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Table 16.4. Empiric antibiotic regimens for treatment of odontogenic infections of soft tissues

A.Immunocompetent host

Penicillin G, 1–4,000,000 IU, i.v. q4–6 h Clindamycin, 600 mg, i.v. q6–8 h Cefoxitin, 1–2 g, i.v. q6 h

Amoxicillin/clavulanic acid, 1.2 g, i.v. q6–8 h Ampicillin/sulbactam, 3 g, i.v. q8 h

B.Immunocompromised host Piperacillin, 4 g, i.v. q6h

Ticarcillin/clavulanic acid, 3.2–5.2 g, i.v. q6–8 h Piperacillin/tazobactam, 4.5 g i.v. q6–8 h Imipenem, 0.5 g i.v. q6 h

Meropenem, 1 g i.v. q6–8 h

The above may have to be used in conjunction with an aminoglycoside

16.2

Prophylactic Use of Antibiotics

16.2.1

Prophylaxis of Bacterial Endocarditis

Most dental procedures or oral manipulations usually cause transient (lasting less than 15 min) and lowgrade [<10 cfu/ml (microbial colonies per milliliter of blood)] bacteremia, as a result of trauma of mucosal surfaces with rich microbial flora (Table 16.5).

As such, patients suffering from certain anatomic defects of the heart or of large vessels are at greater risk for bacterial endocarditis or endarteritis. Bacterial endocarditis, even though not very common, is a serious infection with a high mortality rate (10–30%), and most of the cases are due to bacteria (streptococci), which under normal circumstances are found in the oral cavity. Prophylactic administration of antibiotics is thus recommended for patients who run the risk of endocarditis and on whom dental procedures or oral manipulations likely to cause bacteremia are performed. Generally, prophylaxis is effective when administered a short while before the procedure (1– 2 h earlier) and in doses capable of achieving sufficient concentration in the serum, both during and for some time after the procedure. Administered antibiotics prevent endocarditis mainly by inhibiting adhesion of bacteria to valves and, under certain circumstances, by way of intravascular killing of bacteria. Due to the fact that there are no controlled clinical studies in

Table 16.5. Frequency of bacteremia associated with oral manipulations and dental procedures

Type of manipulation	Frequency %
or procedure	(range)
Tooth extraction	60 (18–85)
Periodontal surgery	88	(60–90)
Tooth brushing	40	(7–50)
or use of irrigation devices

humans for prophylaxis of endocarditis, because of ethical reasons and because the disease is so rare, the recommendations of international associations

(American Heart Association, British Society for

Antimicrobial Chemotherapy) are based on animal studies and clinical experience. Furthermore, because endocarditis may occur in spite of appropriate antibiotic prophylaxis, dentists must have a high awareness level concerning any clinical signs and symptoms, and especially inexplicable fever, following dental manipulations in patients at risk for endocarditis. In such a case, fever must not be masked with antibiotics, because it would only delay diagnosis of existing endocarditis.

Bad oral hygiene and periodontal and periapical abscesses may cause bacteremia even without dental procedures being performed. Therefore high-risk patients must be informed and encouraged to have as good oral hygiene as possible. Ulceration as a result of prosthetic appliances may even cause bacteremia. Even though it has not been proven in clinical studies, it appears that the use of antibacterial mouth rinses

(e.g., chlorhexidine, povidone iodine) in patients belonging to the above category before a tooth extraction may lessen bacteremia following the extraction by 2–4 times.

As a guide to prophylactic antibiotic administration, Tables 16.6 describes the dental procedures and oral manipulations that have the potential to cause significant bacteremia, and Table 16.7 describes the cardiac conditions that predispose patients to endocarditis. Antimicrobial prophylaxis may be administered safely up to 2 h after a procedure that unexpectedly produced soft tissue trauma, for which the patient had not been administered antibiotic prophylaxis.

The main changes in the recent revision of guidelines recommended by the American Heart Association (Journal of the American Medical Association

1997) concerning prophylaxis of bacterial endocarditis, compared to the recommendations that were in effect up to then (New England Journal of Medicine

1995), include:

356 G. Perdikaris, A. Pefanis, E. Giamarellou

Table 16.6. Dental procedures and oral manipulations

A.Antibiotic prophylaxis recommended fora

Dental extractions

Periodontal procedures including surgery, scaling and root planing, probing, and recall maintenance

Placement of dental implants and reimplantation of avulsed teeth

Endodontic therapy or surgical procedures performed beyond the apex

Subgingival placement of antibiotic fibers or strips Initial band and archwire placement, but not brackets, for orthodontic treatment

Intraligamentary local anesthetic injections

Prophylactic cleaning of teeth or implants where bleeding is anticipated

B.Antibiotic prophylaxis is not recommended for

Restorative dentistryb (dental surgery and prosthetic restorations) with or without gingival retraction cordc

Administration of local anesthesia (except for periodontal ligament injection)

Intracanal endodontic treatment, post placement and buildup

Placement of rubber dam Postoperative removal of sutures

Placement of prosthetic denture or orthodontic appliance

Taking of impression Fluoride treatment Intraoral radiographs

Adjustment of orthodontic bands and appliances Exfoliation of deciduous teeth (shedding of primary tooth)

a Involves patients with heart diseases with high and intermediate degree of risk (see Table 16.7)

b Restoration of carious teeth (fillings) is included as well as replacement of missing teeth

cThe administration of antibiotics may also be indicated in certain situations, which may cause significant hemorrhage, as deemed necessary by the dentist

a.A decrease of the initial dose of amoxicillin from 3 g to 2 g and eliminating the second dose that was administered 6 h after the initial dose.

b.No longer recommending erythromycin, due to gastrointestinal disturbances and the complex pharmacokinetics of its various compounds, to persons allergic to penicillin.

Table 16.7. Underlying heart diseases and conditions

A.Antibiotic prophylaxis is recommended for

Prosthetic cardiac valves, including bioprosthetic and homograft valvesa

Patients with a history of previous endocarditis, even if heart disease is not presenta

Complex cyanotic congenital heart diseasea

Most other congenital heart malformationsa

Surgically corrected shunts of systemic-pulmonary circulationa

Rheumatic or other acquired valve defects, even after surgical correction Hypertrophic cardiomyopathy

Mitral valve prolapse with valve regurgitation and/or thickening of cusps

B.Antibiotic prophylaxis is not recommended for Isolated secundum atrial septal defect

Surgical repair, without residuary defect, of atrial septal or ventricular septal defect or patent ductus arteriosus after 6 months or more have elapsed

Previous coronary by-pass graft surgery

Mitral valve prolapse without valvar regurgitation Physiologic, functional or innocent heart murmurs

Patients with a history of Kawasaki disease without valve defect

Patients with a history of rheumatic fever without valve defect

Cardiac pacemakers and implanted defibrillators

aPatients belonging to these groups are considered high risk for endocarditis, while for the patients of the rest of the groups in A, the risk is considered intermediate

c.Recommending various other antibiotics such as cefalexin, cefadroxil, cefazolin, and the newer macrolides azithromycin and clarithromycin as alternative regimens of prophylaxis.

As far as patients with underlying cardiac defects are concerned, and who are administered supplementary prophylaxis against rheumatic fever with monthly administration of benzathine penicillin (Penadur∙), this regimen does not suffice for prophylaxis of bacterial endocarditis. Therefore, when these patients are to be administered prophylaxis for a dental procedure or oral manipulation, the antibiotic used must not be amoxicillin but one of the other alternative

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Table 16.8. Recommendations of the American Heart Association for prophylaxis of bacterial endocarditis in patients undergoing dental procedures or oral manipulations

Antibiotic	Regimen
Standard general prophylaxis
Amoxicillin	2 g orally (p.o.) 1 h before surgery
Patients allergic to penicillin/amoxicillin
Clindamycin	600 mg p.o. 1 h before surgery
or
Cefalexin or cefadroxila	2 g p.o. 1 h before surgery
or
Azithromycin or clarithromycin	500 mg p.o. 1 h before surgery
Patients unable to use oral medication
Ampicillin or amoxicillin	2 g intramuscularly (i.m.) or intravenously (i.v.) 30 min before surgery
or
Cefazolina	1 g i.m. or i.v. 30 min before surgery
Patients unable to use oral medication, allergic to penicillin/ampicillin
Clindamycin	600 mg i.v. 30 min before surgery
or
Cefazolina	1 g i.m. or i.v. 30 min before surgery
Children
Amoxicillin or ampicillin	50 mg/kg p.o. or i.m. or i.v.
Clindamycin	20 mg/kg p.o. or i.v.
Cefalexin or cefadroxil	50 mg/kg p.o.
Cefazolin	25 mg/kg i.m. or i.v.
Azithromycin or clarithromycin	15 mg/kg p.o.

aCephalosporins should not be used in patients with a history of immediate type hypersensitivity reaction (urticaria, angioneurotic edema or anaphylaxis) to penicillins

regimens, because, due to the long-term administration of penicillin, the mucosal surfaces of the mouths of these patients, as a rule, present streptococci relatively resistant to penicillin and amoxicillin. The same applies to patients who have been administered even one dose of penicillin, amoxicillin, or another antibiotic within the last 14 days for other reasons. If such is the case, if possible, the procedure should be performed 10–14 days after cessation of the antibiotic, whereupon the same antibiotic may be administered again.

As such, it is obvious that for patients requiring prophylaxis of bacterial endocarditis, any dental procedure involving blood must be performed in one session, if possible. If that is not feasible, the sessions must either be scheduled at least 10–14 days apart, or the prophylactic antibiotics given at each session should belong to different categories. For example, if amoxicillin was administered in the first session and the second session has been scheduled 5 days later than the first, the antibiotic administered before the second session must be a macrolide or clindamycin.

The antibiotics used and their regimens, as recommended by the American Heart Association, are described in Table 16.8.

The need for antibiotic prophylaxis before dental procedures for patients with prosthetic joints is still subject to debate today. Even though animal studies show that inoculation of the prosthetic joint from remote sites of infection is possible, there are few proven cases of infection of prosthetic joints due to transient bacteremia of dental origin. Even so, for patients with orthopedic prostheses, orthopedists usually recommend, and dentists usually administer, antibiotic prophylaxis similar to that used for endocarditis. In a recent analysis of data by the Mayo Clinic, it was demonstrated that the overall incidence (due to infection because of Streptococcus viridans) in large joint prostheses was 0.06/1000 joints per year, a percentage similar to that of endocarditis in the general population and much lower than that of the group of patients for whom the American Heart Association recommends prophylaxis for endocarditis. Therefore, routine antibiotic prophylaxis is not recommended for patients

358 G. Perdikaris, A. Pefanis, E. Giamarellou

Table 16.9. Classification of surgical procedures according to risk of causing postoperative infections

Classification	Type of procedure	Description	Expected incidence
			of postoperative
			infection (%)
I	Clean	Surgical procedure without entering respiratory,	2
		gastrointestinal, or genito-urinary system
II	Clean – contaminated	Surgical procedure on respiratory,	10–15
		gastrointestinal or genito-urinary system
		without significant bacterial infection
III	Contaminated	Recent trauma (<8 h)	20–30
		Entering genito-urinary system
		with infection present
		Operation on biliary ducts
		Operation on gastrointestinal system
		with significant bacterial infection
IV	Dirty	Surgical procedure in an area	50
		with ascertained infection
		Old trauma (>8 h)

Table 16.10. Classification of immunocompromised patients
Description		Representative diseases
1.	Inadequately controlled metabolic disease	Diabetes mellitus, liver cirrhosis, malnutrition,
		end-stage chronic renal failure
2. Hematologic disorders		Lymphoma, leukemia, hypogammaglobulinemia, etc.
3.	Administration of immunosuppressive agents,	Patients with transplants, cancer patients,
	e.g., cytotoxic drugs, cortisone, ciclosporin	patients with collagen diseases, etc.

with prosthetic joints and the decision for certain patients [e.g., patients with advanced periodontal disease, rheumatoid arthritis, recent (<2 years) arthroplasty, obvious infection or abscess at the site of the dental procedure, prolonged dental procedure, uncontrolled diabetes, corticosteroid treatment] with total hip arthroplasty must be determined by the dentist in consultation with the patient’s orthopedic surgeon and physician.

16.2.2

Prophylaxis of Wound Infections (Perioperative Chemoprophylaxis)

The principles of antimicrobial prophylaxis against postoperative infections were described approximately 30 years ago, based on experimental and clinical studies conducted by Burke, Polk and Stone. These principles, which apply to every aspect of surgery, are:

First principle:

In order to administer antibiotics prophylactically, the risk of postoperative infection must be significant. The incidence of postoperative infection depends on the type of surgery (Table 16.9) and on the state of host defenses of immunocompromised patients (Table 16.10). It must be emphasized that clean surgical techniques and the prophylactic use of antibiotics in certain patients may significantly reduce the incidence of postoperative infections.

Second principle:

The antibiotics to be used for prophylaxis against postoperative infections must: (a) be effective against pathogenic microorganisms that have the potential to cause these infections, (b) achieve a high level of drug in the plasma, and (c) not have significant untoward side-effects. The most common microorganisms considered responsible for infection after procedures in the oral cavity are streptococci, anaerobic Gram-positive cocci, and

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anaerobic Gram-negative rods. Because postoperative infections due to anaerobes are unusual, prophylaxis must mainly focus on aerobic streptococci. Based on these data, penicillin and amoxicillin are the most appropriate antibiotics for prophylaxis. When there is a history of allergic reactions (usually urticarial rash) to penicillin, a first-generation cephalosporin may be administered, provided that the patient has not previously had a severe anaphylactic shock reaction; if this is the case clindamycin is preferred. If the surgical procedure is to be performed through the skin, the most common microorganisms implicated in postoperative infections are staphylococci, which are usually found on the skin. Cefazolin (first-generation cephalosporin) is preferred in surgical procedures with cutaneous access.

Third principle:

The antibiotic level in tissues during the surgical procedure must be high. This means administering higher doses than usual a few minutes before the operation, preferably at the onset of general anesthesia, or if oral surgery is involved that entails local anesthesia, 1 h before the procedure. Administration of antibiotics must not start the day before the procedure or hours before the operation, because we aim for peak drug levels at the site of intervention when the procedure is underway, whereupon the possibility of wound infection due to manipulations is greatest.

Fourth principle:

The antibiotics used for perioperative chemoprophylaxis must be administered for a limited period of time. Usually one dose of the antibiotic half an hour to an hour before the operation begins is enough. In the case of prolonged surgery, a second dose of antibiotic 4 h after the initial dose (for amoxicillin and cefazolin) is recommended. The administration of antibiotics for a greater period of time is not recommended, because it has been proven that, on the one hand, better prophylaxis is not achieved, while on the other hand, the cost is increased, as is the possibility of untoward side-ef- fects or resistance to antibiotics.

Another fundamental principle concerning the prophylactic administration of antibiotics is that the benefit from their use must be significantly greater than the possibility of adverse reactions or side-effects. Keeping these principles in mind, the indications for prophylactic administration of antibiotics in oral and maxillofacial surgery are mentioned below.

The incidence of postoperative infections after a simple tooth extraction or surgical extraction, as well as after surgical procedures involving benign tumors of the oral cavity, e.g., fibromas, lipomas, soft tissue tumors, etc., is very low. As such, in otherwise healthy persons prophylactic administration of antibiotics is not deemed necessary before most dental procedures. The same applies to patients with metabolic diseases that are controlled. A typical example involves diabetic patients, who do not require prophylactic administration of antibiotics when the diabetes is under good medical control2). On the other hand, patients undergoing antineoplastic chemotherapy must be administered antibiotic prophylaxis, if the surgical procedure cannot be postponed until after cessation of the therapy. The same applies to patients with pharmaceutical immunosuppression secondary to transplantation of a solid organ (e.g., kidney).

Orthognathic procedures and certain procedures involved in preprosthetic surgery mainly of the hard tissues, as well as operations with combined intraoral and extraoral access for treatment of tumors, have an expected incidence of postoperative infections of 10– 15% (category II operations). Prophylaxis is recommended for these surgical procedures with one to two doses of antibiotics, even though as far as orthognathic procedures are concerned, that recommendation has not been fully justified, as a result of lack of prospective clinical studies. As for mandibular fractures, because of the high incidence of postoperative infections (50%), the short-term perioperative administration of antibiotics is deemed necessary.

Of all the surgical procedures of the mouth and jaws, the operation that has created the most controversy as whether to administer antibiotic prophylaxis is the extraction of the impacted third molar. Despite the fact that most dentists and oral and maxillofacial surgeons administer antibiotics prophylactically to their patients, existing studies do not justify this widely used practice. The possibility of postoperative infection after such a procedure ranges from 1% to 6%, while the majority is limited to infections of minor significance. With this information in mind and knowing that most available studies (which have compared the incidence of postoperative infections after the administration of, or without administration of,

2)According to recent guidelines of the American Diabetic Association (1999), a patient with controlled diabetes is one that has fasting blood glucose levels <140 mg/dl, or glycosylated hemoglobin (HbA, C) value <7%.