Role of antibiotics in paediatric endodontics.

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REVIEW

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Gurusamy Kayalvizhi

Role of antibiotics in paediatric endodontics

Gurusamy Kayalvizhi

Key words

antibiotics, drugs, infected tooth, irreversible pulpitis, prophylactic, root canal treatment, systemic, topical

Bacteria have been implicated in the pathogenesis and progression of pulpal and periapical diseases.

The primary aim of endodontic treatment is to remove as many bacteria as possible from the root canal system and then create an environment in which remaining microorganisms cannot survive.

Antibiotics form an important part of routine endodontic practice. They have been used routinely in children as an adjunct in a number of ways: systemically, locally and prophylactically. Systemic antibiotics have been used in clinical practice far more than is necessary. As topical agents they have been used as an intra-canal pulpotomy/pulpectomy medicament and root canal irrigant. Although their inadvertent use raises concern, the most important decision in antibiotic therapy should not be about which antibiotic should be used but whether antibiotics should be used at all. This paper reviews the role of antibiotics in paediatric endodontics by highlighting their effects and concerns in detail.

n Introduction Over a century ago, Miller wrote that bacteria are connected in some manner with pulpal diseases, and he raised the hypothesis that they are the causative factor for diseases of endodontic origin. This hypothesis has been proved, as bacteria have been implicated in the pathogenesis and progression of pulpal and periapical diseases1. The child with an infected pulp presents a unique challenge to the clinician. Bacterial composition of an infected root canal is complex, mainly consisting of the obligate

anaerobes and facultative aerobes2. The primary aim of endodontic treatment is to remove as many bacteria as possible from the root canal system and then create an environment in which the remaining microorganisms fail to thrive3.

Antibiotics play an important role as an adjunct to paediatric endodontics. They are compounds that act to kill or inhibit the growth of bacteria. Penicillin and other antibiotics were viewed as ‘miracle drugs’ owing to their ability to cure life-threatening diseases during World War II4. This paper highlights their systemic, topical and prophylactic role in paediatric endodontics.

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Department of Pedodontics and Preventive Dentistry, M. R. Ambedkar Dental College and Hospital, Bangalore, India Correspondence to: Gurusamy Kayalvizhi Department of Pedodontics and Preventive Dentistry No 9, 8th Maruthi Cross, Post Office Road Ramamurthy Nagar Bangalore 560016, Karnataka, India Tel: (0091) 988 612 0559 Email: drfisheyes22@gmail.com

Kayalvizhi

Role of antibiotics in paediatric endodontics

Antibiotics have been extensively used for the management of odontogenic infections since their discovery.

n Commonly used drugs in endodontics4,5,8,9

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edge6,7. If in doubt, recommended.

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n Role of systemic antibiotics in endodontics5

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The child is not a miniature adult, thus paediatric dentists must consider their differences when making therapeutic choices for young patients, especially when treatment includes drug therapy. These include the following: t Young children tend to lack medical antecedents suggesting the possibility of drug allergies or adverse reactions. t The greater proportion of water in the tissues of children and their increased bone sponginess facilitate faster diffusion of infection; hence, adequate dose adjustment is recommended. t The gastrointestinal tract undergoes continuous developmental change from birth to old age. Infants and young children secrete low levels of acid due to immature gastric mucosa until 3 years of age; this favours absorption of weakly acidic drugs like penicillins and cephalosporins. Longer gastric emptying times combined with irregular peristalsis of infancy result in slower gastric drug absorption. t Alteration in drug metabolism due to deficiency of hepatic enzymes, i.e. they are at a higher risk of toxicity if not given the correct dose. t Drug metabolism and excretion are profoundly affected by the size of various body fluid compartments. t Children need smaller drug doses to maintain therapeutic drug concentration, and those smaller doses are enough to produce toxicity. The ‘maximum safe dose’ listed in standard drug reference manuals is enough to overdose a paediatric patient, thus weight-based formulas are much safer in the paediatric population. t The severity of the infection has to be taken into account.

Accordingly, antibiotics should be selected based on the assessment of the overall state of the patient’s health and most up-to-date microbiological knowl-

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t Penicillin VK is effective against most aerobic and anaerobic bacteria associated with endodontic infections. t Erythromycin, which is commonly prescribed for penicillin-allergic patients, has been found to be ineffective against most of the anaerobes associated with endodontic infections. t Clindamycin is an appropriate substitute in patients allergic to penicillin. It is beta-lactamaseresistant and is highly effective against facultative and strict anaerobic bacteria associated with endodontic infections. It penetrates into abscesses and any other areas of poor circulation. t Clarithromycin has a more limited spectrum of activity than clindamycin but has some advantages over erythromycin. Clarithromycin is effective against facultative anaerobes and some of the obligate anaerobic bacteria associated with endodontic infections. It is also less likely than some other antibiotics to cause gastrointestinal problems. t Metronidazole is a synthetic antibiotic that is highly effective against obligate anaerobes but is ineffective against facultative anaerobic bacteria.

If penicillin is ineffective after 48 to 72 hours, metronidazole is a valuable antimicrobial agent for combination antibiotic therapy. t Tetracycline kills the broadest spectrum of microbes. It is recommended in endodontics, since periodontal pathogens invade the root canal and periapical tissues. It is of limited use in children below 8 years of age, as it causes tooth discoloration, and can continue to do so beyond this age by becoming deposited in secondary dentine10.

n Root canal: To culture or not?5,11,12,13 The microflora of the necrotic pulps has been studied for more than 100 years by direct microscopy and cultivation. Although adjunctive antibiotic therapy for endodontic infections is based on the past knowledge of those organisms most likely to be associated

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Role of antibiotics in paediatric endodontics

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with endodontic infection, at times culturing may provide valuable information for a better selection of antibiotics. Culturing of the root canal for endodontic infections is rarely recommended. The variety of microorganisms involved makes a positive identification of the main pathogen unlikely. Culturing may be helpful if the infection persists/progresses, or in the case of a medically compromised patient where extra precaution is necessary to prevent a systemic infection.

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n Problems in root canal cultures t Sampling: a technical difficulty, associated with obtaining samples for culturing, as sterile asepsis is necessary during sampling due to the risk of contamination from teeth (plaque of caries), oral mucosa, saliva, fingers and instruments. t Transport: death of microorganisms/overgrowth of others. t Cultivation: inadequate media, uncultivable organisms. t Identification: time-consuming – as it takes 1 to 2 weeks to identify anaerobes – and expensive. t Exact time of initial infection is difficult to ascertain. The antibiotic treatment should begin immediately, even when culture is taken, because oral infections progress very rapidly.

In future, the advent of molecular genetic methods may solve some of these problems and help rapid detection and identification of known opportunistic bacteria within 24 to 48 hours.

n Duration of antibiotic therapy As each infection is unique, clinical judgement must be applied; a standard therapy of the same dose and duration for all cases will not only lead to bacterial resistance but also treatment failures. The ideal duration should be the shortest cycle capable of preventing both clinical and microbiological relapse. Thus a high-dose regimen for a short duration is preferred to a low dose for a longer time. The patient must be instructed clearly that adherence to the dosing schedule is critical in order to eliminate the infection5,8,11,14.

Fig 1 Persistent swelling.

Fig 2 Swelling continues to spread despite disinfection of the root canal system.

n Indications for the use of systemic antibiotics in endodontics4,5,8,9,11 t Antibiotics should only be used as an adjunct to definitive non-surgical or surgical endodontic therapy. Removal of the aetiology should be the ultimate goal of treatment. Pulpal debridement and/or surgical access are the primary treatment for all endodontic infections. t For progressive or persistent infections that have systemic signs and symptoms, the use of adjunctive antibiotics is recommended in conjunction with appropriate endodontic treatment for the effective debridement of the root canal (Fig 1). t Use of antibiotics is indicated if swelling continues to spread despite attempts to disinfect the root canal system and establish drainage (Fig 2). t If bacteria are too virulent or the immune system becomes too weak to control their growth, then antibiotics are necessary.

n Contraindications for the use of systemic antibiotics in endodontics4,5,8,13 t Irreversible pulpitis with or without acute periradicular periodontitis (no systemic signs of infection): it is an immune system mediated event, usually not due to bacterial infection but, rather, a result of inflammatory mediators overcoming the host defences. A Cochrane systematic review15 found no evidence to support the use

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Role of antibiotics in paediatric endodontics

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of antibiotics for pain relief in irreversible pulpitis, and the conclusion from various studies has shown that penicillin does not reduce the pain, percussion sensitivity or amount of analgesics required in untreated teeth diagnosed with irreversible pulpitis. Studies have shown inappropriate prescription of antibiotics16,17,18 by dentists and endodontists19. The practice of using antibiotics as ’analgesics’ in endodontics should be avoided. t Symptomatic apical periodontitis. t Localised swelling: the circulation within the pulp is compromised in the presence of the inammation or infection, because when an antibiotic is carried by the vascular system, its ability to reach bacteria in a therapeutic concentration will be limited, diminishing the efďŹ cacy of the antibiotic. t Draining the sinus tract: occasionally the infectious process will move beyond the tooth and bone into the soft tissue, creating an intraoral swelling. Swellings can be drained through the tooth, by a soft tissue incision or through a naturally occurring sinus tract. Even if antibiotics are used, the immune system cannot function optimally until the purulence is eliminated.

n Over-prescription and misuse of antibiotics4,13,20 Over-prescription of antibiotics for upper respiratory tract infections and dental pain is emerging as a growing threat. t It increases the chances of super-infections with the development of multi-drug resistant strains of bacteria (super bugs). t Allergic reactions, adverse reactions and drug– drug interactions may occur. t Antibiotic resistance: bacteria can become resistant to drugs through mutation and ‘selective pressure’. With designer drugs12 on the horizon, re-

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Table 1 CDC recommendations for appropriate antibiotic use.

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searchers believe that studying bacterial function at the molecular level holds the key to rapid new drug development. Future antibiotics may be ’customised’ to disarm bacteria chemically and thus prevent the development of resistant strains. t To prescribe too little or for too short a duration will kill weaker organisms, leaving more substrate available for those with greater virulence to become entrenched.

n Recommendations for the prudent use of antibiotics4,5,21 Researchers at the Centers for Disease Control and Prevention (CDC) estimate that approximately one third of all outpatient antibiotic prescriptions are unnecessary. As clinicians discover the gravity of this situation, they are re-evaluating how and when to prescribe antibiotics. Understanding the microbiology of diseases and recognising when the immune system requires antibiotic assistance to eliminate an infection can help both dentists and physicians make better treatment decisions (Table 1).

The vast majority of infections of endodontic origin can be managed effectively without the use of antibiotics. Systemically administered antibiotics are not a substitute for proper endodontic treatment.

Chemo-mechanical debridement with drainage through the root canal system or by incision and drainage of soft tissue will decrease the bioburden so that a normal healthy patient can begin the healing process.

n Topical antibiotics The interest in topical antibiotics reached a peak in endodontics 40 years ago and subsequently declined2. Bacteria within the root canals are inaccessible to irrigation and the mechanical cleaning

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Disinfection of the root canal and the periradicular region results in good healing of the periradicular region. The application of antibacterial drugs to endodontic lesions is one of the clinical procedures that can be used to sterilise such lesions. One such technique is LSTR (lesion sterilisation and tissue repair), which employs the use of a mixture of antibacterial drugs for disinfection of oral infectious lesions, including dentinal, pulpal and periapical lesions24.

3Mix-MP (macrogol, propylene, glycol) medicament has been found to be effective as a pulpotomy24 and pulpectomy25 medicament in the treatment of infected primary teeth. In children, excellent clinical outcomes have been observed in the first- and second-year area oral health programme26,27.

preparation. The reliance on mechanical instrumentation and aversion to the use of cytotoxic agents has led to the lack of use of an intra-canal dressing by many clinicians. Calcium hydroxide has been found to be more successful as an intra-canal medicament, but it has a few limitations and it is difficult to completely remove it from the root canal walls before obturation, which might adversely affect the quality of the apical seal. Recent reports also suggest that, due to its strong alkalinity, it may de-nature the carboxylate and phosphate groups leading to a collapse in the dentine structure. Therefore it is not recommended for long periods28. Moreover, it did not totally eliminate bacteria from the root canal system5,11.

Antibiotics in different combinations have been tried in root canal dressings and found to be effective2. Triple antibiotic paste was successful in the healing of non-surgical, endodontically treated, large cyst-like periradicular lesions29 and dens invaginatus in a mandibular premolar with a large periradicular lesion30. It was found to be effective in the disinfection of immature teeth31 in dogs, and in inhibiting enterococcal growth20,32. Thus, with further research, it could possibly be used as an intra-canal medicament in children.

n Root canal irrigant Although mechanical instrumentation of root canals can reduce the bacterial population, effective elimination of the bacteria cannot be achieved without the use of antimicrobial root canal irrigation and medication. A new root canal irrigant, BioPure MTAD, which is a mixture of a tetracycline isomer (3% doxycycline), an acid (4.25% citric acid) and a detergent (0.5% polysorbate 80), has been introduced, as it is known to remove the smear layer more effectively than sodium hypochlorite and EDTA (ethylenediaminetetraacetic acid). In addition, it has been effective against Enterococcus faecalis and may have substantive antimicrobial action lasting up to 4 weeks. It fulfils the requirements of an ideal root canal irrigant as it is able to remove most of the smear layer, and possesses superior bactericidal activity.

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t Grossman’s polyantibiotic paste (penicillin, bacitracin, chloremphenicol, streptomycin) was introduced in 1951. It was ineffective against anaerobes and the use of penicillin induced an allergic reaction. t A mixture of neomycin, polymyxin and nystatin was found to be unsuitable against endodontic bacteria. t Clindamycin has been tried as a root canal dressing23. It was unsuccessful, as clindamycinresistant enterococci were recovered from the root canal 10 days after placement of the root canal dressing. Besides, it had no advantage over calcium hydroxide. t Three-mix medicament (ciprofloxacin, metronidazole, minocycline): a combination of drugs was preferred due to the complexity of root canal infections. They were also known to reduce the development of resistant bacterial strains24.

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n History of topical antibiotics in endodontics3,22

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process. It is hoped that antibiotics contained within intra-canal/pulpotomy medicaments might be able to diffuse into these areas to reduce the number of viable bacteria present and improve periapical healing3.

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Role of antibiotics in paediatric endodontics

Role of antibiotics in paediatric endodontics

n Concerns t The use of systemic antibiotics for topical application is questionable. t Although metronidazole use is considered to be clinically safe, ciprofloxacin and minocycline side effects have to be taken into consideration. t Leakage of antibiotic paste into the oral cavity could have an effect on oral microflora. t Potential for bacterial resistance, risk of drug hypersensitivity and the potential to mask certain aetiological factors limit their usefulness.

There is still no clear scientific evidence for the use of topical antibiotics in root canal therapy21,36.

n Prophylactic antibiotics The American Heart Association (AHA) has made recommendations for the prevention of infective endocarditis (IE) over the past 50 years. Its goal was to prevent clinical infection by helping to destroy small numbers of bacteria present before treatment or introduced during instrumentation37.

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Tetraclean, like MTAD, is a mixture of an antibiotic, an acid and a detergent. However, the concentration of antibiotic doxycycline (50 mg mL-1) and the type of detergent (propylene glycol) differs from that of MTAD. It has very low surface tension and a high degree of efficacy against bacterial biofilms. However, these effects have recently been challenged by different investigators21,33,34,35, warranting further research.

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n Recommendations for antibiotic prophylaxis37,38 Based on the recent guidelines, prophylaxis is recommended before dental procedures only for those at high risk (AHA) or at risk (NICE [National Institute for Health and Clinical Excellence] guidelines) of developing infective endocarditis (Table 2).

n Antibiotic prophylaxis recommended for dental procedures AHA: ‘All dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of oral mucosa’37.

NICE: This guideline recommends that antibiotic prophylaxis solely to prevent IE should not be given to people at risk of IE undergoing dental and non-dental procedures. It emphasises that antibiotic therapy should still be thought necessary to treat active or potential infections.

n The bases to support this recommendation are: There is no consistent association between having an interventional procedure, dental or non-dental, and the development of IE. t Regular toothbrushing almost certainly presents a greater risk of IE than a single dental procedure because of repetitive exposure to bacteraemia with oral flora. t The clinical effectiveness of antibiotic prophylaxis is not proven. t Antibiotic prophylaxis against IE for dental procedures may lead to a greater number of deaths through fatal anaphylaxis than a strategy

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n Controversies37,38,39 Five clinical guidelines on the prevention of IE – American Heart Association (AHA) 2007, British Society for Antimicrobial Chemotherapy (BSAC) 2006, European Society of Cardiology (ESC) 2004, British Cardiac Society (BCS)/Royal College of Physicians (RCP) 2004, National Institute for Health and Clinical Excellence (NICE) 2008 – indicate: t There is no consensus on the specific regimen to be adopted; conflicts exist between different guidelines: – The ESC guideline discussed that antibiotic prophylaxis may not be effective in preventing bacterial endocarditis if the amount of bacteraemia, in terms of colony forming units (CFU), is very large.

– The BCS/RCP continued to recommend antibiotic prophylaxis for many dental and nondental procedures.

– The AHA recommended prophylaxis in cases where root canal instrumentation is done beyond the root apex, whereas BSAC excluded prophylaxis for endodontic therapy extending below the gingival margin.

– NICE recommended no prophylaxis for dental procedures. t No age distinctions as they are prescribed more frequently for the young than the old. In addition, none of the above bodies present specific guidelines for antibiotic prophylaxis in patients with prior antibiotic therapy for periapical/other infections. t There is insufficient evidence to determine whether antibiotic prophylaxis in those at risk of developing infective endocarditis reduces the incidence of IE when given before a defined in-

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Patients at risk of infective endocarditis should maintain good oral hygiene to prevent it, since systemic antibiotics, local antiseptics or antibiotics cannot eliminate the periodontal or pulpal microflora.

Bacteria may still survive in the dentinal tubules and other canal ramifications that are inaccessible to mechanical instrumentation and irrigation.

cific, they require constant revision in order to reduce the risks associated with antibiotic prophylaxis and to spell out relevant details for all aspects of dental (including endodontic) therapy, rather than undergoing modification by individual dentists.

Hence, dentists and physicians ought to rely upon their clinical judgement to balance the costs and benefits of such regimens and consult a paediatrician to assess the status of a child and to determine individual susceptibility to infections induced by bacteraemia. Following AAPD/ EAPD guidelines will help in being prudent and conservative in the use of antibiotics with children8,40.

n Conclusion The prudent use of antibiotics to treat an endodontic infection is an integral part of appropriate treatment. Dentists performing endodontic treatment are clearly implicated in the growth of resistant strains by over-administration of antibiotics in cases not calling for their use. Dental professionals should realise their responsibility towards their patients and the community as a whole and restrict the use of antibiotics only to those situations that actually require them.

n References 1. Siqueira JF, Janeiro RD. Endodontic infections: concepts, paradigms and perspectives. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:281-293.

2. Dahlen G, Haapasalo M. Microbiology of apical periodontitis. In: Ørstavik D and Pittford TR. Essential Endodontology: Prevention and Treatment of Apical Periodontitis. Oxford: Blackwell Science 1998:107.

3. Athanassiadis B, Abbott PV, Walsh LJ. The use of calcium hydroxide, antibiotics and biocides as antimicrobial medicaments in endodontics. Aust Dent J 2007;52(1 Suppl): S64-S82.

4. Crumpton BJ, McClanahan SB. Antibiotic resistance and antibiotics in endodontics. Clinical Update 2003;25:23-25.

5. Baumgartner JC, Bakland LK, Sugita EI. Microbiology of endodontics and asepsis in endodontic practice. In: Ingle JI and Bakland LK (eds). Endodontics, ed 5. Hamilton, ON: BC Decker 2002:74-79.

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Pediatric Dentistry: Infancy through Adolescence, ed 4. St. Louis, MO: Saunders 2005:89-95.

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of no antibiotic prophylaxis, and is not costeffective36.

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12. Thelaide E. The microbiology of the necrotic pulp. In: Bergenholtz G, Horsted-Bindslev P, Reit C. Textbook of Endodontology. London: Blackwell Mungsgaard 2003:116-118.

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Available at: http://www.Scholarware.com/ulsd 2003/responsible.doc. Accessed 22 Sept 2008.

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15. Keenan JV, Farman AG, Fedorowicz Z, Newton JT. A Cochrane systematic review finds no evidence to support the use of antibiotics for pain relief in irreversible pulpitis. J Endod 2006;32:87-92.

16. Whitten BH, Gardiner DL, Jeansonne BG, Lemon RR. Current trends in endodontic treatment: report of a national survey. J Am Dent Assoc 1996;127:1333-1341.

17. Dailey YM, Martin MV. Are antibiotics being used appropriately for emergency dental treatment? Antibiotics use and misuse: a prospective clinical study. Brit Dent J 2001;191:391-393.

18. Nagle D, Reader A, Beck M, Weaver J. Effect of systemic penicillin on pain in untreated irreversible pulpitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:636-640.

19. Yingling NM, Byrne BE, Hartwell GR. Antibiotic use by members of the American Association of Endodontists in the year 2000: report of a national survey. J Endod 2002;28:396-404.

20. Mohammadi Z. Antibiotics as intracanal medicaments: a review. J Calif Dent Assoc 2009;37:99-108.

21. Abott PV. Selective and intelligent use of antibiotics in endodontics. Aust Endod J 2000;26:30-39.

22. Karim IE, Kennedy J, Hussey D. The antimicrobial effects of root canal irrigation and medication. Oral Surg Oral Med Oral Pathol Endod 2007;103:560-569.

23. Molander A, Reit C, Dahlen G. Microbiological evaluation of clindamycin as root canal dressing in teeth with apical periodontitis. Int Endod J 1990;23:113-118.

pyrig No Co t fo 24. Takushige T, Cruz EV, Moral AA, Hoshino rE.PEndodontic ubantibactreatment of primary teeth using a combination of lica terial drugs. Int Endod J 2004;37:132-138. ti 25. Prabhakar AR, Sridevi E, Raju OS, Satish te V. Endodontic on treatment of primary teeth using combination ssofeantibactenc e rial drugs: an in vivo study. J Indian Soc Pedod Prev Dent

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2008:5-10.

26. Hoshino E, Asgor MA, Yagi M, Cruz EV et al. 2044 LSTR 3 Mix – MP NIET in Area Oral Health Program. Under ‘Cariology research’. In: Dental material for prevention.

Report presented at IADR/AADR/LADR 83rd general session, Baltimore, MD 2005.

27. Hoshino E, Asgor MA, Yagi M, Garcia EV. 1786 Oral health program using LSTR 3mix-MP NIET therapy. Available at: http://iadr.confex.com/iadr/2006Orld/techprogram/abstract_73714.htm. Accessed 22 Nov 2008.

28. Rosenberg B, Murray PE, Namerow K. The effect of calcium hydroxide root filling on dentine fracture strength. Dent Traumatol 2007;23:26-29.

29. Ozan U, Er K. Endodontic treatment of a large cyst-like periradicular lesion using a combination of antibiotic drugs: a case report. J Endod 2005;31:898-900.

30. Er K, Kustarci A, Ozan U, Tasdemir T. Nonsurgical endodontic treatment of dens invaginatus in a mandibular premolar with large periradicular lesion. J Endod 2007;33:322-324.

31. Windley W, Teixeira F, Levin L, Sigurdsson A, Trope M. Disinfection of immature teeth with a triple antibiotic paste.

J Endod 2005:31:439-443.

32. Alam T, Nakazawa F, Nakajo K, Uematsu H, Hoshino E. Susceptibility of enterococcus faecalis to a combination of antibacterial drugs (3mix) in vitro. J Oral Biosci 2005;47:315-320.

33. Mohammadi Z, Abott PV. On the local application of antibiotics and antibiotic-based agents in endodontics and dental traumatology. Int Endod J 2009;42:555-567.

34. Torabinejad M, Khademi AA, Babagoli J, Cho Y, Johnson WB, Bozhilov K et al. A new solution for the removal of the smear layer. J Endod 2003;29:170-175.

35. Torabinejad M, Shabahang S, Aprecio RM, Kettering JD. The antimicrobial effect of MTAD: an in vitro investigation.

J Endod 2003;29:400-403.

36. Lesion sterilization and tissue repair technique. Available at: www.pediatricdentistry. com.ph/PPDSI/LSTR.puff. Accessed 21 Jan 2009.

37. Wilson W, Taubart KA, Gewitz M, Lochardt PB, Baddour LM, Levison M et al. Prevention of infective endocarditis: guidelines from the American Heart Association. J Am Dent Assoc 2008; 139:3S-24S. 38. Prophylaxis against infective endocarditis: antimicrobial prophylaxis against infective endocarditis in adults and children undergoing interventional procedures (issued by National Institute for Health and Clinical Excellence, March 2008).

39. Lavelle CLB. Is antibiotic prophylaxis required for endodontic treatment? Endod Dent Traumatol 1996;12:209-214.

40. Guidelines on appropriate use of antibiotic therapy for pediatric dental patients. AAPD reference manual 2007/08;29:199-201.

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