Case ReportPersistent Cutibacterium (Formerly Propionibacterium) acnesBacteremia and Refractory Endocarditis in a Patient withRetained Implantable Pacemaker Leads

M. Freedman, J. O. Aflatooni, R. Foster, P. G. Haggerty , and C. J. Derber

Internal Medicine, Division of Infectious Disease, Eastern Virginia Medical School, 825 Fairfax Avenue,Suite 461 Hofheimer Hall, Norfolk, VA 23507, USA

Correspondence should be addressed to P. G. Haggerty; haggerpg@evms.edu

Received 4 April 2020; Revised 16 June 2020; Accepted 7 July 2020; Published 26 July 2020

Academic Editor: Gernot Walder

Copyright © 2020M. Freedman et al. *is 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.

Cutibacterium (formerly Propionibacterium) acnes (C. acnes) is a commensal bacteria commonly found on the human skin and inthe mouth.While the virulence of C. acnes is low in humans, it does produce a biofilm and has been identified as an etiologic agentin a growing number of implant-associated infections. C. acnes infections can prove diagnostically challenging as laboratorycultures can often take greater than 5 days to yield positive results, which are then often disregarded as contaminant. Patients withrecurrent bacteremia in the setting of implantable devices warrant further studies to evaluate for an associated valvular or leadendocarditis. *e patient in this report demonstrates how cardiac device-related endocarditis secondary to C. acnes can beoverlooked due to the indolent nature of this pathogen.*is patient presented with an implanted cardiac pacemaker device, as wellas retained leads from a prior pacemaker. Transesophageal echocardiography was required to confirm the diagnosis in the settingof multiple positive blood cultures and negative transthoracic echocardiograms over a period of 4 years.*e purpose of this reportis to highlight the difficulties encountered in diagnosing C. acnes endocarditis in a patient with a cardiac implantable electronicdevice and persistently positive blood cultures.

1. Introduction

C. acnes is a Gram-positive anaerobe that is recognized as a partof the commensal flora of human skin. *is nonmotile, non-spore-forming Bacillus is one of the predominant microor-ganisms of the dermatologicmicrobiota, especially in sebaceousgland-rich areas such as the chest, face, and scalp [1, 2]. Whilebest known for its role in acne, recent studies have identified C.acnes as the etiologic agent in a growing number of implant-associated infections. Shoulder prosthetic joint infections andcerebrovascular shunt infections are the most common, butinfections of cardiovascular devices are also being identifiednow [2]. It is hypothesized that the ability of certain strains ofC.acnes to produce biofilms can lead to colonization of cardiacpacemaker devices without overt signs of clinical infection [3].

Diagnosing C. acnes as the causative source of infectioncan prove exceedingly difficult for a variety of reasons.Positive blood cultures may take more than 5 days to grow

and are often disregarded as a contaminant; blood culturesin patients with deep-seated infections can be negative in upto one-third of cases. [4, 5] We present a case of pacemakerlead infection with C. acnes that was repeatedly eitherconsidered a skin contaminant or inadequately treateddespite persistently positive blood cultures.

2. Patient History

A 52-year-old man with a past medical history significant foruncontrolled type 2 diabetes, remote traumatic brain injury,and complete heart block of unknown etiology presented tothe emergency department (ED) due to symptomatic hy-poglycemia, intermittent fevers and chills, and a swollen,erythematous, tender fluctuance at the pocket of his previousright-sided pacemaker that had been removed years ago, asseen in Figure 1. *e patient had no documented history ofpacemaker pocket infections.

HindawiCase Reports in Infectious DiseasesVolume 2020, Article ID 8883907, 6 pageshttps://doi.org/10.1155/2020/8883907

In regards to his cardiac history, the patient had requiredextensive surgical management of his complete heart block.He had a permanent pacemaker (PPM) implanted at 22years of age for this condition, which had since requiredthree different surgeries for pulse generator and cardiac leadreplacement and revision. At the time of his presentation tothe ED, the patient had a dual chamber PPM in the left chestimplanted 6 years prior; he also had the aforementionedpocket in his right chest, a potential space remaining afterthe removal of his previous PPM. Additionally, he had tworetained ventricular leads from another previous pacemakerembedded in his myocardium, which had been trimmedback as much as possible and capped off, but never removedsince they could not be safely extracted. *e exact lengths ofthe retained leads were not discussed in the postoperativereports.

Due to high clinical suspicion for infection of the right-sided pocket, as well as concerns for sepsis, the patient wasstarted on empiric antibiotic therapy (piperacillin/tazo-bactam and intravenous (IV) vancomycin). He was thentaken to the operating room for incision and drainage (I&D)of the infected pocket site and placement of a wound vac-uum. On hospital day (HD) 4, despite his I&D, woundvacuum, and antibiotic regimen, the patient was still havingfevers and leukocytosis. Later that day, his blood culturesgrew Gram-positive rods in both anaerobic bottles, and theinfectious diseases service was subsequently consulted. Dueto concern for infective endocarditis, a transthoracicechocardiogram (TTE) was ordered, though it did not showany evidence of heart failure, valvular abnormalities, orvegetations. On HD 6, C. acnes was isolated from the an-aerobic blood cultures from admission and from intra-operative wound cultures taken from the right-sided

pacemaker pocket. His antibiotic regimen was, then, nar-rowed to ceftriaxone 2 grams IV daily.

Of note, the patient had six other recorded instances overthe previous 4 years in which he had blood cultures drawn,all of which were initially positive for C. acnes. Per his notes,the majority of these cultures had either been attributed tocontaminant or dismissed. If follow-up blood cultures werepursued, it was usually after the patient had receivedmultiple days of empiric antibiotic therapy, making it dif-ficult to interpret their negative results. An overview of thecircumstances surrounding the patients most recent and sixprevious C. acnes-positive blood cultures, as well as atimeline of these blood cultures, can be seen in Table 1 andFigure 2, respectively. Also, over the same four-year period,the patient had four TTEs for various reasons, none of whichshowed any evidence of infective endocarditis. *e patientnever had a transesophageal echocardiogram (TEE) prior tothis admission.

Considering the positive wound and blood cultures fromthis hospitalization and his history of persistent C. acnes-positive blood cultures in the presence of an implantablecardiac device and retained leads, infective endocarditis wasstill suspected and a TEE was recommended. *is study wasperformed on HD 9 and revealed vegetations across multiplepacemaker leads, highly suggestive of infective endocarditis.*e largest vegetation was 1 cm in diameter, as seen inFigure 3.

Cardiothoracic surgery was consulted and, due to theinfection, recommended removal of the left-sided dualchamber PPM, as well as extraction of the retained, em-bedded leads from the previous pacemaker. *e left-sidedPPM was removed without complication, but the retainedleads were fractured and deeply embedded in the

Figure 1: Patient’s chest at initial presentation to the emergency department, with erythematous fluctuance at the pocket of his previousright-sided pacemaker visible.

2 Case Reports in Infectious Diseases

Tabl

e1:

Overview

ofthecircum

stancessurrou

ndingeach

ofthepatients’C.

acnes-po

sitivebloo

dcultu

res,includ

ingthosefrom

thispresentatio

n.

Positivebloo

dcultu

reset(tim

epriorto

final

diagno

sisof

infective

endo

carditis)

Reason

for

presentatio

n/pertinent

finding

sat

presentatio

n

Locatio

npresentedto

Results

ofbloo

dcultu

redraw

nat

presentatio

n

Daysafter

beingdraw

nthat

bloo

dcultu

res

resulted

positive/

speciated

C.acnes

Was

thepatient

admitted

after

initial

presentatio

n?

Did

thepatient

receiveTT

Eevaluatin

gfor

infective

endo

carditisdu

eto

this

presentatio

n?

Did

thepatient

receiveantib

iotics

therapyor

other

relatedinfectious

managem

entd

ueto

thispresentatio

n?

Werethere

managem

ent

changesafter

return

ofpo

sitive

bloo

dcultu

res?

Reason

ingformanagem

ent

plan

follo

wingreturn

ofpo

sitivebloo

dcultu

res

Was

thereno

ted

ackn

owledgem

entof

previous

positiveb

lood

cultu

res?

Did

thepatient

ever

receiveTE

Ein

theevaluatio

nof

thesebloo

dcultu

reresults?

#1(4

yearsprior)

Fevers,rigors,and

leuk

ocytosis

Emergency

department

C.acnesin

2/2

anaerobic

bottles

3/6

No

No

No

Nochangesin

managem

ent

Whenthepatient

was

follo

wed

upwith

7days

after

presentatio

n,he

hadsin

cebeen

assessed

byan

outside

physicianandwas

currently

asym

ptom

atic.P

ositive

bloo

dcultu

reswereno

tfurther

addressed

n/a

No

#2(3

years,11

mon

thsprior)

Fevers

and

leuk

ocytosis

Emergency

department

C.acnesin

2/2

anaerobic

bottles

4/9

No

No

Disc

harged

with

course

oflevoflo

xacinand

out-patient

follo

w-

upwith

infectious

disease

Nochangesin

managem

ent

*epatient

was

alreadytaking

antib

ioticsandhadfollo

w-up

with

infectious

disease

schedu

ledto

determ

ine

etiology.O

utcomeof

follo

w-up

unkn

own,

thou

ghthepatient

didno

thave

anotherpo

sitive

bloo

dcultu

refor3yearsafter

thisadmiss

ion

Yes,which

helped

guide

recommendatio

nto

seeou

t-patient

infectious

disease.

No

#3(10mon

ths

prior)

Fevers,d

entalp

ain,

andleuk

ocytosis

Emergency

department

C.acnesin

2/2

anaerobic

bottles

5/7

No

No

Disc

harged

with

10days

ofcourse

ofpenicillinandou

t-patient

follo

w-up

with

oral

surgery

Nochangesin

managem

ent

Patient

was

alreadytaking

antib

ioticsa

ndwas

planning

tofollo

w-upwith

oralsurgeryfor

apresum

eddental

infection

No

No

#4(6

mon

ths

prior)

Pleuritic

chestpain,

fevers,leuko

cytosis

,andachestX-ray

show

ingleft-sid

edinfiltrateandalarge

left-sid

edpleural

effusion

Emergency

department

C.acnesin

1/2

anaerobic

bottles

5/8

Yes

Yes,which

was

negativ

efor

infective

endo

carditis

Startedem

piric

board-spectrum

antib

ioticsat

presentatio

nfor

presum

edpn

eumon

ia

Infectious

disease

consulted,

aTT

Ewas

ordered,

and

repeat

bloo

dcultu

reswere

draw

n

Toevaluate

foretiology

ofrecurrentC.acnesbacterem

ia.

Nofurtherevaluatio

nwas

pursuedafternegativ

eTT

E,2

subsequent

sets

ofnegativ

ebloo

dcultu

res,andthe

patient’ssymptom

atic

improvem

ent.Itwas

stated

that

thepo

sitivebloo

dcultu

rewas

likelytheresultof

contam

ination,

ason

ly1/2

anaerobicbo

ttles

grew

out

C.acnesandthesubsequent

bloo

dcultu

resw

erealln

egative

Yes,ackn

owledged

“previou

sC.acnes-

positivebloo

dcultu

res

ofun

clearetiology”.

No

#5(1

mon

thprior)

Und

ocum

ented

Skilled

nursing

facility

C.acnesin

2/2

anaerobic

bottles

5/7

No

No

No

Nochangesin

managem

ent

Nono

tedactio

nstakenafter

return

ofpo

sitivebloo

dcultu

res,thou

ghthepatient

presentedto

theED

the

follo

wingday

No

No

#6(3

weeks

prior)

Fevers,sho

rtness

ofbreath,a

ndan

erythematou

s,tend

errigh

tchest

fluctuance

Emergency

department

C.acnesin

1/2

anaerobic

bottles

4/6

No

No

No

Nochangesin

managem

ent

Believedpo

sitivebloo

dcultu

reto

bedu

eto

acontam

inant

Yes,ackn

owledged

“positive

bloo

dcultu

resfrom

prior”.

No

#7(1

weekprior)

hypo

glycem

ia,fevers,

andan

erythematou

s,tend

errigh

tchest

fluctuance

Emergency

department

C.acnesin

2/2

anaerobic

bottles

4/6

Yes

Yes,which

was

negativ

efor

infective

endo

carditis

Startedem

piric

board-spectrum

antib

ioticsat

presentatio

nfor

presum

edsepsis

TEEwas

ordered

Suspicionforinfection

endo

carditisdespite

negativ

eTT

E

Yes,which

help

guide

decisio

nto

obtain

TEE.

Yes,which

show

edvegetatio

nson

multip

lepacemaker

leads,thelargest

being1cm

.

Case Reports in Infectious Diseases 3

myocardium and, thus, could not be safely extracted again.Open thoracotomy to remove the embedded leads was of-fered; however, the patient opted for conservative man-agement entailing 6weeks of ceftriaxone, followed byindefinite suppression with oral doxycycline. He was dis-charged on HD 25 to a skilled nursing facility for furtherrehab and completion of his IV antibiotic therapy.

*e patient was followed up for 15 months after hisdischarge. During this period, he was compliant with hisantibiotic therapy, as well as had multiple routine bloodcultures drawn, none of which showed any growth.

3. Discussion

C. acnes is a Gram-positive, nonmotile, non-spore-forming,commensal bacillus of human skin. It is most widely rec-ognized as contributing to the pathogenesis of acne, whileless appreciated in the pathogenesis of other conditions. *eability of C. acnes to form biofilms may be its most rec-ognized virulence factor, as it can colonize artificial sub-strates [3]. It has been recently suggested that lysis ofbacterial cells and release of cytoplasmic contents facilitate

the formation of their biofilm [3]. Biofilm production mayhave been an important factor in the case presented, as thepatient continued to have several positive blood culturesover the course of 4 years that were incompletely treatedwith antibiotics.

Achermann et al. suggests that a possible risk factor forhematogenous seeding of C. acnes and subsequent coloni-zation of implanted devices are invasive procedures in-volving sebaceous gland-rich skin where C. acnes counts arethe greatest [2]. Even with adequate topical sanitationtechniques, studies have shown viable C. acnes skinrecolonization of wound edges after 90–180 minutes, thepoint at which hematogenous seeding is possible. [2].

One study found blood cultures to be positive in only62% of people with proven C. acnes infections [5]. In a caseseries by Sohail et al., 7 of 8 patients diagnosed with C. acnesendocarditis from 1967–2005 were men who ranged from 46to 80 years of age. Two of these seven patients had positivelead cultures from either a PPM or implantable cardiacdefibrillator. *e remainder had some form of cardiacprosthesis [5, 6]. Our patient had characteristics consistentwith those of the population in this study, and so his multiple

Bloodculturegroup

#1

Bloodculturegroup

#2

Bloodculturegroup

#3

Bloodculturegroup

#4

Bloodculturegroup

#5

Bloodculturegroup

#6 Bloodculturegroup

#7

Patient diagnosed withC. acnes infective

endocarditis

(1 week prior)(3 week prior)

(1 months prior)(6 months prior)(10 months prior)

(3 years, 11months prior)

(4 years prior)

Figure 2: Each C. acnes-positive blood culture in relation to the time at which the patient was diagnosed with infective endocarditis.

Figure 3: Transesophageal echocardiogram showing 1 cm vegetation (red arrow) adhered to the tricuspid valve suggestive of infectiveendocarditis.

4 Case Reports in Infectious Diseases

episodes of symptomatic C. acnes bacteremia were onlytreated with short courses of a beta-lactam antibiotics beforefinally being diagnosed with an endocardial vegetation onold pacemaker leads.

Our study adds to the growing body of relatively newliterature suggesting that C. acnes should be considered asmore than just a skin contaminant when found in the blood ofpatients with implantable cardiac devices. Clinicians shouldhave a low threshold to investigate these devices as a source ofinfection when C. acnes is isolated from the blood. Addi-tionally, these patients should be treated aggressively withappropriate therapies including hardware removal, if possible.In the absence of hardware removal, long-term suppressiveantibiotic therapy should be considered, as was decided by ourpatient, since inadequate treatment of C. acnes infectiveendocarditis can have devastating consequences. Although C.acnes endocarditis is rare, it has been demonstrated to beassociated with abscess formation in up to 36% of cases. Incases of C. acnes bacteremia, mortality can occur in up to5.9–16% of patients [7]. Clayton et al. identified several factorsthat contributed to more negative outcomes in patients with C.acnes endocarditis. *ese include an indolent clinical course,negative or delayed culture results, and the tendency to con-sider the organism as a skin contaminant, many of whichoccurred in our patient’s disease course [8]. For our patient, thelower sensitivity of TTE for endocarditis was also an importantfactor contributing to delay in proper treatment.

Gomes et al. found that patients with retained pacemakerlead fragments following attempted transvenous lead ex-traction had a significantly increased risk of cardiac deviceinfection compared to those who had complete removal oftheir leads (13.5% vs. 3%, P � 0.001) [9]. Similar results werefound by a recent propensity-matched analysis of theMEDIC trial [10]. According to the Heart Rhythm Society(HRS), the goal for extraction of a pacemaker in a patientwith an implantable cardiac electronic device-related in-fection should be complete removal [11]. *is recommen-dation stemmed from findings that one-third of patientswith infection of retained leads ultimately required openheart surgery for infective endocarditis of the leads, despiteantibiotics [12]. *e American Association for *oracicSurgery guidelines for treatment of patients with cardiacdevice-associated endocarditis with relapsing bacteremiadespite appropriate antibiotic treatment also recommendsurgical extraction (Grade IIa recommendation). [13].

*roughout the 15 months of therapy that we were ableto follow, the patient had multiple routine blood culturesdrawn that showed no growth, but further monitoring isnecessary because of the long duration of cardiac device-related infections due to C. acnes. However, thus far, this isthe first case to our knowledge in which indefinite sup-pressive antibiotics have been used successfully to controlrecurrent cardiac device-related infections when the pace-maker leads could not be completely removed.

4. Conclusions

C. acnes should be considered as a potential source of in-fection in patients with implanted medical devices and

positive cultures. While often regarded as a blood culturecontaminant, positive findings should not be immediatelydiscounted due to the potential pathogenicity of the or-ganism in this population. *is bacterium is known toproduce biofilms giving it a predilection for implantedmedical devices and artificial surfaces. Echocardiographyshould be considered for diagnosis in patients with pros-thetic cardiac valve and pacemakers. *ere should be a lowthreshold for transesophageal echocardiography in patientswith multiple C. acnes-positive blood cultures, even if thetransthoracic echocardiogram does not show signs of veg-etations. Although unavailable in our case, histopathologicaland microbiologic studies of resected specimens are addi-tional opportunities for reaching a potential diagnosis.Patients with persistently positive cultures will likely requiresurgical explantation of infected hardware to achieve cure.When surgical removal is not possible, suppressive antibiotictherapy should be considered.

C. acnes is an emerging, clinically relevant pathogen,especially when considering the rising rates of prostheticsurgical implants. In our patient, retained lead wires were thenidus for his endocarditis by this commensal organism.Persistently positive blood cultures in the setting of im-plantable cardiac devices should prompt a work-up forendocarditis, regardless of the bacterium. *is case dem-onstrates how serious infections of implantable cardiacdevices can be missed when pathogens of low-virulence,such as C. acnes, are overlooked as contaminants.

Conflicts of Interest

*e authors declare no conflicts of interest.

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Case Reports in Infectious Diseases 5

analysis of 524 episodes,” Journal of Clinical Microbiology,vol. 49, no. 4, pp. 1598–1601, 2011.

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6 Case Reports in Infectious Diseases