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| Journal of the New Zealand Medical Association,
11-May-2012, Vol 125 No 1354
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Unusually virulent coagulase-negative
Staphylococcus lugdunensis is frequently associated with infective
endocarditis: a Waikato series of patients
Michael Liang, Chris Mansell, Clyde Wade, Raewyn Fisher,
Gerard Devlin
Staphylococcus lugdunensis, a species of
coagulase-negative staphylococcus (CoNS), was first described by Freney et al in
1988.1 This organism is a rare contaminant in
culture and commonly found on human skin. In addition this pathogen is
associated with a wide variety of infections ranging from mild skin and soft
tissue infections to serious infections such as brain abscess, septicaemia,
chronic osteomyelitis and infective
endocarditis.2–4
Case reviews have demonstrated that S. lugdunensis
infective endocarditis is associated with a high mortality and early operation
is often advised.4–7 A positive blood
culture for this pathogen is frequently an indication of invasive
infection.
We report a case series of S. lugdunensis
bacteraemia and clinical management and outcomes from our institution.
MethodsAll blood cultures reported positive for S.
lugdunensis at Waikato Hospital between March 2006 to April 2011 were
retrospectively reviewed. Patient’s presenting complaints, diagnosis,
duration of antibiotics therapy and longer term outcomes were assessed.
Microbiological data were retrieved from the laboratory database and
antimicrobial susceptibility was recorded. All cases of infective endocarditis
fulfilled the modified Duke’s
Criteria.8
ResultsEleven consecutive cases of S. lugdunensis
bacteraemia were identified from our microbiology laboratory. The cases are
summarised in Table 1. Overall, 3 (27%) patients had
infective endocarditis, 1 (9%) patient had deep tissue infection, 1 (9%) had
necrotizing fasciitis, 1 (9%) patient had multiple organism sepsis, 2 (18.5%)
had skin infection, 1 (9%) had post-pacemaker insertion bacteraemia, and 2
(18.5%) had a diagnosis of fever of unknown origin.
Transthoracic or transoesophageal echocardiography was
performed in 6 (55%) of the patients. All isolates were susceptible to
Flucloxacillin and Vancomycin. The majority of patients were successfully
managed with Flucloxacillin alone. Cephalosporin (intravenous Cefazolin and oral
Cefaclor) were used successfully in one case where the patient had penicillin
allergy.
All but one (91%) patient survived the acute presentation of
bacteraemia. Mortality occurred in the patient who had nosocomial sepsis
following pelvic radiotherapy, this patient progressed rapidly to multiorgan
failure on the background of terminal metastatic prostate carcinoma. During the
median follow-up period of 10 months, the cumulative mortality was 45%.
Case synopsesEndocarditis—Three cases (Case 4, 9,
11) of infective endocarditis related to S. lugdunensis were identified
in our series. One patient had native aortic valve involvement, one had
mechanical mitral valve involvement and the third case had native mitral valve
vegetation identified on a long standing prolapsing mitral valve leaflet.
An 80-year-old woman (Case 4) who presented with fever,
general malaise and rigors, subsequently had native aortic valve infective
endocarditis associated with severe aortic regurgitation diagnosed. She was
successfully managed with high dose intravenous Flucloxacillin for a total
duration of 6 weeks. The presence of severe aortic regurgitation led to
deterioration in cardiac function (ejection fraction). Surgical intervention was
not recommended due to general frailty and co-morbidities. She died 9 months
post admission due to cardiac failure.
A second case of endocarditis case was diagnosed in a
70-year-old man (Case 9) with a previous St Jude mitral valve replacement who
presented with several days of fever. He was aggressively managed with
intravenous Flucloxacillin (6 weeks), Gentamicin (2 weeks) and oral Rifampicin
(6 weeks). He had good response to the medical treatment and transoesophageal
echocardiography did not demonstrate significant valvular or para-valvular
dysfunction. This patient died 4 months later due to an unrelated subarachnoid
haemorrhage; computed tomography of the head did not show features to suggest
mycotic aneurysm.
The final case of infective endocarditis was in a
56-year-old man (Case 11) with known mitral valve prolapse, associated with
moderate mitral regurgitation under regular cardiology follow-up. He presented
to the hospital 2 weeks prior with recent onset of fever and malaise which
settled spontaneously. On that admission there was documented left hemiplegia,
which resolved completely within several hours. A computed tomography scan of
the brain did not reveal any acute lesions. A diagnosis of transient ischaemic
attack (TIA) was made. On that particular admission, only a single blood culture
was taken, and it grew a CoNS, which was not further identified at that time.
Thus, based on the resolution of fever, it was believed that CoNS was a
contaminant.
He subsequently returned to hospital with intermittent
fever, rigors and abdominal pain; the working diagnosis communicated to the
laboratory was suspected appendicitis or diverticulitis. This time, the first
blood culture set grew two CoNS, one of which was identified as S.
lugdunensis. A third set, taken 2 days later, grew only the S.
lugdunensis. An urgent transthoracic echocardiography revealed a vegetation
on the anterior mitral leaflet associated with severe mitral regurgitation which
was confirmed on transoesophageal echocardiography. This patient underwent
urgent mitral valve replacement surgery and a 6 week course of intravenous
Flucloxacillin.
Other infections—A number of other
infections including deep tissue infection, necrotising fasciitis, severe
nosocomial systemic sepsis, superficial skin infection, post-pacemaker
implantation bacteraemia, and fever of unknown origin have also been associated
with S. lugdunensis.
The patient characteristics, diagnosis, antibiotics regime,
duration, echocardiographic investigations and outcomes were summarized in Table
1. Flucloxacillin, Vancomycin, Amoxycillin-Clavulanate, second and
third-generation of Cephalosporin monotherapy or combination had been used in
treatment. Two of these eight patients died in the follow-up with associated
comorbidities that resulted immunosuppression (Case 2 & 6, Table 1). One
patient with end stage prostate cancer died in hospital due to nosocomial
infection which progressed to multiorgan failure (Case 8, Table 1).
DiscussionS. lugdunensis infection, unlike sepsis due to
other species of CoNS, is frequently aggressive and life threatening in
nature.9 In our single centre report of 11
patients with S. lugdunensis bacteraemia presenting over a 5-years
period, this organism was associated with serious clinical infection in almost
half of the cases. This observation is similar to other published experience,
where S. lugdunensis is reported as a virulent pathogen, causing
invasive infection similar to Staphyloccocus aureus, particularly in
the setting of infective endocarditis.4,10-12
In our series, 3 (27%) cases of S. lugdunensis
bacteraemia were due to infective endocarditis which merits further discussion.
The incidence of endocarditis in patients with S. lugdunensis
bacteraemia is not well established. It is reported as high as 46% by
Zinkernagel et al.11 Other studies report a
much lower incidence of infective endocarditis with S. lugdunensis
bacteremia from 0 -7%.12–14 Of note, in
the presence of multiple positive blood cultures, systemic inflammatory response
syndrome, sepsis or septic shock, the incidence of endocarditis was considerably
higher in most series; 1 (17%) of 6 by Ebright et al and 4 (27%) of 15 by Choi
et al.12,14 In our series, both native and
prosthetic valves proved susceptible to infection which is in concordance with
other series. In addition, pacemaker lead infection, as described in our series,
can result in infective endocarditis, which was not clinically suspected in our
patient, although no echocardiography was undertaken.
Our series revealed that only 6 (55%) patients had
echocardiogram performed with 4 (66%) of this cohort also undergoing
transoesophageal echocardiography. The 2009 European Society of Cardiology (ESC)
guidelines on the prevention, diagnosis and treatment of infective endocarditis
recommends echocardiography in cases where infective endocarditis were highly
suspected and/or in patients with S. aureus
bacteriaemia.15 Recommendation of
echocardiography in patients with S. lugdunenesis bacteraemia, however,
is not clear. Due to its aggressive nature and high association with infective
endocarditis and devastating effects once intracardiac infection is established,
we support, as a minimum, routine transthoracic echocardiography in this group
of patients.
S. lugdunensis endocarditis is associated with a
high mortality rate with frequent surgical intervention considered necessary.
Anguera et al, in a series of 912 consecutive endocarditis, reported the overall
mortality of S. lugdunensis, S. aureus and Staphylococcus
epidermidis as 50%, 14.5% and 20% respectively; surgery was performed in
70%, 36.9% and 60% respectively. Although S. lugdunensis accounts for
1.1% cases of endocarditis in this series, the high mortality rate highlights
the aggressive nature of this particular CoNS in the setting of
endocarditis.4 Liu et al, in their recent
review of 67 cases of S. lugdunensis infective endocarditis from 1988
to 2008, documented that 82.5% of cases were left-sided valvular endocarditis,
78.7% occurred in native valves, with surgery performed in 66.7% of cases and a
mortality rate of 38.8%.5
Unlike most of the CoNS, S. lugdunensis appears
susceptible to a wide range of antibiotics including Penicillin, Cefazolin,
Linezolid, Moxifloxacin, Nafcillin, Quinupristin-Dalfopristin, Rifampicin,
Tetracycline, Trimethoprim-Sulfamethoxazole, and Vancomycin, using standard
in vitro methods.16 However, Linezolid
and Vancomycin were not bactericidal. In a biofilm model, the activity of most
antibiotics was severely reduced and Nafcillin (a congener of the Flucloxacillin
used in our case series) increased the production of
biofilm.16
The 2009 European Society of Cardiology guidelines on the
prevention, diagnosis and treatment of infective endocarditis has acknowledged
the aggressive nature of S. lugdunensis and the recommended treatment
is the same for Staphylococcus species which involves 4–6 weeks
of Flucloxacillin (or Oxacillin) with 3–5 days of Gentamicin for native
valve infection. For patients with prosthetic valve infection or
Methicillin-resistant strains, addition of Rifampicin or the use of Vancomycin
may be considered.15 All isolates in our series
were susceptible to Flucloxacillin and Vancomycin. Oral treatment with
Cephalosporin (Cefuroxime & Cefaclor) in simple soft-tissue infection
appeared to be effective in our case series. The high rate of susceptibility to
beta-lactams in our series is in concordance with available
data.4,10,11 Multiple antibiotics resistance is
rare in the literature and was not observed in our study.
One of the described cases of infective endocarditis had
CoNS identified on the admission blood culture which was initially considered to
be a contaminant. As a consequence, no further identification was carried out.
It is recommended that three sets of blood cultures are performed in cases of
suspected endocarditis as continuous bacteraemia occurs. Contamination usually
only affects one sample. This particular patient presented as fever and
transient ischaemia attack which retrospectively may have represented an embolic
event secondary to infective endocarditis. On the second presentation to the
hospital 2 weeks later, three sets of blood cultures demonstrated S.
lugdunensis and the initial culture was then re-studied and confirmed to be
the same organism. Reliable methods for identification of of S.
lugdunensis have been well
described.1,17,18 S. lugdunensis
colonies usually appear similar to other CoNS after 24 hrs incubation: small,
white and non haemolytic. After 48 hrs, a faint yellow colour is often visible
and they may resemble S. aureus. A high degree of skill and awareness
is required for prompt recognition. Many laboratories use slide and rapid latex
agglutination tests to distinguish S. aureus from CoNS but these kits
do not detect staphylococcal coagulase itself. S. lugdunensis can be
falsely identified as S. aureus due to the presence of clumping factor.
In an experienced hand, phenotypic characteristics such as colony pleomorphism
and beta-haemolysis are useful in detecting S. lugdunensis, in contrast
to clumping and synergistic haemolysis, which characterize several CoNS
species.19 Bocher et al in their study found
that, S. lugdunensis has a prominent beta-haemolysis and characteristic
Eikenella-like odour 2 days after incubation on Columbia agar with 5%
sheep blood; by combining with these features and colony pleomorphism they were
able to increase the yield of S. lugdunensis identification by 11-fold
in all types of cultures.20
ConclusionS. lugdunensis bacteraemia is associated with
infective endocarditis in one in three patients. Investigation for suspected
endocarditis should include at least three sets of blood cultures, to
distinguish contamination or transient bacteraemia from the continuous
bacteraemia of endocarditis. Assessment for the presence of endocarditis with
echocardiography should be considered strongly in all cases of S. lugdunensis
bacteraemia.
Competing interests: None
declared.
Author information: Michael Liang,
Cardiology Registrar, Department of Cardiology; Chris Mansell, Clinical
Microbiologist, Department of Microbiology; Clyde Wade, Cardiologist, Department
of Cardiology; Raewyn Fisher, Cardiologist, Department of Cardiology, Gerard
Devlin, Cardiologist, Department of Cardiology; Waikato Hospital, Hamilton
Correspondence: Dr Gerard Devlin.
Department of Cardiology, Waikato Hospital, Pembroke & Selwyn Sts, Private
Bag 3200, Hamilton 3240, New Zealand. Email: Gerard.Devlin@waikatodhb.health.nz
References:
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