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What are t he

Antibiotics of Choice
f o r Od o n t o g e n i c
Infections, and How
L o n g S h o u l d th e
Tre a t m e n t C o u r s e L a s t ?
Thomas R. Flynn, DMD

KEYWORDS
 Antibiotics  Odontogenic infection  Treatment course

In view of the constantly changing antibiotic sensi- Laboratory studies of the antibiotic sensitivities
tivity patterns of orofacial pathogens and anec- of a large number of pathogens from OI are infor-
dotal reports of treatment failures in orofacial mative, but they cannot account for the effects
odontogenic infections (OI), oral and maxillofacial of surgical treatment, bacterial interactions, and
surgeons (OMS) must continually make clinical immune response in the clinical situation.
decisions on the choice of empiric antibiotic the- The OMS must take into account the potential
rapy in the face of uncertainty. In addition, we morbidities of the antibiotic and surgical treat-
must decide on the duration of antibiotic treatment ments, plus their economic costs, before making
empirically, knowing that patients commonly do the antibiotic prescription.
not complete the prescribed antibiotic course, This article is an attempt to answer these ques-
usually without adverse effect. tions with a systematic review of the currently
Therefore, OMS need updated answers to these available scientific literature on this multifaceted
2 questions: topic.

1. What are the empiric antibiotics of choice
for OI?
MATERIALS AND METHODS
2. How long should the treatment course last?
Formulation of the Questions
As the introduction to this article indicates, this
The first question is the more complex. A contem- broad topic must be broken down into multiple
porary double-blind, randomized controlled clinical answerable questions, using the PICO format:
trial comparing all of the relevant antibiotics in P 5 patients; I 5 intervention(s); C 5 controls;
a large, multicenter, North American population of O 5 outcomes. Those questions are:
patients with well-defined OI, combined with app-
ropriate surgical treatments, would be ideal. A 1. In patients with orofacial OI (ie, an OI presenting
similar study of the duration of the antibiotic treat- with swelling going beyond the alveolar process
ment course, with its long-term effects on selection into soft tissue), does administration of 1 antibi-
oralmaxsurgery.theclinics.com

for antibiotic-resistant bacteria, would provide the otic, compared with another antibiotic or no
answer to the second question. However, such antibiotic, result in: (a) faster resolution, (b) less
studies do not exist. morbidity from the infection or the treatment,

The author has nothing to disclose.
1055 Waverly Drive, Reno, NV 89519, USA
E-mail address: thomasrflynndmd@gmail.com

Oral Maxillofacial Surg Clin N Am 23 (2011) 519–536
doi:10.1016/j.coms.2011.07.005
1042-3699/11/$ – see front matter Ó 2011 Elsevier Inc. All rights reserved.

selec- of pathogens in OI indicate that no one antibi. vant articles were selected for review of their biotic sensitivity testing of bacterial strains cultured abstracts. significant symptom relief. 2010. such as incision combined with appropriate surgical treatment. resistant organisms. be- base. of various antibiotics against individual strains of In addition. swelling. and application of “review resolution. locate systematic reviews on the topic. such as resolution of fever. Because some of them. 3. The 2. and drainage. the author’s list of references was bacteria that may or may not be present in a given also reviewed for such articles. from odontogenic orofacial infections. (c) less selection for antibiotic. and various studies may focus on only was also searched in the same manner. Target population: patients presenting with The hypotheses of this systematic review are: an oral. 2. no antibiotic and/or surgery alone) all searches is documented in Box 1. (b) less morbidity from the infection or articles” as a publication-type limit. and expense. facial. albeit Selection Criteria separately. Cochrane Library were searched for the period isms. The formulation of a comprehensive of the continually changing nature of bacterial answer to these questions also must take into resistance to antibiotics. The Specialized Register of possible significant outcomes that may be mea.520 Flynn (c) less selection for antibiotic-resistant organ. Types of studies: with appropriate surgical treatment. or (d) less expense? To identify relevant clinical trials. The strategy for a control (ie. and the Controlled Trials Register of the patterns over time. and whether published since January 1. or clindamycin. point. In vivo studies that measure the thus identified were read and evaluated for pos- comparative clinical success of various empirically sible inclusion in this study. administered antibiotics more closely simulate the clinical situation posed by the first question. was used in the study design. or the entire article. In vitro studies report anti. The following criteria were used to include or exclude articles from this systematic review: Hypotheses 1. does administration of an anti. the laboratory studies of account whether surgical treatment was com. the PubMed data. Laboratory studies of the antibiotic sensitivities caused by the disease or the treatment. or (d) less expense? from their inception to December 27. of care 3. In patients with OI. endodontic the- results in equal or better clinical outcomes rapy. otics. 2010. DARE (Database of Abstracts of Reviews of cause of changing antibiotic resistance Effects). selection for tiveness of 2 or more antibiotics. The titles of articles found by these search There are 2 categories of study that may shed methods were examined and all potentially rele- light on the first question. tooth extraction. Administration of narrow-spectrum antibiotics. Outcome measures: time to a clinical end otic. and the cost otic is effective in all cases. antibiotic sensitivity patterns were limited to those bined with the antibiotic course. Antibiotic courses of 4 days or less. compared apeutic use”. combined 4. tion of antibiotic-resistant strains. Clinical Trials of the Cochrane Oral Health Group sured. azithromycin. possibly antibiotic-resistant strains. if available. mor. Interventions: systemically administered antibi- such as penicillin. these data- bases were searched from their inception to These 2 questions indicate that there are 4 December 27. as measured controlled clinical trials comparing the effec- by time to resolution. 2000. and observation than broader-spectrum antibiotics or no antibi. or and expense. or bidity. drainage. reference lists of these articles were also reviewed. They measure only the comparative effectiveness and possibly relevant articles were also obtained. or cervical infected swelling of odontogenic origin 1. or gingival curettage. morbidity or death 2. All of the articles clinical infection. Clinical studies of antibiotic treatments: equal or better clinical outcomes. selection for antibiotic-resistant strains. as measured by time to resolution. local surgical measures. result in a. were used to the treatment. morbidity. return to work. The from specimens sampled from clinical infections. Both in vitro and in vivo studies are evaluated. result in: (a) faster published in English. with a negative control (no antibiotic) b. only laboratory studies . term “antibacterial agent” with a subtopic of “ther- biotic for a 4-day or shorter course. and the clinical studies are given greater weight than the laboratory studies. with limitations of human studies and with a 5-day or longer course. hospital discharge. Laboratory studies of the comparative antibi- Search Methodology otic sensitivity of bacterial strains cultured Before this review was initiated.

Randomization: nonrandomized trials Fields] OR “antibiotic”[All Fields] OR “anti. Bacteria: studies that did not report on (“Abscess”[Mesh] OR “Periapical Abscess” [Mesh] OR “Retropharyngeal Abscess”[Mesh] both viridans group Streptococci and oral OR “Periodontal Abscess”[Mesh]) AND anaerobes (“Anti-Bacterial Agents”[Mesh] OR “Anti. with or without surgical therapy. Antibiotic Selection for Odontogenic Infections 521 Box 1 of orofacial OIs comparing 4 days or less Search strategy with 5 days or more of antibiotic treatment. It is described fully in Table 1. c. Language: articles written in languages other bacterial agents”[Pharmacologic Action]) than English. Population: OI limited to the periodontium or the periapical region. Antibiotics: studies that did not report sensitiv- “Soft Tissue Infections/drug therapy”[Majr] ities to a penicillin and to clindamycin 3. mixed-cause Terms] OR (“mouth”[All Fields] AND “disea. published in the last 10 years score. The quality assessment scale adapted from tice Guideline. with examples: Fields] OR (“bacterial”[All Fields] AND “in- fection”[All Fields]) OR “bacterial infection” 1. The criteria on which each included article were as- sessed include randomization. Inappropriate outcome measure: pain relief Diseases/drug therapy”[Majr] alone as an outcome measure ((“anti-bacterial agents”[MeSH Terms] OR 4. Controls: lack of clearly stated control or com- (“anti-bacterial”[All Fields] AND “agents” parison group in clinical studies [All Fields]) OR “anti-bacterial agents”[All 5. 5. Clinical Trial. Publication date: studies published before ty”[All Fields] AND “tests”[All Fields]) OR January 1. from 0 to 5. Fields]) OR “mouth diseases”[All Fields])) Assessment of Methodological Quality Limits Activated For Clinical Trials The clinical studies were amenable to an assess- ment of the likelihood of the introduction of bias. Language: articles written in languages other (“mouth diseases”[MeSH Terms] OR (“mouth”[All Fields] AND “diseases”[All than English. Study type: case series or reports. The included highest possible quality score was 5. and published between 2000 and 2010 were a description of withdrawals and dropouts. AND (“bacterial infections”[MeSH Terms] OR (“bacterial”[All Fields] AND “infections” Laboratory studies were excluded for the [All Fields]) OR “bacterial infections”[All following reasons. review articles “Periapical Diseases”[Majr] AND “Periapical 3. where available OR (“microbial”[All Fields] AND “sensitivi. Clinical studies of the duration of antibiotic In 1998. blinding or double- blinding (as appropriate to the study design). mixed-cause Each search included 1 or more of the search head and neck infections without separate re- terms and the limits activated porting of odontogenic cases For Clinical Trials 2. Randomized Controlled Trial Jadad and colleagues1 by Matthews and col- For Laboratory Studies leagues2 was used to assign a numerical quality Humans. 2001 “microbial sensitivity tests”[All Fields]) AND 6. non-OIs. head and neck infections without separate re- ses”[All Fields]) OR “mouth diseases”[All porting of odontogenic cases Fields])) 2. with examples: PubMed Search Terms 1. Prac. non-OIs. Sensitivity standards: studies that did not use Bacterial Agents/therapeutic use”[Mesh]) the National Committee for Clinical Laboratory Standards (NCCLS)/Clinical and Laboratory For Laboratory Studies Standards Institute breakpoints for minimum ((“microbial sensitivity tests”[MeSH Terms] inhibitory concentration. the US Food and Drug Administration treatment courses: controlled clinical trials (FDA) issued guidelines for the development of . Database MEDLINE (1966 to present) Exclusion Criteria Search Engine Clinical studies were excluded for the following reasons. Population: OI limited to the periodontium or [All Fields]) AND (“mouth diseases”[MeSH the periapical region. 6. 4. Humans. Meta-Analysis.

and sensi- tivity to 80% and to 90% of all strains of all species Eight studies met the selection criteria for clinical isolated. outcome measures exclusion criteria. and the method was described and 2 appropriate Yes. and the method of double-blinding 2 was described 3. sample treatment course duration were selected for size. There the number of strains per case.522 Flynn Table 1 Jadad quality scale Question Answer Points 1. Some trials re- a greater number of bacterial strains isolated ported both on comparative antibiotic treatments in each case. provide a detailed prescription was divided by the cost of a standard clinical description of the patients. and 3 trials of antibiotic clinical study. cost ratio. trials. based on the to antibiotic sensitivity in OI. the oral cavity). Was there a description of withdrawals No 0 and dropouts? Yes 1 Total possible score 5 Adapted from Jadad AR. antimicrobial drugs for the treatment of complicated Costs of Oral Antibiotics skin and soft tissue infections. exclu- macy chain in the Boston area. Carroll D. with their controls and study groups. However. including CLINICAL TRIALS OF ANTIBIOTICS antibiotics tested.3 The 7 guidelines The retail cost an uninsured patient would pay for state that such studies should include infections a 1-week prescription for commonly prescribed in areas predisposed to polymicrobial infections antibiotics for OIs was obtained from a large phar- (eg. anti. geographic location. after detailed review are listed in Table 2.17(1):1–12. eligibility criteria. In the search for review articles. and on bacterial sensitivities.4–31 and results. In the preliminary search for number of strains isolated in the study was relevant studies. they are listed in Table 3.32–40 along with . including study design. as appropriate. 3 review articles were selected for discus- sessed by the number of strains per case. uation. and the method was inappropriate 0 2. The cost of a given sion. After evaluation. detailed review. consider the amoxicillin prescription to produce the amoxicillin primary outcome measure to be clinical cure. to provide a numeric means of com- provide culture data in at least 70% of patients. and outcome definitions. and after eval- The quality of laboratory studies was as. with permission. patient characteristics. The sion in this article. No 0 blind? Yes 1 Yes. stratify the analysis of outcomes by surgical inter- vention. and by clinical cure with evidence of RESULTS bacterial eradication. 228 articles potentially relevant microbiologic methods used. relevant review articles were found. 23 clinical trials of antibi- otic treatments in OI. The number of these 7 criteria that each included study met was re. 1003 articles potentially relevant divided by the number of patients to calculate to any of the 3 study questions were found. Moore RA. provide clear inclusion. Similar data from laboratory-based studies were extracted. and 3 trials of antibi- assumption that better methods would result in otic treatment course duration. paring antibiotic costs. 18 laboratory studies of anti- Pertinent information was extracted from each biotic sensitivity from OI. Was the study described as randomized? No 0 Yes 1 Yes. none of these met the criteria for inclusion as laboratory Data Extraction studies. Assessing the quality of reports of randomized clinical trials: is blind- ing necessary? Control Clin Trials 1996. The articles that were excluded biotic regimen. 40 potentially corded. et al. Was the study described as double. surgical interventions allowed. as an additional measure of quality. This statistic were 772 articles potentially relevant to antibiotic was used as a measure of the quality of the treatments in OI.

36 effective against 90% or more of all strains of all Nearly significant differences were found in species. 5 articles and 1 letter are 7 FDA antimicrobial drug development guidelines. These studies are listed in cularly and amoxicillin/clavulanate were used in Table 4 in decreasing order of strains per case. fluoroquinolones tested. as defined by no one antibiotic is likely to be effective in vitro the individual study. The mean quality assessment scale LABORATORY STUDIES was 2. which is the number of patients selection criteria for laboratory studies of antibiotic multiplied by the quality assessment scale. All of the studies tested the antibiotic sensiti- halexin (1). respectively. although Blandino There was only 1 study that reported a statistically and colleagues40 stated that the combination of significant difference between treatment groups. and the b-lactam/b-lacta- ized patients. with a mean of 70  28 (SD) and A penicillin was either the intervention or a range of 37 to 94 patients per study. a b-lactam/b-lac- Only 1 study used a nonantibiotic control. with or without intraoral. Penicillin V number of strains per case was 3. None of the 8 studies found a statistically signif. These 4 studies included with a range of 3 to 6. cephalexin. consis- icillin/clavulanate with penicillin. and sisting of surgery alone. In a randomized. tooth extraction.5. levofloxacin. with the number of trials listed in paren.40. 2 each in the ornidazole and the penicillin alosporins were not tested.40 In 3 of the 4 gery alone. with the more recent studies reporting more tested. possibly in combination. a cephalosporin. incision and drain. All patients received ex. cephalexin.7 days nation was effective against 80% of all strains of versus 6. 280 patients. anaerobes only. Other antibiotics tion. a b-lactam/b-lactamase inhibitor combi- time to clinical cure. deviation [SD]) and a range of 19 to 106 patients per study. were: clindamycin (2). study.2 days for amoxicillin. minocycline. there was no adjust- 488 patients. clindamycin. The mean comparator antibiotic in all studies. a range of 2. tamase inhibitor combination. consisting of a fluoroquinolone. These 8 studies included groups. various cephalosporins. penicillin and metronidazole would have been In a randomized.4 to 5. included in Table 4.43 In 1 study. nonblinded and cefotaxime were also effective against 90% trial comparing amoxicillin. including doxycycline. although imipenem and ceph- patients. a few other studies. and vities of the isolated aerobic and anaerobic moxifloxacin (1). effective against all strains of all species. In 2 of the 4 was no difference in clinical cure. against viridans group Streptococci. there were significantly fewer days with species.3 (range 1–5).45 found that no antibi- failures in the penicillin group (nearly statistically otic was even 80% effective against all strains of significant. surgery alone. canal therapy.9  1.44. Only 1 study used hospital. In the clinical portion of . lincomycin (1). whereas ampicillin and amoxicillin which roughly corresponds to the date of publica- were used in 1 study each.42. 2 studies each. strains per case. with a mean of 61  29 (standard ment for the multiple statistical tests used. both antibiotic groups had a shorter studies. Surgery. amoxicillin/clavulanate or imipenem was observed in all patients by day 7. ornidazole (1). and all species. metronidazole (1). and gentamicin was tested only age. There and another for the oral anaerobes. which was studies. The overall results of these studies indicate that icant difference in clinical cure rate. cefoxitin. was used erythromycin.43–45 pain in the ornidazole group and more treatment The most recent study44. a significantly tent with the clinical strategy of using 1 antibiotic lower pain level on days 2 and 3 of treatment was highly effective against the oral Streptococci found in the amoxicillin/clavulanate group. or root antibiotics. Some studies included other incision and drainage. with orally was used in 3 studies.5 days versus 4. and sur. or tooth extraction.1  1. separate portions of their data in 2 separate publi- The 8 studies met a mean of 4. imipenem. metronidazole was tested against obligate traoral. nonblinded trial comparing amox. 4 of the 60 all species isolated. Antibiotic Selection for Odontogenic Infections 523 selected characteristics. clindamycin. Either levofloxacin or moxifloxacin were the all of the study groups.)39 However. or more of all strains of all species.32 Intravenous moxifloxacin and mase inhibitor combinations were either amoxi- amoxicillin/clavulanate (available intravenously in cillin/clavulanate or ampicillin/sulbactam.41. received no surgery.38 In a randomized. with sensitivity.40–45 Two of these studies reported a mean of 150  78 and a range of 38 to 245.1 of the cations. con. The studies are listed in Table 3 in decreasing order of the power  Four studies reported in 6 publications met the quality score. against all strains of all species. strains to penicillin or ampicillin. or a fluoroquinolone operator-blinded study comparing ornidazole and was effective against 80% of all strains of all penicillin. in this study.40–43 In 2 of the 4 studies. and imipe- in all of the studies as an adjunctive treatment in nem.6  1. cep.3.45 Thus. theses. In 1 Europe) were compared. penicillin G intramus. 4.

J 2 Antimicrob Chemother 1993. Ear Nose Throat J 2005. Efficacy of azithromycin compared with spiramycin in the treatment of odontogenic infections. Phlegmonous and abscess-forming ENT infections: comparative efficacy of ceftriaxone versus amoxicillin-clavulanic acid. Comparison of moxalactam with the combination of clindamycin and an aminoglycoside in the 2 treatment of common surgical infections. Penicillin as a supplement in resolving the localized acute apical abscess. J Clin Periodontol 2000. Chisari G.30(1):146–517 Daramola OO. Antibiotics in surgical treatment of septic lesions.71(4):496–811 3 Herrera D. The role of phenoxymethylpenicillin. J Antimicrob Chemother 1978. Flanagan CE.31(Suppl E):119–2714 Matijevic S. Oral Surg Oral Med Oral Pathol Oral 2 Radiol Endod 1996. Del Bene VE.206(7):357–629 Fouad AF. in the treatment of multidrug-resistant gram-positive bacterial infections. Otolaryngol Head Neck Surg 2 2009. et al. 524 Flynn Table 2 Excluded articles Reason for Reference Exclusion Clinical Trials Adriaenssen CF. The periodontal abscess (II). Walton RE. The place of metronidazole in the treatment of acute oro-facial infection. Kucia ML. Odontogenic signs and symptoms as predictors of odontogenic infection: a clinical trial. Oral Surg Oral Med Oral Pathol 1991. Rev Infect Dis 1982. 2 Clin Infect Dis 2000. Vojnosanit Pregl 2009. J Int Med Res 1998. amoxicillin. an oxazolidinone. O’Connor A. J Am Dent 4 Assoc 2006. Salata RA. Lazic Z.141(1):123–308 Ellison SJ. Batts JJ. et al. Comparison of the efficacy. et al. metronidazole and clindamycin in the management of acute dentoalveolar 3 abscesses–a review.81(5):590–510 Hanna Jr CB. clindamycin and inpatient i. safety and tolerability of azithromycin and co-amoxiclav in the treatment of acute periapical 2 abscesses. Rivera EM. Aygenc E.4(Suppl C):71–313 3 Lo Bue AM. Br Dent J 2009. Sammartino R. Nonkovic Z [Clinical efficacy of ampicillin in treatment of acute odontogenic abscess].4(Suppl):S683–718 . Use of linezolid. et al. Unsal E.26(5):257–654 Benson EA. Roldán S. Runyon MS. Burkey LG.137(1):62–66 Chien JW. ampicillin/sulbactam 2 following needle aspiration. Cefadroxil in the management of facial cellulitis of odontogenic origin. Diagnosis and treatment of deep neck space abscesses. Peritonsillar abscess: a comparison of outpatient i.m. Lancet 1970.1(7658):12335 3 Brennan MT.27(6):395–40412 Hood FJ. Short-term clinical and microbiological efficacy of 2 systemic antibiotic 2 regimes. et al. Maisel RH. et al.54(2):95–917 Rambo WM.66(2):123–815 1 Ozbek C. ORL J 2 Otorhinolaryngol Relat Spec 1992.v.84(6):366–816 Panosetti E.

J Antimicrob Chemother 2006. J Clin Microbiol 1985. Evaluation of the mandibular third molar pericoronitis flora and its susceptibility to different 2 antibiotics prescribed in France. design not prospective. Maeurer M. 7 Br Dent J 2005. Renaissance of the penicillins?]. et al. Nakagawa K.22(4):285–828 Lo Bue AM. Gilmore WC. 4. 5 [Epub 2007 Nov 12]20 Eckert AW. 8 lactam antibiotics. Jolivet-Gougeon A. Chisari G. Ann Otol Rhinol Laryngol Suppl 6 1991. et al. Eur Surg Res 2008. Oral Microbiol Immunol 2002. Karasawa T. Satoh T. J 2 Antimicrob Chemother 1993. 5. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000. In vitro antimicrobial susceptibility of oral strains of Actinobacillus actinomycetemcomitans to 7 2 antibiotics. 7 producing bacteria in patients with orofacial odontogenic infections. Karasawa T. Yanagisawa M. type not randomized clinical trial. 7. Wilhelms D. Longman LP.9(6):377–8321 Gorbach SL. publication date before 2001. Clinical appearance of orofacial infections of odontogenic origin in relation to microbiological 6 findings.29(8):736–4229 Sixou JL. et al. 8. Laboratory Studies Al-Nawas B.17(5):285–925 Kuriyama T. von Konow L. Microbiology and antibiotic resistance in odontogenic infections.41(12):5794–730 Duration of Antibiotic Therapy Martin MV. J Clin Periodontol 2002. Efficacy of azithromycin compared with spiramycin in the treatment of odontogenic infections. Language other than English. 6.31(Suppl E):119–2714 Müller HP. Sammartino R. Holderrieth S. Oral Microbiol Immunol 2007. 2.183(4):135–731 1. et al. Antimicrobial susceptibility of 800 anaerobic isolates from patients with dentoalveolar 2 infection to 13 oral antibiotics. Mund 1 Kiefer Gesichtschir 2005. An increased prevalence of {beta}-lactamase-positive isolates in Japanese patients with 8 dentoalveolar infection. Antimicrobial susceptibility of major pathogens of orofacial odontogenic infections to 11 beta.154:40–222 Heimdahl A. Jacobus NV. population not OI. 525 . et al. Absi EG. An outcome audit of the treatment of acute dentoalveolar infection: impact of penicillin resistance. Williams DW. et al [Bacterial spectra and antibiotics in odontogenic infections.89(2): Antibiotic Selection for Odontogenic Infections 186–9227 Kuriyama T. Acute dentoalveolar infections: an investigation of the duration of antibiotic therapy. et al. Williams DW. Burkhardt U. Williams DW. type not a comparison of antibiotics or duration of antibiotic therapy. Past administration of beta-lactam antibiotics and increase in the emergence of beta-lactamase. et al. Maurer P. 3.198(12):759–6324 Kuriyama T. et al. Magaud C. sensitivities not reported for all isolates.22(2):299–30223 Kuriyama T. J Clin Microbiol 2003. sensitivities do not include at least penicillin and clindamycin. et al. et al. Karasawa T.58(3):708–926 Kuriyama T. Br Dent J 3 1997. Severe versus local odontogenic bacterial infections: comparison of microbial isolates. et al. Nakagawa K.40(2):220–4. Hill JB.

1) 240 4 ORN PCN N N Only surgery was I&D. ext/RCT et al.34 1988 performed only after study completion von Konow and 1983 60 4 (2. more failures in PCN group (NSD) Mangundjaja 1990 106 2 (1.1. ext/RCT and Hardjawinata. 2 Nord.1) 245 6 PCN CLI N N Only surgery was I&D. or pain . Not all patients were cured by 7 d Lewis et al.2. 526 Flynn Table 3 Included clinical trials of antibiotics in OI Number Significant Quality Power 3 of FDA Difference Assessment Quality Guidelines Intervention Comparator Surgical Between Reference Year N Scalea Score Met Group Group Control Groups? Comment Gilmore 1988 49 5 (2.0.1) 156 3 AM/CL PCN N N Surgery was either I&D or ext 1993 or RCT.05).39 1983 patients in each group did not receive surgery. Fewer days of pain in ornidazole group (P<. Greater pain reduction at 1–2 d and 2–3 d in amoxicillin/clavulanate group.1) 212 4 CLI AMP N N Only surgery was I&D. temperature. otherwise NSD in swelling.36 1993 78 2 (1.37 performed only after study 1990 completion. lymphadenopathy.0.

no. withdrawals/dropouts). NSD. afebrile Antibiotic Selection for Odontogenic Infections Abbreviations: AMP. AMOX. ORN. “marked clinical improvement” was noted in all patients Al-Nawas et al. ext. incision and drainage. Y. root canal therapy.38 2009 90 1 (1. moxifloxacin. no pain on palpation. requiring extraoral and/or intraoral I&D.35 1977 37 2 (1. clindamycin. ampicillin. AM/CL. yes. no significant difference. amoxicillin.1.1) 38 5 MOXI AM/CL N N Only study of hospitalized 2009 patients. LIN. intramuscularly. CLI. N. PCNG.” At 24–48 h. ornidazole. CEPH.1) 147 3 LIN (IM and PCNG (IM N N 9 patients had trauma and Balcom 3rd. amoxicillin/clavulanate. 527 .32 2009 19 2 (1. metronidazole. penicillin V. Davis Jr and 1969 49 3 (1. extraction. cephalexin.0) 74 3 MET PCNG (IM N N Patients received “appropriate 1977 once daily) surgery when necessary. a The numbers in parentheses are the components of the Jadad score as in Table 1 (randomization. blinding. including 1969 mouth) osteomyelitis Matijevic et al. RCT.0. I&D.0) 90 5 AMOX CEPH Y N Antibiotic groups had shorter 2009 treatment time than surgery alone (not statistically significant) Ingham et al. Cure 5 improving trismus. penicillin G.1. IM. MET.33 by mouth) and by fractures. lincomycin. PCN. MOXI.0.

39 Japan CLI. None MOXI was effective in at least 90% 2008 AM/CL. MET AM/CL. MINO was tested only against obligate CEFOT. IMI GENT was tested only against VGS. LEV.40 2007 56 4. IMI CEFAZ. CEFMET. doxycycline. MET LEV. CEFOT. MINO resistant Kuriyama et al. PCN 1 MET METa.44 2008 Data from this report are combined 2008 with the above report Blandino et al. erythromycin.20 Italy PCN. MOXI. AMP/SUL. LEV. IMI. MET. amoxicillin/clavulanate. CLI. DOXY. AM/CL. None PCN. LEV. LEV. GENT. PCN. cefoxitin. for all strains IMI Kuriyama et al. MINO. . anaerobes. CLI. DOXY of all strains. ERY. CLI. levofloxacin. LEV. ERY.35 Germany PCN. gentamicin. CEFOT. except Clostridium sp DOXY and Pseudomonas aeruginosa (1 isolate).41 2002 Data from this report are combined 2002 with the above report Sobottka et al. MOXI PCN. penicillin. 528 Flynn Table 4 Laboratory studies of the antibiotic sensitivity of pathogens in OI Antibiotics Antibiotics Antibiotics Effective for ‡ Not Effective Effective for ‡ Strains 80% of All for ‡ 80% of 90% of All Per Antibiotics Strains of All All Strains of Strains of All Reference Year N Case Location Tested Species All Species Species Comment 45 Warnke et al. clindamycin. moxifloxacin. CLI. CLI. CEFOT. metronidazole. ERY. CEFAZ. IMI IMI would have been effective CEFOX. CEFMET. MET not tested on aerobic/ 2007 AM/CL. ERY. Antibiotic 1 surgery was effective in 98% of all patients Warnke et al. CEFOX. AM/CL.43 2002 37 2. ampicillin. AM/CL. AM/CL Only AM/CL was effective against all 2002 LEV. AMP/SUL. CEFOX. CEFAZ. with 10% of strains IMI. AM/CL. CEFOT. LEV. minocycline. CEFMET. CLI. DOXY strains of all species DOXY Abbreviations: AMP. cefazolin. with 30% of strains resistant. CEFOX.42 2001 93 3. MOXI. facultative strains. ampicillin/sulbactam. AMP. cefotaxime. MOXI. CLI. PCN. MOXI. CEFOT. 2001 AMP/SUL. AMP. ERY. 2008 94 5. impenem. AM/CL.50 Germany PCN. CLI. cefmetazole.

However. 300-mg capsule. In 2 cases (2%). and . The choice among no anti.47 cillin cost ratio allows numeric comparison of the The 2 studies included 101 patients. broader-spectrum antibiotics have lower resis. language bias (only English articles and colleagues47 compared amoxicillin 1 g by were reviewed). resistant strains. extraction. penicillin. Lewis and colleagues46 compared 2 3-g language-restricted and language-inclusive meta- doses of amoxicillin by mouth 8 hours apart with analyses do not seem to differ in their estimate penicillin V 250 mg by mouth 4 times a day. as cost of the 150-mg capsule of generic clindamycin described in Table 1. in less selection for the survival of amoxicillin- The recent in vitro studies of the antibiotic sensi. but there was no statis- response to penicillin. analysis of the data was not attempted in this ment between groups in either of the 2 included review. which of 51  13 (SD) and a range of 41 to 60 patients is one of the least costly of antibiotics listed. for 7 days. studies. study was not included among the antibiotic trials. quate randomization methods can exaggerate ence between groups at any measurement interval the estimated effect of treatment by 41%. Potential sources of bias in this systematic review consisting of incision and drainage. was 4. The mean quality assessment scale. The amoxi- Table 5.48 Meta- was no difference in clinical cure at 7 days of treat. appropriate surgery alone (36% in any of the study parameters (pain. swelling. possibly in combination. 4 times a day for the generic formulation. because only mouth twice a day for 3 days with the same regimen the author reviewed and selected articles. Neither study used a nonantibiotic control Clinical trials that are not randomized or blinded consisting of surgery alone. tical adjustment for the multiple tests used. an antibiotic change may indicate more rapid antibiotic effectiveness to cefotaxime was required because of a poor in the amoxicillin group. in combination with appropriate necessary and often sufficient treatment of orofa. long course groups was minimal and nonsignifi- monly used antibiotics. The statisti- (64%). Both studies compared short (1–3 days) with long (5–7 days) courses of a penicillin. they are listed in regimens for OI are listed in Table 6.1 It has been shown that inade- the amoxicillin group.5–0. There of the effectiveness of an intervention. In biotic.46. and subjective bias. or include publication bias (unpublished studies were pulpal drainage. or in combination with an antibiotic lymphadenopathy. resulted in satisfactory recovery in 92 of cally significant difference in swelling at 24 hours the 94 cases. Thus. The per study. along with selected characteristics. or amoxicillin/clavulanate was this study. without the DISCUSSION use of a surgery-alone group as a control. The 2 included studies found no significant tance rates than older. DURATION OF ANTIBIOTIC THERAPY Costs of Oral Antibiotics Two studies met the selection criteria for trials of the The retail costs of commonly prescribed antibiotic duration of antibiotic therapy. Clindamycin was used lined earlier defined clinical cure of the infection. The clinical portion of this which was achieved at 7 days. there a 1-day to 3-day or a 5-day to 7-day course of anti- is evidence to indicate that surgical therapy is biotics was used. The Both studies met 3 of the of the 7 FDA antimicrobial brand-name formulation costs even more for the drug development guidelines. surgery. which is the number of 2 150-mg capsules of generic clindamycin 4 times patients multiplied by the quality assessment scale. a day is only 63% of the cost of 1 300-mg capsule with a mean of 225  21 and a range of 210 to 240. is significantly less than half of the cost of the The studies are listed in decreasing order of the generic 300-mg capsule.7 (range 4–5). All patients received appropriate surgical treatment. and that newer and cant at the end of the 30-day observation period. Although the Chardin and colleagues47 study because the patients were not randomly allocated claimed that a shorter treatment course would result to treatment groups. Chardin not sought). difference in clinical cure at 7 days when either otics. clinical parameters may have cial OIs. with a mean other antibiotics to the cost of amoxicillin. in penicillin allergy. narrower-spectrum antibi. or temperature). However. even among these studies. the difference in carriage of amox- tivity of isolates from OIs indicate that there is icillin-resistant organisms between the short and a trend toward increasing resistance to the com. Antibiotic Selection for Odontogenic Infections 529 this study. but there was no other differ. In 1 study. normalization of the 4 parameters out- based on clinical severity. indicated a more rapid decrease of swelling with amoxicillin than penicillin. have a greater likelihood of reporting results that Lewis and colleagues46 observed less swelling favor treatment over control than randomized at 24 hours after the beginning of treatment in and blinded ones. of cases). a prescription for power  quality score.

Abbreviations: AMOX.47 2009 2009 41 5 (2. then  7d Streptococci between placebo groups at 30 d after treatment. 1986 1986 60 4 (2. N. . Data from Jadad AR. amoxicillin.1) 210 5 AMOX 1 g AMOX 1 g N N No difference in carriage of twice a day twice a day AMOX-resistant  3d.  2 doses day  5 d AMOX group or lymphadenopathy at day 7 Chardin et al. Moore RA.2. penicillin V.0) 240 5 AMOX 3 g PCN 250 mg N Less swelling No significant difference in every 8 h 4 times a at 24 h in pain. swelling. PCN. blinding.17(1):1–12. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996. Carroll D. et al. 530 Flynn Table 5 Included trials of the duration of antibiotic therapy Number Significant Quality Power of FDA Difference Assessment 3 Quality Guidelines Intervention Comparator Surgical Between Title/Reference Year N Scalea Score Met Group Group Control Groups? Comment 46 Lewis et al. temperature. withdrawals/dropouts). a The numbers in parentheses are the components of the Jadad score as in Table 1 (randomization.2. no.

well-accepted.99 10.15 64. Antibiotic Selection for Odontogenic Infections 531 Table 6 Costs of oral antibiotics 1-Week Usual Usual Wholesale Retail Amoxicillin Antibiotic Dose Interval Cost 2010 ($) Cost 2010 ($) Cost Ratio Penicillins Amoxicillin 500 mg 8h 0.60 49.blinding.00 Penicillin V 500 mg 6h 0.79 2.19 31.38 59.99 1.78 120.59 2.50 Clarithromycin (Biaxin XL) 500 mg 24 h 5.99 7.99 11.38 108.73 34.66 11.52 102.00 Clindamycin (generic) 300 mg 6h 3. An additional of the included trials did not further describe their point is added each for randomization and double- randomization methods.69 2.49 4.27 Cefadroxil (first) 500 mg 12 h 3.34 Augmentin XR 2000 mg 12 h 7. a maximum of 1 point can be given for .01 34.39 Cefdinir (third) 600 mg 24 h 10. a maximum of 2 points each can be given methodological quality of clinical trials based on for randomization and double-blinding.37 11.49 Only trials that were described as random.99 4.99 8.03 Augmentin 875 mg 12 h 5. if the method of each was appropriate.09 Telithromycin (Ketek) 800 mg 24 h 11.99 1.00 Linezolid (Zyvox) 600 mg 12 h 91.19 1. which could exaggerate blinding.59 5.20 25.05 51. One point is given for each of these 30%.13 Cefuroxime (second) 500 mg 8h 8. parameters if there is a statement that the param- ized were included in this review.89 Azithromycin (Zithromax) 250 mg 12 h 7.76 87.30 17.23 15.14 11. Amoxicillin cost ratio 5 retail cost of antibiotic for 1 week/retail cost of amoxicillin for 1 week.88 OTHER Trimethoprim/ 160/800 mg 12 h 0.74 12.22 65.13 Moxifloxacin (Avelox) 400 mg 24 h 16.31 13. and the grading of 3 parameters: randomization.99 5.49 2.31 Metronidazole 500 mg 6h 0.89 Ciprofloxacin 500 mg 12 h 5.00 sulfamethoxazole Vancomycin 125 mg 6h 29. parameters if the method was inappropriate.10 849. when the methods of randomization are unclear.35 138.59 Anti-anaerobic Clindamycin (generic) 150 mg 6h 1. and are not to be considered prescriptive.02 84.99 110. some eter was used in the study methods. the estimate of treatment effect. CPhT (Certified Pharmacy Technician). yet simple scale for evaluating Thus.13 Cephalosporins (generation) Cephalexin Caps (first) 500 mg 6h 1.09 Dicloxacillin 500 mg 6h 1.99 1.97 1322.47 ERYTHROMYCINS Erythromycin base 500 mg 6h 0.29 1.99 1. and description of withdrawals estimate of treatment effect is exaggerated by and dropouts.99 70. Courtesy of Aaron Van Dolson.59 Doxycycline 100 mg 12 h 1. the double. and a point is taken away for each of these Jadad and colleagues1 developed a validated. However.09 Cefaclor ER (generic) 500 mg 12 h 4.59 7.65 Clindamycin (2 T generic) 300 mg 6h 2.99 9.49 1.59 5.34 Notes: Usual doses and intervals are for moderate infections.

Matthews and colleagues’ findings were did. side effects.53 The 4 laboratory studies included plish when intraoral drainage has been performed. This is high-quality evidence to indicate that the rials section. whereas severe infections were treated with Brennan and colleagues6 performed a random- hospital admission. the report of outcome (clin. drug interactions have been discussed in multiple This historical review. and intrave. On multivariate analysis. the control antibiotic. Antibiotic toxicities. In assessing similar to those of this review: only 1 of the studies randomization. and antibiotic resistance in a comprehensive Ellison9 has reviewed the rational use of peni- manner. unculturable bacteria have been frequently identi- rial eradication at clinical cure) were not con. molecular methods are likely to affect our The studies identified in this review did not understanding of the flora and antibiotic resistance measure the outcomes of antibiotic morbidity patterns of OI. that antimicrobial trials should show commonly given antibiotic prescription for tooth- to be considered valid for new antibiotic develop. 1 point was awarded if the methods reported a significant treatment effect. and if it review. ache does not prevent a spreading infection. A study was not only control concluded that there was no sig- considered randomized if treatment allocation nificant difference in the number of days to pain was stratified by severity. domization. senting to a hospital emergency room with opment of antimicrobial drugs for the treatment toothache. in this review all used conventional culturing These criteria do not apply to the laboratory methods. RNA.5 mm at the painful tooth.51. which may be of assistance in the combined with the appropriate surgical interven- individualized selection of antibiotic for a given tion. In the studies. double-blind clinical trial comparing penicillin nous antibiotics. and confirmed bacte. Further. day 2 to 3 in the amoxicillin/clavulanate group. Swelling was a criterion for inclusion in this unaware of whether surgery occurred. Three criteria (analysis of outcomes strati. comes to the conclusion available literature for more information on those that these 3 antibiotics should be effective. or ran.52 ical cure) was stratified by surgical intervention. and metronidazole in dentistry.3 OIs are considered antibiotic. In a recent review of the microbiology of periap- fied by surgical intervention. which is the current standard. interval did not exclude the possibility that there domization. the 95% confidence of random numbers or computer-generated ran. present. In 2 studies. which is difficult to accom. such as fever. When all studies were and it was appropriate. The Jadad scale was used in this atic review and meta-analysis of treatments. Robertson and Smith50 noted that microbiologically evaluable. including antibiotic therapy. . 70% of patients ical abscess. 70% or more of the subjects were identify bacteria in pus specimens by their DNA or cultured. fied in significant proportions from periapical sistently met. when signs of systemic involvement are patient. Some of the procedure is involved requires that the evaluator articles included in that review are also included is not the surgeon. There was no difference in the develop- of uncomplicated and complicated skin and ment of OI in patients receiving penicillin or no skin-structure infections. In 5 of the 8 clinical trials of abscesses by using molecular methods to directly antibiotics. include 7 characteristics. review. randomly. for Matthews and colleagues2 performed a system- a total of 5. This finding has also been reported in OI. Diaz-Torres and colleagues have used molecular None of the studies reported bacterial eradication methods to identify antibiotic resistance genes in by follow-up culture. the nature of the procedure. for acute apical Double-blinding in studies in which a surgical abscesses with or without swelling. The guidelines cency larger than 1. V and no antibiotic in preventing OI in patients pre- The FDA has published guidelines for the devel. alone groups.532 Flynn a description of withdrawals and dropouts. the oral flora. such as the use of a table combined by meta-analysis. the only vari- complicated infections according to these guide. such as minor infections resolution between the antibiotic and the surgery- receiving outpatient surgery and oral antibiotics. espe. ment. ized. swelling. An additional point was awarded if compared with penicillin V. The reader is referred to the selected by the author. less pain on included words such as random. in which the references were texts and reviews. and that the evaluator is here. when topics. was used. extraoral surgery. these investigators’ such as alternating patients or odd/even medical meta-analysis of 2 studies that included a surgery- record numbers. listed earlier in the mate. future. the presence of a filling or a periapical radiolu- cially involving anaerobic bacteria. The first point was taken away if an was no difference between the intervention and inappropriate (predictable) allocation method. and cillin. clindamycin. tachycardia. ables that predicted the development of OI were lines because of their polymicrobial nature. but no difference in the randomization method was further described clinical cure at 7 days.

and drainage and/or tooth extraction or root The b-lactam antibiotics have an excellent canal therapy.38 the time to resolution was Metronidazole shorter when an antibiotic was added to surgery. such as fever. shorter and the longer course of treatment. extraction. randomized clinical trials com- that penicillin-resistant strains were isolated from paring 3 to 4 days and 7 days of antibiotic the infection in 54% of cases. Azithromycin otic. The significant difference in the number of patients costs of penicillin V and amoxicillin are low and cured between the intervention and compar- comparable. In patients with orofacial OIs receiving appro- by penicillin allergy. or trismus are pre. investigation. and canal therapy. In a prospective case series of severe OI 3. He also noted that metronidazole used alone has been shown to be Severity/Penicillin Antibiotics effective in OI when combined with appropriate Allergy of Choice surgery. with only minor resistance and virulence in OI warrants further consideration given to the comparative effective. including . Moxifloxacin but this result was not statistically significant. Flynn and colleagues priate surgical treatment consisting of incision found a 21% therapeutic failure rate of intravenous and drainage and/or tooth extraction or root penicillin G in severe. the surgeon’s choice of antibiotic should This apparent association between antibiotic depend on cost and safety. includ. A 3-day In penicillin allergy. amoxicillin may provide ator antibiotics. tion. even although its spectrum includes Outpatient Amoxicillin only obligate anaerobes. such as ampicillin/sulbactam as the first-line ing incision and drainage. Ellison states that Table 7 surgical treatment alone is effective when Empiric antibiotics of choice for OIs systemic signs are absent. Azithromycin swelling. metronidazole sary and often sufficient treatment of orofacial OIs. randomized clinical trials com- safety profile when allergic reaction has been ruled paring 1 antibiotic with another have found no out by a thorough medical history review. compliance with the prescribed antibiotic OIs indicate that newer and broader-spectrum regimen may be better with amoxicillin because of antibiotics are more effective in vitro than older. there is Vancomycin 1 evidence to indicate that surgical therapy is neces. Clindamycin tivity of isolates from OIs indicate that there is Penicillin 1 a trend toward increasing resistance to the metronidazole commonly used antibiotics. In 1 study. Antibiotic-associated colitis (AAC) cau- Based on this review. The choices are is a concern with multiple antibiotics. hospitalized cases of OI. Intravenously available antibi- priate surgical treatment consisting of incision otics are listed for inpatient infections. or trismus. stratified by severity (inpatient vs outpatient) and 1. it seems reasonable to conclude that to use a b-lactam/b-lactamase inhibitor combina- when combined with appropriate surgery. the antibiotics of choice sed by colonic overgrowth of Clostridium difficile for OI are listed in Table 7. therapy. However. even among these studies. Penicillin allergy Clindamycin sent. In patients with orofacial OIs receiving appro- requiring hospitalization. Clindamycin When systemic signs of infection. lymphadenopathy. narrower-spectrum antibiotics. and that newer and Ceftriaxone broader-spectrum antibiotics have lower resistance Penicillin allergy Clindamycin rates than older. Inpatient Ampicillin/sulbactam The recent in vitro studies of the antibiotic sensi. These findings indicate that it may be prudent Thus. its longer dosage interval. narrower-spectrum antibiotics. sensitivities of bacterial isolates from orofacial Further. The results of this systematic review allow us to arrive at a few conclusions. more rapid improvement in pain or swelling. reasons.54. Laboratory studies describing the antibiotic it is slightly less expensive than penicillin V. or root canal antibiotic in severe OI requiring hospitalization. ness of antibiotics within a given class.55 Al-Nawas and therapy have found no significant difference in colleagues32 found an increased rate of penicillin the number of patients cured between the resistance in hospitalized versus outpatient OI. Moxifloxacin However. clindamycin replaces the b- to 4-day regimen of antibiotic therapy should be lactam antibiotics as the drug of choice for safety adequate in otherwise healthy patients. Antibiotic Selection for Odontogenic Infections 533 lymphadenopathy. it seems reasonable to prescribe an antibi. and 2.

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