• 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 semiambulaloryfacilities for the elderly and dental operatories.

• Report any emergence of antibiotic-resistant bacteria worldwide to a publichealth facilitv such as tfie CDC in the United States so that the natural historyof 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 toovercome drug resistance.

We in the dental profession must continue our scientific education as itrelates to health promotion, disease prevention, diagnostics, and therapeuticsWe are living at a time in human history that accommodates emerging and re-emerging infectious diseases. We must continue to follow universal precautionsand infection control recommendations (ADA Council on Scientific Affairs, Coun-cil on Dental Practice, J Am Dent Assoc, 1996) with our patients, and to obtainapproved vaccinations tor our heaith care personnel. We must prevent antibioticabuse 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 PRINCIPLESOF ANTIBIOTIC THERAPYAND PROPHYLAXIS

ROGER E. ALEXANDER, DDS

Basic Principles of Appropriate Antibiotic Usage

In 1996, physicians and dentists wrote more than 2.4 billion prescriptions, anincrease of 4% over the preceding year (Buckley B, Pharm Times, 1997¡, Althoughit is not known what percentage of these prescriptions were for antibiotics, six ofthe top 30 prescribed drugs were antibiotics, including the second most pre-scribed drug of the year, a brand of amoxicillin Among generic drug prescriptionswritten in 1995, antibiotics compnsed 50% of the top 10 drugs prescnbed tfiatyear. These data reflect the extensive role that antimicrobial drugs piay clinically inboth medicine and dentistry, often for inappropriate prophylaxis or for localized,self-limiting, minor infections This inappropriate use of antibiotics has an indirectimpact on infection management because organisms are no longer susceptible tomany of our chemical weapons. Antibiotic resistance is becoming a growing con-cern worldwide, and scattered strains of bacteria that are resistant to even/ drug inthe arsenal are appearing. Currently there are no new antibiotics with substantiallydifferent 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 pharmacotherapeuticsand the function of the human immune system by physicians and dentists. Antibi-otics, by themselves, do not cure or prevent disease. Antibiotics are nothing morethan'weapons to be used to enhance the performance of the "soldiers" of theimmune system By themselves, antibiotics are only part of the necessaryresponse, and without an intact and participating immune system an antibiotic willeventually fail. This has been underscored by patients with acquired immune defi-ciency syndrome, who frequently expire from opportunistic infections despiteintensive pharmacologie therapy. Prior to the antibiotic era, patients were treatedwith nothing more than removal of the infection source, drainage of pus, and thenatural immune system.

Quintessence International Voiume 28. Number 12, 1997 815

Or Alexander is Associate Professor and Direc-tor tor Urdergraduale Sjrgical Euucatmr forthe Depar lmer t of Oral and Maxi l lofacia lSurgery and Pharmacology, Tenas A&ti/I Univsr-sity System—Baylor College of Dentistry in Dal-las, Tesas.

Acknowledgment. The author wishes to thankTommy W Gage, RPh, DDS, PhD, Professor andDireclor of the Ptiarniacology Division, Oepan-ment of Oial and Maxil lofacial Surgery andPiiarmacclogy, Tenas ASM tlniversity System—Baylor College of Dentistry for his will irgress tosfiare his experience, insight, and knowledgeduring the prepaiatior otthis article.

As many as 264 morphologically and biociiemically distinct bacterial groupscolonize the oral cavity, including aerobic, facultative, and obligate anaerobic,gram-positive, and gram-negative organisms. These microorganisms supporteach other in a synergistic fashion. During an infection, individual members ofthe microbe community (!} produce metabolites that facilitate growth of othermicrobes; (2) create an increasingly acidic tissue pH that facilitates enhancedgrowth of certain microbes; and 13) consume oxygen, which allows growth ofone or more opportunistic anaerobes (Moenning JE et al, J Oral Ma illofac Surg,1989). As a result of this symbiotic environment among oral organisms, mostodontogenic infections ultimately involve five to seven ditferent microorganisms.Anaerobic organisms usually dominate, outnumbering aerobes by a ratio ot atleast 2 1 (Moenning JE et al, J Oral Maxillofac Surg, 1989). It is increasingly com-mon for infections to demonstrate growths of Peptacocci, Peptostreptococci,fusobacterium. and Bacteroides species. H isn't necessary for an antibiotic to beeffective against all bacterial strains involved in an infection Elimination of selectstrains may alter local tissue conditions sufficiently so that the immune system,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 thepatients cannot be separated, in preparing to examine appropriate antibiotic usein dentistry it is valuable to review some of the basic axioms of clinical infectionmanagement:

• Pus follows the paths of least resistance: usually along fascial planes andthrough 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 thelocation of pus relative to certain masticatory and facial muscle attachments.

• Pus must be drained and the source of the infection controlled as soon aspossible. 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 ofcausative organisms (Flynn TR, J Oral Maxillofac Surg, 19931. Drainage isusually accompanied by profuse irrigation ("the solution to pollution isdilution").

• The most optimal drainage can often be through an alveolar socket (followingextraction 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 cannotwait for 24 to 72 hours for therapeutic impact, then parenteral routes arepreferable.

" Intrabony infections may not be radiographically evident until one or both bonycortices are involved.

• Failure to use the thermometer is one of the most common mistakes made inclinical evaluation of infection It provides valuable information on how thebody IS dealing with the infectious process The aggressiveness of clinicaltreatment is influenced significantly by the degree of elevation of a patient'stemperature.

• The risk of antibiotic administration should be justified by the need and an-ticipated benefit. All doctors should carefully evaluate the potential for adversereactions, side effects, and interactions before prescribing antibiotics.

• Although interference with birth control medication has not been conclusivelyproven, legal defense of a practitioner is very difficult if a female patientbecomes serendrpitously pregnant during therapeutic administration of anantibiotic. It is therefore prudent for a practitioner to warn such patients totake additional precautions lor abstain) during and after antibiotic administra-tion and document the warning in the patient record.

816 Quintessence international Volume 28, Number 12 1997

Much ofthe abuseof antibiotics occurswhen they are used

for prophylaxis.

The infectious process is confusing to many practitioners. Infection is noth-ing more than invasion and multiplication of microorganisms in the body. Thisresults in celluiar injury, which induces infiammatory and immunoiogic respons-es. Initiaiiy, the local inflammatory process responds to the invaders. Once theinfection breaks out of its localized confines, cellulitis follows, characterized bya diffuse, unlimited, purulent extension of the infiammatory process throughadjacent, deeper tissues. As cellular and biochemical debris, killed bacteria, andliquified dead cells accumulate, they are walled off and confined, becoming puscontained in one or more abscess spaces. This accumulation of waste prod-ucts of the "war within" must be removed or the inflammatory process willcontinue

Common abuses. Much of the abuse of antibiotics occurs when they areused 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 therisk of administenng the antibiotic.

"The most appropriate antibiotic for the anticipated fiora involved should beused.

• The antibiotic shouid be administered in doses sufficient to attain high bioodieveis, for as short a period of time as possible Administration must begin im-mediateiy prior to the procedure, to minimize the development of resistantstrains. 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 areaimost never mixed (because one may interfere with the actions of the other),

• A narrow-spectrum antibiotic that is generally effective against oral flora ispreferred if information from a culture and sensitivity study is unavailable andempiric 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 weresusceptible to bela-lactam antibiotics af one time are now resistant, but therate of this transformation is not yet known.

• When two or more antibiotics are prescribed simultaneously, each shouid beprescribed as if it were the only one being prescribed Dosages should not bereduced in anticipation of synergism, etc,

" Patients who have compromised or impaired immune systems may requiremore aggressive and proionged antibiotic protocois than patients with intactimmune systems.

• Close follow-up of patients with infection is essentiai Patients who are initiallytreated for odontogenic infections should be examined and/or called at leastevery 24 hours until it is assured that the infection is coming under controland no longer a threat to the patient. Additionally, doctors must be accessibleto patients 24 hours a day, in the event the patient needs to notify the doctorof adverse changes in signs or symptoms, such as dramatic increases in tem-perature, swelling, or difficulty swallowing. It is inappropriate for a patient withan acute infection to be told to return in "a week or so" because any infectionhas the capacity to endanger life in 24 hours or less through contiguousspread or airway encroachment,

• Difficult chronic and subacute infections, such as osteomyelitis, should bereferred to an oral and maxillofacial surgeon upon diagnosis Managementgenerally involves surgical and therapeutic interventions that are beyond thecapability of most general practitioners to provide.

Quintessence International Volume 28, Number 12, 1997 817

If judgment suggestsan infection is best

controlled bypenicillin,then

theoretic concernfor potential

side effects andreactions should not

preclude itsclinical use.

Which antibiotic? When a patient presents to the general dentist with aninfection, a detailed workup should be accomplished and include (V review of themedical and dental history, Í2I thorough physical examination (which must includeexamination of the airway and oropharynx to verify lack of encroachment on tfieairway, a primary concern in serious infections), 131 record of the oral temperature,¡4) appropriate radiographs, and (5) evaluation of the extent of fascial spacesinvolvement. Based on the various factors, generally an empiric initial choice ismade, seiecting the antibiotic(s) that experience has shown to be effective againstmost 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 thepatient 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 soonas possible. If the pus fias spread more extensivelv throughout the spaces, an oraland maxillofacial surgeon should be consulted as soon as possible.

Only oral forms of antibiotics will be discussed here because very few generaldental offices are equipped to administer parenteral (intravenous and intramuscu-lar) antibiotics. The vast maiority of dentists deal with infections using oral formsof the antibiotics.

Incipient and minor to moderate infections (oral temperature < 1OO''F±) Amember of the penicillin family is still the initial drug of choice in a nonallergic pa-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 higherblood levels, and has an extended half life If significant improvement is not notedin 24 to 48 hours, the empirical addition of metronidazole is considered reasonablebecause nonsusceptible, ß-lactamase-emittmg, gram-negative strains may be par-ticipating in the infection Metronidazoie, on the other hand, is highly effectiveagainst gram-negative organisms, complementing the actions of the penicillin.

Many clinicians are concerned about the potential for allergic reactions withpenicillin usage. While this is always a potential with any drug usage, it should beremembered that only a small percentage of patients will react (variousiy reportedas 3% to 6% with oral use), and the reaction to oral administration is usually in theform of a rash or dermal erythema and is rarely life-endangering. If ludgment sug-gests an infection is best controlled by penicillin, then theoretic concern for poten-tial side effects and reactions should not preclude its clinical use.

Some articles have suggested substituting clindamycin for penicillin if the lat-ter is not therapeutically successful. Tfiere is disagreement in the literature onthis course of action, however. Clindamycin has an excellent clinical track recordin orofacial infections, is ß-lactamase-resistant, and performs as weii as penicillinIFIynn 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 andanaerobic activity, including against Bacteroides tragiiis (Moenning JE et al, JOral Maxillofae Surg, 1989) Some authors feel clindamycin should be reservedfor more severe infections because it reportedly has a higher nsk profile. Othersfeel the risks of clindamycin administration (for example, antibiotic-associated,pseudomembranous colitis lAAPCI due to Clostridium difficile overgrowth) aieoverstated and clindamycin should be a prominent part of our oral arsenalPerusal of the literature shows that the vast majority of patients who experienceAAPC are eideriy, femaie, hospitalized, on high doses of the drug, and have hadabdominal surgery or abdominal complaints Since most dental patients do notfall 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 hadreports 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 manageappropriately

Another antimicrobial alternative for moderate odontogenic infections innon-pen ICI Ilin-allergic patients is ampiciilin combined with a (3-lactamase inhibitor.

818 Quintessence Internationai Volume 28, Number 12,199?

A Dictionaryof Confusing Definitions

inflammation:A localized, protective reaction intissues following injury or irritation,which serves to wall off, dilute, anddestroy the miurious agent orinjured tissue. Eollowed by aprocess of repair and healing In theacute form, it is characterized bypain, heat, swelling, redness, andloss of function.

Infection:Invasion and multiplication of micro-organisms in the body, resulting mlocal cellular injury, which inducesinflammatory and immunologie re-actions. (You can have inflammationwitbout infection, but not usuallyvice versa).

Cellutitis:A diffuse, unlimited, purulent ex-tension of the inflammatory processthrough deeper contiguous tissues,not circumscribed or confined toone anatomic area.

Abscess:A localized, confined collection ofpus within a space created in thetissues; usually accompanied byinflammation.

Pus.Liquified dead cells, debris, bacteria,tissue enzymes, etc. ¡If pus breaksout of its confined space, it resultsin eel lu litis.)

such as sulbactam (Augmentin, SmithKline Beecham).Severe odontogenic infections (oral temperature > 100°F±, spreading cetlulitis,

and systemic symptoms). The initial empiric antibiotic of choice is clmdamycin mthis author's opinion. Using clindamycin for early or less severe infections is alsoappropriate if the patient is allergic to pencillin or when the patient has notresponded to surgical intervention and initial penicillin therapy (Moenning JE et al,JOral Ma>;illofac Surg, 1989; Gilmore WC et al, J Oral Maxillofac Surg, 1988).

Although used for many years for routine prophylactic uses, the erythromycmsoften perform poorly m infection therapy. Higher doses are required for the drug tobecome bactericidal, and those higher doses induce nausea and vomiting in manypatients, For that reason, they are rarely used as empiric therapeutic drugs forodontogenic infections Some newer, long-acting forms of erythromycin (clar-itbromycin, azithromycin, and diritbromycin) have shown some therapeuticpromise, but there are too few clinical data to recommend widespread usage atthis time.

First generation cephalosporins are less ideal as initial antibiotics because theyhave a wider spectrum of action and are not as effective as penicillin or clm-damycin against some of the more common gram-positive and anaerobic strains(Gill Y and Scully C, Oral Surg Oral Med Oral Pathol, 1990) They are also suscepti-ble to ß-lactamase, like penicillin, so there is generally very little therapeutic advan-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 anycephalosponn Second and third generation cephalosporins are not indicated as ini-tial empiric choices Their use is predicated on the results of sensitivity testing.

Tetracyclines are bacteriostalic drugs, and there are significant numbers ofresistant strains of oral bacteria already noted (Moenning JE et al, J Oral MaxillofacSurg, 1989). They are noi indicated for use in any significant odontogenic infection.Even in penodontics, where tetracyclines are used extensively for localized peri-odontal infections, many authors feel tbe benefit is not well substantiated m thescientific literature.

Fluoroquinalones (eg, ciprofloxacin) are inappropriate for use in oral infectionsbecause they have poor actions against oral streptococci and most anaerobes(Frieden TR and Mangi RJ, JAMA, 1990). This group of anti-microbials has beenlabeled by some experts as the most abused antibiotic group m clinical medicalpractice, and resistant strains have developed rapidly.

Antibiotic Prophylaxis for Patients Susceptibleto Bacterial Endocarditis

The use of prophylactic antibiotics to "prevent" bacterial endocarditis (formerlyknown as subacute bacterial endocarditis] following dental treatment has resultedin confusion, noncompliance, misunderstandings, and even ignorance in bothmedicine and dentistry for more than 40 years. Even though the American HeartAssociation (AHA) first released recommendations for prophylactic coverage ofsuch patients in the early 1950s and several subsequent modifications to theserecommendations (not guidelines) have received extensive coverage in theprofessional literature and continuing education venues, there still remains a virtualmountain 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 propertiming of the regimens, and only one of five knew the proper antibiotic regimenfor a 40-pound pédiatrie patient In a history-based, telephone survey published in1984, less than half of the dentists followed the recommendations of the AHAand only 11% recognized the need to use antibiotic prophylaxis with patientswith congenital heart diseases. One third of the respondents incorrectlyanswered questions regarding management of patients with prosthetic heartvalves. In another published survey of physicians and dentists, physiciansdemonstrated 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

Only the high- andmedium-risk patients

require antibioticprophylaxis and onlyforthose procedures

identified as high-risk procedures.

19891, Overall, only 27% of physicians and 39% of dentists demonstrated ade-quate knowledge for managing all types of "at risk" patients. The author believesthat this trend continues even today.

Since 1923, it has been known that multiple bacteremias occur every day inpatients with periodontal disease and poor oral hygiene and are known to occurduring 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 theheart. However, in patients who have sustained damage to the cardiac vafves,such as damage secondary to rheumatic heart disease, or in patients who haveother 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, witfiour increasingly aged patient population there has been an upsurge of endocardi-tis cases in the elderly, due to atherosclerotic and degenerative changes in theircardiac structures. Significant numbers of cases are also being seen in intra-venous drug abusers.

In a compromised heart, a chain of events can be triggered that renders theaffected area(s) susceptible to future bacteremias:

• The altered architecture results m local eddying or jet effects (for exarnple,blood jetting through a defective valve leaflet) during cardiac compression.

• The delicate endothelium is stripped off or damaged in the areals) of alteredflow, exposing underlying collagen.

• These altered surfaces encourage adhesion of platelets and fibrin, creating asterile thrombus,

• If the thrombus is exposed to a bacteremia. bacteria can become lodged m thethrombus, colonizing and infecting it.

• 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 as10% (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 isforever susceptible to bacterial endocarditis from bacteremias from any source,including dental treatment

Acute rheumatic fever |RF¡ results from an immunologie response to GrcupA, ß-hemolytic streptococcal throat infection, but the exact nature of thisresponse continues to evade researchers. More recent studies have shown thatcertain bacterial strains vary in their ability to cause endocarditis and plateletaggregation 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 isendemic in many developing countries. The incidence of RHD originating as ssequelae to RF is unknown, but that relationship has led many dentists toassume that any patient with a history of RF must be endocarditis-susceptibleand therefore requires antibiotic prophylaxis In fact, that is not true m the UnitedStates, where an advanced state of medical treatment availability allows mostcases 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 iieartdisease 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 torequire 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, bulmedical consultation is often needed to diagnose these situations. Likewise, orîlVpatients with conditions that present clinical evidence of cardiac damage bywayof 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

Standard regimen 'Amoxicilhn

Alternate standard regimensClindamycmCepfialexin' or Celadroxil 'Azithromycin/Clarithromycin

Parenteral regimenAmpicillin

Alwrnate parenreral regimenClindamycm

Cefazolin

Basefl on information contained in Ame(booklet ll7t-0117V 1997IM = intramuscularly. IV ^ intravenously

Adults and children> 60 Ib 127 kg)

2 g orally, 1 h preop¡no follow-up dosel

600 mg orally, 1 h preop2 g orally, 1 h preop500 mg orally, 1 fi preop

2 g IM or IV, less tfian30 min preop

600 mg IM or IV, less than30 mm preop

1 g IM or IV, less tfian30 mm preop

Children< 60 Ib (27 kg}

50 mg/kg, 1 h preop(not to exceed adultdose}

20 mg/kg, 1 h oreop50 mg/kg, 1 h preop15 mg/kg, 1 h preop

50 mg/kg, less than3D mm preop

20 mg/kg, less than30 mm preop

25 mg/kg, less than30 min preoD

can Heart Association Prevention of Bacterial Endocarditis

Alternate regimens are for patients allergic to penicillins, incluOing amoxiciParenteral regimens are for patients who are unable to take oral medtcatio"In Ihe event of unanticipated tileeding.Sure and still he effective.

antibiotics can be administered w

'Cephalexin or CefadiozM mav cause reactions m penicrflin-ailergic patiartsimmjnoglobiilin E-mediated reactions.

in and ampicillinshin 2 hours of the proce-

who give liistory ol

endocarditis development, in the absence of régurgitation, the risk is very low.Overall, the incidence of infective endocarditis is extremely low in the UnitedStates, estimated to be between 11 and 50 cases per million population per year.

Over the years, erroneous advisories have been provided to dentists by generalpractice physicians and paraprofessionals who did not have a clear understandingof 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 inpatients 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 fromthe 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 fromInterpolation 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 coverageor who had no known prior risk. Many authors dispute whether antibiotic prophyl-axis IS indicated at all, without more substantial evidence of its benefits (UyemuraMC, 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 healthof susceptible patients be optimal. In the presence of chronic infection, food de-bris, and plaque around the dentition, everyday experiences of mastication and oralhygiene 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 paventsCardiac prosthetic valvels) (mcludmg bioprosthetic and homograft valves!Hislory of D'evious bacterial endocarditis ISBEI infection(slComplex cyanotic congenital heait disease (eg. Tetralogy of Fallot, transposition of

great arteries, single ventricles)Surgically corrected pulmonaiy-systemic shunts or conduits

Moderate-risk patientsCongenital cardiac conditions not listed above or belowAcquired valvular dysfunction (eg, RHD)Mitral valve prolapse with régurgitation or leaflet thickeningHypertrophie cardiomyopathy (eg, ideopathic hypertrophie subaortic stenosis IIHSSI)

Low-Znegligible-risk patients 'History of previous rheumatic fever Wft/ioi/f present valvulai dysfunctionPhysiologic, functional, or "innocent" cardiac murmursImplanted cardiac pacemakers or defibrillatorsMitral valve prolapse without régurgitationPrevious ccronafy artery bypass graft surgeryHistory of Kawasaki disease without valvular dysfunctionIsolated secundum atrial septal defectSurgical 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 bacterialendocarditis

Prophylaxis recommended"

Dental extractionsDental impianl placementMost periodontal procedures (including

surgery, scaling, root planing, probing.recall, subgingival antibiotic tiberplacement, etc!

Reimplantation ot avulsed teethEndodontic surgery or instrumentation

beyond apexOrthodontic banding (not bracket placement!

Intrahgamental local anesthesia injectionsProphylaxis of teeth or implants where bieeding

IS anticipated

Prophylavis not recommended'

Operative or prosthetic proceduresincluding with retraction coro)

Local anesthesia injections(except intraligamental)

Endodontic or postplacementwithin tfie canal

Rubber dam placementPostoperative suture removalsOral impression takingUse of rntraorai radiograph

appliancesInsertion of prostfietic or

orthodontic appliancesOrthodontic adiustmentsFluoride treatment5heddjng primary teeth

Based an intormation contained in American Heari Association Prevention of Bacterial EndocarditislOcoklet «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?

"... there isinsufficient scientificevidence to support

routine antibioticprophylaxis forpatients with

prosthetic jointswho are receiving

dental care."American Academy

of Orai P^edicine

9

patients should be kept at least 9 to 14 days apart. Fleming et al (Oral Surg OralMed 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, generallydo not require prophylactic coverage, but the clinical ludgment of the treatingdentist must prevail For example, if greater-than-usual gingival bleeding is antici-pated for a restorative procedure, antibiotic coverage might be instituted despitethe 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 rarelypersists for more than 15 minutes during most procedures), it will create a lessfavorable environment for bacterial growth on internal cardiac surfaces.

In summary, the incidence of bactenal endocarditis has not subsided over thepast 4 decades and may even be increasing due to the growing number of elder-ly patients and intravenous drug abusers. It is imperative that every dental clini-cian understand the recommendations (and limitations) of the American HeartAssociation and be familiar with the periodic changes in protocols Thesechanges evolve from the ongoing, dynamic process of learning about the causesand pathophysiology of bacterial endocarditis. The alternative is for our professionto collectively live with the knowledge that patients' lives were lost unnecessarilybecause some dentists and dental hygienists drd not properly exercise their pro-fessional duty to understand the diseases, the risks, and the pharmacology of thechemical weapons of prevention.

Antibiotic Prophylaxis for Patients With Artificial Jointsand Other Orthopedic Appliances

Artificial hip and knee replacements have been in common use m orthopedicsurgery 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, including115,000 patients who receive artificial knees each year. Countless tens of thou-sands of other patients receive penile and digital implants, intraocular lenses,breast implants, and shunts, as well as orthopedic rods, plates, and screws fortrauma-related iniunes.

Management cf post orthopedic surgery patients during dental treatment haslong been a topic of controversy and "mythology," and management protocolsfiave largely been driven by anecdotal case rationalizations, medicolegal con-cerns, and suppositions unsupported in the scientific literature. The rationalesthat have prevailed in medicine and dentistry were typified m a 1985 survey thatrevealed that 57.3% of the orthopedic surgeons either did not believe therewas a clear relationship established between transient dental bacteremias andlate 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 dentaltreatment, and 70% identified a cephalosporin as their drug of choice.

Yet another survey in 1994 revealed that 93% of orthopedic surgeons and75% of dentists believed that dental bacteremias are a significant risk to jointprostheses (despite the lack of published scientific evidenoe), and 92% of theformer 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). Thepreferred 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 jointsattain a nearly avascular status over time, precluding a hematogenous spread ofbacteria from the oral cavity. Most (more than 60%) orthopedic |oint infectionsare known to be caused by Staphylococcus organisms, which are not generallyfound in the oral flora common to dental bacteremias. There is a paucity of actu-

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TABLE 4 ADA/AAOS-re CO m mended antibioticregimens

Standard adult regimens(no ¡ollow-up dosel

Ceolialexin. 2 g orally, 1 h preop(or) Cephradme, 2 g oolly. t h preoplor) Amoxicillin, 2 g orally, 1 h preop

Alternate' standard regimenClmdamycin, 600 nig orally, t h preop

Paren teral regimens'Cefazolin, 1 g IM or IV, 1 h preop(or) Ampicillin, 2 g llvt or IV, 1 h preoptor) Clindamvcin,' 600 mg IV, 1 h preop

BaseO or inlo'nistion conlainefl in J Am DentAssoc 1997,1ZB.1004-100BIM = inlrarnuscularlv. IV = inlravenojslv."Alternate rEgimen is tor patients allergic topenicillins and cephalosporins (which includeEamoïicillin and ampicillinl.'Parenteral regimens are for paiienis whocannot take oiäl medications

al documented cases in the literature of late prosthetic joint infections sec-ondary to dental treatment and almost no valid research data conclusively sub-stantiating a cause-effect relationship.

Nevertheless, confusion and concern prevailed in many dental practicesregarding the need for antibiotic prophylaxis in this patient population prior tcdental treatment. Despite the risks for development of resistant strains, andside effects and allergic reactions from antibiotic overuse, thousands of patientswere unnecessarily placed on antibiotic regimens during their dental treatmentover the years.

In t987, the American Academy of Oral Medicme published an opinion state-ment, which read, in part, "... there is insufficient scientific evidence to supportroutine antibiotic prophylaxis for patients with prosthetic joints who are receiv-ing dental care. Therefore, it appears that a blanket recommendation for antibi-otic coverage would be inappropriate at this time" lEskinazi D and Rathbun W,Oral Surg Oral Med Oral Pathol, 1987). In 1990, the American Dental Associa-tion released a position paper that stated "there is no scientific evidence thatprophylactic antibiotics actually prevent late prosthetic ¡oint infections ... fromtransient bacteremias caused by dental treatment" (Council on Dental Thera-peutics, J Am Dent Assoc, 1990) The statement went on to emphasize that thedecision should be made by the dentist, in consultation with the patient's physi-cian or orthopedic surgeon. This was followed by a 1992 statement of theBritish Society for Antimicrobial Chemotherapy that paralleled these viewpointsand 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 icintadvisory statement by the American Academy of Orthopedic Surgeons (AAOSIand the American Dental Association (ADA) in 1997 (J Am Dent Assoc). Thisreport culminated a comprehensive evaluation of available data and was formal-ly adopted by both organizations. Key points that were emphasized in the reportinclude the following:

• The most critical period for bacteremias occurs within 2 years after jointplacement.

• There is no evidence to support prevention of hematogenous infections inpatients with total loint prostheses through antibiotic prophylaxis.

• There is no comparison between late prosthetic lOint infections and infectiveendocarditis 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 areimmunocompromised or immunosuppressed, patients who have type 1 (juve-nile, insulin-dependent [IDDM]) diabetes mellitus, patients who have had priorprosthetic 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 surgeryor 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 effectiveoral 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 medicationsshould be given cefaxolin or ampicillin parenterally. Patients who are allergic topenicillin 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

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clinieal judgment and management decisions clearly falls to the dentist, and thedentist must include tfie patient in the informed consent process by making thepatient aware of the treatment options. If, m the dentist's judgment, improperrecommendations have been received from a physician who is unfamiliar withthe guidelines, the dentist should proceed without antibiotic prophylaxis. When-ever antibiotic prophylaxis is utilized, the perceived benefits must be weighedagainst the known risks, including occurrence of allergic reactions, excessivetreatment costs, and development of microbial resistance. The dentist whoblindly follows a physician's erroneous recommendation will not be able todefend those actions if harm befalls the patient from improper prescribing ofantibiotics.

Little et al have summarized the findings for patients with other implanteddevices who undergo dental treatment (Dental Management of the MedicallyCompromised Patient, Mosby, 1997) There is no clear rationale for the use ofantibiotic prophylaxis in dental patients who have received artificial finger joints,penile or breast implants, and the like If antibiotics are used, the use should beaccompanied 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 prescriptionsuntil the patient either dies or is cured by nature," Voltaire 11694-1778) onceremarked, "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 onsound scientific principles and a working knowledge of pharmacotherapeutics.The time has arrived for dentists to shed the cloud of uncertainty and doubt andto restrict the use of prophylactic antibiotics only to those defined patients whoclearly have a benefit potential that outweighs the risk factors. Recent additionsto the literature from organized groups have provided the tools necessary toachieve those goals, but these tools are of value only if used by practitioners.

PERIODONTICINDICATIONS

THOMAS J. PALLASCH, DDS, MS

Antibiotics are employed in penodontal therapy in one of three situations: (1) themanagement of acute periodontal conditions, primarily periodontal abscessesusually in conjunction with incision and drainage, (21 as "prophylaxis" to "pre-vent" posttreatment infectious sequeilae, and 13) as definitive or adjunctive thera-py in the management of chronic periodontitis. The treatment protocol for acuteperiodontal conditions is well established, little if any data support the use ofantibiotics to prevent dental treatment sequeilae (other than endocarditis), and theuse of antimicrobials to manage chrome periodontitis is both controversial andmisunderstood.

Acute periodontal conditions (abscesses, necrotizing gingivitis) do not differsubstantially 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 microbialresistance development. The usual package insert doses are adequate with theexception that a loading dose (2 to 4 times the maintenance dose depending onthe severity of the infection) should be employed to achieve high blood levelsrapidly because acute orofacial infections tend to have a very rapid onset. Withouta loading dose, it may take 6 to 12 hours to achieve therapeutic tissue levels withmany antibiotics. Amoxicillin is exceptional because an oral dose is very rapidlyand 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 ofchoice, utilizing an appropriate loading dose for acute infections.

The use of antibiotics as prophylaxis to prevent infectious sequeilae to routinedental treatment procedures is unfortunately still advocated in some quarters

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