role of antibiotics in paediatric endodontics

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REVIEW

Gurusamy KayalvizhiDepartment of Pedodontics and Preventive Dentistry, M. R. Ambedkar Dental College and Hospital, Bangalore, India

Correspondence to:Gurusamy KayalvizhiDepartment of Pedodontics and Preventive Dentistry No 9, 8th Maruthi Cross, Post Office RoadRamamurthy Nagar Bangalore 560016, Karnataka, IndiaTel: (0091) 988 612 0559Email: [email protected]

Gurusamy Kayalvizhi

Role of antibiotics in paediatric endodontics

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

Introduction n

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 causa-tive 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, top-ical and prophylactic role in paediatric endodontics.

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 antibi-otics 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.

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Role of systemic antibiotics in nendodontics5

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

Selecting an antibiotic n

The child is not a miniature adult, thus paediatric dentists must consider their differences when mak-ing therapeutic choices for young patients, espe-cially when treatment includes drug therapy. These include the following:

Young children tend to lack medical antecedents suggesting the possibility of drug allergies or ad-verse reactions.The greater proportion of water in the tissues of children and their increased bone sponginess facilitate faster diffusion of infection; hence, ad-equate dose adjustment is recommended.The gastrointestinal tract undergoes continuous developmental change from birth to old age. In-fants 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.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.Drug metabolism and excretion are profoundly affected by the size of various body fluid com-partments.Children need smaller drug doses to maintain therapeutic drug concentration, and those smaller doses are enough to produce toxicity. The ‘maxi-mum safe dose’ listed in standard drug reference manuals is enough to overdose a paediatric pa-tient, thus weight-based formulas are much safer in the paediatric population.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-

edge6,7. If in doubt, paediatrician consultation is recommended.

Commonly used drugs in nendodontics4,5,8,9

Penicillin VK is effective against most aerobic and anaerobic bacteria associated with endodon-tic infections. Erythromycin, which is commonly prescribed for penicillin-allergic patients, has been found to be ineffective against most of the anaerobes associ-ated with endodontic infections. Clindamycin is an appropriate substitute in pa-tients allergic to penicillin. It is beta-lactamase-resistant and is highly effective against facultative and strict anaerobic bacteria associated with en-dodontic infections. It penetrates into abscesses and any other areas of poor circulation. Clarithromycin has a more limited spectrum of activity than clindamycin but has some advan-tages over erythromycin. Clarithromycin is effec-tive 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.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.Tetracycline kills the broadest spectrum of mi-crobes. 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 discolora-tion, and can continue to do so beyond this age by becoming deposited in secondary dentine10.

Root canal: To culture or not? n 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 knowl-edge of those organisms most likely to be associated

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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 endodon-tic infections is rarely recommended. The variety of microorganisms involved makes a positive identifica-tion 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.

Problems in root canal cultures n

Sampling: a technical difficulty, associated with obtaining samples for culturing, as sterile asep-sis is necessary during sampling due to the risk of contamination from teeth (plaque of caries), oral mucosa, saliva, fingers and instruments.Transport: death of microorganisms/overgrowth of others.Cultivation: inadequate media, uncultivable or-ganisms.Identification: time-consuming – as it takes 1 to 2 weeks to identify anaerobes – and expensive.Exact time of initial infection is difficult to as-certain. 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.

Duration of antibiotic therapy n

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 dura-tion should be the shortest cycle capable of prevent-ing 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 infec-tion5,8,11,14.

Indications for the use of systemic nantibiotics in endodontics4,5,8,9,11

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.For progressive or persistent infections that have systemic signs and symptoms, the use of adjunc-tive antibiotics is recommended in conjunction with appropriate endodontic treatment for the effective debridement of the root canal (Fig 1).Use of antibiotics is indicated if swelling con-tinues to spread despite attempts to disinfect the root canal system and establish drainage (Fig 2).If bacteria are too virulent or the immune system becomes too weak to control their growth, then antibiotics are necessary.

Contraindications for the use of systemic nantibiotics in endodontics4,5,8,13

Irreversible pulpitis with or without acute peri-radicular periodontitis (no systemic signs of in-fection): it is an immune system mediated event, usually not due to bacterial infection but, rather, a result of inflammatory mediators overcom-ing the host defences. A Cochrane systematic review15 found no evidence to support the use

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

Fig 1 Persistent swelling.

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of antibiotics for pain relief in irreversible pul-pitis, and the conclusion from various studies has shown that penicillin does not reduce the pain, percussion sensitivity or amount of an-algesics 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.Symptomatic apical periodontitis. Localised swelling: the circulation within the pulp is compromised in the presence of the inflamma-tion or infection, because when an antibiotic is carried by the vascular system, its ability to reach bacteria in a therapeutic concentration will be lim-ited, diminishing the efficacy of the antibiotic.Draining the sinus tract: occasionally the infec-tious 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 natu-rally occurring sinus tract. Even if antibiotics are used, the immune system cannot function opti-mally until the purulence is eliminated.

Over-prescription and misuse nof antibiotics4,13,20

Over-prescription of antibiotics for upper respira-tory tract infections and dental pain is emerging as a growing threat.

It increases the chances of super-infections with the development of multi-drug resistant strains of bacteria (super bugs).Allergic reactions, adverse reactions and drug–drug interactions may occur.Antibiotic resistance: bacteria can become resist-ant to drugs through mutation and ‘selective pres-sure’. With designer drugs12 on the horizon, re-

searchers believe that studying bacterial function at the molecular level holds the key to rapid new drug development. Future antibiotics may be ’cus-tomised’ to disarm bacteria chemically and thus prevent the development of resistant strains.To prescribe too little or for too short a duration will kill weaker organisms, leaving more substrate available for those with greater virulence to be-come entrenched.

Recommendations for the prudent use nof antibiotics4,5,21

Researchers at the Centers for Disease Control and Prevention (CDC) estimate that approximately one third of all outpatient antibiotic prescriptions are un-necessary. As clinicians discover the gravity of this situation, they are re-evaluating how and when to prescribe antibiotics. Understanding the microbiol-ogy 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 ori-gin 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 heal-ing process.

Topical antibiotics n

The interest in topical antibiotics reached a peak in endodontics 40 years ago and subsequently de-clined2. Bacteria within the root canals are inac-cessible to irrigation and the mechanical cleaning

For the clinician Advice to the patients

likely to be beneficial to the patient.

pathogens.

dose and duration.

else; they may not be appropriate for the current infection and might allow bacteria to multiply.

antibiotics and do not ‘save’ medication for later use.

Table 1 CDC recom-mendations for appro-priate antibiotic use.

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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.

History of topical antibiotics in nendodontics3,22

Grossman’s polyantibiotic paste (penicillin, baci-tracin, chloremphenicol, streptomycin) was intro-duced in 1951. It was ineffective against anaer-obes and the use of penicillin induced an allergic reaction.A mixture of neomycin, polymyxin and nystatin was found to be unsuitable against endodontic bacteria.Clindamycin has been tried as a root canal dressing23. It was unsuccessful, as clindamycin- resistant enterococci were recovered from the root canal 10 days after placement of the root canal dressing. Besides, it had no advantage over calcium hydroxide.Three-mix medicament (ciprofloxacin, metroni-dazole, 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.

Pulpotomy/pulpectomy medicament n

Disinfection of the root canal and the periradicular region results in good healing of the periradicular region. The application of antibacterial drugs to en-dodontic lesions is one of the clinical procedures that can be used to sterilise such lesions. One such tech-nique is LSTR (lesion sterilisation and tissue repair), which employs the use of a mixture of antibacte-rial 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 clini-cal outcomes have been observed in the first- and second-year area oral health programme26,27.

Root canal medicaments nThe use of an intra-canal medicament might be help-ful in eliminating remaining bacteria that survived inside root canals after complete chemo-mechanical preparation. The reliance on mechanical instrumenta-tion 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 api-cal 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 bac-teria from the root canal system5,11.

Antibiotics in different combinations have been tried in root canal dressings and found to be effec-tive2. 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 disin-fection of immature teeth31 in dogs, and in inhib-iting enterococcal growth20,32. Thus, with further research, it could possibly be used as an intra-canal medicament in children.

Root canal irrigant n

Although mechanical instrumentation of root ca-nals can reduce the bacterial population, effective elimination of the bacteria cannot be achieved with-out 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 in-troduced, 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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Tetraclean, like MTAD, is a mixture of an anti-biotic, an acid and a detergent. However, the con-centration of antibiotic doxycycline (50 mg mL-1) and the type of detergent (propylene glycol) differs from that of MTAD. It has very low surface ten-sion and a high degree of efficacy against bacterial biofilms. However, these effects have recently been challenged by different investigators21,33,34,35, war-ranting further research.

Concerns n

The use of systemic antibiotics for topical applica-tion is questionable. Although metronidazole use is considered to be clinically safe, ciprofloxacin and minocycline side effects have to be taken into consideration. Leakage of antibiotic paste into the oral cavity could have an effect on oral microflora.Potential for bacterial resistance, risk of drug hy-persensitivity 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.

Prophylactic antibiotics n

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.

Recommendations for antibiotic nprophylaxis37,38

Based on the recent guidelines, prophylaxis is recom-mended before dental procedures only for those at high risk (AHA) or at risk (NICE [National Institute for Health and Clinical Excellence] guidelines) of develop-ing infective endocarditis (Table 2).

Antibiotic prophylaxis recommended nfor dental procedures

AHA: ‘All dental procedures that involve manipula-tion of gingival tissue or the periapical region of teeth or perforation of oral mucosa’37.

NICE: This guideline recommends that antibi-otic 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.

The bases to support this nrecommendation are:

There is no consistent association between having an interventional procedure, dental or non-dental, and the development of IE.

Regular toothbrushing almost certainly presents a greater risk of IE than a single dental procedure because of repetitive exposure to bacteraemia with oral flora. The clinical effectiveness of antibiotic prophylaxis is not proven. Antibiotic prophylaxis against IE for dental procedures may lead to a greater number of deaths through fatal anaphylaxis than a strategy

AHA (2007): High-risk group NICE (2008): At-risk group

approved the guidelines for the prevention of bacterial endocarditis developed by the AHA. These guidelines stress that children with a history of intravenous drug administration and children with certain syndromes (e.g. Down’s syndrome, Marfan syndrome) may be at risk of developing bacterial endocarditis, due to associated cardiac anomalies7.

-gitation

-cally corrected or palliated structural conditions, but excluding isolated atrial septal defect, fully repaired ventricular septal defect or fully repaired patent duc-tus arteriosus, and closure devices that are judged to be endothelialised.

Table 2 Antibiotic prophylaxis recom-mended to those individuals at high risk (AHA) and at risk (NICE guidelines) of develop-ing infective endocar-ditis.

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of no antibiotic prophylaxis, and is not cost-effective36.

Patients at risk of infective endocarditis should maintain good oral hygiene to prevent it, since sys-temic antibiotics, local antiseptics or antibiotics can-not eliminate the periodontal or pulpal microflora. Bacteria may still survive in the dentinal tubules and other canal ramifications that are inaccessible to me-chanical instrumentation and irrigation.

Controversies n 37,38,39

Five clinical guidelines on the prevention of IE – American Heart Association (AHA) 2007, British So-ciety 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:

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 bacter-aemia, in terms of colony forming units (CFU), is very large.

– The BCS/RCP continued to recommend anti-biotic prophylaxis for many dental and non-dental procedures.

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

– NICE recommended no prophylaxis for dental procedures.

No age distinctions as they are prescribed more frequently for the young than the old. In addi-tion, none of the above bodies present specific guidelines for antibiotic prophylaxis in patients with prior antibiotic therapy for periapical/other infections. 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-

terventional procedure (both dental and non-dental).

Although these guidelines are broad and non-spe-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 (in-cluding 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 paedia-trician to assess the status of a child and to deter-mine 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.

Conclusion n

The prudent use of antibiotics to treat an endodon-tic infection is an integral part of appropriate treat-ment. 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 commu-nity as a whole and restrict the use of antibiotics only to those situations that actually require them.

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role of antibiotics in paediatric endodontics

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