Pre-Operative Antibiotic Agents for Facial Fractures: Is More than One Day Necessary?

Abstract

Background:

Despite a paucity of evidence, patients with facial fractures often receive long courses of pre-operative antibiotic agents. This study compared the effect of a short versus long pre-operative antibiotic course on the development of post-operative head/neck infections in this population.

Patients and Methods:

All adult patients admitted between January 2010 and May 2015 to a level 1 trauma center with isolated head/neck injuries who underwent surgery for facial fracture(s) were included. Patients with infections prior to surgery were excluded. Our primary analysis compared head/neck infections between patients given a short (≤24 hours) versus long (>24 hours) course of pre-operative antibiotic agents. Bivariate analysis and multivariate logistic regression (MLR) were performed to identify risk factors for head/neck infections.

Results:

This study included 188 patients; median age was 38.5 years, 83% were male, 81% had blunt injuries, 51.6% had fractures in multiple facial thirds, and 48.9% required intensive care unit (ICU) admission. One hundred twenty-five (66.5%) patients received a short course and 63 (33.5%) received a long course of pre-operative antibiotic agents. Head/neck infections were higher in the long course group (28.6% vs 15.2%; p = 0.034), but median days to infection were similar. Factors associated with head/neck infections included penetrating injury, mandible fracture, involvement of multiple facial thirds, ICU admission, operative time, and receiving a long pre-operative antibiotic course. Multivariable logistic regression found mandible fracture (odds ratio [OR], 2.9; p = 0.01) and ICU admission (OR, 3.3; p = 0.003) to be independent predictors of head/neck infections (area under the curve [AUC] = 0.706), but pre-operative antibiotic course was not. Patients with isolated mandible fractures (n = 42) had higher rates of head/neck infections in the long course group (29.4% vs 4.0%; p = 0.032), despite similar demographics.

Conclusion:

Long (>24 hours) course of continuous pre-operative antibiotic prophylaxis before surgery for facial fractures did not reduce the development of head/neck infections.

Administration of pre-operative antibiotic prophylaxis has become a key component in the prevention of surgical site infections [1]. Whereas there are well-established guidelines for appropriate antibiotic administration in a variety of surgical procedures, controversy still remains in the area of maxillofacial trauma [2 –4]. Early research in this field established the benefit of peri-operative antibiotics, particularly for surgically managed mandibular fractures, but antibiotic agents and durations varied widely [5]. More recently, studies have focused on evaluating the efficacy of various post-operative antibiotic courses and many have concluded that extended courses of antibiotic prophylaxis beyond 24 hours post-operatively do not appear to reduce infections [4,6 –8]. A recent systemic review by Delaplain et al. [9] did not demonstrate a lower rate of surgical site infection with any duration of post-operative antibiotic prophylaxis after repair of any facial fracture, and in fact showed a higher rate of surgical site infection for more than 72 hours of post-operative antibiotic prophylaxis after repair of mandible fractures.

When it comes to determining the most appropriate duration of pre-operative antibiotic prophylaxis in facial fractures, the literature is scarce. Even in the most well-studied subsets of patients with mandible fractures, the evidence for administering pre-operative antibiotics from the time of injury until repair often appears anecdotal. Previously our group evaluated the association between an initial extended course of antibiotic agents at the time of admission and the prevention of head or neck infections in critically ill patients with facial fractures and found no benefit to extended courses beyond one day [10]. In that study a large portion of patients who received extended antibiotic courses underwent surgery for their facial fracture and this brought about questions regarding peri-operative dosing of antibiotics for facial fractures. Thus, the purpose of this study was to evaluate the specific issue of peri-operative antibiotic administration to patients with facial fractures.

Despite a paucity of evidence, patients with facial fractures often receive several days of pre-operative antibiotics [4,11]. The reasons for this are likely multifactorial. Facial fracture patients are frequently managed by multidisciplinary teams in a variety of healthcare settings and decisions regarding surgical management and peri-operative care are often made by surgeons from different training backgrounds, each with their own set of literature resources and practice patterns [12]. Additionally, these decisions may be delayed until soft tissue swelling subsides, which may be several days after the initial injury. Given the lack of consensus and limited evidence to guide pre-operative antibiotic duration, we sought to evaluate the relation that a short (≤24 hours) versus long (>24 hours) course of pre-operative antibiotic prophylaxis had on the development of head or neck infections after surgical management of traumatic facial fractures.

Patients and Methods

This study included all adult patients with at least one facial bone fracture who were admitted to a level 1 trauma center from January 2010 through May 2015. Patients were identified by querying the trauma registry for abbreviated injury score (AIS) codes corresponding to facial fractures. All patients with concomitant head and neck injuries, such as traumatic brain injuries, vascular injuries, and cervical spine fractures, were included. Patients with injuries in any other body region, defined as AIS of the chest, abdomen, extremity, or external greater than one, were excluded. Other exclusion criteria included initial presentation more than 24 hours from the time of injury, operative intervention for head or neck injury at another hospital prior to transfer, and presence of active infection prior to operation for facial fracture.

Patient demographics, mechanism of injury, facial bone fractures, associated injuries, operative interventions, infectious complications, and timing and duration of antibiotics prescribed in first 30 days were recorded. Computed tomography scans of the face, head, and neck were reviewed for each patient to identify specific fractures and associated injuries. Facial fractures were classified by specific bone(s) and facial third involved (upper face, midface, and mandible.)

Patients were categorized into two groups, short course (≤24 hours) and long course (>24 hours), based on the total consecutive days antibiotic agents were administered pre-operatively. These courses were all continuous with the day of surgery. Patients who received only a single pre-operative dose of antibiotic agents were included in the short course group. There was no standardized protocol for antibiotic administration for facial fractures during the study period. The duration of antibiotic course was decided by the treating service taking into consideration consultant recommendations.

The primary outcome analyzed was the incidence of head or neck infections, determined through documentation in the electronic medical record by a treating physician of signs and symptoms of infection (swelling, erythema, purulent drainage, etc.) involving the face, skull, brain, meninges, or neck that was treated with either antibiotic agents or a debridement/drainage procedure. These included craniofacial abscesses, osteomyelitis, cellulitis, sinusitis, otitis, meningitis, wound or surgical site infections, and skin or soft tissue infections of the neck. Patient records were reviewed up to their most recent follow-up visit with a facial or trauma surgeon. Other inpatient infections recorded were pneumonia, urinary tract infection, bacteremia, and soft tissue infection in any other body region. Growth of a multi-drug–resistant organism (MDRO) from any of the cultures was also recorded.

Inpatient and outpatient records were reviewed via Epic (Epic Systems Corp, Madison, WI), which was available at our institution throughout the time of this study period. Data was collected in REDcap (Research Electronic Database Capture). Statistical analysis was performed using IBM SPSS version 23 (IBM, Armonk, NY). Continuous variables were compared using the Mann-Whitney U test. Categorical data were analyzed using either χ² test or Fisher exact test as appropriate. A p value <0.05 was deemed statistically significant. Medians in this study are reported as median (interquartile range [IQR]). Bivariate analysis was performed to identify factors that were associated with head/neck infections. Appropriate variables identified with a p < 0.05 after bivariate analysis were then analyzed using backward conditional multivariate logistic regression (MLR) to identify independent predictors of head/neck infections. Receiver-operating curves were generated from the logistic regression analyses, and the areas under the curve were calculated and expressed as the C-statistics. The odds ratios are reported with 95% confidence intervals. This study was approved by the local Institutional Review Board.

Results

Overall population

There were 197 patients with isolated head or neck trauma and concomitant facial fractures who underwent surgical management of their facial fracture during the study period. Nine patients developed an infection prior to surgery and were excluded. This left a total of 188 patients who were included in the primary analysis. The median age was 38.5 years, 83% were male, and 81% had blunt injuries. The midface was the most common fracture location (76.6%), followed by mandible (54.8%). More than half (51.6%) of the patients had fractures in multiple facial thirds and 44.7% had an open fracture. Ninety-two (48.9%) patients required an intensive care unit (ICU) admission. An open surgical approach was utilized in 86.2% of patients. The most common antibiotic agents administered pre-operatively were first-generation cephalosporins (36.2%), followed by β-lactam/β-lactamase inhibitors (23.4%), and clindamycin (14.4%). Less common antibiotic agents including penicillin, vancomycin, and tetracycline were given in 3.2% of cases and 15.4% of patients received multiple antibiotic agents in the pre-operative period. Fourteen (7.4%) patients did not receive any antibiotic agents within 24 hours prior to surgery. The majority of patients (93.6%) had follow-up at our institution, with a median follow-up length of 8.1 (1.7–30.4) months with any provider and 1.8 (1.1–3.2) months with a facial or trauma surgeon. There were no deaths within 30 days. The overall rate of any head or neck infection was 9.6% at 30 days, 16.5% at 90 days, and 19.7% over the entire study period.

Short versus long pre-operative course of antibiotic agents

There were 125 patients who received a short course and 63 who received a long course of pre-operative antibiotic agents. We compared these two groups to evaluate the effect of a long course of pre-operative antibiotic agents on the development of head or neck infections and secondary outcomes. Demographics and outcomes are shown in Table 1. There were no significant differences in age, gender, injury severity score, or mechanism of injury between the two groups. Patients who received a long pre-operative course of antibiotic agents were more likely to have a mandible fracture, but otherwise there were no differences in the rates of other fractures or injuries. Median days from initial presentation to fracture fixation were similar between the two groups. In the short course group, 14 patients received no antibiotic agents and 78 received a single pre-operative dose. Patients in the long course group received a median of four days of pre-operative antibiotic agents, but this ranged anywhere from just over one day to 14 days. They also received a longer course of post-operative antibiotic agents compared with the short pre-operative antibiotic group. Despite the additional antibiotic days, patients in the long pre-operative antibiotic course group had higher rates of head or neck infections over the entire study period at 28.6% compared with 15.2% in the short course group (p = 0.034), however, there were no statistically significant differences in 30- and 90-day infection rates. The time from surgery to diagnosis of head or neck infection was also not different between the two groups. Long pre-operative course patients had longer length of stay (LOS), ICU days, and ventilator days. They also had a greater median number of facial operations, however, 9.5% of patients in the long course group required additional operative intervention for an infectious process of the head or neck, compared with 7.2% in the short course group (p = 0.579). Both groups had similar follow-up rates and lengths.

Table 1.

Comparison of Short versus Long Pre-Operative Antibiotic Course for All Patients

	Short course	Long course	p^a
	n = 125	n = 63	p^a
Median age, y	38.0 (28.0–52.5)	39.0 (26.0–50.0)	0.684
Male gender	108 (86.4%)	48 (76.2%)	0.100
Blunt injury	103 (82.4%)	49 (77.8%)	0.440
Median ISS	9.0 (5.0–14.0)	6.0 (5.0–14.0)	0.970
Consulting service			0.034
ENT	51 (40.8%)	18 (28.6%)
Plastic surgery	34 (27.2%)	29 (46.0%)
OMFS	40 (32.0%)	16 (25.4%)
Comorbidities
Diabetes mellitus	11 (8.8%)	7 (3.7%)	0.608
Smoker	60 (48.0%)	28 (44.4%)	0.757
Hypertension	20 (16.0%)	7 (11.1%)	0.509
Fractures and Injuries
Upper face fracture	35 (28.0%)	21 (33.3%)	0.500
Middle face fracture	98 (78.4%)	45 (73.0%)	0.466
Mandible fracture	57 (45.6%)	46 (73.0%)	<0.001
Skull fracture	17 (13.8%)	5 (8.1%)	0.338
Multiple facial third fractures	59 (47.2%)	38 (60.3%)	0.122
Open fracture	51 (41.1%)	32 (51.6%)	0.211
TBI	37 (29.6%)	21 (33.3%)	0.619
Peri-operative parameters
Median days to surgery	5.0 (1.0–10.0)	5.0 (3.0–7.0)	0.837
Surgery during initial hospitalization	64 (51.2%)	40 (63.5%)	0.122
Open surgical approach	105 (84.0%)	57 (90.5%)	0.269
Implanted hardware	91 (72.8%)	52 (83.9%)	0.102
Median operative time, h	2.4 (1.3–4.2)	3.3 (2.3–5.1)	0.009
Antibiotic duration
Median pre-operative antibiotic days	0 (0–0.02)	4.0 (2.5–6.0)	<0.001
Median post-operative antibiotic days	6 (0-10.0)	8 (5.0–12.0)	<0.001
Median total antibiotic days in 30 d	8.0 (4.9–11.4)	14.0 (11.0–17.0)	<0.001
Outcomes
Head or neck infection (30 d)	10 (8.0%)	8 (12.7%)	0.306
Head or neck infection (90 d)	16 (12.8%)	15 (23.8%)	0.055
Head or neck infection (overall)	19 (15.2%)	18 (28.6%)	0.034
Facial infection	18 (14.4%)	13 (20.6%)	0.302
Skull infection	2 (1.6%)	5 (7.9%)	0.043
Neck infection	2 (1.6%)	1 (1.6%)	1.000
Meningitis	0 (0%)	3 (4.8%)	0.036
Median days from surgery to infection	17.0 (10.0–60.0)	31.5 (7.5–75.3)	0.693
Median days from admission to infection	25.0 (14.0–70.0)	37.5 (16.3–85.5)	0.670
Any MDRO infection	1 (0.8%)	2 (3.2%)	0.260
Median hospital LOS, d	2.0 (1.0–6.0)	4.0 (2.0–9.0)	0.002
ICU admission	56 (44.8%)	36 (57.1%)	0.124
Median ICU days	0 (0-3.0)	2.0 (0–8.0)	0.004
Median ventilator days	0 (0–1.0)	0 (0–4.0)	0.007
Follow-up after discharge	118 (94.4%)	58 (92.1%)	0.540

ISS = injury severity score; ENT = ear, nose, and throat; OMFS = oral and maxillofacial surgery; TBI = traumatic brain injury; MDRO = multi-drug–resistant organism; LOS = length of stay; ICU = intensive care unit.

Groups were compared using χ² test or Fisher exact test for categorial variables as appropriate, and Mann-Whitney U test for continuous variables. A two-tailed p value of <0.05 was considered significant.

Factors associated with head and neck infections

We then compared patients who developed head or neck infections to those who did not. Factors associated with development of head or neck infections included penetrating injury, mandible fracture, fractures in multiple facial thirds, ICU admission, operative time, and a long pre-operative antibiotic course (Table 2). Based on these findings, the following independent parameters were entered into an MLR: mechanism of injury, mandible fracture, ICU admission, operative time, and pre-operative antibiotic course. The only factors that were shown to be independent predictors of head or neck infections were mandible fracture (OR 2.9; 95% CI, 1.3–6.7; p = 0.012) and ICU admission (OR 3.3; 95% CI, 1.49–7.50; p = 0.003; C-statistic 0.705; 95% CI, 0.611–0.802).

Table 2.

Factors Associated with Head or Neck Infections

	No infection	Head/neck infection	p^a
	n = 151	n = 17	p^a
Median age, y	43.0 (28.0–53.0)	36.0 (28.5–42.5)	0.179
Male gender	128 (84.8%)	28 (75.7%)	0.222
Penetrating injury	23 (15.2%)	13 (35.1%)	0.010
Median ISS	9.0 (5.0–14.0)	9.0 (5.0–18.5)	0.470
Fractures and injuries
Upper face fracture	41 (27.2%)	15 (40.5%)	0.159
Middle face fracture	114 (75.5%)	30 (81.1%)	0.525
Mandible fracture	75 (49.7%)	28 (75.7%)	0.005
Skull fracture	19 (12.8%)	3 (8.1%)	0.575
Multiple facial third fractures	70 (46.4%)	27 (73.0%)	0.005
Open fracture	63 (42.0%)	21 (56.8%)	0.140
TBI	46 (30.5%)	12 (32.4%)	0.844
Peri-operative parameters
Median days to surgery	5.0 (1.0–9.0)	4.0 (1.5–9.0)	0.930
Open surgical approach	131 (86.8%)	31 (83.8%)	0.603
Implanted hardware	114 (75.5%)	29 (80.6%)	0.663
Median operative time, h	2.7 (1.4–4.0)	3.5 (2.3–5.3)	0.019
Antibiotic duration
Long pre-operative antibiotic course	45 (29.8%)	18 (48.6%)	0.034
Median pre-operative antibiotic days	0.01 (0–2.0)	1.0 (0–4.5)	0.092
Median post-operative antibiotic days	7.0 (1.0–11.0)	6.0 (2.0–11.0)	0.918
Outcomes
Median hospital LOS, days	3.0 (1.0–6.0)	4.0 (2.0–15.5)	0.015
ICU admission	65 (43.0%)	27 (73.0%)	0.002
Median ICU days	0 (0–3.0)	2.0 (0.5–9.5)	<0.001
Median ventilator days	0 (0–1.0)	1.0 (0–4.0)	0.003

ISS = injury severity score; TBI = traumatic brain injury; LOS = length of stay; ICU = intensive care unit.

Groups were compared using χ² test or Fisher's exact test for categorial variables as appropriate, and Mann-Whitney U test for continuous variables. A two-tailed p-value of <0.05 was considered significant.

Subgroup analysis

We performed a subgroup analysis of patients with mandibular fractures to assess if longer pre-operative antibiotic administration prevented infections in this particular high-risk group. There were 103 patients with a mandible fracture, 57 of whom received a short pre-operative antibiotic course and 46 received a long course. There were no differences in overall demographics or time to surgery between short and long course groups (Table 3). There were also no statistically significant differences in the rates of head or neck infections, hospital LOS, or ICU days between the two groups.

Table 3.

Comparison of Short versus Long Pre-Operative Antibiotic Course for Patients with Mandible Fracture

	Short course	Long course	p^a
	n = 57	n = 46	p^a
Median age, y	35.0 (28.0–49.5)	36.5 (25.3–48.5)	0.811
Male gender	50 (87.7%)	37 (80.4%)	0.413
Blunt injury	40 (70.2%)	33 (71.7%)	1.000
Median ISS	5.0 (4.0–13.5)	5.0 (5.0–14.0)	0.423
Consulting service			0.009
ENT	23 (40.4%)	12 (26.1%)
Plastic surgery	12 (21.1%)	23 (50.0%)
OMFS	22 (38.6%)	11 (23.9%)
Fractures and Injuries
Upper face fracture	8 (14.0%)	12 (26.1%)	0.140
Middle face fracture	30 (52.6%)	29 (63.0%)	0.321
Skull fracture	6 (10.9%)	4 (8.9%)	1.000
Multiple facial third fractures	32 (56.1%)	29 (63.0%)	0.548
Open fracture	35 (61.4%)	30 (65.2%)	0.837
TBI	12 (21.1%)	13 (28.3%)	0.489
Peri-operative parameters
Median days to surgery	4.0 (1.0–9.0)	4.5 (3.0–7.3)	0.195
Surgery during initial hospitalization	36 (63.2%)	28 (60.9%)	0.840
Open surgical approach	49 (86.0%)	43 (93.5%)	0.338
Implanted hardware	46 (80.7%)	40 (88.9%)	0.228
Median operative time, h	3.1 (1.7–4.4)	3.5 (2.5–5.2)	0.076
Antibiotic duration
Median pre-operative antibiotic days	0.01 (0–1.0)	4.0 (2.0–6.3)	<0.001
Median post-operative antibiotic days	6.0 (0–10.5)	8.5 (6.0–12.3)	0.002
Median total antibiotic days in 30 d	9.0 (5.0–13.0)	14.0 (11.2–18.0)	<0.001
Outcomes
Head or neck infection (overall)	14 (24.6%)	14 (30.4%)	0.514
Median days from surgery to infection	17.0 (7.0–59.0)	18.0 (7.0–75.5)	0.880
Median days from admission to infection	20.0 (12.0–68.0)	21.0 (11.0–88.0)	0.777
Any MDRO infection	1 (1.8%)	2 (4.3%)	0.585
Median hospital LOS, days	2.0 (1.0–9.0)	4.0 (2.0–9.8)	0.216
Median ICU days	0 (0–5.5)	1.0 (0–6.3)	0.261
Median ventilator days	0 (0–2.8)	0 (0–4.0)	0.233

aGroups were compared using χ² test or Fisher's exact test for categorial variables as appropriate, and Mann-Whitney U test for continuous variables. A two-tailed p-value of <0.05 was considered significant.

Additional analysis of 42 patients with isolated mandible fractures, comparing 25 short course and 17 long course patients, resulted in similar demographics and hospital outcomes. There was a higher rate of head or neck infections in the long course group over the study period (29.4% vs 4.0%; p = 0.032; Table 4).

Table 4.

Comparison of Short versus Long Pre-Operative Antibiotic Course for Subgroups

	Short course	Long course	p^a
Isolated mandible fractures	n = 25	n = 17
Open fracture	14 (56.0%)	10 (58.8%)	1.000
Open surgical approach	23 (92.0%)	16 (94.1%)	1.000
Head or neck infection (overall)	1 (4.0%)	5 (29.4%)	0.032
Isolated midface fractures	n = 41	n = 8
Open surgical approach	33 (80.5%)	7 (87.5%)	1.000
Head or neck infection (overall)	3 (7.3%)	1 (12.5%)	0.522
Closed fractures	n = 74	n = 30
Mandible fracture	22 (29.7%)	16 (53.3%)	0.027
Open surgical approach	62 (83.8%)	26 (86.7%)	1.000
Head or neck infection (overall)	8 (10.8%)	8 (26.7%)	0.042
Open fractures	n = 51	n = 33
Mandible fracture	35 (68.6%)	30 (90.9%)	0.018
Open surgical approach	43 (84.3%)	31 (93.9%)	0.302
Head or neck infection (overall)	11 (21.6%)	10 (30.3%)	0.442
Open surgical approach	n = 105	n = 57
Mandible fracture	49 (46.7%)	43 (75.4%)	<0.001
Head or neck infection (overall)	16 (15.2%)	15 (26.3%)	0.087

Groups were compared using χ² test or Fisher's exact test as appropriate. A two-tailed p-value of <0.05 was considered significant.

We performed several additional subgroup analyses of patients with isolated midface fractures, closed fractures, open fractures, and those who had an open surgical approach. There were few differences in patient characteristics comparing short and long course groups. Patients with isolated midface fractures in the long course group had higher median injury severity score (14.0 vs 6.0; p = 0.021), also open fracture patients who received a long course had longer median time to surgery (4.0 vs 1.0 days; p = 0.001) and higher use of implanted hardware (93.9% vs 76.5%; p = 0.040). However, there were no other significant differences in patient characteristics or peri-operative parameters for the remaining groups. Comparison of rates of head or neck infections by pre-operative antibiotic course are presented in Table 4 for each subpopulation.

Discussion

This study evaluated the relation between long versus short pre-operative antibiotic courses and the development of head or neck infections in operative facial fractures. We found that long courses, given for more than 24 hours prior to surgery, were not associated with reduced post-operative rates of head or neck infections. Paradoxically, patients who received long courses of pre-operative prophylaxis had higher rates of head or neck infection, over the entire study period, than those who received a short course.

In the 1970s, Zallen and Curry [5] were among the first to establish the utility of peri-operative antibiotic agents for surgically managed facial fractures. They found that administering antibiotic agents reduced infections from 53% to 6% in patients with compound mandible fractures, however, patients in their study received varying antibiotic agents with different durations. Since then, several studies have confirmed the benefit of pre-operative antibiotic agents, particularly for mandible fractures, but many relied on comparisons of groups who received no antibiotic agents at all [13]. Data regarding what the most appropriate pre-operative duration of therapy are lacking. Much of the current research has focused on evaluating post-operative antibiotic duration and these studies often exclude high-risk patients who have penetrating injuries or require ICU admission [6,8,9,14 –16]. A 2015 meta-analysis conducted by Mundinger et al. [4] reviewed 44 studies in an attempt to give evidence-based guidelines for antibiotic use in facial fracture surgery. The resultant recommendations called for limited peri-operative antibiotic agents (immediately before surgery and up until 24 hours post-operative) for facial fractures in all facial thirds and pre-operative antibiotic agents only for compound mandibular fractures.

Despite this, surveys of physician prescribing patterns show marked deviation from existing evidence [4,11]. At our own institution, we found that patients received anywhere from zero to 14 days of continuous pre-operative antibiotic agents. Close examination of the literature reveals little to justify the prolonged pre-operative antibiotic courses that are often administered. Early animal experiments performed by Burke [17] has been cited as evidence for continued pre-operative antibiotic agents from the time of injury until surgery in mandible fractures. In his study, he found that giving antibiotic agents longer than three hours after bacterial contamination of a surgical site resulted in similar inflammatory changes as if no antibiotic agents were given. Burke also concluded that the maximum antibiotic effect is attained when given prior to bacterial contamination [17]. Although his findings support the scientific foundation behind administering antibiotic agents within one hour prior to incision, there is no hard evidence for prolonged antibiotic administration after bacterial contamination has already occurred. One of the earliest studies by Chole and Yee [13] in 1988 found that administering a single pre-operative dose of cefazolin with one additional post-operative dose decreased the infection rate from 43% to 14% in patients with mandibular and midface fractures. Since this time, others have similarly determined that a single dose of pre-operative prophylactic antibiotic agents is sufficient in reducing post-operative infections [15].

However, it is difficult to ascertain what constitutes an acceptable infection rate, given varying inclusion criteria and follow-up periods reported in the literature. Our overall rate of head or neck infections at 30 days (9.6%) is comparable to rates reported by others who included multiple fracture locations (3%–9%), but was fairly higher over the entire study period (19.7%) [8,15,16]. This is likely because of a higher risk population, which included only admitted patients with 48.9% requiring ICU admission. We also had a broader definition of head and neck infections that included meningitis along with other head and neck soft tissue infections diagnosed up until the last time of follow-up. The majority of patients in our study (86.2%) underwent an open surgical approach and 76.1% had implanted hardware. Additionally, more than half (54.8%) of the patients included in our study had a mandible fracture. Mandibular fractures in particular are known to carry some of the highest risk for developing post-operative infections with reported rates ranging from 1.9%– 29.4% when antibiotic agents are given [6,7,14,18]. Our overall rate of head or neck infections in mandible fracture patients was 27.2% for the entire study period, with lower rates seen in patients with isolated mandible fractures.

The higher long-term rates of infection seen for the entire population and the isolated mandible patients generates some concern. By giving prolonged courses, we may be actually selecting out for more virulent organisms that have the potential to contribute to delayed infectious complications. In a study by Miles et al. [6] evaluating the benefit of a long antibiotic course in mandible fractures managed by open reduction and internal fixation, it was found that patients who received extended antibiotic courses developed infections at later time points than the short course patients [6]. These outcomes highlight the importance of continued follow-up beyond the acute post-operative period for this patient population.

Our findings, and those of others, demonstrate little, or any, benefit of administering long pre-operative courses of antibiotic prophylaxis greater than one day for facial fracture surgery [13,15]. In our MLR we did not find antibiotic duration (short or long course) as having an independent effect on head or neck infections, whereas having a mandible fracture or requiring ICU admission did. These results support our opinion that patient risk factors play a greater role in the development of infections and suggest that there is little to be gained from prolonging pre-operative antibiotic agents.

These results also leave us to wonder: is there a tipping point at which prolonged antibiotic exposure begins to cause deleterious effects on the microbiome, without adding to the intended benefit of preventing infections? Growing antibiotic resistance is a serious problem in today's healthcare system. The US Centers for Disease Control and Prevention have highlighted the need to improve antibiotic use as one of four key strategies required to address the problem of antibiotic resistance in the United States [19]. Fortunately, in our study the rates of MDRO were low at 1.6% with no differences detected between the short and long pre-operative course groups, but there is concern that differences may develop over greater time and with a larger sample size.

It is important to note that the data presented in this study are not without limitations. Because this is a retrospective analysis at single institution, it is difficult to eliminate any selection bias that exists in the placement of patients in the short or long duration antibiotic groups. Furthermore, it was difficult to stratify the patients into subgroups beyond the mandibular group because of increased potential for type 2 errors. However, an MLR was performed to control for relevant patient and injury characteristics that might contribute to infection and this still failed to show antibiotic duration as being an independent predictor of infection. In this analysis, it was also discovered that some variability exists in provider-specific pre-operative antibiotic selection; as such, it is difficult to make any conclusions currently regarding which antibiotics are best suited for which injuries or which antibiotic agents should be avoided altogether. Finally, the short duration antibiotic group could have been further stratified into those who had only received a single pre-incision dose versus those who had received longer durations of antibiotics (still <24 hours).

Conclusions

The considerable variability in prescribed antibiotic durations seen both in this study and throughout the literature highlights the need for further research and more definitive guidelines for the use of pre-operative antibiotic prophylaxis in facial trauma. In our study, we did not find long pre-operative antibiotic courses to decrease the rates of head or neck infections for facial fractures. In fact, our data suggest that overprescribing practices may contribute to increased long-term infectious complications. Based on this work, and current available evidence, it is these authors' opinion that shortening the duration of pre-operative antibiotic prophylaxis to one day or less for all facial fractures should be sufficient.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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