Gutiérrez JL, Bagán JV, Bascones A, Llamas R, Llena J, Morales A, Noguerol B, Planells P, Prieto J, Salmerón JI. Consensus document on the use of antibiotic prophylaxis in dental surgery and procedures.

Consensus document on the use of antibiotic prophylaxis in dental surgery and procedures

Gutiérrez JL1, Bagán JV2, Bascones A3, Llamas R4, Llena J5, Morales A6, Noguerol B7, Planells P8, Prieto J9, Salmerón JI10

SUMMARY

The goal of antibiotic prophylaxis in Odontology is to prevent the onset of infections through the entrance way provided by the therapeutic action, therefore it is indicated provided there is a considerable risk of infection, either because of the characteristics of the operation itself or the patient’s local or general condition. Nonetheless, clinical trials with antibiotics in dental pathologies scarcely adhere to the required methodological criteria and, in addition, are not sufficiently numerous. This text presents the results of an expert conference comprising the Presidents of the most representative Scientific Societies in Spain who have analyzed the existing literature and have drawn on their valuable professional experience. It describes the technical circumstances, analyzes the biological and pharmacological foundations and their application to the most representative medical situations. It is concluded that antibiotic prophylaxis in Odontology has certain well-founded, precise indications and offers the international scientific community a practical protocol for action.

Key words: Profilaxis, antibióticos, infecciones orales.

Aceptado para publicación: Octubre 2005

1 Spanish Society for Mouth Surgery. 2 Editor of the “Revista Medicina Oral, Patología Oral, Cirugía Bucal” Journal. 3 Spanish Society for Oral Medicine. 4 Spanish Society for Conservative Odontology. 5 Spanish Society for Dental Prosthetics. 6 Spanish Society for Implantology. 7 Spanish Society for Periodontics. 8 Spanish Society for Paediatric Odontology. 9 Spanish Society for Chemotherapy. 10 Spanish Society for Oral and Maxillofacial Surgery.

Gutiérrez JL, Bagán JV, Bascones A, Llamas R, Llena J, Araceli Morales, Noguerol B, Planells P, Prieto J, Salmerón JI. Consensus document on the use of antibiotic prophylaxis in dental surgery and procedures. Av. Odontoestomatol 2006; 22-1: 69-94.

INTRODUCTION complication and the corresponding clinical conse- quences. Classically, prophylaxis has been considered pre- or peri-operative administration of an antibiotic for The aim of antibiotic prophylaxis in surgery is to prevention of a local and/or systemic infectious prevent the possible appearance of infection in the

AVANCES EN ODONTOESTOMATOLOGÍA/69 AVANCES EN ODONTOESTOMATOLOGÍA Vol. 22 - Núm. 1 - 2006 surgical wound, through antibiotic concentrations infecting innoculant increases as the surgical time in blood that avoid bacterial proliferation and extends. Thus, the probability of infection around dissemination right from the point of entry that the dental implants depends basically on how traumatic surgical wound represents. or prolonged the surgery is4, it being considered that the infrequent precocious losses of the implant5 10% of antibiotic prescriptions made in our country are due to contamination during the insertion are used for odontogenic infections, and a significant phase6. part of them are for prophylaxis in dental surgery and procedures1. Like recommendations about use of Mono-microbial systemic infections are infections that antibiotics in odontogenic infection treatment, take root in patients with infection-susceptible focal antibiotic prophylaxis recommendations cannot be point (endocardial alterations, bone or joint based on clinical trials (nor on Evidence-Based Me- prostheses), in patients with higher susceptibility to dicine), since clinical trials with antibiotics in dental systemic infection by certain micro-organisms pathologies respond little to the required metho- (splenectomized patients or those with infection by dological criteria, and furthermore are not sufficiently encapsulated bacteria of the Streptococcus or numerous to establish a line of conduct. Therefore, Haemophilus genera), or in patients with generalized the general therapeutic or prophylactic antibiotic alterations of the immune system that facilitate prescription strategy is based on professional septicaemia (immunodepressed, immuno-compro- agreement and consensus documents. mised and malnourished). Generally, the first step tends to be bacteraemia, which is produced after an The recommendations proposed in this document invasive procedure. This bacteraemia is well studied are based on the consensus of the professionals who in very prevalent periodontal disease (periodontitis) participated in developing it. which seems to occuer due to the permeability of the epithelium that surrounds the tool-tissue interface, and the levels of prostaglandin in the local circulation that increase the number of leukocytes and fibrinogen THEORETICAL BACKGROUND levels, slowing down circulation in these cases, thus favouring the passage of bacteria to the blood.7 Thus, in animal models, endocarditis subsequent to Complications to avoid bacteraemia is 48% in rats with periodontal diseases versus 6% in healthy rats.8 In humans, bacteraemia Multi-microbial local infections are cutaneous-mu- subsequent to invasive procedures is around 51- cosa, dental or bone infections that are encouraged 55%.9 following invasive dental procedures2 and they translate clinically into swellings, abscesses, loss of teeth, implants or prosthetic structures. In a study Cost-Benefit balance done in our country, it was demonstrated that the complications subsequent to extraction of the third The physician’s criterion for choosing antibiotic molar are an infection and not exclusively inflam- prophylaxis or not must be based on the benefit matory, since statistically significant differences were and the cost of the risk. The economic cost of found in the frequency of infectious complications prophylactic operations (usually short-term) is among groups who received preventive treatment (5 acceptable when compared with the total cost of days) or pre-operative prophylaxis (single dose) with dental treatment. Obviously, the benefit is the amoxicillin / clavulanate 2000/125 mg, and the group prevention, by the antibiotic, of the infectious that received placebo (2.7%, 5.3% and 16% complications subsequent to surgery and/or respectively)3. Rates of infectious complication procedures. Lastly, the risk of antibiotic prophy- were higher in the case of osteotomy or longer laxis is the appearance of adverse reactions surgical duration, treatment being clearly better in (fundamentally allergic) and the selection of these cases than prophylaxis or placebo. The resistances.

70/AVANCES EN ODONTOESTOMATOLOGÍA Gutiérrez JL, Bagán JV, Bascones A, Llamas R, Llena J, Morales A, Noguerol B, Planells P, Prieto J, Salmerón JI. Consensus document on the use of antibiotic prophylaxis in dental surgery and procedures.

Target bacterial population The micro-organisms most frequently involved are Streptococcus of the viridans group, followed by coa- The target bacterial population depends on the gulase-negative (epidermidis) and coagulase-positive location of the infectious complication to be covered. (aureus, and perhaps lugdunensis) species of the Thus, local infections following odontogenic proce- genus Staphylococcus, of oral origin,18 and lastly in dures are habitually multi-microbial, since many of 4-7% of cases, Gram-negative bacilli of the HACEK the species isolated tend to go in pairs (Bacteroides group (Haemophilus, Actinobacillus, Cardio- sp and Fusobacterium; Peptostreptococcus sp. and bacterium, Eikenella, Kingella), several of which are Prevotella sp.; Prevotella sp. and Eubacterium sp.)10,11 considered odontopathogens.19 Nor must we forget with a strong aerobic/anaerobic component,12,13,14 and the high percentage of bacteraemias by anaerobes to a much lesser degree, a micro-aerophil component, (Eubacterium, Peptostreptococcus, Propionibac- corresponding to the possible contamination/ terium, Lactobacillus) that are detected when the infection during surgery by a normal microbiote of proper methods are used (blood cultures for the mouth and saliva, as well as by odontopathogens anaerobes).20,21 Table 1 shows the most frequent of periodontal disease, which has very high prevalence odontogenic pathogens. (50% of the adult population has gingivitis and 30% periodontitis).15 Antibiotic administration regimen The systemic infections to be prevented in patients with underlying disease are those subsequent to post- The main goal of antibiotic prophylaxis is to attain dental manipulation bacteraemia that generally occur elevated levels of antibiotic in serum during the after invasive procedures. This bacteraemia is surgical process, and for some hours after the incision generally mono-microbial, and is originated by is closed. In this sense, the dose used must be high, contamination/infection by a normal microbiote or never lower than that used as treatment. odontopathogen during surgery. We have known Administration prior to surgical intervention or the since the 1930s that, following dental manipulation, procedure may be sufficient in most interventions. the number of blood cultures positive for Strepto- Only in those cases in which the half-life of the coccus is 75% in individuals with caries, gingivitis antibiotic is less than one hour and the duration of and periodontitis, versus 30% in healthy subjects.16,17 the intervention 2-3 hours, or more than twice the

TABLE 1.- PATHOGEN ISOLATES OF PATIENTS WITH ODONTOGENIC INFECTION

Aerobc Nº Anarerobc Nº Streptococcus grupo viridans 139 Peptostreptococcus 105 Staphylococcus 9 Prevotella pigmentada 93 Corynebacterium 9 Fusobacterium 90 Campylobacter 9 Prevotella no pigmentada 56 Neisseria 8 Gemella 36 Actinomyces 7 Porphyromonas 35 Lactobacillus 6 Bacteroides 14 Others 13 Others 35 Total 200 Total 464

AVANCES EN ODONTOESTOMATOLOGÍA/71 AVANCES EN ODONTOESTOMATOLOGÍA Vol. 22 - Núm. 1 - 2006 half-life of the antibiotic, would it be necessary to Generally speaking, the incidence of adverse effects repeat the dose. Similarly, if there is more than 1-2 L of antibiotics or idiosyncratic reactions to them is of blood loss during the procedure, administration of low. This allows, e.g. for prophylaxis in situations such an additional dose of antibiotic should be as bacterial endocarditis in patients with no history considered.22,23,24,25 of penicillin allergy, the use of a single dose of amoxicillin 2 g without fear of encountering anaphylactic reactions.28 The patient’s state of health Selection of resistance in normal flora (pharyngeal or Invasive oral dental procedures (intraligamentary lo- intestinal) depends on the type of antibiotic used, cal anaesthesias, endodontia procedures, curettage, since the resistance selection capacity is different for placement of probes, single and multiple dental each compound,29,30 and less with short periods at extraction, transplants/re-implants; and periapical, high prophylaxis or treatment doses.31 periodontal, bone and implant surgery or surgery of the mucosa as well as biopsy of the salivary glands, etc.) entail a risk of infection in healthy subjects in Decision making (equational empiricism) some cases, and always in individuals at risk for local and/or general infection (individuals with transplants, In the last instance, the decision prophylaxis is up to implants, immuno-depressed, or suffering from the physician, who will use the equation: risk = degree malnourishment or uncontrolled associated of damage x probability of suffering it. This approach pathology, etc.).2,26 is subjective. Faced with the probability, even remote, of irreparable damages, the prevention of systemic Non-invasive oral-dental procedures (application of infectious complications (for ex. infectious endocardi- fluoride or sealing of fissures, blood-free prosthetic tis, late-onset infection of a joint prosthesis) can be care, post-surgical suture removal, orthodontia, seen as more important by the specialists treating them radiology and non-intraligamentary anaesthesia) do (cardiologists, traumatologists, infectologists, …). The not present risk of infection either in healthy subjects prevention of local complications (for ex. peri-implantitis) or in those at risk, and therefore they are never as a result of dental manipulations is preceived as more candidates for antibiotic prophylaxis.2,26 important by the specialist in question.

In the case of subjects with risk of systemic infection (individuals with risk of endocarditis and those with CLINICAL BASES joint prostheses), prophylaxis will be indicated for invasive procedures, and will be true pre-operative The appearance of a continuity solution in the skin, prophylaxis (the concept of preventive treatment is not mucosa or hard tissues of the mouth consequent to applicable in this case)2,26 and generally in a single surgical or procedural trauma leads to the alteration dose. It is in these latter cases that medical and legal of the main barrier that stops invasion by micro- implications are discussed most, as legal disputes have organisms. This is how pathogens enter and can arisen due to the absence of prophylaxis or due to the colonize and infect deep tissues. This means that, administration of incorrect antibiotics or at incorrect depending on the bacterial inoculate, the possibility times in the prevention of bacterial endocarditis.27 of infection increases depending on whether the procedure or surgery is clean, clean-contaminated, contaminated or dirty. The greater the degree of conta- Undesirable effects (economic, biological mination, the greater the risk of post-surgical infection. resistance, medical and allergic) The risk of contamination of the surgical field Due to the exclusive action of antibiotics on bacterial increases with exposure time and complexity of the structures, the adverse effects are not frequent when continuity edge involved, and is minimized with compared to other types of drug. proper surgical technique and the good condition of

72/AVANCES EN ODONTOESTOMATOLOGÍA • Pag. Gutiérrez JL, Bagán JV, Bascones A, Llamas R, Llena J, Morales A, Noguerol B, Planells P, Prieto J, Salmerón JI. con n Consensus document on the use of antibiotic prophylaxis in dental surgery and procedures. • Pag. «entr the patient. However, antibiotic prophylaxis has been To that end, patients could be classified as: a) healthy shown to be a more critical factor and a subject for patients, b) patients with local or systemic infection discussion. risk factors, and c) patients with post-bacteraemia focal infection risk factors. The control measures in the surgical technique to minimize the risk of infection are: clean incisions; In the healthy individual, prophylaxis is based • Pag. 26 tear-free mucoperiostial examinations; irrigation as a exclusively on the risk of the procedure, with «crea method for cooling and removing drilled alveolar- transplants, re-implants, grafts, tumour/bone surgery • bone particles; constant aspiration and careful (as with orthopaedic and trauma surgery) having a Pag. haemostasis. If local anaesthesia is used, avoid high risk, and also periapical surgery and dental “….m possible tissue tearing with the needle and ensure inclusions, where the co-existence of prior infection (peri slow administration of the anaesthesia. Detailed care is also frequent.2,26 • Pag 5 must also be taken with dividers, retractors and tongue depressors on the lips, flaps and tissues. If Patients with local or systemic infection risk factors drains and compression dressings have to be put in are those that have an increased general place, do so in the right position. Lastly, we have to susceptibility to infections. These are oncological remember that some of the sutures made bring edges patients, patients with congenital or immunological together and there is therefore a transfer of both the immunodepression (for ex. lupus erythematosus), moist environment of the oral cavity itself as well as patients with immunodepression due to medication food residues, and it is consequently recommended (corticotherapy, chemotherapy) after transplantation, that antiseptic or normal saline rinses be started 24 implant or for any other reason, patients with hours after the surgery. infectious immunodepression (AIDS), patients with metabolic disorders (diabetes) and patients with re- As a general rule, prophylaxis is always indicated when nal or hepatic insufficiency.26 There are also there is an important risk of infection, either because splenectomized patients who have a higher risk of of the characteristics of the operation or because of infection by the genera Streptococcus and • the patient’s local or general conditions. Among the Haemophilus.32,33 Pag 5 factors that will determine the possible appearance y 11: of infection are notably the type and duration of Patients with post-bacteraemia focal infection risk • Pag 6 surgery and the surgical risk of the patient due to co- factors are those who present risk of infectious en- END morbidity (assessable in terms of anaesthetic risk or docarditis or infection of joint prostheses. With END ASA class): diabetes, kidney disease, liver disease respect to infectious endocarditis, 14-20% have an (cirrhosis), cardiopathies and therapies immuno- oral origin.9,34 Antibiotics, apart from minimizing the suppressants (corticoids, radiotherapy, chemo- prevalence and magnitude of bacteraemia9,35 (they therapy, prior infections with antibiotic therapy either never manage to eliminate it completely), prevent not well-known or not rationalized). Minor inter- the bacterial adherence to the endocardium,36 which ventions in healthy patients do not generally require could be the ultimate prophylactic effectiveness prophylaxis. mechanism. The pathological conditions associated with risk of infectious endocarditis have been defined by the American Heart Association (AHA) in the What types of patient require antibiotic United States, the British Society of Antimicrobial prophylaxis? Chemotherapy (BSAC) in the United Kingdom and the Agence Française de Sécurité Sanitaire des Using antibiotic prophylaxis or not in dental surgical Produits de Santé (Afssaps)2,37,38 among others. With procedures and techniques will depend on the type respect to infections of joint prostheses, the choice of patient and the type of procedure performed. of antibiotic prophylaxis of the dental procedure Certain patients are candidates for prophylaxis in would be based on its devastating morbidity and high invasive procedures. And in contrast, non-invasive mortality,39 and not on the low prevalence of these procedures do not require prophylaxis in any case. infections’ association with dental procedures.32

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Despite this low prevalence, prophylaxis is indicated — Type I. Clean wounds (no opening of mucosa in in prostheses implanted less than 2 years previously the oral cavity): Confirmed infection rate of 1 to or when there has been prior prosthesis infection.2 4%. Antibiotic prophylaxis not required. — Type II. Clean-contaminated wounds (opening of Table 2 indicates patients considered at risk. mucosa in the oral cavity, insertion of dental implants or intervention on inflammatory pathology): Confirmed infection rate of 5 to 15%. These require What dental procedures require antibiotic antibiotic prophylaxis with drugs covering Gram prophylaxis? positive and anaerobic micro-organisms. — Type III. Contaminated wounds (oncological Considering these facts, we need to differentiate pathology in which there is simultaneous action between invasive oral-dental procedures, those likely on the oral cavity and the neck): Confirmed to produce significant bleeding (Table 3), and non- infection rate of 16 to 25%. Antibiotic prophylaxis invasive ones, those not likely to produce significant must be carried out to cover Gram negative bleeding. Generally, invasive procedures may be organisms whose coverage in clean and clean- considered to be high risk in fragile patients. contaminated surgeries is disputed. — Type IV. Dirty and infected wounds. Confirmed Surgical wounds were classified by Altemeier in infection rate of above 26%. These always need accordance with their potential risk of contamination adequate antibiotic treatment. and infection, in a classification40 that time has confirmed as of practical utility; All the invasive procedures cited in Table 3 are candidates for prophylaxis in patients with risk factors for local or system infection (patients with immuno- depressive factors). TABLE 2.- PATIENTS AT RISK Prophylaxis is always indicated prior to invasive 1. INFLAMMATORY ARTHROPATHIES: rheu- procedures performed on patients with post- matoid arthritis, systemic lupus erythematosus. bacteraemia risk of focal infection (endocarditis, 2. IMMUNOSUPPRESSION due to Disease, prosthetic infection). Drugs, Transplants or Radiotherapy. In healthy subjects, prophylaxis is only recommended 3. DIABETES Mellitus type I. in the case of included tooth exodontia, periapical 4. Risk of INFECTIOUS ENDOCARDITIS: prior surgery, bone surgery, implant surgery, bone grafts endocarditis, valve prostheses, congenital heart and benign tumour surgery. disease, surgical bypasses, acquired valve disease, hypertrophic cardiomyopathy, mitral prolapse, sustained murmur and Marfan’s Selection criteria: bacterial target, normal flora, syndrome. pharmacokinetic and pharmacodynamic aspects 5. Risk of osteoarticular prosthesis infections: less and selection of the right antibiotic than 2 years after implant and having experienced PRIOR INFECTION in the Antibiotics and the bacterial target of the prosthesis. prophylaxis 6. MALNUTRITION. 7. HAEMOPHILIA. The bacteria that cause odontogenic infections are 8. GRAFTS (local factor). generally saprophytes. During evolution of dental caries, the bacteria penetrating dentinal tubules are 9. Other associated UNCONTROLLED factors basically opportunistic anaerobes such as Strepto- (RENAL or HEPATIC INSUFFICIENCY) and coccus spp, Staphylococcus spp and lactobacilli. SPLENECTOMIZED subjects. When the pulp is necrosed, the bacteria advance

74/AVANCES EN ODONTOESTOMATOLOGÍA Gutiérrez JL, Bagán JV, Bascones A, Llamas R, Llena J, Morales A, Noguerol B, Planells P, Prieto J, Salmerón JI. Consensus document on the use of antibiotic prophylaxis in dental surgery and procedures.

along the root canal and the process evolves TABLE 3.- INVASIVE PROCEDURES AND toward periapical inflammation. Predominating in RIS this phase are Prevotella spp, Porphyromonas spp, Fusobacterium spp and Peptostreptococci spp. Procedure Risk The microbiology of infectious complications is Use of staples for absolute isolation with varied: there are many combinations of all these rubber dike...... Low risk organisms, with different characteristics, but both Periodontal prophylaxis and implants.. Low risk anaerobic and aerobic bacteria are habitually present. Periodontal probing ...... Low risk Periodontal maintenance ...... Low risk Against aerobic or opportunistic Gram positive bacilli Intraligamentous anaesthesia ...... High risk involved (Eubacterium, Actinomyces and Propio- nibacterium) and spirochetes, all the groups of Trunk anaesthesia techniques ...... Low risk antibiotics normally used (aminopenicillins, amoxicillin Extractions ...... High risk + clavulanate, macrolides, lincosamides and Dental re-implants (intentional and metronidazole) are active except for metronidazole. traumatic) ...... High risk Against the Gram positive cocci involved (Streptococ- cus, Staphylococcus and Peptostreptococcus) only Biopsies ...... High risk amoxicillin + clavulanate present adequate coverage.2 Drainage incisions ...... High risk Against Veillonella, all are active except the macrolides Bone implants ...... High risk (erythromycin, clarithromycin and azithromycin). Against the Gram negative bacilli involved (Prevotella, Application and removal of surgical Porphyromonas, Fusobacterium, Selenomonas, sutures ...... Low risk Eikenella, Capnocytophaga, Actinobacillus, Campy- Radicular scraping and smoothing ..... High risk lobacter rectus and Tanerella forsythensis), amoxicillin Periodontal surgery ...... High risk + clavulanate and clindamycin present adequate coverage (except for Eikenella corrodens in the case Implant insertion surgery ...... High risk of lincosamide). The high prevalence of b-lactamase Mucosa-gingival surgery ...... High risk production in normal or pathologic oral anaerobic Removal of implant posts...... Low risk flora means that without b-lactamase inhibitor (clavulanate) amoxicillin is not an adequate antibiotic Endodontia ...... Low risk from the physiopathological point of view. Table 4 Endodontia surgery and apicectomy... High risk summarizes the activity of the main antibiotics against 41 Procedures for and placement of the most frequent odontogenic pathogens . orthodontia bands ...... Low risk

Placement of removable orthodontia Antibiotics and normal flora apparatus ...... Low risk Taking impressions ...... Low risk The right antibiotic regime will be the one that acts Placement of retraction thread ...... Low risk most selectively on the bacteria that may produce complications, respecting as much as possible, the Sculpting procedures with bleeding .... High risk usual saprophyte flora. Pre-prosthetic surgery ...... High risk Orthognatic surgery...... High risk It is important to consider the ecological aspect when choosing the antibiotic regime to use. Choose the Reduction of maxillary fractures ...... High risk antibiotic and the dose (this factor with less impor- Surgery on salivary glands ...... High risk tance if the prophylactic course is short or of a single Maxillo-facial oncological surgery...... High risk dose) that least alters the normal saprophyte flora. Taking Escherichia coli as an intestinal flora index,

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TABLE 4.- ACTIVITY OF VARIOUS ANTIMICROBIALS ON PERIODONTAL PATHOGENS

Aa Peptostrepto- Prevotella Porphyro- Fusobacte- Oral Actinobacillus coccus spp monas rium Streptococci actinomycetem- spp spp spp comitams Penicillin G ± + ± ± + + Amoxicillin + + ± ± + + Amoxicillin/ Clavulanate + + + + + + Doxicycline + ± ± + + Clindamycin O + + + + + Metronidazole O + + + + O Macrolides ± ± ± ± ± +

+ More than 80% of strains sensitive. O Less than 30% of strains sensitive. ± 30-80% of strains sensitive.

macrolides and cetolides are respectful since this mi- twice daily, but they are not drugs of choice in cro-organism is resistant to these compounds. dentistry and particularly, macrolides administered Quinolones, however, have selected a high degree of once or twice a day in S. pneumoniae and S. pyoge- resistance,42 but these compounds are not indicated in nes. These facts are visible in the species of the dentistry. While amoxicillin has selected high rates of viridans group of the genus Streptococcus, where resistance to E. coli due to production of ß-lactamase, the high resistance to macrolides (erythromycin, the susceptibility of amoxicillin combined with clarithromycin)49 is frequently associated with high clavulanate is very high. Where normal flora has been resistance to tetracyclines50 and to clindamycin and studied most extensively, is in the nasopharynx, taking azalides (azithromycin).52 Considering that con- Streptococcus pneumoniae as the index bacteria, a sumption of antibiotics in dentistry assumes 10% of micro-organism of the same genus as other species the total consumption of antibiotics in the community, that are prevalent isolates in odontogenic infections as mentioned above, it is possible to suspect a not (viridans group)43. unappreciable degree of responsibility in the selection of resistances due to antimicrobial treatments in With respect to streptococci, the consumption of dentistry. A high prevalence of oral iatrogenic antibiotics has been reported as the sole cause of bacteraemia has been described in our country resistance in the species S. pyogenes and S. pneu- caused by Streptococci resistant to erythromycin moniae, both from a time point of view44,45 and from (40.8%) and clindamycin (21%), the majority of the a geographical standpoint,45,47 with resistance to isolates being sensitive to aminopenicillins.52 macrolides in these two species being connected at the local level.48 While the responsibility of aminopenicillins in the selection of resistances in S. Pharmacokinetic and pharmacodynamic aspects pneumoniae is low, the drugs that select most resistances to penicillin and macrolides in S. pneu- For some antibiotics, the antibiotic concentrations in moniae are the oral cephalosporins administered the gingival fluid are similar to or above the serum

76/AVANCES EN ODONTOESTOMATOLOGÍA Gutiérrez JL, Bagán JV, Bascones A, Llamas R, Llena J, Morales A, Noguerol B, Planells P, Prieto J, Salmerón JI. Consensus document on the use of antibiotic prophylaxis in dental surgery and procedures. concentrations, as seen in the case of amoxicillin + at a dose of 875/125 mg every 8h or the new formula clavulanate53,54 spiramycin, metronidazole,55 and of 2,000/125 mg every 12h as well as clindamycin quinolones (drugs not indicated in the dental field at 3,200 mg every 6-8 h comply with the pharma- present). Pharmacodynamic coverage is understood codynamic requirements.43,56,57 However, clindamycin as the value of the “relationship between the serous offers worse coverage against oral streptococci and pharmacokinetic parameters and in vitro suscep- adequately for Peptostreptococcus, presenting a not tibility” predicting for efficacy: a) percentage of the unappreciable level of resistances. Metronidazole has dosing interval at which the antibiotic levels surpass no activity against aerobic bacteria and macrolides, the MIC (minimum antibiotic concentration that pro- including spiramycin, have a high percentage of duces inhibition of bacterial growth in vitro) that has resistance to oral streptococci and offer very limited to be above 40-50% for ß-lactamics, macrolides and activity against Peptostreptococcus spp and lincosamides, and b) relationship of the area under Fusobcterium nucleatum. the curve of the serous levels/MIC that must be above 25 for azalides (azithromycin). Papers have been Table 5 shows the recommended doses for published that apply these concepts in dentistry, prophylaxis with different antibiotics. analyzing different antibiotics against the five most prevalent isolates (but not against all the bacteria involved) in odontogenic infections (Streptococcus, Selection of the right antibiotic group viridans, Peptostreptococcus sp., Prevotella intermedia, Porphyromonas gingivalis and Fusobac- The antibiotic of choice (if prophylaxis is consi- terium nucleatum).43 Only amoxicillin + clavulanate dered necessary because of the type of procedure

TABLE 5.- INITIAL PRE-INTERVENTION DOSES RECOMMENDED IN PROPHYLAXIS

Antibiotic Adult dose Paediatric dose† Amoxicillin 2 g VO 50 mg/Kg VO Ampicillin 2 g IM o IV 50 mg/Kg IM o IV Amoxicillin + Clavulanate 2 g +125 mg VO 50 + 6,25 mg/Kg VO 2 g + 200 mg IV 50 + 5 mg/Kg IV Cefazolin* 1 g IM o IV 25 mg/kg IM o IV Cephalexin or cefadroxil* 2 g VO 50 mg/Kg VO Clindamycin 600 mg VO 20 mg/Kg VO 600 mg IV 15 mg/Kg IV Clarithromycin and azithromycin 500 mg VO 15 mg/kg VO Gentamycin 1,5 mg/Kg IV (do not exceed 120 mg) 1,5 mg/kg IV Metronidazole 1 g IV 15 mg/kg IV Vancomycin 1 g IV 20 mg/Kg IV

† The total dose in children should not surpass the adult dose; follow-up doses one-half the initial dose. * Cephalosporins should not be used in patients with type I penicillin hypersensitivity reaction (rash, angioedema or anaphylaxis). VO: orally; IM: intramuscular; IV: intravenous.

AVANCES EN ODONTOESTOMATOLOGÍA/77 AVANCES EN ODONTOESTOMATOLOGÍA Vol. 22 - Núm. 1 - 2006 and patient type) must fulfil the following charac- clarithromycin and azithromycin, may also be used if teristics: the patient is allergic to penicillin. Metronidazole tends to be used only against anaerobes and is generally 1. Adequate bacterial spectrum, covering all the reserved for situations in which only anaerobic bac- species involved in local multi-microbial infections teria are suspected. Tetracyclines are of very limited or distal focal mono-microbial infections, use in dentistry. Since tetracyclines can cause including aerobic micro-organisms, micro- changes in the colour of the teeth, they should not aerophils, without forgetting the anaerobes that, be prescribed for children under 8, pregnant women, because of the difficulty in isolating them, are or breast-feeding mothers. sometimes not considered prevalent in oral-origin bacteraemias. 2. Wide clinical spectrum, covering the greatest Value of antiseptics and oro-dental hygiene number of dental procedures. 3. Restricted ecological spectrum in order to limit The use of topical antiseptics in the oral cavity redu- the effects on the usual saprophyte flora as much ces the bacterial inoculate, but it has not been shown as possible. to be effective in the prophylaxis of bacterial 4. Adequate pharmacokinetics and pharmaco- colonization. However, the pre-operative use of dynamics, to allow use in single pre-operative antiseptics in the oral cavity can reduce complications dose in the case of prophylaxis, or wide dosing derived from trauma in the mucosa, especially in intervals in preventive, short-term treatment, with patients with valve disease, implants of alloplastic half-lives or prolonged-release formulas that material, bone grafts, immunodepressed subjects, the maintain adequate concentrations locally (gingi- elderly and in patients with bad oral hygiene. val fluid) or systemically (serum) during the entire time the dental procedure lasts (prophylaxis). 5. Adequate safety profile, including in paediatric ANALYSIS OF DENTAL PATHOLOGY and elderly populations. Tooth decay is a multi-factorial disease involving, Antibiotics administered orally that have traditionalyy among other factors, a wide variety of microbiote; been used against odontogenic infections include the most frequent bacteria are streptococci of the penicillins, clindamycin, erythromycin, cefadroxil, mutans group, followed by the genus Lactobacillus. metronidazole and the tetracyclines. These These bacteria are involved in the formation of antibiotics are effective against oral streptococci and bacterial plaque, but with a different composition anaerobes. Penicillin V is the penicillin of choice for depending on the location.58,59 odontogenic infections. It is a bactericide, and although its spectrum of action is relatively narrow, Bacterial penetration of the tooth occurs without an it is appropriate for odontogenic infection edge being necessary on the outside surface, and is treatments. For the prophylaxis of endocarditis produced fundamentally through flakes or cracks, pits associated with dental treatments, amoxicillin is the and the inter-prism areas of the enamel, even in nor- antibiotic of choice.37 Amoxicillin plus clavulanate is mal teeth without caries. In cases of incipient enamel currently the drug of choice for this group as it has caries without cavity, bacterial invasion in the deeper the great advantage of keeping its activity against layers of the enamel can be observed, reaching the the ß-lactamases produced commonly by dentin amelar limit and even the deep dentin microorganisms associated with odontogenic layers,60,61 where basically Lactobacillus is detected infections. during the initial stages of dentine caries, prior to later colonization by Streptococcus and Actinomyces One option, where patients are allergic to penicillins, spp. is clindamycin. It is a bacteriostatic, but its bactericide activity is obtained clinically with the generally Streptococci of the mutans group (S. mutans, S. recommended dose. The latest macrolides, sobrinus, S. cricetus, S. ratius, S. ferus, S. downwi

78/AVANCES EN ODONTOESTOMATOLOGÍA Gutiérrez JL, Bagán JV, Bascones A, Llamas R, Llena J, Morales A, Noguerol B, Planells P, Prieto J, Salmerón JI. Consensus document on the use of antibiotic prophylaxis in dental surgery and procedures. and S. macacae)62 are the most important in the prophylaxis. In general terms antibiotic therapy pre- aetiopathogeny of tooth decay. Consequently, and post-operatively is recommended in those cases prescribing antibacterial treatment in patients at that have a high risk of infection or obvious clinical high risk is advisable for prophylactic purposes even signs of infection. when they do not have an evident lesion.63 Chlorhexidine, topical fluoride and vancomycin type Surgical interventions can be classified in two antibiotics are used (to block protein synthesis), large groups, depending on the presence or as well as iodine- and fluorine-based halogenated absence of germs in the surgical zone. A series of solutions.63 standard operations in the speciality are listed below: The number of bacteria that invade the pulp or the periapical tissues is directly proportional to the degree 1. Surgery with the presence of germs: undescended of extension of the routes for penetration. Bacterial teeth; exostosis, torus; odontogenic tumours, invasion of the pulp is always a condition for cysts (uninfected epulis, pre-prosthetic and pre- inflammatory pulp response and the seriousness of orthodontic surgery; maxillary fractures (closed); the process that develops will depend on a series of glandular affection; osteotomies; grafts, flaps, and factors such as: the nature of the invasion, the others. microbiote, the number of micro-organisms, the 2. Surgeries in the presence of germs: pericoronari- endotoxins, the exoenzymes, the metabolites, the tis of the third molar, inflammatory cysts, radicu- exotoxins, the acting time and the host’s defensive lar remains, granulomas, etc.; sialolithiasis, open capability.64 fractures, traumas, wounds with contusions; su- per-infection added to the tumour lesion, radio- The bacteria that contaminate pulp tissue can also necrosis and others. invade the periapical tissues, but the degree of bacterial invasion depends not only on the ability to multiply, but also on the motility of the bacte- Oral surgery ria.64 The infection rate is low, and therefore, in healthy Most of the bacteria that originate periapical patients most oral surgery procedures do not pathology are sensitive, in order of effectiveness, to require antibiotic therapy. Prophylactic antibiotic treatment with amoxicillin/clavulanate, ampicillin/ treatment will be used in cases of active infection, sulbactam, clindamycin, metronidazole, macrolides, patients with co-morbidity or who are immunocom- and penicillins (ampicillins, amoxicillins). promised.

One of the big problems of endodontal failure is due Exodontia de wisdom teeth: Some series seem to to the persistence of bacterial invasion at the canal demonstrate that the use of antibiotic therapy post- or periapical level: Actinomyces israelii65 and Ente- operatively does not improve prognosis in relation rococcus faecalis.66 Actinomyces israelli67 has been to the possibility of post-operative infection.69,70 observed to be resistant to metronidazole and Ente- However, some authors recommend the use of rococcus faecalis to clindamycin.68 prophylaxis based on the significant drop in post- surgical complications such as pain, trismus, delayed scarring of the wound and tumefaction.71,72,73,74 In a ANALYSIS OF ORAL AND MAXILLO-FACIAL recent randomized, double blind clinical trial of SURGICAL PATHOLOGY parallel groups the efficacy of pre- and post-operative antibiotherapy was compared with placebo. In the The data in the literature are contradictory, although study patients were randomized to three groups: the series seem to indicate that the reduction in post- Placebo group, pre-operative prophylaxis group operative complications is due as much to improved (amoxicillin/clavulanate 2000/125 mg in a single surgical technique as to rational use of antibiotic dose prior to surgery) and post-operative prophylaxis

AVANCES EN ODONTOESTOMATOLOGÍA/79 AVANCES EN ODONTOESTOMATOLOGÍA Vol. 22 - Núm. 1 - 2006 or preventive treatment group (amoxicillin/ Mandibular and dentoalveolar fractures: the clavulanate 2000/125 mg every 12 hours for 5 days, antibiotic treatment plans are the classic ones for starting in the first 3 hours after surgery). The other cervical-facial pathology (penicillin and prevalence of post-operative infection was derivatives and third-generation cephalosporins). significantly higher (p = 0.006) in the group of Prophylactic antibiotic treatment in uncompli- patients treated with placebo (16%) than in the group cated fractures does not seem to provide any of patients who received amoxicillin/clavulanate benefit although many professionals do treat these 2000/125 mg, either as pre-operative (5.3%) or post- fractures in order to cover possible infections and operative prophylaxis (2.7%). In surgeries that need so reduce their incidence. Antibiotic treatment in osteotomy, preventive treatment was better than pre- the first 72 hours is not necessary. Antibiotic operative prophylaxis and placebo (24%, 9% and 4% treatment of infectious complications (abscesses, respectively).3 pseudoarthrosis, osteomyelitis…) is where there is more consensus, although in this case it stops Implantology. Conceptually included within type II being prophylactic antibiotherapy and becomes injuries, a recent review of the literature on efficacy therapeutic. of antibiotics in preventing complications and failures following dental implants concluded that Orbital fractures: there is no consensus in the there is no evidence either to recommend or to literature (some authors defend antibiotic treatment discourage the use of antibiotics for prevention of while others do not). dental implant complications and failures, due to the absence of randomized, controlled clinical Mid and upper third fractures: Antibiotic trials.75 prophylaxis is used in those cases where there is liquorrhea. Gynther et al. compared the efficacy of penicillin V administered before and after the surgery against placebo in 279 patients, without differences being Orthognatic surgery and pre-prosthetic found in relation to post-operative infection rate or surgery survival of the implant among the two groups.76 Dent et al., in a multi-centric study of 2,641 dental Clean-contaminated surgeries, in which some se- implants, found a significantly smaller rate of failures ries have demonstrated effectiveness of post- in those that had received pre-operative antibiotics operative antibiotic prophylaxis (penicillin, in comparison with those who had not. Lastly, in a cephalosporins that do not improve prognosis and recent study, no greater efficacy was observed with involve higher cost), although other authors the use of post-operative antibiotherapy during 7 appear to demonstrate there is no evidence of days as against a single dose during surgery.77 In better prognosis related to infection due to post- patients with prior radiotherapy, prolonged operative antibiotherapy, especially if administered antibiotherapy regimes are used to avoided the orally. presence of osteomyelitis or loss of the osteoin- tegrated implant devices. Likewise, based on clinical Greater incidence of infections in bi-maxillary experience, the use of antibiotics would be surgery without antibiotic treatment has been recommended in patients with immunodeficiency, described. metabolic diseases (like diabetes) and risk factors for endocarditis. In prior publications, the treatment time had been established at 5 days for prophylactic antibiotic coverage, but the incidence of post-operative Traumatology infection is the same in regimens of 1 or 5 days, although there is a certain improvement in post- Prophylactic antibiotherapy in complex or multiple operative morbidity by prolonging treatment during compound fractures is widely accepted. 5 days.

80/AVANCES EN ODONTOESTOMATOLOGÍA Gutiérrez JL, Bagán JV, Bascones A, Llamas R, Llena J, Morales A, Noguerol B, Planells P, Prieto J, Salmerón JI. Consensus document on the use of antibiotic prophylaxis in dental surgery and procedures.

Salivary Glands The duration of treatment is not standardized and in many cases is at the discretion of the surgeon. No effectiveness with the use of antibiotic prophylaxis Post-operative antibiotherapy tends to be main- has been demonstrated in surgeries such as tained until removal of drains, although it is parotidectomy or submaxillectomy. prolonged in cases of surgical wound infection, dehiscence or fistula.

Oncological, reconstructive and cervical surgery ANALYSIS OF PERIODONTAL PATHOLOGY

It has been demonstrated that peri-operative use Although most rules for antibiotic prophylaxis in of antibiotics significantly lowers the rate of post- periodontia are based on concepts that can be operative infections. As in the above cases, in cer- generalized to prophylaxis for surgical oral vical pathology and, fundamentally, in oncological procedures, periodontal infections present particular surgery, prophylactic antibiotherapy regimens can situations that should be treated separately. be used combining clindamycin and cefazolin, cephalosporins, aminoglucosides, quinolones or penicillin derivatives with betalactamase inhibi- What procedures in periodontia require tors. prophylactic treatment with antibiotherapy?

The risk of infection arises with the possibility of clean This question could be posed in another way: what areas being put in contact with the oral mucosa, since procedures in periodontia produce bacteraemias? the principal source of contamination in these patients is saliva, which transports a large number of All dental procedures that induce bleeding will develop bacteria. Other contributing factors are a bad gene- bacteraemia that will rarely persist more than 15 ral condition, immunosuppression states, radio- minutes.78 The following procedures or techniques therapy or chemotherapy pre-operatively, recons- could be considered to fulfil these criteria in Periodontia: truction flaps or those procedures that expose tissues to tissue ischemia or necrosis. The sources of mi- It has been observed that periodontal probing in cro-organisms in these pathologies are saliva, skin, humans causes transitory bacteraemia, confirmed via teeth and the tumour itself, and therefore the blood cultures.79,80 Studies in animals have also antibiotic of choice must cover not just the common demonstrated that radicular scraping and smoothing micro-organisms of saliva, such as Gram positive techniques can cause it.81 In humans, it has been cocci and anaerobes, but also Gram negative observed that radicular scraping and smoothing organisms that are commonly isolated in tumours. A techniques cause transitory bacteraemia, whether large number of references in the literature do not these are with curette instruments or ultrasonic consider that Gram negative micro organisms have instruments are used.82,83 Application of chlorhexidine to be covered in oncological surgery of the head and 0.12% by subgingival irrigation, immediately or during neck, but recent publications do seem to associate use of ultrasonic apparatus or curettes reduces but better prognosis with coverage of Gram negative does not eliminate the transitory bacteraemia.82,83 The organisms. use of other antiseptics such as povidone iodide after periodontal use of instruments has not been shown An antibiotherapy guideline may be gentamycin + to be effective in reducing or eliminating the transitory clindamycin, that do well in covering Gram positive, bacteraemia.84 Gram negative and anaerobic organisms (not so cefazolin that does not cover anaerobes). Amoxicillin- Periodontal surgery causes transitory bacteraemia clavulanate and ampicillin-sulbactam also have the that is significantly reduced with the use of antibiotic same spectrum as against clindamycin that does not prophylaxis.85 Although the use of antibiotherapy in cover anaerobes sufficiently. periodontal surgery procedures is discussed a great

AVANCES EN ODONTOESTOMATOLOGÍA/81 AVANCES EN ODONTOESTOMATOLOGÍA Vol. 22 - Núm. 1 - 2006 deal, post-operative infections occur despite the fact inflammation and healthy gums are found in very that the prevalence of these infections is low.86 low percentages of the population.95 Transitory bacteraemia also occurs with suture removal.87 ANALYSIS OF THE PATHOLOGY IN CHILDREN The controversy could occur when the evidence of bacteraemias produced by non-invasive manoeuvres Antibiotic prophylaxis in children follows the same such as tooth brushing or gum chewing is principles as for adults, taking into account only the analyzed.88,89 Table 6 shows the rate of bacteraemias, pharmacokinetic and toxicity peculiarities. In this comparing dental treatment actions and oral hygiene respect, and by way of example, the use of antibiotics operations.90,91,92 such as quinolones is not recommended for children. Likewise, tetracyclines should not be administered to The question that arises then is, if bacteraemia- children less than 8 years of age. producing stimuli occur spontaneously several times a day with no type of antibiotic coverage, do other As a starting point, we believe it necessary to define a invasive procedures related to surgical manipulations series of distinctive peculiarities regarding antibiotic have to be done under antibiotic coverage? treatment in children: a) in the early stages of life, children do not have any medical history leading to Although it is said that the extent of the inflammation suspicion of the presence of possible adverse and its seriousness might be related to the magnitude reactions or drug allergies; b) the larger proportion of the bacteraemia and it is logical to think this, it of water in children’s tissues, plus the greater has not been connected in experiments with the sponginess of the bone tissues, allow faster clinical-anatomical-pathological degree of the dissemination of infection on the one hand, and on inflammation. the other, makes it necessary to ensure a proper adjustment of the dose of the medication prescribed; Histological studies have demonstrated that even c) anaesthetic procedures in milk teeth in the process under normal clinical conditions, a certain tissue of rhizolysis can include intraligamentary injections, alteration is always present that would be compatible which however, increase the possibility of bacte- with a favourable environment for bacteraemias.93 Nor raemia; d) the deficient oral hygiene of most children has any difference been established between gingivitis and the consumption of saccharose-rich foods and periodontitis in the production of bacteraemias.94 contribute to increasing the number of germ colonies in the oral cavity, and with this, the risk of bacteraemia Besides, epidemiology studies report that most of after oral treatments; and e) in children, resistance the population at any age has a certain level of clinical to antibiotics presents extraordinary complexity both

TABLE 6.- INCIDENCIA DE BACTERIEMIAS COMPARANDO ACTUACIONES DE TRATAMIENTO DENTAL Y LAS MANIOBRAS DE HIGIENE BUCAL90,91,92

Bacteraemia due to dental treatments Bacteraemia due to oral hygiene Dental extraction 51-85% Tooth brushing 0-26% Periodontal surgery 36-88% Flossing 20-58% Radicular scraping and smoothing 8-80% Use of dental picks 20-40% Periodontal prophylaxis 0-40% Irrigation 7-50% Endodontia 0-15% Chewing 17-51%

82/AVANCES EN ODONTOESTOMATOLOGÍA Gutiérrez JL, Bagán JV, Bascones A, Llamas R, Llena J, Morales A, Noguerol B, Planells P, Prieto J, Salmerón JI. Consensus document on the use of antibiotic prophylaxis in dental surgery and procedures. because of its high incidence and due to its associated 1. High risk: endovascular prosthesis, prior endocar- circumstances (46,47). ditis, complex cyanogenic congenital cardiopathy or systemic-pulmonary fistulas made surgically. Several studies have assessed the prevalence and 2. Moderate risk: other congenital cardiopathies, extent of bacteraemias after different dental acquired valve disease, mitral prolapse with procedures in children. It was demonstrated that just insufficiency, hypertrophic myocardiopathy. tooth brushing is associated with bacteraemia in more 3. Low risk: isolated secundum atrial septal than one in three children.96 Conservative dental defect, surgical repair of atrial septal defect, treatments, in which wedges or matrices are put in, ventricular septal defect (VSD), prior by-pass, mi- or orthodontic procedures such as placement or tral prolapse without regurgitation, pacemakers, removal of bands can cause bacteraemia in a implantable defibrillator. significant number of children.97 In simple tooth extraction, bacteraemia appears in 40-50% of the High and moderate risk patients who are going to children examined.96 The highest levels of have surgery in the maxillo-facial area require bacteraemia are found after intraligamentary antibiotic prophylaxis, using 1 hour before by the oral injections in local anaesthesia procedures (96.6% of route or 30 minutes before intravenously as the children).98 Streptococci of the viridans group were antibiotic standards. Table 7 shows the antibiotics isolated in more than 50% of cases. recommended for children and adults. In addition, children with a history of IV drug use, and The level of oral hygiene has a considerable influence certain syndromes (e.g. Down Syndrome, Marfan’s on levels of bacteraemia. Because of this, optimal Syndrome) can have a risk of bacterial endocarditis oral hygiene could be the most important factor because of the associated cardiac anomalies. in preventing complications consequent to a bacteraemia; in the opinion of some authors, more Although not sustained by scientific evidence, the than any antibiotic course.99 American Academy of Cardiology recommends that “individuals with a risk of developing bacterial endo- Dental trauma pathology is an aetiological factor of carditis need to maintain the best possible oral infection in the oral area, particularly when there is hygiene”. Other authors have stated that “maintaining direct exposure of the pulp tissue and/or alteration of good oral health, thus reducing daily bacteraemias, the periodontal space. The possibilities of infection is probably more important in preventing endocardi- will increase when the presence of open wounds in tis than preventive administration of antibiotics before skin or mucosa is added to the trauma in the hard or specific dental interventions.” It is therefore necessary support dental tissue. to emphasize the upkeep of good periodontal health as a means of preventing bacterial infections and thus the risk of endocarditis. PROPHYLAXIS OF BACTERIAL ENCOCARDITIS Another aspect that has to be cleared up in the future is whether bacteraemias associated with active pe- These recommendations are a summary of the riodontitis are significantly reduced with control of agreements and consensus documents of the the periodontal infection and therefore, if treatment American Academy of Cardiology,37 that has since is a form of prophylaxis effective against endocardi- been accepted by most scientific and professional tis. Periodontal pathogenic bacteria rarely cause, societies. being oral streptococci the most frequent bacteria, although the HACEK group of micro-organisms, It will be applied in all patients with predisposing heart including Actinobacillus actinomycetemcomitans disease who are going to be submitted to a procedure and Eikenella corrodens, has increased in with risk of bacteraemia in oral and maxillo-facial importance in the aetiology, which would sustain the surgery. In relation to the endocarditis risk, we can hypothesis of a relative increase in the importance of classify cardiopathies as:37 periodontal diseases in the aetiology of endocarditis.

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TABLE 7.- ENDOCARDITIS PROPHYLAXIS RECOMMENDATIONS

Prophylaxis Adults Children† Standard Amoxicillin 2 g VO o IV Amoxicillin 50 mg/kg VO. (Maximum 2 g) Allergic to betalactames Clindamycin 600 mg VO Clindamycina 20 mg/kg VO. (Maximum 600 mg) Azithromycin500 mg VO Azithromycin 15 mg/kg VO Claritromicina 500 mg VO Clarithromycin 15 mg/kg VO Oral intolerance Ampicillin 2 g mg IM o IV Ampicillin 50 mg/kg IM o IV Oral intolerance and penicillin allergy Cefazolin 1 g IM o IV* Cefazolin 25 mg/kg IM o IV (Maximum 1 g)* Clindamycin 600 mg IV Clindamycin 15 mg/kg IV o IV (Maximum 600 mg)

† The total dose in children should not surpass the adult dose; follow-up doses one-half the initial dose. * Cephalosporins should not be used in patients with type I penicillin hypersensitivity reaction (rash, angioedema or anaphylaxis). VO: orally; IM: intramuscular; IV: intravenous.

CONCLUSIONS 5. The risk of contamination of the surgical field increases with the time of exposure and the 1. The aim of antibiotic prophylaxis in surgery is complexity of the trauma produced and is to prevent the possible appearance of infection minimized with adequate surgical technique of the surgical wound, creating a state of and with the good condition of the patient. resistance to micro-organisms through However, antibiotic prophylaxis has been shown antibiotic concentrations in blood that avoid to be a more critical factor and a subject for the proliferation and dissemination of bacteria discussion. from the point of entry represented by the surgical wound. 6. Local multi-microbial infections are cutaneous- mucosa or bone infections that occur 2. 10% of antibiotic prescriptions are used for consequent to invasive dental procedures. odontogenic infections and a significant part of these are used in prophylaxis. 7. Mono-microbial systemic infections are infections that take root in patients with a focus 3. Clinical trials with antibiotics in dental susceptible to infection (endocardial changes, pathologies respond little to the required bone or joint prostheses). methodological criteria, and furthermore are not sufficiently numerous. 8. The physician’s criterion for choosing antibiotic prophylaxis or not must be based on the benefit 4. As a general rule, prophylaxis is always indicated and the cost of the risk. In the last instance, the when there is an important risk of infection, prophylaxis decision is the choice of the either because of the characteristics of the physician, who will use the equation: risk = operation or due to the patient’s local or general degree of damage x probability of experiencing conditions. it. This approach is subjective.

84/AVANCES EN ODONTOESTOMATOLOGÍA Gutiérrez JL, Bagán JV, Bascones A, Llamas R, Llena J, Morales A, Noguerol B, Planells P, Prieto J, Salmerón JI. Consensus document on the use of antibiotic prophylaxis in dental surgery and procedures.

TABLE 8.- ANTIBIOTIC PROPHYLAXIS IN DIFFERENT PROCEDURES

Procedure Prophylaxis Prophylaxis Antibiotic and regime in pathient in healthy (pre-intervention dose) at risk patient (YES/NO) (YES/NO) Use of staples for YES NO Amoxicillin + Clavulanic Acid absolute isolation with Adults: 2 g+125 g V.O. / 2 g+200 g I.V. rubber dikes Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children 20 mg/kg V.O. / 15 mg/kg I.V. Periodontal prophylaxis YES NO Amoxicillin + Clavulanic Acid and implants Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Periodontal probing YES NO Amoxicillin + Clavulanic Acid Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Periodontal maintenancel YES NO Amoxicillin + Clavulanic Acid Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Intraligamentous YES YES Amoxicillin + Clavulanic Acid anaesthesia Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Trunk anaesthesia YES NO Amoxicillin + Clavulanic Acid techniques Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Extractions YES YES Amoxicillin + Clavulanic Acid Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V.

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TABLE 8 (continuation).- ANTIBIOTIC PROPHYLAXIS IN DIFFERENT PROCEDURES

Procedure Prophylaxis Prophylaxis Antibiotic and regime in pathient in healthy (pre-intervention dose) at risk patient (YES/NO) (YES/NO)

Dental re-implants YES YES Amoxicillin + Clavulanic Acid (intentional and Adults: 2 g+125 g V.O. / 2 g+200 g I.V. traumatic) Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adultos: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Biopsies YES YES Amoxicillin + Clavulanic Acid Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Drainage incisions YES YES Amoxicillin + Clavulanic Acid Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Bone implants YES YES Amoxicillin + Clavulanic Acid Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Application and removal YES NO Amoxicillin + Clavulanic Acid of surgical sutures Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Radicular scraping YES YES Amoxicillin + Clavulanic Acid and smoothing Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Periodontal surgery YES YES Amoxicillin + Clavulanic Acid Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V.

86/AVANCES EN ODONTOESTOMATOLOGÍA Gutiérrez JL, Bagán JV, Bascones A, Llamas R, Llena J, Morales A, Noguerol B, Planells P, Prieto J, Salmerón JI. Consensus document on the use of antibiotic prophylaxis in dental surgery and procedures.

TABLE 8 (continuation).- ANTIBIOTIC PROPHYLAXIS IN DIFFERENT PROCEDURES

Procedure Prophylaxis Prophylaxis Antibiotic and regime in pathient in healthy (pre-intervention dose) at risk patient (YES/NO) (YES/NO)

Implant insertion YES YES Amoxicillin + Clavulanic Acid surgery Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Mucosa-gingival YES YES Amoxicillin + Clavulanic Acid surgery Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Niños: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Niños: 20 mg/kg V.O. / 15 mg/kg I.V. Removal of implant YES NO Amoxicillin + Clavulanic Acid posts Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Endodontia YES NO Amoxicillin + Clavulanic Acid Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Endodontia surgery YES YES Amoxicillin + Clavulanic Acid and apicectomy Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Procedures for and YES NO Amoxicillin + Clavulanic Acid placement of wedges, Adults: 2 g+125 g V.O. / 2 g+200 g I.V. moulds, orthodontia bands Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. abd pre-formed crowns Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Placement of removable NO NO orthodontia apparatus

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TABLE 8 (continuation).- ANTIBIOTIC PROPHYLAXIS IN DIFFERENT PROCEDURES

Procedure Prophylaxis Prophylaxis Antibiotic and regime in pathient in healthy (pre-intervention dose) at risk patient (YES/NO) (YES/NO)

Taking impressions YES NO Amoxicillin + Clavulanic Acid Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Placement of retraction YES NO Amoxicillin + Clavulanic Acid thread Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Sculpting procedures YES YES Amoxicillin + Clavulanic Acid with bleeding Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Pre-prosthetic surgery YES YES Amoxicillin + Clavulanic Acid Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Orthognatic surgery YES YES Amoxicillin + Clavulanic Acid Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Dental and alveolo-dental YES NO Amoxicillin + Clavulanic Acid trauma Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V. Reduction of maxillary YES YES Amoxicillin + Clavulanic Acid fractures Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V.

88/AVANCES EN ODONTOESTOMATOLOGÍA Gutiérrez JL, Bagán JV, Bascones A, Llamas R, Llena J, Morales A, Noguerol B, Planells P, Prieto J, Salmerón JI. Consensus document on the use of antibiotic prophylaxis in dental surgery and procedures.

TABLE 8 (continuation).- ANTIBIOTIC PROPHYLAXIS IN DIFFERENT PROCEDURES

Procedure Prophylaxis Prophylaxis Antibiotic and regime in pathient in healthy (pre-intervention dose) at risk patient (YES/NO) (YES/NO)

Surgery on salivary YES YES Amoxicillin + Clavulanic Acid glands Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Niños: 20 mg/kg V.O. / 15 mg/kg I.V. Maxillo-facial YES YES Amoxicillin + Clavulanic Acid oncological surgery Adults: 2 g+125 g V.O. / 2 g+200 g I.V. Children: 50 mg+6,25 mg/Kg V.O./ 50 mg+5 mg/Kg I.V. Clindamycin Adults: 600 mg V.O. / 600 mg I.V. Children: 20 mg/kg V.O. / 15 mg/kg I.V.

9. To that aim, patients could be classified as: a) intervals in preventive, short-term treatment, healthy patients, b) patients with local or with half-lives or prolonged-release formulae systemic infection risk factors, and c) patients that maintain adequate concentrations locally with post-bacteraemia focal infection risk factors. (gingival fluid) or systemically (serum) during In healthy subjects, prophylaxis is based the entire time the dental procedure lasts exclusively on the risk of the procedure. (prophylaxis). • Adequate safety profile, including in paediatric 10. The antibiotic of choice (if prophylaxis is and elderly populations. considered necessary because of the type of procedure and patient type) must fulfil the following characteristics: ACKNOWLEDGEMENTS • Adequate bacterial spectrum, covering all the species involved in local multi-microbial Our thanks to the following collaborators for their infections or distal focal mono-microbial assistance in the bibliographical search and their infections, including aerobic micro-organisms, participation in some sections of the document: Lo- micro-aerophils, without forgetting the renzo Aguilar Alfaro, Juan Carlos Asurmendi, Maria anaerobes that, because of the difficulty in José Barra Soto, Antonio Bowen, Pedro Buitrago isolating them, are sometimes not considered Vega, Alvaro Del Amo, Eva Santa Eulalia prevalent in oral-origin bacteraemias. Troisfontaines, Pedro Fernández Palacios, Rafael Flo- • Wide clinical spectrum, to cover the greatest res Ruiz, Manuel García Calderón, Ignacio García number of dental procedures. Moris, Maria José Giménez Mestre, Conchita Gonzá- • Restricted ecological spectrum in order to limit lez-Morán, Pilar Hita Iglesias, Luis Ilzarbe, Pedro In- the effects on the usual saprophyte flora as fante Cossío, Amparo Jimenez Planas, Carlos Labaig, much as possible. Natale Magallanes Abad, Jose E. Martín Herrero, • Adequate pharmacokinetics and pharmaco- Manuel Menéndez Núñez, Francisco Pina, Rafael Po- dynamics, to allow use in single pre-operative veda Roda, José Quijada, Daniel Torres Lagares, dose in the case of prophylaxis, or wide dosing Manuel Zaragoza.

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