Adjunctive Antibacterial Chemotherapy

Routine antibacterial chemotherapy for the treatment of uncomplicated odontogenic infections, in the absence of timely debridement, i.e., primary dental care, has not been shown to be effective.^{11,12,15,20,71,80-87,89-93,97-102} Consequently, clinicians should avoid "rational activism" and "reflex prescribing." The rational activist assumes that it is better to over-treat than not to treat at all; the reflex prescriber caters to the patient’s expectations regardless of the diagnosis.

Uncomplicated odontogenic infections that have not been debrided in a timely manner or have failed to respond to debridement may spread, especially in immunocompromised patients, into anatomical spaces contiguous with fascial planes and can lead to serious, even life-threatening infections.^15,103 Adjunctive antibacterial chemotherapy, predicated on sound principles, is imperative in the treatment of complicated odontogenic infections (Table 2).^71,103,104

Table 2. Principles of Adjunctive Antibacterial Chemotherapy.

Establish a clear indication for adjunctive antibacterial chemotherapy.
- The patient presents with malaise, fever, chills, trismus, rapid respiration, swelling, lymphadenopathy, or hypotension.
  - The signs and symptoms of infection escalated rapidly (within 24 to 48 hours).
  - The oral soft tissue swelling appears to be spreading into adjacent anatomical spaces and affects breathing and swallowing.
  - Patients presenting with signs of impending airway obstruction, marked trismus (< 25mm), dehydration, malaise, disorientation, tachycardia, and hypotension should be admitted to the hospital for urgent or emergent care.
Determine the patient’s health status.
- Systemic considerations.
- History of adverse drug reactions.
- Potential drug-drug interactions.
Select an appropriate antibacterial agent with a narrow spectrum and low toxicity.
- Immune status of the patient.
  - Bactericidal versus bacteriostatic antibacterial agent.
- Empirical therapy (correlate to most likely organisms associated with odontogenic infections).
- Focused therapy (correlate to culture and susceptibility tests).
Establish a dosage regimen, duration of therapy, and route of administration.
- Consider the seriousness of the illness.
- Consider potential compliance issues.
Follow-up in 48 to 72 hours.
- Determine efficacy.
  - Inadequate debridement.
  - Inadequate bacteriological information.
  - Sub-optimal doses of antibacterial agents.
  - Noncompliance (including the issue of cost).
- Monitor patient for adverse drug effects.

Based on best available evidence, penicillin V potassium or amoxicillin formulations, alone or in combination with metronidazole; and clindamycin are reasonable empirical options to consider for the treatment of complicated odontogenic infections (Figure 10).^11,42,71 Azithromycin may be an empirical option in some instances. Ultimately, the empirical drug of choice should be an effective agent with the narrowest spectrum and the least potential for adverse drug effects.

Figure 10. Percent Antibacterial Susceptibility of 98 Strains of Oral Bacteria.

Image: Percent antibacterial susceptibility of 98 strains of oral bacteria.

Figure 10. Percent Antibacterial Susceptibility of 98 Strains of Oral Bacteria.

Based on data from Baumgartner JC, Xia T. Antibiotic susceptibility of bacteria associated with endodontic abscesses. J Endod 2002;29(1):44-47.⁴²

Primary Line of Antibacterial Chemotherapy

Unless the patient has an allergy to the penicillins, the empirical drug of first choice for the treatment of odontogenic infections is narrow spectrum penicillin V potassium (Table 3).^9,20,42 Most infections require 5 days of antibacterial chemotherapy. An initial loading dose is followed by maintenance doses for the remainder of the time. It is prudent to schedule the patient for a follow-up in 2 to 3 days. This will provide an opportunity to assess response to treatment. Hypersensitivity reactions are potentially the most serious adverse drug effects (see the Prescription-precautions Associated with the Administration of Antibacterial Agents section).¹⁰⁵

Table 3. Empirical Antibacterial Agents for the Treatment of Complicated Odontogenic Infections.

Indications	Adult dosages (Pediatric dosages*)
Primary line of treatment:	R_x
Patient has no history of allergy to β-lactam antibacterial agents.	Penicillin V potassium, 500 mg tablets Disp. 21 tablets Sig. Take two tablets stat, then one tablet four times a day for 5 days.
	R_x
Patient did not respond optimally to penicillin VK in 48 to 72 hours.	Metronidazole, 500 mg tablets Disp. 21 tablets Sig. Take one tablet stat, then one tablet four times a day 5 days.
Secondary line of treatment:	R_x
Patient has a history of allergy to β-lactam antibacterial agents.	Azithromycin, 250 mg tablets Disp. 6 Tablets Sig. Take two tablets stat, then one tablet a day for 5 days.
Tertiary line of treatment:	R_x
Patient has a history of allergy to β-lactam antibacterial agents. Unresolved infection following treatment with a β-lactam drug. Initial empirical drug for the treatment of serious infections.	Clindamycin, 300 mg capsules Disp. 21 tabs Sig. Take two capsules stat, then one capsule four times a day for 5 days.
Pediatric dosages: penicillin V potassium, 25-50 mg/kg/day, divided q6-8h; metronidazole, 30 mg/kg/day, divided q6h; azithromycin, 5-10 mg, once daily; clindamycin, 10 mg/kg, q8h. Pediatric dosages should not exceed maximum adult doses. * Metronidazole is added in addition to, not in lieu of, penicillin V regimen.

If significant improvement is not noted in 48 to 72 hours, the empirical addition (for 5 days) of metronidazole to penicillin V potassium is reasonable. Metronidazole is β-lactamase resistant and it provides excellent coverage for obligate anaerobes (Table 3).^61,106,107 The safety and effectiveness of metronidazole in pediatric patients have not been established. In patients receiving metronidazole, the concurrent use of alcohol may produce severe gastrointestinal symptoms; serious convulsive seizures and peripheral neuropathy has also been reported (see the *Prescription-precautions Associated with the Administration of Antibacterial Agents* section).

Secondary Line of Antibacterial Chemotherapy

A macrolide is an empirical option for the treatment of odontogenic infections in patients allergic to β-lactam antibiotics. While there is a paucity of data demonstrating the efficacy of azithromycin in the treatment of odontogenic infections, among macrolides it may be the best alternative because of its extended spectrum against facultative and some obligate anaerobes (Table 3).^75,76 However, a recent FDA drug safety communication warns about the risk of QT prolongation and cardiac arrhythmias (see the Prescription-precautions Associated with the Administration of Antibacterial Agents section).¹⁰⁸

It is also of note, that the single most important driver of the emergence of macrolide resistance in vivo is macrolide use.¹⁰⁹ Macrolide-resistant organisms can block ribosomal macrolide-receptor sites, and because of receptor-site overlap, these organisms will also be resistant to clindamycin; and efflux pump-related macrolide-resistance also affects the intracellular concentration of β-lactam antibiotics and β-lactamase inhibitor, i.e., macrolide-resistance often confers multidrug-resistance. Clindamycin may also be an empirical option (see below).¹¹⁰

Tertiary Line of Antibacterial Chemotherapy

Clindamycin is the empirical drug of choice for unresolved infections following treatment with a β-lactam antibacterial agent.^71,111 It is also the initial empirical drug of choice for the treatment of severe complicated odontogenic infections (Table 3).^{15,50,51,112,113} It is β-lactamase resistant and has excellent activity against gram-positive cocci and most gram-negative anaerobes.^{47,50,112,114-117} However, the risk of Clostridium difficile-associated superinfections, which may range in severity from mild diarrhea to fatal colitis, should prompt caution and mandates close follow-up (see the Prescription-precautions Associated with the Administration of Antibacterial Agents section).^118,119

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