Infectious intracranial aneurysm associated with Lactococcus garvieae: A case report and literature review

Highlights • Lactococcus garvieae is a known fish pathogen. Its role as an emerging zoonotic pathogen is increasingly recognised as more cases are reported.• Infective endocarditis (both native and prosthetic valve) accounts for the majority of human L. garvieae infections, but infections of other organ systems and contamination of platelet concentrates have also been reported.• The risk factors associated with L. garvieae infection include raw fish contact or consumption and underlying gastrointestinal diseases. Exposure to raw fish was found in one-third of the reported cases of L. garvieae infection, while around half of the reported cases had underlying gastrointestinal disorders.• β-lactams are the drug of choice for infections due to L. garvieae, clindamycin should be avoided as the organism is intrinsically resistant.• There were two cases of infectious intracranial aneurysm due to L. garvieae infection reported in the literature, but both cases could be attributed to the underlying infective endocarditis. We report the first case of a ruptured infectious intracranial aneurysm in a patient with L. garvieae bacteraemia without concomitant endocarditis.


Case report
A 59-year-old man, who had undergone mechanical aortic valve replacement 25 years ago for aortic stenosis, experienced severe acute onset occipital headache for five days associated with dizziness, neck pain and vomiting.There was no history of head injury.The patient was afebrile and conscious upon admission.There was nuchal rigidity but no focal neurological deficit.
His complete blood count was significant for microcytic hypochromic anaemia and neutrophil-predominant leukocytosis.Liver and renal function tests were unremarkable.Blood culture taken on admission was positive for Gram-positive cocci in chains after one day of incubation in the BD BACTEC TM FX blood culture system ( Fig. 1A and B).The organism was identified as Lactococcus garvieae by matrix-assisted laser desorption ionization-time of flight mass spectrometry with Bruker Microflex® LT (Bruker Daltonics, Bremen, Germany) and automated biochemical testing system with Abbreviations: CT, computed tomography; IE, infective endocarditis; PCA, posterior cerebral artery; IIA, infectious intracranial aneurysm.* Corresponding author.
Non-contrast computed tomography (CT) of the brain showed acute subarachnoid haemorrhage in the left parieto-occipital region ( Fig. 2A ).A CT angiogram detected a 12 mm distal posterior cerebral artery (PCA) fusiform aneurysm at the praecuneus.Three additional sets of blood culture from separate sites were all positive for L. garvieae after one day of incubation.The patient was managed with intravenous ceftriaxone (1 g Q12H), which resulted in clearance of the bacteraemia..A transthoracic and transoesophageal echocardiogram revealed no evidence of infective endocarditis (IE).There were also no evidence of other embolic or immunological phenomena.
In view of the L. garvieae bacteraemia, history regarding fish exposure was explored.The patient consumed  a takeaway assorted sushi and sashimi platter with his family four days prior to the onset of his headache and developed diarrhoea two days afterwards, which subsided before hospitalisation.He had no history of undercooked food intake otherwise.His family members remained asymptomatic.
After two weeks of antibiotics, the patient's headache subsided, and serial CT scans showed resolution of the subarachnoid haemorrhage.However, a catheter angiogram revealed an expansion of the distal PCA aneurysm to a diameter of 14 mm ( Fig. 2B -D).In view of the aneurysm's enlargement despite antibiotics, a craniotomy for its resection was performed.Histopathological examination of the aneurysm tissue demonstrated mixed neutrophilic and lymphocytic infiltrates compatible with an infected aneurysm ( Fig. 1C and D).The patient was discharged after completing six weeks of ceftriaxone.
A screening contrast-enhanced CT of the abdomen and pelvis and colonoscopy were performed.The CT scan was unremarkable, but two tubular adenomas at the caecum and transverse colon were identified by colonoscopy and excised.One year after the subarachnoid haemorrhage, the patient remained well with a modified Rankin score of 1.

Discussion
L. garvieae is a Gram-positive, facultatively anaerobic organism appearing as cocci in chains.It is known to cause lactococcosis, an acute septicaemic syndrome affecting multiple marine and freshwater animal species [ 1 , 2 ].Owing to a high mortality rate of up to 50%, lactococcosis outbreaks can cause significant economic losses in the aquaculture industry.Apart from aquatic organ-  1 ).For L. garvieae IE, both sexes are affected; the male-to-female ratio of the reported cases is 1.4:1.The median age of affected patients is 68 (interquartile range: 59.0-77.5).Nearly half of the patients affected (48.4%, 15/31) had prosthetic valve IE and fatal infections occurred in five cases (16.1%).All patients were treated with systemic antibiotics and around onethird (11/31) of the patients required valve replacement.
L. garvieae has also been reported to cause infections other than IE, including primary bacteraemia, osteoarticular infections, urinary tract infections, meningitis and intra-abdominal infections ( Table 2 ).Interestingly, L. garvieae has been implicated in cases of platelet concentrates contamination, which led to recipient sepsis [3][4][5].These case reports suggest the potential role of L. garvieae as an emerging pathogen associated with the contamination of blood products and increased vigilance is warranted.
The risk factors associated with L. garvieae infection include raw fish contact or consumption and underlying gastrointestinal diseases [ 6 ].Exposure to raw fish was confirmed in one-third of patients with L. garvieae infection, among whom, 63.2% (12/19) developed IE.Gastrointestinal disorders were noted in 54.8% (17/31) and 42.3% (11/26) of IE and non-IE patients, respectively.Upper gastrointestinal disorders such as gastroesophageal reflux disease, gastritis or peptic ulcers were the most common, followed by lower gastrointestinal disorders including diverticulosis and colonic polyps.The use of gastric acid suppressants may facilitate the survival of the pathogen.Intestinal mucosal breaches due to polyps, diverticulosis or malignancies predisposes individuals to infection by providing a portal of entry [6][7][8].Our patient consumed an assorted platter containing salmon, tuna and yellowtail from a sushi chain prior to the onset of his neurological symptoms.It is possible the patient ac-quired the infection from the sushi and sashimi in view of the temporal relationship between their consumption and his symptoms.However, a definitive relationship cannot be made as sampling of the food was not possible.Colonoscopy revealed two tubular adenomas which may have predisposed the patient to the infection.
Infectious intracranial aneurysms (IIAs) are most frequently caused by Staphylococcus aureus and viridans group streptococci, other bacteria such as coagulasenegative staphylococci, -haemolytic streptococci, enterococci and Gram-negative bacteria such as the HACEK organisms ( Haemophilus spp., Aggregatibacter spp., Cardiobacterium hominis, Eikenella corrodens and Kingella kingae ) are sometimes implicated, while fungi may also cause IIAs especially in immunocompromised hosts [9][10][11].There have been two reported cases of IIA due to L. garvieae , but both could be attributed to underlying IE.Watanabe et al .described a patient with L. garvieae native mitral valve endocarditis causing two IIAs, as well as cerebral and renal infarction [ 12 ].Makhoul et al. reported a patient suffering from L. garvieae prosthetic aortic valve IE complicated by mycotic aneurysm in the inferior middle cerebral artery and left frontal haematoma [ 13 ].To our knowledge, this is the first case of an IIA secondary to L. garvieae bacteraemia without concomitant IE.The distal PCA location, fusiform nature and histopathology of the aneurysm were highly suggestive of an infected aneurysm, as opposed to the more frequently encountered aneurysms that are generally saccular and located proximally at the circle of Willis.
-lactam antibiotics such as penicillin and ceftriaxone are the drug of choice for L. garvieae infections [ 7 , 8 , 14 ].Combination with aminoglycosides can be considered in severe infections to achieve a rapid bactericidal effect [ 1 ].Clindamycin should be avoided as the organism is intrinsically resistant [ 14 ].Neurosurgical or endovascular intervention should be considered in the case of IIAs, in addition to antibiotics.
In conclusion, we report a case of ruptured IIA associated with L. garvieae bacteraemia without concomitant IE.In managing invasive infections due to this organism, clinicians should seek history of raw fish exposure and underlying gastrointestinal pathologies.At-risk patients such as those with prosthetic heart valves should be edu-

Fig. 2 .
Fig. 2. Axial non-contrast-enhanced CT head scan revealing subarachnoid haemorrhage in the left parieto-occipital region (A).Catheter angiogram after two-weeks of intravenous antibiotics demonstrating an enlarged left distal posterior cerebral artery aneurysm (B, white arrow, left vertebral artery injection lateral view; C, white arrowhead, AP view 3D reconstruction; D, lateral view 3D reconstruction).

Table 1
Published literature on cases of infective endocarditis caused by Lactococcus garvieae .

Table 2
Published literature on non-infective endocarditis cases caused by Lactococcus garvieae .
Survived( continued on next page )