Keywords
Endocarditis - Gemella haemolysans - mitral - regurgitation
INTRODUCTION
Infective endocarditis (IE) remains a concerning pathology given the increasing incidence
and the growing rate of requiring valve replacement surgery.[1] Furthermore, the associated rates of morbidity and mortality are high, with reported
short-term mortality, that is, within 30 days from the diagnosis, of 10%–30%, making
IE a great burden on global health.[2],[3]
IE is classified into acute and subacute depending on timing and severity. Acute IE
usually has an aggressive course with a rapidly progressive illness, where subacute
IE has usually a more indolent course and may extend over many months, which may lead
to a delay in the diagnosis.[4] The classic clinical manifestation, which combines fever, heart failure, new cardiac
murmurs, and embolic and immunologic phenomena, is rare.[5] Modified Duke criteria aid in making the diagnosis and include clinical, microbiological,
pathological, and imaging features.[6],[7] In a previous study, it was shown that modified Duke criteria helped with 10% increase
in the frequency of cases being deemed clinically as definite IE, compared with Duke
criteria, with no loss of specificity.[3],[6]
Elderly patients can have atypical presentations and the diagnosis may become challenging.[8] Treatment of IE relies on microbial eradication by antibiotics. In some cases, surgery
is indicated, mainly if the infection is not well controlled (evidence of an abscess
or an enlarging vegetation), if there is indication for prevention of embolic events
(as in left-sided IE with a very large vegetation >30mm, or an evidence of an embolic
event despite appropriate antibiotic therapy), and in the case of heart failure.[3],[9]
The bacteriology of IE varies depending on the cohort examined; however, Staphylococcus aureus and Streptococci comprise most of the organisms involved.[9],[10] Change in the causative organisms have been noted in recent years with emerging
species that are often difficult to grow.[1],[11],[12]
Gemella species is present in the human oropharynx, the genitourinary system, and the gastrointestinal
system. It has been implicated in several diseases primarily in adults, including
meningitis and septic shock but rarely IE.[13],[14] The genus currently includes six subspecies that cause similar clinical illness:
morbillorum, haemolysans, bergeriae, sanguinis, palaticanis, and cuniculi, in addition to other subspecies that are restricted to animals.[15]
Gemella morbillorum was initially thought to be part of the genus Streptococcus until 1988 when it was
found to be related to G. haemolysans at the genus level.[16]
The literature on Gemella has been scarce and based mainly on case reports as the incidence is rare. In this
paper, we report a case of IE caused by G. haemolysans and review the related literature, aiming to gather what is known about this infection
in one source.
CASE REPORT
An 81-year-old man presented with dyspnea. He had a medical history of coronary artery
disease, hypertension, chronic obstructive pulmonary disease (COPD), and atrial fibrillation.
He underwent a coronary artery bypass grafting (CABG) 2 months preceding presentation
but was in his usual state of health until 2 weeks before presentation when he developed
weakness and exertional dyspnea.
He denied any fever, rigors, or chest pain. On physical examination, he was afebrile
and edentulous. On cardiac auscultation, he had an irregular heart rhythm with a 4/6
soft blowing systolic murmur in the left lower sternal border radiating to the axilla
along with bilateral lung wheezing. His skin exam did not reveal any Osler nodes or
Janeway lesions, and no Roth spots were noted in the eye examination.
Initial laboratory work showed a white cell count of 15,400/mm3, hemoglobin of 8.7g/dL, creatinine level of 1.74mg/dL, pro-brain natriuretic peptide
of 11,341 pg/mL, and procalcitonin level of 28.66ng/mL (with normal value of below
0.15ng/mL in healthy adults without kidney injury). A transthoracic echocardiogram
was obtained to assess for a possible cardiac etiology for the patient’s symptoms,
and that revealed a normal ejection fraction; however, a new moderate mitral regurgitation
with a 1x1 cm uniform, round and immobile mass on the atrial surface of the anterior
mitral leaflet [Figure 1]. [Figure 2] is included for comparison, and it shows a transthoracic echocardiogram that was
obtained couple months before the current presentation, when he underwent CABG.
Figure 1: Transthoracic echocardiogram, parasternal long access view showing the vegetation
on the anterior mitral leaflet. AML = anterior mitral leaflet, IVS = interventricular
septum, LA = left atrium, LV = left ventricle, PML = posterior mitral leaflet, PW
= posterior wall, RVOT = right ventricle outflow tract, V = vegetation
Figure 2: Transthoracic echocardiogram, parasternal long access view obtained couple
months before current presentation. AML = anterior mitral leaflet, IVS = interventricular
septum, LA = left atrium, LV = left ventricle, PML = posterior mitral leaflet, RV
= right ventricle, V = vegetation
Because of concerns for endocarditis, the patient was started on vancomycin and ceftriaxone
after blood cultures were obtained. Transesophageal echocardiogram showed an anterior
leaflet mass measuring 1.3 × 0.8cm, consistent with vegetation on the atrial aspect
with moderate mitral regurgitation.
Preliminary report showed gram-positive cocci that turned out to be G. haemolysans by mass spectrometry (MS)-based molecular identification (Microflex, matrix-assisted
laser desorption ionization time-of-flight [MALDI-TOF]), which was later confirmed
by the Michigan State Laboratory. Follow-up antimicrobial susceptibility results showed
the isolate to be highly sensitive to penicillin (≤0.03mg/mL), ceftriaxone (≤0.06mg/mL),
meropenem (≤0.06mg/mL), and vancomycin (≤0.5mg/mL). The treatment was then changed
to penicillin and gentamicin.
As a part of the workup to find a source for the bacteremia, and as the patient was
edentulous, he underwent a colonoscopy, which showed a tubular villous adenoma that
measured 9cm with a focus of high-grade dysplasia.
The patient did not have any embolic phenomena. He was advised to undergo a surgical
replacement of the mitral valve; however, he opted to pursue conservative management
and was discharged to complete a 6-weeks course of ceftriaxone and 2 weeks of gentamicin.
He returned to the hospital 3 days following discharge complaining of increasing dyspnea
and was hypotensive. He was started on vasopressors. A repeat transesophageal echocardiogram
showed a rupture in the mitral leaflet with increased mitral regurgitation and multiple
regurgitation jets [Figure 3].
Figure 3: Four chamber view of transesophageal view showing mitral regurgitation jet
and vegetation. AML = anterior mitral leaflet, IVS = interventricular septum, J =
mitral regurgitation jet, LA = left atrium, LV = left ventricle, V = vegetation
The patient subsequently developed cardiogenic shock and was enrolled in hospice and
passed away couple of days later.
REVIEW OF THE LITERATURE
We reviewed PubMed for cases of Gemella-associated endocarditis using appropriate key words. The articles in languages other
than English and those that do not include case reports were excluded. The articles
were reviewed to gather information about patients’ demographics, symptoms, microbiology,
echocardiographic findings, and treatment options.
RESULTS
We found a total of 75 articles that included our key words in their titles, of these,
62 were included, depicting 65 cases, after adding our case, we analyzed a total of
66 cases. The characteristics of these cases are shown in [Table 1] and [Table 2]. The mean age was 50.5 years (range, 4–84 years) with the majority being men (46,
72%).
Table 1
Characteristics of cases of Gemella infective endocarditis
|
Characteristics
|
Participants (N = 66)
|
|
Age group (years; N = 64)
|
50.5 ± 23
|
|
0-10
|
3 (5%)
|
|
1 1-20
|
5 (8%)
|
|
21-30
|
6 (9%)
|
|
31-40
|
7 (11%)
|
|
41-50
|
8 (13%)
|
|
>51
|
35 (55%)
|
|
Gender (N = 64)
|
|
Male
|
46 (72%)
|
|
Female
|
18 (28%)
|
|
Source (N = 30)
|
|
Dental/oral
|
22 (73%)
|
|
Intravenous drug abuse
|
4 (13%)
|
|
Colonic
|
4 (13%)
|
|
Presentation
|
|
Fever
|
40 (61%)
|
|
Fatigue
|
7 (11%)
|
|
Dyspnea
|
6 (9%)
|
|
Miscellaneous
|
13 (19%)
|
|
Gemella species (N = 63)
|
|
G. morbillorum
|
34 (54%)
|
|
G. haemolysans
|
17 (26%)
|
|
G. sanguinis
|
6 (10%)
|
|
G. bergeriae
|
5 (8%)
|
|
G. taiwanensis
|
1 (2%)
|
Table 2
Valve affected, surgery, and outcomes of Gemella infective endocarditis
|
Characteristics
|
Participants (N = 66)
|
|
Valve affected (N = 62)
|
|
Mitral valve
|
24 (39.1%)
|
|
Aortic valve
|
15 (24%)
|
|
Prosthetic mitral valve
|
9 (14%)
|
|
Others
|
14 (23%)
|
|
Surgery
|
|
No
|
31 (50%)
|
|
Yes
|
31 (50%)
|
|
Aortic valve
|
13 (42%)
|
|
Mitral valve
|
13 (42%)
|
|
Mitral and aortic valve
|
5 (16%)
|
|
Others
|
7 (23%)
|
|
Outcomes (N = 57)
|
|
Survived
|
47 (82%)
|
|
Died
|
10 (18%)
|
|
Outcomes based on treatment type (N = 53)
|
|
Required surgery and died
|
24 (45%)
|
|
Conservative approach and died
|
23 (43%)
|
|
Required surgery and survived
|
5 (9%)
|
|
Conservative approach and survived
|
1 (2%)
|
Onset of illness was subacute in majority of cases (37, 63%), and fever was the most
common chief complaint in 40 (61%) patients. The mitral valve was the most affected
valve (24 cases, 39%), followed by the aortic valve in 15 cases (24%).
The source of infection was described in 30 cases of which dental source (22, 73%)
was the most common source.
Surgical intervention was pursued in 31 (50%) of the reported cases, of these 13 patients
(42%) underwent aortic valve replacement and 13 patients (42%) underwent mitral valve
replacement, whereas 5 patients (32%) underwent both aortic and mitral valve replacement.
Outcomes were available in 57 patients with a mortality rate of 18%. The mortality
rate was similar with no significant difference between the group that proceeded with
surgical intervention (45%) and the group that received conservative approach (43%).
G. morbillorum was the most common subtype in the 63 cases that reported the subtype (34, 54%),
followed by G. haemolysans (17, 26%).
DISCUSSION
Gemella species is a gram-positive, facultative anaerobic bacterium that was first reported
in 1917.[17] It was initially thought to be a part of the Neisseriaceae family[18],[19] until 1961, when it was found to be sufficiently distinctive to form a different
genus.[20] The virulence factors are not well studied; however, the production of exopolysaccharide
may contribute to its capability of causing endocarditis.[21]
The demographic findings in our results may represent those of IE as a whole, recent
data have shown a shift toward older patients and more males being affected with IE.[22] This can also be attributed to the higher frequency of predisposing conditions such
as dental disease and colon cancer in older individuals.[23],[24] The high number of cases caused by G. morbillorum may be due to the fact that it
was the first subtype to be discovered, this finding may change over time with more
cases reported.
Gemella isolates have shown to be susceptible to β-lactams and vancomycin, with less response
to other antibiotics such as macrolides, levofloxacin, and clindamycin.[25],[26],[27] As it is impossible to clinically differentiate Gemella from other causes of IE, antibiotic therapy is empiric in acutely ill patients, with
vancomycin being the best choice after obtaining sufficient blood cultures.[28] Once Gemella is isolated, choice of antibiotics and length of treatment depend on minimal inhibitory
concentration of penicillin on susceptibility testing.[29]
Gemella species is generally sensitive to penicillin G, and a combination of penicillin G
and gentamicin is the current treatment of choice for these infections, whereas vancomycin
can be used in patients with penicillin allergy. In our patient, the isolate was highly
sensitive to penicillin, ceftriaxone, and vancomycin and the decision was made to
discharge him on ceftriaxone and gentamicin given the ease of administration.
The source of bacteremia should be sought in all cases of Gemella IE, and potential risk factors include dental procedures, poor dentition, colorectal
disease and procedures, bypass surgery, as well as immunocompromised status.[30]
Gemella has been found to be more abundant in the stool of patients with colorectal cancer
compared with healthy individuals,[31] and more abundant in the cancerous tissue specifically.[32] Some studies defend that the lesioned mucosa, that is undergoing chronic inflammation,
is propitious to translocation of organisms including Gemella, leading to bacteremia and subsequently endocarditis.[33]
The organism can be difficult to be identified with standard techniques, and the 16S
rRNA identification method seems to be the most accurate mean of diagnosis.[34] We detected the organism by MALDI-TOF MS, which shows strong potential as a new
method for species identification of many bacteria in clinical microbiological laboratories.
CONCLUSION
Gemella spp. is a rare cause of IE, but it should be identified and treated properly as it
can otherwise result in a significant morbidity and mortality. The main source of
Gemella IE is dental; however, colonic etiologies should also be suspected in patients without
apparent source. The infection can be destructive and must be promptly treated to
avoid complications. In addition, optimal therapy should include valve repair or replacement
in patients with clinical progression, despite appropriate antimicrobial therapy.
