Antimicrobial therapies for odontogenic in children and adolescents. Literature review and clinical recomendations. Caviglia Inés *, Techera Adriana *, García Graciela *.

Abstract Oral infections are caused by an imbalance in the patient’s indigenous flora which changes from commensal to opportunistic. Odontogenic infections are the most common reason for consultation in children and adolescents. Rational use of is the best strategy to avoid microbial resistance. Dental infections should first receive proper local treatment, which can also be complemented with a systemic method. Appropriate drug selection and dosing should be made. Amoxicilin is the first choice for antimicrobial agents in pediatric dentistry. Clindamycin and clarithromycin are the best alternative for patients with penicillin hypersensibility. In this literature review, the authors intended to establish clear clinical management guidelines for emergency treatment and subsequent final resolution.

Keywords: Antibiotics, microbial drug resistance, dental focal , children and adolescents.

The original version of Antimicrobial therapies for odontogenic infections in children and adolescents. Literature review and clinical recomendations was published in J Oral Res 2014; 3(1): 50-56 (DOI: 10.17126/joralres.2014.013). Permission to reproduce the paper in Odontoestomatología was granted on 31 March,2016.

* Facultad de Odontología, Universidad de la República, Uruguay. Receipt: 10/19/2013 Revised: 11/11/2013 Acceptance: 12/10/2013 Online: 12/10/2013

4 Odontoestomatología / Vol. XVIII Nº 27 / May 2016 Introduction These oral infections can show themselves in an acute form (acute onset, quick evolution Oral infections are polymicrobial and mixed. and evident signs and symptoms), or in They arise when normal flora changes a chronic form (slow onset and evolution from commensal to opportunistic due to showing less obvious signs and symptoms). a broken balance with the host in certain 1. They are classified as odontogenic and non- circumstances odontogenic. Odontogenic infections are the The oral microbial flora starts to grow in the most frequent and begin affecting peridental newborn’s mouth about 8 hours after birth. and dental structures. Non-odontogenic This is followed by a continuous change in infections start in extra dental structures, its composition from the time the child is such as mucous, glands, tongue, etc6. edentulous until teeth appearance2-5. (Table 1)

Table 1. Microbial flora evolution comparison between edentulous and dentate children.

These infections are usually localized and children and adolescents. Therefore, body size respond well to treatment. However, favored and composition, immature gastrointestinal, by children’s special features, they can spread renal and immune system and nutritional to remote regions and cause serious processes status should be considered when assessing compromising even the patient’s life. General odontopediatric patients7-8. anatomical and physiological characteristics of In the same way, jaw anatomical features also children are varied because the age range covered differ. They present dental follicles, more by Pediatric Dentistry is wide. For instance, cancellous bone with bigger medular holes the percent of body water and fat, as well as and growth sites which make the infectious liver enzymes and plasma proteins levels, are process spread quicker than in adults. For different in neonates and infants from those of this reason, control in children should be

Antimicrobial therapies for odontogenic infections in children and adolescents. Literature review and clinical recomendations. 5 in a short time. The pediatric dentist must About 10% of prescribed antibiotics are used take patient evolution into account and pay for treating oral infections6, 10-13. attention to alarm signs which may lead to Antimicrobials are indicated for therapeutic hospitalization. The Consensus Document purposes: to eliminate infection, make it less on Antimicrobial Treatment of Odontogenic severe, make evolution shorter and prevent Bacterial Infections9, written by specialists in general complications. Besides, they are microbiology and odontology in Spain and used for preventive purposes in subjects with modified for Pediatric Dentistry (Table 2), underlying diseases such as cardiac illnesses or considers these causes for hospitalization of a immunocompromised patients. child or adolescent with odontogenic cellulitis: Inappropriate and irrational use of • General affectation and/orantimicrobials creates favorable conditions immunocompromisedpatient (, for resistant organisms to appear, spread , HIV, etc). and persist, causing infections which do not • Rapidly progressive cellulitis. respond to standard treatment14. • Cellulitis extending to deep facial spaces. For odontogenic infections in temporary or • Fever higher than 38°C, dyspnea and/or young permanent dentition, local treatment dysphagia and/or severe trismus limiting is imposed. It always includes access opening mouth opening less than 10 mm. to the infected tooth debridement with • Patient or family unable to comply with or without ducts in order to decompress the prescribed treatment. the affected area. Sometimes, it must be • Failure of initial treatment. supplemented with mucosal drainage if there is a real collection of suppurative process. This is performed by an incision or mucosal necrosis with trichloroacetic acid in the largest decline. For limited to ground tooth abscesses, for example, local procedure is usually enough. However, if the abscess is more diffuse (covering neighboring areas, bottom of vestibule or other facial regions or affecting the patient’s general appearance), local treatment should be supplemented with an therapy to limit the infectious process expansion. If local handling is not properly done and only antibiotics are prescribed, the virulence process decreases. Consequently, it will become acute again when medication is discontinued. Once the process is reverted, it is time to decide whether the best treatment is conservation Table 2. Hospitalization criteria for pediatric of the causal tooth with proper endodontic patients with odontogenic infections, modified treatment and restoration or extraction. Just for dentistry use from “Consensus Statement on then, the urgency is considered resolved. Antimicrobial Treatment of Odontogenic Bacterial Infections. Bascones Martinez et al.” Extracting the causal tooth during the

6 Caviglia Inés, Techera Adriana, García Graciela emergency while the infection is acute is the current means of transport harm the absolutely contraindicated in children and effectiveness of health care and security. Fast adolescents. Local treatments are always mobility for humans and goods also enables performed with and without adjuvant microorganism transportation between antimicrobial medication, as described, until continents14. Therefore, a serious updated the infection is controlled and becomes study of antimicrobials is imposed for their chronic or the process cools; the reason is proper use, without excesses generating new to avoid producing bacteremia through the resistance. spreading routes. When anesthesia does not go deep in infected areas with acid pH, it produces pain which can affect children and Rational use of medicines (RUM) adolescents’ subsequent care. Among strategies to prevent microbial There is enough scientific evidence linking resistance, one of the most important is the oral infections to systemic diseases15-19. rational use of antimicrobials. However, although odontogenic infections It is important for patients to receive the are common in children and adolescents, appropriate medications for their clinical there are few published works and a needs: dosing to meet individual requirements striking dispersion criteria in terminology, for an adequate period of time at the lowest classification and treatment guidelines9, 20. cost for them and their community14, 22. The purpose of this literature review is These are other mechanisms currently used to to establish clear and updated guidelines prevent antimicrobial resistance: for clinical management, prevention and • Graduate and postgraduate medical treatment of oral infections in this age group. education on infectious diseases and evidence-based antimicrobial prescription. Overview • Monitoring programs for resistant Antibiotics era begins with the discovery strainsemergence23. of penicillin by Fleming in 1928. This is a • Rational use of antimicrobials for animal substantial change for successful infection food production in veterinary medicine treatment. From then on, new types of • Cyclic rotation of antibiotics in health antimicrobial agents have constantly arisen institutions (a novel concept with to control infections and overcome resistance questionable results)21-24. caused by bacteria, viruses, fungi and protozoa, • Hospital infections control and prevention and their destructive action21. Presently, • Increasing vaccines use21. the speed at which new multi-resistant microorganisms grow, far exceeds the rate at which new antimicrobial substances arise. Choosing an antimicrobial. This serious problem concerns the medical It is vital to choose the correct antimicrobial and scientific community who fear the threat and dosage considering odontopediatric of mankind going back to pre-antibiotic patients’ characteristics. That includes their era, making many infections untreatable. different life stages as well as anatomical, The rapid spread of these organismsphysiological and metabolic characteristics, together with the efficiency and speed of namely, size and body composition,

Antimicrobial therapies for odontogenic infections in children and adolescents. Literature review and clinical recomendations. 7 immature gastrointestinal, hepatic, renal and Considering all these elements and the immunological systems. infected area (oral cavity) and flora associated Anatomical features of children’s jaws are with it, drug choice is made empirically6-25. unique because they present dental follicles, In children and adolescents, it is necessary larger amount of less trabeculated cancellous to inquire about the type of presentation, bone but with larger trabeculae, highly whether pediatric tablets or solution, vascularized with extensive marrow spaces they commonly use. Regardless of age, it and presence of bone growth centers7-8. can happen some children take pills and These conditions vary as the child grows. teenagers prefer a pediatric solution. It is In this patient, health status should also be essential to give correct, detailed and accurate assessed (well-constitution, any previous information to the person responsible for the disease or if he is immunologically depressed) drug administration. and the type and severity of infection (mild, The indicated time and frequency between moderate or severe)1,25-27. takes must be respected for successful In order to arrive at the correct diagnosis and treatment26, 29, 30. prognosis to indicate a proper treatment plan When the presentation is in oral solution, it is for the patient, a complete medical history necessary to explain how to prepare, dispense should be performed. It details certain and preserve it. Emphasis should be made information about the patient, such as living not to change the dosage form by dissolving environment, customs, health coverage, solution in juices or opening capsules, to age, family and personal background, body, improve drug acceptance by the child in all fitness, nutrition, general and oral health. cases. Additionally to patient’s characteristics, which The practitioner must observe short-term are very important when choosing treatment, response to treatment, especially in children, other factors should also be considered when since infectious processes spread very fast prescribing medications. because of their anatomical, physiological, The drug, an antimicrobial agent in this case, immunological and pathological should be indicated in clinically justified characteristics25. The first control must situations and usually as a relevant adjuvant be within 24 hours after the emergency treatment6, 12, 25. Quality tested drugs consultation even by telephone if necessary. should be used in order to ensure that, with Recommended length of time must not the correct dosage according to the severity of be excessively long because it favors the infection, the patient’s age, weight, liver and emergence of resistance and possible side kidney function, the result will be as expected. effects. Neither should it be less than 7 days For selecting the administration via, nature for bacteriostatics or 5 days for bactericidals and severity of the infection and absorptive to avoid recurrence of the infection, forcing capacity of the drug need to be considered28. to repeat the treatment and favoring the When infections threaten the patient’s life, appearance of resistance by using frequent intravenous via (IV) is usually indicated. subtherapeutic doses1, 6, 12, 26. Those drugs with good oral absorption (VO) Finally, the least costly alternative compared can be used in children even in severe cases to the same benefit and safety should be because they are very well tolerated. The quite considered22. painful intramuscular route must be avoided in children and adolescents whenever possible.

8 Caviglia Inés, Techera Adriana, García Graciela Antimicrobials commonly used in organisms producing beta-lactamases through Dentistry mutations. Amoxicillin, associated with irreversible The first choice is penicillins. Among them, betalactamase inhibitors such as clavulanic Amoxicillin has bactericidal activity, good oral acid or sulbactam pivoxil, offers the chance absorption (75-90%)1, can be administered to treat infections caused by producing beta- with food intake and its half-life is longer lactamases bacteria. than the rest31. Dosing every 8 hours allows This type of associated antibiotic is the choice schedule flexibility to let the patient sleep at for patients who have been systemically night, especially when he is a child. Moreover, treated, but have not received adequate local the difference between therapeutic and toxic treatment (access opening and drainage), doses is very broad, allowing a safe dosage making the infectious process to persist. It is range32, 33. also indicated for subjects who do not do or Aantimicrobial resistance (AMR) is a do not receive an adequate antibiotic therapy growing global problem. Indiscriminate and (Table 3). excessive use of penicillins generated resistant

Table 3. Antimicrobials commonly used in pediatric dentistry. Choice and dose for patients with and without penicillin hypersensitivity. Ampicillin, due to its poor oral absorption, tissues, and is available in pediatric tablets food intake incompatibility and dosing and oral solution. Its disadvantage is the frequency (50 to 100 mg/kg/day every therapeutic and toxic doses are very close so 6 hours), is preferred to be administered it should not exceed a gram daily. parenterally. Clindamycin is taken every 6 hours and may Clindamycin (lincosamide) or clarithromycin cause diarrhea due to Clostridium Difficile (macrolide) are indicated for patients infection1. This makes it difficult for the with penicillin hypersensitivity in the patient to comply with all the indicated doses reviewed literature1, 12, 25, 27 (Table 4). but it has good distribution in bone tissue. Clarithromycin has the advantage of a more Besides, it is very effective against facultative convenient dosing every 12 hours, generates and obligate anaerobes, thus, it is reserved for less resistance, has good distribution in soft those cases.

Antimicrobial therapies for odontogenic infections in children and adolescents. Literature review and clinical recomendations. 9 In some countries there is no oral solution for occuring more than 72 hours after penicillin clindamycin presentation which is considered administration, are possibly not allergic to it. a drawback in Dentistry34-36 (Table 4). For these subjects, penicillin can be used for a severe infection if necessary.

Discussion Odontogenic infection is common and often leads to widespread and severe processes. In spite of this, the recommended treatments are not based on scientific evidence because the available clinical trials are difficult to implement and very diverse. Instead, they are based on professional agreements and consensus documents6. Due to the special characteristics explained above, the severity of these infections may be higher in children. Conducting clinical trials is more difficult in this group; that is the reason for such few publications on Table 4. Comparison table for antimicrobials used this particular population, especially in the in penicillin allergic patients oromaxillo-facial field. This motivated a literature review to generate a clear guideline for clinical resolution of The most important penicillin adverse effect is these processes in pediatric dentistry. hypersensitivity, which can go from a simple To prescribe an antimicrobial, literature rash to an anaphylactic reaction. Allergic shows it is essential to respect the reactions to penicillin are described in 0.7-10 characteristics of the drug used (time or % of exposed individuals, and anaphylactic concentration dependent), dosage form, reactions in less than 0.004 to 0.2 %32- patient characteristics, type and severity 36. It is contraindicated for individuals of infection dental care so it must be a with anaphylaxis history, urticaria or rash positive experience. It is important to immediately after penicillin administration avoid additional pain and effectively solve because of the immediate hypersensitivity the patient’s problem. For this reason, it is risk. In such cases, neither cephalosporins or recommended to use procedures to calm other beta -lactam antibiotics are used as they the infectious process during emergency share the basic structure30, 34. Subjects with treatment and, later, the definitive treatment a minor eruption history (not confluent and can be done. (Table 5) restricted to a small area of the body) or one

10 Caviglia Inés, Techera Adriana, García Graciela Table 5. Schematization of the integral treatment recommended in pediatric dentistry for odontogenic infections in non- allergic and allergic penicillin patients.

These guidelines aim to rationalize the use of improve acceptance by the child. There are antibiotics in pediatric dentistry, providing few references in the literature to provide clear criteria for treatment that minimizes information on antimicrobial use in dental antimicrobial resistance according to the origin infections in pediatric dentistry. RUM current criteria. Clinical experience Literature and clinical experience show shows that urgency is often the entrance for amoxicillin is the first choice for children. the child or adolescent’s Amoxicillin associated with sulbactam pivoxil or clavulanic acid is indicated in patients who previously received inadequate systemic Conclusions treatment. Dental Infections, should first receiveFor patients with penicillin hypersensitivity, the appropriate local therapy which can clindamycin or clarithromycin are the correct sometimes be complemented with a systemic choice. Literature and clinical experience treatment. Therefore, treatment of anindicate it is convenient to avoid radical odontogenic infection is based on local or procedures such as extractions at the acute combined (local and general) methods25. stage of infection, taking into account It is vital to obtain a correct diagnosis the patient’s anatomophysiological and through a complete medical history to offer psychological aspects The best thing to do is an appropriate treatment. If antimicrobial to limit and cool the process and decide the therapy is decided, the professional must definitive treatment then. Correct emergency make the correct drug choice according handling can change an unpleasant situation to the patient and case. Submedication into a valuable opportunity for the patient should be avoided (at a dose and/or time) and his family to be incorporated in oral as well as changes in the dosage form to health care. This emphasizes health education, prevention, rehabilitation and periodical

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Graciela García: dragracielagarcí[email protected]

14 Caviglia Inés, Techera Adriana, García Graciela