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 the 'Septicaemia and sepsis syndrome' section).
Septicaemia and sepsis syndrome
Aetiology
Some common predisposing factors and agents that cause septicaemia are shown in Table 24.1.
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
Infective endocarditis
Important pathogens that cause pericarditis, myocarditis and endocarditis are shown in Fig. 24.1. Of these, infective endocarditis is the most important disease of relevance to dentistry.
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. Campylobacter spp. |
|
Meningitis |
Streptococcus pneumoniae Neisseria meningitidis Haemophilus influenzae |
|
Immunosuppressed patients |
Enterobacteria Staphylococcus aureus, etc. |
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 (cumulative data from several sources)
|
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 |
Fig. 24.1 Major infectious agents of aortitis, pericarditis, myocarditis and endocarditis.
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.
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 Fig. 23.2:
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 re-infection.
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).
Fig. 24.2 Micrograph of an infected heart valve teeming with Gram-positive streptococci.
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 toothbrushing 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. Additionally, in USA, a Wallet Card may be obtained by patients, from the American Heart Association containing information on the proper antibiotic dose (Table 24.4), if endocarditis prophylaxis is warranted.
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 British recommendations (National Institute for Health and Care Excellence (NICE) Guidelines), as opposed to the American, state that there is no need for routine antibiotic prophylaxis for any dental procedure due to the following reasons:
■ 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.
British and American guidelines on prophylaxis against infective endocarditis in patients undergoing interventional procedures
British guidelines
Adults and children with the following cardiac conditions should be considered as being at increased risk of developing infective endocarditis:
■ acquired valvular heart disease with stenosis or regurgitation
■ hypertrophic cardiomyopathy
■ previous infective endocarditis
■ structural congenital heart disease, including surgically corrected or palliated structural conditions, but excluding isolated atrial septal defect, fully repaired ventricular septal defect or fully repaired patent ductus arteriosus, and closure devices that are judged to be endothelialized
■ valve replacement.
Any episodes of infection in the aforementioned categories of people at risk of infective endocarditis should be investigated and treated promptly to reduce the risk of endocarditis developing.
Patient advice
People at increased risk of infective endocarditis should be offered clear and consistent information about prevention, including:
■ the benefits and risks of antibiotic prophylaxis, and an explanation of why antibiotic prophylaxis is no longer routinely recommended
■ the importance of maintaining good oral health
■ symptoms that may indicate infective endocarditis and when to seek expert advice
■ the risks of undergoing invasive procedures, including non-medical procedures such as body piercing or tattooing
■ why chlorhexidine mouthwash is not offered as prophylaxis against infective endocarditis as there is no evidence base to substantiate its effectiveness.
American guidelines
As mentioned earlier, American authorities still maintain that antibiotic prophylaxis for infective endocarditis is necessary for a relatively small group of patients and 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:
■ a prosthetic cardiac valve
■ a history of infective endocarditis
■ certain congenital heart defects including:
• unrepaired cyanotic congenital heart disease and children with surgical shunts and conduits
• 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, such as persisting leaks or abnormal flow at or adjacent to a prosthetic patch or prosthetic device.
Dental procedures that need antibiotic prophylaxis
The aforementioned 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 according to 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.
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 earlier) 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 are of dubious value.
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 according to 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.
Review questions (answers on p. 366)
Please indicate which answers are true, and which are false.
24.1 Bacteraemia:
A. May be produced by tooth-brushing
B. Will occur in healthy individuals
C. Differs from septicaemia in that there is no active multiplication of organisms
D. Might lead to endocarditis in patients with rheumatic carditis
E. Always precedes septicaemia
24.2 Which of the following statements on infective endocarditis are true?
A. Normal oral flora are key agents
B. It can precipitate cardiogenic shock
C. It is always managed by parenteral antibiotics
D. It can always be diagnosed by a single blood culture
E. Congenital cardiac defects significantly increase the risk
24.3 When obtaining blood for bacteriological cultures:
A. A total of 2 ml blood is sufficient
B. The procedure should be done before the commencement of antibiotics
C. The procedure is likely to yield the best result if collected at peaks of temperature
D. Multiple specimens are required
E. All of the above are true
24.4 Endocarditis:
A. is always precipitated by a microbial infection
B. viridans streptococci cause rheumatic fever leading to the condition
C. always requires more than a single antibiotic
D. can be prevented by education of susceptible groups
E. due to enterococci is commonly of endogenous origin
24.5 According to American Guidelines (AHA) prophylaxis against endocarditis in patients undergoing dental procedures is necessary if they have:
A. a prosthetic heart valve
B. certain congenital heart diseases
C. a past history of endocarditis
D. third molar surgery
E. atherosclerosis
Further reading
American Heart Association. Dental Procedures and Infective endocarditis. Available from: http://www.heart.org/HEARTORG/Conditions/ CongenitalHeartDefects/ThelmpactofCongenitalHeartDefects/ Infective-Endocarditis_UCM_307108_Article.jsp#.WSv13GiGOHu.
Lever, A., & Mackenzie, I. (2007). Sepsis: definition, aetiology and diagnosis. British Medical Journal, 335, 879-883.
Martin, M. V., Kanatas, A. N., & Hardy, P. (2005). Antibiotic prophylaxis and third molar surgery. British Dental Journal, 198, 327-330.
National Institute for Health and Care Excellence (NICE). NICE
Guidelines: Prophylaxis against infective endocarditis (July 2016 update). Available from: https://www.nice.org.uk/guidance/cg64/chapter/ Recommendations#prophylaxis-against-infective-endocarditis.
Oliver, R., Roberts, G. J., & Hooper, L. (2004). Penicillins for the prophylaxis of bacterial endocarditis in dentistry (Cochrane review). Australian Dental Journal, 49, 3.
Wilson, W., Taubert, K. A., Gewitz, M., et al. (2007). Prevention of infective endocarditis: Guidelines from the American Heart Association. Journal of the American Dental Association, 138, 739-760.