Penicillins (e.g., penicillin, amoxicillin)

Cephalosporins (e.g., cephalexin)

Macrolides (e.g., erythromycin, clarithromycin, azithromycin)

Fluoroquinolones (e.g., ciprofloxacin, levofloxacin)

Sulfonamides (e.g., sulfamethoxazole, trimethoprim)

Tetracyclines (e.g., tetracycline, doxycycline)

Aminoglycosides (e.g., gentamicin, tobramycin)

The objective is to help the body’s defenses clear tissues of pathogenic microorganisms by achieving levels in the infected sites that are equal or greater than the minimum inhibitory concentrations (MIC).

Eliminate the causative agents physically (incision and drainage).

• Odontogenic infections rarely rebound, particularly if the source of the infection has been eliminated (root canal or extraction).

The pathogenic organisms must be susceptible to the antimicrobial agent.

There should be sufficient drug concentration at the site of infection during the course of therapy.

Local factors that may interfere with the drug’s effect must be minimized.

Antibiotics should be used aggressively and for a sufficient duration of time to result in clinical improvement/resolution.

Host defenses must be adequate for the eventual eradication of pathogens and associated toxins.

Most odontogenic infections begin and peak rapidly.

High antibiotic level must be reached quickly.

• This is achieved by loading doses.

• Loading doses are two to four times the maintenance doses.

• If a loading dose is not used, approximately four maintenance doses spaced at the recommended intervals are required to achieve a steady-state blood level of the antibiotic.

For antibiotics with exceptional bioavailability (e.g., amoxicillin), a loading dose is not as crucial as it is with penicillin V or cephalexin, which are not absorbed as readily.

Diffusion to the infection site:

• Diffusion through capillary endothelium is easy for metronidazole.

• Diffusion is difficult for beta-lactams and aminoglycosides, while tetracyclines and fluoroquinolones demonstrate intermediate diffusion profiles.

Lipid solubility:

• Lipophilic agents (e.g., tetracyclines, macrolides, and fluoroquinolones) pass through barriers (such as cellular membranes) better than hydrophilic beta-lactams and aminoglycosides.

Plasma protein binding ability:

• Lower plasma protein binding may be preferred (e.g., amoxicillin vs. penicillin VK) because they pass more readily.

Inoculum effect:

• The principle that antibiotics lose efficacy against a dense mass of microbial population.

• May significantly affect antibiotic activity and the ability of the drug to penetrate to the core of infection.

  • This is the benefit of incision and drainage.

Surface/volume ratio:

• Incision and drainage generate a high vascularity, low infection volume situation.

• This promotes better antibiotic penetration.

Pregnancy.

• Most antibiotics commonly used in dentistry are safe for the pregnant patient; but there is potential for some to harm the developing baby.

• It is not uncommon for patients to require antibiotics to treat a dental infection while pregnant.

• Some antibiotics are known to be teratogenic and should be avoided entirely during pregnancy.

  • These include streptomycin and kanamycin (may cause hearing loss) and tetracycline (can lead to weakening, hypoplasia, and discoloration of long bones and teeth).

• Recommend and prescribe antibiotics for pregnant patients only if absolutely indicated.

• If possible, avoid initiating antibiotic therapy during the first trimester, as this is the period of fetal structural development; and therefore, the highest risk for iatrogenic teratogenicity.

• Select a safe antibiotic medication.

  • This often means selecting an established antibiotic with a proven track record in pregnancy.

• Whenever clinically indicated, single-agent antibiotic therapy is preferred over polypharmacy.

• Narrow-spectrum antibiotics are preferred over broad-spectrum for the treatment of established odontogenic infection.

• Prescribe the lowest effective dose of antibiotic to treat the infection.

• Discourage the use of over-the-counter drugs that may interfere with the efficacy and/or metabolism of prescription antibiotic medications.

Renal and hepatic functions.

• Renal dysfunction: as a general rule, the dose interval should be increased for concentration-dependent antibiotics and decreased for time-dependent antibiotics.

• Renal insufficiency: some antibiotics do not require dosage adjustments (e.g., clindamycin, azithromycin).

Antibiotic prescriptions should be initially aggressive but administered for a minimum amount of a time that is compatible with remission of disease.

• The ideal duration is the shortest time that prevents clinical and microbiological relapse.

Antibiotic success is best determined by clinical symptom improvement.

Example: prescribe a reasonable regimen (5–7 days) with an initial loading dose (not needed for amoxicillin) and then re-evaluate shortly into the infection (1 or 2 days) and monitor patient’s progress until symptoms improve.

Prolonged antibiotic duration does not destroy resistant organisms.

Prolonged treatment is not necessary to prevent rebound oral infections.

Antibiotic dosage and duration cannot be extrapolated from one infection to another.

There is no guaranteed way to know how long the infection will last.

• Definite treatment of the infection source is the most effective treatment.

Dosing guidelines do not take into consideration issues related to microbial virulence, anatomic location of the infection, feasibility of incision and drainage, microbial resistance, and status of host defenses.

Concentration-dependent effect:

• Some antibiotics are most effective if very high blood concentrations are achieved periodically.

• Examples include:

  • Aminoglycosides.

  • Metronidazole.

  • Fluoroquinolones.

Time-dependent effect:

• Effective if blood levels are maintained above MIC for as long as possible.

• Examples include beta-lactams and vancomycin.

• The goal of dosing with cell wall synthesis inhibitors is to maximize the time of exposure and maintain the blood and tissue concentrations above the organisms’ MIC for as long as possible.

• Time-dependent effects are better achieved with longer half-life agents (e.g., amoxicillin) than those with shorter half-lives (e.g., penicillin VK, cephalexin).

In general, the concentration of the antibiotic in the blood should exceed the MIC by a factor of 2 to 8 times to offset tissue barriers that restrict access to the infected site.

Allergic reactions: penicillins, sulfa drugs.

Antibiotic-induced diarrhea and pseudomembranous colitis: amoxicillin, clindamycin.

Potential for disturbances of endogenous flora and superinfection.

• Acquisition and transfer of drug-resistant genes: tetracyclines, vancomycin.

Antibiotic-associated photosensitivity and phototoxicity: sulfonamides, tetracyclines.

Antibiotic-induced agranulocytosis: sulfonamides, beta-lactams, aminoglycosides, macrolides.

Long QT interval syndrome: fluoroquinolones, macrolides, clindamycin.

Antibiotic-associated mania: clarithromycin, fluoroquinolones.

Antibiotic therapy initiated after surgery to prevent infection that is unlikely to occur or lacks efficacy for this purpose as demonstrated by clinical trials.

Failure to use prophylactic antibiotics according to the principles established for such use.

Use of antibiotics as analgesics in endodontics.

Overuse in situations in which patients are not at risk for metastatic infections.

Treatment of chronic periodontitis almost completely amenable to mechanical therapy.

Long-term administration in the management of periodontitis.

Antibiotic therapy instead of incision and drainage.

Antibiotic recommendation for avoiding claims of negligence.

Administration of antibiotics in improper situations, dosage, and duration of therapy can lead to antibiotic resistance.

According to the CDC, at least 2 million Americans are infected each year with bacteria that are resistant to antibiotics.

• Of these, 23,000 or more die as a result of these infections.

Inappropriate use of antibiotics is the major culprit.

Challenge: maintain and preserve the efficacy of current antibiotics.

• Antibiotic development is not an easy task.

• All microbial resistance is local (i.e., related to use in a particular community).

• Antibiotics are societal drugs that cumulatively affect the individual receiving the drug and many others.

Microbial resistance accelerates when subtherapeutic doses are used.

• This gives bacteria opportunity to react via mutation, acquisition, or transfer of resistance genes, virulence factors, or expression of latent resistance (also known as induction).

• The gastrointestinal tract is a massive reservoir for resistance genes readily transferred within and between enteric microbial species, a process greatly enhanced by antibiotics and agents such as tetracyclines, imipenem, cefoxitin, and clavulanic acid.

• Tissue levels should ideally contain 8- to 10-fold the MIC of an antimicrobial agent to reduce or prevent the emergence of resistant subpopulations.

  • Unfortunately, this is often impossible because of complications or toxic side effects of many antibiotic classes.

Known evasion mechanisms for antibiotics:

• Enzymatic inactivation (e.g., beta-lactams, acetyltransferases).

• Modification or occlusion of the target site (e.g., penicillin-binding proteins for penicillins and DNA gyrase for fluoroquinolones).

• Ribosomal point mutation (e.g., macrolides, clindamycin).

• Limitation of antibiotic diffusion often via alteration of cell membrane permeability (e.g., beta-lactams, fluoroquinolones).

• Active drug efflux (e.g., tet genes effect efflux of tetracyclines out of microbes).

• Decreased activation of antibiotic compounds (e.g., metronidazole).

• Overproduction of target sites (e.g., sulfonamides; overproduction of beta-lactamase).