Ce 450 - pharmacology of systemic antibacterial agents: clinical implications

Pharmacology of Systemic Antibacterial Agents:
Leena Palomo, DDS, MSD; Géza T. Terézhalmy, DDS, MA
Continuing Education Units: 3 hours Online Course:
Disclaimer: Participants must always be aware of the hazards of using limited knowledge in integrating new techniques or
procedures into their practice. Only sound evidence-based dentistry should be used in patient therapy. Participants in this course will be introduced to evidence-based information related to the microbiology of odontogenic infections, the pharmacology of systemic antibacterial agents, and the rationale for the selection of an antibacterial agent for the treatment of odontogenic infections.
Conflict of Interest Disclosure Statement
• Dr. Palomo reports no conflicts of interest associated with this work.
• Dr. Terézhalmy has done consulting work for Procter & Gamble and is a member of the dentalcare.com Advisory Board.
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ADA CERP is a service of the American Dental Association to assist dental professionals in identifying quality providers of continuing dental education. ADA CERP does not approve or endorse individual courses or instructors, nor does it imply acceptance of credit hours by boards of dentistry.
Concerns or complaints about a CE provider may be directed to the provider or to ADA CERP at: http://www.ada.org/cerp Approved PACE Program Provider
The Procter & Gamble Company is designated as an Approved PACE Program Provider by the Academy of General Dentistry. The formal continuing education programs of this program provider are accepted by AGD for Fellowship, Mastership, and Membership Maintenance Credit. Approval does not imply acceptance by a state or provincial board of dentistry or AGD endorsement. The current term of approval extends from 8/1/2013 to 7/31/2017. Provider ID# 211886 Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 Participants in this course will be introduced to evidence-based information related to the microbiology of odontogenic infections, the pharmacology of systemic antibacterial agents, and the rationale for the selection of an antibacterial agent for the treatment of odontogenic infections.
Upon completion of this course, the dental professional should be able to:
• Discuss the microbiology of odontogenic infections.
• Discuss the pharmacology of systemic antibacterial agents.
• Select the most appropriate antibacterial agent to treat an odontogenic infection.
• Discuss potential ADEs associated with the administration of antibacterial agents.
the normal flora establish symbiotic relationships (mutualism, commensalisms, or parasitism) with • Microbiology of Odontogenic Infections their human host and each other.2,3 • Pharmacology of Systemic Antibacterial Agents Inhibitors of Bacterial Cell Wall Synthesis Factors that modify or shift the balanced Inhibitors of DNA Synthesis or Integrity environment of the normal flora (age, altered Inhibitors of Transcription or Translation anatomy, diet, local and systemic conditions, • Strategies for the Treatment of Odontogenic or pharmacotherapy) may predispose an individual to infection.4,5 Infection, the invasion Primary Dental Care and multiplication of microorganisms in body Adjunctive Antibacterial Chemotherapy tissues, results in cellular injury due to competitive Prophylactic Antibacterial Chemotherapy metabolism, toxin production, or immune-mediated • Prescription-precautions Associated with reactions. An infection may be autogenous, Antibacterial Agents caused by the body's normal flora; or it may be Antibacterial Drug-resistance a cross-infection, related to the proliferation of Gastrointestinal Distress transient organisms.6 Hypersensitivity Reactions Cardiovascular Effects Microbiology of Odontogenic Infections
Central Nervous System Effects Predicated on their metabolic characteristics, i.e., Oral Candidiasis their metabolic demand for oxygen, bacteria are Antibacterial Drugs and Pregnancy classified as aerobic, facultative, or anaerobic. Antibacterial Drugs and Nursing Morphologically, they are characterized as cocci Drug-drug Interactions or bacilli (rods). Based on Gram's Method of staining (Box 1), bacteria are further classified • Course Test Preview as gram-positive or gram-negative. The distinct staining properties of bacteria are related to their • About the Authors architectural and biochemical differences.7 Gram-positive bacteria possess a thick The human fetus is free of microorganisms.1 peptidoglycan cell wall interspersed with After initial exposure at birth, most organisms are lipoteichoic acid underlain by the cytoplasmic soon eliminated, but others become permanently membrane (Figure 1).8 Gram-negative bacteria established and the dynamic process of have an outer membrane with lipopolysaccharides colonization begins. The adult body harbors a and a lipoprotein layer underlain by a thin dense, diverse, indigenous flora that includes peptidoglycan layer and the cytoplasmic bacteria, viruses, fungi and protozoa. Interaction membrane (Figure 2).8 The ability of antibacterial between these various microbial ecosystems agents to diffusion into bacteria is also affected by determines the normal flora. Microorganisms of these structural differences.
Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014

Box 1. Gram's Method of staining.7
Figure 1. Gram-positive bacteria.
Figure 2. Gram-negative bacteria.
Images 1&2, modified from Kasmar AG, Hooper D. Pharmacology of bacterial infections: cell wall synthesis. In Golan DE, Tashjian, Jr. AH, Armstrong EJ, Armstrong AW. Ed. Principles of pharmacology. The pathophysiologic basis of drug therapy. 2nd ed. 2008. Wolters Kluwer/Lippincott Williams & Wilkins. Baltimore, MD.8 Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014

Figure 3. Gram-negative organisms.
Figure 4. Mixed gram-positive and gram negative organisms.
During staining, crystal violet interacts with iodine acidic environment and decreased oxygenation forming a complex. Acetone extracts lipids from to support the growth and proliferation of its the outer membrane, cell wall, and cytoplasmic members. Ultimately, facultative and anaerobic membrane of bacteria.7 The damage to gram- gram-positive and gram-negative cocci and bacilli negative organisms is more extensive and they predominate in all types of odontogenic infections lose their crystal violet-iodine complexes, i.e., they are decolorized; and when counterstained with safranin, they appear red (Figure 3).7 Gram- Pharmacology of Systemic Antibacterial
positive bacteria retain their crystal violet-iodine complexes and appear deep purple (Figure 4).7 Pharmacological strategies are predicated on targeting differences between prokaryotic An average adult harbors at least 300 oral bacterial and eukaryotic host cells. Selective bacterial species and more than 700 strains of toxicity can be achieved by (1) attacking targets bacteria have been isolated from test cases.9-11 unique to bacteria, (2) attacking targets in bacteria Most odontogenic infections are polymicrobial. similar but not identical to those in host cells, and The number of strains per infection ranges from (3) attacking targets that are shared, but vary 1 to 10 with an average number of 4 isolates.9,12-24 in importance between bacteria and host cells The predominant flora creates an ecosystem (Figure 5).32 Drugs targeting unique differences of synergism by elaborating a more favorable are the least toxic to host cells.
Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014

Table 1. Bacteria detected in odontogenic infections.26,27
Figure 5. Mechanisms of action of antibacterial agents.
Based on Harbison H, Rose HS, Coen DM, Golan DE. Principles of antibacterial and antineoplastic pharmacology. In Golan DE, Tashjian, Jr. AH, Armstrong EJ, Armstrong AW. Ed. Principles of pharmacology. The pathophysiologic basis of drug therapy. 2nd ed. 2008. Wolters Kluwer/Lippincott Williams & Wilkins. Baltimore, MD.32 Antibacterial agents are either bactericidal or Inhibitors of Bacterial Cell Wall Synthesis
bacteriostatic. Bactericidal drugs attack targets Most pathogenic bacteria have a cell wall that essential for bacterial survival, e.g., inhibitors provides tensile strength and maintains intracellular of cell wall synthesis and most inhibitors of osmotic pressure. Its synthesis progresses in DNA synthesis and integrity.32 Bacteriostatic three steps: (1) monomers are synthesized in drugs attack targets that are necessary for the cytoplasm from amino acid and sugar building bacterial growth but not for survival, e.g., most blocks; (2) Bactoperol transfers the monomers inhibitors of transcription and translation.32 Since across the cytoplasmic membrane where they bacteriostatic drugs block bacterial replication, are polymerized into linear peptidoglycan chains; they antagonize the effects of bactericidal drugs.
finally, (3) transpeptidase cross-links peptidoglycan chains into a three-dimensional mat (Figure 6).8 Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 Figure 6. Bacterial cell wall synthesis.
Modified from Kasmar AG, Hooper D. Pharmacology of bacterial infections: cell wall synthesis. In Golan DE, Tashjian, Jr. AH, Armstrong EJ, Armstrong AW. Ed. Principles of pharmacology. The pathophysiologic basis of drug therapy. 2nd ed. 2008. Wolters Kluwer/Lippincott Williams & Wilkins. Baltimore, MD.8 A number of drugs inhibit cell wall synthesis. potassium and broad-spectrum amoxicillin and Most important are Vancomycin, which targets amoxicillin with clavulanic acid have the requisite monomer polymerization; and the β-lactams, spectra to be considered as empirical options e.g., penicillins and cephalosporins, which block in treating odontogenic infections.10,42 However, polymer cross-linking.8,33-41 β-lactam antibacterial neither narrow-spectrum nor broad-spectrum agents also activate autolysins. Autolysins punch penicillins are active against β-lactamase holes in bacterial cell wall and disrupt its integrity.8 producing bacteria; and certain β-lactamases Transpeptidase antagonism and autolysis prevent produced by bacteria now confer resistance to bacterial self-maintenance, i.e., remodeling and clavulanic acid as well.8,43-51 repair; and replication.
Penicillin V potassium and amoxicillin formulations are not inactivated by gastric acid and also have Vancomycin is bactericidal in susceptible the advantage that they may be given with meals. organisms. It is primarily effective against aerobic They are widely distributed to most tissues and gram-positive cocci and bacilli.8,33,36,37 It does have body fluids, cross the placenta and they are activity against some anaerobic gram-positive, excreted into breast milk. The penicillins undergo but not against gram-negative bacilli. Since hepatic biotransformation. The metabolites and facultative and anaerobic gram-positive and the unchanged fraction of the drugs are excreted gram-negative cocci and bacilli predominate in all rapidly in individuals with normal renal function.
types of odontogenic infections, Vancomycin does not have the requisite spectrum to be considered an empirical option in treating odontogenic The cephalosporins are bactericidal in susceptible organisms.8,35,40,41,52 Most are primarily active against aerobic gram-positive cocci and bacilli. Second generation cephalosporins (e.g., cefaclor) Penicillins are bactericidal in susceptible have an overlapping spectra with those of organisms.8,38,39 Narrow-spectrum penicillin V penicillin V potassium and amoxicillin formulations Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 Figure 7. Folate synthesis.
Modified from Harbison H, Rose HS, Coen DM, Golan DE. Principles of antibacterial and antineoplastic pharmacology. In Golan DE, Tashjian, Jr. AH, Armstrong EJ, Armstrong AW. Ed. Principles of pharmacology. The pathophysiologic basis of drug therapy. 2nd ed. 2008. Wolters Kluwer/Lippincott Williams & Wilkins. Baltimore, MD.32 and are more β-lactamase resistant than the aerobic gram-positive and gram-negative first generation cephalosporins. However, cocci and bacilli.53-57 The newer agents (e.g., cephalosporins, in general, offer no therapeutic moxifloxacin) have some anaerobic activity.10,58,59 advantage over penicillins as empirical options in Fluoroquinolones are indicated for the treatment treating odontogenic infections.
of infections with designated, susceptible bacteria and are not empirical options in treating Inhibitors of DNA Synthesis or Integrity
Cell wall inhibitors cannot kill all bacteria because some bacteria lack a cell wall. Other bacteria have unique structures that inherently resist the A metabolite of metronidazole directly binds accumulation or action of cell wall inhibitors. DNA, causes loss of its helical structure, and However, bacteria, in preparation for cell division, effects strand breakage.50,60,61 It is bactericidal in must replicate their double stranded DNA. To susceptible organisms. Metronidazole is active facilitate replication, topoisomerase type II, a against most obligate anaerobes, but lacks bacterial DNA gyrase, must first unwind and clinically relevant activity against obligate aerobes separate, and then reassemble the original DNA and facultative anaerobes.61,62 Metronidazole, during the process.53 in combination with an agent active against aerobic/facultative organisms (e.g., penicillin), In the replication process, bacteria must is an empirical option in treating odontogenic synthesize folate. Its synthesis begins with the formation of dihydropteroic acid from pteridine and para-aminobenzoic acid (PAPA), a Metronidazole is well absorbed after oral reaction catalyzed by dihydropteroate synthase administration and reaches peak plasma (Figure 7).32 Dihydropteroic acid and glutamate concentrations in 1 to 2 hours.61 It is distributed condense to form dihydrofolate (DHF).32 to most body fluids and tissues, including bone; Dihydrofolate reductase (DHFR) reduces DHF crosses the placenta, and reaches concentrations to tetrahydrofolate (THF). THF is an essential in saliva and human milk similar to those found in cofactor in the synthesis of DNA, RNA, and plasma.61 Metronidazole is metabolized by hepatic proteins (Figure 7).32 oxidation and glucuronic conjugation.61 The major route of elimination of metronidazole and its metabolites is via the kidneys.61 Fluoroquinolones block topoisomerase type II activity and disrupt the integrity of bacterial DNA.53-57 They are bactericidal in susceptible Sulfamethoxazole (SMX) and trimethoprim organisms and are primarily active against (TMP), block succeeding steps in folate synthesis Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 (see Figure 7).32,63 SMX-TMP formulations are The P-site initially is occupied by the fMet-tRNA bacteriostatic in susceptible organisms. It has complex. As the next charged tRNA binds to activity against a broad spectrum of aerobic gram- the 70S ribosomal unit, but before it is allowed positive and gram-negative organisms, but it is not to enter the unoccupied A-site, the rRNA must active against anaerobes.63 SMX-TMP does not confirm that the charged tRNA carries the specific have the requisite spectrum to be considered an amino acid called for by the mRNA codon.54 If empirical option in treating odontogenic infections.
access is allowed, the rRNA catalyzes the formation of a peptide bond between the carboxy- Inhibitors of Transcription or Translation
terminal of the fMet residing in the P-site and the Bacteria, like mammalian cells, must synthesize new amino acid occupying the A-site (Figure 9).53 proteins for self-maintenance and replication. DNA serves as the "instruction manual;" it provides Once the peptide bond is formed, the tRNA the information necessary for protein synthesis. originally linked to fMet is ejected from the P-site The first step in this process is transcription, and the second tRNA located at the A-site, which the synthesis of a single-stranded ribonucleic is now linked to two amino acids, translocates to acid (RNA) from the DNA template catalyzed by the unoccupied P-site (Figure 9).53 As the process RNA polymerase.53 The function of the newly repeats itself, a growing peptide chain emerges synthesized RNA is translation.
from the exit tunnel.53 Translation continues until a stop codon is encountered in the mRNA and the In the process of translation, RNA serves three newly synthesized protein is released from the functions: (1) as messenger RNA (mRNA), it tells ribosomes which proteins to synthesize; (2) as transfer RNA (tRNA), it transports specific amino acids called for by mRNA codons from the Tetracycline and its semi-synthetic derivatives cytoplasm to ribosomes; and (3) as ribosomal (e.g., minocycline and doxycycline) bind to 30S RNA (rRNA), it ensures that the amino acid carried ribosomal subunits and reversibly block the by the charged tRNA is the one called for by the attachment of the charged tRNA to the aminoacryl corresponding mRNA codon.53 or A-site.53,64-66 They have bacteriostatic activity against aerobic gram-positive and gram-negative Protein synthesis is initiated when the mRNA joins organisms, but in vivo many strains have been with the 30S ribosomal subunit and tRNA-linked shown to be resistant. Tetracyclines are not formyl methionine (fMet).53 As the first amino empirical options in the treatment of odontogenic acid encoded by every bacterial mRNA, fMet binds the initiation codon on the mRNA.53 Next, the 30S-fMet-tRNA complex joins with the 50S It is also of note that tetracyclines are ribosomal subunit to form the complete initiation teratogenic.65-67 They produce higher rates of complex, i.e., the 70S ribosomal unit, which neuronal-tube defect, cleft palate, and multiple contains two binding sites, an aminoacyl or A-site congenital abnormalities, e.g., neuronal-tube and a peptidyl or P-site (Figure 8).53 defect with cardiovascular malformation. Figure 8. Formation of the 70S ribosomal initiation complex.
Modified from Ryou M, Coen DM. Pharmacology of bacterial infections: DNA replication, transcription, and translation. In Golan DE, Tashjian, Jr. AH, Armstrong EJ, Armstrong AW. Ed. Principles of pharmacology. The pathophysiologic basis of drug therapy. 2nd ed. 2008. Wolters Kluwer/Lippincott Williams & Wilkins. Baltimore, MD.53 Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 Figure 9. The process of protein synthesis.
Modified from Ryou M, Coen DM. Pharmacology of bacterial infections: DNA replication, transcription, and translation. In Golan DE, Tashjian, Jr. AH, Armstrong EJ, Armstrong AW. Ed. Principles of pharmacology. The pathophysiologic basis of drug therapy. 2nd ed. 2008. Wolters Kluwer/Lippincott Williams & Wilkins. Baltimore, MD.53 Furthermore, tetracyclines induce enamel hypoplasia and discoloration of teeth. Before Macrolides bind 50S ribosomal subunits and block prescribing tetracycline during pregnancy and/or translocation and peptide movement through the tooth development the benefits and risks must be exit tunnel.53 They are bacteriostatic in susceptible organisms and are active against aerobic gram- positive cocci and gram-negative bacilli, but anaerobic gram-negative organisms are resistant. Aminoglycosides (e.g., gentamicin) bind to 30S Azithromycin has an extended spectrum that ribosomal subunits and induce misreading of includes some anaerobic gram-positive cocci mRNA codons.53,68,69 They are bactericidal in and gram-negative bacilli and may be considered susceptible organisms and are active against an empirical option in treating odontogenic many aerobic and facultative gram-positive and gram-negative cocci and bacilli, but most species of streptococci and anaerobic gram-negative Azithromycin is rapidly absorbed after oral bacilli are resistant.53,68,69 Aminoglycosides do administration. When administered with food, not have the requisite spectra to be considered however, its rate and extent of absorption is empirical options in treating odontogenic reduced by about 50%. The drug is widely distributed throughout the body, accumulating in high concentration within cells resulting in higher tissue than plasma concentrations. Azithromycin is Clindamycin binds to 50S ribosomal subunits and metabolized minimally and is principally eliminated blocks peptide bond formation between amino as unchanged drug via the liver.
acids located in the P- and A-sites (Figure 8).53,62,70 It has excellent activity against gram-positive Strategies for the Treatment of
aerobes and anaerobes, as well as gram-negative anaerobes.10,42,71 Consequently, clindamycin Uncomplicated odontogenic infections manifest has the requisite spectrum to be considered an primarily as caries; and pulpal, periodontal, and empirical option in treating odontogenic infections.
pericoronal problems. Signs and symptoms include pain, erythema, edema, and difficulty chewing.71,79 Clindamycin is rapidly and almost completely Complicated odontogenic infections reflect the absorbed after oral administration and reaches extension of an uncomplicated odontogenic infection peak plasma concentration in about 45 minutes. into surrounding tissues and manifest as cellulitis, It is widely distributed in body fluids and tissues osteomyelitis, and space infections. Signs and (including bone). Clindamycin is extensively symptoms include lymphadenitis, trismus, difficulty metabolized in the liver and its metabolites are swallowing or breathing; and less frequently, fever excreted primarily by the kidneys.
and hypotension.71,79 Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 Primary Dental Care
course of penicillin administered to patients with acute pain related to a tooth with an amalgam restoration without clinical signs of infection, Patients with reversible pulpitis usually report in the absence of definitive dental care, did sensitivity or pain in response to hot, cold, not prevent the emergence of clinical signs of sweets, and mechanical stimuli. Caries in infection within 5 days.89 proximity of the pulp, defective restorations, exposed dentinal tubules, and traumatic occlusion Acute Apical Periodontitis
appear to be common etiologies. Provoked pain, Irreversible pulpitis and pulpal necrosis (an described as sharp or intense, primarily reflects asymptomatic complication of irreversible hyperemia or mild inflammation of the pulp and pulpitis), if left untreated, lead to the spread of stimulus-induced fluid movement in dentinal irritants and bacteria into periradicular tissues and result in acute apical periodontitis. Patients complain of tenderness or mild to moderate pain Reversible pulpitis is a reactive process. Caries associated with the apical area of the offending should be excavated and a temporary sedative tooth. The pain may be intermittent, secondary restoration placed. Faulty restorations should to manipulation of the tooth, or unprovoked and be removed and replaced. Exposed dentinal tubules should be etched and sealed. To reduce inflammation and shorten recovery time a The removal of bacteria and their byproducts disease-modifying analgesic, i.e., a nonsteroidal by debridement and obturation of the root canal anti-inflammatory drug (NSAIDs) should be system effectively eliminates infection, curtails prescribed. It is intuitive that antibacterial agents inflammation, and promotes healing. The would have no effect on clinical outcome.
administration of a disease modifying analgesic, i.e., a NSAID, may shorten recovery time. It has been shown that once the source of infection Bacteria may gain access to the pulpal system is eliminated, the administration of penicillin through caries, defective restorations, and provides no statistically significant added benefit.90 exposed dentinal tubules. Other portals may include apical, lateral, or furcation canals Acute Apical Abscess
associated with advancing periodontal disease. Infection associated with acute apical periodontitis Pain may be spontaneous, but usually it is in may extend into alveolar bone and soft tissues response to hot, cold, sweets, and mechanical initiating apical abscess formation. The pain is stimuli reflects hyperemia or inflammation usually severe, unprovoked and constant. The secondary to infection, fluid movement in dentinal tooth is usually mobile and the accumulation of tubules, and increased intrapulpal pressure.
fluid in the periodontal ligament space may cause supraeruption. Manipulation of the tooth causes Acute dental pain associated with a tooth with exquisite sensitivity and mastication is difficult; deep carious lesion may reflect a reactive swelling, malaise and fever may be present.
process to caries, but most likely to bacteria that have infected pulpal tissues.80-85 In case The removal of bacteria and their byproducts of irreversible pulpitis endodontic debridement by debridement and obturation of the root canal and obturation of the root canal system is the system effectively eliminates infection, curtails most predictable method of treatment.86 To inflammation, and promotes healing. The reduce inflammation and shorten recovery time a swelling, when present, may be drained through disease-modifying analgesic, i.e., a NSAID should the tooth, by a soft tissue incision, or there may be prescribed.
already be drainage through a naturally occurring sinus tract. A disease modifying analgesic, i.e., a In untreated irreversible pulpitis, penicillin does NSAID, may shorten recovery time.
not reduce spontaneous pain, percussion induced pain, or the amount of analgesics taken by In a prospective study, a five-day course of patients.87,88 In a prospective study, a five-day penicillin administered to patients with acute Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 pain related to a tooth with large periapical rinse with warm saline every 2 hours for two days. radiolucency, but without clinical signs of Routine antibacterial therapy is not indicated.
infection, in the absence of debridement did not prevent the development of clinical signs of infection within 5 days.89 Another study confirmed A periodontal abscess may be secondary to that once the source of infection is eliminated, the impacted foreign objects into the orifice of a administration of penicillin provides no statistically periodontal pocket, closure or narrowing of significant added benefit.91 the pocket orifice, or improper use of irrigating devices. Mild to moderate pain may be acute or Draining Sinus Tract
chronic. The swelling rarely spreads beyond the Inflammatory degeneration of the pulp and mucogingival junction and may be associated with periradicular tissues may follow a chronic a draining sinus tract located in the gingival crevice subclinical course. The infection progresses or at the mucogingival junction.
slowly through cancellous bone along the path of least resistance. It perforates the Drainage should be established with the careful thin cortical plate and forms a subperiosteal use of a periodontal probe. Once the opening to abscess. Once through the periosteum, it the pocket is located, the root surface should be spreads into surrounding soft tissues and leads gently debrided. If drainage cannot be established to the formation of either an intraoral or extraoral through the orifice of the pocket, a vertical incision draining sinus tract; swelling and pain are usually should be made and the area should be irrigated with warm saline. The patient should continue to rinse with warm saline every 2 hours for two days. In restorable teeth, chronic draining sinus Routine antibacterial therapy is not indicated.
tracts will respond to nonsurgical endodontic therapy. Successful healing depends on optimal debridement and obturation of the canal system. Necrotizing ulcerative gingivitis (NUG) is Non-restorable teeth and/or those with extensive characterized by localized necrosis and ulceration alveolar bone loss require extraction. There usually of the interdental papillae, which may is no evidence that the routine administration extend to the marginal gingiva and rarely the whole of an antibacterial agent improves therapeutic mouth. Microorganisms have been implicated, but outcome.92 The residual cutaneous defect or scar it is unclear if they are causative or opportunistic. may require subsequent surgical revision.
Patients report a putrid odor, a foul metallic taste, and constant radiating pain intensified by spicy or hot foods, and gentle probing.
Gingival abscess is a localized, rapidly evolving, painful infection of the marginal or interdental The initial treatment of necrotizing ulcerative gingiva usually secondary to the impaction of gingivitis includes gentle irrigation of the affected foreign bodies, e.g., popcorn shells, peanut areas with warm saline; followed by careful husks, seeds, fish bones, toothbrush bristles, curettage of necrotic/ulcerative lesions and root or toothpick splinters into the gingival crevice. surfaces to reduce the bioburden. Patients are The abscess may drain through the crevice or a instructed to rinse with warm saline every 2 hours draining sinus tract through the gingiva. Affected and undergo daily repeat debridement until the teeth may be extruded and tender to percussion.
lesions have resolved. Routine antibacterial therapy is not indicated and response to Foreign objects tend to adhere to the soft tissue debridement is noted within 2-3 days. Patients wall of the gingival crevice. Following the may require gingivoplasty to correct residual crater- application of a topical anesthetic agent, the like gingival defects.
gingival tissue should be gently distended; the foreign object removed, the soft tissue wall of the lesion should be gently curetted to induce Alveolar osteitis is a relatively common drainage, and the area should be irrigated with complication of tooth extraction, usually of warm saline. The patient should continue to mandibular molars. A foul taste, putrid odor, and Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 deep, radiating pain of increasing intensity is noted three to four days following extraction. When pulpal, periodontal or pericoronal infections The surrounding soft tissues appear normal overwhelm host resistance, the infection may but the alveolar socket is empty or contains extend into the surrounding tissues and cause necrotic debris. Alveolar osteitis is primarily cellulitis.93,95 The affected area becomes an inflammatory condition, which may become edematous and feels indurated when palpated suggesting diffuse inflammation. Patients present with pain, malaise, trismus, regional A common protocol to manage alveolar osteitis lymphadenopathy, and fever. The tissues consists of gentle debridement of the socket, overlying the infected area may appear bluish.
irrigation with warm saline, and placement of an iodophor gauze impregnated with eugenol. The Patients with cellulitis should be referred to a patient should be reevaluated every 24 to 48 surgical specialist who may collect a sample hours, the dressing removed, the socket irrigated of the purulent exudate, usually by aspiration, with warm saline and redressed. This cycle may and initiate empirical, usually oral antibacterial have to be continued for up to 14 days. Routine chemotherapy. As the infection consolidates and antibacterial therapy is not indicated.
becomes fluctuant, it will be incised at its most dependent area, the purulent material evacuated, and a drain inserted. Once a subacute condition Pericoronitis is an acute infection most often has been attained appropriate primary dental associated with soft tissue overlying a partially intervention should be initiated.
erupted mandibular third molar. Signs and symptoms include pain, malaise, fever, lymphadenopathy, trismus, and difficulty Osteomyelitis is another potential complication swallowing. Abscess formation may be evident of odontogenic infection. It most often affects buccally or lingually to the offending tooth, which cancellous medullary bone of the mandible. As may progress to cellulitis or osteomyelitis; or purulence accumulates, it restricts blood flow to spread through the fascial planes of the head and the area, which causes osseous necrosis and the formation of sequestrum. Signs and symptoms include paresthesia or deep persistent pain, To establish drainage from under the operculum, malaise, fever, lymphadenopathy, loose teeth, a periodontal probe should be inserted into the and in the later stages, alveolar radiolucencies.
follicular space enlarging the opening. The area under the operculum should be irrigated with When osteomyelitis is suspected, the patient warm saline and iodophor gauze impregnated should promptly be referred to a surgical with eugenol placed to maintain drainage. If specialist who will collect a sample of the purulent the opposing maxillary tooth is traumatizing the exudate, usually by aspiration, for culture and operculum and deemed nonfunctional, it may be susceptibility testing and begin immediate extracted. Otherwise, the cusps may be slightly empirical, usually intravenous antibacterial reduced to minimize further trauma to the soft chemotherapy. Drainage is established at the tissue below.
earliest possible time. Close monitoring and modification of antibacterial chemotherapy, if The patient should rinse with warm saline every indicated, is imperative.
2 hours. Depending on associated signs and symptoms, i.e., clinical evidence of induration as the infection is spreading buccally or lingually and The inflammatory process associated the presence of trismus, empirical antibacterial with cellulitis is usually restricted to the therapy may be initiated. When a subacute jaws. However, if timely treatment is not condition has been attained, usually within 48 initiated, the infection may spread through hours, and the tooth is to be maintained, the the fascial planes of the head and neck into operculum should be removed at this time; the canine, buccal, masticatory, submental, otherwise the tooth may now be extracted.
sublingual, submandibular, vestibular, parotid, Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 parapharyngeal, retropharyngeal, and deep patients, into anatomical spaces contiguous with spaces of the head and neck and mediastinum fascial planes and can lead to serious, even life- creating life-threatening situations.
threatening infections.20,101 Adjunctive antibacterial chemotherapy, predicated on sound principles, When space infection is suspected, the patient is imperative in the treatment of complicated should immediately be referred to a surgical odontogenic infections (Table 2).71,101,102 specialist for evaluation and management. The specialist will collect a sample of the Based on best available evidence, penicillin V purulent exudate, usually by aspiration, for potassium or amoxicillin formulations, alone or in culture and susceptibility testing and begin combination with metronidazole; and clindamycin immediate empirical intravenous antibacterial are reasonable empirical options to consider chemotherapy.96 Drainage is established at the for the treatment of complicated odontogenic earliest possible time and measures to protect infections (Figure 10).10,42,71 Azithromycin may be the airway are instituted if necessary. Close an empirical option in some instances. Ultimately, monitoring and modification of antibacterial the empirical drug of choice should be an effective chemotherapy, if indicated, is imperative.
agent with the narrowest spectrum and the least potential for adverse drug effects.
Adjunctive Antibacterial Chemotherapy
Routine antibacterial chemotherapy for the Primary Line of Antibacterial Chemotherapy
treatment of uncomplicated odontogenic Unless the patient has an allergy to the infections, in the absence of timely debridement, penicillins, the empirical drug of first choice for i.e., primary dental care, has not been shown the treatment of odontogenic infections is narrow to be effective.10,16,17,20,71,80-87,89-92,95-99 Consequently, spectrum penicillin V potassium (Table 3).9,16,42
clinicians should avoid "rational activism" and Most infections require 5 days of antibacterial "reflex prescribing". The rational activist assumes chemotherapy. An initial loading dose is followed that it is better to over-treat than not to treat at by maintenance doses for the remainder of the all; the reflex prescriber caters to the patient's time. It is prudent to schedule the patient for expectations regardless of the diagnosis.
a follow-up in 2 to 3 days. This will provide an opportunity to assess response to treatment. Uncomplicated odontogenic infections that Hypersensitivity reactions are potentially the most have not been debrided in a timely manner serious adverse drug effects (see the Prescription- or have failed to respond to debridement may precautions Associated with the Administration of spread, especially in immunocompromised Antibacterial Agents section).103 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 Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 Table 2. Principles of adjunctive antibacterial chemotherapy.
Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 Table 3. Empirical antibacterial agents for the treatment of complicated odontogenic infections.
If significant improvement is not noted in 48 azithromycin in the treatment of odontogenic
to 72 hours, the empirical addition (for 5 days) infections, among macrolides it may be the best of metronidazole to penicillin V potassium
alternative because of its extended spectrum is reasonable. Metronidazole is β-lactamase against facultative and some obligate anaerobes resistant and it provides excellent coverage for (Table 3).75,76 However, a recent FDA drug obligate anaerobes (Table 3).61,104,105 The safety safety communication warns about the risk of and effectiveness of metronidazole in pediatric QT prolongation and cardiac arrhythmias (see patients have not been established. In patients the Prescription-precautions Associated with the receiving metronidazole, the concurrent use of Administration of Antibacterial Agents section).106 alcohol may produce severe gastrointestinal symptoms; serious convulsive seizures and It is also of note, that the single most important peripheral neuropathy have also been reported driver of the emergence of macrolide resistance (see the Prescription-precautions Associated with in vivo is macrolide use.107 Macrolide-resistant the Administration of Antibacterial Agents section).
organisms can block ribosomal macrolide- receptor sites, and because of receptor-site Secondary Line of Antibacterial Chemotherapy
overlap, these organisms will also be resistant A macrolide is an empirical option for the to clindamycin; and efflux pump-related treatment of odontogenic infections in patients macrolide-resistance also affects the intracellular allergic to β-lactam antibiotics. While there is concentration of β-lactam antibiotics and a paucity of data demonstrating the efficacy of β-lactamase inhibitor, i.e., macrolide-resistance Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 often confers multidrug-resistance. Clindamycin
Consequently, antibacterial agents given to may also be an empirical option (see below).108 healthy people in association with third molar extractions to prevent infection may cause more Tertiary Line of Antibacterial Chemotherapy
harm than benefit, both to patients and the Clindamycin is the empirical drug of choice for
community at large.118 unresolved infections following treatment with a β-lactam antibacterial agent.71,109 It is also the Prevention of Surgical-site Infection in
initial empirical drug of choice for the treatment Patients Undergoing Placement of Dental
of severe complicated odontogenic infections (Table 3).20,47,48,110,111 It is β-lactamase resistant Bacteria introduced during the placement of and has excellent activity against gram-positive dental implants can lead to infection and implant cocci and most gram-negative anaerobes.45,47,111-115 failure. A critical review of the literature identified However, the risk of Clostridium difficile- four randomized controlled clinical trials, with a associated superinfections, which may range in follow up of at least 3 months, comparing the severity from mild diarrhea to fatal colitis, should efficacy of various prophylactic antibacterial prompt caution and mandates close follow-up regiments versus no antibiotics in patients (see the Prescription-precautions Associated undergoing dental implant placement.119 The with the Administration of Antibacterial Agents implant failure rate among patients not receiving antibiotics was 5%.119 There is some evidence to suggest that A significant percentage of antibacterial agents amoxicillin 2g administered 1 hour preoperatively are putatively prescribed by dental practitioners significantly reduces the failure rate of dental for the prevention of infection. In general, when implants placed under ordinary conditions.119 an effective antibacterial agent is used to prevent The number needed to treat (NNT) to prevent infection by specific bacteria or to eradicate them one individual from having an implant failure is immediately or soon after they have become 33. No significant adverse drug effects were established, the strategy is frequently successful. reported, although the issue of antibacterial However, prophylactic antibacterial chemotherapy drug resistance was not addressed. There is no in dentistry should be limited to the prevention evidence that postoperative antibacterial agents of those infections that are proven or strongly are beneficial.119 suspected to be procedure-specific.
Prevention of Infective Endocarditis in
Prevention of Surgical-site Infection in
Patients Undergoing Dental Procedures
Patients Undergoing Tooth Extractions
The American Heart Association (AHA) publishes Tooth extraction is the indicated therapy for a clinical practice guideline, with periodic updates, teeth deemed non-restorable. However, there for the prevention of infective endocarditis in is no evidence to support the prophylactic use patients undergoing dental procedures.120 The of antibacterial agents in association with the 2007 guideline stratifies cardiac conditions as extraction of non-restorable teeth.118 Another to the risk of developing endocarditis and the common reason for tooth extraction is poorly severity of associated morbidity. Only patients aligned or impacted third molars. The infection with the highest-risk of adverse outcome from rate after third molar extraction is about 10%.118 endocarditis (Table 4) should be considered for In debilitated or immunocompromised patients, antibacterial prophylaxis prior to invasive dental the infection rate may be as high as 25%.118 procedures (Table 5).120 Antibacterial drugs administered just before and/ In situations where no chemoprophylaxis or just after third molar extractions do reduce the was given, but in which unexpected bleeding risk of infection, pain, and dry socket, but there occurred, the institution of antibacterial therapy is no evidence that antibacterial agents reduce within 2 hours is recommended. Patients at fever, swelling, or trismus. The practice also risk already taking an antibacterial agent should contributes to adverse drug effects, including be prescribed one of the drugs from a different the likelihood of bacterial drug resistance. class recommended for chemoprophylaxis. Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 Table 4. Conditions associated with the highest risk of adverse outcome from endocarditis for
which antibacterial prophylaxis is reasonable.120
Table 5. Antibacterial prophylaxis before procedures that involve manipulation of gingival tissue,
periapical region of teeth, or perforation of the oral mucosa.120
Clinicians should allow at least 9-14 days 2003 guideline was prescriptive, patients with between appointments to reduce the risk for the one or more high-risk conditions were considered development of resistant organisms.
candidates for antimicrobial prophylaxis in association with invasive dental procedures.122 Prevention of Orthopaedic Implant Infection in
Patients Undergoing Dental Procedures
The 2012 AAOS-ADA Clinical Practice Guideline, The American Academy of Orthopedic Surgeons which was developed using a systematic (AAOS) in cooperation with the American evidence-based process, replaces all previous Dental Association (ADA) publishes a clinical advisory or information statements.121 It provides practice guideline, with periodic updates, for the no specific direction in managing individual prevention of orthopaedic implant infection in patients (Table 6).121 Until scientific prospective patients undergoing dental procedures.121 The data becomes available, the development of Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 Table 6. Recommendations of the 2012 AAOS-ADA clinical practice guideline.121
therapeutic and preventive strategies for each the efficacy of post-operative prophylactic patient should be based on dialogue between oral antibacterial chemotherapy in association with healthcare provider, physician, and patient.121 open reduction and internal fixation of mandibular fractures and found no statistically significant Prevention of Infection in Patients with
benefit.129 However, investigators concluded that Various Medical Conditions Undergoing Dental
tobacco and alcohol appear to be significant risk factors for post-operative infections.
A number of systemic conditions, e.g., neutropenia, asplenia, diabetes mellitus, end-stage renal Prevention of Surgical-site Infection in Patients
disease, immunosuppression, systemic lupus Undergoing Head and Neck Oncology Surgery
erythematosus, and others are commonly cited as The incidence of wound infection in patients conditions that predispose a patient to bacteremia- undergoing head and neck oncology surgery induced infections. Evidence that a particular has been reported to be as high as 87%, often bacteremia-producing dental procedure caused a with devastating consequences.130 Based on the specific case of infection is circumstantial at best best current evidence, it is recommended that and no definitive, scientific evidence supports the prophylactic antibacterial agents, covering aerobic use of prophylactic antibiotics.123-125 gram-positive cocci and gram-negative bacilli, and anaerobic bacteria be administered in association Most importantly, clinicians should amplify their with clean and clean-contaminated head and neck efforts to ensure that all patients understand oncology surgery.130 There is no evidence that the critical importance of maintaining optimal prophylactic antibacterial agents offer any benefit oral health, which could serve to reduce the in clean surgery for benign disease.
severity of both self-induced and treatment- induced bacteremia. In the absence of evidence Prescription-precautions Associated with
or consensus on the issue, oral healthcare providers should weigh the benefits of antibacterial There are no "absolutely" safe biologically active prophylaxis against the risks of ADEs, including the therapeutic agents, i.e., drugs seldom exert development of drug resistance.
their beneficial effects without also causing adverse drug events (ADEs). The penicillins, Prevention of Surgical-site Infection in Patients metronidazole, azithromycin, and clindamycin,
Undergoing Open Reduction and Fixation of
like other drugs, even after the administration of a single dose, can produce ADEs.
The benefit of pre- and intra-operative antibacterial chemotherapy when treating open mandibular fractures has long been established.126-128 More The widespread and ever increasing use of recently, a prospective randomized trial evaluated antibacterial agents contributes to the development Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 of antibacterial drug-resistance.102,107,131-143 Unless medications for the treatment of abnormal heart healthcare providers change their practices, rhythm or arrhythmias. Increased risk of death many currently available antibacterial agents may from cardiovascular causes has been reported become ineffective. When antibacterial agents in persons treated with a 5-day course of are used appropriately to treat complicated odontogenic infections or to prevent infections in high-risk patients, clinicians must accept Central Nervous System Effects
the ecological consequences of antibacterial Metronidazole should be administered with chemotherapy. However, when other therapeutic caution to patients with central nervous system means are available, antibacterial agents should disorders. Severe convulsive seizures and not be routinely prescribed to treat or to prevent peripheral neuropathy, characterized by numbness or paresthesia of the extremities, have been reported.61 Infrequently, neuropathy has been noted with penicillin formulations, but when Common ADEs associated with antibacterial present, it is usually associated with high doses agents, but especially with macrolides, are of parenteral penicillin.38,39 nausea, vomiting, epigastric distress, and diarrhea.38,39,61,70,73 These symptoms may be amplified in patients on metronidazole with Superinfections with Candida sp. can occur concurrent use of alcohol.70 When a patient has in association with all, but especially broad- been taking an antibacterial agent for 1 to 2 days, spectrum antibacterial agents.38,39,61,70,73 Acute diarrhea is probably due to the mild irritating pseudomembranous oral candidiasis appears action of the drug; however, bloody diarrhea as white, raised, or cottage cheese-like that with abdominal cramping is highly suggestive of can be scraped off, leaving a red, sometimes pseudomembranous colitis, a superinfection with hemorrhagic base. Patients may also present Clostridium difficile.117 Colitis has been reported with hairy tongue and complain of burning, with the use of nearly all antibacterial agents, but itching, or a metallic taste. Candidiasis especially with clindamycin.38,39,61,70,73 occurring in a patient with a dry mouth may present as areas of patchy erythema with little or no evidence of cottage cheese-like curds. Hypersensitivity reactions, characterized by Candida sp. may spread to the esophagus or maculopapular to exfoliative dermatitis, urticaria, lungs via swallowing or droplet aspiration; or angioedema, and rarely, anaphylaxis may occur systemically via the blood stream, especially in with all antibacterial agents, but especially with the β-lactams.103,38,39,61,70,73 Allergic reaction to the penicillins is more likely to occur in individuals Antibacterial Drugs and Pregnancy
with sensitivity to multiple allergens and in those There is no firm evidence that the penicillins, with asthma; and patients with a history of allergy metronidazole, azithromycin, and clindamycin to the penicillins have experienced allergic are teratogenic in humans; however, drugs in reactions when treated with cephalosporins. general should be prescribed with caution during Rare instances of erythema multiforme and pregnancy. To assist practitioners in prescribing Stevens-Johnson syndrome have been reported drugs for the pregnant patient, the Food and Drug with clindamycin and azithromycin.70,73 Administration (FDA) has established a code for categorizing drugs according to their potential to cause fetal injury.145 Azithromycin and other macrolides can cause abnormal electrical activity in the heart that The penicillins, metronidazole, azithromycin, and may lead to a potentially fatal irregular heart clindamycin all have an FDA Pregnancy Category rhythm.73,106 Patients at particular risk for B rating, i.e., animal studies have revealed no developing this condition include those with evidence of harm to the fetus; however, there known risk factors such as existing QT interval are no adequate and well-controlled studies in prolongation, bradycardia, and those taking pregnant women.38,39,61,70,73,145 Since animal studies Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 are not always predictive of a drug's teratogenic However, the theoretical possibility that effect in humans, antibacterial agents should antibacterial agents may reduce the efficacy of only be prescribed during pregnancy if clearly oral contraceptives must be addressed directly. An exhaustive review of the literature found no credible pharmacokinetic data, with the possible Antibacterial Drugs and Nursing
exception of rifampin, to substantiate such Mechanisms of drug excretion in human milk interactions.150 The U.S. District Court for the include both passive diffusion and carrier- Northern District of California also concluded mediated transport. The amount of drug that "scientific evidence regarding the alleged excreted in milk depends on the drug's molecular interaction between antibacterial agents and oral weight, lipid solubility, pKa, and plasma contraceptives" does not satisfy the "Daubert protein binding.146,147 Once in milk, the pKa of standard of causality."151 the drug is an important determinant of the drug's concentration in milk. Consequently, at However, the American Medical Association equilibrium some drugs may accumulate in milk in states that such interactions cannot be completely higher concentration relative to plasma.
discounted and recommends that women be informed of the possibility of such interactions.152 The penicillins are excreted in milk and may lead Similarly, the American Dental Association Council to sensitization of infants.38,39 Metronidazole, on Scientific Affairs recommends (1) that patients which has been shown to be carcinogenic in rats be advised of the potential risk, (2) that patients and mice, is excreted in milk in concentrations comply with their oral contraceptive regimen, and similar to those found in plasma.61 Clindamycin is (3) that patients consider alternative contraception also excreted in milk.70 The fate of azithromycin during periods of antibacterial chemotherapy.153,154 is unknown.73 Considering the potential risks to the nursing infant and benefits to the mother, a decision should be made whether to discontinue The routine use of antibacterial agents in the nursing or not to prescribe an antibacterial treatment of uncomplicated odontogenic infections has not been shown to be effective. Most such infections respond to timely debridement. When treating complicated odontogenic infections, the Two or more drugs administered in therapeutic adjunctive use of antibacterial agents is justified. dosages at the same time or in close sequence, The empirical drug of choice should be the most may act (1) independently, (2) interact to effective and least toxic agent with the narrowest increase or diminish the effect of one or more spectrum. Prophylactic antibacterial chemotherapy drugs, or (3) interact to cause an unintended in dentistry should be limited to the prevention reaction. Potentially serious interactions can of those infections that have been proven or are occur between antibacterial agents and other strongly suspected to be procedure-specific. It is medications. An awareness of the patient's axiomatic that before prescribing an antibacterial medical history, including medications taken, is agent, the clinician must consider the diagnosis, helpful in minimizing or avoiding potential drug- the need for drug therapy, and the benefits versus drug interactions. Two excellent reviews of the risks of treatment.
subject are presented elsewhere.148,149 Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 Course Test Preview
To receive Continuing Education credit for this course, you must complete the online test. Please go to: 1. Invasion and multiplication of bacteria in body tissues result in local cellular injury due to
a. competitive metabolism b. toxin production c. immune-mediated reactions d. All of the above.
2. Which of the following statements is correct with respect to Gram-positive and Gram-
a. Acetone extracts lipids from the outer membrane, cell wall, and cytoplasmic membrane of bacteria.
b. The damage to gram-negative organisms is more extensive and they lose their crystal violet-iodine complexes, i.e., they are decolorized; and when counterstained with safranin, they appear red.
c. Gram-positive bacteria retain their crystal violet-iodine complexes and appear deep purple.
d. All of the above.
3. All of the following statements is correct with respect to odontogenic infections EXCEPT
which one?
a. Most odontogenic infections are polymicrobial.
b. The predominant flora create an ecosystem of synergism by elaborating a more favorable alkaline environment and increased oxygenation to support the growth and proliferation of its members.
c. In odontogenic infections, the number of isolated strains ranges from 1 to 10 organisms.
d. The average number of organisms responsible for an odontogenic infection is 4.
4. Pharmacological strategies are predicated on targeting differences between prokaryotic
bacterial and eukaryotic host cells. Selective toxicity can be achieved by _.
a. attacking targets unique to bacteria b. attacking targets in bacteria similar but not identical to those in host cells c. attacking targets that are shared, but vary in importance between bacteria and host cells d. All of the above.
5. Which of the following statements is correct with respect to bacterial cell walls?
a. Monomers are synthesized in the cytoplasm from amino acid and sugar building blocks.
b. Bactoperol transfers the monomers across the cytoplasmic membrane where they are polymerized into linear peptidoglycan chains.
c. Transpeptidase cross-links peptidoglycan chains into a three-dimensional mat.
d. All of the above.
6. All of the following statements are correct with respect to inhibitors of cell wall synthesis
EXCEPT which one?
a. Vancomycin targets monomer polymerization, it is bactericidal, but does not have the requisite spectrum to be considered an empirical option in treating odontogenic infections.
b. Penicillin V potassium and amoxicillin formulations, which block polymer cross-linking, are bactericidal, and have the requisite spectra to be considered as empirical options in treating c. Second generation cephalosporins have an overlapping spectra with those of penicillin V potassium and amoxicillin formulations.
d. 2nd generation cephalosporins are more β-lactamase resistant and offer a significant therapeutic advantage over the penicillins as empirical options.
Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 7. Which of the following statements relative to inhibitors of DNA synthesis and integrity is
a. Fluoroquinolones block topoisomerase type II activity, disrupt the integrity of bacterial DNA, and are b. Sulfamethoxazole (SMX) and trimethoprim (TMP), block succeeding steps in folate synthesis and the combination is bactericidal.
c. A metabolite of metronidazole directly binds DNA, causes loss of its helical structure, effect strand breakage, and is bactericidal.
d. Metronidazole, in combination with penicillin V potassium or amoxicillin, is an empirical option in treating odontogenic infections.
8. Which of the following statements is correct with respect to inhibitors of transcription and
a. Tetracyclines are teratogenic and produce higher rates of neuronal-tube defect, cleft palate, and multiple congenital abnormalities.
b. Clindamycin has excellent activity against gram-positive aerobes and anaerobes, as well as gram- negative anaerobes.
c. Azithromycin has an extended spectrum that includes some anaerobic gram-positive cocci and gram- negative bacilli.
d. All of the above.
9. Uncomplicated odontogenic infections manifest primarily as caries; and pulpal, periodontal,
and pericoronal problems with signs and symptoms that include pain, erythema, edema,
and difficulty chewing.
10. Complicated odontogenic infections reflect the extension of an uncomplicated odontogenic
infection into surrounding tissue with Signs and symptoms that include lymphadenitis,
trismus, difficulty swallowing or breathing; and less frequently, fever and hypotension.
11. Which of the following statements about the routine use of antibacterial agents in the
treatment of uncomplicated infections is correct?
a. Reversible pulpitis is a reactive process and there is no evidence that antibacterial agents would have any effect on clinical outcome.
b. In untreated irreversible pulpitis, penicillin does not reduce spontaneous pain, percussion induced pain, or the intake of analgesics.
c. In the treatment of acute apical periodontitis, once the source of infection is eliminated, the administration of penicillin provides no added benefit.
d. All of the above.
12. In a prospective study, a five-day course of penicillin administered to patients with acute
pain related to a tooth with an amalgam restoration without clinical signs of infection, in
the absence of definitive dental care, did not prevent the emergence of clinical signs of
infection within 5 days.
Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 13. In a prospective study, a five-day course of penicillin administered to patients with acute
pain related to a tooth with large periapical radiolucency, but without clinical signs of
infection, in the absence of debridement did not prevent the development of clinical signs
of infection within 5 days.
14. In the treatment of draining sinus tract, there is convincing evidence that the routine
administration of an antibacterial agent improves therapeutic outcome.
15. There is convincing evidence that the routine administration of an antibacterial agent
improves therapeutic outcome in association with which of the following conditions?
a. Gingival and periodontal abscesses b. Necrotizing ulcerative gingivitis c. Alveolar osteitis d. None of the above.
16. Depending on pericoronitis-associated signs and symptoms, i.e., clinical evidence of
induration as the infection is spreading buccally or lingually and the presence of trismus,
the adjunctive antibacterial therapy may be appropriate.
17. Which of the following conditions should be considered a complicated odontogenic
infection and an indication for adjunctive antibacterial chemotherapy?
c. Space infections d. All of the above.
18. 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.
19. The empirical antibacterial agent drug of choice should be an effective agent with the
narrowest spectrum and the least potential for adverse drug effects.
20. Which of the following statements is correct with respect to primary line antibacterial
a. 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.
b. Most infections require 5 days of antibacterial chemotherapy - an initial loading dose followed by maintenance doses for the remainder of the time.
c. If significant improvement is not noted in 48 to 72 hours, the addition (for 5 days) of metronidazole to penicillin V potassium is reasonable.
d. All of the above.
Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 21. Which of the following statements is correct with respect to secondary line antibacterial
a. A macrolide is an empirical option for the treatment of odontogenic infections in patients allergic to b. While there is a paucity of data demonstrating the efficacy of azithromycin in the treatment of c. Clindamycin may be a better empirical option in patients allergic to β-lactam antibacterial agents.
d. All of the above.
22. Which of the following statements is correct with respect to tertiary line antibacterial
a. Clindamycin is the empirical drug of choice for unresolved infections following treatment with a β-lactam antibacterial agent.
b. Clindamycin is the initial empirical drug of choice for the treatment of severe complicated c. Clindamycin is β-lactamase resistant and has excellent activity against gram-positive cocci and most d. All of the above.
23. All of the following statements are correct with respect to the prevention of surgical-site
infection in patients undergoing tooth extractions EXCEPT which one?
a. There is no evidence to support the prophylactic use of antibacterial agents in association with the extraction of non-restorable teeth.
b. The infection rate after third molar extraction is about 10%.
c. In debilitated or immunocompromised patients, the infection rate after third molar extraction may be as high as 25%.
d. Antibacterial drugs administered just before and/or just after third molar extractions do reduce the risk of infection, pain, and dry socket.
e. There is solid evidence that an antibacterial agent given to healthy people in association with third molar extractions is more beneficial than harmful.
24. All of the following statements are correct with respect to the prevention of surgical-site
infection in patients undergoing placement of dental implants EXCEPT which one?
a. Bacteria introduced during the placement of dental implants can lead to infection and implant failure.
b. The implant failure rate among patients not receiving antibiotics is about 5%.
c. There is no evidence to suggest that amoxicillin 2g. administered 1 hour preoperatively significantly reduces the failure rate of dental implants placed under ordinary conditions.
d. There is no evidence that postoperative antibacterial agents are beneficial to reduce infection and implant failure.
25. All of the following statements are correct with respect to the prevention of infective
endocarditis in patients undergoing dental procedures EXCEPT which one?
a. The 2007 guideline stratifies cardiac conditions as to the risk of developing endocarditis and the severity of associated morbidity.
b. Only patients with the highest-risk of adverse outcome from endocarditis require antibacterial prophylaxis prior to dental procedures.
c. Antibacterial prophylaxis is indicated before procedures that involve manipulation of gingival tissue, periapical region of teeth, or perforation of the oral mucosa.
d. In situations where no chemoprophylaxis was given, but in which unexpected bleeding occurred, the institution of antibacterial therapy within 24 hours is recommended.
Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 26. Which of the following statements is correct with respect to the prevention of orthopaedic
implant infection in patients undergoing dental procedures?
a. The practitioner might consider discontinuing the practice of routinely prescribing prophylactic antibiotics for patients with hip and knee prosthetic joint implants undergoing dental procedures.
b. There is no evidence to recommend for or against the use of topical oral antimicrobials in patients with prosthetic joint implants or other orthopaedic implants undergoing dental procedures.
c. In the absence of reliable evidence linking poor oral health to prosthetic joint infection, it is the consensus that patients with prosthetic joint implants or other orthopaedic implants maintain appropriate oral hygiene.
d. All of the above.
27. Which of the following statements is correct with respect to the prevention of infection in
patients with various medical conditions undergoing dental procedures?
a. Evidence that a particular bacteremia-producing dental procedure caused a specific case of infection is circumstantial at best.
b. No definitive, scientific evidence supports the use of prophylactic antibiotics in patients with various medical conditions undergoing dental procedures.
c. Clinicians should amplify their efforts to ensure that all patients understand the critical importance of maintaining optimal oral health, which could serve to reduce the severity of both self-induced and d. All of the above.
28. Which of the following statements is correct with respect to the prevention of surgical-site
infection in patients undergoing open reduction and fixation of mandibular fractures?
a. The benefit of pre- and intra-operative antibacterial chemotherapy when treating open mandibular fractures has long been established.
b. A prospective randomized trial evaluated the efficacy of post-operative prophylactic antibacterial chemotherapy in association with open reduction and internal fixation of mandibular fractures and found no statistically significant benefit.
c. A prospective randomized trial evaluated the efficacy of post-operative prophylactic antibacterial chemotherapy in association with open reduction and internal fixation of mandibular fractures concluded that tobacco and alcohol appear to be significant risk factors for post-operative infections.
d. All of the above.
29. Which of the following statements is correct with respect to the prevention of surgical-site
infection in patients undergoing head and neck oncology surgery?
a. The incidence of wound infection in patients undergoing head and neck oncology surgery has been reported to be as high as 87%, often with devastating effect.
b. Based on the best current evidence, it is recommended that prophylactic antibacterial agents, covering aerobic gram-positive cocci and gram-negative bacilli, and anaerobic bacteria be administered in association with clean and clean-contaminated head and neck oncology surgery.
c. There is no evidence that prophylactic antibacterial agents offer any benefit in clean surgery for benign disease.
d. All of the above.
30. Which of the following statements is correct with respect to antibacterial drug-resistance?
a. The widespread and ever increasing use of antibacterial agents contributes to the development of b. Unless healthcare providers change their practices, many currently available antibacterial agents may become ineffective.
c. When other therapeutic means are available, antibacterial agents should not be routinely prescribed to treat or to prevent infections.
d. All of the above.
Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 31. All of the following statements are correct with respect to gastrointestinal disturbances in
association with antibacterial agents EXCEPT which one?
a. Common ADEs associated with antibacterial agents, but especially with macrolides, are nausea, vomiting, epigastric distress, and diarrhea.
b. Gastrointestinal symptoms may be amplified in patients on clindamycin with concurrent use of alcohol.
c. When a patient has been taking an antibacterial agent for 1 to 2 days, diarrhea is probably due to the mild irritating action of the drug.
d. Bloody diarrhea with abdominal cramping is highly suggestive of pseudomembranous colitis, a superinfection with Clostridium difficile.
32. Which of the following statements is correct with respect to hypersensitivity or other
immune-related reactions to antibacterial agents?
a. Maculopapular to exfoliative dermatitis, urticaria, angioedema, and rarely, anaphylaxis may occur with all antibacterial agents.
b. Allergic reaction to the penicillins is more likely to occur in individuals with sensitivity to multiple allergens and in those with asthma.
c. Rare instances of erythema multiforme and Stevens-Johnson syndrome have been reported with clindamycin and azithromycin.
d. All of the above.
33. Which of the following statements is correct with respect to potential cardiac complications
associated with macrolides antibacterial agents?
a. Azithromycin and other macrolides can cause abnormal electrical activity in the heart that may lead to a potentially fatal irregular heart rhythm.
b. Patients at particular risk for developing cardiac complications include those with existing QT internal prolongation and bradycardia; and those taking medications for the treatment of abnormal heart rhythm or arrhythmias.
c. Increased risk of death from cardiovascular causes has been reported in persons treated with a 5-day course of azithromycin.
d. All of the above.
34. Penicillins should be administered with caution to patients with central nervous system
disorders because severe convulsive seizures and peripheral neuropathy, characterized by
numbness or paresthesia of the extremities are common.
35. Superinfections with Candida sp. can occur in association with all, but especially broad-
spectrum antibacterial agents.
36. Which of the following statements is correct with respect to antibacterial agents and
a. There is no firm evidence that the penicillins, metronidazole, azithromycin, and clindamycin are teratogenic in humans.
b. The penicillins, metronidazole, azithromycin, and clindamycin all have an FDA Pregnancy Category B rating, i.e., animal studies have revealed no evidence of harm to the fetus; however, there are no adequate and well-controlled studies in pregnant women.
c. Since animal studies are not always predictive of a drug's teratogenic effect in humans, antibacterial agents should only be prescribed during pregnancy if clearly indicated.
d. All of the above.
Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 37. Which of the following statements is correct with respect to antibacterial agents and nursing?
a. The penicillins are excreted in milk and may lead to sensitization of infants.
b. Metronidazole, which has been shown to be carcinogenic in rats and mice, is excreted in milk in concentrations similar to those found in plasma.
c. Considering the potential risks to the nursing infant, a decision should be made whether to discontinue nursing or not to prescribe an antibacterial agent to the mother.
d. All of the above.
38. Which of the following statements are correct in relation to interactions between antibacterial
agents and oral contraceptives EXCEPT which one?
a. There are no pharmacokinetic data at this time to support the contention that antibacterial agents reduce the efficacy of oral contraceptives, except for rifampin, an antituberculin drug.
b. The United States District Court for the Northern District of California concluded that "scientific evidence regarding alleged interaction between antibacterial agents and oral contraceptives did not satisfy the "Daubert" standard of causality.
c. According to the American Medical Association, such interactions cannot be completely discounted.
d. All of the above.
39. The ADA recommends that patients prescribed an antibacterial agent while also taking an oral
a. be advised of the potential risk b. comply with their oral contraceptive regimen c. consider alternative contraception during periods of antibacterial chemotherapy d. All of the above.
40. All of the following statements are correct with respect to the administration of antibacterial
agents in oral healthcare settings EXCEPT which one?
a. The routine use of antibacterial agents in the treatment of uncomplicated odontogenic infections has not been shown to be effective.
b. When treating complicated odontogenic infections, the adjunctive use of antibacterial agents is c. Prophylactic antibacterial chemotherapy in dentistry should be limited to the prevention of those infections that have been proven or are strongly suspected to be procedure-specific.
d. The empirical drug of choice should be the most effective and least toxic agent with the broadest Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 1. Hallman M. The surfactant system protects both fetus and newborn. Neonatology. 2013;103(4): 2. Lederberg J. Infectious history. Science. 2000 Apr 14;288(5464):287-293.
3. Darveau RP, McFall-Ngai M, Ruby E, Miller S, Mangan DF. Host tissues may actively respond to beneficial microbes. ASM News 2003;69(4):186-191.
4. Brito LC, Sobrinho AP, Teles RP, Socransky SS, Haffajee AD, Vieira LQ, Teles FR. Microbiologic profile of endodontic infections from HIV+ and HIV- patients using multiple-displacement amplification and checkerboard DNA-DNA hybridization. Oral Dis. 2012 Sep;18(6):558-567.
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Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014 About the Authors
Leena Palomo, DDS, MSD
Dr. Palomo is Associate Professor of Periodontics and director DMD periodontics. She is a diplomate of the American Board of Periodontology. She published several articles in medical and dental journals. Additionally, she has been invited for presentations at national and international professional meetings. Her commitment to our dental students has been recognized. She earned her undergraduate as well as DDS and MSD degrees from Case Western Reserve University in 1996 and 2004 Géza T. Terézhalmy, DDS, MA
Professor and Dean Emeritus
School of Dental Medicine Case Western Reserve University Dr. Terézhalmy is Professor and Dean Emeritus, School of Dental Medicine, Case Western Reserve University. In addition, he is a Consultant, Naval Postgraduate Dental School, National Naval Medical Center; and Civilian National Consultant for Dental Pharmacotherapeutics, Department of the Air Force.
Dr. Terézhalmy earned a B.S. degree from John Carroll University; a D.D.S. degree from Case Western Reserve University; an M.A. in Higher Education and Human Development from The George Washington University; and a Certificate in Oral Medicine from the National Naval Dental Center. Dr. Terézhalmy is certified by the American Board of Oral Medicine and the American Board of Oral and Maxillofacial Radiology (Life).
Dr. Terézhalmy has many professional affiliations and over the past 40 years, has held more than 30 positions in professional societies. He has served as editor or contributing editor for several publications, co-authored or contributed chapters for several books and has had over 200 papers and abstracts published. Dr. Terézhalmy has accepted invitations to lecture before many local, state, national, and international professional societies.
Crest® + Oral-B® at dentalcare.com Continuing Education Course, May 1, 2014

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