| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
ORIGINAL CONTRIBUTION |
Cardiothoracic Surgical Unit, Royal Prince Alfred Hospital, New South Wales, Australia
For reprint information contact: Clifford F Hughes, AO, FRACS Tel: 61 2 9515 8629 Fax: 61 2 9515 6378 Email: clifford.hughes{at}email.cs.nsw.gov.au, Cardiothoracic Surgical Unit, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia.
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSREVIEW OF THE LITERATUREDISCUSSIONREFERENCES |
|---|
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSREVIEW OF THE LITERATUREDISCUSSIONREFERENCES |
|---|
Though other species of Corynebacterium do cause endocarditis, C. diphtheriae endocarditis is the most common. A review of the literature revealed 70 cases reported so far. The organism is virulent and the outcome is poor in the majority of cases.1–4 We reviewed our experience with this disease over a period of 10 years and reviewed the available literature.
|
PATIENTS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSREVIEW OF THE LITERATUREDISCUSSIONREFERENCES |
|---|
. Seventy reported cases could be traced through a Medline search using "Corynebacterium diphtheriae", "endocarditis", "infections", "pathogenicity", and "epidemiology" as keywords in different combinations, along with examination of relevant review articles on the topic. All cases with evidence of endocarditis in the form of positive blood culture, echocardiographic or autopsy evidence of vegetation, even with incomplete information, were included in the review. These are summarized in Table 2.
|
|
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSREVIEW OF THE LITERATUREDISCUSSIONREFERENCES |
|---|
PATIENT 1
A 26-year-old female was admitted on 21 March 2003 with a clinical diagnosis of moderately severe mitral regurgitation. She had a high-grade fever associated with malaise, myalgia, and a sense of being unwell. She had undergone mitral valve repair for rheumatic heart disease in France in 1987 and was awaiting elective mitral valve replacement. Her laboratory parameters were unremarkable except for evidence of systemic infection with leukocytosis and neutrophilia. Blood cultures grew C. diphtheriae var. gravis and benzyl penicillin (to which it was sensitive) was started.
Transthoracic echocardiogram revealed an echo-dense vegetation measuring 1.5 cm x 1.5 cm on her anterior mitral leaflet, which had multiple perforations causing severe mitral regurgitation. There was moderate tricuspid and aortic valve regurgitation. She was hemodynamically stable with no signs of heart failure. It was thought that she would require at least a redo double valve procedure involving mitral, tricuspid, and possible aortic valve replacement. It was decided to stabilize her condition with antibiotics in an attempt to control infection prior to surgery.
She improved initially, but on the 7th day her mitral regurgitation suddenly worsened and she developed pulmonary edema. She was operated upon urgently and the mitral valve replaced with a CarboMedics 25 mm valve and the tricuspid valve with a CarboMedics 27 mm (mitral model). Her aortic valve did not require replacement, as only mild aortic regurgitation was present on intraoperative transesophageal echocardiogram. The anterior leaflet of the mitral valve was destroyed and there was a large perforation in it. All the chordae of the anterior mitral leaflet were destroyed. There was no evidence of infection on the tricuspid leaflets but it was impossible to achieve valvular competence with repair, hence it was replaced. She tolerated the procedure well and went home after 4 weeks. Initial benzyl penicillin was changed to the more convenient, once daily, intravenous ceftriaxone after 1 week. This continued even when at home for a total of 6 weeks. All her postoperative cultures were sterile. Her postoperative course was unremarkable and her transthoracic echocardiogram revealed normally functioning prosthetic mitral and tricuspid prostheses with mild aortic regurgitation and good left ventricular function.
Histopathological examination of the mitral valve revealed an irregular cream-colored vegetation on the valve leaflet. There was evidence of acute endocarditis in the form of fibrinous vegetations with early organization, destruction, necrosis, and granulation in the underlying valve stroma. The valve leaflet itself showed fibrinous thickening, nodular calcification, and a thin layer of endothelial cells and fibropurulent debris on the surface. Valve tissue sent for culture was sterile and a Gram stain did not reveal any organism.
PATIENT 2
A 33-year-old male with known mitral valve prolapse and a bicuspid aortic valve was admitted on 24 March 1994 with a diagnosis of moderately severe aortic regurgitation and a high-grade fever. He had been on oral penicillin prophylaxis since 1980 for his incompetent aortic valve. His blood cultures grew C. diphtheriae var. gravis. His laboratory results revealed a systemic infection with leukocytosis and neutrophilia. A transthoracic echocardiogram demonstrated a bicuspid aortic valve with a flail anterior leaflet; mobile echo-dense vegetation and moderate diastolic prolapse of the posterior leaflet. As there was no evidence of heart failure, he was treated with benzyl penicillin and gentamicin with an aim to stabilize his condition before surgical intervention.
Two weeks after initiating antibiotic therapy, he suddenly developed pulmonary edema and deteriorated hemodynamically. Repeat echocardiogram revealed severe diastolic prolapse of both aortic leaflets and free aortic regurgitation. There was echo-dense vegetation in the left ventricular outflow tract. He was taken for emergency aortic valve replacement.
At operation there was mild mitral regurgitation. The aortic valve was largely destroyed and grossly regurgitant. There was an abscess cavity around each commissure. These were debrided and plicated with pledgeted 2–0 prolene sutures. His aortic valve was replaced with an 11A Starr Edwards prosthetic valve. Culture of valve tissue did not grow any organism. He was continued on intravenous antibiotics for 6 weeks. He progressed well and remained afebrile, but developed gentamicin ototoxicity. He was discharged 7 weeks after operation. Echocardiogram at the time of discharge was unremarkable showing a normally functioning prosthetic valve with a peak trans-prosthetic gradient of 40 mm Hg and good left ventricular function.
PATIENT 3
A 21-year-old male was transferred to our neurosurgery unit with the diagnosis of intracerebral hematoma on 27 May 2002. He had a left hemiparesis and a high-grade fever. He had an associated right internal maxillary artery mycotic aneurysm, which was subsequently treated with coil embolization. He had a deep vein thrombosis in his right leg and had been on subcutaneous anticoagulant therapy. The intracerebral hematoma was possibly the result of excessive anticoagulation. Blood cultures grew C. diphtheriae var. gravis and benzyl penicillin therapy had been initiated prior to inter hospital transfer.
His echocardiogram revealed mitral valve prolapse with moderate mitral regurgitation. There was a 0.6 cm x 0.9 cm vegetation on his posterior mitral leaflet with normal leaflet motion and normal left ventricular function. The intracerebral hematoma was urgently evacuated through a craniotomy when his left hemiparesis worsened. He responded well to antibiotic therapy and left ventricular dimensions remained static without evidence of heart failure. He was treated conservatively with benzyl penicillin for 6 weeks and was discharged in a stable condition.
PATIENT 4
A 22-year-old male was admitted to our cardiology unit from a nearby hospital with a diagnosis of sub acute bacterial endocarditis on 20 August 1993. He had a high-grade fever, malaise, and myalgia. Blood cultures grew C. diphtheriae var. gravis. He also had osteomyelitis in the left fibular head and septic arthritis of the knee joint. He was treated with flucloxacillin, penicillin, and gentamicin. Transesophageal echocardiogram showed a mobile vegetation measuring 1 cm in size on the posterior mitral leaflet near its free edge. There was mild mitral regurgitation. He was treated with intravenous antibiotics for 3 weeks and responded well with disappearance of the vegetation. He was discharged in a stable condition with oral penicillin for 3 weeks.
|
REVIEW OF THE LITERATURE |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSREVIEW OF THE LITERATUREDISCUSSIONREFERENCES |
|---|
).
RISK FACTORS
Of 57 cases for which information was available, predisposing factors could be found in 38 (70%) cases. Incompetent cardiac valves and intravenous drug use were the most common risk factors (50%); however, prosthetic valve and congenital cardiac anomalies contributed some (Table 2).
DIAGNOSIS AND BIOTYPE
The diagnosis was made on clinical grounds with evidence of positive blood culture of C. diphtheriae. Echocardiography was available in only 18 cases. Autopsy evidence of vegetation was found in 10 cases. The most common biotype was gravis 22/40 (55%), followed by mitis 17/40 (42.5%), and intermedius 1/40 (2.5%). Of 41 cases for which information was available, 36 (88%) were non-toxigenic with only 5 (12%) cases being due to a toxigenic strain (Table 2).
CLINICAL PRESENTATION AND HOSPITAL COURSE
Fever (high-grade), malaise, arthralgia, and pharyngitis were the most common symptoms at presentation.1–3,5–8 Other presentations included peripheral vascular complications of embolism (9 cases), mycotic aneurysm (8 cases), cerebrovascular accident due to embolism or infarction (11 cases), and septic arthritis in 7 cases.1–3,6,8–12 No specific clinical features could be seen in relation to the different biotypes. There was documented evidence of sudden deterioration in 12 patients in the course of medical treatment, 6 were operated on and 5 survived. All of the other 6 patients who were not operated on died (Table 2).
OUTCOME AND COMPLICATIONS
Excluding 3 patients for which no clear information is available, there were 29 deaths constituting an overall mortality of 43%. The case fatality rate for the mitis biotype was 8/17 (47%), followed by 5/22 (23%) for the gravis biotype. The most common complication was involvement of the vascular tree, presenting as a cerebrovascular accident or a peripheral mycotic aneurysm or embolism in 21/57 (34%) cases. Septic arthritis was seen in 7/57 (12%) cases with cerebral, hepatic or splenic abscess in a few cases (Table 2).
OUTCOME IN PATIENTS WITH NORMAL VALVES
There were 18 patients with previously normal valves of whom 5 were operated on and 13 treated conservatively. Of the 5 operated patients, 2 died and 3 survived. Out of 13 patients who were treated conservatively, 5 died (44%) and 8 survived (Table 2).
TREATMENT
CONSERVATIVE TREATMENT
The majority of cases were treated entirely conservatively with antibiotics, however, 12 needed operation. The choice of antibiotics depended on culture and sensitivity report, however, benzyl penicillin was usually the initial choice.1,7,8,11,12 A combination of antibiotics, including an aminoglycoside, was used in the majority of cases. Few cases were treated with vancomycin as well.1,8 The apparent diversity in the choice of antibiotics reflects institutional preference (Table 2).
MEDICAL VERSUS SURGICAL TREATMENT
Excluding 14 cases for which no clear information about treatment is available, 44 cases were treated medically. Of those, 27 died, constituting a mortality of 61% for medical treatment. One case reported by Van der Horst et al5 deteriorated so dramatically that he died before surgical intervention could be performed. Twelve cases were operated on and 3 died (25% mortality). The first, a 4-year-old boy, died after mitral valve replacement due to low cardiac output (Davidson et al3), the second a 24-year-old male intravenous drug user died of intracerebral hemorrhage (Gubler et al10), while the third, a 7-year-old girl died due to acute prosthetic valve dysfunction (Lortholary et al12) (Table 2).
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSREVIEW OF THE LITERATUREDISCUSSIONREFERENCES |
|---|
Our first case had pre-existing moderately severe mitral regurgitation following previous mitral valve repair and indicates the propensity of this organism to infect structurally abnormal valves. Similarly, in our second patient with pre-existing aortic incompetence, initial improvement was followed by acute deterioration and pulmonary edema. The development of an annular abscess despite apparent antibiotic control indicates the destructive virulence of this organism. A sudden deterioration in hemodynamics demands immediate surgical intervention.
One of the 7 cases reported by Tiley et al1 had mitral valve prolapse and needed surgery in similar circumstances. Two other patients, one with a mitral prosthesis and the other with mitral valve prolapse survived with conservative treatment alone. Of 4 patients with an apparently normal valve prior to infection, only one died of valve destruction.
Similar cases of sudden deterioration leading to death of the patient have been reported by Davidson et al,3 Van der Horst et al,5 Sutherland and Willis,13 and Chi-Wu and Ts’un.14 However, in recent years, similar deterioration has been treated surgically with survival as reported by Holthouse et al,2 Booth et al,6 and Belco et al.8
Our third patient is probably atypical, as deep vein thrombosis in association with this organism has not been reported. The development of a mycotic aneurysm of the right internal maxillary artery is, we believe, due to vascular involvement by this organism. Similar reports of mycotic aneurysms of the popliteal, posterior tibial, and superficial femoral arteries have been reported by Tiley et al1 and Holthouse et al,2 respectively, in the past. This patient recovered without sequelae.
The fourth patient with endocarditis and septic arthritis of the left knee also recovered without sequelae. This indicates the responsiveness of the organism to appropriate antibiotics. The vegetation in this patient also resolved. But these last 2 patients had apparently normal valves before operation.
Similarly, in the literature, 4 patients with apparently normal valves have been treated conservatively by Hogg et al,9 Merzbach et al,15 and Guard,16 with survival. This would suggest that normal valves are not as prone to destruction and that the organism will usually respond well to an appropriate antibiotic regime. Surgical intervention may not always be mandatory for previously normal valves with only small vegetations. Surgical treatment, however, should be individualized and the patient kept under extremely close observation.
Given the relatively few reports of this condition, it is not surprising that there will be some variation in antibiotic regimes. The organism in general is sensitive to the cell wall acting antibiotics, i.e. all of the penicillins and cephalosporins as well as vancomycin and teicoplanin. Penicillin and gentamicin act synergistically and most infectious disease specialists would recommend this combination. A sensitivity test will determine the best antibiotic regime.
In a patient with an abnormal valve, we recommend at least 48 hours of intravenous antibiotic therapy. Early surgical intervention should be undertaken as clinical circumstances allow. It may be possible in some patients to achieve 4 to 6 weeks of antibiotic therapy before this occurs. In patients with normal valves we recommend intravenous antibiotics for at least 4 to 6 weeks.1,11,17
This organism seems to be very virulent and destructive. It may be possible to select those who need urgent surgery on the basis of underlying valve pathology. Patients with abnormal or prosthetic valves should be prepared for urgent surgery if necessary. Surgery must include extensive debridment of all infected tissue, similar to that necessary for staphylococcal endocarditis. Patients with previously normal valves may be managed conservatively, but those with hemodynamic instability or echocardiographic evidence of deterioration should undergo urgent surgery.
We conclude that infective endocarditis due to C. diphtheriae, while uncommon, is on the rise4,5,10,12 (Table 2) and may be aggressive.1–3 Those patients with an abnormal (including prosthetic) valve should be subjected to surgery at the earliest appropriate opportunity after 48 hours (if possible) of antibiotic therapy. Patients with normal valves may be treated with antibiotics alone as long as immediate surgery can occur if needed.
Poster presentation at ASCTS ASM 2003 annual meeting, Queensland, Australia.
|
ACKNOWLEDGMENTS |
|---|
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSREVIEW OF THE LITERATUREDISCUSSIONREFERENCES |
|---|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
