrespective of the side of endocarditis,
most patients were treated with a prolonged course
of penicillin or β-lactam antibiotics. Four cases had
surgery (three aortic valves [4,13,18]andoneEusta-
chian valve [22], an embryologic remnant of the valve
of the inferior vena cava).
Two cases of infective endocarditis by A. neuii were
previously reported [4,24]. Both were in older men
with preexisting aortic valvular anomalies (one had a
bicuspid valve and the other a prosthetic valve). Both
presented with subacute endocarditis, large aortic veg-
etations (2 cm) and root abscesses. The patient with a
native valve underwent surgery [4]. Both patients
were cured from the infection. One was initially
treated with ampicillin, then ceftriaxone due to inter-
stitial nephritis, and finally doxycycline for 9 months
[4]. The other was treated with penicillin, followed by
amoxicillin for 12 months [24].
Discussion and conclusion
Infections caused by Actinomyces species, including clas-
sic actinomycosis and a range of other infections, usually
have indolent courses and favorable outcomes [2]. This
pattern was also supported by our review of endocarditis
patients. Actinomyces species are also very susceptible to
antibiotics, except for metronidazole [3,34]. Such sus-
ceptibility to antibiotics, along with advances in diagno-
sis and management of infective endocarditis, likely
contributed to the temporal drop of mortality and sys-
temic complication rates observed from our literature
review. Therefore, it was unexpected for our patient to
present with an acute course and severe complications.
Little is known about the virulence properties of Actino-
myces spp. [2], but we hypothesize that the valvular
damage from previous endocarditis and relative immune
deficiency from his end stage renal disease and mono-
clonal gammopathy may have weakened our patient’s
host defense mechanism, and consequently led to a
Fig. 2 Gram stain morphology of A. neuii bacteria. Legend: A. neuii bacteria were shown as small, Gram- positive rods. They are non-filamentous
and do not produce sulfur granules seen commonly with other Actinomyces species
Yang and Grant BMC Infectious Diseases (2019) 19:511 Page 3 of 7
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Table 1 Review of 26 previously published primary infective endocarditis cases caused by Actinomyces species
Author Year Sex Age Duration of
symptoms
Valve(s) Predisposing
factor(s)
Organism Diagnosis Therapy Complication Outcome
Uhr [5] 1939 M 24 1 month MV, AV None Actinomyces
bovis
Autopsy Sodium iodide Septic emboli (lungs, small
intestine, kidneys)
Died
Beamer [6] 1945 M 55 9 months MV, AV Dental caries Actinomyces
graminis
Autopsy None Septic emboli (spleen,
kidneys, brain)
Died
Mac Neal [7] 1946 M 39 6 weeks MV Heart murmur Actinomyces
septicus
Clinical PCN Septic emboli (skin, mucosa,
brain)
Survived
Wedding [8] 1947 M 37 NA MV Rheumatic heart Actinomyces
spp.
Clinical Sulfathiazole Septic emboli (spleen, ileum,
kidneys, mucosa, brain)
Died
Wedding [8] 1947 F 71 NA AV Rheumatic heart Actinomyces
spp.
Autopsy None NA Died
Walters [9] 1962 F 43 2 months MV Rheumatic heart.
Dental caries
Actinomyces
bovis
Clinical PCN Septic embolic (mesentery,
skin)
Survived
Dutton [10] 1968 M 6 NA MV Rheumatic heart Actinomyces
israelii
Autopsy PCN CHF. Arrhythmia Died
Gutschik
[11]
1976 M 70 5 months Left
side
Dental abscess Actinomyces
viscosus
Clinical PCN Aphasia. Diplopia. CHF Survived
Lam [12] 1993 M 65 4 weeks MV, AV Rheumatic heart.
Endocarditis history
Actinomyces
israelii
Clinical PCN None Survived
Moffatt [13] 1996 M 48 > 2 weeks AV None Actinomyces
meyeri
Clinical
and
surgical
PCN. Surgery CHF. Aortic root abscess Survived
Hamed [14] 1998 M 81 2–3 weeks AV Poor dental
hygiene
Actinomyces
viscosus
Clinical PCN allergy. Ceftizoxime and ceftriaxone None Survived
Huang [15] 1998 F 55 NA MV None Actinomyces
meyeri
Clinical Ampicillin/sulbactam None Survived
Mardis [16] 2001 M 38 2 weeks MV None Actinomyces
viscosus
Clinical Vancomycin/gentamicin/cefotaxime ➔PCN Cutaneous emboli Survived
Westling
[17]
2002 F 40 2 weeks TV IVDU. Endocarditis
history
Actinomyces
funkei
Clinical Cefuroxime ➔cefuroxime/ clindamycin/rifampicin ➔
ceftriaxone ➔clindamycin
Pulmonary emboli Survived
Julian [18] 2005 F 43 2 weeks AV Bicuspid AV. Dental
cleaning
Actinomyces
viscosus
Clinical Ampicillin/azithromycin ➔vancomycin/gentamicin/
ceftriaxone ➔surgery ➔vancomycin/ceftriaxone
CHF Survived
Oh [19] 2005 M 33 2 months TV IVDU. Dental
procedure
Actinomyces
odontolytica
Clinical PCN/metronidazole Pulmonary emboli Survived
Cohen [4] 2007 M 68 3 weeks AV Bicuspid AV. Dental
procedure
Actinomyces
neuii
Clinical Ampicillin/gentamicin/ceftriaxone ➔ampicillin ➔
ceftriaxone ➔doxycycline
Aortic root abscess Survived
Oddo [20] 2007 M 34 NA MV Rheumatic heart.
Endocarditis history
Actinomyces
spp.
Autopsy NA Multi-organ failure Died
Jitmuang
[21]
2008 M 46 1 month MV None Actinomyces
georgiae
Clinical PCN ➔ceftriaxone ➔ampicillin ➔amoxicillin CHF Survived
Yang and Grant BMC Infectious Diseases (2019) 19:511 Page 4 of 7
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Table 1 Review of 26 previously published primary infective endocarditis cases caused by Actinomyces species (Continued)
Author Year Sex Age Duration of
symptoms
Valve(s) Predisposing
factor(s)
Organism Diagnosis Therapy Complication Outcome
Kennedy
[22]
2008 F 27 2 days EV IVDU. Endocarditis
history
Actinomyces
israelii
Clinical Surgery. Unclear antibiotic Pulmonary emboli Unclear
Adalja [23] 2010 M 87 2 months MV Dental cleaning Actinomyces
israelii
Clinical PCN None Survived
Grundmann
[24]
2010 M 66 2 months PAV Prosthetics Actinomyces
neuii
Clinical PCN/meropenem/erythromycin ➔PCN ➔
amoxicillin. No surgery
Aortic root abscess Survived
Mehrzad
[25]
2013 M 49 NA TV IVDU Actinomyces
spp.
Clinical Vancomycin/ceftriaxone,/ciprofloxacin/metronidazole Septic emboli (lungs, skin,
spleen). Glomerulonephritis.
Survived
Morgan [26] 2014 M 67 6 weeks PAV Prosthetics. Dental
cleaning
Actinomyces
naeslundii
Clinical Ceftriaxone Arrhythmia. Septic shock Died
Cortes [27] 2015 F 51 2 months PAV Prosthetics. Dental
implant
Actinomyces
naeslundii
Clinical Ceftriaxone ➔ertapenem ➔amoxicillin Roth spots. Survived
Toom [28] 2018 F 55 8 months MV, AV HOCM with LVOT
obstruction
Actinomyces
israelii
Clinical PCN Severe hemolytic anemia Survived
Mmale, Ffemale, MV mitral valve, AV aortic valve, TV tricuspid valve, EV Eustachian valve, an embryologic remnant of the valve of the inferior vena cava, PAV prosthetic aortic valve, NA not available, PCN penicillin,
CHF congestive heart failure, IVDU intravenous drug use, HOCM hypertrophic obstructive cardiomyopathy, LVOT left ventricular outflow tract
Yang and Grant BMC Infectious Diseases (2019) 19:511 Page 5 of 7
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more fulminant course from a pathogen of lower
virulence.
A. neuii was classified to the genus of Actinomyces in
1994. It is a small, non-filamentous rod that does not
produce sulfur granules commonly seen in other Actino-
myces species. Unlike most Actinomyces spp. that are an-
aerobic or at best aerotolerant organisms, A. neuii grows
in both anaerobically and aerobically incubated samples
[35]. It was the third most common diphtheroid and the
most common Actinomyces species isolated from a ter-
tiary center [36]. It has been reported in infected athero-
mas [37], abscesses [37], infected foreign bodies [2],
urine [36] and endophthalmitis [38,39]. There have
been only a few case reports of classic actinomycosis
caused by A. neuii. Notably they were all related to
breast infections [40–44]. The infection caused by it is
thought to be endogenous [35]. The affinity of A. neuii
to atheromas was only reported in one of the earliest re-
ports, and how infections in atheromas were determined
is unclear [37]. However, with such propensity to endovas-
cular infection, it is possible that frequent cannulation for
hemodialysis might have contributed to our patient’sin-
fection by A. neuii. The outcomes from infections by A.
neuii are favorable [45]. Given the paucity of cases, our
antibiotic selection was based on a previously successfully
treated A. neuii endocarditis case [4]. The evaluation of
neurological complications, and the timing of surgery
were challenging, but our management was in line with
the latest surgical guideline [46]. The patient’s subsequent
possible prosthetic valve endocarditis and eventual death
likely reflected his overall poor prognosis, rather than re-
current A. neuii endocarditis.
Gram-positive rods, “diphtheroid”or “coryneform”,
are often disregarded as contaminants from skin or mu-
cosal surfaces, but 20% of diphtheroid isolates were
found to cause clinically significant infections in a large
study [36]. Actinomyces spp. are among these Gram-
positive rods, and their identification in clinical micro-
biology laboratories can be challenging [2,47]. As such,
delayed diagnoses are common [13,18,23], and it is
thought endocarditis by Actinomyces spp. is underesti-
mated and Actinomyces spp. are likely a cause of culture
negative endocarditis. Advances in laboratory methods,
primarily MALDI-TOF MS, are correctly and increas-
ingly identifying Actinomyces spp. from clinical samples.
Clinicians should carefully evaluate the relevance of an
Actinomyces spp. isolate before disregarding it, especially
in a vulnerable patient like ours, and in a species that is
associated with endovascular infection like A. neuii.
To conclude, we reported a successfully treated acute
infective endocarditis case with severe complications by
A. neuii, a rare but increasingly clinically relevant Acti-
nomyces species associated with endovascular infection.
Our review showed Actinomyces spp. infective
endocarditis is usually indolent and responds favorably
to treatment. Clinicians should carefully evaluate the
relevance of Actinomyces spp. in infections to avoid de-
layed or missed diagnoses.
Abbreviations
CT: Computed tomography; GI: Gastrointestinal; IUD: Intrauterine device;
IV: Intravenous; MALDI-TOF MS: Matrix-assisted laser desorption ionization
time-of-flight mass spectrometry; MRI: Magnetic resonance imaging
Acknowledgements
Not applicable.
Authors’contributions
WTY attended to the patient, did the literature review, and wrote the case
report. MG provided pictures of echocardiography and was responsible for
reviewing and revising the manuscript. Both authors have read the
manuscript and accepted the final version.
Funding
Not applicable.
Availability of data and materials
Not applicable. No datasets were generated for this study.
Ethics approval and consent to participate
Not applicable.
Consent for publication
WTY personally obtained a written consent from the patient before his
demise. The patient was made aware of the fact that his anonymity cannot
be fully guaranteed and that there is a possibility that he could be identified
based on the case report information and/or clinical images.
Competing interests
The authors declare that they have no competing interest.
Author details
1
Department of Internal Medicine, Yale New Haven Health Bridgeport
Hospital, 267 Grant Street, Bridgeport, CT 06610, USA.
2
Department of
Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, PO
Box 208022, New Haven, CT 06510, USA.
Received: 2 April 2019 Accepted: 31 May 2019
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