Abstract
Antibiotics are prescribed by dentists in dental practice, during dental treatment as well as for prevention of infection. Indications for the use of systemic antibiotics in dentistry are limited because most dental and periodontal diseases are best managed by operative intervention and oral hygiene measures. The use of antibiotics in dental practice is characterised by empirical prescription based on clinical and bacteriological epidemiological factors, resulting in the use of a very narrow range of broad-spectrum antibiotics for short periods of time. This has led to the development of antimicrobial resistance (AMR) in a wide range of microbes and to the consequent inefficacy of commonly used antibiotics. Dentists can make a difference by the judicious use of antimicrobials – prescribing the correct drug, at the standard dosage and appropriate regimen – only when systemic spread of infection is evident. The increasing resistance problems of recent years are probably related to the over- or misuse of broad-spectrum agents. There is a clear need for the development of prescribing guidelines and educational initiatives to encourage the rational and appropriate use of drugs in dentistry. This paper highlights the need for dentists to improve antibiotic prescribing practices in an attempt to curb the increasing incidence of antibiotic resistance and other side effects of antibiotic abuse. The literature provides evidence of inadequate prescribing practices by dentists for a number of factors, ranging from inadequate knowledge to social factors.
Key words: Dental practice, periodontal disease, oral hygiene
INTRODUCTION
Antibiotics are routinely prescribed in dental practice for either prophylactic or therapeutic use. Prophylactic antibiotics are prescribed to prevent diseases caused by the introduction of members of the oral flora to distant sites or to a local, compromised, site in a host at risk1. In most cases, prophylaxis is used to prevent endocarditis, whereas therapeutic antibiotics are prescribed mostly to treat diseases of the hard and soft tissues in the oral cavity after local debridement has failed2.
Dentists prescribe medications for the management of a number of oral conditions, mainly orofacial infections3. As most human orofacial infections originate from odontogenic infections, the prescription of antibiotics by dental practitioners has become an important aspect of dental practice. For this reason, antibiotics account for the vast majority of medicines prescribed by dentists4.
Dentists’ use of antibiotics is characterised by a number of particularities. In effect, antibiotic prescription is empirical; the clinician does not know what microorganism is responsible for the infection because cultures are not commonly grown from the patient’s pus or exudate. Based on clinical and bacterial epidemiological data, the types of microorganisms responsible for the infectious process are suspected, and treatment is decided on a presumptive basis, fundamental on probabilistic reasoning5.
Antibiotic use may be associated with unfavourable side effects, ranging from gastrointestinal (GI) disturbances to fatal anaphylactic shock and development of resistance. The increasing antibiotic-resistance problems of recent years are probably related to the over- or misuse of broad-spectrum agents, such as cephalosporins and fluoroquinolones6. As a result, a new era has emerged in which some species of bacteria are resistant to the full range of antibiotics presently available, with methicillin-resistant Staphylococcus aureus being the most widely known example of this extensive resistance. These serious complications associated with antibiotic use have encouraged studies investigating the antibiotic-prescribing practices of dentists7., 8., 9., 10..
The empirical and broad use of antibiotic prophylaxis is clearly no longer acceptable, but details on responsible prescribing remain problematic. In the dental community, there has been a general trend towards over-prescribing11., 12.. One of the surveys in USA found that only 39% of dentists and 27% of physicians followed guidelines for antibiotic prophylaxis appropriately13. Many practitioners rely on the recommendations of other practitioners — who often cite anecdotal evidence — or decide that, when in doubt, the wise and conservative course is to prescribed14.
The present review discusses the specific prescribing practices of general dentists with regard to antibiotic prophylaxis for dental procedures and the guidelines generally used in dental practice for the prescription of antibiotics.
RATIONALE FOR ANTIBIOTIC USAGE IN DENTAL PRACTICE
The human oral cavity contains a very broad range of microorganisms. Some authors speak of more than 500 different species, and Liebana et al.15 even reported that all known microorganisms associated with humans are at some time found in the oral cavity as either transient (the majority) or resident (only a few) species.
The bacteria that cause odontogenic infections are generally saprophytes. The microbiology in this sense is varied, and multiple microorganisms with different characteristics can be involved. Anaerobic and aerobic micro-organisms are usually present in the oral cavity, and numerous aerobic species cause odontogenic infections — the most common being Streptococcus spp. The microorganisms most commonly isolated from the oral and maxillofacial regions are listed in Table 1.
Table 1.
Infection | Aerobic and facultative anaerobic organisms | Anaerobic organisms |
---|---|---|
Cervical lymphadenitis | Staphylococcus aureus* | Pigmented Prevotella |
Mycobacterium spp. | Porphyromonas spp.* | |
Peptostreptococcus spp. | ||
Postoperative infection disrupting oral mucosa | Staphylococcus spp. | Fusobacterium spp. |
Enterobacteriaceae* | Bacteroides spp.* | |
Staphylococcus spp.* | ||
Pigmented Prevotella | ||
Porphyromonas spp. | ||
Peptostreptococcus spp. | ||
Deep neck sites | Streptococcus spp. | Bacteroides spp.* |
Staphylococcus spp.* | Fusobacterium spp.* | |
Peptostreptococcus spp. | ||
Odontogenic complications | Streptococcus spp. | Pigmented prevotella |
Staphylococcus spp.* | Porphyromonas spp.* | |
Peptostreptococcus spp. | ||
Ororpharyngeal: Vincent’s angina necrotic ulcerative gingivitis | Streptococcus spp. | Fusobacterium necrophorum* |
Staphylococcus spp.* | ||
Spirochetes | ||
Prevotella intermedia | ||
Fusobacterium spp. |
Organisms that have the potential to produce beta-lactamase.
In the course of dental caries, the bacteria that penetrate the dentinal tubules are mainly facultative anaerobes (i.e. Streptococcus spp., Staphylococcus spp. and Lactobacillus spp.). When the pulp tissue becomes necrosed, the bacteria advance through the pulp canal and the process evolves towards periapical inflammation16. The peri-apical infection warrants the rationale for the systemic administration of the antibiotics.
WHEN ANTIBIOTICS SHOULD BE INDICATED
Antibiotic prophylaxis for infectious diseases of dental or oral origin is more prevalent than the antibiotic treatment of such infections. Antibiotics are not an alternative to dental intervention; rather they are adjunctive to clinical intervention. The major use of antibiotic prophylaxis in dental procedures is for procedures that cause bleeding in the oral cavity, and administration of antibiotics for such cases has become common practice among dentists14. Antibiotics are also commonly indicated in dental practice for treating immunocompromised patients, patients with evident signs of systemic infection and if the signs and symptoms of infection progress rapidly17.
Antibiotics are typically prescribed in dental practice (i) for the treatment of acute and chronic infections of odontogenic and non-odontogenic origins, (ii) as prophylactic treatment to prevent focal infection in patients at risk (as a result of systemic conditions such as endocarditis, artificial heart valves and congenital heart disease) and (iii) to prevent local infection and systemic spread among patients undergoing surgical oral or dental treatment.
Antibiotics for odontogenic infections
Despite the high incidence of odontogenic infections, there are no uniform criteria regarding the use of antibiotics to treat them. A considerable percentage of pain of dental origin originates from acute and chronic infections of pulpal origin, which necessitates operative intervention, rather than antibiotics. Non-indicated clinical cases for antibiotic use, which are commonly practised by dentists, include acute periapical infection, dry socket and pulpitis18.
The clinical situations that require antibiotic therapy on empirical basis are limited, and they include oral infection accompanied by elevated body temperature and evidence of systemic spread, such as lymphadenopathy and trismus19. Facial cellulitis, which may or may not be associated with dysphagia, is a serious disease that should be treated promptly by antibiotics because of the possibility of spread of infection via lymph and blood circulation, with the development of septicaemia.
Chronic inflammatory periodontal conditions do not require routine use of antibiotics; systemic antimicrobials should only be used in acute periodontal conditions where drainage or debridement is impossible, where there is local spread of the infection or where systemic spread has occurred9.
Whereas some authors consider the natural and semisynthetic penicillins (amoxicillin) to be the options of first choice20, others prefer the combination of amoxicillin and clavulanic acid owing to the increase in resistance to the penicillins and low level of bacterial resistance to this combination, with a broad-spectrum action, pharmacokinetic profile, tolerance and dosing characteristics21.
Penicillinase-resistant penicillin or an ampicillin-like derivative is prescribed for infections caused by penicillinase-producing Staphylococcus spp. or those involving gram-negative bacteria. Patients allergic to penicillin are treated with clindamycin 300 mg (65%), which is the drug of choice, azithromycin (15%) or metronidazole-spiramycin combination (13%)22. Some authors have proposed clindamycin as the drug of choice in view of its good absorption, low incidence of bacterial resistance and the high antibiotic concentrations reached in bone23. The antibiotics useful for treating patients with odontogenic infections are listed in Table 2.
Table 2.
Antibiotic | Administration route | Posology |
---|---|---|
Amoxicillin | p.o. | 500 mg/8 hours |
1000 mg/12 hours | ||
Amoxicillin/clavulanic acid | p.o. or i.v. | 500–875 mg/8 hours* 2000 mg/12 hours* 1000–2000 mg/8 hours† |
Clindamycin | p.o. or i.v. | 300 mg/8 hours* |
600 mg/8 hours† | ||
Azithromycin | p.o. | 500 mg/24 hours, three consecutive days |
Ciprofloxacin | p.o. | 500 mg/12 hours |
Metronidazole | p.o. | 500–750 mg/8 hours |
Gentamycin | i.m. or i.v. | 240 mg/24 hours |
Penicillin | i.m. or i.v. | 1.2–2.4 million IU/24 h‡Up to 24 million IU/24 hours † |
i.m., intramuscular; i.v., intravenous; p.o., per os (oral).
p.o. administration.
i.v. administration.
i.m. administration.
Antibiotics for non-odontogenic infection
Non-odontogenic infections require prolonged treatment. Such infections include tuberculosis (TB), syphilis, leprosy and non-specific infections of the mucosal membranes, muscles and fascia, salivary glands and bone.
New synthetic antibiotics, such as fluoroquinolones, are the drug of choice for management of non-odontogenic infections and are indicated for bone and joint infections, genitourinary (GU) tract infections and respiratory tract infections and extend the bacterial spectrum to include gram-negative bacilli, gram-positive aerobic cocci and, in the case of third-generation fluoroquinolones (moxifloxacin), anaerobic organisms24. Bone and anaerobic infections are managed by prescribing clindamycin (orally) or lincomycin (parenterally)25.
In the case of a primary oral tubercular lesion, an empirical treatment given for TB can cure the oral tubercular lesion, even in the absence of histopathological evidence26. The treatment of specific infections caused by mycobacteria requires the use of antibiotics for long periods of time (6 months to 2 years) and includes the administration of dapsone, clofazimine and rifampicin for leprosy, and associations of ethambutol, isoniazid, rifampicin, pyrazinamide and streptomycin for TB27.
Prophylactic use of antibiotics
Prophylactic antibiotics, taken before a number of dental procedures, have been advocated (i) to reduce the likelihood of postoperative local complications (such as infections or dry socket) or serious systemic complications (such as infective endocarditis), (ii) in surgical excision of benign tumours and (iii) in immunocompromised patients.
Prophylaxis against systemic spread
The use of antibiotics as prophylaxis for focal infection is a common practice. Although the potential exists for oral microorganisms to seed and infect distant tissues after oral procedures, there is no substantiated evidence that this occurs. Consequently, the issue of when and for what conditions systemic prophylactic antibiotics are necessary is controversial.
Infective endocarditis is an uncommon, but serious and often life-threatening, condition. Some studies have shown that dental procedures are trigger factors for few cases of endocarditis28. Lockhart reported an increased incidence of infective endocarditis following dental extraction and periodontal surgery29. Ottent et al. reported that bacteraemia was associated with 74% of patients following tooth extraction30.
The American Heart Association (AHA) 2007 guideline31 recommends infective endocarditis prophylaxis only for those whose underlying cardiac conditions are associated with the highest risk of an adverse outcome. Such conditions include: the presence of prosthetic heart valves; previous history of infective endocarditis; unrepaired cyanotic congenital heart disease; in the 6-month period following complete repair of a congenital heart defect with prosthetic material or a device; repaired congenital heart disease with residual defects or adjacent to the site of a prosthetic patch or device; and cardiac transplantation recipients who develop valvulopathy.
Even if all patients at risk of developing infective endocarditis were given antibiotic prophylaxis, it might only prevent 5.3% of cases28. There is a larger likelihood of bacteraemia related to normal daily activities than from dental procedures32; therefore, some argue that the era of antibiotic prophylaxis is over33. In the case of bacterial endocarditis (infective endocarditis), the absolute risk rate after dental treatment, even in at-risk patients, is considered very low34. This is consistent with recent guidelines from the British Society for Antimicrobial Chemotherapy35, which recommended that only patients in the high-risk category require coverage with Antibiotics.
Recently, the AHA36 has also provided the following new talking points for clinicians: infective endocarditis is much more likely to occur following frequent exposure to random bacteraemias associated with daily activities than from bacteraemia caused by a dental, GI tract or GU tract procedure; prophylaxis may prevent an exceedingly small number of cases of infective endocarditis, if any, in people who undergo a dental, GI tract or GU tract procedure; the risk of antibiotic-associated adverse events exceeds the benefit, if any, from prophylactic antibiotic therapy; and maintenance of optimal oral health and hygiene may reduce the incidence of bacteraemia from daily activities and is more important than prophylactic antibiotics for a dental procedure to reduce the risk of infective endocarditis.
Prophylaxis against local infection
Prophylaxis of local infection is taken to comprise the administration of antibiotics on a pre-, intra- or postoperative basis, to prevent the proliferation and dissemination of bacteria within and from the surgical wound. Various surgical procedures are routinely covered by administration of systemic antimicrobials, including impacted third molars, orthognathic surgery, implant surgery and periapical surgery.
The evidence for antibiotics acting to prevent infection of surgical wounds in the mouth is poor to non-existent, indicating that pre-operative parenteral antibiotic prophylaxis for routine third-molar surgery in medically fit patients is unwarranted37. For most dentoalveolar surgical procedures in fit, non-medically compromised patients, antibiotic prophylaxis is not required or recommended35.
Immunocompromised patients represent a special category of patients for dental professionals because such patients are more prone to bacteraemia, which may rapidly lead to septicaemia. Therefore, antibiotic prophylaxis may be given in such cases. Antibiotic coverage is also mandatory in patients with uncontrolled diabetes, who have to undergo invasive dental treatment38.
There is no scientific basis for recommending systemic antibiotic prophylaxis before invasive dental treatment in patients with total joint prostheses39. According to the American Dental Association and the American Academy of Orthopedic Surgeons, evaluation is required of antibiotic prophylaxis in patients with total joint prostheses in the presence of immune deficiency40. The use of antibiotics in endodontics should be indicated for those patients with signs of local infection and fever41.
APPROPRIATE SELECTION OF ANTIBIOTIC: DOSAGE AND DURATION
Oral antibiotics that are effective against odontogenic infections include penicillin, clindamycin, erythromycin, cefadroxil, metronidazole and the tetracyclines42. The type of antibiotic chosen and its dosage are dependent on the severity of infection and the predominant type of causative bacteria.
The most commonly used antibiotics in dental practice, penicillins in general, were found to be the most commonly prescribed antibiotics by dentists43; the most popular antibiotic was amoxicillin7, followed by penicillin V10, metronidazole and the combination of amoxicillin and clavulanic acid44.
Patients who are allergic to penicillin should benefit from clindamycin; which is active against some oral anaerobic and facultative bacteria and has the advantage of good bone penetration. However, increasing the dose of this antibiotic may increase the possibility of serious side effects such as neutropenia and pseudomembranous colitis45.
The ideal duration of antibiotic treatment is the shortest cycle capable of preventing both clinical and microbiological relapse. Most acute infections are resolved within 3–7 days. When oral antibiotics are used, a high dose should be considered to help achieve therapeutic levels more rapidly46.
In recent years, more attention has been given to short courses of antibiotic. Rubenstein explained that short-course antibiotic therapy requires antibiotics to have certain characteristics, such as: rapid onset of action; bactericidal activity; lack of propensity to induce resistant mutants; ease of penetration into tissues; activity against non-dividing bacteria; unaffected by adverse infection conditions (low pH, anaerobiasis, presence of pus, etc.); administration at an optimal dose; and an optimal dosing regimen47.
CONDITIONS NOT WARRANTING/CONTRAINDICATIONS FOR THE USE OF ANTIBIOTICS
Consideration for antibiotic prophylaxis should be given in patients with kidney and/or liver failure and in pregnant or lactating mothers (as antibiotics may have an indirect effect on their infants). Dose adjustments are required for dental procedures in patients with kidney failure to avoid an increased plasma concentration of the drug. Almost all antibiotics, except cloxacillin, clindamycin, metronidazole and macrolides, require dose modification in patients with renal insufficiency48. Dose adjustment can be carried out by reducing the amount administered in each dose or by increasing the interval between doses (without modifying the amount of drug)49.
Patients with liver failure require a dose reduction of erythromycin, clindamycin, metronidazole and anti-tuberculosis drugs. Oral zinc supplementation is effective in hepatic encephalopathy and consequently improves patients’ health-related quality of life50.
Almost all antibiotics are contraindicated during pregnancy as a result of their major side effects. Risk of having a spontaneous abortion during the early pregnancy are associated with gestational use of diclofenac, naproxen, celecoxib, ibuprofen and rofecoxib, alone or in combination51.
In general, all antibiotics can cause three potential problems for nursing infants. First, they can modify the bowel flora and alter gut defence mechanisms; this can result in diarrhoea and malabsorption of nutrients. Second, they may have direct effects that may or may not be dose related. Lastly, and often ignored, is that antibiotics can alter and interfere with microbiological culture, resulting in babies being investigated for sepsis52.
DISCUSSION AND CONCLUSION
Antibiotic therapy is mandatory and essential in medicine and dentistry. Dentists are not always aware of the most current clinical guidelines regarding antibiotic prophylaxis, even though guidelines are available. This is the reason for the empirical prescription of antibiotics and the adverse consequences of antibiotic use. Antibiotic use may be associated with unfavourable side effects, ranging from gastrointestinal disturbances to fatal anaphylactic shock and development of anti-microbial resistance. Minimising the occurrence of antibiotic misuse and abuse has global implications for the containment of antibiotic-resistant strains of bacteria.
Development of resistance to drugs by microbes is a natural phenomenon but is enhanced by the inappropriate use of antimicrobials. A few strains that are naturally resistant and those with acquired resistance emerge as the dominant forms as a result of the selective pressure exerted following exposure to antimicrobials53. The antibiotic sensitivity of the bacteria found within the oral cavity is gradually decreasing, and a growing number of resistant strains have been detected – particularly Porphyromonas and Prevotella54 – although the phenomenon has also been reported for Streptoccocus viridans and for drugs such as the macrolides, penicillin and clindamycin55. Resistance has been reported against all beta-lactam antibiotics (including penicillin derivatives and cephalosporins), clindamycin, ciprofloxacin, erythromycin and tetracycline56.
The proper use of antibiotics is related to the principles of infection management, microbiology of infectious agent and host response, and the pharmacology of the particular agent. In the clinical setting, these principles are modulated by a number of factors. These factors need to be understood to ensure appropriate prescribing of antibiotics.
Acknowledgement
None declared.
Conflicts of interest
None declared.
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