An Unusual cause of Endocarditis
- 1 Northern General Hospital Emergency Department, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- 2 Centre for Urgent and Emergency Care Research (CURE), School of Health and Related Research (ScHARR), The University of Sheffield, Sheffield, UK
- 3 Department of Medical Microbiology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- 4 Department of Infection, Immunity and Cardiovascular Disease and the Florey Institute for Host-Pathogen Interactions, The University of Sheffield, Sheffield, UK
- 5 Cardiothoracic Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Correspondence to Dr Rhys Watkins; rhys.watkins2@nhs.net
Abstract
A man in his 20s attended the emergency department with three days of fever, headache, reduced appetite and a sore throat. COVID-19 point-of-care test was negative. Blood cultures grew a gram-negative coccobacillus, Neisseria elongata. Following an episode of confusion, MRI head revealed septic emboli. Prolapse of the mitral valve with regurgitation was noted on echocardiography. Infection was found to have originated from multiple dental caries and treatment required a combination of dental extraction, prolonged antibiotic therapy and surgery for mitral valve repair.
N. elongata is part of the normal oropharyngeal flora but is also a rare cause of endocarditis. There are no established treatment guidelines for endocarditis of this aetiology. N. elongata endocarditis may present atypically, with a murmur only developing several days later. ‘Classical’ stigmata should not be relied on to make a diagnosis. N. elongata predominantly affects the left side of the heart and predisposes to embolic events.
Background
Infective endocarditis caused by Neisseria elongata is very rare (<2% cases),1 but patients may develop serious sequelae, such as thromboembolism, if not diagnosed and treated promptly.2 3 This form of endocarditis often presents without classical signs (e.g. absence of a murmur on initial examination), which may lead to delayed diagnosis.4 At present, there are no official guidelines which outline the optimal management of N. elongata endocarditis.2 It is hoped that this case report will raise awareness of this unusual cause and may contribute to the development of guidelines for its management.
Case presentation
A normally fit-and-well man in his 20s, who was originally from East Asia but had lived in the UK for 6 months, presented to the emergency department with 3 days of headache, fever, sore throat and vomiting.
On examination, he was flushed, tachycardic with a regular pulse at 110 beats per minute and feverish at 38°C. There were no features of meningism. Glasgow Coma Score was 15 with unremarkable neurological, respiratory and cardiovascular examinations. No heart murmurs were heard on auscultation.
Following discussion with the infectious diseases team, the patient was started on intravenous fluids and paracetamol and admitted under acute medicine. Although the patient presented with signs of infection, he did not meet any of the high-risk criteria for sepsis.5 Antibiotics were, therefore, initially withheld so that the infective source could be identified. However, while on the ward, the patient continued to spike temperatures and developed a temporary new oxygen requirement, and so he was transferred to respiratory medicine.
Several days into his admission, the patient experienced a transient episode of short-term memory loss and confusion, with otherwise normal neurological examination. Suspecting meningitis/encephalitis, the team started him on intravenous ceftriaxone and aciclovir.
The following day, the reviewing infectious diseases consultant noted a new pansystolic murmur on examination. Bedside echocardiogram demonstrated mitral regurgitation with prolapse of the valve. Meanwhile, an MRI revealed septic emboli in the brain. Infective endocarditis was considered, and the patient was admitted under cardiology.
By this stage, three sets of blood cultures, taken throughout the admission, had grown a bacterium called Neisseria elongata (figure 1). This is commonly found as an oropharyngeal commensal but can, rarely, cause invasive infection.4 Due to the lack of published case reports, no trust guidelines for management of this bacterium existed. The microbiology team reviewed the literature and advised a 6-week course of ceftriaxone and gentamicin to be given via a Peripherally Inserted Central Catheter (PICC) line. Gentamicin was switched after 5 days to ciprofloxacin following the development of acute kidney injury, although this too was later discontinued.
(A) Microscopy of Neisseria elongata: gram-negative coccobacillus. (B) N. elongata: cultures on blood agar. (C) N. elongata: cultures on chocolate agar.
Orthopantomogram showed that the infection likely originated from multiple dental caries. The maxillofacial team removed five of the patient’s teeth during his inpatient stay to prevent further bacteraemia. Cardiothoracic surgical opinion was also sought due to the severe mitral valve prolapse. Following 4 weeks of antibiotic therapy, the patient had surgery to repair the mitral valve. He was also incidentally found to have a patent foramen ovale (PFO), which was closed intraoperatively. Intravenous ceftriaxone was continued for 2 weeks postoperatively (completing a course of 6 weeks in total) and the patient started on a beta-blocker for 6 weeks.
Investigations
Bedside investigations
On arrival, the patient was febrile (T 38°C) and tachycardic (110 bpm) but remained haemodynamically stable. Regular ECGs throughout admission were normal. The PR interval can be prolonged in aortic root abscess, a possible complication of endocarditis.
Laboratory investigations
COVID-19 PCR and other respiratory virus tests were negative throughout admission.
Initial bloods revealed markedly raised C reactive protein (CRP) (222 mg/L) with lymphopenia (0.52×109/L). Overall white cell count was normal (6.3×109/L). Blood-borne virus screen for HIV, hepatitis B and C was negative. Urine culture was unremarkable, but blood cultures grew N. elongata. This was subsequently found in two more sets of cultures.
Opening pressure on lumbar puncture was 13cmH2O and cerebrospinal fluid (CSF) was clear, with glucose and protein within normal ranges and no growth on culture.
Imaging investigations
Admission chest X-ray showed clear lung fields bilaterally with no evidence of consolidation, cardiomegaly or fluid overload.
No acute abnormalities were seen on CT head.
Following the episode of transient confusion, MRI head showed multiple emboli in the brain (figure 2).
(A) Diffusion-weighted MRI head demonstrating left cerebellar infarcts (red arrows). (B) T2-weighted MRI head demonstrating left cerebellar infarcts (blue arrow). (C) Diffusion-weighted MRI head demonstrating right thalamic infarction (red arrow). (D) T2-weighted MRI head demonstrating right thalamic infarction (blue arrow).
Orthopantomogram displayed multiple right-sided dental caries (the likely source of infection) and previous root canal work (figure 3).
Orthopantomogram: multiple dental caries are present (red arrows) and there is evidence of previous root canal treatment (blue arrow).
Mitral valve regurgitation with prolapse of the posterior leaflet was noted on transthoracic and transoesophageal echocardiograms. No thrombus or vegetations were visualised but this is not unusual.6 PFO was noted on intraoperative echocardiogram.
Differential diagnosis
COVID-19 was considered at triage due to the ongoing high prevalence in the community, but lateral flow and subsequent PCR tests were negative.
Given the range of symptoms exhibited, a viral infection was initially diagnosed. This differential was supported by the blood tests (see the Investigations section).
Over the next few days, symptoms did not improve and a clear infective source remained elusive. Although the patient denied photophobia, he was found lying in a dark room when reviewed on the ward round, which suggested he had some aversion to light. A CT head and lumbar puncture were subsequently requested, which excluded meningitis as a diagnosis.
These findings were especially important following the transient episode of confusion. Subsequent MRI brain revealed multiple septic emboli, which led to a clinical suspicion of endocarditis.
This was reinforced by the discovery of a new pansystolic murmur, positive findings on echocardiogram and growth of N. elongata in multiple blood cultures. In addition, orthopantomogram indicated that endocarditis had originated from infected caries.
Treatment
The patient was originally managed with intravenous fluids and paracetamol. Initial advice from the infectious diseases team was to withhold antibiotics as there was no clear source of infection and a lumbar puncture might become necessary later if the patient deteriorated. In this case, antibiotics might confound the results.
However, broad-spectrum intravenous antibiotics were started when his fevers persisted.
Following the episode of confusion, treatment was changed to intravenous ceftriaxone (2 g two times per day) and intravenous aciclovir (600 mg three times per day), to treat possible meningoencephalitis.
After endocarditis was diagnosed, once daily intravenous gentamicin (5 mg/kg) was started alongside the intravenous ceftriaxone. Gentamicin was later changed to oral ciprofloxacin (750 mg two times per day) following an acute kidney injury. Ciprofloxacin was also stopped when bacterial resistance was suspected. Intravenous ceftriaxone was given for the full 6-week course.
In addition to treatment with antibiotics, it was important to find and eliminate the source of any deep-seated infection to prevent further bacteraemia. An orthopantomogram showed multiple right-sided dental caries and five affected teeth were extracted during his inpatient stay.
Ultimately, cardiothoracic surgery was required to repair the mitral valve due to the severity of prolapse and regurgitation. The surgeon used a thoracoscopic approach, leaving the patient with a scar less than 3 cm long.
Intraoperatively, it was apparent that the P1 leaflet had been destroyed by endocarditis (figure 4). It was not possible to determine if there was any underlying valve pathology but the surgeon noted that there appeared to have been a vegetation that had either resolved with treatment or departed as an embolus.
Intraoperative transoesophageal echocardiogram. The prolapsing mitral valve leaflet (indicated by the green arrow) is P1.
Incidentally, it was discovered that the patient had a small PFO, which was closed during the operation. Prior to discharge, he was commenced on a 6-week course of a beta-blocker (the main drugs recommended for prevention of postoperative atrial fibrillation),7 colchicine (an effective, inexpensive and short-acting drug, used to reduce postoperative pain from pericardial and right pleural inflammation) and a proton-pump inhibitor (gastroprotective cover following intraoperative transoesophageal echocardiogram).
Outcome and follow-up
Following surgery, the patient was initially transferred to the cardiac intensive care unit (a specialist ward managing perioperative patients undergoing cardiothoracic surgery) before being stepped down to the ward. He developed a small pneumothorax post chest drain removal, which was managed conservatively.
He was followed up in the outpatient parenteral antibiotic therapy clinic the day after discharge and antibiotics continued for three more days, completing a total duration of 6 weeks. The PICC line was removed and the patient discharged. All medication was stopped at 4-week follow-up before the patient returned to East Asia.
Discussion
While normally harmless, N. elongata can occasionally cause severe, deep-seated infection, such as endocarditis (as in this patient) or osteomyelitis.8 The most commonly implicated subspecies is N. elongata subsp. nitroreducens.3 4 Pre-existing valvular or congenital heart disease and dental disease appear to be the leading risk factors for infection with N. elongata.2 3
Unlike cases of gram-positive endocarditis, there is comparatively little in the literature about managing gram-negative, non-HACEK bacterial pathogens, which account for <5% of causes of infective endocarditis.1 9 Currently only a handful of case reports on treating N. elongata exist (on which our management of the patient was based—see table 1) and there are no standard guidelines.2 The duration of 6 weeks of antibiotic therapy was extrapolated from existing guidance for other gram-negatives and HACEK group (i.e. Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella and Kingella) organisms.
Summary of cases of Neisseria elongata infective endocarditis
| Reference | Antibiotics | Valve affected | Surgery | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| All the patients in the above case reports survived (no mortalities reported). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Our case report | Ceftriaxone (6 weeks) with gentamicin (5 days) then ciprofloxacin (16 days) | Mitral | MV repair with PFO closure. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Youssef et al, 20192 | Ceftriaxone and ciprofloxacin (6 weeks) | Aortic | AVR | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Banjari et al, 20213 | Cefotaxime and levofloxacin (6 weeks) | Mitral | N/A | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haddow et al, 20034 | Ceftazidime (7 weeks) and gentamicin (4 weeks) | Aortic | AVR | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sawas et al, 201510 | Ceftriaxone (6 weeks) | Aortic and Mitral | AVR and MVR | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apisarnthanarak et al, 200111 | Ceftriaxone (6 weeks) | Mitral | N/A | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sammanodi et al, 201612 | Ceftriaxone (6 weeks) | Aortic | AVR | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Perez, 198613 | Ampicillin (43 days) and tobramycin (26 days) | Aortic | AVR | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Simor and Salit, 198314 | Penicillin (2 days), gentamicin (2 days), ampicillin (4 weeks) | Mitral | MVR | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Kaplan and Flaherty, 199115 | Ceftazidime (10 days), gentamicin (16 days), ampicillin (4 weeks) | Mitral | MVR | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Struillou et al, 199316 | Ceftriaxone (6 weeks), gentamicin (3 weeks) | Mitral | N/A | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Picu et al, 200317 | Ceftriaxone (6 weeks) and gentamicin (2 weeks) | Aortic | N/A | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Andersen et al, 199518 | Penicillin (5 weeks), gentamicin (5 weeks) | Aortic | N/A | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Meuleman et al, 199619 | Ampicillin (6 weeks), gentamicin (2 weeks) | Aortic | N/A | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nawaz et al, 199620 | Ampicillin and vancomycin (3 days), then ceftriaxone and gentamicin (6 weeks) | Mitral | Removal of brachial pseudoaneurysm | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dominguez and Smith, 199821 | Vancomycin and gentamicin then ampicillin (4 weeks) | Aortic | AVR | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Evans et al, 200722 | Amoxicillin and gentamicin (3 weeks) then ceftriaxone (2 weeks) | Aortic | N/A | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hsiao et al, 200823 | Penicillin and gentamicin (1 week) then ceftriaxone (7 weeks) | Mitral | Resection of vegetation and chordae. MV repair. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bousquet et al, 201324 | Ampicillin (6 weeks), gentamicin (3 weeks), ampicillin (3 weeks) | Aortic | N/A | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Yoo et al, 201425 | Cefazolin (1 day), vancomycin (2 weeks) | Tricuspid | N/A | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Herbert, 201426 | Ciprofloxacin (7 weeks) | Mitral | N/A | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Jenkins et al, 201527 | Ceftriaxone (4 days) then ciprofloxacin (duration not specified) | Mitral | MV repair | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osuka et al, 201528 | Meropenem (4 days), then ceftriaxone (2 weeks), then ampicillin (2 weeks) | Aortic | AVR | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rossella et al, 201629 | Gentamicin and ceftazidime (5 weeks) | Mitral | N/A | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Ethics statements
Patient consent for publication
Acknowledgments
Many thanks to all involved in the production of this case report. In addition to the named authors, thank you to Dr Graeme Kirkwood from the cardiology team who provided some initial advice on the content of the report, Dr Gayti Morris (microbiology consultant) for providing images of cultures and microscopy, Dr Saminderjit Kular (neuroradiology fellow) for providing the MRI and OPG images and to the Language Line interpreters who helped with interpretation around the consent form.
Footnotes
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Contributors The idea for the case report was conceived by RW, who was also responsible for writing and submitting the article. CM, TL and SH read, commented on and approved the final manuscript and provided information on the patient that contributed to the case report. SH offered invaluable information regarding the operation and provided the intraoperative TOE image. MRI and OPG images supplied by Dr Saminderjit Kular (Neuroradiology Fellow, Sheffield Teaching Hospitals). Images of cultures and microscopy provided by Dr Gayti Morris (Microbiology Consultant, Sheffield Teaching Hospitals). Patient supplied own testimonial.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.
References
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