Professional Documents
Culture Documents
Objective. To find out whether the frequency of postoperative infectious and inflammatory complications (IC) in subjects treated
with placebo (Pl) is greater than those treated with antibiotic (Ab) after extraction of an impacted mandibular third molar (M3).
Our hypothesis is there are more IC in Pl than in Ab, with a maximum ratio difference of 0.067.
Study design. A double-blind placebo-controlled randomized clinical trial. The sample was derived from the population of
subjects attending Cruces Hospital for evaluation and extraction of 1 M3 under local anesthesia. Patients were treated with
postoperative placebo or amoxicillin/clavulanic acid 500/125 mg 3 times a day during 4 days. The outcome variable was
infectious and inflammatory complications. Sex, age, smoking, molar depth, angulation, need for sectioning, ostectomy, and
operation time were recorded. Analysis was by intention to treat, risk measures, and logistic regression.
Results. In 490 subjects (259 Ab and 231 Pl), the frequency of IC was 1.9% in the Ab and 12.9% in the Pl group (OR 7.6, 95%CI
2.9-19.9; P \ .001). The number needed to treat was 10 (7-16). Unadjusted relative riskwas 0.15 (0.06-0.38) (P \ .001).
Absolute reduction risk was 0.11(0.066-0.155)]. Therefore, the hypothesis cannot be rejected. Multivariate analysis shows
treatment with antibiotic (OR = 8.66 (3.17-23.67); P \ .001) and age (OR = 1.08 (1.00-1.16); P = .029) are the only variables to
be included in the logistic regression model.
Conclusion. Amoxicillin/clavulanic acid is efficacious in reducing the incidence of IC following third molar extraction but
should not be prescribed in all cases.
(Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;100:E11-8)
The incidence of infectious and inflammatory complications (IC) following an impacted mandibular third
molar (M3) extraction varies between 0% and 45%,
according to different published studies1-16 Controversy
exists over the use of systemic antibiotics for its prevention. While there is some evidence that antibiotics
can reduce the incidence of postoperative complications,2-4,9,10,14,15,17,18 there is equally convincing evidence to the contrary.1,5-7,11-13,16,19,20 As the Cochrane
Library has published, better evidence is needed
regarding the use of antibiotic prophylaxis in patients
undergoing tooth extraction.21
The specific aim of this study was to assess the
efficacy of amoxicillin/clavulanic acid 500/125 mg in
preventing infectious and inflammatory complications
(IC) in M3 subjects using a double-blind placebocontrolled randomized clinical trial. Our hypothesis
was that the occurrence of IC was greater in patients
treated with placebo (Pl) than in those treated with
antibiotic (Ab), with a maximum ratio difference of
0.067.
Likewise we analyzed variables such as age, sex,
smoking, molar depth and angulation, ostectomy, need
for sectioning and intervention time to identify risk
factors associated with post-operative IC.8,10,22-26
PATIENTS AND METHODS
The randomized clinical trial (RCT) was unicentric,
prospective, placebo-controlled, and double-blinded
of 2 parallel groups. The RCT was approved by the
E11
OOOOE
July 2005
E12 Arteagoitia et al
Table I. Characteristics of the control variables recorded for each of the groups
Variable
Age:
Mean
SD
Gender:
Man
Woman
Smoking, cigs/day:
None
0-10
11-20
[20
Depth type*:
II
III
IV
Angulation:
vertical
mesioangular
distoangular
horizontal
Intervention time, sec**:
mean
SD
Sectioning
No
Yes
Ostectomy***:
None
1/3
2/3
3/3
Ab, n = 259
Pl, n = 231
Total, n = 490
Pl lost, n = 2
Ab lost, n = 2
26.33
2.56
24.33
2.58
0.59a
24.26
5.1
24.01
4.89
24.15
5.01
0.36b
99
160
98
133
197
293
1
1
1
1
1
1
0
0
0
0
2
0
2
0
0
0
1
1
1
0
0
1
0
0
2
0
330.5
13.4
832.5
378.3
1
1
0
2
0
2
0
0
0
2
0
0
0.43c
160
65
31
3
139
62
30
4
295
127
61
7
85
107
67
70
82
79
155
189
146
77
85
21
76
64
82
19
66
141
167
40
142
0.13c
0.93c
0.84a
517.21
276.29
522.03
255.78
519.5
266.56
120
139
96
135
216
274
0.32b
0.03c
14
208
34
3
6
170
50
5
20
378
84
8
Ab, Subjects treated with antibiotic; Pl, subjects treated with placebo.
*Type II: totally covered by soft tissue and without bone coverage; type III: totally covered by soft tissue and partially by bone; type IV: totally covered by bone.
**Time measured using chronometer, from commencement of incision to the cutting of the last suture, by an external observer.
***1/3: Between crown and dental neck; 2/3: between dental neck and 2/3 of roots; 3/3: between 2/3 of roots and apexes.
a,b,c
P, statistical significance of the homogeneity tests between the groups Pl and Ab. a: Logistics regression; b: Fisher exact bilateral test; c: Pearsons bilateral
chi square.
OOOOE
Volume 100, Number 1
Arteagoitia et al E13
Diagnosis of postoperative infection and inflammatory complication was performed by the main
researcher, according to previously published clinical
criteria:7,9,10,24,27,28
Oral temperature [37.88 after 24 h for no other
justifiable cause
Intraoral abscess diagnosed via fluctuation pus
drainage (yes/no)
Dry socket defined as absence of clot with necrotic
remains present in the alveolus accompanied by
severe mandibular pain (yes/no)
Severe pain persisting or increasing 48 h after
surgery accompanied by intraoral inflammation
(moderate or severe) and/or intraoral erythema
(moderate or severe)
Severe pain after 7th day accompanied by intraoral
inflammation (moderate or severe) and/or intraoral erythema (moderate or severe) for no other
justifiable reason which improves with antibiotic
treatment
Inflammation, erythema and pain were measured
qualitatively (none, slight, moderate, or severe). In
addition, pain was measured quantitatively, using the
visual analog scale (VAS) of 100 mm.
Likewise we analyzed whether variables such as age,
sex, smoking, molar depth and angulation, ostectomy,
odontosection, and intervention time, could be considered risk factors associated with postoperative infectious and inflammatory complications (Table I).
All extractions were performed by maxillofacial
surgeons, under locoregional anesthetic of the inferior
OOOOE
July 2005
E14 Arteagoitia et al
Table II. Description of patients diagnosed with IIC
Variables defining IIC
Patient
no.
61
62
66
75
77
87
99
109
129
131
151
161
183
185
200
211
222
224
225
239
251
290
330
339
342
353
367
392
395
413
415
436
442
458
424
Groupa
1
2
2
2
1
2
2
2
2
2
2
1
2
1
2
2
2
2
2
2
2
2
2
2
2
1
2
2
2
2
2
2
2
2
2
Infection
typeb
early
early
early
early
late
early
early
late
late
late
late
late
early
late
early
early
late
early
early
early
early
early
late
early
early
early
early
early
early
early
late
late
early
early
early
Fever
Intraoral
Abscess
Alveolitis
Inflam.c
Erythemad
Dehis.e
Pain 48 hf
Pain 6 daysg
Ageh
Inclusion
typei
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
mod
mod
mod
mod
mod
mod
mod
mod
mod
mod
mod
mod
mod
mod
mod
sev
sev
sev
sev
sev
sev
sev
mod
mod
mod
mod
mod
mod
mod
mod
mod
sev
sev
sev
sev
mod
sev
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
26.5
25.3
27.5
19.2
18
24.4
42.2
22.4
24.1
28.4
28.4
19.7
22.2
32.9
18.2
21.9
22.2
24.8
23.2
25.2
22.9
40.1
29.1
20.4
29.1
29.6
21.9
21.5
33.1
36.6
24.3
31.4
25.8
25.4
20.7
III
IV
III
III
IV
III
III
II
IV
III
IV
IV
III
IV
IV
III
IV
III
III
III
II
III
III
IV
IV
II
IV
IV
IV
IV
II
IV
II
II
III
OOOOE
Volume 100, Number 1
Arteagoitia et al E15
Risk
measurements
Complication,
n = 490
Complication,*
n = 49014
Infection/
inflammation
OR
95% confidence
interval
Risk in Ab
Risk in Pl
ARR (95%CI)
NNT (95%CI)
0.019
0.129
0.11 (0.066-0.155)
10 (7-16)
0.027
0.137
0.11 (0.06-0.16)
10 (7-17)
Group
Age
Sex 2
Smokes 2
Smokes 3
Depth 2
Depth 3
Angulation 2
Angulation 3
Angulation 4
Time
Sectioning
Ostectomy 2
Ostectomy 3
Ostectomy 4
8.66
1.08
0.936
1.07
1.34
2.32
2.6
1.03
1.44
2.69
0.98
1.04
0.60
0.46
1.61
0.000
0.029
0.9
0.87
0.59
0.11
0.1
0.96
0.63
0.1
0.38
0.94
0.66
0.54
0.76
3.17-23.67
1.00-1.16
0.33-2.62
0.45-2.59
0.47-3.99
0.84-6.60
0.83-8.11
0.33-3.26
0.33-6.28
0.83-8.75
0.89-1.02
0.39-2.73
0.60-5.95
0.04-5.5
0.076-34.10
Estimation with 483 patients because the statistical study excluded 7 patients,
who smoked over 20 cigarettes a day and none of whom were infected/
inflamed.
OR, Odds ratio; Sex 2, women; Smokes 2, #10 cigarettes/day; Smokes 3, 11-20
cigarettes/day; Depth 2, type III (partially covered by bone); Depth 3, type IV
(totally covered by bone); Angulation 2, mesioangular; Angulation 3,
distoangular; Angulation 4, horizontal; Sectioning, yes; Ostectomy 2, 1/3
(between the crown and dental neck); Ostectomy 3, 2/3 (between the dental
neck and 2/3 of the roots); Ostectomy 4, 3/3 (between 2/3 of the roots and
apexes).
OOOOE
July 2005
E16 Arteagoitia et al
Table V. Stratified analysis of the risk measurements of the depth and angulation variables
Depth
Type II
Type III
Type IV
Angulation
Vertical
Mesioangular
Distoangular
Horizontal
P bilateral
OR (95% CI)
0.091
0.000
0.053
17 (8-infinite)
7 (5-13)**
9 (5-102)
0.059 (0.001-0.12)
0.149 (0.077-0.221)
0.107 (0.01-0.204)
0.155 (0.015-1.58)
0.049 (0.005-0.504)
0.261 CI 0.074-0.92
0.092
0.017
0.033
0.001
15
12
9
5
0.065
0.086
0.11
0.186
0.155
0.112
0.268
0.099
(8-infinite)
(7-54)
(3-infinite)
(4-12)**
(0.001-0.13)
(0.019-0.153)
(0.073-0.293)
(0.086-0.286)
(0.015-1.581)
(0.014-0.924)
(0.024-2.986)
(0.198-0.498)
**The number of patients needed to treat (NNT) with antibiotic to prevent infectious and inflammatory complications shows antibiotic efficacy has clinical
relevance in third molars type III and those in horizontal position.
OOOOE
Volume 100, Number 1
Arteagoitia et al E17
6. Happonen RP, Backstrom AC, Ylipaavalniemi P. Prophylactic
use of phenoxymethylpenicillin and tinidazole in mandibular
third molar surgery, a comparative placebo, controlled clinical
trial. Br J Oral Maxillofac Surg 1990;28:12-5.
7. Ritzau M, Hillerup S, Branebjerg Ersbol B. Does metronidazole
prevent alveolitis sicca dolorosa? A double-blind, placebocontrolled clinical study. Int J Oral Maxillofac Surg 1992;21:
299-302.
8. Chiapasco M, De Cicco L, Marrone G. Side effects and
complications associated with third molar surgery. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod 1993;76:412-20.
9. Lloyd J, Earl PD. Metronidazole: two or three times daily,
a comparative controlled clinical trial of the efficacy of two
different dosing schedules of metronidazole for chemoprophylaxis following third molar surgery. Br J Oral Maxillofac Surg
1994;32:165-7.
10. Piecuch F, Arzadon J, Lieblich S. Prophylactic antibiotics for
third molar surgery: a supportive opinion. J Oral Maxillofac Surg
1995;53:53-60.
11. Monaco G, Staffolani C, Gatto MR, Checchi L. Antibiotic
therapy in impacted third molar surgery. Eur J Oral Sci 1999;
107:437-41.
12. Sekhar CH, Narayanan V, Baig MF. Role of antimicrobials in
third molar surgery: prospective, double blind, randomized,
placebo-controlled clinical study. Br J Oral Maxillofac Surg
2001;39:134-7.
13. Bulut E, Bulut S, Etikan I, Koseoglu O. The value of routine
antibiotic prophylaxis in mandibular third molar surgery: acutephase protein levels as indicators of infection. J Oral Sci 2001;
43:117-22.
14. Yoshii T, Hamamoto Y, Muraoka S, Furudoi S, Komori T.
Differences in postoperative morbidity rates, including infection
and dry socket, and differences in the healing process after
mandibular third molar surgery in patients receiving 1-day or 3day prophylaxis with lenampicillin. J Infect Chemother 2002;8:
87-93.
15. Delilbasi C, Saracoglu U, Keskin A. Effects of 0.2% chlorhexidine gluconate and amoxicillin plus clavulanic acid on the
prevention of alveolar osteitis following mandibular third molar
extractions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
2002;94:301-4.
16. Poeschl PW, Eckel D, Poeschl E. Postoperative prophylactic
antibiotic treatment in third molar surgery a necessity? J Oral
Maxillofac Surg 2004;62:3-8.
17. Krekmanov L. Alveolitis after operative removal of third molars
in the mandible. Int J Oral Surg 1981;10:173-9.
18. Lyall JB. Third molar surgery. The effect of primary closure
wound dressing and metronidazole on postoperative recovery.
J R Army Med Corps 1991;137:100-3.
19. Peterson LJ. Antibiotic prophylaxis against wound infections in
oral and maxillofacial surgery. J Oral Maxillofac Surg 1990;48:
617-20.
20. Capuzzi P, Montebugnoli L, Vaccaro MA. Extraction of
impacted third molars. A longitudinal prospective study on
factors that affect postoperative recovery. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod 1994;77:341-3.
21. van der Sanden WJM, Mettes TG, Verdonschot EH, vant Hof
MA, Nienhuijs M, Plasschaert AJM. Interventions for treating
trouble-free impacted wisdom teeth in adults (Protocol).
Cochrane Oral Health Group. Cochrane Database of Systematic
Reviews. Available online: http://www.cochrane.org/cochrane/
revabstr/ORALAbstractIndex.htm
22. de Boer MP, Raghoebar GM, Stegenga B, Schoen PJ, Boering G.
Complications after mandibular third molar extraction. Quintessence Int 1995;26:779-84.
23. Santamara J, Arteagoitia I. Impacted inferior third molar:
predictive model of surgical difficulty. J Dent Res 1997;76:
1128.
24. Muhonen A, Venta I, Ylipaavalniemi P. Factors predisposing to
postoperative complications related to wisdom tooth surgery
among university students. J Am Coll Health 1997;46:39-42.
OOOOE
July 2005
E18 Arteagoitia et al
25. Macgregor AJ, Addy A. Value of penicillin in the prevention
of pain, swelling and trismus following the removal of
ectopic mandibular third molars. Int J Oral Surg 1980;9:
166-72.
26. Worrall SF. Antibiotic prescribing in third molar surgery. Br J
Oral Maxillofac Surg 1998;36:74-5.
27. Al-Kahateeb T, El-Marsafi A, Butler N. The relationship
between the indications for the surgical removal of impacted
tird molars and the incidence of alveolar osteitis. J Oral
Maxillofac Surg 1991;49:141-5.
28. Marx RE. Chronic osteomyelitis of the jaws. Oral Maxillofac
Surg Clin N Am 1991;3:367-81.
29. Hermesch CB, Hilton TJ, Biesbrock AR, Baker RA, Cain-Hamlin
J, McClanahan SF, et al. Perioperative use of 0.12% chlorhexidine
gluconate for the prevention of alveolar ostetis. Efficacy and risk
factor analysis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
1998;85:381-7.
Reprint requests:
Itziar Arteagoitia
Departamento de Estomatologa
Universidad del Pas Vasco
Barrio Sarriena s/n Leioa 48940
Spain
arteagoitia@infomed.es