Antibiotics produce their antibacterial effect either by a bactericidal or bacteriostatic mechanisim of action. Bacteriostatic antibiotics inhibit the growth and multiplication of microorganisms while bactericidal andibiotics kill or destroy microorganisims. In general, bacteriostatic antibiotics alter the metabolic pathways or synthesis of cellular components. In contrast, bactericidal drugs interfere with the synthesis or function of either the cell wall, cell membrane or both.

When two bactericidal antibiotics are given together, they may exert a greater effect than when each is given separately. This is called antibiotic synergism. However, when a bacteriostatic and a bactericidal antibiotic are given together, their effectiveness is negater or reduced. This is called antibiotic antagonism. In the majority of dental infections, combination thereapy is not usually necessary. However, since patients may present to an office with a dental infection requiring and antibiotic and they may already be taking an antibiotic for a systemic infection, a drug intereaction based on mechanism of action may occur. In Table 2 some frequently prescribed antibiotics are listed with their mechanism of action. When concomitant usage of two or more antibiotics is necessary, the general rule is to administer bacteriocidal agents with bacteriocidal agent, bacteriostatic agents with bacteriostatic agents, but never bacteriocidal with bacteriostatic agents.

Macrolide antibacterials used in dentistry include erythromycin, azithromycin and clarithromycin.  The primary mechanism by which they interact with other drugs is inhibition of liver metabolism. Certain macrolide antibiotics, such as erythromycin and troleandomycin are fairly potent hepactic enzyme inhibitors while other macrolides, including clarithromycin are less effective enzyme inhibitors. Azithromycin and dirithromycin do not appear to cause significant clinical drug interactions. Increased serum levels of the drugs shown in Table 3 may occur when they are administered with macrolide antibiotics, especially erythromycin. Recently, it has been reported that erythromycin may interact with the calcium channel blockers, Diltiazem and Verapamil and result in cardiac toxicity. The potential for a similar cardiac effect may be present with concomitant use of some antidepressants but which ones are not clear at this time. However, this interaction has not been reported with Clarithromycin and Azithromycin. In view of its highly interactive effects with a number of medications, erythromycin should be prescribed mainly when other antibiotics with a similar antibacterial spectrum cannot be prescribed.

The bioavailability of tetracycline is reduced by 46% to 57% when taken with food, by 50% to 65% when taken with dairy products and by up to 85% when taken with iron supplements. Tetracycline chelates with polyvalent cations (e.g. iron, calcium, magnesium, and aluminum) in the gut preventing its absorption and resulting in potential treatment failures.

Oral contraceptive failure rate with antibiotics other than the anti-tuberculosis drug Rifampin is unclear. Antibiotics that do not induce cytochrome P-450 may reduce the plasma levels of steroids based on indirect interference with the circulation in the liver of the estrogen component of the oral contraceptive. Antibiotics that kill the intestinal bacteria involved in the deconjugation processes can inhibit this recirculation. However, this mechanism has not been proven. Except for rifampin, there is no evidence that antibiotics significantly affect the plasma concentration of the oral contraceptive. However, due to a number of existing retrospective case reports, it is possible that certain individuals may be at risk of this interaction. The American Dental Association has published the following:

"Therefore, it is the opinion of the ADA Council on Scientific Affairs that, considering the possible consequences of an unwanted pregnancy, when prescribing antibiotics to a patient using oral contraceptives, the dentist should do the following:

• Advise the patient of the potential risk of the antibiotic’s reducing the effectiveness of the oral contraceptive;

• Recommend that the patient discuss with her physician the use of an additional nonhormonal means of contraception;

• Advise the patient to maintain compliance with oral contraceptives when concurrently using antibiotics"

Metronidazole is an antibiotic used in dentistry, alone or in combination with penicillin to increase its spectrum of activity. Metronidazole’s chemical structure contains an imidazole ring, which is found in many other drugs known to inhibit drug metabolism in the liver (e.g. cimetidine, ketoconazole, miconazole and omperazole). Also, metronidazole inhibits the metabolism of warfarin, resulting in accumulation of warfarin and an enhanced anticoagulant effect. This combination should be avoided if possible. Further, alcohol is contraindicated when taking metronidazole since this combination can result in severe nausea and vomiting. It is possible that inadvertent swallowing of alcohol when using alcohol-containing mouthrinses may produce mild to moderate nausea and gastrointestinal distress.

Alprazolam, diazepam, midazolam and triazolam are substrates for the hepactic P-450 enzyme. Drug interactions associated with oral administration have been well documented with the end result being benzodiazepine accumulation and prolonged and excessive sedation. Erythromycin and clarithromycin interact with these drugs and may significantly increase their duration of effect and side effects.

In addition, azole antifungal drugs (azoles), protease inhibitors, fluvoxamine, nefezadone (both antidepressants), and grapefruit juice, can significantly increase blood levels, and the sedative and psychomotor impairment effects of diazepam, alprazolam, midazolam and triazolam.