Vol. 110 No. 1 July 2010

EDITORIAL

Decisions and antibiotics use: more questions and some answers

We, as dentists, are confronted every day with deci-sions, and I am fascinated by how we make properdecisions and by what shapes these decisions. An areaof particular interest is how we make treatment deci-sions and the evidence we use for making those deci-sions. The overarching question in my mind is: Are wemaking appropriate decisions regarding the use of an-tibiotics? Let’s look at a few example, and ask ques-tions about how our decisions are being made.

For a nonlife-threatening acute dental infection in apatient with normal immune and metabolic status, anantibiotic (i.e., penicillin) is typically prescribed for acourse of 7-10 days. However, what is so magical aboutthis time frame? The usual oral infection of bacterialorigin requires an average of 4-7 days to resolve withantibiotics.1,2 This raises the question, “Could ourpatients take an antibiotic for fewer days and stillbenefit from the antibiotic regimen?” Clearly, studieshave shown that many individuals are not totallycompliant with the prescribed antibiotic regimen andoften have pills left over to take at a later date.3-5

Furthermore, the indication that many patients sur-vive the infection so that they could take the pills ata later date or share them with a relative or loved onesuggests that the full course of antibiotic therapy wasnot required originally.

It is also generally accepted that an antibiotic mustreach the site of infection in amounts above the mini-mum inhibitory concentration (MIC) or minimum le-thal concentration (MLC) for the infecting microorgan-isms. However, what about the immune response of ahealthy individual? Could a concentration that is nearthe MLC be bacteriostatic and shift the balance enoughso that the infection is controlled, particularly in anotherwise healthy patient? Alternatively, could theplasma concentration of the antibiotic be above theMIC for a minimum duration (e.g., just long enough,perhaps a few days) such that the immune system iscapable of controlling the infection without taking a

7-day course of antibiotics?

In dentistry we have the luxury often not afforded inmedicine that we can reduce the bacterial load or re-move the source of infection which can limit the needfor antibiotics. For odontogenic infections, we can re-move/reduce the source of infection by several means,including extraction, incision and drainage, or root ca-nal therapy. In these circumstances, antibiotics can bediscontinued after 2-3 days or may not even be neededprovided that proper drainage has been established.6-8

The need for many antibiotic prescriptions in dentistryis generally lacking, with one study reporting that only�5% of patients who received a prescription for anti-biotics had an acute infection.9 Yet, many dentists writeprescriptions for penicillins and do so using empirical7-10 day dosing. This empirical approach could beoptimized by studies that provide scientific evidenceand by asking important questions before deciding toprescribe an antibiotic, questions such as: Is an antibi-otic needed? Are the signs and symptoms consistentwith an infection? Does the patient’s health or currentsituation place them at risk for the infection spreading?If an antibiotic is needed, what duration of therapy isappropriate? By reevaluating the patient at 24, 48, and72 hours after initial presentation for alleviation ofsigns and symptoms, the clinician could assess whetherthe proper drug was selected, whether the dose is ef-fective/ineffective, and whether more days are needed.This approach could reduce exposure to the antibiotic.

Now, some may say that giving a shorter course ofhigh-dose antibiotics could lead to antibiotic resistance.But how does antibiotic resistance develop? Evidenceindicates that long-term and repetitive use of antibioticsis what promotes antibiotic resistance.10,11 Also, anadequate concentration needs to be maintained for along enough period of time to promote selectivity forthe development of resistant strains.12 Furthermore,several lines of evidence support the concept that ashort-course high-dose antibiotic regimen can be effec-

tive and should be considered for discontinuation after

1

OOOOE2 Miller July 2010

3 days when proper drainage has been establishedand/or signs of the infection are resolving.7,8,13-15

So, let’s take this intellectual debate a step further.Recently, the need for antibiotic prophylaxis for dentalprocedures for patients with joint prosthesis has reap-peared in the news. In February 2009, the AmericanAcademy and American Association of OrthopedicSurgeons (AAOS) recommended that clinicians “con-sider antibiotic prophylaxis for all total joint replace-ment patients prior to any invasive [dental] procedurethat may cause bacteremia” [http://www.aaos.org/research/committee/ptsafety/ptsafety.asp (accessed Feb.11, 2010)].

Several things are interesting about this new recom-mendation. First, it more expansive than the AmericanDental Association (ADA) and AAOS advisory state-ment on the dental management of patients with pros-thetic joints published in 1997 and revised in 2003.16,17

This new recommendation includes “any invasive pro-cedure that may cause bacteremia.” The main premisefor this recommendation is that: 1) bacteremia fromoral flora arising from dental procedures causes lateprosthetic joint infections (LPJIs); 2) there is a temporalrelationship between dental procedures and LPJIs; 3)antibiotic prophylaxis would prevent bacterial seedingand subsequent LPJIs; and 4) treatment of LPJIs isexpensive, involving hospitalization, pain, immobility,and possible implant removal.

In a recent commentary, Dr. Arthur Friedlander sup-ported the AAOS recommendation by presenting a casefor the presence of staphylococci in the oral cavity,especially in the elderly and those with rheumatoidarthritis, as well as around implants, root canals, andodontogenic infections.18-26 He reviews the rates ofbacterial infections of prosthetic joints temporally andbacteriologically associated with dental procedures andreiterates the findings from 2 large studies by Laporte etal.27 and Waldman et al.,28 where 12 “dentally-related”joint infections were identified from more than 6,400patients with prosthetic joints. His commentary statesthat “the oral microbial environment are more diversethan originally believed and . . . [thus], it logicallyfollows that invasive dental procedures (oral and peri-odontal surgery, scaling, root planing, probing, dentalimplant placement, endodontic instrumentation beyondroot apex, placement of subgingival fibers or strips,intraligamentary injections, and prophylactic cleaningof teeth or implants where bleeding is anticipated) maycause both staphylococcus and streptococcus bactere-mias which have been implicated in late joint prosthe-ses infections.” Dr. Friedlander then presents an anti-biotic regimen supported by orthopedic societies that he

and they recommend for use.

Here is where our decision-making skills are put tothe test. No one will disagree that bacteria in the oralcavity may be associated with bacteremias, and fewwill disagree that these organisms have a temporalrelationship with a small number of LJPIs. However,closer scrutiny of the evidence is required. Bacteremiasassociated with daily activities are common, yet no onerecommends (yet) the need for daily prophylactic anti-biotics when these patients chew gum or brush theirteeth.29 Second, no one has cultured the organisms inthe mouth before and then during the LJPI, so there-fore the relationship between the 2 sites is onlypredicted and not proven. Third, analyses of repor-ted cases of LJPIs demonstrate that these infectionsare rarely caused by bacterial species common to themouth.27,28,30 Fourth, a recent well designed, case-control study performed at the Mayo Clinic in responseto the AAOS posting demonstrated that dental proce-dures were not risk factors for subsequent total hip orknee infections.31 Finally, no study exists that hasshown that prophylactic antibiotics reduce the risk ofdistant site infections in humans.32-34 In fact, one of the9 “dentally related” joint infections documented in theWaldman et al.28 report received prophylactic antibiot-ics, but the antibiotics failed to be protective. So, onecould extrapolate from these data that the risk of LJPIis small with or without dental treatment, and antibioticprophylaxis is at best 89% efficient in preventing LJPIs.

Let’s consider additional factors that could help inthe decision process. Pertinent questions include: First,what is the bacterial load in the oral cavity at the timeof the procedure, and how does the load relate to risk ofprosthetic joint infections? Second, which proceduresinvolve significant risk of bacteremia (e.g., incision intoinfected tissues vs. placement of subgingival fibers orstrips)? Third, how does the duration of the procedureinfluence the outcome? In the original reports providedby LaPorte et al. and Waldman et al., the duration of theinvasive dental procedures associated with the infec-tions were 45-90 minutes and 75-205 minutes, respec-tively. One could speculate that the duration of theinvasive procedure being �45 minutes was an impor-tant risk factor, because in theory bacteria could havehad an increased opportunity to enter the blood streamif the invasion was longer. Also potentially contribu-tory is the patient’s immune and metabolic status. In theLaPorte et al. and Waldman et al. reports, �50% of thepatients who developed LJPIs were immune- or meta-bolically compromised, and these systemic alterationshave been identified as potentially higher risk since the1997 ADA/AAOS advisory statement.

In conclusion, much data and controversy exist re-garding the proper use of antibiotics for infections and

prophylactically. However, clinicians are encouraged

OOOOEVolume 110, Number 1 Miller 3

to weigh the evidence from weakest (empirical ap-proaches and expert opinions) to strongest (carefullycontrolled clinical trials) for guiding their clinical judg-ment. After all, that is how practice guidelines shouldbe established. Rest assured that in the future, theseguidelines will be strengthened based on studies thataddress the effects of antibiotics at the site of interest,adverse effects associated with antibiotic use, develop-ment of antibiotic resistance, cost implications (prophy-laxis vs. joint replacement surgery), and quality of lifeissues.

Craig Miller, DMD, MSSection Editor, Oral Medicine Section

doi:10.1016/j.tripleo.2010.03.022

REFERENCES1. Matijevic S, Lazic Z, Kuljic-Kapulica N, Nonkovic Z. Empirical

antimicrobial therapy of acute dentoalveolar abscess. VojnosanitPregl 2009;66:544-50.

2. Mongtomery EH. In: Yagiela JA, Neidle EA, Dowd FJ, editors.Pharmacology and therapeutics for dentistry. St. Louis: Mosby;1998. p. 482-95.

3. Feder HM Jr, Gerber MA, Randolph MF, Stelmach PS, KaplanEL. Once-daily therapy for streptococcal pharyngitis with amoxi-cillin. Pediatrics 1999;103:47-51.

4. Clegg HW, Ryan AG, Dallas SD, et al. Treatment of streptococ-cal pharyngitis with once-daily compared with twice-dailyamoxicillin: a noninferiority trial. Pediatr Infect Dis J 2006;25:761-767.

5. Lennon DR, Farrell E, Martin DR, Stewart JM. Once-dailyamoxicillin versus twice-daily penicillin V in group A beta-haemolytic streptococcal pharyngitis. Arch Dis Child 2008;93:474-8.

6. Ellison SJ. The role of phenoxymethylpenicillin, amoxicillin,metronidazole and clindamycin in the management of acutedentoalveolar abscesses—a review. Br Dent J 2009;206:357-62.

7. Pallasch TJ. How to use antibiotics effectively. J Calif DentAssoc 1993;21:46-50.

8. Pogrel MA. Antibiotics in general practice. Dent Update1994;21:274-80.

9. Lewis MA, Meechan C, MacFarlane TW, Lamey PJ, Kay E.Presentation and antimicrobial treatment of acute orofacial in-fections in general dental practice. Br Dent J 1989;166:41-5.

10. Naiman RA, Barrow JG. Pencillin-resistant bacteria in themouths and throats of children receiving continuous prophylaxisagainst rheumatic fever. Ann Intern Med 1963;58:768-72.

11. Sprunt K, Redman W, Leidy G. Penicillin resistant alpha strep-tococci in pharynx of patients given oral penicillin. Pediatrics1968;42:957-68.

12. Bilavsky E, Eliahou R, Keller N, Yarden-Bilavsky H, Harel L,Amir J. Effect of benzathine penicillin treatment on antibioticsusceptibility of viridans streptococci in oral flora of patientsreceiving secondary prophylaxis after rheumatic fever. J Infect2008;56:244-8.

13. Paterson SA, Curzon ME. The effect of amoxycillin versuspenicillin V in the treatment of acutely abscessed primary teeth.Br Dent J 1993;174:443-9.

14. Marsh P, Martin MV. Oral mcirobiology. Edinburgh: Wright;

1999.

15. Martin MV, Longman LP, Hill JB, Hardy P. Acute dentoalveolarinfections: an investigation of the duration of antibiotic therapy.Br Dent J 1997;183:135-7.

16. American Dental Association, American Academy of Orthopae-dic Surgeons. Advisory statement. Antibiotic prophylaxis fordental patients with total joint replacements. J Am Dent Assoc1997;128:1004-8.

17. Antibiotic prophylaxis for dental patients with total joint replace-ments. J Am Dent Assoc 2003;134:895-9.

18. Percival RS, Challacombe SJ, Marsh PD. Age-related microbi-ological changes in the salivary and plaque microflora of healthyadults. J Med Microbiol 1991;35:5-11.

19. Marsh PD, Percival RS, Challacombe SJ. The influence of den-ture-wearing and age on the oral microflora. J Dent Res1992;71:1374-81.

20. Honda E. Oral microbial flora and oral malodour of the institu-tionalised elderly in Japan. Gerodontology 2001;18:65-72.

21. Baena-Monroy T, Moreno-Maldonado V, Franco-Martinez F,Aldape-Barrios B, Quindos G, Sanchez-Vargas LO. Candidaalbicans, Staphylococcus aureus and Streptococcus mutans col-onization in patients wearing dental prosthesis. Med Oral PatolOral Cir Bucal 2005;10(Suppl 1):E27-39.

22. Jacobson JJ, Patel B, Asher G, Woolliscroft JO, Schaberg D.Oral staphylococcus in older subjects with rheumatoid arthritis.J Am Geriatr Soc 1997;45:590-3.

23. Murdoch FE, Sammons RL, Chapple IL. Isolation and charac-terization of subgingival staphylococci from periodontitis pa-tients and controls. Oral Dis 2004;10:155-62.

24. Fischer CC, Persson RE, Persson GR. Influence of the menstrualcycle on the oral microbial flora in women: a case-control studyincluding men as control subjects. J Periodontol 2008;79:1966-73.

25. Salvi GE, Furst MM, Lang NP, Persson GR. One-year bacterialcolonization patterns of Staphylococcus aureus and other bacte-ria at implants and adjacent teeth. Clin Oral Implants Res2008;19:242-8.

26. Egusa H, Watamoto T, Abe K, et al. An analysis of the persistentpresence of opportunistic pathogens on patient-derived dentalimpressions and gypsum casts. Int J Prosthodont 2008;21:62-8.

27. LaPorte DM, Waldman BJ, Mont MA, Hungerford DS. Infec-tions associated with dental procedures in total hip arthroplasty.J Bone Joint Surg Br 1999;81:56-9.

28. Waldman BJ, Mont MA, Hungerford DS. Total knee arthroplastyinfections associated with dental procedures. Clin Orthop RelatRes 1997:164-72.

29. Hupp JR. Infective endocarditis—stop blaming the dentist. OralSurg Oral Med Oral Pathol Oral Radiol Endod 2009;108:145-6.

30. Lindqvist C, Slatis P. Dental bacteremia—a neglected cause ofarthroplasty infections? Three hip cases. Acta Orthop Scand1985;56:506-8.

31. Berbari EF, Osmon DR, Carr A, et al. Dental procedures as riskfactors for prosthetic hip or knee infection: a hospital-basedprospective case-control study. Clin Infect Dis;50:8-16.

32. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infectiveendocarditis: guidelines from the American Heart Association: aguideline from the American Heart Association Rheumatic Fe-ver, Endocarditis, and Kawasaki Disease Committee, Council onCardiovascular Disease in the Young, and the Council on Clin-ical Cardiology, Council on Cardiovascular Surgery and Anes-thesia, and the Quality of Care and Outcomes Research Interdis-ciplinary Working Group. Circulation 2007;116:1736-54.

33. Lockhart PB, Loven B, Brennan MT, Fox PC. The evidence basefor the efficacy of antibiotic prophylaxis in dental practice. J AmDent Assoc 2007;138:458-74.

34. Oliver R, Roberts GJ, Hooper L, Worthington HV. Antibioticsfor the prophylaxis of bacterial endocarditis in dentistry. Co-

chrane Database Syst Rev 2008:CD003813.