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CURRENT THERAPY

J Oral Maxillofac Surg


64:1664-1668, 2006

A Systematic Review of Prophylactic


Antibiotics in the Surgical Treatment of
Maxillofacial Fractures
Jens O. Andreasen, DDS, Odont Drhc,* Simon S. Jensen, DDS,†
Ole Schwartz, DDS, LDS,‡ and Yören Hillerup, DDS, Dr Odont§

Purpose: A systematic review was performed to find evidence for prophylactic administration of
antibiotics in relation to treatment of maxillofacial fractures.
Methods: Four studies were retrieved that fulfilled most of the requirements of being randomized
controlled clinical trials.
Results: An analysis of these studies showed a 3-fold decrease in the infection rate of mandibular
fractures in the antibiotic treated groups compared with the control groups. A variety of antibiotics had
been used with an apparently uniform effect. A “1-shot” regimen or a 1-day treatment course had a similar
or perhaps even better effect than 7 days of treatment. No infections were related to condylar, maxillary,
or zygoma fractures.
Conclusion: A 1-shot or 1-day administration of prophylactic antibiotics seem to be the best docu-
mented to reduce infections in the management of mandibular fractures not involving the condylar
region.
© 2006 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg 64:1664-1668, 2006

Evidence-based treatment strategies depend on applica- For many years, prophylactic antibiotic treatment
tion of the best knowledge a discipline can offer. Sys- has been considered a must in the surgical treatment
tematic reviews should aim at extracting the current of jaw fractures.1 The evidence for this preventive
best evidence within a well-defined area, and thereby intervention, however, has been weak in a series of
give the clinician an intended unbiased tool in keeping other surgical disciplines.2-5 For many indications,
up with an exponentially growing knowledge base. prophylactic antibiotics have been shown to have no
positive and sometimes even a negative effect (ie, a
higher infection rate in antibiotic treated situations).6
*Consultant, Department of Oral and Maxillofacial Surgery, Uni- The latter event being explained by the fact that no
versity Hospital (Rigshospitalet), Copenhagen, Denmark. single antibiotic can eliminate all kinds of invading
†Assistant Professor, Department of Oral and Maxillofacial Sur- bacteria and thereby may give an advantage to oppor-
gery, University Hospital (Glostrup), Copenhagen, Denmark; and tunistic infection.7
the Department of Oral Surgery and Stomatology, School of Dental Several factors with a known impact on the incidence
Medicine, University of Berne, Switzerland. of infections in relation to maxillofacial trauma must be
‡Department Chairman, Department of Oral and Maxillofacial taken into consideration before the specific role of a
Surgery, University Hospital (Rigshospitalet), Copenhagen, Den-
prophylactic antibiotic regimen can be evaluated.
mark.
Two different situations exist in relation to the
§Professor, Department of Oral and Maxillofacial Surgery, Uni-
invasion of bacterias into the fracture site, namely a
versity Hospital (Rigshospitalet), Copenhagen, Denmark.
closed fracture (eg, mandibular condyle or ramus frac-
Address correspondence and reprint requests to Dr Andreasen:
tures and maxillary Le Fort I–III fractures) on 1 side
Department of Oral and Maxillofacial Surgery, University Hospital
and open fractures with direct communication to the
(Rigshospitalet), Blegdamsvej 9, DK-2100 Copenhagen, Denmark;
oral cavity and/or the skin surface on the other. No
e-mail: RH11323@RH.dk
study has so far evaluated the actual invasion of bac-
© 2006 American Association of Oral and Maxillofacial Surgeons
teria in a healing fracture site; but the importance of
0278-2391/06/6411-0014$32.00/0
this differentiation is apparent by the fact that healing
doi:10.1016/j.joms.2006.02.032
of fractures located in the condylar region is never

1664
ANDREASEN ET AL 1665

Table 1. SURVEY OF STUDIES INCLUDED

Zallen and Aderhold et Gerlach and Chole and Heit et al,15 Abubaker et
Curry,12 1975 al,13 1983 Pape,14 1988 Yee,8 1987 1997 al,16 2001

Randomization ⫹ ⫹* ⫹* ⫹ ⫹* ⫹*
Patient blinded to treatment ⫺ ⫺ ⫺ ⫺ ? ⫹
Assessor blinded to treatment ⫺ ⫺ ⫺ ⫺ ⫹ ⫹
Drop-outs accounted for ⫺ ⫺ ⫺ ⫺ ⫺ ⫺
Outcome measures clearly defined ⫺ ⫹ ⫹ ⫹ ⫺ ⫹
Statistical method ⫺ ⫹ ⫹ ⫹ ⫺ ⫹
*Claimed, but the method is not provided.
Andreasen et al. Antibiotics for Maxillofacial Fractures. J Oral Maxillofac Surg 2006.

followed by infection compared with the more fre- 1) Does antibiotic prophylaxis decrease the inci-
quent occurrence of infections in the mandibular an- dence of post-trauma infections in jaw fracture
gle, body, and symphysis regions.8 treatment?
Another factor to be analyzed is the treatment pro- 2) Are there situations where an antibiotic prophy-
cedure used (ie, open versus closed reduction of the laxis is not indicated?
fracture). From a previous analysis, it became appar- 3) Which antibiotic is the drug of choice? In what
ent that an open procedure may lead to a 4-fold dose? And for how long?
higher rate of infection.9 The type of treatment pro-
cedure (open or closed) should therefore also be Material and Methods
included in an analysis of the effect of antibiotics.
Mandibular fractures are more prone to infection ANALYSIS OF THE LITERATURE
than maxillary fractures8; and within the mandible, The databases MEDLINE and Cochrane were
the location of the fracture in the dental arch also searched for relevant studies, using the following key
seems to be of importance with the third molar region words: jaw fractures, mandibular fractures, maxillary
showing the highest frequency of infections.8 Thus, fractures, antibiotic treatment, infection, and random-
the topography of the jaw fractures is another factor ized studies. This search was supplemented by a hand
to be considered. search of relevant German journals not electronically
Concerning the administration of antibiotics, a listed and by a review of reference lists of potentially
number of factors have to be taken into account. First, eligible studies.
the type of antibiotics administered; the dose, dura- For each retrieved study, the following questions
tion, and route of administration, and finally the tim- were asked (Table 1):
ing of administration in relation to injury and surgical
treatment. All of these factors have been shown to 1) Were the patients randomly allocated to the
have significant influence on the chance of avoiding treatment groups?
infection.5 2) Were the patients blind to treatment allocation?
The term prophylaxis implies preventive use of 3) Were the treatment outcomes assessed blind?
antibiotics. In the present review, antibiotic prophy- 4) Were all dropouts to follow-up accounted for?
laxis is interpreted as given, when no clinical signs of 5) Were the clinical outcome variables clearly de-
infection are present at the time of surgery, although fined?
it may be argued that any fracture open to the skin or 6) Were details given of the statistical evaluation
oral cavity should be considered contaminated, and method?
that antibiotics thereby are indicated as a part of
treatment rather than prophylactic. Based on this, each individual study was character-
Finally, an analysis of the literature should concen- ized as a randomized controlled trial or a controlled
trate on randomized studies, and in this regard whether clinical trial. To meet the criteria of a randomized
the studies meet the requirements for a reliable study controlled trial, the study should involve at least 1 test
design, proper randomization, limited number of drop- treatment and 1 control treatment and concurrent
outs, sufficient number of patients included, and utiliza- enrollment and follow-up of the test- and control-
tion of relevant statistical methods.10 treated groups, in which the treatments to be admin-
It was the purpose of the present systematic review istered are selected by a random process such as a
to evaluate available randomized clinical trials to an- random number table. Studies where the patients are
swer the following questions: appointed to the different treatment groups using
1666 ANTIBIOTICS FOR MAXILLOFACIAL FRACTURES

quasi- or pseudo-randomization techniques such as losporin) 1 hour before surgery and 8 hours after. A
coin flips, social security numbers, or days of the total of 150 fractures were diagnosed in the 101
week, are considered controlled clinical trials.11 patients (6 maxillary, 24 zygomatic, and 120 mandib-
ular fractures). None of the maxillary, zygomatic, and
subcondylar mandibular fractures got infected, irre-
Results
spective of antibiotic prophylaxis given or not. In the
Four randomized studies8,12-14 were retrieved con- 79 patients with mandibular fractures, the 37 who
cerning the possible benefit of prophylactic antibiot- received antibiotics experienced an infection rate of
ics in the treatment of maxillofacial fractures. Two 14%, whereas 42 patients in the control group devel-
clinical randomized studies were found that com- oped infections in 43% (P ⫽ .01) of the cases.
pared different antibiotic regimens without including In a separate nonrandomized analysis, it was con-
a control group.15,16 A critical analysis of these firmed whether the infection rate in relation to closed or
showed that none of them fulfilled all the require- open reduction of the mandibular fractures was influ-
ments for a randomized controlled trial. The short- enced by the administration of antibiotics. It turned out
comings of the studies are presented in Table 1. that antibiotic prophylaxis had virtually no influence on
However, as these studies represent the best knowl- the infection rate when the fractures were treated with
edge available at the present time, the results are closed reduction (23% infections with administered an-
summarized below. tibiotics/28% infections with no antibiotics). In the open
The first randomized study on the effect of prophy- reduction group, however, 62% developed infections
lactic antibiotics in the treatment of compound man- when no antibiotics were used compared with 8% in the
dibular fractures was published by Zallen and Curry in antibiotic group (Table 2).
1975.12 The material consisted of 32 patients with It was concluded that antibiotic prophylaxis is in-
compound mandibular fractures who received antibi- dicated for mandibular fractures.
otics (a wide variety of different antibiotics), and 30
In 1988, Gerlach and Pape14 examined the influ-
patients treated without antibiotics. A control of the
ence of antibiotic treatment on infection rates in 200
stratification was made and shown to be effective.
mandibular fractures all treated with open reduction
The administration of antibiotics was in 20 cases par-
and miniplate osteosynthesis through an intraoral ap-
enterally and in 10 cases orally. A highly significant
proach. In group I (n ⫽ 50), a 1-day antibiotic treat-
difference in complication rates was found as 6%
ment was given, starting immediately before surgery.
developed infection complications in the antibiotic-
In group II (n ⫽ 50), a 1-shot prophylaxis of antibiot-
treated group, whereas 53% developed infection in
ics was administered immediately before surgery. In
the nontreated group (P ⫽ .0001) (Table 2).
In 1983, Aderhold et al13 published a study on the group III (n ⫽ 51), a 3-day course was used. Finally, a
effect of antibiotic treatment of 120 mandibular frac- control group (n ⫽ 49) received no prophylactic
tures. All fractures had communication to the oral antibiotics. The control group showed a significantly
cavity and were treated with miniplate osteosynthe- higher infection rate (22%) compared with the 3 pro-
sis. Forty cases were treated without antibiotics, 40 phylactic groups (2%, 6%, and 8%, respectively) (P ⫽
cases with antibiotic coverage up to 48 hours, and 40 .001). It was concluded that a “1-shot administration”
cases with treatment for more than 48 hours. Type of antibiotics in relation to intraoral osteosynthesis in
and dosage of the prescribed antibiotics are not pre- the mandible is sufficient to protect the patient from
sented. Proper stratification was checked and found wound infection (Table 2).
to be reliable, and the numbers of open and closed Two different antibiotic prophylactic regimens were
reductions in the 2 groups are comparable. An almost compared in a prospective and nonrandomized clinical
significantly higher infection rate was found in the study by Heit et al15 in 1997. A total of 90 patients with
nontreated group (20%), whereas cases treated with compound mandibular fractures were divided into 2
short-term antibiotics showed a frequency of 5% and groups of 45 patients. In group I, the prophylaxis con-
beyond 48 hours of 10% (n ⫽ .06). It was concluded sisted of ceftriaxone (a cephalosporin) 1 g daily pre- and
that short-term antibiotic prophylaxis was effective in perioperatively until the intravenously administration
reducing infection; furthermore, that long-term treat- was discontinued and thereafter penicillin VK 500 mg
ment did not significantly reduce the risk of infections every sixth hour orally 1 week postoperatively. Group II
as compared with the control group (Table 2). received an intravenous administration of penicillin G 2
In 1987, Chole and Yee8 reported a prospective million U every fourth hour pre- and perioperatively
clinical trial of 101 patients with facial fractures. The until the intravenously administration was discontinued
patients were randomly assigned to either no antibi- and thereafter the same orally administered doses of
otic treatment or a short-term prophylaxis with an penicillin VK as for group I. Two patients in each group
intravenous administration of cefazolin 1 g (a cepha- developed an infection and thus there could not be a
ANDREASEN ET AL 1667

Table 2. COMPARISON OF POSTOPERATIVE INFECTION RATES RELATED TO THE USE OR NOT OF ANTIBIOTICS

Control Group Test Group


No Antibiotics Antibiotics
Study Administration No. x % No. x % Probability Level

Zallen and Curry,12


1975 30 16 53 32 2 6 0.001
13
Aderhold et al, Control 40 8 20
1983 ⱕ48hours 40 2 5 0.06
⬎48hours 40 4 10
Gerlach and Pape,14 Control 49 11 22
1988 1 day 50 1 2
1 shot 50 3 6 0.001
3 days 51 4 8
Chole and Yee,8
1987 42 18 62 37 5 14 0.01
Abbreviation: x, Number of infections.
Andreasen et al. Antibiotics for Maxillofacial Fractures. J Oral Maxillofac Surg 2006.

demonstrated significant difference between the 2 reg- shown a positive effect on infection rates.21 It might
imens. be expected that the same exposure to all bacteria
Abubaker and Rollert16 reported in 2001 preliminary may occur in orthognathic surgery.
results of a comparative, double-blind, placebo-con- However, in jaw fracture treatment a multitude of
trolled study of a 1-day prophylaxis versus a 5-day treat- external sources exist for contamination of the
ment with penicillin. In a limited number of patients wound. In this aspect the fracture can, in most cases,
(n ⫽ 30), no benefit of a prolonged administration of be considered contaminated,17 with the known ele-
antibiotics could be seen. However, the results should vation in infection risk and that was also the general
be interpreted with caution because of the small num- finding in this survey.
ber of patients and that both open and closed reductions However, the difference might be that the injured
were mixed in the material. tissue had a short exposure to oral bacteria in com-
parison to jaw fractures where bacteria might have
Discussion invaded the tissues for days (although it was shown
In maxillofacial fracture treatment a multitude of that the time delay until treatment did not influence
external sources exist for contamination of the the infection rate).8
wound. In this aspect the fracture can, in most cases, Combining the evidence from all 4 studies, the
be considered contaminated, implying an elevated following can be concluded about infection rates: It
risk of infection.17 appears that there is a significant reduction in the
From this perusal of the literature, it appears strongly number of post injury infections. As a whole, a 3-fold
indicated to use a short-term antibiotic coverage to de- decrease in the infection rate took place by the ad-
crease the infection rate in relation to the treatment of ministration of antibiotics.
compound mandibular fractures. Approximately a 4-fold
INFECTION RATES IN DIFFERENT LOCATIONS
reduction in the number of infections was found. It is
also of interest to observe that open reduction was All studies had their analysis primarily confined to
highly influenced by the use of antibiotics. This seems to the dentate part of the mandible (ie, excluding the
indicate that the cause of infection could be related to condylar region). In 1 study, the infection rate was
the surgical approach itself, namely damaging the prin- compared between various locations (Table 3). It ap-
cipal blood supply to perform an osteosynthesis and pears that infection was not found in the maxilla, the
thereby additionally exposing an injured area to bacteria condylar region, or the zygoma, irrespective of admin-
from the oral cavity or external environment. istration of antibiotics.8
An interesting analogue to the surgical treatment of
jaw fractures appears in orthognathic surgery where INFECTION RATES RELATED TO ANTIBIOTIC
the infection rate is normally very low, and in 3 ADMINISTRATION
studies has been shown not to be related to the There appears to be no difference in the reduction
administration of antibiotics.18-20 Only 1 study has rate of infection in the 4 studies.
1668 ANTIBIOTICS FOR MAXILLOFACIAL FRACTURES

Table 3. COMPARISON OF POSTOPERATIVE


existence of infection complications in condylar frac-
INFECTION RATES ACCORDING TO FRACTURE tures, antibiotic treatment in the latter types of frac-
LOCATION tures does not seem indicated.
Infection References
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