Discussion:
This frail octogenarian presented non-specifically, with relatively
limited haematological and biochemical derangement of acute phase
reactants associated with symptoms of bleeding PR, functional decline
and anaemia. The initial working diagnosis was acute diverticulitis with
associated sepsis. While the patient had initial clinical improvement on
IV co-amoxiclav, she had further bleeding PR and evidence of sepsis
following a switch to oral antibiotics prompting further imaging of the
abdomen and subsequently the heart. The confirmation of A.
defectiva bacteraemia with known AS and evidence of potential
embolisation prompted the investigations which lead to a diagnosis of
aortic valve IE. Following the initiation of penicillin-based
antimicrobial therapy repeat blood cultures were sterile. Post-mortem
examination confirmed evidence of aortic valve IE with the likely cause
of intermittent major PR bleeding being haemorrhoids. It is possible
that the source of bacteraemia was secondary to bowel translocation in
the context of recurrent haemorrhagic episodes.
A. defectiva is an NVS considered part of the normal flora of the
oral cavity, GI and urogenital tract in humans. In 1961, Fenkel and
Hirsch first isolated a series of satellite streptococci growing
adjacent to larger bacteria on agar media. The larger colonies were
noted to be supplementing the growth of the satellite bacteria, later
termed NVS [1]. NVS was further speciated in 1991 by Bouvet et al.
to Streptococcus defectivus and Streptococcus adjacens[5]. In 1995 a new genus of NVS was identified through 16S rRNA
sequencing, named Abiotrophia [6]. Further sequencing carried
out by Collins et al. brought about the reclassification of a number ofAbiotrophia strains in 2000 and the Granulicatella genus
was named [7].
Fastidious in nature, NVS characteristically require the addition of
L-cysteine or pyridoxal to grow on blood agar [1,7]. Due to the
variation in Gram stains, colony morphology and difficulty culturing by
routine laboratory methods, NVS must be considered a potential pathogen
in all culture negative endocarditis [1]. However, the introduction
of molecular methods of identification such as matrix assisted laser
desorption ionization-time of flight (MALDI-TOF) mass spectrometry has
made it increasingly possible to identify these pathogens in the
clinical laboratory by providing a rapid, accurate and cost effective
means of bacterial identification [9–11]. Following ionization of
samples, isolates are separated according to mass and analysed by their
‘time of flight’ to the detector where sample analysis is cross
referenced to a data base and the bacteria is matched and identified
[8].
NVS account for 5-6% of all streptococcal endocarditis [1].A. defectiva is rarely cultured successfully and has been
attributed to <1% of all bacterial endocarditis [9]. The
organism has a number of virulence factors such as the production of
exopolysaccharide and the ability to bind with fibronectin which may
account for its propensity to adhere to heart valves and produce the
associated embolic phenomenon which have been previously described
[13,15,16]
Evidence suggests that resistance of A. defectiva to penicillin
is increasing [10]. Alberti et al. carried out an extensive
investigation of susceptibility patterns of a number of NVS. One third
of the isolates examined in the study were susceptible to penicillin,
14% were resistant and the remaining 53% were of intermediate
sensitivity. In general A. defectiva was found to be more
resistant than G. adiacens with 18.9% of A. defectivaresistant to penicillin. No resistance of A. defectiva to third
generation cephalosporins was observed whereas 50% of G.
adiacens isolates were resistant to cefotaxime. All isolates were fully
susceptible to meropenem and vancomycin [11]. Choice of
antimicrobial treatment in the setting of NVS IE is often not
straightforward, as guidelines on treatment vary and results of
susceptibility testing can often be delayed if isolates are sent to
reference laboratories for work-up. The European Society of Cardiology
(ESC) recommend a number of antimicrobial treatment options including
benzylpenicillin, ceftriaxone and vancomycin combined with an
aminoglycoside for the first 2 weeks of treatment [12]. However the
British Society of Antimicrobial Chemotherapy do not advise the use of
ceftriaxone with gentamicin in the setting of prosthetic valve
endocarditis or if there is an extra-cardiac focus of infection or if
the person is deemed a candidate for surgery. This is due the risk of
nephrotoxicity and Clostridium difficile infection [12]. The
isolate in this case report was sensitive to both penicillin and
ceftriaxone with minimum inhibitory concentrations of 0.125 mg/L and
0.5mg/L respectively. Despite the sensitivity of this organism the
clinical outcome was poor, reflecting the frequent presence of life
threatening comorbidities in older patients, such as severe IHD in this
case as well as the high pathogenicity and virulence of NVS which is
independent to its antimicrobial sensitivity.
There are over one hundred-case reports of A defectivadeep-seated infection in the literature. These range from
quadruple-valve endocarditis, vertebral osteomyelitis to endophthalmitis
and peritonitis [15, 21–23]. This pathogen affects all age groups
from young children to very old patients [13]. However outcomes in
children are much better as surgical intervention is generally
successful despite the presence of embolic complications [14]. The
sudden mortality of this case is consistent with other case reports of
this age-group and is often a reflection of the high rates of valvular
endothelial damage observed in patients over the age of 60, or severe
comorbidities as in this case [19,26].
The vast majority of NVS endocarditis cases evaluated in the literature
refer to presentations with pyrexia associated with features of septic
shock and heart failure [15]. Cases of A. defectiva IE
reported often involve immunocompromised patients and/or the presence of
non-native or structurally defective valves. ?need reference
The atypical presentation of this older patient with non-specific
symptoms represents an unusual manifestation of infection with a rare
organism which classically presents with more florid signs of sepsis
often with devastating consequences. Given the difficulty with culture
and identification of this organism, it is likely that A.
defectiva may be associated with a higher proportion of
culture-negative IE than previously reported [16]. Moreover, it is
conceivable that the prevalence of A. defectiva infection in
older patients is higher than reported in the literature.
In this case an intra-abdominal source of sepsis was thought to be
likely. Persistent bleeding PR during the patient’s admission against a
background of apparent septic splenic emboli, raised the possibility of
colonic septic embolisation with associated bowel ischaemia. However,
the patient’s serum lactate level was always within normal parameters
and her clinical status was not consistent with extensive bowel
ischaemia. Unfortunately, she was unfit for proctoscopy, sigmoidoscopy
or colonoscopy but acute diverticulitis and/or colonic carcinoma were
the most plausible clinical causes for bleeding PR. However, at
post-mortem, haemorrhoids were the likely actual source, with no
pathological evidence of bowel ischaemia, tumour or diverticulitis. This
suggests that bacterial translocation from the lower GI tract was the
most likely source of bacteraemia.
This pathogen is rarely identified clinically and can have devastating
complications often associated with septic embolisation in up to one
third of cases [17]. This case highlights the importance of
performing blood cultures in non-specifically unwell older adults and
cardiac imaging, especially with known or suspected valvular disease.
The patient, albeit frail and unfit for invasive tests, responded to IV
antibiotics and was returning towards her baseline functional status,
emphasising the importance of accurate diagnosis and definitive
treatment in this frequently encountered population. Her pre-existing
established severe IHD was the likely attributable cause of death,
probably resulting in fatal arrythmia.
Prompt diagnosis, pathogen isolation and commencement of targeted
antimicrobial therapy is essential in older patients with A.
defectiva IE. This is particularly important in order to prevent
potentially fatal complications, since presenting symptoms are highly
variable and, non-specific especially in older patients.