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8 Dental Tribune Middle East & Africa Edition | September-October 2015mCME < Page 7 bined antibiotic therapy results in a greater selective pressure on the microbial population to develop drug resistance. The greater the antibacterial spec- trum of the antimicrobials used, the greater the number of drug- resistant microorganisms that develop, and the more difficult it is to treat a resulting super- infection. The primary clinical indication for combined anti- microbial therapy is a severe infection in which the offend- ing organism(s) is unknown and major consequences may ensue if antibiotic therapy is not instituted immediately before culture and sensitivity tests are available.3 Myth No. 6: Bactericidal agents are always superior to bacte- riostatic agents. Bactericidal agents are required for patients with impaired host defenses.3 However, bacteriostatic agents are usually satisfactory when the host’s defenses against infections are unimpaired. Postantibiotic effects (PAEs — persistent suppression of bac- terial growth after previous ex- posure to antibiotics) are more persistent and reliable with bacteriostatic agents (erythro- mycin, clindamycin) than with bactericidal agents (beta-lacat- amase) because the clinical ef- fects of bacteriostatic agents are less dose-dependent. Myth No. 7: Antibiotic dosages, dosing intervals and duration of therapy are established for most infections. After more than 80 years of antibiotic usage, the proper dosages, dosing inter- vals and duration of therapy are essentially unknown for most specific infections.3 Infectious diseases are associated with a high number of variables that affect treatment outcome (mi- crobial characteristics and drug sensitivity, diverse resistance mechanisms, tissue barriers to antibiotic diffusion, and the in- tegrity and activity of the host’s defense mechanisms). How- ever, basic principles are avail- able to guide the dental health care provider in establishing proper dosages, dosing inter- vals and duration of therapy once the microbial pathogen(s) is suspected or identified and a rational choice of antimicrobial agent is made. The following principles of an- tibiotic dosing are adapted from Dr. Thomas J. Pallasch3 : 1. The current recommendation is to employ an antimicrobial on an intensive basis with vigorous dosage for as short a period of time as the clinical situation permits. The major factor in the clinical success of most antimi- crobial agents is the height of the serum concentration of the drug and the resulting amount in the infected tissue(s). Also important is to expose the host to the antimicrobial agent for as short a duration of therapy as possible. The shorter the du- ration of therapy the lower the risk to the patient for the devel- opment of antibiotic-induced toxicity and/or allergy, and a re- duced risk of developing resist- ant microorganisms. 2. The goal of antibiotic dos- ing is to achieve drug levels in the infected tissue equal to or exceeding the minimal inhibi- tory concentration of the tar- get organism. Serum levels of antibiotics do not necessarily reflect those in tissues. Blood concentrations of the antibiotic should exceed the MIC by a fac- tor of two to eight times in order to offset the tissue barriers that restrict access of the drug to the infected site. 3. It is advisable to initiate an- tibiotic therapy with a loading dose (an initial dose higher than the maintenance dose). An antibiotic loading dose should be used whenever the half-life of the drug is longer than three hours or whenever a delay of 12 hours or longer to achieve a therapeutic blood level is expected. Most antibiot- ics used in the treatment of oro- facial infections have a half-life shorter than three hours but, due to their acute nature, most orofacial infections require therapeutic drug blood levels sooner than 12 hours. Steady- state blood levels of any drug are usually achieved in a time equal to three to five times the drug’s half-life. Amoxicillin has a half-life of one to one-and-a- half hours. A steady-state blood level would then be achieved in three to seven-and-a-half hours, thereby leading to a substantial delay in achieving therapeutic antibiotic blood levels. A load- ing dose of two times the main- tenance dose is recommended for acute orofacial infections, which better achieves the goal of rapid, high blood levels rath- er than initiating therapy with the maintenance dose. 4. An oral antibiotic should ide- ally be administered at dosing intervals of three to four times its serum half-life, particularly if steady-state blood levels are desired (as may be indicated with beta-lactam agents). For example, the serum half-life of Pen-V-K is 0.75 hours. Higher continuous blood levels of this antibiotic are more likely to be obtained with four-hour rather than six-hour dosing intervals. The shorter the serum half-life of the drug, the shorter the dos- ing interval will need to be in order to maintain continuous therapeutic blood levels of the drug. When determining the appropriate dosing interval, it is also important to consider the following: 1) The postantibiotic effects of the drug; and 2) the relative merits of continuous or pulse dosing. PAEs are more persistent (two to seven hours) with antibiotics that act intra- cellularly within the microbial cytoplasm (erythromycin, clin- damycin and tetracycline) or by suppression of nucleic acid syn- thesis (metronidazole, quinolo- nes). As a result, these antibiot- ics are more effective with pulse dosing (high antibiotic dosing at widely spaced intervals). The beta-lactam antibiotics, howev- er, have a slow, time-dependent killing activity and demonstrate very little PAE. Beta-lactam microbial killing requires mi- crobes in the process of cell division (interference with cell wall development); hence, they must be continuously present (steady-state blood levels) be- cause bacteria divide at differ- ent rates or times. Myth No. 8: Bacterial infections require a “complete course” of antibiotic therapy. There is no such thing as a “complete course” of antibiotic therapy.3 The only guide for determining the effectiveness of antibiotic therapy, and hence, the dura- tion of treatment, is the clinical improvement of the patient.16 A common misconception asserts that prolonged (after clinical remission of the disease) antibi- otic therapy is necessary to pre- vent “rebound” infections from occurring. Orofacial infections do not “rebound” if the source of the infection is properly erad- icated. Most orofacial infections persist for two to seven days, and often less. Patients placed on antibiotic therapy for an oro- facial infection should be clini- cally evaluated on a daily basis. When there is sufficient clinical evidence that the patient’s host defenses have regained control of the infection and that the in- fection is resolving or resolved, the antibiotic therapy should be terminated. Antibiotic prophylaxis for medically at-risk patients Antibiotic prophylaxis is the administration of antibiotics to patients without evidence of infection to prevent bacterial colonization and reduce sub- sequent postoperative or post- treatment complications. The only established use of antibiot- ic prophylaxis in dentistry is in the attempt to reduce the poten- tial consequences of bacteremi- as induced by dental treatment in certain medically at-risk pa- tients. The principle indication for antibiotic prophylaxis for dental patients is the prevention of infective endocarditis during specified dental treatment of patients who also have specific medical conditions. Controver- sial indications include dental patients with orthopedic pros- thetic devices, indwelling cath- eters and impaired (immuno- suppressed) host defenses. Dental patients presenting for treatment with impaired host defenses (chemotherapy, or- gan transplant or tissue graft recipient, insulin-dependent diabetes, alcoholics) or patients with indwelling catheters (he- modialysis) may benefit from antibiotic prophylaxis if their white cell count is below 2,500 (normal = 4,000-11,000). It is not currently recommended that patients with AIDS receive routine antibiotic prophylaxis prior to dental treatment. The opportunistic pathogens com- mon to this disorder are not sus- ceptible to routine prophylactic antibiotics and such a practice may result in the development of antibiotic-resistant microor- ganisms, thereby resulting in a serious superinfection.3 Antibiotic prophylaxis for prevention of infective endo- carditis The American Heart Associa- tion has published guidelines for the prevention of IE in medically at-risk patients for more than 50 years. The most recent guidelines, published in April 2007, represent a signifi- cant change from the previous guidelines.17 One of the stated reasons for the development of the current revised guidelines was that the risk of antibiotic- associated adverse events ex- ceeds the benefit, if any, from prophylactic therapy (Table 1). It is well accepted that the risk for developing bacterial resist- ant strains to the antibiotic drug used is considered an antibiot- ic-associated adverse event. The majority of published stud- ies regarding IE being caused by oral bacteria have focused on dental procedures. Although the infective dose required to cause IE in humans is un- known, the number of micro- organisms present in the blood following a dental procedure is low. It has long been assumed that dental procedures may cause IE in patients with un- derlying cardiac risk factors and that antibiotic prophylaxis is effective. However, scientific proof is lacking to support this assumption. Cases of IE caused by oral bacteria probably result more from exposures to low inocula of bacteria in the blood- stream that result from routine daily activities (brushing and flossing) and not from a dental procedure.17 The 2007 AHA report regarding prevention of IE concludes: “If prophylaxis is effective, such therapy should be restricted to those patients with the highest Table 3. (Tables/Provided by American Association of Endodontists) Table 4. (Tables/Provided by American Association of Endodontists) Table 4 Patients at Potential Risk of Experiencing Hematogenous Total Joint Infection19 Patient Type Condition Placing Patient at Risk All patients during first two years following joint replacement N/A Immunocompromised/immunosuppressed patients Inflammatory arthropathies such as rheumatoid arthritis, systemic lupus erythematosus Drug or radiation-induced immunosuppression Patients with comorbidities (Conditions listed for patients in this category are examples only; there may be additional conditions that place such patients at risk of experiencing hematogenous total joint infection) Malnourishment Hemophilia HIV infection Insulin-dependent (type 1) diabetes Malignancy Table 3 Dental Procedures for Which Antibiotic Prophylaxis is Reasonable • Dental extractions • Periodontal procedures, including surgery, subgingival placement of antibiotic fibers/ strips, scaling and root planing, proving, recall maintenance • Dental implant placement • Replantation of avulsed teeth • Endodontic (root canal) instrumentation only if beyond the root apex and endodontic surgery • Initial placement of orthodontic bands (not brackets) • Intraligamentary and intraosseous local anesthetic injections • Postoperative suture removal (in selected circumstances that may create significant bleeding) • Prophylactic cleaning of teeth or implants where bleeding is anticipated Table 5 Suggested Patient Type, Drug and Regimen for Antibiotic Prophylaxis for Total Prosthetic Joint Infection Patient Type Drug Regimen* Patients not allergic to penicillin Cephalexin, cephradine or amoxicillin 2g orally 1 hour prior to dental procedure Patients not allergic to penicillin and unable to take oral medication Cefazolin or ampicillin Cefazolin 1g or ampicillin 2g IM or IV 1 hour prior to dental procedure Patients allergic to penicillin Clindamycin 600mg orally 1 hour prior to dental procedure Patients allergic to penicillin and unable to take oral medication Clindamycin 600mg IV 1 hour prior to dental procedure *Note: No second doses are recommended for any of these dosing regimens. Endodontics: Colleagues for Excellence Use and Abuse of Antibiotics: Winter 2012 Table 4 Patients at Potential Risk of Experiencing Hematogenous Total Joint Infection19 Patient Type Condition Placing Patient at Risk All patients during first two years following joint replacement N/A Immunocompromised/immunosuppressed patients Inflammatory arthropathies such as rheumatoid arthritis, systemic lupus erythematosus Drug or radiation-induced immunosuppression Patients with comorbidities (Conditions listed for patients in this category are examples only; there may be additional conditions that place such patients at risk of experiencing hematogenous total joint infection) Malnourishment Hemophilia HIV infection Insulin-dependent (type 1) diabetes Malignancy • Initial placement of orthodontic bands (not brackets) • Intraligamentary and intraosseous local anesthetic injections • Postoperative suture removal (in selected circumstances that may create significant bleeding) • Prophylactic cleaning of teeth or implants where bleeding is anticipated Table 5 Suggested Patient Type, Drug and Regimen for Antibiotic Prophylaxis for Total Prosthetic Joint Infection Patient Type Drug Regimen* Patients not allergic to penicillin Cephalexin, cephradine or amoxicillin 2g orally 1 hour prior to dental procedure Patients not allergic to penicillin and unable to take oral medication Cefazolin or ampicillin Cefazolin 1g or ampicillin 2g IM or IV 1 hour prior to dental procedure Patients allergic to penicillin Clindamycin 600mg orally 1 hour prior to dental procedure Patients allergic to penicillin and unable to take oral medication Clindamycin 600mg IV 1 hour prior to dental procedure *Note: No second doses are recommended for any of these dosing regimens. Use and Abuse of Antibiotics: Winter 2012 Table 1. (Tables/Provided by American Association of Endodontists) Table 4 Patients at Potential Risk of Experiencing Hematogenous Total Joint Infection19 Patient Type Condition Placing Patient at Risk All patients during first two years following joint replacement N/A Immunocompromised/immunosuppressed patients Inflammatory arthropathies such as rheumatoid arthritis, systemic lupus erythematosus Drug or radiation-induced immunosuppression Patients with comorbidities (Conditions listed for patients in this category are examples only; there may be additional conditions that place such patients at risk of experiencing hematogenous total joint infection) Malnourishment Hemophilia HIV infection Insulin-dependent (type 1) diabetes Malignancy Table 3 Dental Procedures for Which Antibiotic Prophylaxis is Reasonable • Dental extractions • Periodontal procedures, including surgery, subgingival placement of antibiotic fibers/ strips, scaling and root planing, proving, recall maintenance • Dental implant placement • Replantation of avulsed teeth • Endodontic (root canal) instrumentation only if beyond the root apex and endodontic surgery • Initial placement of orthodontic bands (not brackets) • Intraligamentary and intraosseous local anesthetic injections • Postoperative suture removal (in selected circumstances that may create significant bleeding) • Prophylactic cleaning of teeth or implants where bleeding is anticipated Table 5 Suggested Patient Type, Drug and Regimen for Antibiotic Prophylaxis for Total Prosthetic Joint Infection Patient Type Drug Regimen* Patients not allergic to penicillin Cephalexin, cephradine or amoxicillin 2g orally 1 hour prior to dental procedure Patients not allergic to penicillin and unable to take oral medication Cefazolin or ampicillin Cefazolin 1g or ampicillin 2g IM or IV 1 hour prior to dental procedure Patients allergic to penicillin Clindamycin 600mg orally 1 hour prior to dental procedure Patients allergic to penicillin and unable to take oral medication Clindamycin 600mg IV 1 hour prior to dental procedure *Note: No second doses are recommended for any of these dosing regimens. Endodontics: Colleagues for Excellence Use and Abuse of Antibiotics: Winter 2012 > Page 9