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.