Introduction
Infective endocarditis (IE) is estimated to occur in 11.6 per 100.000 inhabitants per year1, it can be caused by several agents, but mostly by bacteria.
Several mechanisms lead to colonization and infection of the vascular endothelium and bacteraemia, namely turbulent blood flow, electrodes and catheters, inflammation and degenerative valve changes2-6. The differential diagnosis should be considered in several scenarios, such as in the presence of fever of unknown origin.
Clinical presentation of IE is variable, depending on patient characteristics, underlying/concomitant cardiac disease, microorganisms’ presence and other complications4,6. The disease has a high mortality rate2,7.
The epidemiology of IE has changed in the last decades regarding microbiological germs and epidemiology. Traditionally, isolated agents were Staphylococcus aureus, negative-coagulase Staphylococcus and Enterococcus4. However, with the increasing number of hospital procedures and the use of wide spectrum antibiotics, other species have emerged (such as Corynebacterium striatum).
Corynebacterium striatum (CS) is a specie of the Corynebacterium genera which includes Gram positive bacilli, ubiquitous and can be found in the normal flora of skin and mucous membranes4,5,8. However, CS has been implicated in several infections, including meningitis, pulmonary abscess, septic arthritis, vertebral osteomyelitis, catheter-related blood stream infection and endocarditis5,9,10.
Risk factors for infection by CS include prosthetic devices other than artificial heart valves, like pacemakers, ventriculoperitoneal shunts or intravascular devices; pre-existing cardiac disease; and history of bacterial endocarditis11,12.
Most strains of CS are susceptible to several antimicrobials namely β-lactams, vancomycin, gentamicin and rifampin13.
The purpose of this study is to describe a clinical case of IE caused by CS and contextualize it in the available literature.
Case report
The authors present the case of an 86-year-old caucasian female patient, with a history of heart failure due to severe aortic stenosis. She had a bioprosthetic aortic valve implanted 7 years before, with prosthetic dysfunction identified in the previous year, she was proposed surgery but refused. Additionally, she presented atrial fibrillation, arterial hypertension, dyslipidemia and infra-renal abdominal aorta aneurism.
She was admitted to the Emergency Department due to worsening dyspnoea, orthopnoea and productive cough for several weeks. Physical examination on admission reported a temperature of 37.4ºC, blood pressure of 151-57 mmHg, heart rate of 96 beats per minute, respiratory rate of 16 breaths per minute, oxygen saturation was 85% breathing room air. Auscultation revealed a IV/VI systolic murmur, clear breath sounds with rhonchi and basal rales. Lower extremities presented oedema up to the knees bilaterally.
Complete blood count and basic metabolic panel revealed normocytic normocromic anemia with haemoglobin of 11.5 g/dL and leukocyte left shift, acute renal injury with a creatinine of 1.15 mg/dl and there was an hypoxic respiratory failure on arterial blood gasimetry. The chest X-ray revealed bilateral interstitial and alveolar oedema with cotton wool appearance.
Assuming the diagnosis of decompensated heart failure by a lower respiratory tract infection the patient started amoxicilin/clavulanate and intravenous diuretic.
Despite resolution of the infection and of renal injury (creatinine of 0.71 mg/dl), the patient remained in class III/IV of the NYHA (New York Heart Association) classification.
A transthoracic echocardiogram was performed on the 20th day and showed an aortic bioprosthetic valve with an exocentric long jet of prosthetic regurgitation directed to the anterior mitral valve leaflet, quantified has moderate insufficiency grade III/IV; preserved ejection fraction.
On the 25th day, she presented acute pulmonary oedema and fever, leucocytosis with neutrophilia and C-reactive protein of 15.66 mg/dl. Piperacilin/tazobactam and vancomycin were empirically initiated, with apirexia within the first 24 hours. Two sets of blood cultures grew CS only susceptible to vancomycin. Transoesophageal echocardiogram showed moderate to severe prosthetic insufficiency grade III/IV, and small echogenic lesion on the ventricular side of the prosthesis; preserved ejection fraction.
Fulfilling 2 major and 2 minor of the modified Duke criteria, the patient was diagnosed prosthetic valve endocarditis and received a 6-week course of intravenous vancomycin, with clinical and analytical improvement. Control blood cultures (at 14th antibiotic therapy day) were negative. Re-evaluation transthoracic echocardiogram (at the 35th day of antibiotic) reported an aortic bioprosthetic valve with an exocentric long jet of prosthetic regurgitation directed to the anterior mitral valve leaflet, quantified has moderate to severe insufficiency grade III/IV; reserved ejection fraction, no vegetation was visible.
The patient was considered to have a high surgical risk, therefore, she was refused for valve replacement surgery and was discharged home after completing the antibiotic therapy in class II/IV of the NYHA classification.
One month later, she was admitted with decompensated heart failure, with hypoxic respiratory failure, left lower extremity cellulitis, and again leucocytosis, neutrophilia and high C-reactive protein. She empirically started imipenem and vancomycin. The first 2 sets of blood cultures grew CS, the following 2 sets (4 days latter) had no growth. A new transthoracic echocardiogram was similar to the last and also revealed no vegetations. Despite cellulitis improvement, there was a worsening of the heart failure that culminated with the patient’s death at the 8th in-patient day.
Discussion
Even though Corynebacteria isolated in blood cultures are usually considered contaminants, they can be infective agents. They are ubiquitous in the environment and can colonize the skin and mucous membranes of normal or immunocompromised hosts. Thus, skin or mucosal injury may cause bacteraemia and infection.
The authors conducted a literature review in Medline to identify other described cases of IE due to CS, to integrate the clinical case with the available evidence. This search revealed 28 previously reported cases that are summarized in Table 1.
We acknowledge that case series study corresponds to one of the lowest levels of evidence, as usually only non-common cases are reported and therefore a publication bias generally exists. In addition, a descriptive analysis is impaired and inferential analysis is impossible. However, our main goal was to contextualize our case among similar cases and develop a comprehensive review of this situation.
As depicted in Table 1, most episodes occurred in male patients (18/28, 64%), with a mean age of 59 years (ranging from 24 to 83). The majority were native valve endocarditis (20/28, 71%), with a preference for the left heart, especially the mitral valve. However, 5 were pacemaker associated. More than half of the subjects had a history of cardiac disease, including valvular disease, heart failure and recently implanted pacemaker (< 1 year). Infections were commonly healthcare associated. As we could not determine if healthcare associated infections were nosocomial in several articles, we have decided to separate them only as healthcare associated or not. Eleven patients required surgery and 5 (nearly 18%) died.
We reinforce that outcomes were usually measured at discharge, when not mentioned otherwise (Table 1). In all cases, antibiotic therapy was adjusted to the susceptibility of CS, being the most commonly used vancomycin and daptomycin. However the treatment protocols were heterogeneous and therefore it was not possible to detect any pattern.
We highlight that clinically significant infections have been reported mostly in patients with immunodepression and/or indwelling intravascular catheters.
As we can note there is no typical patient that can develop IE due to CS, as several patients have none of the risk factors described for CS endocarditis.
The case that we report corresponds to a female with the highest age ever reported (86 years), with prosthetic aortic valve endocarditis. She had a pre-existing cardiac disease as a risk factor for CS endocarditis. Yet, she did not have any recent admissions nor invasive procedures. Even though a thorough investigation was performed we were not able to identify the source of the infection and of the relapse of the bacteraemia after directed antibiotic therapy.
In summary, although present in our flora, CS can be an infective agent, causing for example endocarditis.
Although there are several cases described in the literature, there is a lack of consistency and so a pattern could not be identified. More cases of IE due to CS should be described.
Quadro I
Table 1. Reported cases of infective endocarditis by Corynebacterium striatum
| Reference | Sex | Age | Underlying illnesses | Underlying cardiac illness | Clinical presentation | Valve | Echocardiogram | Treatment | Outcome | Healthcare associated |
| 2 (Marrull J, 2008) | F | 73 | HTN, CRF, DM, 9-day hospitalization 2 weeks before | Diastolic HF | Fever, chills, fatigue, lower extremity trace edema, 3/6 non-radiating systolic murmur at the apex | Mitral native | TTE; TEE | Medical (refused surgery) | Survived | Yes |
| 3 (Tran T, 2012) | M | 56 | DM, terminal CRF, two 6-week courses of daptomycin in the previous year for catheter related bloodstream infection and osteomyelitis of the left foot, the last one completed 3 weeks before | - | Fever, jugular venous distension, lung rales bilaterally, 3/6 pansystolic murmur at the apex | Mitral native | TEE | Medical and surgery | Died 3 weeks after discharge | Yes |
| 5 (Tibrewala A, 2006) | F | 69 | Debulking surgery for metastatic endometrial carcinosarcoma 4 weeks before | - | Weakness, fever, lower extremity edema, new murmur | Mitral native | TEE | Medical and surgery | Survived | Yes |
| 6 (Mashavi M, 2006) | M | 68 | HTN, stroke 2 years before, recent admission with pneumonia | Congestive HF; AF; prosthetic aortic valve 3 years earlier; prosthetic mitral valve 1 year before | Appeared ill, fever, palpable spleen edge, known grade 2 holosystolic murmur at the apex radiating axilla and left sternal border | Mitral prosthetic (spleen infarct) | TTE | Medical (refused surgery) | Survived | Yes |
| 8 (Arriba J, 2002) | F | 72 | HTN, DM | Ischaemic heart disease; severe aortic stenosis replaced by metallic prosthesis 52 days earlier | Fever post-surgical repair of hip fracture, precordial systolic murmur | Mitral native | TTE | Medical and surgery | Died | Yes |
| 9 (Bhat Y, 2008) | M | 83 | Metastatic prostate cancer, secondary hyperfibrinolysis syndrome with intracerebral bleed with full recovery, treatment for UTI during the previous 3 weeks | - | Fever, joint pain, ejection systolic murmur | Mitral native | TTE | Medical | Died 2 weeks after discharge | Yes |
| 10 (Jagadeeshan N, 2016) | M | 27 | Lower limb lymphedema | Rheumatic heart disease | Fever, pansystolic murmur at the apex radiating to axilla | Mitral native | Echocardiography | Medical | Survived | No |
| 11 (Melero-Bascones M, 1996) | M | 73 | - | Pacemaker, recent infection of the battery site with a supraclavicular draining sinus tract | Fever | Pacemaker electrode and tricuspid native | TTE; TEE | Medical and electrode removal | Survived | Yes |
| 12 (Hong HL, 2016) | M | 55 | Car accident with traumatic subdural hemorrhage 5 weeks earlier | - | Fever, lethargy, drowsiness | Mitral native | TEE | Medical and surgery | Survived | Yes |
| 13 (Shah M, 2005) | F | 46 | CRF on hemodialysis, removal of an infected left femoral graft used to repair a pseudoaneurysn of the left femoral artery 1 month before | - | Fever, chills, chest pain, grade 2/6 systolic murmur at the left sternal border, cerebral right frontal bleed and right occipital infarct | Tricuspid native | TEE | Medical | Survived | Yes |
| 14 (Oliva A, 2010) | F | 71 | - | Pacemaker replacement 2 months before | Fever and generator site pain with purulent drainage, 2/6 systolic murmur | Pacemaker intracardic lead | TTE | Medical, device removal and implantation of a new pacemaker | Survived | Yes |
| 15 (Guerrero M, 2012) | M | 78 | CRF, DM | Pacemaker implantation 6 months earlier | Fever, back pain, weakness of the lower limbs, mild systolic murmur, paresis of the lower limbs with loss of sensation below D11-D12 | Intracardiac lead (spondylodiscitis) | TTE | Medical, electrode wire removal and implantation of a new ones | Survived | Yes |
| 16 (Boltin D, 2009) | M | 71 | DM, fall with head injury 5 months earlier complicated with 2 episodes of aspiration pneumonia with hospital admission | - | Fever, respiratory symptoms, emboli in the left common femoral vein, splenic infarct | Mitral native | TEE | Medical (not eligible for surgery) | Died | Yes |
| 17 (Tattevin P, 1996) | M | 24 | Congenital hydrocephalus with ventriculo-atrial shunt and paraplegia, sacral sore, recent antibiotic treatment for UTI | - | Fever | Pulmonary native | TTE; TEE | Medical | Survived | Yes |
| 18 (Belmares J, 2007) | M | 62 | HTN, mild CRF, alcoholism | Diagnostic cardiac catheterization the week before | Fever, lower back pain, new onset urinary retention, spondylodyscitis | Aortic native | TEE | Medical and surgery | Survived | Yes |
| 19 (Stoddart B, 2005) | F | 72 | - | Childhood rheumatic fever, mitral valvulotomy 45 years earlier, mitral valve prothesis 15 years before; culture negative endocarditis 18 months previously | Weight loss, malaise, sweats, dizziness and arthralgia | Mitral prosthesis | TEE | Medical | Survived | No |
| 19 (Stoddart B, 2005) | F | 61 | Cutaneous lupus, multiple episodes of pulmonary embolism, hypothyroidism | Coronary heart disease, childhood rheumatic fever | Dizziness, nausea, back pain, palpitations, lethargy, low grade fever, bilateral retinal hemorrhages | Mitral native | TTE | Medical | Survived | No |
| 20 (Houghton T, 2002) | F | 62 | Recently admitted with a bout of diarrhoea | Bioprosthetic aortic valve 5 months before | Lethargy, malaise, fever | Aortic prosthesis | TTE; TEE (no vegetations; presumption diagnosis) | Medical | Survived | ? |
| 21 (Xu J, 2017) | M | 63 | HTN | AF | Progressively worsening dyspnea on exertion and aggravated lower leg edema for a month. Admission and surgery for a atrial apex thrombus. During the admission fever | Aortic native | Echocardiography | Medical and surgery | Survived | Yes |
| 22 (Mizoguchi H, 2014) | F | 53 | - | - | Fever, leg edema, grade 4/6 cardiac systolic ejection murmur | Aortic native (quadricuspide) | TTE; TEE | Medical and surgery | Survived | No |
| 23 (Abi R, 2012) | M | 51 | - | Pacemaker implantation 7 months before | Migrant polyarthralgia, fever, holosystolic murmur | Pacemaker electrocatheter | TEE | Medical and pacemaker removal | Survived | Yes |
| 24 (Batalla A, 2011) | M | 62 | DM, calcaneum osteitis with osteosynthesis material, recent admission for foot osteitis | Dilated cardiomyopathy, mitral insufficiency, Aortic stenosis, AF | Dyspnea, fever, mitral and aortic systolic murmurs, splenic infarct | Mitral and aortic native | TEE | Medical and surgery | Survived | Yes |
| 25 (Kocazeybek B, 2002) | M | 50 | Surgery for a distal aneurysm of the left posterior communicating artery and the right middle cerebellar artery in another health center | - | Palpitations related to effort | Aortic native | TEE | Medical and surgery | Survived | Yes |
| 26 (Juurlink D, 1996) | M | 68 | DM, HTN, smoker, COPD | Congestive HF | Anorexia, fatigue, confusion, fever, AF, elevated central venous pressure, signs of left ventricular failure, loud pansystolic murmur at the apex radiating to the left axilla | Mitral native | TTE | Medical | Survived | No |
| 27 (Guerrero M, 2013) | M | 78 | - | Pacemaker implantation 6 months earlier | Fever and weakness of the lower limbs, mild systolic murmur, spondylodyscitis | Pacemaker electrocatheter | TTE | Medical and electrocatheters removal and substitution | Survived | Yes |
| 28 (Rufael D, 1994) | M | 54 | HTN, hemorrhoids, former smoker | - | Fever, cough, shortness of breath, audible 3th heart sound, grade 2/6 systolic murmur | Aortic native | TTE; TEE | Medical and surgery | Survived | No |
| 29 (Hashizume K, 2016) (abstract) | F | 49 | - | - | Disturbance of consciousness and nosebleeds | Mitral and aortic native | ? | Medical and surgery | Survived | No |
F: female; M: male; HTN: arterial hypertension; CRF: chronic renal failure; DM: diabetes mellitus; TTE: trans-thoracic echocardiogram; TEE: trans-esophageal echocardiogram; HF: heart failure; AF: atrial fibrillation; UTI: urinary tract infection; COPD: chronic obstructive lung disease
BIBLIOGRAFIA
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