Upon completion of this course, participants will be able to:
The oral cavity is colonized by more than 400 species of aerobic and anaerobic bacteria. Anaerobic bacteria outnumber their aerobic counterparts by a ratio of 10:1 to 100:1. These organisms inhabit the teeth, the gingival crevice, the mucous membranes, the dorsum of the tongue, and saliva. Dental infections can occur in a number of ways: (1) via the introduction of pathogens of extra-oral origin, (2) through a change in the balance of the indigenous flora, or (3) with the entry of bacteria into the normally sterile vital pulp of the tooth.
Although an individual's host defenses can affect the progression and severity of symptoms, it is essential that most dental infections be treated with antibiotics, antifungal, or antiviral medications. Systemic medications can inhibit and kill pathogens located at sites that are out of reach of dental instruments and topical antiseptics.
The goals of this Clinical Update are to provide an overview of infectious etiology of odontogentic infections, the proper selection of various antimicrobial agents for the prevention and treatment of dental infections, and the management of sequelae that may occur in association with dental procedures. Recommendations are based on the current literature and on the known susceptibility of the microorganisms involved in infections of the oral cavity.
It is important to recognize that differences in susceptibility to a particular organism may be seasonal and may also vary according to geographical location. Clinicians should be aware of the antimicrobial susceptibility unique to the area where their practice is located. Clinical resources, such as the package insert, should be consulted for information about the current dose, indications for use, and adverse effects for each prescription written.
Odontogenic infections are among the most common human infections.[1] Scientific evidence has linked severe infections with increased susceptibility to certain important systemic diseases and conditions such as cardiovascular disease, diabetes mellitus, adverse pregnancy outcomes, and pulmonary infections.[2] This is because the gram-negative bacilli that cause periodontal disease trigger production of lipopolysaccharides, heat-shock proteins, and proinflammatory cytokines. Because of the association between periodontal disease and other medical problems, it is imperative that dental infections be prevented when possible, or promptly recognized and adequately treated. Both dentists and physicians should be aware of the clinical implications of the inter-relationships between odontogenic infections and other medical conditions and treat affected patients in collaboration when needed.
The standards for the classification of periodontal diseases agreed upon during the 1989 World Workshop in Clinical Periodontics[3] were changed in 1999[4] in response to a number of criticisms of the earlier guidelines. The following weaknesses were cited: unclear criteria for diagnosis; overlapping disease categories; inappropriate classification of patients into 1 category; and an overemphasis on patient age at disease onset and on the rate of progression, which are frequently difficult to determine.
An International Workshop for a Classification of Periodontal Diseases and Conditions was organized in 1999 by the American Academy of Periodontology for the purpose of revising the classification system (Table 1). The workshop proceedings were subsequently published in the Annals of Periodontology.[4]
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* Can be further classified on the basis of extent and severity; "chronic periodontitis" replaced "adult periodontitis"
†Aggressive periodontitis replaced "early onset," "destructive," and "juvenile periodontitis
Dental infections fall into 3 general categories: localized (eg, acute periodontal abscess, peri-implantitis), spreading (eg, early cellulitis, deep space infection), and life-threatening (eg, fasciitis, Ludwig's angina). The most common dental infections include dental caries, dentoalveolar infections (pulpal infections and periapical abscess), gingivitis (including necrotizing ulcerative gingivitis), periodontitis (including pericoronitis and peri-implantitis), deep fascial space infection, and osteomyelitis. If left untreated, dental infections can spread and contribute to polymicrobial infections at other sites, including the sinuses, the sublingual space, palate, central nervous system, pericardium, and lungs.
There are at least 400 morphologic and biochemically distinct bacterial groups or species that colonize the oral and dental ecologic sites. The complexity of the oral and dental flora has prevented the clear elucidation of specific etiologic agents in most types of oral and dental infections, but most are caused by mixed gram-positive aerobic and anaerobic polymicrobial bacteria. The microorganisms recovered from infections generally reflect the host's indigenous oral flora. In the gingival crevice, there are approximately 1.8 x 1011 anaerobes/gram.[5] Because anaerobic bacteria are part of the normal oral flora and outnumber aerobic organisms by a ratio of 10:1 to 100:1 at this site, it is not surprising that these predominate in dental infections.
Most odontogenic infections result initially from the formation of dental plaque. Once pathogenic bacteria become established, they can cause local and disseminated complications including bacterial endocarditis, infection of orthopaedic or other prostheses, pleuropulmonary infection, cavernous sinus infection, septicemia, sinusitis, mediastinal infection, and brain abscess.
Periodontal disease refers to all disorders involving the supportive structures of the teeth (peridontium). Two events occur in the oral cavity that lead to the development of periodontal disease: an increase in the quantity of anaerobic gram-negative bacteria and a shift in the overall balance of bacterial types from harmless to disease-causing bacteria. It most commonly begins as gingivitis and progresses to periodontitis. How rapidly these infections progress depends on the type of bacteria present, the individual's level of bacterial resistance, and the amount of self-care the patient undertakes.
With the increased use of dental implants, a new type of periodontitis has emerged. Peri-implant disease refers to the general category of pathologic changes that can occur in the hard and/or soft tissues surrounding the implant. Even the initial integration of an implant can be jeopardized by the presence of bacteria in the tissues and concomitant inflammatory reactions. Most peri-implant diseases are plaque-induced and have an etiology similar to that of periodontitis.
Among the bacteria most commonly implicated in periodontal disease and bone loss are Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. Other bacteria associated with periodontal disease are Bacteroides forsythus, Prevotella intermedia, Prevotella nigrescens, Fusobacterium spp, Peptostreptococcus micros, Capnocytophaga, Treponema denticola, and Treponema sokranskii (Table 2).
Aerobic and Facultative Anaerobic Bacteria | Anaerobic Bacteria |
Gram-positive cocci Streptococcus spp Beta-hemolytic streptococci Streptococcus milleri group Streptococcus mutans group* Gram-positive bacilli Rothia dentocariosa Lactobacillus spp* Gram-negative cocco-bacilli Actinobacillus spp Actinobacillus Campylobacter spp Campylobacter rectus Capnocytophaga spp Eikenella spp Gram-negative rods Pseudomonas spp‡ Enterobacteriaceae‡ | Gram-positive cocci Peptostreptococcus spp Peptostreptococcus micros Gram-negative bacilli Veillonella spp Gram-positive bacilli Actinomyces spp Eubacterium spp Propionibacterium spp Lactobacillus spp. Spirochetes Treponema denticola Treponema sokranskii Gram-negative bacilli Prevotella spp Prevotella intermedia Prevotella nigrescens Porphyromonas spp Porphyromonas gingivalis†Bacteroides spp Bacteroides forsythus Fusobacterium spp Fusobacterium nucleatum Selenomonas sputigena |
*Microorganisms associated with dental carries.
†Common in aggressive periodontitis. (previously called "juvenile periodontitis")
‡Rare
Other groups of bacteria are consistently recovered from odontogenic and orofacial infections, suggesting that many pathogens may also be capable of producing clinical signs and symptoms of disease. Fusobacterium nucleatum has been recovered most often from patients with severe odontogenic infections.[6] The differences in rate of recovery of these organisms is influenced by age, underlying systemic disease, and local factors. Most pathogens are indigenous to the oral cavity, but in the immunocompromised host, bacteria such as Escherichia coli and Bacteroides fragilis can also colonize and cause infection.
The polymicrobial nature of these infections has been evident in many studies, including a study by Brook and colleagues[7] involving 32 periapical abscesses. A total of 78 bacterial isolates (55 anaerobic and 23 aerobic and facultative) were recovered, accounting for 2.4 isolates per specimen (1.7 anaerobic and 0.7 aerobic and facultative). Anaerobic bacteria only were present in 16 (50%) patients, aerobic and facultative in 2 (6%), and mixed aerobic and anaerobic flora in 14 (44%). The predominant isolates were anaerobic cocci (Peptostreptococcus spp), Bacteroides, Prevotella, and Porphyromonas spp (mainly P gingivalis). The primary aerobic pathogen was Streptococcus, and there were few gram-negative organisms. This study highlighted the polymicrobial nature and importance of anaerobic bacteria in periapical abscess.
The severity of infections involving anaerobes such as the Prevotella, Porphyromonas, Fusobacterium, and Peptostreptococcus species is enhanced by the synergy these anaerobes display with each other and with aerobes. Such synergy is common in periodontal disease because of the multiplicity of organisms and the fact that these organisms have complementary requirements.[8] Several mechanisms explain the microbial synergy in these mixed infections, including protection from mutual phagocytosis and intracellular killing and the production of essential growth factors. The lowering of oxidation-reduction potentials in host tissues produced by the aerobic component of the infection creates the physical conditions that are appropriate for replication and invasion by the anaerobic component of the infection. Such environmental factors are known to be critical for anaerobic growth. The more chronic the infection, the greater the lack of oxygen in the tissues, which spurs the growth of anaerobic bacteria. Therefore, although aerobic organisms are the most immediately virulent pathogens, as the condition becomes chronic, anaerobes thrive and bolster the infection.
Obligate anaerobes can interfere with the phagocytosis and killing of aerobic bacteria. P gingivalis isolated from cells or supernatant culture fluid was shown to possess the greatest inhibitory effect among the gram-negative anaerobic bacilli.[9] It has been demonstrated that supernatants of cultures of Prevotella and Porphyromonas, and P gingivalis are capable of inhibiting the chemotaxis of leukocytes to the chemotactic factors of P mirabilis.[10] Bacteria may also provide nutrients for each other. Klebsiella produces succinate, which supports Porphyromonas asaccharolytica, and oral diphtheroids produce vitamin K1, which is a growth factor for Prevotella melaninogenica.[11]
The role of anaerobic organisms in periodontal disease is strengthened by the finding of elevated levels of serum IgG antibodies specific for these organisms in patients diagnosed with periodontitis.[12] This immunoserologic observation is strongly supported by several bacteriologic studies, including one in which P gingivalis was the predominant isolate observed in the serum of patients with advancing chronic periodontitis lesions.[13] Several oral anaerobes and streptococci, including P gingivalis, Porphyromonas intermedia, Prevotella melaninogenica, Capnocytophaga spp, Streptococcus sanguis, and Streptococcus mitis, produce IgA proteases[14] that may impair local immunity.
Oral anaerobic bacteria possess several important virulence factors and resist beta-lactam antibiotics through production of the enzyme beta-lactamase (Table 3). Anaerobic gram-negative bacilli (Prevotella and Porphyromonas spp) possess a capsule that inhibits phagocytosis, and they produce potent enzymes and metabolic by-products. These include the production of succinic acid (inhibits polymorphonuclear migration), superoxide dismutase, catalase, immunoglobulin proteases, coagulation-promoting and -spreading factors (such as hyaluronidase, collagenase, and fibrinolysin), and adherence factors.
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Other factors that enhance the virulence of anaerobes include mucosal damage, oxidation-reduction potential drop, and the presence of hemoglobin or blood in an infected site. The significance of these factors has been previously demonstrated in vitro and in experimental animal studies.[15]
More than half of the gram-negative anaerobic bacilli (including Prevotella, Porphyromonas, Bacteroides, and Fusobacteria spp) are capable of producing the enzyme beta-lactamase, which is responsible for many treatment failures in dental infections, as well as in head and neck infections. In a study evaluating 32 periapical abscesses, beta-lactamase-producing bacilli (BLPB) were identified in one third of the cases.[7]
BLPB may have an important clinical role in infections. They can have a direct pathogenic effect as well as an indirect effect through their ability to produce beta-lactamase. BLPB may not only survive penicillin therapy but also may "shield" co-pathogens that are penicillin susceptible from the activity of penicillin by releasing the free enzyme into their environment.[16]
High levels of beta-lactamase in saliva may reflect colonization with many BLPB. It has been demonstrated that patients with recurrent group A beta-hemolytic streptococcal (GABHS) tonsillitis had detectable amounts of beta-lactamase in their saliva, compared with patients who had uncomplicated tonsillitis.[17] These data support the increasing role of BLPB in polymicrobial and oropharyngeal infections. Findings also demonstrate the rapidity with which BLPB can appear and spread to other household members.
Although penicillins have traditionally been the agents of choice for the treatment of dental bacterial infections, an increased resistance to these drugs has been documented over the past 3 decades. In addition to bacteria now known to be penicillin resistant, such as Staphylococcus aureus and Enterobacteriaceae, other organisms that were previously susceptible, such as Haemophilus influenzae and anaerobic gram-negative bacilli, have shown increased resistance due to several mechanisms. The primary mechanism is the ability to produce the enzyme beta-lactamase.
Penicillin administration has been associated with the emergence of BLPB in the oropharynx. Two studies[18,19] demonstrated the rapid emergence of BLPB following penicillin therapy. BLPB were isolated in 14% of children prior to penicillin therapy, and in 48% following a course of 7 days of oral penicillin therapy. Three months later, 25% of patients were still colonized by resistant bacteria.[18] These organisms were also isolated from household contacts of children repeatedly treated with penicillin, suggesting possible transfer within a family.[19]
Some patients are at greater risk than others for developing penicillin-resistant flora. For example, administration of amoxicillin chemoprophylaxis for the prevention of otitis media can contribute to increased resistance.[20] Although amoxicillin prophylaxis has been shown to prevent ear infections in susceptible individuals, patients receiving the drug have been shown to have increased risk for developing BLPB in the nasopharynx.
When 10 healthy volunteers were treated for 10 days with penicillin, significant increases in the number of beta-lactamase-producing Bacteroides spp (from 8/35 to 21/30) and Fusobacterium nucleatum (from 1/10 to 3/7) were observed.[19] Beta-lactamase activity in saliva was demonstrated in all volunteers, and its concentration was proportional to the increase in BLPB.
Brook and colleagues[21] evaluated the rate of recovery of aerobic and anaerobic penicillin-resistant bacteria in the oropharynx of 30 children who presented with upper respiratory tract infections over a 2-year period. During the winter months, presumably when antibiotic use is highest and individuals spend more time indoors, 50% of the patients were colonized with BLPB, compared with only 10% during the summer months. The winter season is therefore an important risk factor for colonization with BLPB.
Judicious use of antimicrobials may reduce and control the emergence of penicillin-resistant organisms. Therapy for infections that involve anaerobic gram-negative organisms, some of which can also produce beta-lactamase, should be directed against these bacteria.
Antimicrobials used to treat odontogenic infections can be divided into 2 main categories: broad or narrow spectrum. Narrow-spectrum antimicrobials include penicillin, amoxicillin, cephalexin, the macrolides (erythromycin, clarithromycin, and azithromycin), and the tetracyclines (including doxycycline). These agents have a limited antimicrobial efficacy (Table 4), as they are not effective against aerobic and anaerobic beta-lactamase producers, as well as other specific organisms.[22]
Penicillin | Oxacillin | Amoxicillin/clavulanate | Cef/1 | Macrolides | Chloro | |
Aerobic Bacteria | ||||||
Streptococcus Group A | + | + | + | + | + | + |
Streptococcus spp | + | + | + | + | + | + |
Staphylococcus spp | 0 | + | + | + | + | ± |
Capnocytophaga spp | + | + | + | ± | ± | + |
Eikenella spp | + | 0 | + | 0 | ± | 0 |
Anaerobic Bacteria | ||||||
Peptostreptococcus spp | + | + | + | + | + | ± |
Actinomyces spp | + | + | + | + | + | + |
Prevotella spp. | +_ | ± | + | 0 | 0 | + |
Porphyromonas spp | ± | ± | + | 0 | 0 | + |
Fusobacterium spp | ± | ± | + | 0 | ± | + |
Bacteroides spp | ± | ± | + | 0 | 0 | + |
Clindamycin | Metronidazole | Tetracycline | Levofloxacin | Gatifloxacin | |
Aerobic Bacteria | |||||
Streptococcus Group A | + | 0 | ± | + | + |
Streptococcus spp | + | 0 | + | + | + |
Staphylococcus spp | + | 0 | ± | ± | + |
Capnocytophaga spp | + | 0 | + | + | + |
Eikenella spp | 0 | 0 | + | + | + |
Anaerobic Bacteria | |||||
Peptostreptococcus spp | + | ± | ± | ± | + |
Actinomyces spp | + | + | ± | + | + |
Prevotella spp. | + | + | ± | ± | ± |
Porphyromonas spp | + | + | ± | 0 | ± |
Fusobacterium spp | + | + | ± | 0 | ± |
Bacteroides spp | + | + | ± | 0 | ± |
Cef/1 = first-generation cephalosporins; Chlor = chloramphenicol
Broad-spectrum antimicrobials include clindamycin; the combination of a penicillin (ie, amoxicillin) plus a beta-lactamase inhibitor (ie clavulanate); and the combination of metronidazole plus penicillin, amoxicillin, or a macrolide. These possess a broad spectrum of activity against most odontogenic pathogens, including aerobic and anaerobic beta-lactamase producers (Table 4). Furthermore, some agents (eg, clindamycin and amoxicillin-clavulanate) provide better pharmacokinetic and pharmacodynamic properties against the odontogenic pathogens compared with the others. The clinical efficacy of an agent can be predicted by taking into account its pharmacokinetic and pharmacodynamic properties, which include concentration at the site of the infection and the susceptibility of the particular pathogens.
The choice between broad- and narrow-spectrum antimicrobials should be individualized in each patient. Utilization of a broad-spectrum antimicrobial can ensure efficacy against most potential pathogens. Some patients can be treated with a narrow-spectrum antimicrobial. However, many patients are infected by organisms that are resistant to these agents. Among these patients, there is an increased risk of antimicrobial therapy failure and of developing complications. There will also be some individuals with serious underlying medical conditions or who are suffering from a serious dental infection where failed therapy will complicate their health or dentition. These situations would also preclude the use of a narrow-spectrum antimicrobial. Treatment with a broad-spectrum agent or a combination of agents is especially important in such patients.
Referral to a dental specialist or physician may be necessary when the patient presents with any of the following complications: spreading cellulites; swallowing difficulty; suspected sepsis (ie, tachycardia, hypotension, high fever, lethargy); dehydration; and signs of worsening condition, such as inability to achieve drainage and treatment failure. Such patients may require systemic antimicrobial therapy. Intravenous antibiotics are recommended when patients have swelling of the eyelid or neck, inadequate hydration, fever, lethargy and drooling. Management of these patients should be aggressive, as rapid, systemic involvement can ensue.
The oral antimicrobials that provide the broadest spectrum of efficacy against dental pathogens, including coverage for resistant aerobic and anaerobic bacteria, are:
Metronidazole is only effective against anaerobic gram-negative bacilli. Therefore, other agents are coadministered with metronidazole to provide coverage of both aerobic and anaerobic gram-positive bacteria. Other medication classes have poor activity against anaerobic bacteria. These include the aminoglycosides, sulfa agents, the monobactams, and the first-generation quinolones[23].
A number of antimicrobial agents are used for the treatment of odontogenic infections. Specific antimicrobial efficacy against potential oral pathogens is shown in Table 4. Each of these agents will be described in more detail.
Penicillin has long been a mainstay in the treatment of dental infections. The carboxyl- and ureidopenicillins (carbenicillin, ticarcillin, mezlocillin, piperacillin) are active against Pseudomonas aeruginosa and hospital-acquired gram-negative microorganisms. The carbapenems (imipenem, meropenem, ertapenem) are the most active penicillins, effective against most aerobic and anaerobic bacteria.
Although penicillin is active against streptococci and all anaerobic non-BLPB, it does not provide good coverage of anaerobic BLPB. More than half of anaerobic gram-negative bacilli that are prevalent in orofacial infections have shown increased resistance to penicillin through the production of beta-lactamase. These include Fusobacterium spp, pigmented Prevotella, and Porphyromonas spp.
The increasing number of penicillin-resistant bacterial strains has important implications for antimicrobial therapy. Many penicillin-resistant bacteria can produce enzymes that degrade penicillins or cephalosporins by releasing the enzyme in the area of the infection. Therefore, these organisms may protect not only themselves but also penicillin-sensitive pathogens. Penicillin therapy directed against a susceptible pathogen might therefore be rendered ineffective by the presence of BLPB.
Antimicrobial therapy for penicillin-resistant bacteria includes clindamycin (oral and parenteral), the combination of a penicillin plus a beta-lactamase inhibitor (eg, amoxicillin-clavulanate [oral] or piperacillin-tazobactam [parenteral]), the combination of metronidazole plus penicillin, amoxicillin/ampicillin, a macrolide (oral and parenteral), cefoxitin or cefotetan (parenteral), and the carbapenems (imipenem [parenteral]).
Amoxicillin is similar to penicillin in its spectrum of coverage against oral pathogens. The addition of a beta-lactamase inhibitor (such as clavulanic acid) makes amoxicillin active against most aerobic and anaerobic BLPB. However, if other mechanisms of resistance emerge, blockage of the enzyme beta-lactamase will not prevent resistance. Other mechanisms of resistance include alteration in the porin canal through which the antimicrobial penetrates into the bacteria and changes in the penicillin-binding protein that inhibit binding of the drug into the bacterial cell wall. The last mechanism is resistance to penicillin among Streptococcus spp, including S pneumoniae.
Cephalosporins have shown variable efficacy in the treatment of dental infections. The first-generation cephalosporins are most effective against aerobic gram-positive bacteria (streptococci and staphylococci), but they do not cover aerobic gram-negative organisms. The second-generation cephalosporins are similar to the first-generation with regard to coverage of aerobic gram-positive bacteria, and are more effective against aerobic gram-negative organisms (ie, H influenzae, Moraxella). Cefoxitin and cefotetan have significant activity against anaerobes including the B fragilis group. Third-generation cephalosporins are active against gram-negative aerobic bacteria including enterobacteriaceae, but are not effective against penicillin-resistant Streptococcus spp (including S pneumoniae and S aureus), making them less appealing for the treatment of dental infections. All 3 generations of the oral cephalosporins have failed to show activity against anaerobic BLPB.
Chloramphenicol has in vitro activity against most anaerobic bacteria, enterobacteriaceae, and aerobic gram-positive cocci. Resistance of aerobic Streptococcus spp to chloramphenicol has increased, however. The toxicity of chloramphenicol, which has been linked to the development of aplastic anemia (a rare but potentially fatal condition) and dose-dependent leukopenia, limit its use.
These agents are effective against aerobic gram-positive cocci and have broader coverage against anaerobes, including BLPB, all of which are responsible for dental infections. Clindamycin has demonstrated effectiveness in the treatment and prophylaxis of dental infections and their associated complications because of its ability to achieve high tissue concentration, intracellular penetration, and increased phagocytosis, as well as its ability to inhibit toxin production.[24] Some strains have demonstrated resistance to clindamycin and lincomycin, such as Bacteroides fragilis (5% to 10%) and Clostridium spp other than C perfringens.[23]
Antibiotic-associated colitis caused by Clostridium difficile was first described after clindamycin therapy.[25] However, colitis is more frequently associated with other antimicrobial agents, such as penicillins and cephalosporins.
Metronidazole is very effective against anaerobic gram-negative bacilli, including those that produce beta-lactamase. However, it is not effective against aerobic organisms, and has only marginal coverage for some of the anaerobic gram-positive organisms (ie, Actinomyces, Peptostreptococcus). Metronidazole should always be administered with an agent effective against aerobic or facultative streptococci.
Macrolide antibiotics -- azithromycin, clarithromycin, and erythromycin -- have moderate to good in vitro activity against anaerobic bacteria other than Fusobacteria. They are active against Prevotella and Porphyromonas spp, microaerophilic and anaerobic streptococci. They possess inconsistent activity against gram-negative anaerobic bacilli. Resistance of Group A streptococci, as well as other Streptococcus spp, is increasing and has been associated with previous macrolide use.
This agent is primarily effective against aerobic gram-negative organisms but is not reliable against aerobic gram-positive cocci, including Streptococcus spp. It is also not effective against anaerobic bacteria.
Tetracyclines are of limited usefulness in the treatment of dental infections because of the development of resistance by all types of anaerobes, including gram-negative bacilli. The newer tetracycline analogs, doxycycline and minocycline, are more active than the parent compound. Because there is significant resistance to these drugs, they can be used if the organisms are susceptible or in less severe infections in which a therapeutic trial is feasible. The use of tetracyclines is not recommended in patients younger than 8 years or during pregnancy or breastfeeding, because of its adverse effect on developing teeth in the fetus, infants, and young children.
First-generation fluoroquinolones (eg, ciprofloxacin and ofloxacin) are inactive against most anaerobic bacteria as well as aerobic gram-positive cocci. Gatifloxacin, moxifloxacin, and trovafloxacin are more effective against most groups of anaerobes. Quinolones with the greatest in vitro activity against anaerobes are clinafloxacin and sitafloxacin. Use of quinolones is restricted in growing children because of their possible adverse effects on the cartilage.
Odontogenic infections are almost always associated with specific bacterial pathogens and often require the use of systemic antimicrobial therapy. Such therapy may inhibit or kill gingival and periodontal pathogens that are located out of reach of dental instruments and topical antiseptics. Acute and chronic dento-alveolar infection often require such therapy. These include endodontic abscess, periodontal abscess, pericoronitis, periodontitis, periodontal-endodontal lesions (especially necrotizing ulcerative gingivitis, chronic periodontitis, and aggressive periodontitis), and peri-implantitis (Table 5).
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Treatment consists of identifying the cause and extent of the infection, eradicating the infection and its cause, providing drainage when appropriate, using topical antiseptic rinses to aid in supragingival plaque control, and using systemic antimicrobials as adjunctive therapy to limit the local and systemic spread of the infection.
Identifying the causative organisms and determining antimicrobial susceptibility are helpful in selecting the proper drug therapy. Identification can be done by culture or DNA probing methods.[26] Systemic antimicrobial therapy is generally not recommended for root caries, dry socket, or gingivitis.
Consideration should be given to administering an initial loading dose of an antimicrobial as the first treatment dose. This is done to rapidly achieve a high tissue concentration and is generally the approach used with agents that are administered every 6 to 8 hours (ie, amoxicillin, clindamycin, and penicillin). An exception to this is azithromycin, for which an initial loading dose is indicated, although the antimicrobial is given once every 24 hours.
Therapy should not be changed until it has been given for at least 48 to72 hours. The patient needs to take the antimicrobial for the entire recommended length of time. A short course of an anti-infective therapy may not produce long-term results, because it may be insufficient to eradicate the infection or because the patient may become re-infected.
A combination of antimicrobials instead of a single agent may be considered, especially in the case of a periodontal infection due to multiple pathogens with different antimicrobial susceptibility. In such a situation, a combination of drugs is chosen to cover all the important pathogens. A combination of antimicrobials can be synergistic and may delay the emergence of bacterial resistance. However, antagonism between the drugs can occur, and there is a greater likelihood of adverse effects.
Conditions that may increase the risk of infection with antimicrobial-resistant organisms are: recent administration of antimicrobial therapy or prophylaxis (within the past 6 weeks), close contact with individual(s) who were recently treated with an antimicrobial (ie, household, school, daycare center), failure of a previous antimicrobial regimen, direct or indirect exposure to smoking, and a high rate of antimicrobial resistance in the community.
When considering the optimal treatment approach for a particular infection, antibiotics are not always the answer. Sometimes, surgery is required. In other cases, the best course of action is debridement, irrigation, and drainage.
Therapy always includes one of the following procedures: root canal therapy or re-treatment, surgery of the periradicular area, or tooth extraction. Oral-antral fistulae may require surgical closure. However, the fistulae source needs to be explored and removed prior to closure.
Endodontic therapy does not require the use of antimicrobials unless local or systemic spread of the infection is present, local drainage is not possible or is delayed, or the patient is immunocompromised and requires prophylaxis. The antimicrobials available for therapy of this infection are outlined in Table 6.
Antimicrobials | Adult Dosage | Pediatric Dosage |
Narrow-spectrum agents | ||
Penicillin VK | 250-500 mg q6h | 50 mg/kg q8h |
Amoxicillin | 500 mg q8h | 15 mg/kg q8h |
Cephalexin§ | 250-500 mg q6h | 25-50 mg/kg/d q6-8h |
Erythromycin†| 250 mg q6h | 10 mg/kg q16h |
Azithromycin†¶ | 500 mg x 1d, then 250 or 500 mg q24h | 10 mg/kg/d x 1d, then 5 mg/kg/d q24h x 4d |
Clarithromycin†| 250-500 mg q12h or | 15 mg/kg/d q12h |
Doxycycline†‡ | 100 mg q12h | 1-2 mg/kg q12h x 1d, then 1-2 mg/kg q24h |
Tetracycline†‡ | 250 mg q6h | 12.5-25.0 mg/kg q12h |
Broad-spectrum agents | ||
Clindamycin†| 150-300 mg q8h | 10 mg/kg q8h |
Amoxicillin/clavulanate | 875 mg q12g | 45 mg/kg q12h |
Metronidazole plus 1 of the following:†| 250 mg q6h or 500 mg q12h | 7.5 mg/kg q6h or 15 mg/kg q12h |
Penicillin VK | 250-500 mg q6h | 50 mg/kg |
or Amoxicillin | 500 mg q8h | 15 mg/kg q8h |
or Erythromycin†| 250 mg q6h | 10 mg/kg q6h |
*Duration of therapy: 7-10 days. Consideration should be given to administering an initial loading dose of an antimicrobial as the first dose.
†Also in penicillin-allergic individuals.
‡Not recommended for children younger than 8 years of age or for pregnant women.
§Cross-allergy with penicillins is about 10%.
¶First dose is a loading dose and should consist of twice the regular amount. This is the required schedule with azithromycin.
The microorganisms that cause gingival disease can usually be controlled without the use of systemic antibiotics. Clinical care includes local treatment that removes calculus and plaque (bacterial biofilm) and disinfects the gingival crevices. Patients need to be taught how to use self-care measures that will keep disease-related bacteria under control. Helpful measures may include twice-daily rinsing with chlorhexidine gluconate 0.12% mouthwash, brushing with a mixture of baking soda plus hydrogen peroxide, and/or frequent salt-water rinses.
In general, antimicrobials are not recommended for gingivitis. However, streptococcal gingivitis and necrotizing ulcerative gingivitis (NUG) are 2 types of gingivitis that may require antimicrobial therapy.
Streptococcal gingivitis is caused by GABHS (S pyogenes) and is generally associated with acute streptococcal tonsillitis. Systemic antimicrobials therapy is directed at the eradication of GABHS.
NUG, previously called acute necrotizing ulcerative gingivitis (also known as trench mouth or Vincent's infection), is a very painful, fetid, ulcerative disease that occurs most often in persons under severe stress with no or very poor oral hygiene. It is manifested by acutely tender, inflamed, bleeding gums, and is associated with interdental papillae necrosis and loss. Halitosis and fever are often present. Microbiologic examinations of the bacterial biofilms found in NUG reveal high numbers of spirochetes and Fusobacteria.
Management of NUG includes generalized gross debridement of all teeth with copious irrigation, preferably with an ultrasonic scaler. The topical application of antibacterial mouth rinses such as 0.12% chlorhexidine gluconate and/or saline rinses is an effective measure to control the pain and ulceration of NUG.
Systemic antibiotics are necessary if constitutional symptoms such as fever or malaise develop (Table 6). The choice of antimicrobials should be based, whenever possible, on culture and susceptibility testing of the subgingival flora. Cultures should also be obtained after therapy to ensure eradication of the pathogens.
Management includes debridement and drainage of pus. Antimicrobial therapy is necessary whenever local or systemic spread is present (Table 6). Extraction of the involved tooth may be necessary if antibiotic therapy fails.
Debridement and thorough scaling and root planing to remove the subgingival and supergingival deposits of calculus and plaque (bacterial biofilm) are first-line interventions.
When pockets are more than 5 mm deep, local therapy rarely adequately suppresses the involved pathogens. Therefore, subgingival irrigation to disinfect the gingival crevices can be accomplished with the use of either ultrasonic scalers or individual irrigating syringes. Effective antiseptic solutions are povidone iodine, chlorhexidine, chloramine-T, or salt water.
Helpful measures may include twice-daily rinsing with chlorhexidine-gluconate 0.12% mouthwash, brushing with a mixture of baking soda plus hydrogen peroxide, and/or frequent salt-water rinses. Local therapy with antimicrobial delivery systems is to be considered as adjunctive therapy and not as an alternative to instrumentation.
The use of systemic antimicrobials is especially indicated in chronic periodontitis and aggressive periodontitis (Table 6). Appropriate systemic antibiotic regimens should be based on culture and susceptibility testing of the subgingival flora whenever possible (Table 4). Cultures should also be taken after therapy to insure eradication of pathogens.
Pericoronitis is an infection of the pericoronal soft tissue (opercula) that partially overlie the crown of the tooth. The teeth most often involved are the mandibular third molars. The infection is caused by microorganisms and debris that become entrapped between the tooth and the overlying soft tissue. In most cases, antibiotic treatment is necessary to avoid spread of the infection.
Therapy is local and includes debridement, irrigation, and drainage of the involved area (including abscess), followed by relief of the occlusion or extraction of the opposing tooth. After infection is controlled, when appropriate, the impacted tooth is extracted. Antimicrobials are used when local or diffused swelling exists despite local therapy, the temperature is elevated, and trismus is present (Table 6).
The key to minimizing implant failure is the proper diagnosis and effective treatment of problems in their early stages. Essential therapy includes individual plaque and calculus control and regular professional mechanical debridement of plaque deposits. Adjuvant therapy includes rinsing with chlorhexidine gluconate for 30 seconds after tooth-brushing for 21 days. Antibiotics can be used as prophylactic treatment at the time of implant placement, or in cases or peri-implant mucositis, peri-implantitis, ailing implants, and failing implants. The recommended antibiotics are clindamycin; amoxicillin/clavulanate; or metronidazole plus penicillin G or ampicillin or a macrolide (Table 7).
Antimicrobial | Adult Dosage |
Clindamycin†| 300 mg, then 150-300 mg q8h |
Amoxicillin/clavulanate | 875 mg q12h |
Metronidazole†plus 1 of the following: | 500 mg, then 250 mg q6h or 500 mg q12h |
Penicillin VK | 250-500 mg q6h |
or Amoxicillin | 1000 mg, then 500 mg q12h |
or Erythromycin†| 250 mg q6h |
or Azithromycin†| 500 mg x 1d, then 250 or 500 mg q24h x 4d |
or Clarithromycin†| 250-500 mg q12h or |
*Duration of therapy: 7-10 days.
†Also in penicillin-allergic individuals.
Treatment of serious fascial and deep neck infections generally requires parenteral antimicrobial therapy (Table 8) in order to enhance healing and prevent local and systemic spread of the infection. The recommended antibiotics are clindamycin; metronidazole plus penicillin G or ampicillin or a macrolide; ticarcillin/clavulanate; piperacillin/tazobactam; or a carbapenem (eg imipenem).
Antimicrobial | Adult Dosage | Pediatric Dosage |
Clindamycin†| 300-600 mg q8h | 10 mg q8h |
Metronidazole†plus | 250 mg q6h | 7.5 mg/kg q6h |
Penicillin G | 1-2 x 106 U q4-6h | 50,000 U/kg q6h |
or Ampicillin | 500 mg q8h | 15 mg/kg q8h |
or Erythromycin†| 250-500 mg q6h | 20-40 mg/kg/d q6h |
Ticarcillin/clavulanate | 3 g (Tic) q4-6h | 60 mg (Tic)/kg q6h |
Piperacillin/tazobactam | 3 g (Pip) q6h | 60 mg (Pip)/kg q6h |
Imipenem | 0.5-1.0 g q6h | 15-25 mg/kg 6h |
Meropenem | 0.5-1.0 g q8h | 20 mg/kg q8h |
*Duration of therapy: 10-14 days; surgical drainage is mandatory.
†Also in penicillin-allergic individuals.
The increasing incidence of bacterial resistance has produced a major challenge for the successful therapy of many dental infections. The emergence of resistant bacteria during the course of antimicrobial therapy can also result in clinical failure. Numerous studies conducted during the past 10 to 15 years have demonstrated that the success of a specific dose of drug is dependent on both a measure of drug exposure, such as the serum peak level, the area under the serum concentration vs time curve (area under the curve [AUC]), and the duration of time the serum levels exceed the bacterial minimal inhibitory concentration (MIC) of the potency of the drug against the infecting organisms. These so-called pharmacokinetic/pharmacodynamic (PK/PD) parameters can be major determinants of the in vivo efficacy of antimicrobial agents.[27]
The specific parameters most commonly correlated with outcome include the ratio of peak to minimum inhibitory concentration (peak/MIC ratio), the ratio of the 24-hour AUC to MIC (24-h AUC/MIC ratio), and the duration of time serum levels exceed the MIC, expressed as the percentage of the dosing interval. For beta-lactam antibiotics (ie, cephalosporins and penicillins), macrolides, clindamycin, and linezolid, free drug levels in serum need to exceed the MIC for at least 40% to 50% of the dosing interval. The 24-hour AUC/MIC should be at least 25-35 for azithromycin, metronidazole, and fluoroquinolones when treating patients with gram-positive bacteria infections. Higher ratios (>/= 100) for the 24-hour AUC/MIC are required for these agents to have efficacy against gram-negative bacilli.
Increasing amounts of data from in vitro and animal infection models illustrate the relationships between the magnitude of these PK/PD parameters for different antimicrobial agents and their ability to treat less susceptible organisms and to prevent the emergence of resistance. Studies in humans are more limited, but the availability of pharmacologic tools, such as optimal sampling and population pharmacokinetic modeling, have greatly improved the ability of researchers to estimate the extent of drug exposure in individual patients.
Since there are few controlled, double-blind clinical trials on the use of antibiotics in endodontal and periodontal infections, antibiotic usage in these infections is completely empirical.[28] Application of the PK/PD parameters for dental infections revealed that the antimicrobials for orofacial infections that provide better efficacy indexes against all of the most common aerobic and anaerobic bacterial isolates are clindamycin and amoxicillin clavulanate. Metronidazole possesses good indexes only against anaerobic bacteria[29] (Tables 9 and 10).
Antimicrobials are indicated as prophylaxis in noninfected individuals who undergo dental procedures or surgery, to prevent local and systemic infections in high-risk patients, and to reduce postsurgical complications after certain high-risk procedures. The goal is to achieve sufficient concentration of the anti-infective(s) at the potential site of infection (tissue or blood) before the potential spread of the organism(s). After an initial loading dose, the antimicrobial agent is continued as long as contamination persists. The selection of the antimicrobial is made by determining which microorganisms are most likely to cause an infection.
Table 11 illustrates the types of patients who should receive prophylaxis, such as immunocompromised patients and those with increased susceptibility to infections, among others. Antimicrobial prophylaxis regimens for patients with increased susceptibility to infections are shown in Table 12.
|
*Post-procedure therapy.
Route | Antimicrobial | Adult | Pediatric |
Oral | Amoxicillin Clindamycin* | 2 g 1h 600 mg 1h | 50 mg/kg 1h 20 mg/kg 1h |
Parenteral (IV) | Ampicillin Clindamycin* | 2 g </= 30 m 600 mg </= 30 m | 50 mg/kg </= 30 m 20 mg/kg </= 30 m |
*Also in penicillin-allergic individuals.
The incidence and magnitude of bacteremia following dental procedures can be reduced by using antiseptic mouth rinses such as chlorhexidine gluconate and 10% povidone-iodine.
Poor dental hygiene and periapical or periodontal infection can produce spontaneous bacteremia even without a dental procedure. Maintaining oral health in susceptible individuals can prevent bacteremia. In patients who are already receiving an antibiotic, a different agent should be administered for prophylaxis. Table 13 provides a list of conditions that do or do not require bacterial endocarditis prophylaxis. A list of dental and oral procedures that do or do not require bacterial endocarditis prophylaxis is shown in Table 14, and a list of endocarditis prophylactic regimens appears in Table 15.
Conditions Requiring Prophylaxis | Conditions Not Requiring Prophylaxis |
High Risk Prosthetic cardiac valve, including bioprosthetic and homograph valves Prior bacterial endocarditis Complex cyanotic congenital heart defects Surgically constructed systemic pulmonary shunts or conduits Moderate Risk Rheumatic and other congenital and acquired valvular dysfunction Ventriseptal and atrial septal defect or patent ductus arteriosus Hypertrophic cardiomyopathy Mitral valve prolapse with valve regurgitation Marfan's syndrome Coarctation of bicuspid aortic valve | Past (> 6 months) surgical repair without residual of secundum atrial defect Isolated secundum atrial septal defect Past coronary bypass surgery Mitral valve defect without regurgitation Physiologic or functional or innocent heart murmurs Cardiac pacemakers and implanted defibrillators Prior Kawasaki's disease or rheumatic heart disease without valve dysfunction |
Prophylaxis Recommended | Prophylaxis May or May Not Be Needed | Prophylaxis Not Recommended |
Procedures causing gingival or mucosal bleeding Periodontal, periapical, and oral surgery Periodontal procedures Root canal Subgingival placements Surgical endodontics Intraligamentary local anesthetic injections Dental implant placement Surgical procedures that involve the mucosa Incision and drainage Orthodontic bands placement or removal | Radiography of root canal length Restoration of multiple subgingival cavities Periodontal probing | Procedures that are not likely to cause gingival bleeding Placement of rubber dams Placement of removable prosthodontic or orthodontic appliances Fluoride treatments Impressions Orthodontic appliance adjustment Injection of local intraoral anesthetics Shedding of the primary teeth Endodontic procedures that do not extend beyond the root apex |
Route | Antimicrobial | Adult Dosage/Time of Administration Before Procedure | Pediatric Dosage/Time of Administration Before Procedure |
Oral | Amoxicillin | 2.0 g/1h | 50 mg/kg/1h |
Clindamycin†| 600 mg/1h | 20 mg/kg/1h | |
Cephalexin‡ or Cefadroxil‡ | 2 g/1h | 50 mg/kg/1h | |
Azithromycin†§ or Clarithromycin†§ | 500 mg/1 h†| 12 mg/ kg 1h | |
Parenteral | Ampicillin | 2.0 g IM or IV </= 30 m | 50 mg/kg IV/IM </= 30 m |
Clindamycin§ | 600 mg IV </= 30 m | 20 mg/kg IV </= 30 m | |
Cefazolin‡ | 1g IM/IV </= 30 m | 25 mg/kg IV/IM </= 30 m |
*Adapted from JAMA. 1997;277:1794-1801.
†Activity of macrolides against viridans streptococci is not optimal.
‡Cross-allergy with penicillins is about 10%.
§Also in penicillin-allergic individuals.
Bacteremia of dental origin (generally streptococcal) has been implicated in infections of implanted prosthetic joints. Antimicrobial prophylaxis is recommended in patients with elevated risk prior to dental treatments, induced immunosuppression, type 1 insulin-dependent diabetes mellitus, previous prosthetic joint infections, loose prostheses, re-operated joints, acute infections at a distant site, hemophilia, malnutrition, and inflammatory arthropathies. It is also recommended during the first 2 years after patients have undergone joint replacement. Therapeutic agents recommended in these situations are shown in Table 16.
Route | Antimicrobial | Dosage/Time Administered Before | |
Oral | Adult | Pediatric | |
Clindamycin†| 600 mg/1 h | 20 mg/kg/1 h | |
Amoxicillin- | 875 mg/1 h | 45 mg/kg/1 h | |
Parenteral (IV) | Clindamycin* | 600 mg/ </= 30 m | 20 mg/kg </= 30 m |
*An additional dose may be indicated if the procedure lasts more than 3 hours.
†Also in penicillin-allergic individuals.
The pathogens that cause infectious diseases and the appropriate antimicrobials to treat them change frequently. The emergence of resistance to penicillin and other antimicrobial agents has presented an urgent and worldwide treatment challenge.
This Clinical Update provides general guidance for selecting the appropriate antimicrobial therapy for various odontogenic conditions. However, it is becoming common for dentists to obtain a culture that reveals the pathogens that are present and to determine the appropriate treatment agent on the basis of antimicrobial susceptibility. Pathogens are constantly changing and new resistance patterns continue to emerge -- presenting an urgent and worldwide treatment challenge. However, since the resistance patterns of most odontogenic pathogens are predictable, an empiric choice of the proper therapy is still possible in most instances. This approach could enhance resolution of the infection and facilitate recovery.