Infective endocarditis due to staphylococci, Viridans streptococci, nutritionally variant streptococci, and HACEK group of pathogens are discussed in this chapter. The other etiological agents of IE are discussed under different systems they principally infect.

Staphylococcal Endocarditis

S. aureus is the most common cause of IE; usually runs an acute course.

- S. aureus IE presents with larger vegetations (>10 mm in diameter), and therefore is more frequently associated with features of septic embolization (due to breaking of vegetations leading to formation of emboli) such as subungual hemorrhage, Osler’s nodes, etc.

* Cerebrovascular emboli can cause strokes or occasionally encephalopathy

* Embolization risk is higher for mitral valve IE.

- S. aureus appears gram-positive cocci arranged in cluster, produces golden yellow hemolytic colonies on blood agar and gives a positive coagulase test

- Coagulase-negative staphylococci (e.g. S. epidermidis) are increasingly associated with prosthetic valve endocarditis (at least 68–85% of cases) and majority of them are methicillin resistant

Staphylococci can cause infections of various other systems such as skin and soft tissue.

 Viridans Streptococci

 Viridans streptococci are commensals of mouth and upper respiratory tract. Usually, they are nonpathogenic, however occasionally cause diseases such as:

- Subacute bacterial endocarditis (SABE): Viridans streptococci are the most common cause of SABE. The commensal viridans streptococci (S. sanguinis) in the oral cavity can enter blood to cause transient bacteremia while chewing, tooth brushing and dental procedures that can account for the predilection of these organisms to cause endocarditis

- Dental caries: It is mainly caused by S. mutans which breaks down dietary sucrose to acid and dextrans with the help of an enzyme glucosyl transferase. Acid damages the dentine, while adhesive dextran binds together with food debris, mucus, epithelial cells and bacteria to produce dental plaques

- In cancer patients: Viridans streptococci can cause prolonged bacteremia among neutropenic patients undergoing cancer chemotherapy

- S. milleri group (includes S. intermedius, S. anginosus, and S. constellatus): Produce suppurative infections, particularly brain abscess and empyema.

Laboratory Diagnosis

- On Gram stain, they appear as gram-positive cocci arranged in long chains (Fig. 1A)

- They produce minute α-hemolytic green-colored (rarely non-hemolytic) colonies on blood agar (“viridis” means green, Fig. 1B)

- They can be differentiated from Streptococcus pneumoniae (which is also α-hemolytic) by a number of tests such as resistant to optochin and insoluble in bile

- Accurate species identification is made by automated methods such as MALDI-TOF.

Fig1. a and B: viridans streptococci: a. Gram-positive cocci in long chains; B. α-hemolytic colonies on blood agar. Source: Department of Microbiology, Pondicherry Institute of Medical Sciences, Puducherry (with permission).

Nutritionally Variant Streptococci

 Abiotrophia and Granulicatella species are known as nutritionally variant streptococci as they require vitamin B (pyridoxal) in the culture medium for their growth. Earlier, they were grouped along with viridans streptococci.

- Manifestation: They are normal inhabitants of the oral cavity and similar to other oral commensals, they can also cause endocarditis

- Diagnosis: They can be recovered in automated blood cultures such as BacT/ALERT. Multiple blood cultures and prolonged incubation may be necessary

* They fail to grow when subcultured on solid media. However, they sometimes produce satellite colonies near the colonies of “helper” bacteria (e.g. near Staphylococcus aureus streak line). Therefore, they are also called as Satelliting streptococci

* They are catalase negative, gram-positive cocci arranged in short chains

* Species identification is made by automated systems such as MALDI-TOF.

- Treatment: Combination therapy with penicillin plus gentamicin is recommended for IE cases.

S. gallolyticus Endocarditis

 S. gallolyticus (formerly S. bovis) is a group D Streptococcus, found as a commensal in intestine of animals. In humans, it occasionally causes bacteremia, subacute endocarditis, and also associated with colorectal cancer or polyps. Penicillin is the drug of choice.

HACEK Endocarditis

 HACEK is an abbreviation used to represent a group of highly fastidious, slow-growing, capnophilic, gram negative bacteria, that normally reside in the oral cavity as commensal, but occasionally have been associated with local infections of the mouth and systemic infections such as bacterial endocarditis. Species belonging to this group include:

- Haemophilus parainfluenzae

- Aggregatibacter species: A.actinomycetemcomitans, A.aphrophilus and A.paraphrophilus

- Cardiobacterium hominis

- Eikenella corrodens

- Kingella kingae.

HACEK endocarditis accounts for 3% of total endocarditis cases.

- Typically has a subacute course

- Occurs in patients with preexisting valvular defects or those undergoing dental procedures

- The aortic and mitral valves are most commonly affected.

Clinical Manifestations

 -Haemophilus parainfluenzae: It is a commensal in mouth and throat

* Occasionally, it can be an opportunistic pathogen causing endocarditis, conjunctivitis, abscesses, genital tract infections and bronchopulmonary infections in patients with cystic fibrosis

* It can be differentiated from H. influenzae either by its growth requirement (requires only factor X, but not V), or by automated identification systems such as MALDI-TOF or VITEK.

- Aggregatibacter actinomycetemcomitans: Formerly called as Actinobacillus actinomycetemcomitans

* It is the most common member of HACEK to cause endocarditis

* It can also be isolated from soft tissue infections and abscesses associated with Actinomyces israelii

* Rarely, it can cause periodontitis, brain abscess, meningitis and endophthalmitis.

- Aggregatibacter aphrophilus and A. paraphrophilus: Earlier members of Haemophilus, now are renamed under genus Aggregatibacter

* They are commensals of mouth and occasionally cause endocarditis, head and neck infections, invasive bone and joint infections

* A. aphrophilus requires only factor X, whereas A. paraphrophilus requires only factor V.

- Cardiobacterium hominis: It frequently affects the aortic valve. It is also associated with arterial embolization, immune complex glomerulonephritis or arthritis

- Eikenella corrodens: Apart from endocarditis, it can also occasionally cause skin and soft tissue infections. The name ‘corrodens’ refers to the characteristic pitting or corroded colonies on blood agar

- Kingella kingae: In addition to endocarditis, it can also cause infections of bones, joints and tendons.

Laboratory Diagnosis

The laboratory diagnosis of HACEK endocarditis is as follows:

- Culture: Blood cultures are performed on automated systems such as BacT/ALERT

* As they are highly fastidious, require multiple blood cultures, and prolonged incubation up to 1 week

* They are capnophilic, growth is optimum in presence of 5–10% of CO2

* Identification is made by automated systems such as MALDI-TOF.

- Molecular methods: Simultaneous detection of HACEK members from clinical specimen is possible by performing (i) broad-range bacterial PCR targeting 16S rRNA gene followed by sequencing; (ii) multiplex PCR or multiplex real-time PCR.

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