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The article explores infective endocarditis (IE) caused by rare and fastidious bacteria, which frequently lead to culture-negative cases and complicate the diagnostic process. While IE is typically diagnosed through persistent bacteremia with gram-positive cocci and the detection of vegetations via echocardiography, advanced echocardiographic techniques—particularly transesophageal echocardiography—significantly enhance the sensitivity of the Duke criteria. However, echocardiography is more effective in confirming the presence of IE rather than identifying the specific microbial cause, with approximately 24% of proven IE cases being misclassified as “possible” when blood cultures are negative. In older patients, the most prevalent underlying heart disease factor is prosthetic valve replacement, observed in one-third of such cases. Additionally, poor dental hygiene or recent oral surgery has been associated with an increased risk of infection.

**Uncommon Pathogens and Specialized Diagnostics:**

Uncommon pathogens such as **Bartonella spp.**, **Coxiella burnetii**, **Lactobacillus**, **Legionella spp.**, **Chlamydia psittaci**, and members of the **HACEK** group necessitate specialized diagnostic approaches. For instance, *Bartonella spp.*, including *B. henselae* and *B. quintana*, are small facultative intracellular gram-negative bacteria that cause various clinical syndromes. *B. henselae* is associated with cat scratch disease and endocarditis in patients with prior valve injury and cat exposure, whereas *B. quintana* is linked to trench fever and endocarditis in homeless or alcoholic individuals exposed to body lice. Specialized diagnostics for these pathogens involve serological tests (e.g., immunofluorescence assays), polymerase chain reaction (PCR) amplification of specific genes (such as the 16S rRNA gene), special staining techniques like Warthin-Starry, and optimized culture conditions.

Additionally, **Whipple's Disease** caused by *Tropheryma whippelii* presents unique diagnostic challenges. Diagnosed through the presence of PAS-positive macrophages in duodenal or valvular biopsy specimens and confirmed by PCR and sequencing, Whipple's disease endocarditis is likely underreported due to its subtle presentation and reliance on invasive diagnostic methods.

**Legionella spp.** endocarditis, though exceedingly rare, is associated primarily with nosocomial infections and prosthetic valves, requiring specialized culture techniques such as buffered charcoal yeast extract (BCYE) media and PCR for accurate identification. **Chlamydia psittaci** endocarditis is often misdiagnosed due to cross-reactivity with Bartonella spp. in serological tests, necessitating advanced molecular techniques for definitive identification. **Coxiella burnetii** (Q fever) endocarditis is another significant etiology, particularly prevalent in individuals with occupational exposure to farm animals, diagnosed through high-phase I IgG and IgA antibodies, PCR, and histologic observation of infected tissues.

**HACEK Group Bacteria:**

The HACEK group comprises fastidious, small gram-negative bacilli primarily from the oropharyngeal flora, responsible for approximately 3% of all endocarditis cases. This group includes *Haemophilus parainfluenzae*, *H. influenzae*, *H. aphrophilus*, *H. paraphrophilus*, *Actinobacillus actinomycetemcomitans*, *Cardiobacterium hominis*, *Eikenella corrodens*, and *Kingella spp.* These organisms are slow-growing, with growth enhanced by carbon dioxide, and require specific culture conditions. Each HACEK organism demonstrates unique epidemiological and clinical characteristics:

- **Haemophilus paraphrophilus**: Rare, often associated with mitral valve prolapse and previous valve abnormalities. Clinical features include fever, cardiac murmurs, and embolic events. Valve replacement is required in 24% of cases.
  
- **Haemophilus aphrophilus**: Commonly linked to dental procedures and upper respiratory infections. Echocardiography detects vegetations in 70% of patients. Improved diagnostic delay has led to better prognoses in recent reports.
  
- **Haemophilus parainfluenzae**: Presents insidiously, often following dental procedures. Embolic complications are frequent, with a case fatality rate between 10-35%.
  
- **Actinobacillus actinomycetemcomitans**: Associated with periodontal disease and prior dental infections. Affects young to middle-aged patients, with a case fatality rate of 9-15% and valve replacement required in 28% of cases.
  
- **Cardiobacterium hominis**: Linked to dental infections and underlying heart disease, predominantly affecting the aortic valve. Mortality is around 13%, with 30% requiring valve replacement.
  
- **Eikenella corrodens**: Often found in intravenous drug users due to syringe contamination. Generally causes a mild course with a 15% fatality rate and rare need for valve replacement.
  
- **Kingella spp.**: *Kingella kingae* primarily affects young children, while *Kingella denitrificans* is less common. In older patients, prosthetic valves are a significant risk factor. Kingella spp. predominantly colonize the upper respiratory tract, particularly the tonsils, and are not primary pathogens but exploit mucosal impairments resulting from viral infections. Concomitant stomatitis, pharyngitis, or varicella virus-induced buccal ulcers have been reported in children with *Kingella* bacteremia. A fatality rate of 16% has been reported in *K. kingae* endocarditis, with central nervous system emboli detected in 25% of cases.

**Effective Identification Strategies:**

Effective identification strategies include obtaining multiple blood cultures under stringent conditions—typically three sets within 24 to 48 hours with adequate blood volume—to establish culture-positive endocarditis. Due to the slow growth of HACEK bacteria, prolonged incubation times (3 to 5 days, potentially up to 30 days for organisms like *A. actinomycetemcomitans*) are essential. Specialized culture methods, such as subculture on 5 to 8% sheep blood and chocolate agar at 35 to 37°C in 5 to 10% CO₂, are required. Molecular techniques using 16S rRNA gene analysis may be necessary for difficult identifications. Prior antibiotic therapy, common in many patients, can significantly reduce blood culture yields. To mitigate this, methods such as diluting blood samples in broth, using antimicrobial agent removal devices, and employing specialized culture media are essential for isolating fastidious organisms. No significant difference in bacterial growth was found between the Septicheck bottle and the Isolator tube.

**Clinical Presentations and Diagnostic Challenges:**

IE caused by these atypical organisms may present with subacute and insidious symptoms, often lacking conventional signs like fever and cardiac murmurs, especially in elderly patients or those who have received prior antibiotics. Additional clinical manifestations include:

- **Digital Clubbing**: Observed in one-third of patients, a higher rate than typically seen in other forms of endocarditis.
  
- **Purpuric Rash**: Found in one-fifth of patients, usually occurring on the extremities and mucosa. Skin biopsies reveal immune complex vasculitis.
  
- **Renal Involvement**: Proliferative glomerulonephritis has been reported, increasing the risk of renal insufficiency. Laboratory findings may include microscopic hematuria, elevated serum hepatic transaminases, lactate dehydrogenase, creatine phosphokinase, cryoglobulins, and hyperglobulinemia.
  
- **Embolic Manifestations**: Occur in about 20-41% of patients, involving cerebral and extremity vessels. Arterial embolism may present as stroke, potentially requiring embolectomy or amputation.
  
- **Pulmonary and Pleural Manifestations**: Can be complications of endocarditis.

**Specific Presentations in Rare IE Types:**

- **Whipple's Disease Endocarditis**: May include systemic symptoms like diarrhea, weight loss, neurological manifestations, and acute congestive heart failure.
  
- **Legionella Endocarditis**: Associated with chronic symptoms such as low-grade fever, night sweats, weight loss, and signs of congestive heart failure without embolic events.
  
- **Coxiella burnetii Endocarditis (Q Fever)**: Typically affects individuals with preexisting valvular injuries, presenting with prolonged fever, cardiac dysfunction, splenomegaly, and hepatomegaly. Laboratory findings often include high-phase IgG and IgA antibodies, circulating immune complexes, rheumatoid factor, anemia, thrombocytopenia, hyperglobulinemia, and various autoantibodies.

Advanced molecular and histological techniques have substantially improved the identification and management of these challenging IE cases. Techniques such as PCR amplification of the 16S rRNA gene, immunohistologic testing, and specialized histologic stains (e.g., Warthin-Starry, Gimenez) are invaluable. Additionally, thorough patient histories regarding animal contact, occupational exposures, and potential sources of infection are crucial for accurate diagnosis.

**Treatment and Prognosis:**

Treatment of IE caused by rare pathogens like *Bartonella spp.* typically involves a combination of antibiotics tailored to the specific organism's susceptibility profile. For instance:

- **Bartonella Endocarditis**: Often treated with aminoglycosides in combination with doxycycline or ceftriaxone for a prolonged course.
  
- **Whipple's Disease Endocarditis**: Requires prolonged antibiotic therapy targeting *T. whippelii*, often necessitating surgical intervention such as valve replacement due to extensive valvular damage.
  
- **Legionella Endocarditis**: Treated with macrolides or fluoroquinolones.
  
- **Coxiella burnetii Endocarditis (Q Fever)**: Typically requires doxycycline combined with hydroxychloroquine for an extended duration (at least 18 months). This combination has proven more effective than doxycycline with quinolones, reducing relapse rates and shortening therapy duration. Serum antibody surveillance and plasma level monitoring of hydroxychloroquine are essential. 

For **HACEK Group Bacteria**, medical treatment alone or in combination with surgical intervention can cure 82-87% of patients. The current treatment strategy includes β-lactamase-stable cephalosporins instead of ampicillin due to the prevalence of β-lactamase-producing organisms. The American Heart Association recommends treating native-valve and prosthetic-valve endocarditis for 4 and 6 weeks, respectively. Prophylaxis for dental procedures is currently amoxicillin, with alternatives like clindamycin or pristinamycin for allergic patients. However, resistance patterns necessitate the use of tetracycline in some cases.

The prognosis can be poor, especially in cases with delayed diagnosis and treatment, as evidenced by higher mortality rates among certain populations like homeless individuals with *B. quintana* endocarditis and *Brucella* endocarditis in patients with underlying conditions. Nevertheless, advancements in diagnostic and therapeutic strategies have improved outcomes for many patients.

**Other Rare Etiologies:**

Beyond Bartonella and the newly detailed pathogens, other rare causative agents of IE include:

- **Mycobacterium spp.**: Acid-alcohol-resistant bacteria causing exceptionally rare forms of endocarditis, often associated with prosthetic valves or medical procedures. Diagnosis typically relies on histologic examination and specialized culture techniques, with combination antibiotic therapy recommended.
  
- **Mycoplasma spp.**: Cell wall-deficient bacteria implicated in very few reported cases of IE. Detection is challenging due to their inability to be visualized by Gram stain and growth in routine cultures. Strategies for isolation include specific agar media and PCR techniques.
  
- **Pasteurella spp.**: Small, gram-negative, nonmotile coccobacilli commonly associated with close contact with cats or dogs (44% of cases). Endocarditis caused by Pasteurella spp. has been reported in 21 cases, with a mortality rate of 31%, often related to diagnostic delays rather than antibiotic resistance.
  
- **Brucella spp.**: Small, facultative, gram-negative, intracellular bacteria causing zoonotic infections primarily through ingestion of contaminated milk or close contact with infected animals. Brucella endocarditis is a rare but severe complication, occurring in 0.3-0.6% of brucellosis cases, with a high fatality rate. Diagnosis relies on prolonged blood culture incubation and serological tests, while treatment typically involves a combination of doxycycline and rifampin or streptomycin for several months, often accompanied by surgical intervention.
  
- **Bordetella spp.**: Only one reported case of *Bordetella holmesii* endocarditis, diagnosed via molecular techniques after isolation from blood culture in a patient with a bicuspid aortic valve.
  
- **Francisella tularensis**: A single reported case of endocarditis, identified through extended blood culture incubation using radiometric systems.
  
- **Aeromonas hydrophila**: Two reported cases of endocarditis in cirrhotic patients, associated with waterborne exposure.
  
- **Yersinia enterocolitica**: Twelve reported cases of endocarditis, often in patients with underlying conditions such as iron-overloading states or immunosuppression. Treatment typically involves broad-spectrum cephalosporins and gentamicin, with a 25% mortality rate in untreated cases.
  
- **Salmonella spp.**: Thirty-three reported cases of endocarditis, primarily *Salmonella enterica* serovar Enteritidis. Occurs mostly during or after concomitant Salmonella infections like gastroenteritis, especially in immunocompromised individuals or those with prosthetic valves. Echocardiography usually demonstrates large vegetations with positive blood cultures.

**Conclusion:**

The integration of enhanced echocardiographic methods with the Duke criteria, combined with advanced microbiological and molecular diagnostics, significantly improves the detection and management of infective endocarditis caused by less common and fastidious bacterial agents. Understanding the epidemiology, clinical presentations, and appropriate diagnostic and therapeutic strategies for these rare pathogens is essential for improving patient outcomes. Active investigation for atypical organisms, especially in culture-negative cases, and a high index of suspicion based on patient history and clinical features are crucial for timely and accurate diagnosis and effective treatment.
We have the opportunity to refine the existing summary (only if needed) with some more context below.
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Echocardiography usually demonstrates large vegetations, and blood cultures are positive.

A cardiac murmur is frequently reported but may be absent or missed in patients with right-sided endocarditis.

Occasionally, blood cultures are negative in patients with myocardial abscess in whom the diagnosis is eventually made after surgery.

Death occurs in 10% of reported cases, but treatment with a broad-spectrum cephalosporin or a fluoroquinolone is efficacious even in patients with prosthetic heart valve endocarditis81.

Klebsiella spp.

and other rarely isolated enterics.

The rarity of endocarditis caused byKlebsiella spp.

limits its recognition and awareness of an often malignant course.

Both K. pneumoniae and K. oxytoca have been reported to cause endocarditis, but the species of Klebsiella involved in endocarditis is rarely noted in published series.

Klebsiella endocarditis has been reported in 50 patients 9.

Characteristics of Klebsiellaendocarditis include an antecedent Klebsiella urinary tract infection as a probable origin in 50% of patients and a high degree of virulence evidenced by native-valve endocarditis and prosthetic-valve involvement in 60 and 30% of patients, respectively 9.

Infection of a pacemaker is also suspected to be a potential source by which endocarditis is established.

Blood cultures are always positive, and continuous bacteremia with this organism suggests the diagnosis of endocarditis.

When diagnosis is delayed, death occurs in 49% of patients despite efficient antibiotic therapy with broad-spectrum cephalosporins and aminoglycosides, and 42% of patients need valve replacement.

Serratia marcesens has been reported to cause endocarditis, but the number of published cases is difficult to evaluate precisely.

From 1969 to 1974, 19 cases of S. marcesens endocarditis were observed in the San Francisco Bay Area (186).

Seventeen of these patients were intravenous drug users, and S. marcesenscaused 14% of all addict-associated endocarditis cases in San Francisco.

Aortic or mitral valves were involved in 13 patients, and heart failure developed in 9 of these.

Twelve patients had embolic episodes to the brain, iliofemoral arteries, or lungs.

One of six patients with tricuspid valvulitis was cured by surgery combined with antibiotics, and the other five were cured by antibiotics alone.

All 12 patients with aortic or mitral valvulitis treated medically died; 11 of these had unremitting sepsis.

Aortic valve replacement and antibiotics were effective in one patient.

There are only four reported cases of endocarditis due to Citrobacter freudii, with one being found in an intravenous drug abuser 216a.

Streptobacillus moniliformis.

Sixteen cases ofStreptobacillus moniliformis endocarditis have been reported in the latest review of the literature 243.

No other cases have been reported since that time.

Endocarditis is a rare complication of septicemia after a rat bite.

Endocarditis occurs most often in the setting of previously damaged heart valves, usually as a result of rheumatic heart disease 243.

In two of four cases in which it was performed, echocardiography showed vegetations.

Therapy with adequate doses of penicillin is usually curative.

Gram-Negative Cocci
The gram-negative cocci that cause endocarditis are listed in Table 4 and discussed below.

Neisseria gonorrhoeae.

N. gonorrheaeis a gram-negative diplococcus which was first suggested as a potential cause of endocarditis in 1834 292.

The incidence of this apparently frequent disease seems to have dropped sharply in incidence just after the beginning of the antibiotic era, and since that time only 40 proven cases of gonococcal endocarditis have been recorded in the English literature 128, 138, 292.

The mean age of the patients is 27 years.

The mean duration of symptoms before diagnosis is approximately 45 days, fever is recorded in 60% of patients, and acute congestive heart failure is found at presentation in one-third of patients.

The most common presenting symptoms resemble those of other forms of endocarditis, except that renal failure with or without glomerulonephritis may complicate the course of disease; uremia is the cause of death in 40% of patients.

A history of sexually transmitted disease including urethral, vaginal, or cervical discharge with proven active gonococcal disease is recorded in 35% of patients292.

Concurrent pharyngitis and/or sore throat is also found frequently.

Vegetations are found by echocardiography in most patients (95%).

Preexisting valvular disease is found in only 15% of patients.

Valve replacement is required in 50% of patients, and 25% of patients die despite active antibiotic therapy 292.

Other Neisseria spp.

Endocarditis can also be caused by Neisseria elongata subsp.nitroreducens, N. elongata subsp.elongata, N. sicca, or N. subflava.

In the literature, 27 cases of N. elongata subsp.nitroreducens have been reported 62, 185, 300.

Endocarditis occurs in young middle-aged adults with a mean age of 39 years, preexisting valve conditions that predispose to infection include prosthetic valves (80% of patients) and previous dental procedures (20% of patients).

Infection results in acute febrile endocarditis with very large vegetations and a destructive process that often causes severe cardiac and systemic complications including acute congestive heart failure, myocardial abscess (30% of patients), and renal failure (30% of patients); surgical valve replacement is required in half of the patients.

The organisms are sensitive to a wide array of antibiotics including aminopenicillins and aminoglycosides, and despite the active destructive process, no deaths have been reported when appropriate medical and surgical therapy was administered.

N. elongata subsp.

elongata differs from N. elongata subsp.

nitroreducens by its morphology (rod/coccobacillus) and by its lack of nitrate reduction.

It is unclear if these two subspecies have different pathogenicity.

A single case of endocarditis due to N. elongata subsp.elongata has been published 199.

Fourteen cases of endocarditis due to N. sicca have been reported (94, 118, 240; Lopez-Velez et al., Letter), predominantly involving young patients; all but one cases were heralded by embolic manifestations (Lopez-Velez et al., Letter).

This infection leads to an acute disease with high-grade fever.

Intravenous drug use was documented in 3 of 14 patients.

Preexisting heart disease was observed in four patients with rheumatic valvular damage, one with an aortic bicuspid valve, and one with a prosthetic valve.

Before 1941, the fatality rate of N. sicca endocarditis was high, but no deaths have been noted in recent reports (Lopez-Velez et al., Letter).

Twelve cases of endocarditis cause by Neisseria subflavahave been reported; all but one patient presented with fever8.

This infection occured in middle-aged immunocompromised adults such as patients with AIDS, chronic alcoholism, asplenia, diabetes mellitus, and intravenous drug use.

Sources of infection included dental abscesses in 3 patients, and the prognosis was severe since 5 of the 12 patients died (Lopez-Velez et al., Letter).

Appropriate antibiotic therapy and valve replacements have improved the recovery, and no deaths have been reported since 1981.

Gram-Positive Bacilli
The gram-positive bacilli that cause endocarditis are listed in Table 4 and discussed below.

Listeria monocytogenes.

Listeria monocytogenes is a small gram-positive bacteria that is widely distributed in nature.

A recent review of the world literature found 58 cases of endocarditis due to L. monocytogenes260.

Clinically, it appears as a subacute disease in which the most remarkable signs and symptoms are fever, weakness, dyspnea, and cardiac murmur 93.

Acute congestive heart failure is found in 50% of patients.

An underlying immunocompromised situation, such as cancer, lymphoma, prolonged corticosteroid therapy, kidney transplantation, chronic hemodialysis, HIV infection, diabetes mellitus, chronic alcoholism, or pregnancy, is recorded in most patients (38, 93, 260; L. M. Baddour, Letter, Rev.

Infect.

Dis.

11:669, 1989).

A previous valvular disease, including rheumatic heart disease, prosthetic valve endocarditis, and mitral valve prolapse, is found in 50% of patients.

Etiologic diagnosis is confirmed by blood cultures, which are always reported to be positive.

Treatment includes ampicillin and aminoglycoside 93.

Lactobacillus spp.

Lactobacillus spp.

are large, gram-positive, aerobic bacteria that are ubiquitous and generally nonpathogenic inhabitants of the oral cavity, gastrointestinal tract, and female genital tract.

Although bacteremia without valvular involvement is frequently reported, only 30 cases of Lactobacillus endocarditis have been reported in the literature (127, 270; S. Antony, S. Dummer, and C. Stratton, Letter, Clin.

Infect.

Dis.26:1483–1484, 1998).

Common characteristics ofLactobacillus endocarditis are a high frequency of systemic emboli (42%) and dental manipulations (75%) as portals of entry.

Underlying heart disease is reported in 83% of patients including 20% with valvular prostheses, 20% with rheumatic heart disease, and 30% with congenital heart disease such as tetralogy of Fallot, transposition of great vessels, or tricuspid atresia 270.

Cultivation of Lactobacillus from blood is easy, but classical identification is obtained in only half of the isolates and molecular analysis of the 16S rRNA gene is useful for complete identification 209.

The recommended treatment is high-dose penicillin and aminoglycoside.

Relapse occurs in 39% of inadequately treated patients, and death occurs in 25%.

Nocardia spp.

To our knowledge, only three cases of endocarditis due to the gram-positive Nocardia spp.

have been reported in the literature, all in patients with prosthetic valves 74, 76, 289.

A blood culture was positive in one patient 74, and the organism was isolated from a surgically excised valve in the other two.

Two of the three patients died, and the survivor was treated with intravenous imipenem and amikacin and valve replacement surgery, followed by co-trimoxazole74.

Care must be taken that the filamentous appearance of this microorganism at Gram staining does not lead to misidentification and a diagnosis of fungal endocarditis.

Erysipelothrix rhusiopathiae.

Erysipelothrix rhusiopathiae is a gram-positive bacterium that is easily decolorized by alcohol using the Gram stain protocol.

These organisms are ubiquitous in nature and are found wherever nitrogenous substances decompose.

They can be isolated from a variety of animals worldwide.

The bacterium may be a commensal in swine.

It is thought that the excretion of organisms by infected and colonized animals leads to contamination of the environment and subsequent acquisition by humans.

E. rhusiopathiae infection in humans occurs mainly among those who have direct contact with animals or with organic matter in which the organism in commonly found—swine, fish, poultry, clams, geese, crabs, and fertilizer.

The literature reports 44 cases of endocarditis (104, 121, 230; M. R. Bibler, Letter, Rev.

Infect.

Dis.

10:1062–1063 1988; W. R. Grandsen and S. J. Eykyn, Letter, Rev.

Infect.

Dis.10:1228, 1988).

In 89% of cases, an occupational exposure is found, including butchers (34%), fishermen (14%), homemakers (14%), farmers (11%), and veterinarians (6%) 104.

Sources of contamination include pork (42%) and fish or shellfish (22%).

Prior heart disease is found in 40% of patients, alcohol abuse is found in 33%, and other sources of immunocompromise are rarely reported.

E. rhusiopathiae endocarditis is associated with the characteristic skin lesions (erysipeloid) at the site of inoculation in 40% of patients 121.

Etiologic diagnosis is made on the basis of blood cultures, which are always positive.

Overall mortality is 38%, and valve replacement is necessary in one-third of patients 230.

Penicillin G at 12 × 106 U/day is the drug of choice.

The duration of therapy is recommended to be 4 to 6 weeks.

In penicillin-allergic patients, cephalosporins are the most appropriate alternatives since both clindamycin and erythromycin are only bacteriostatic 230.

Clostridium spp.

Clostridia are large, sporulated anaerobes.

Most species stain gram positive during early stages of growth.

However, some species, such as Clostridium ramosun and Clostridium clostridioforme, almost always stain gram negative.

Endocarditis caused by anaerobes is uncommon.

Despite claims in the older literature that these are responsible for 2 to 10% of all cases of endocarditis, the largest published series failed to report any cases.

Anaerobic and microaerophilic streptococci and Bacteroides spp.

are by far the most commonly isolated anaerobes (M. Montejo, G. Ruiz-Irastorza, K. Aguirrebengoa, E. Amutio, J. L. Hernandez, and C. Aguirre, Letter, Clin.

Infect.

Dis.20:1431, 1995, R. Moyano, J. M. Gomez-Mateos, F. Lozano de Leon, C. Florez, C. Jimenez-Ocana, and F. Gamboa, Letter, Clin.

Infect.

Dis.

18:837, 1994).

Among all anaerobes, endocarditis due to Clostridia spp.

is exceedingly rare.

A total of 21 cases of clostridial endocarditis have been reported in the literature, and the majority were due to Clostridium perfringens7, 50, 144.

The likely portals of entry include the oropharynx, skin, gastrointestinal tract, and genitourinary tract.

Intravenous drug use was reported in two patients (144; Moyano et al., Letter).

It is interesting that a study of street heroin and injection paraphernalia in Washington, D.C., revealed that bacterial contamination was common and thatC.

perfringens was frequently cultured 144.

Other reported underlying conditions include carcinoma of the colon or cervix.

Fever is reported frequently, and embolic manifestations are observed in 50% of patients.

The most characteristic clinical sign is the occurrence of “clostridial sepsis,” which includes shock, jaundice, and intravascular hemolysis; although reported in only one-third of patients, these symptoms are very suggestive of the etiology.

Preexisting valve disease, including prosthetic valves and rheumatic heart disease, is reported in 50% of patients.

Anaerobic endocarditis is associated with culture-negative endocarditis.

There is one report in which the diagnosis was made by visualization of gram-positive bacilli on a blood smear 7.

Penicillin is the treatment of choice in clostridial endocarditis, but metronidazole should be considered in patients with prolonged bacteremia144.

The prognosis is poor, and 47% of patients die despite antibiotic treatment 50.

Nontoxigenic Corynebacterium diphtheriae.

Few laboratories perform tests for identification of the gram-positiveCorynebacterium diphtheriae.

A total of 67 cases of nontoxigenic C. diphtheriae endocarditis have been reported in the literature, and half were reported before 1950 (197, 278; O. Lortholary, A. Buu-Hoi, L. Gutmann, and J. Acar, Letter, Clin.

Infect.

Dis.

17:1072–1074, 1993).

Sporadic cases may be observed, but most occur as small outbreaks or in clusters278.

Since the source of the organism is likely to be the upper respiratory tract or skin, a history of pharyngitis or intravenous drug use is frequent.

Underlying heart diseases, including valve damage and prostheses, rheumatic heart disease, and congenital heart defects, have been reported.

The recommended treatment is a combination of penicillin and aminoglycoside (Lortholary et al., Letter).

Gram-Positive Cocci
The gram-positive cocci that cause endocarditis are listed in Table 4 and discussed below.

Abiotrophia spp.

Endocarditis due to streptococcal L-forms that required metabolic products of other bacteria for growth were first reported in 1961; these organisms are now known as Abiotrophia defectiva and A. adjacens90.

Numerous synonyms were given to these fastidious organisms, such as satelliting Streptococcus, thiol-requiring Streptococcus, vitamin B6-dependant Streptococcus, pyridoxal-dependantStreptococcus, symbiotic Streptococcus, and nutritionally variant streptococci, before they were classified as a new genus, Abiotrophia141 (Fig.8).

Fig.

8.

(i) Epidemiology.
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