Chapter 24 Infections of the cardiovascular system

In health, the cardiovascular system is sterile, but a few organisms may enter the blood stream (even in health) during routine procedures such as tooth-brushing, especially in the presence of periodontitis. However, these bacteria have only a transient existence as the efficient defences of the blood quickly destroy them.

Bacteraemia, septicaemia and sepsis syndrome

Definitions

Bacteraemia: literally ‘bacterial presence in the blood’, where the bacterial burden in blood is usually very low and is clinically insignificant – i.e. bacteraemia is asymptomatic. Bacteraemia could be produced simply by brushing of teeth or chewing, especially in the presence of periodontitis.

Septicaemia: literally ‘sepsis of the blood’, seen when large numbers of organisms enter and/or actively multiply and persist in the blood stream, producing clinical signs and symptoms such as hypotension, fever and rigors.

Sepsis syndrome: a systemic response to microbial products or constituents circulating in the blood mediated by inflammatory cytokines (see below).

Septicaemia and sepsis syndrome

Aetiology

Some common predisposing factors and agents that cause septicaemia are shown in Table 24.1.

Table 24.1 Some common predisposing factors and agents of septicaemia

Predisposing factor	Agent
Abdominal sepsis	Enterobacteria
	Bacteroides fragilis
	Enterococcus faecalis
Infected wounds, burns	Staphylococcus aureus
	Streptococcus pyogenes
	Enterobacteria
Osteomyelitis	Staphylococcus aureus
Pneumonia	Streptococcus pneumoniae
Intravascular devices	Staphylococcus aureus
	Staphylococcus epidermidis
	Enterobacteria
Food poisoning	Salmonella spp.
Food poisoning	Campylobacter spp.
Meningitis	Streptococcus pneumoniae
	Neisseria meningitidis
	Haemophilus influenzae
Immunosuppressed patients	Enterobacteria
Immunosuppressed patients	Staphylococcus aureus, etc.

Pathogenesis and clinical features

Once the blood stream is invaded by microbes, the host responds by activating its defence mechanisms, leading to the production of a cascade of inflammatory cytokines (e.g. interleukin-1, tumour necrosis factor; see Chapter 10). The cytokine release is orchestrated by endotoxins of Gram-negative bacteria, peptidoglycan of Gram-positive bacteria and exotoxins from both these groups. Generally, these cytokines are beneficial in eliminating the organisms, but excessive production may lead to organ dysfunction and circulatory septic shock – the sepsis syndrome.

Some of these patients are said to develop the systemic inflammatory response syndrome (SIRS) depending on their clinical signs; these include hypotension, fever, rigors, oliguria and renal failure. Sometimes the infection may trigger a pathological activation of the coagulation system (disseminated intravascular coagulation (DIC)) and due to the resultant consumption of platelets and clotting factors, severe bleeding disorders.

Diagnosis

Blood should be cultured for a diagnosis of septicaemia. As the number of organisms circulating in the blood may vary from time to time, depending on the disease condition, more than one blood culture may be required; whenever possible, this should be carried out before antibiotic therapy is instituted. Several positive cultures are required to ensure that the culture result is not due to contamination from the venepuncture site. Cultures from sites suspected to be causing the infection are useful (e.g. pus from an abscess) to establish and localize the infective focus.

Treatment

The principles of therapy are:

• aggressive bactericidal (rather than bacteriostatic) intravenous antimicrobial therapy in adequate dosage

• stabilization of the haemodynamic status (e.g. intravenous fluids, cardiogenic drugs, oxygen)

• identification of the focus of infection and appropriate action (e.g. removal of a foreign body, surgical intervention by draining an abscess).

Infections of the heart

Important pathogens that cause pericarditis, myocarditis and endocarditis are shown in Figure 24.1. Of these, infective endocarditis is the most important disease of relevance to dentistry.

Fig. 24.1 Major infectious agents of aortitis, pericarditis, myocarditis and endocarditis.

Page 206

Infective endocarditis

Definition

Inflammation of the endocardium of the heart valves, and sometimes the endocardium around congenital defects, resulting from an infection.

Microbial aetiology

Bacteria are predominantly involved, although other organisms, such as fungi, rickettsiae and chlamydiae, may occasionally cause endocarditis (Table 24.2). More than 80% of infective endocarditis is caused by streptococci and staphylococci. The position held by the viridans group of organisms in the league table indicates the major role played by the oral commensals in causing this life-threatening disease. It is noteworthy that nearly all patients with viridans endocarditis have a previous heart lesion, and about a quarter give a history of a recent dental procedure as a precipitating factor.

Table 24.2 Causative microorganisms in infective endocarditis

Microorganisms	Cases (%)
Total streptococci	60
Viridans group	35
Enterococcus faecalis	13
Microaerophilic streptococci	3
Anaerobic streptococci	2
Others	7
Total staphylococci	25
Staphylococcus aureus	20
Staphylococcus epidermidis	5
Miscellaneous	5
Culture-negative	10

(cumulative data from several sources)

Clinical features

Although two clinical forms of the disease – acute and subacute – have been identified, the line of demarcation between these forms is not often clear. The acute form is a rapidly progressive condition and is caused by bacteria such as Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus pyogenes. The subacute form is more insidious and chronic, and progresses rather slowly. The agents of this form of the disease are less virulent bacteria, such as viridans streptococci, Staphylococcus epidermidis and Enterococcus faecalis.

Page 207

Signs and symptoms

The classic signs are fever, malaise, loss of weight, anaemia, splinter haemorrhages, petechiae, cardiac murmur, haematuria and splenomegaly.

Diagnosis

Clinical signs supported by positive blood culture are used to make the diagnosis. Repeated culture may be necessary to isolate the causal organism owing to the low-grade bacteraemia. If possible, blood should be collected when the temperature of the patient rises, indicating fever due to bacteraemia. At least 10 ml of blood should be collected prior to antibiotic therapy and cultured under aerobic and anaerobic conditions (see Fig. 6.4). Any agent isolated from two different blood culture sets (on separate occasions) is considered significant. Identification and antibiotic sensitivity tests are then performed on the isolate.

Pathogenesis and epidemiology

Infective endocarditis normally occurs in patients with some pathological condition of the endocardium, although those with apparently normal heart valves may rarely be affected. The predisposing conditions include valve prostheses, septal defects, atheroma of the valve, congenital valve deformities and pre-existing rheumatic fever (Table 24.3). Infective endocarditis is the end result of the sequential interaction of events shown in Figure 23.2:

Table 24.3 Cardiac valvular disease predisposing to infective endocarditis

Disease	Degree of risk
Aortic valvular disease	High
Prosthetic valves
Mitral insufficiency
Ventricular septal defect
Patent ductus arteriosus
Coarctation of aorta
Previous infective endocarditis
Mitral valve prolapse and stenosis	Intermediate
Pulmonary and tricuspid valve disease
Degenerative (calcific) aortic valve disease
Non-valvular intracardiac prosthetic implants
Atrial septal defect	Low/negligible
Coronary artery disease
Cardiac pacemakers
Arteriosclerotic plaques

1. A breach of the endocardium, or an abnormality of the endocardial surface per se, is the first event that makes the valvular surface finally succumb to infection. Such a breach may occur because of the acute inflammatory valvulitis of rheumatic fever (consequential to Streptococcus pyogenes infection; see Fig. 23.2) or in congenital heart diseases such as aortic valve disease and ventricular septal defect, when alterations of the blood flow patterns (haemodynamic turbulence) may result in the deposition of fibrin and platelets at foci where high-velocity jets of blood hit the valvular surface.

2. The microscopic platelet aggregates that form on the breached endocardium detach and embolize harmlessly or stabilize and consolidate through fibrin deposition, forming a sterile thrombus. The latter is a potential trap for circulating microbes. Such sterile thrombus formation is called non-bacterial thrombotic endocarditis. Platelets also have the potential to adhere to other ‘foreign’ surfaces such as prosthetic valves.

3. The next critical event occurs when organisms circulating in the blood (e.g. after a tooth extraction or scaling) attach to or become trapped in the thrombotic endocardium or the prosthetic device. The resultant platelet–fibrin–bacterial mass, now called the bacterial vegetation, constitutes the primary pathology of infective endocarditis (Figs 23.2 and 24.2).

4. Once the organisms are attached to the lesion, they multiply and colonize this niche in an exuberant manner. As a result, further aggregation of platelets and fibrin deposition ensues, protecting the organisms from the body defences. The organisms now reside in a sanctuary inaccessible to phagocytes by virtue of the fibrin–platelet barrier. Further, the bacteria may be sheltered from antibiotics and host antibodies as the vegetation is essentially avascular in nature. As a result, it is necessary to use an intensive course of prolonged, high-dose antibiotic therapy to eradicate such an infective focus.

5. Even if endocarditis is successfully treated, the healed valve is permanently scarred and thickened, and such residual abnormalities make the patient highly vulnerable to episodes of reinfection.

Fig. 24.2 Micrograph of an infected heart valve teeming with Gram-positive streptococci.

Page 208

Treatment

High-dosage single or combination antibiotic therapy, guided by the microbiological findings from the blood culture, is necessary. The antibiotic regimen selected should be:

• bactericidal and not bacteriostatic

• parenterally delivered

• prolonged, of several weeks’ duration (usually up to 4 weeks).

The rationale behind management is:

1. to eradicate the organisms totally, without leaving residual pockets or reservoirs

2. to administer high concentrations of antibiotic so that it may penetrate, by diffusion, into the focal aggregates of bacteria in the avascular cardiac vegetations

3. to assess antibiotic levels in blood regularly, by laboratory monitoring, throughout the treatment period. Special sensitivity tests such as the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the antibiotic (see Chapter 6) need to be performed regularly to ascertain the optimal level of antibiotics that should be present in the circulation to eradicate the organisms and to avoid the toxic effects (e.g. nephrotoxicity, ototoxicity) of aminoglycosides such as gentamicin, which is commonly prescribed in combination with other drugs.

Infective endocarditis and dentistry

The oral cavity acts as a portal of entry for organisms causing bacteraemia, and dental manipulations may set in motion the disease process leading to infective endocarditis. Bacteraemia can occur after dental procedures such as extractions, surgical or non-surgical endodontics, gingivectomy, root-planing, scaling and flossing, intraligamentary injections, and reimplantation of avulsed teeth. The frequency of bacteraemia is also related to the preoperative oral sepsis of the patient and the degree of trauma and tissue injury; a routine activity such as tooth-brushing may also cause bacteraemia, depending on the degree of oral sepsis.

The real risk of development of infective endocarditis in a ‘risk’ patient following dental procedures is difficult to ascertain, and the evidence base is rather contradictory; it has been estimated that bacteraemias vary between 10% and 90%. Clearly, a proportion of infections is associated with random transient bacteraemias that commonly follow mastication, and even tooth-brushing, in patients with chronic periodontitis.

Infective endocarditis prophylaxis

As eventual development of endocarditis may well be the most common potentially fatal complication of dental treatment, all dentists must have a good working knowledge of the problem and the appropriate preventive measures.

Accurate identification of at-risk patients

The main risk conditions are shown in Table 24.3. Dentists usually identify patients at risk from their medical history. It is also important to obtain confirmatory and expert information from the patient’s medical practitioner.

Patient awareness of risk status and dental involvement in cardiac clinics

Warning cards given to patients with cardiac disease increase their awareness of the disease. Dentists should be part of the medical team involved in the preoperative and post-operative management of patients undergoing cardiac surgery who are at risk.

Preventive dental care

Susceptible patients should be exposed to risky operative procedures as rarely as possible; this can be best achieved by careful and intensive oral hygiene instruction, dietary advice and regular dental examinations. The aim should be to reduce the amount of treatment to the absolute minimum necessary for the maintenance of a healthy natural dentition for life. The need to administer prophylactic antibiotics for dental procedures that could produce a bacteraemia capable of initiating infective endocarditis must be weighed carefully, and the respective guidelines in each jurisdiction should be strictly adhered to.

Awareness of post-operative morbidity

Even when antibiotic cover has been provided, patients at risk should be instructed to report any unexplained illness because of the insidious origin of infective endocarditis.

Cardiac patients who need antibiotic prophylaxis

There is some controversy as to the need of antibiotic prophylaxis solely to prevent infective endocarditis in people at risk, undergoing either dental or non-dental procedures. Hence, the recent British recommendations (National Institute for Health and Clinical Excellence (NICE) Guidelines), as opposed to the American, state that there is no need for antibiotic prophylaxis for any dental procedure due to the following reasons:

Page 209

• There has been no consistent association between having an interventional procedure, dental or non-dental, and the development of infective endocarditis.

• Regular tooth-brushing presents a greater risk of infective endocarditis than a single dental procedure because of repetitive exposure to bacteraemia with oral flora.

• The clinical effectiveness of antibiotic prophylaxis is not proven.

• Antibiotic prophylaxis against infective endocarditis for dental procedures may lead to a greater number of deaths through fatal anaphylaxis than a strategy of no antibiotic prophylaxis, and is not cost-effective.

Despite the foregoing, American authorities still maintain that antibiotic prophylaxis for infective endocarditis is necessary for a relatively small group of patients and as this textbook is used worldwide in various jurisdictions, the current US guidelines are provided below.

According to the American Heart Association, the following groups of patients are the only cohorts that should be given antibiotic prophylaxis and include those with:

• prosthetic cardiac valve

• previous infective endocarditis

• congenital heart disease:

unrepaired cyanotic congenital heart disease

repaired congenital heart defect with prosthetic material or device during the first 6 months after procedure (as it takes 6 months for endothelialization)

repaired congenital heart disease with residual defects

• cardiac transplantation recipients who develop cardiomyopathy.

Dental procedures that need antibiotic prophylaxis

The above groups of patients must be given antibiotics for all dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa.

Presurgical antibiotic regimens for a dental procedure as per the American Heart Association Guidelines are given in Table 24.4. It should be borne in mind that these recommendations are regularly reviewed by the authorities, and practitioners need to keep abreast of such developments.

Table 24.4 Antibiotic regimens for preventing infective endocarditis given for a dental procedure

Antibiotic prophylaxis for miscellaneous conditions

Prosthetic cardiac valve

The dental management of patients with a prosthetic cardiac valve can be undertaken by dentists (as described above) as long as the patients require local anaesthesia and are not hypersensitive to penicillin. If the patient has received penicillin more than once within the past month, oral clindamycin should be given.

Hip joint replacements

There are few data on post-operative infection of hip prostheses to suggest that bacteria derived from the mouth are involved. There is wide consensus that patients with prosthetic joint implants, including total hip replacements, do not require antibiotic prophylaxis, because the risks of prophylaxis outweigh the benefits. Nevertheless, it is important that the possible need for prophylactic cover should be discussed with the patient’s doctor before dental treatment starts. Further, there should be liaison between orthopaedic surgeons and dentists to render patients dentally fit prior to insertion of replacements or implants.

Third molar surgery

A number of properly controlled trials have conclusively indicated that antimicrobial agents have no statistically significant effect on swelling, pain, trismus or post-operative infection in third molar surgery.

Dental implants

Surgical placement of dental implants is an elective procedure performed under relatively aseptic conditions. Hence, it does not warrant antibiotics either pre- or post-surgically, although many surgeons prefer to do so worldwide. A number of reviews have indicated that pre- or post-surgical antibiotics during implant placement is of dubious value.

Page 210

Key facts

• In health, the cardiovascular system is sterile, but a few organisms may transiently enter the blood stream during routines such as tooth-brushing.

• Bacteraemia is asymptomatic and the bacterial burden in blood is very low, while in septicaemia, large numbers of organisms enter and/or actively multiply and persist in the blood stream, producing clinical signs and symptoms such as hypotension, fever and rigors.

• Bacteraemia can occur after dental procedures such as extractions, surgical or non-surgical endodontics, gingivectomy, root-planing and scaling, and flossing.

• Sepsis syndrome is a systemic response to microbial products or constituents circulating in the blood mediated by inflammatory cytokines.

• Infective endocarditis is defined as the inflammation of the endocardium of the heart valves, and sometimes the endocardium around congenital defects, caused by an infection.

• More than 80% of infective endocarditis is caused by streptococci and staphylococci.

• Infective endocarditis is diagnosed by positive blood culture; repeated culture may be necessary to isolate the causal organism.

• The predisposing conditions for infective endocarditis include valve prostheses, septal defects, atheroma of the valve, congenital valve deformities and pre-existing rheumatic fever.

• High-dose single or combination antibiotic therapy, guided by the microbiological findings from the blood culture, is necessary to treat infective endocarditis.

• Infective endocarditis prophylaxis is based on accurate identification of patients at risk, patient awareness of risk status, dental involvement in cardiac clinics, preventive dental care, antibiotic prophylaxis as per the local guidelines and patient awareness of post-operative morbidity.

• Cardiac patients who may need antibiotic cover (as dictated by US guidelines) include those with congenital cardiac defects, prosthetic cardiac valves, previous history of endocarditis, and cardiomyopathy after cardiac transplantation.

• Drugs used in antibiotic prophylaxis of infective endocarditis include amoxicillin, clindamycin, vancomycin and erythromycin.