Cardiovascular disorders

II/2.8: Some pathogens causing bacterial endocarditis

II/2.8.1: Streptococcus pneumoniae (Pneumococcus)

Gram positive lancet shaped bacteria measuring 1-2 microns and forming couples; the facing parts are rounded and the opposite part is pointed. The polysaccharide capsule surrounding the cell pairs defends pneumococci from phagocytosis and it plays an important part in their virulence. Mutants without a capsule are avirulent. These bactaria can also form short chains. S. pneumoniae is part of the natural flora of the upper airways in humans and mammals, and it can be isolated from the throat in 30 to 70 percent of the cases throughout the year. These facultative aerobic bacteria can be cultured in blood or chocolate agar, and after 24 to 48 hours the colonies measure 1-3 mm, and their surfaces are smooth and shiny. After 1 to 2 days the middle of the colonies sink, and it elevates later again due to secondary colony formation, which gives the colonies a special appearance.

The colonies are surrounded by a greenish court due to alpha hemolysis. S. pneumoniae causes homogeneous opacity as it grows in serum or ascitic fluid bouillon. It is an important feature that S. pneumoniae dissolves rapidly in bile, bile acids, or in surfactants. The effect of the bacteria’s autolytic ferments is blocked by an inhibitor; surfactants suspend inhibition caused by this factor and consequently the ferments dissolve the bacteria. S. pneumoniae is sensitive, and shows sensitivity to most antibiotics – especially to penicillin and its derivates.

The number of strains that are resistant to broad-spectrum antibiotics and tetracyclines is increasing. S. pneumoniae is not sensitive to gentamycine. Based on the capsular polysaccharid’s antigen structure, 85 serotypes are distinguished, and type I through VIII are responsible for 55% of all lobar pneumonies. Type XIV is most common in children. Besides this antigen there is a group-specific C carbohydrate and a type-specific M protein. Group-specific carbohydrates precipitate C-reactive protein in the blood of patients with inflammatory diseases. Capsular polysaccharid is used for serological classification. It as a good antigen and can also be used for immunization in humans.

S. pneumoniae’s infective capacity is based on its ability to grow in tissues. Neuraminidase which is produced by the bacteria acts as a toxin since it damages active cation transport by affecting sialic acid gycoprotein macromolecule in the cell membrane. This relatively low molecular weight enzyme is group-specific. S. pneumoniae is the most common cause of lobar pneumonia because microorganisms are present in the airways and when the body’s natural defence decreases they penetrate the lower airways. If cellular and humoral defense mechanisms of the body don’t prevent infection spread, pneumococci get into the blood flow through the lymph nodes and, as a result of bacteremia they might cause endocarditis, pericarditis, meningitis, or peritonitis. Pleuritis may be the consequence of direct spread from the lung. In rare cases, secondary pneumococcus pneumonia develops after a viral infection.

Spreading from the throat to the sinuses and middle ear, S. pneumoniae causes sinusitis and otitis. It can also cause purulent conjunctivits; and it is the only pathogen causing ulcus serpens corneae. The elementary mechnism for pneumococcus destruction is phagocytosis. In immune organizations polymorphonuclear leukocytes and monocytes easily incorporate and destroy the bacteria. Pneumococcus is very sensitive to penicillin: ½ to 1 million units per day bring rapid healing. Larges dose of antibiotic should be given in case of sepsis. Laboratory diagnosis is possible by sputum, throat smear, blood, liquor, etc. culturing.

II/2.8.2: Staphylococci 

The two species of Staphylococcus genus – Staphylococcus areus and Staphylococcus epidermidis – belong to the Micrococcaceae family. The Gram positive spheric microorganisms measuring 0.8-1 microns are members of the resident skin, airway and gastrointestinal tract flora. S. aureus causes illness quite often, while S. epidermidis is rarely pathogenic.

Staphylococcus aureus. It has no capsule, spore or cilia. It usually forms grape-like clusters but it also occurs alone, in pairs, or in short chains. It is an aerobic and facultative anaerobic bacterium which grows well and rapidly on a single culture medium between 10 and 45 °C. On agar plate, its colonies measure 2-3 mm, they have smooth and shiny surface and butter-like consistency. Due to the specific pigment production, the colour of the colonies varies from china-white to gold-yellow. Lipochrome pigment doesn’t diffuse into the culture medium but in a living organization it diffuses into the exudates. Pigment production is the most intense in room temperature. On blood agar, the colonies are surrounded with a beta hemolytic court. S. aureus causes homogeneous opacity as it grows in bouillon. Hyalurionidase, gelatinase, tributirinase, phosphatase and coagulase production should be emphasized of the large number of enzymes in pathogenic strains.

S. aureus is the most resistant of all non-spore-forming bacteria. It remains viable for months when it gets dried in pus. More than 90% of the strains produce penicillinase which hydrolyses the penicillin’s beta lactam ring, thereby inactivating it. Its production is controlled by extrachromosomal plasmids that can be carried from one strain to another by bacteriophags. Their antigen structure is complex and consists of proteins and carbohydrate components. Pathogenic strains produce various toxins; the strongest are alpha-toxin, leukocidin, and enterotoxin. Alpha-toxin causes necrosis in human and animal skin, and in large amounts it is lethal for humans and animals, is cytotoxic in tissue cultures and destroys human white blood cells and platelets. There are three types of hemolysins: alpha, beta and delta hemolysin. Enterotoxin which is produced by some strains has pathogenetic significance in food poisonings.

S. aureus frequently causes diseases in humans. S. epidermidis is only a facultative pathogen. Humans are much more prone to infection then laboratory animals. Clinical forms of the disease depend on the entry site, bacterial number, immune status and hypersensitivity influenced by a possible previous infection and the toxins produced by the bacterial strain.

S. aureus might cause various, mainly purulent diseases which are classified as follows:

• 1) inflammations of the skin and subcutaneous connective tissue include acne, folliculitis, furuncle, carbuncle, sycosis barbae, impetigo and infections of mainly burn wounds;

• 2) of airway infections the most significant is pneumonia occurring in children and the elderly – primarily following viral infections (influenza, measles, RS-virus);

• 3) inflammations of the gastrointestinal tract (stomach, bowels) are classified into two groups: a) staphylococcal enterocolitis, which develops as a consequence of broad-spectrum antibiotic administration (so-called dysbacteriosis), and b) gastroenteritis caused by enterotoxin producing staphylococci is a form of food poisoning;

• 4) urinary infections include perirenal abscesses and chronic pyelonephritis;

• 5) the most important bone and joint infections are osteomyelitis and septic arthritis;

• 6) inflammations of other organs (meningitis, otitis, etc.);

• 7) generalised infection, staphylococcus-sepsis (occurs very rarely);

• 8) cross infections in hospitals.

Acquired immunity against staphylococci is not lasting, therefore no active immunization methods are used widely, but autovaccination proved effective in some recurrent infections caused by strains which are difficult to influence with drugs (drug resistant). Laboratory diagnosis from pus or exudates is quite easy. With direct microscopy, Gram positive grape-like clusters of cocci refer to the pathogen in a number of cases. After 24 hours they can be recognized by their typical colony shape on blood agar.

II/2.8.3: Haemophilus influenzae

Gram negative, polymorphic coccobacillus, measuring 0.5-1.5 microns. It has a capsule in its early life stage. On chocolate agar culture medium, it forms dewdrop-like, smooth, transparent, 0.5-1 mm colonies with a peculiar odour. Only capsulated strains are virulent and pathogenic, and the disease is caused by their endotoxin. Based on the carbohydrate capsule material they are classified into six seotypes and marked from ’a’ to ’f’.

Haemophilus influenzae is present in the nasal-pharyngeal cavity and throat smear in cca. 25% of the healthy population as commensal bacteria. It often causes co-infection in other bacterial or viral infections.

Haemophilus influenzae exacerbates chronic bronchitis and bronchiectasis. Meningitis is most frequently caused by b type Haemophilus influenzae, primarily in young people and children, and the most serious diseases develop under the age of 3. The pathogens enter the blood flow through the nasopharynx and proceed to the meninges. Besides meningococci, it is the other most common pathogen of meningitis. Bacteria that get into the blood flow might also cause endocarditis. Type a usually causes sinusitis, types e and f are common in airway infections. Early diagnosis and treatment is especially important because the mortality of untreated meningitis caused by Haemophilus influenzae reaches 90%.

II/2.8.4: Neisseria gonorrhoeae (Gonococcus) 

Besides being the pathogen of gonorrhea, which is one of the most common sexual transmitted diseases, N. gonorrhoeae takes part in endocardial infections too. They are Gram negative, non-spore-forming diplococci (coccus bacteria forming pairs) measuring 0.6-1 micron. The facing part of the coccus pairs is flattened, roll or coffee bean shaped. It can be well stained by methylene blue. In new infections it is mainly seen inside leukocytes, while in chronic cases it’s mostly extracellular. They are demanding bacteria in terms of culturing; they grow optimally under aerobic circumstances, with 10% CO2 tension, on a culture medium containing protein hydrolysate and growth factors.

Four kinds of colonies are distinguished: virulent strains belong to type 1 and 2, while avirulent mainly laboratory strains belong to type 3 or 4. Fimbriae and pili with 9.5 nm diameter and 4 nm length are seen on the surface of type 1 and 2 colonies with electron microscope. N. gonorrhoeae has catalase, oxydase and dezoxyribonuclease activity. It is a solely human pathogen but chimpanzees can be made sick too. The difference between the surface of virulent and avirulent organisms, which shows by the shape of the colonies and the presence or absence of pili on the surface of the bacteria, refers to the importance of pili in the infection process and in adhesion to mucous membrane surfaces.

Infection caused by N. gonorrhoeae usually affects the genitals and rectal mucous membrane, and less frequently the conjunctiva of the mucous membrane of the upper airways. The disease presents after 2 to 8 days of incubation, and starts with ascending purulent urethritis with a great amount of secretion. This can be accompanied by prostatitis and epididymitis in men and vaginal, cervical, Bartholin gland, and adnexal inflammation in women, which may lead to sterility and even peritonitis. Infection often goes without symptoms: in 60-70% of the cases in women and 5-15% in men. The urethral epithelium gets damaged in spots after the infection and gonococci that enter the connective tissue under the epithelium cause inflammation. After 3 to 5 days the bacteria populate the whole urethral mucous membrane and in1 to 3 percent of the cases they enter the deeper tissues and even the blood flow through the damaged mucosa.

This is followed by septicemia, fever, migrating polyarthritis and skin rash, but endocarditis and meningitis are also possible. Vulvovaginitis and rectal mucous membrane inflammation may also develop. Conjunctiva and vagina are especially sensitive to infection in newborns (neonatal blenorrhea, infant gonococcal vulvovaginitis). Formerly, gonococcal infection was the most common cause of neonatal blindness. Silver nitrate eye drops introduced in 1910 by Credé put an end to neonatal eye inflammations and their consequences, and thereby it is considered the first prophylactic medical act against bacteria.

In terms of immunity it is important that in uncomplicated cases the disease is confined to the mucous membranes and although infection is often followed by an antibody response, permanent immunity doesn’t develop and thus reinfection is frequent. Humoral antibodies can be detected in each Ig classes, but IgA type secretory antibodies that react with thermolabile surface antigens are of special importance. Cellular immune response is also significant in the course and healing of gonorrhea. Laboratory diagnosis is possible by direct microscopic examination of the exudate smear and bacterial culturing. Gonorrhea is treated by 3-5 million units of penicillin, but in case of any contraindication, spectinomycin, gentamycin, tetracycline, or erythromycin is the drug of choice. No significant resistance increase was verified up to now but penicillin sensitivity of the strains might decrease. The most important tool against gonorrhea is prevention.