Antibiotic Efficacy in Third Molar Surgery
Antibiotic Efficacy in Third Molar Surgery
Despite over 50 years of antibiotic use and multiple clinical investigations (>50), no
 definitive studies exist to confirm or refute the use of systemic antibiotics to prevent
 postoperative inflammatory complications after third molar (M3), aka "wisdom teeth" removal.
 Among patients having M3s extracted, does the administration of systemic prophylactic
 antibiotics when compared to placebo, decrease the rate of postoperative inflammatory
 complications? The first specific aim of the study is to implement a randomized,
 placebo-controlled clinical trial to determine if systemic prophylactic antibiotics, when
 compared to placebo, decrease the rate of postoperative alveolar osteitis (AO) after M3
 extraction. For this proposal, postoperative AO is the primary outcome variable.

 The second specific aim is to implement a pilot study using a randomized, placebo-controlled
 clinical trial to determine if systemic prophylactic antibiotics, when compared to placebo,
 decrease the rate of postoperative infection after M3 extraction. For the purposes of this
 proposal, postoperative infection is a secondary outcome variable. Based on sample size
 estimates, we believe it will be necessary to implement a multi-year trial to address the
 second specific aim definitively. As such, we will use the experience and preliminary results
 derived from this clinical trial to develop and implement a future large scale clinical
 trial.

 The third specific aim is to identify risk factors associated with postoperative inflammatory
 complications in order to develop a model to predict if the prophylactic administration of
 antibiotics will prevent the postoperative inflammatory complications of alveolar osteitis
 and infection following the removal of M3's.

 The long-term goal of this project is to provide compelling clinical evidence to support
 recommendations regarding the use of systemic antibiotics in this setting and alter clinical
 practice based on the results of a well-done, definitive clinical investigation.
The management of impacted M3s is a high volume procedure. In the United States, the cost of
 M3 removal has been estimated to be over 2 billion dollars, not including costs for consults,
 x-rays, medications, surgical center charges, or over 5 million surgical extractions and
 treatment of postoperative inflammatory complications (Flick. 1999). Practices associated
 with M3 removal can have a significant impact on large numbers of patients, providers, and
 payers. There is currently no consensus on the use of systemic antibiotic prophylaxis to
 decrease the risk of inflammatory complications following M3 removal.The most common
 post-operative inflammatory complications following M3 extraction are alveolar osteitis (AO)
 and wound infection (Larsen, 1992; Piecuch et al., 1995; Sekar et al., 2001). AO, aka "dry
 socket," is a wound-healing problem characterized by severe, unremitting pain. The reported
 frequency of AO is 6-68%. Bacterial colonization stimulates plasmin production and
 fibrinolysis with dissolution of the extraction site clot . More than 45% of patients who
 sustain AO require 4 or 5 more postoperative appointments for resolution of symptoms (Larsen,
 1992; Andra et al., 1990). Given its common occurrence, identifying treatments, i.e. systemic
 antibiotics, to decrease the rate of AO following M3 extraction would be an important
 contribution to enhancing patient outcomes. The second common postoperative inflammatory
 condition following M3 extraction is wound infection. The reported frequency of postoperative
 infection ranges from 1.2 - 27%, with most studies reporting a frequency of <10%. Because
 wound infections are bacterial, it is hypothesized that using systemic antibiotics will
 reduce the rate of postoperative wound infections. There are, however, no definitive
 prospective studies that support or refute the necessity of systemic antibiotics in the
 prevention of postoperative inflammatory complications of AO or infection.

 All studies published to date addressing the role of systemic antibiotics and M3 removal have
 one or more major methodological flaws in study design characterized as :1) no or ambiguous
 definition of the outcome variable, 2) inadequate sample size, 3) non-uniformity of protocol
 design, 4) lack of randomization techniques and 5) poor-follow-up monitoring. Clearly, there
 is a need for a definitive, rigorous, well-designed placebo-controlled randomized clinical
 trial to ascertain the efficacy of systemic antibiotics in preventing postoperative
 inflammatory complications after M3 removal.

 .
Inclusion Criteria:

 -  Demographics: While all ages are eligible for study enrollment, as a practical matter,
 most patients having M3s removed are usually > 13-14 years of age.

 -  Gender: Males and females will be offered to participate in this study.

 -  Race: All races and ethnicities are eligible for study enrollment.

 -  Clinical status: at least one impacted mandibular third molar ( M3 ) must be scheduled
 for extraction.

 -  Anesthesia: Patient request that the procedure be executed using intravenous sedation
 or general anesthesia. Intravenous sedation will be accomplished with use of an IV
 placed in the antecubital fossa of each patient

 -  Health status: Healthy patients or patients with mild systemic disease, i.e. ASA
 status < 3, are eligible for study enrollment.

 Exclusion Criteria:

 -  Pre-existing infection: Infection is characterised as having an area with frank
 purulence and/or cellulitis characterized by erythema, induration and inability to
 open the mouth wide enough to provide access to the airway.

 -  Pre-existing Systemic Illness: as evidenced by severe dry mouth, patients who have
 undergone radiotherapy for oral cancer, patients that are immunocompromised, patients
 that require antibiotic prophylaxis for endocarditis, as well as, patients who are
 taking antimicrobials for other systemic diseases, i.e., uncontrolled diabetes., ASA
 status > 2.

 -  Allergic Reactions to Medications: Patients who are allergic to Penicillin and
 Clindamycin will be excluded from the study.

 -  Anesthesia: Patient request that the operation be performed with local anesthesia
 without intravenous sedation or general anesthesia.

 -  Pregnancy: Pregnancy is a relative contraindication for study enrollment. If after
 consultation with the obstetrician, there is no contraindication to removing the
 impacted teeth with sedation or contraindication to receiving the test medications
 (penicillin or clindamycin) and the patient wants to pursue treatment, she would be
 considered eligible for study enrollment.