• Maintain high enough levels of the drug in tissues to kill the original popula- tion and halt the first attempts at gene mutation. • Simultaneously administer two or more drugs to delay the emergence of bac- terial mutants that are resistant lo one of the drugs • Restrict the use of drugs known to spawn mutant infections. • Strictly regulate tfie amplification of drug resistance from person to person as could occur m a large hospital or other institutions, including semiambulalory facilities for the elderly and dental operatories. • Report any emergence of antibiotic-resistant bacteria worldwide to a public health facilitv such as tfie CDC in the United States so that the natural history of the disease can be followed and controlled, " Support research that can lead to development of new antibiotics from differ- ent sources, to discovery of how these drugs attack new sites within the bac- terium, and to development of drugs that will help existing medications to overcome drug resistance.

We in the dental profession must continue our scientific education as it relates to health promotion, disease prevention, diagnostics, and therapeutics We are living at a time in human history that accommodates emerging and re- emerging infectious diseases. We must continue to follow universal precautions and infection control recommendations (ADA Council on Scientific Affairs, Coun- cil on Dental Practice, J Am Dent Assoc, 1996) with our patients, and to obtain approved vaccinations tor our heaith care personnel. We must prevent antibiotic abuse or neglect by following established recommendations for the use of antibi- otic agents in dental, oral, and craniofacial surgical procedures and for prophylax- is, And we can meet these challenges!

BASIC PRINCIPLES Basic Principles of Appropriate Antibiotic Usage OF ANTIBIOTIC THERAPY In 1996, physicians and dentists wrote more than 2.4 billion prescriptions, an increase of 4% over the preceding year (Buckley B, Pharm Times, 1997¡, Although AND PROPHYLAXIS it is not known what percentage of these prescriptions were for antibiotics, six of the top 30 prescribed drugs were antibiotics, including the second most pre- ROGER E. ALEXANDER, DDS scribed drug of the year, a brand of amoxicillin Among generic drug prescriptions written in 1995, antibiotics compnsed 50% of the top 10 drugs prescnbed tfiat year. These data reflect the extensive role that antimicrobial drugs piay clinically in both medicine and dentistry, often for inappropriate prophylaxis or for localized, self-limiting, minor infections This inappropriate use of antibiotics has an indirect impact on infection management because organisms are no longer susceptible to many of our chemical weapons. Antibiotic resistance is becoming a growing con- cern worldwide, and scattered strains of bacteria that are resistant to even/ drug in the arsenal are appearing. Currently there are no new antibiotics with substantially different mechanisms of action on the immediate research horizon (Peterson LJ, Oral Surg Oral Med Oral Pathol, 19941. These usage patterns reflect a lack of understanding of pharmacotherapeutics and the function of the human immune system by physicians and dentists. Antibi- otics, by themselves, do not cure or prevent disease. Antibiotics are nothing more than'weapons to be used to enhance the performance of the "soldiers" of the immune system By themselves, antibiotics are only part of the necessary response, and without an intact and participating immune system an antibiotic will eventually fail. This has been underscored by patients with acquired immune defi- ciency syndrome, who frequently expire from opportunistic infections despite intensive pharmacologie therapy. Prior to the antibiotic era, patients were treated with nothing more than removal of the infection source, drainage of pus, and the natural immune system.

Quintessence International Voiume 28. Number 12, 1997 815 As many as 264 morphologically and biociiemically distinct bacterial groups colonize the oral cavity, including aerobic, facultative, and obligate anaerobic, gram-positive, and gram-negative organisms. These microorganisms support each other in a synergistic fashion. During an infection, individual members of the microbe community (!} produce metabolites that facilitate growth of other microbes; (2) create an increasingly acidic tissue pH that facilitates enhanced growth of certain microbes; and 13) consume oxygen, which allows growth of one or more opportunistic anaerobes (Moenning JE et al, J Oral Ma^illofac Surg, 1989). As a result of this symbiotic environment among oral organisms, most odontogenic infections ultimately involve five to seven ditferent microorganisms. Anaerobic organisms usually dominate, outnumbering aerobes by a ratio ot at least 2 1 (Moenning JE et al, J Oral Maxillofac Surg, 1989). It is increasingly com- Or Alexander is Associate Professor and Direc- tor tor Urdergraduale Sjrgical Euucatmr for mon for infections to demonstrate growths of Peptacocci, Peptostreptococci, the Deparlmert of Oral and Maxillofacial fusobacterium. and Bacteroides species. H isn't necessary for an antibiotic to be Surgery and Pharmacology, Tenas A&ti/I Univsr- effective against all bacterial strains involved in an infection Elimination of select sity System—Baylor College of Dentistry in Dal- strains may alter local tissue conditions sufficiently so that the immune system, las, Tesas. coupled with timely surgical intervention, can overcome the microbes (Flynn TR, J Oral Maxillofac Surg, 1993) Prevention and therapy- There are only two basic uses for antibiotics, pre- vention and therapy. Since the use of antibiotics and surgical management of the patients cannot be separated, in preparing to examine appropriate antibiotic use in dentistry it is valuable to review some of the basic axioms of clinical infection management:

• Pus follows the paths of least resistance: usually along fascial planes and through anatomic spaces and potential spaces • All fascial spaces in the head and neck interconnect with each other, some- how, somewhere • Intraoral and exlraoral presentation of infections will be largely guided by the location of pus relative to certain masticatory and facial muscle attachments. • Pus must be drained and the source of the infection controlled as soon as possible. No cure will occur until then. Decompression of the induration, debridement of necrotic tissue, elimination of dead space and pus, and per- haps exposure of deeper tissue to air, all contribute to the demise of causative organisms (Flynn TR, J Oral Maxillofac Surg, 19931. Drainage is usually accompanied by profuse irrigation ("the solution to pollution is dilution"). • The most optimal drainage can often be through an alveolar socket (following extraction of the offending tooth). • Newer, expensive antibiotics may not be any more effective than older, safer, cheaper, established antibiotics. • Antibiotics take time to work, especially if given orally. If an infection cannot wait for 24 to 72 hours for therapeutic impact, then parenteral routes are preferable. " Intrabony infections may not be radiographically evident until one or both bony cortices are involved. • Failure to use the thermometer is one of the most common mistakes made in clinical evaluation of infection It provides valuable information on how the body IS dealing with the infectious process The aggressiveness of clinical treatment is influenced significantly by the degree of elevation of a patient's temperature. • The risk of antibiotic administration should be justified by the need and an- ticipated benefit. All doctors should carefully evaluate the potential for adverse Acknowledgment. The author wishes to thank reactions, side effects, and interactions before prescribing antibiotics. Tommy W Gage, RPh, DDS, PhD, Professor and • Although interference with birth control medication has not been conclusively Direclor of the Ptiarniacology Division, Oepan- proven, legal defense of a practitioner is very difficult if a female patient ment of Oial and Maxillofacial Surgery and becomes serendrpitously pregnant during therapeutic administration of an Piiarmacclogy, Tenas ASM tlniversity System— Baylor College of Dentistry for his willirgress to antibiotic. It is therefore prudent for a practitioner to warn such patients to sfiare his experience, insight, and knowledge take additional precautions lor abstain) during and after antibiotic administra- during the prepaiatior otthis article. tion and document the warning in the patient record.

816 Quintessence international Volume 28, Number 12 1997 The infectious process is confusing to many practitioners. Infection is noth- ing more than invasion and multiplication of microorganisms in the body. This results in celluiar injury, which induces infiammatory and immunoiogic respons- Much ofthe abuse es. Initiaiiy, the local inflammatory process responds to the invaders. Once the infection breaks out of its localized confines, cellulitis follows, characterized by of antibiotics occurs a diffuse, unlimited, purulent extension of the infiammatory process through adjacent, deeper tissues. As cellular and biochemical debris, killed bacteria, and when they are used liquified dead cells accumulate, they are walled off and confined, becoming pus contained in one or more abscess spaces. This accumulation of waste prod- for prophylaxis. ucts of the "war within" must be removed or the inflammatory process will continue Common abuses. Much of the abuse of antibiotics occurs when they are used for prophylaxis. When antibiotics are used prophylacticaiiy to prevent infec- tion, severai axioms apply:

" The procedure should have a sufficient risk of infection morbidity to justify the risk of administenng the antibiotic. "The most appropriate antibiotic for the anticipated fiora involved should be used. • The antibiotic shouid be administered in doses sufficient to attain high biood ieveis, for as short a period of time as possible Administration must begin im- mediateiy prior to the procedure, to minimize the development of resistant strains. Administering prophylactic antibiotic therapy after a procedure is fin- ished compromises any benefit and reduces effectiveness of the protocoi. • There is no scientific justification for prescribing antibiotics "just in case." Potential benefits must be weighed against nsks.

Wherever antibiotics are prescribed for therapeutic management of infection, several other pharmacotherapeutic axioms prevail:

• Bactericidal antibiotics are preferred over bacferiostatic, and the two are aimost never mixed (because one may interfere with the actions of the other), • A narrow-spectrum antibiotic that is generally effective against oral flora is preferred if information from a culture and sensitivity study is unavailable and empiric prescribing is necessan/ • Many microorganisms, especially anaerobes and gram-negative organisms, are ß-lactamase emitters, which will interfere with the more commonly pre- scribed antibiotics (penicillins, cephalosporins, etcl. Some bacteria that were susceptible to bela-lactam antibiotics af one time are now resistant, but the rate of this transformation is not yet known. • When two or more antibiotics are prescribed simultaneously, each shouid be prescribed as if it were the only one being prescribed Dosages should not be reduced in anticipation of synergism, etc, " Patients who have compromised or impaired immune systems may require more aggressive and proionged antibiotic protocois than patients with intact immune systems. • Close follow-up of patients with infection is essentiai Patients who are initially treated for odontogenic infections should be examined and/or called at least every 24 hours until it is assured that the infection is coming under control and no longer a threat to the patient. Additionally, doctors must be accessible to patients 24 hours a day, in the event the patient needs to notify the doctor of adverse changes in signs or symptoms, such as dramatic increases in tem- perature, swelling, or difficulty swallowing. It is inappropriate for a patient with an acute infection to be told to return in "a week or so" because any infection has the capacity to endanger life in 24 hours or less through contiguous spread or airway encroachment, • Difficult chronic and subacute infections, such as osteomyelitis, should be referred to an oral and maxillofacial surgeon upon diagnosis Management generally involves surgical and therapeutic interventions that are beyond the capability of most general practitioners to provide.

Quintessence International Volume 28, Number 12, 1997 817 Which antibiotic? When a patient presents to the general dentist with an infection, a detailed workup should be accomplished and include (V review of the medical and dental history, Í2I thorough physical examination (which must include examination of the airway and oropharynx to verify lack of encroachment on tfie airway, a primary concern in serious infections), 131 record of the oral temperature, ¡4) appropriate radiographs, and (5) evaluation of the extent of fascial spaces involvement. Based on the various factors, generally an empiric initial choice is made, seiecting the antibiotic(s) that experience has shown to be effective against most odontogenic infections It is unusual that information from a culture and sen- sitivity test or Gram stain is available in the general dental setting before the patient is placed on an antibiotic. If it is determined that localized pus is present (abscess), incision for drainage (or extraction of the involved tooth, if indicated) should be accomplished as soon as possible. If the pus fias spread more extensivelv throughout the spaces, an oral and maxillofacial surgeon should be consulted as soon as possible. Only oral forms of antibiotics will be discussed here because very few general dental offices are equipped to administer parenteral (intravenous and intramuscu- lar) antibiotics. The vast maiority of dentists deal with infections using oral forms of the antibiotics. Incipient and minor to moderate infections (oral temperature < 1OO''F±) A member of the penicillin family is still the initial drug of choice in a nonallergic pa- If judgment suggests tient. More specifically, amoxicillin is the preferred orai form for most clinicians be- cause it has a slightly broader spectrum, is more reliably absorbed, attarns higher an infection is best blood levels, and has an extended half life If significant improvement is not noted in 24 to 48 hours, the empirical addition of metronidazole is considered reasonable controlled by because nonsusceptible, ß-lactamase-emittmg, gram-negative strains may be par- ticipating in the infection Metronidazoie, on the other hand, is highly effective penicillin,then against gram-negative organisms, complementing the actions of the penicillin. Many clinicians are concerned about the potential for allergic reactions with theoretic concern penicillin usage. While this is always a potential with any drug usage, it should be remembered that only a small percentage of patients will react (variousiy reported for potential as 3% to 6% with oral use), and the reaction to oral administration is usually in the form of a rash or dermal erythema and is rarely life-endangering. If ludgment sug- side effects and gests an infection is best controlled by penicillin, then theoretic concern for poten- tial side effects and reactions should not preclude its clinical use. reactions should not Some articles have suggested substituting clindamycin for penicillin if the lat- ter is not therapeutically successful. Tfiere is disagreement in the literature on preclude its this course of action, however. Clindamycin has an excellent clinical track record in orofacial infections, is ß-lactamase-resistant, and performs as weii as penicillin clinical use. IFIynn TR, J Oral Maxillofae Surg, 1993; Krishnan V et al, J Oral íVlaxillofac Surg, 1993; Gilmore WC et al, J Oral Maxillofae Surg, 1988). In lower doses it is bacte- riostatic and becomes bactericidal in higher doses. It has excellent aerobic and anaerobic activity, including against Bacteroides tragiiis (Moenning JE et al, J Oral Maxillofae Surg, 1989) Some authors feel clindamycin should be reserved for more severe infections because it reportedly has a higher nsk profile. Others feel the risks of clindamycin administration (for example, antibiotic-associated, pseudomembranous colitis lAAPCI due to Clostridium difficile overgrowth) aie overstated and clindamycin should be a prominent part of our oral arsenal Perusal of the literature shows that the vast majority of patients who experience AAPC are eideriy, femaie, hospitalized, on high doses of the drug, and have had abdominal surgery or abdominal complaints Since most dental patients do not fall in that category, the risk for AAPC is low unless the patient was recently hos- pitalized Furthermore, all of tfie antibiotics commonly used in dentistry have had reports of AAPC in the literature, including cepfialosponns, peniciilin derivatives, and others. Like allergy, it is nothing more than a side effect of antibiotic admin- istration that the clinician must be aware of, recognize if it occurs, and manage appropriately Another antimicrobial alternative for moderate odontogenic infections in non-pen ICI Ilin-allergic patients is ampiciilin combined with a (3-lactamase inhibitor.

818 Quintessence Internationai Volume 28, Number 12,199? A Dictionary such as sulbactam (Augmentin, SmithKline Beecham). of Confusing Definitions Severe odontogenic infections (oral temperature > 100°F±, spreading cetlulitis, and systemic symptoms). The initial empiric antibiotic of choice is clmdamycin m inflammation: this author's opinion. Using clindamycin for early or less severe infections is also A localized, protective reaction in appropriate if the patient is allergic to pencillin or when the patient has not tissues following injury or irritation, responded to surgical intervention and initial penicillin therapy (Moenning JE et al, which serves to wall off, dilute, and JOral Ma>;illofac Surg, 1989; Gilmore WC et al, J Oral Maxillofac Surg, 1988). destroy the miurious agent or Although used for many years for routine prophylactic uses, the erythromycms injured tissue. Eollowed by a often perform poorly m infection therapy. Higher doses are required for the drug to process of repair and healing In the become bactericidal, and those higher doses induce nausea and vomiting in many acute form, it is characterized by patients, For that reason, they are rarely used as empiric therapeutic drugs for pain, heat, swelling, redness, and odontogenic infections Some newer, long-acting forms of erythromycin (clar- loss of function. itbromycin, azithromycin, and diritbromycin) have shown some therapeutic Infection: promise, but there are too few clinical data to recommend widespread usage at Invasion and multiplication of micro- this time. organisms in the body, resulting m First generation cephalosporins are less ideal as initial antibiotics because they local cellular injury, which induces have a wider spectrum of action and are not as effective as penicillin or clm- inflammatory and immunologie re- damycin against some of the more common gram-positive and anaerobic strains actions. (You can have inflammation (Gill Y and Scully C, Oral Surg Oral Med Oral Pathol, 1990) They are also suscepti- witbout infection, but not usually ble to ß-lactamase, like penicillin, so there is generally very little therapeutic advan- vice versa). tage to their use Some patients (not all) who have had an immunoglobin E-medi- ated (ie, anaphylactic) reaction to penicillin can potentially also react to any Cellutitis: cephalosponn Second and third generation cephalosporins are not indicated as ini- A diffuse, unlimited, purulent ex- tial empiric choices Their use is predicated on the results of sensitivity testing. tension of the inflammatory process Tetracyclines are bacteriostalic drugs, and there are significant numbers of through deeper contiguous tissues, resistant strains of oral bacteria already noted (Moenning JE et al, J Oral Maxillofac not circumscribed or confined to Surg, 1989). They are noi indicated for use in any significant odontogenic infection. one anatomic area. Even in penodontics, where tetracyclines are used extensively for localized peri- odontal infections, many authors feel tbe benefit is not well substantiated m the Abscess: A localized, confined collection of scientific literature. pus within a space created in the Fluoroquinalones (eg, ciprofloxacin) are inappropriate for use in oral infections because they have poor actions against oral streptococci and most anaerobes tissues; usually accompanied by (Frieden TR and Mangi RJ, JAMA, 1990). This group of anti-microbials has been inflammation. labeled by some experts as the most abused antibiotic group m clinical medical Pus. practice, and resistant strains have developed rapidly. Liquified dead cells, debris, bacteria, tissue enzymes, etc. ¡If pus breaks Antibiotic Prophylaxis for Patients Susceptible out of its confined space, it results to Bacterial Endocarditis in eel lu litis.) The use of prophylactic antibiotics to "prevent" bacterial endocarditis (formerly known as subacute bacterial endocarditis] following dental treatment has resulted in confusion, noncompliance, misunderstandings, and even ignorance in both medicine and dentistry for more than 40 years. Even though the American Heart Association (AHA) first released recommendations for prophylactic coverage of such patients in the early 1950s and several subsequent modifications to these recommendations (not guidelines) have received extensive coverage in the professional literature and continuing education venues, there still remains a virtual mountain of confusion and misunderstanding about the use of antibiotics in den- tistry to reduce the nsk of bacterial endocarditis. Several publisbed papers in the mid-1980s highlighted the extent of the con- fusion. In one study, less than half of the dentists correctly identified the proper timing of the regimens, and only one of five knew the proper antibiotic regimen for a 40-pound pédiatrie patient In a history-based, telephone survey published in 1984, less than half of the dentists followed the recommendations of the AHA and only 11% recognized the need to use antibiotic prophylaxis with patients with congenital heart diseases. One third of the respondents incorrectly answered questions regarding management of patients with prosthetic heart valves. In another published survey of physicians and dentists, physicians demonstrated poorer knowledge about which dental procedures required antibi- otic coverage than dentists (Nelson CL and Van Blaricum CS, J Am Dent Assoc,

Quintessence International Volume 28, Number 12, 1997 819 19891, Overall, only 27% of physicians and 39% of dentists demonstrated ade- quate knowledge for managing all types of "at risk" patients. The author believes that this trend continues even today. Since 1923, it has been known that multiple bacteremias occur every day in patients with periodontal disease and poor oral hygiene and are known to occur during such daily life events as gum chewing, tooth brushing, flossing, eating, nose blowing, and the like. In a nonsusceptible patient, these mtravascular bac- terial microburdens are managed by the immune system without danger to the heart. However, in patients who have sustained damage to the cardiac vafves, such as damage secondary to rheumatic heart disease, or in patients who have other alterations of architecture or flow dynamics that cause localized "jetting" effects (such as mitral valve prolapse, congenital cyanotic heart disease, etc), these bacteremias can become potentially life-threatening. More recently, witfi our increasingly aged patient population there has been an upsurge of endocardi- tis cases in the elderly, due to atherosclerotic and degenerative changes in their cardiac structures. Significant numbers of cases are also being seen in intra- Only the high- and venous drug abusers. In a compromised heart, a chain of events can be triggered that renders the medium-risk patients affected area(s) susceptible to future bacteremias: require antibiotic • The altered architecture results m local eddying or jet effects (for exarnple, blood jetting through a defective valve leaflet) during cardiac compression. prophylaxis and only • The delicate endothelium is stripped off or damaged in the areals) of altered flow, exposing underlying collagen. forthose procedures • These altered surfaces encourage adhesion of platelets and fibrin, creating a sterile thrombus, identified as high- • If the thrombus is exposed to a bacteremia. bacteria can become lodged m the thrombus, colonizing and infecting it. risk procedures. • This "vegetation" can lead to further destruction of a heart valve or other inter- nal cardiac surface, with accompanying morbidity or mortality.

Presently, the endocarditis mortality rate is variously estimated to be as low as 10% (for Group A Streptococcus] to as high as 67% (for less common organismsl (Hupp JR, J Oral Maxillofac Surg, 1993; Uyemura MC, Postgrad Med, 19951. Regardless of the onginal pathology, once damaged, the internal cardiac surface is forever susceptible to bacterial endocarditis from bacteremias from any source, including dental treatment Acute rheumatic fever |RF¡ results from an immunologie response to Grcup A, ß-hemolytic streptococcal throat infection, but the exact nature of this response continues to evade researchers. More recent studies have shown that certain bacterial strains vary in their ability to cause endocarditis and platelet aggregation and worsen the clinical course of the disease (Hupp JR, J Oral Max- illofac Surg, 1993). The incidence of RF remains low in the United States but is endemic in many developing countries. The incidence of RHD originating as s sequelae to RF is unknown, but that relationship has led many dentists to assume that any patient with a history of RF must be endocarditis-susceptible and therefore requires antibiotic prophylaxis In fact, that is not true m the United States, where an advanced state of medical treatment availability allows most cases of RF to be discovered and treated before they progress to RHD The liter- ature estimates that RHD may account for 20% to 60% of all endocarditis cases, while prosthetic valve involvements account for 10% to 20%, congenital iieart disease for 6% to 24%, and patients with unknown risk factors 30% to 60°/o (Pallasch TJ, J Calif Dent Assoc, 1989). In the absence of heart involvement, a history of RF alone is insufficient to require antibiotic prophylaxis. There must be additional clinical or historic informa- tion that suggests residual cardiac damage (ie, a clinical murmur). Functional mjr- murs of childhood and pregnancy generally do not require antibiotic coverage, bul medical consultation is often needed to diagnose these situations. Likewise, orîlV patients with conditions that present clinical evidence of cardiac damage byway of régurgitation murmurs (eg, mitral valve prolapse) appear to be at high risk for

820 Quintessence International Volume 28. Number 12, TABLE 1 Recommended antibiotic regimens

Adults and children Children > 60 Ib 127 kg) < 60 Ib (27 kg}

Standard regimen ' Amoxicilhn 2 g orally, 1 h preop 50 mg/kg, 1 h preop ¡no follow-up dosel (not to exceed adult dose}

Alternate standard regimens Clindamycm 600 mg orally, 1 h preop 20 mg/kg, 1 h oreop Cepfialexin' or Celadroxil' 2 g orally, 1 h preop 50 mg/kg, 1 h preop Azithromycin/Clarithromycin 500 mg orally, 1 fi preop 15 mg/kg, 1 h preop

Parenteral regimen Ampicillin 2 g IM or IV, less tfian 50 mg/kg, less than 30 min preop 3D mm preop

Alwrnate parenreral regimen Clindamycm 600 mg IM or IV, less than 20 mg/kg, less than 30 mm preop 30 mm preop Cefazolin 1 g IM or IV, less tfian 25 mg/kg, less than 30 mm preop 30 min preoD Basefl on information contained in Ame can Heart Association Prevention of Bacterial Endocarditis (booklet ll7t-0117V 1997 IM = intramuscularly. IV ^ intravenously Alternate regimens are for patients allergic to penicillins, incluOing amoxici in and ampicillin Parenteral regimens are for patients who are unable to take oral medtcatio s "In Ihe event of unanticipated tileeding. antibiotics can be administered w hin 2 hours of the proce- Sure and still he effective. 'Cephalexin or CefadiozM mav cause reactions m penicrflin-ailergic patiarts who give liistory ol immjnoglobiilin E-mediated reactions.

endocarditis development, in the absence of régurgitation, the risk is very low. Overall, the incidence of infective endocarditis is extremely low in the United States, estimated to be between 11 and 50 cases per million population per year. Over the years, erroneous advisories have been provided to dentists by general practice physicians and paraprofessionals who did not have a clear understanding of the pathophysiology of the disease. In other instances, dentists have taken a "when in doubt, cover" approach to providing antibiotic coverage. These unscien- tific practices have led to a concern among infectious disease experts over the in- creased possibility of anaphylactic reactions and microbial resistance problems in patients who receive repetitive doses of antibiotics inappropnately. This is per- ceived to be a greater concern than the likelihood ot developing bacterial endo- carditis, and patients have a greater chance of dying from the antibiotic than from the disease process. Furthermore, there is no assurance that the antibiotic regimens will be success- ful. All the regimens that have been used over the years have been derived from Interpolation of animal-based laboratory data, combined with "informed rationaliza- tion." Although relatively uncommon, there are reported cases of bacterial endo- carditis occurring in patients who had received appropnate prophylactic coverage or who had no known prior risk. Many authors dispute whether antibiotic prophyl- axis IS indicated at all, without more substantial evidence of its benefits (Uyemura MC, Postgrad Med, 1995). It IS also well-known that the oral and gingival health of the patient is an impor- tant part of the equation It is of paramount importance that the penodontal health of susceptible patients be optimal. In the presence of chronic infection, food de- bris, and plaque around the dentition, everyday experiences of mastication and oral hygiene become a nsk to the susceptible patient Even denture sores from ill-fit- ting complete dentures have been identified as an infection source. According to the current recommendations of the American Heart Association (Table 1| (Dajam AS et al, JAMA, 19971, susceptible patients can be classified at

Quintessence International Volume 28, Number 12, 1997 821 high, medium, or low risk for bacterial endocarditis. Specific dental procedures have been identified as low or high risk, based on the likelihood of periodontal or gingival bleeding (although some experimental studies have suggested lymphatic pathways are equally or even more important pathways ol transmission). Signifi- cant bacteremias are most likely to occur during the performance of the high-risk procedures. Generally, it is felt that only the high- and medium-risk patients require antibiotic prophylaxis and only for those procedures identified as high-risk proce- dures. Tables 2 and 3 summarize these classifications. When repeated appoint- ments are needed, the AHA recommends that appointments for susceptible

TABLE 2 Classification of endocarditis-susceptible patients

High-risk pavents Cardiac prosthetic valvels) (mcludmg bioprosthetic and homograft valves! Hislory of D'evious bacterial endocarditis ISBEI infection(sl Complex cyanotic congenital heait disease (eg. Tetralogy of Fallot, transposition of great arteries, single ventricles) Surgically corrected pulmonaiy-systemic shunts or conduits

Moderate-risk patients Congenital cardiac conditions not listed above or below Acquired valvular dysfunction (eg, RHD) Mitral valve prolapse with régurgitation or leaflet thickening Hypertrophie cardiomyopathy (eg, ideopathic hypertrophie subaortic stenosis IIHSSI)

Low-Znegligible-risk patients ' History of previous rheumatic fever Wft/ioi/f present valvulai dysfunction Physiologic, functional, or "innocent" cardiac murmurs Implanted cardiac pacemakers or defibrillators Mitral valve prolapse without régurgitation Previous ccronafy artery bypass graft surgery History of Kawasaki disease without valvular dysfunction Isolated secundum atrial septal defect Surgical repair of atrial or ventricular seplal defect more ttian 6 montfis ago, or patent duclus arteriosus (without sequelae!

BasetJ on information conlairied in American Heait Association. Prevention ot Bacterial Endocarditis (üookiet «71-0117). 1997 •These patients generally do not require antibiolic p'ophylanis for dental procedures.

TABLE 3 Classification of dental procedures at risk of causing bacterial endocarditis

Prophylaxis recommended" Prophylavis not recommended'

Dental extractions Operative or prosthetic procedures Dental impianl placement including with retraction coro) Most periodontal procedures (including Local anesthesia injections surgery, scaling, root planing, probing. (except intraligamental) recall, subgingival antibiotic tiber Endodontic or postplacement placement, etc! within tfie canal Reimplantation ot avulsed teeth Rubber dam placement Endodontic surgery or instrumentation Postoperative suture removals beyond apex Oral impression taking Orthodontic banding (not bracket placement! Use of rntraorai radiograph appliances Intrahgamental local anesthesia injections Insertion of prostfietic or Prophylaxis of teeth or implants where bieeding orthodontic appliances IS anticipated Orthodontic adiustments Fluoride treatment 5heddjng primary teeth

Based an intormation contained in American Heari Association Prevention of Bacterial Endocarditis lOcoklet «71-0117) 1997 'For higii- ana moderate-risk patients onlv. 'Clinical ludgment mav dictate antibiotic use if j nanti cipa ted, significart bleeding results

822 Quintessence International Volume 28, Number 12, 199? patients should be kept at least 9 to 14 days apart. Fleming et al (Oral Surg Oral Med Oral Pathol, 1990) recommend that after three consecutive appointments (with at least 1 week between visits) a change in antibiotic is indicated, to mini- mize the risk for development of resistant bacterial strains. Low-risk patients, especially those undergoing low-risk procedures, generally do not require prophylactic coverage, but the clinical ludgment of the treating dentist must prevail For example, if greater-than-usual gingival bleeding is antici- pated for a restorative procedure, antibiotic coverage might be instituted despite the general recommendation for no coverage. If unexpected bleeding is encoun- tered, modifying the doctor's initial assessment that prophylactic antibiotic cover- age was not indicated, antibiotic coverage can be implemented at that time. Although the coverage will be too late to prevent viable baeteremia (which rarely persists for more than 15 minutes during most procedures), it will create a less favorable environment for bacterial growth on internal cardiac surfaces. "... there is In summary, the incidence of bactenal endocarditis has not subsided over the past 4 decades and may even be increasing due to the growing number of elder- insufficient scientific ly patients and intravenous drug abusers. It is imperative that every dental clini- cian understand the recommendations (and limitations) of the American Heart evidence to support Association and be familiar with the periodic changes in protocols These changes evolve from the ongoing, dynamic process of learning about the causes routine antibiotic and pathophysiology of bacterial endocarditis. The alternative is for our profession to collectively live with the knowledge that patients' lives were lost unnecessarily prophylaxis for because some dentists and dental hygienists drd not properly exercise their pro- fessional duty to understand the diseases, the risks, and the pharmacology of the patients with chemical weapons of prevention.

prosthetic joints Antibiotic Prophylaxis for Patients With Artificial Joints who are receiving and Other Orthopedic Appliances Artificial hip and knee replacements have been in common use m orthopedic dental care." surgery for more than 2 decades In the united States, it is estimated that artifi- cial ]oints are placed m nearly one half million patients annually, including American Academy 115,000 patients who receive artificial knees each year. Countless tens of thou- of Orai P^edicine sands of other patients receive penile and digital implants, intraocular lenses, breast implants, and shunts, as well as orthopedic rods, plates, and screws for trauma-related iniunes. Management cf post orthopedic surgery patients during dental treatment has long been a topic of controversy and "mythology," and management protocols fiave largely been driven by anecdotal case rationalizations, medicolegal con- cerns, and suppositions unsupported in the scientific literature. The rationales that have prevailed in medicine and dentistry were typified m a 1985 survey that 9 revealed that 57.3% of the orthopedic surgeons either did not believe there was a clear relationship established between transient dental bacteremias and late prosthetic joint infections or they believed that the relationship was insignif- icant (Jaspers MT and Little JW, J Am Dent Assoc, 1985). Nevertheless, 93% of the respondents felt prophylactic antibiotics were necessary prior to dental treatment, and 70% identified a cephalosporin as their drug of choice. Yet another survey in 1994 revealed that 93% of orthopedic surgeons and 75% of dentists believed that dental bacteremias are a significant risk to joint prostheses (despite the lack of published scientific evidenoe), and 92% of the former believed the patient required pre-dental treatment prophylactic antibi- otics for the rest of their lives (Shrout MK et al, J Am Dent Assoc, 1994). The preferred antibiotic for 71 % of these orthopedic surgeons was a cephalosporin, whereas 61 % of dentists surveyed preferred amoxicillin or other penicillin vari- ants that are known to be more efficacious against the common oral flora. These unfounded biases confused the issue greatly because artificial joints attain a nearly avascular status over time, precluding a hematogenous spread of bacteria from the oral cavity. Most (more than 60%) orthopedic |oint infections are known to be caused by Staphylococcus organisms, which are not generally found in the oral flora common to dental bacteremias. There is a paucity of actu-

Quintessence International Volume 28, Number 12, 1997 823 al documented cases in the literature of late prosthetic joint infections sec- TABLE 4 ADA/AAOS- re CO m mended antibiotic ondary to dental treatment and almost no valid research data conclusively sub- regimens stantiating a cause-effect relationship. Nevertheless, confusion and concern prevailed in many dental practices Standard adult regimens regarding the need for antibiotic prophylaxis in this patient population prior tc (no ¡ollow-up dosel dental treatment. Despite the risks for development of resistant strains, and Ceolialexin. 2 g orally, 1 h preop side effects and allergic reactions from antibiotic overuse, thousands of patients (or) Cephradme, 2 g oolly. t h preop were unnecessarily placed on antibiotic regimens during their dental treatment lor) Amoxicillin, 2 g orally, 1 h preop over the years. Alternate' standard regimen In t987, the American Academy of Oral Medicme published an opinion state- Clmdamycin, 600 nig orally, t h preop ment, which read, in part, "... there is insufficient scientific evidence to support routine antibiotic prophylaxis for patients with prosthetic joints who are receiv- Paren teral regimens' ing dental care. Therefore, it appears that a blanket recommendation for antibi- Cefazolin, 1 g IM or IV, 1 h preop (or) Ampicillin, 2 g llvt or IV, 1 h preop otic coverage would be inappropriate at this time" lEskinazi D and Rathbun W, tor) Clindamvcin,' 600 mg IV, 1 h preop Oral Surg Oral Med Oral Pathol, 1987). In 1990, the American Dental Associa-

BaseO or inlo'nistion conlainefl in J Am Dent tion released a position paper that stated "there is no scientific evidence that Assoc 1997,1ZB.1004-100B prophylactic antibiotics actually prevent late prosthetic ¡oint infections ... from IM = inlrarnuscularlv. IV = inlravenojslv. transient bacteremias caused by dental treatment" (Council on Dental Thera- "Alternate rEgimen is tor patients allergic to penicillins and cephalosporins (which includeE peutics, J Am Dent Assoc, 1990) The statement went on to emphasize that the amoïicillin and ampicillinl. decision should be made by the dentist, in consultation with the patient's physi- 'Parenteral regimens are for paiienis who cian or orthopedic surgeon. This was followed by a 1992 statement of the cannot take oiäl medications British Society for Antimicrobial Chemotherapy that paralleled these viewpoints and emphasized that exposure of patients to the risks of adverse drug reac- tions, when there is no evidence that such prophylaxis is of any benefit, is unac- ceptable (Simmons NA et al. Lancet, 1992). Confusion continued in both medicine and dentistry until release of a icint advisory statement by the American Academy of Orthopedic Surgeons (AAOSI and the American Dental Association (ADA) in 1997 (J Am Dent Assoc). This report culminated a comprehensive evaluation of available data and was formal- ly adopted by both organizations. Key points that were emphasized in the report include the following:

• The most critical period for bacteremias occurs within 2 years after joint placement. • There is no evidence to support prevention of hematogenous infections in patients with total loint prostheses through antibiotic prophylaxis. • There is no comparison between late prosthetic lOint infections and infective endocarditis because the anatomy, blood supply, microorganisms, and mecha- nisms of infection are entirely different. • Only high-risk patients should receive prophylactic antibiotic coverage, which, after the second year of joint placement, includes only patients who are immunocompromised or immunosuppressed, patients who have type 1 (juve- nile, insulin-dependent [IDDM]) diabetes mellitus, patients who have had prior prosthetic joint infections, hemophiliacs, and malnourished patients • Only procedures with a high incidence of bacteremia probability should be cov- ered, which generally only includes dental extractions, penodontal procedures, dental implant placement, reimplantation of avulsed teeth, endodontic surgery or instrumentation beyond the root apex, intraligamental local anesthesia iniec- tions, and dental prophylactic cleaning where bleeding is anticipated. • Antibiotic prophylaxis is not indicated for patients with orthopedic rods, plates, screws, or pins used for fracture management • Patients who have received total joint arthroplasty should practice effective oral hygiene and maintain optimal gingival health. •The suggested antibiotics for patients requiring coverage is cephalexm, cephradine, or amoNicillin. Patients who are unable to take oral medications should be given cefaxolin or ampicillin parenterally. Patients who are allergic to penicillin can be given clindamycin. The full set of recommendations is sum- marized in Table 4.

The ADA/AAOS ¡oint statement emphasizes that the responsibility for proper

824 Quintessence International Volume 28, Number 12,1997 clinieal judgment and management decisions clearly falls to the dentist, and the dentist must include tfie patient in the informed consent process by making the patient aware of the treatment options. If, m the dentist's judgment, improper recommendations have been received from a physician who is unfamiliar with the guidelines, the dentist should proceed without antibiotic prophylaxis. When- ever antibiotic prophylaxis is utilized, the perceived benefits must be weighed against the known risks, including occurrence of allergic reactions, excessive treatment costs, and development of microbial resistance. The dentist who blindly follows a physician's erroneous recommendation will not be able to defend those actions if harm befalls the patient from improper prescribing of antibiotics. Little et al have summarized the findings for patients with other implanted devices who undergo dental treatment (Dental Management of the Medically Compromised Patient, Mosby, 1997) There is no clear rationale for the use of antibiotic prophylaxis in dental patients who have received artificial finger joints, penile or breast implants, and the like If antibiotics are used, the use should be accompanied by thorough documentation m the patient's records on the ratio- nale for such usage. In summary, two quotations from the past seem appropriate. John Taylor (1694-1761) was quoted saying, "A doctor is a man who writes prescriptions until the patient either dies or is cured by nature," Voltaire 11694-1778) once remarked, "Doctors ... prescnbe medicine of which they know little to cure dis- eases of which they know less, in human beings of which they know nothing." In the intervening 220 years, some things have not changed. The use of prophy- lactic antibiotics should not be predicated on ignorance or fear of litigation but on sound scientific principles and a working knowledge of pharmacotherapeutics. The time has arrived for dentists to shed the cloud of uncertainty and doubt and to restrict the use of prophylactic antibiotics only to those defined patients who clearly have a benefit potential that outweighs the risk factors. Recent additions to the literature from organized groups have provided the tools necessary to achieve those goals, but these tools are of value only if used by practitioners.

PERIODONTIC Antibiotics are employed in penodontal therapy in one of three situations: (1) the management of acute periodontal conditions, primarily periodontal abscesses INDICATIONS usually in conjunction with incision and drainage, (21 as "prophylaxis" to "pre- vent" posttreatment infectious sequeilae, and 13) as definitive or adjunctive thera- THOMAS J. PALLASCH, DDS, MS py in the management of chronic periodontitis. The treatment protocol for acute periodontal conditions is well established, little if any data support the use of antibiotics to prevent dental treatment sequeilae (other than endocarditis), and the use of antimicrobials to manage chrome periodontitis is both controversial and misunderstood. Acute periodontal conditions (abscesses, necrotizing gingivitis) do not differ substantially from other acute orofacial infections, and their antibiotic manage- ment IS similar: high antibiotic blood levels for as short a period of time as possi- ble (until remission of infection), which will reduce the possibility of microbial resistance development. The usual package insert doses are adequate with the exception that a loading dose (2 to 4 times the maintenance dose depending on the severity of the infection) should be employed to achieve high blood levels rapidly because acute orofacial infections tend to have a very rapid onset. Without a loading dose, it may take 6 to 12 hours to achieve therapeutic tissue levels with many antibiotics. Amoxicillin is exceptional because an oral dose is very rapidly and completely absorbed, achieving blood levels 2 to 3 times greater than a com- parable dose of penicillin V. When indicated, amoxicitlin then becomes a drug of choice, utilizing an appropriate loading dose for acute infections. The use of antibiotics as prophylaxis to prevent infectious sequeilae to routine dental treatment procedures is unfortunately still advocated in some quarters

Quintessence International Volume 28, Number 12, 1997 825