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Background:
Systematic Review

Systemic Antibiotic Prophylaxis in Maxillofacial Trauma: A Scoping Review and Critical Appraisal

by
Femke Goormans
1,*,
Ruxandra Coropciuc
1,2,
Maximilien Vercruysse
1,
Isabel Spriet
3,4,
Robin Willaert
1,2 and
Constantinus Politis
1,2
1
Department of Oral and Maxillofacial Surgery, Faculty of Medicine KU Leuven, University Hospitals Leuven, Campus Sint-Rafaël, Kapucijnenvoer 33, 3000 Leuven, Belgium
2
OMFS-IMPATH Research Group, Department of Imaging and Pathology, Faculty of Medicine KU Leuven, University Hospitals Leuven, Campus Sint-Rafaël, Kapucijnenvoer 33, 3000 Leuven, Belgium
3
Department of Pharmaceutical and Pharmacological Sciences, Clinical Pharmacology and Pharmacotherapy, Faculty of Medicine KU Leuven, Campus Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium
4
Pharmacy Department, University Hospitals Leuven, Campus Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium
*
Author to whom correspondence should be addressed.
Antibiotics 2022, 11(4), 483; https://doi.org/10.3390/antibiotics11040483
Submission received: 19 February 2022 / Revised: 27 March 2022 / Accepted: 3 April 2022 / Published: 5 April 2022
(This article belongs to the Special Issue Fracture-Related Infection: An Update on Antimicrobial Therapy)
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Abstract

:
Infection after maxillofacial trauma remains an important complication, with a significant socio-economic impact. While consensus exists that systemic antibiotic prophylaxis reduces the risk of infection in the management of maxillofacial fractures, the type, and duration remain controversial. Therefore, the purpose of this scoping review was to provide an overview of the current evidence that supports the use of prophylactic antibiotics in the treatment of maxillofacial fractures. A comprehensive literature search on 1 January 2022, in PubMed, Web of Science, Embase, and Cochrane, revealed 16 articles. Most studies focused on the duration of systemic antibiotic prophylaxis and compared a one-day to a five-day regimen. Included studies showed considerable variability in design and research aims, which rendered them difficult to compare. Furthermore, a variety of antibiotic regimens were used, and most studies had a short follow-up period and unclear outcome parameters. This scoping review demonstrates the lack of well-constructed studies investigating the type and duration of systemic antibiotic prophylaxis in the treatment of maxillofacial trauma. Based on the included articles, prolonging antibiotic prophylaxis over 24 h for surgically treated fractures does not appear to be beneficial. Furthermore, there is no evidence for its use in conservatively treated fractures. These results should be interpreted with caution since all included studies had limitations.

1. Introduction

Infection after maxillofacial trauma remains an important complication [1], leading to significant morbidity and increased healthcare costs [2]. Overall, infection rates after maxillofacial fractures vary widely across studies and range from 0% to 62% [3,4]. Accurately estimating the incidence and impact of this complication is hampered by the lack of a clear definition, and the variability in outcome parameters renders existing studies difficult to evaluate and compare [5].
Systemic antibiotic prophylaxis is an accepted strategy to prevent infection in daily clinical practice [6]. However, the optimal type and duration remain controversial [7]. An awareness of the need for standardized, evidence-based guidelines has increased in recent years [8]. Furthermore, antimicrobial resistance (AMR) is increasing, and physicians are becoming aware of the importance of limiting antibiotic use [9].
Contemporary guidelines state that antibiotic prophylaxis should be provided for no longer than 24 h [10]. However, these recommendations are mainly based on a handful of clinical studies and uncertainty persists regarding the optimal antibiotic regimen for infection prevention. Previously published systematic reviews often included studies with a significant risk of bias, leading to a misrepresentation of the currently available evidence [1,3,6,7,11,12,13,14,15,16,17]. For these reasons, and on a worldwide scale, heterogeneity in infection prevention protocols still exist. Recent international surveys among maxillofacial trauma surgeons indeed concluded that most surgeons continue antibiotic prophylaxis longer than proposed, which leads to an important overuse of antibiotics [16,17]. Similar issues are currently encountered in infection prevention protocols for long-bone fractures [18,19].
The purpose of this scoping review was to investigate the association between the type and duration of systemic antibiotic prophylaxis and infection in the treatment of maxillofacial fractures. Furthermore, this study provides an overview of the currently available evidence with respect to this topic. Moreover, the aim is to identify the bottlenecks that prevent the maxillofacial community from adhering to guidelines and illustrate the implications of antibiotic overuse.

2. Methods

All aspects of the five-steps methodology proposed by the Joanna Briggs Institute (JBI) guidance were followed and the study was written according to the Preferred Reporting Items for Systematic Reviews and the Meta-Analyses extension for Scoping Reviews (PRISMA-Scr) guidelines [20].

2.1. Data Sources and Search Strategy

The search strategy was peer-reviewed by a certified librarian. A comprehensive search was performed on 1 January 2022, in the PubMed, Web of Science, Embase, and Cochrane databases. The main search concepts were maxillofacial trauma and antibiotic prophylaxis. No date restrictions were applied. Search strings for each database are provided as Supplementary Data.

2.2. Inclusion/Exclusion Criteria

To be included, published studies were required to present original data with the primary aim to investigate the association between systemic antibiotic prophylaxis (i.e., type, duration) and infection, in both surgically and non-surgically treated patients with maxillofacial fractures. There were no restrictions related to the type or timing of the surgical intervention or the type or class of antibiotics. Furthermore, studies were only included when a comparison group was provided and when the antibiotic prophylaxis duration was clearly described. Moreover, studies needed to clearly describe which fractures were treated surgically and which were treated non-surgically. Exclusion criteria were articles that focused on basilar skull fractures and non-traumatic fractures (i.e., pathological fractures). In addition, case reports, published abstracts, conference posters, letters, articles in languages other than English, and articles of which the full text was not available, were excluded.

2.3. Study Selection

References were collected in EndNote and duplicates were removed. Two authors (FG and MV) independently screened the titles and abstracts of references identified in the search. In case of disagreement, a third reviewer (RC) was available for an additional discussion. After the selection of the title and abstract, potentially relevant articles were included for full-text screening. A PRISMA flow diagram provides an overview of the selection process and the number of papers retrieved and excluded (Figure 1).

2.4. Data Extraction and Assessment of Evidence Level

Two authors (FG and MV) independently extracted data from the selected studies and recorded the data for each included study in the ‘characteristics of included studies’ tables (Table 1 and Table 2). An assessment for possible bias was performed using the ROBINS-I tool for non-randomized studies [22] and the RoB 2 tool for randomized controlled trials [23].

3. Results

Overall, 7180 references were collected in EndNote. After the exclusion of duplicates, we retrieved 5480 articles. Based on the title and abstract, 5253 articles were excluded. Of the remaining 227 articles, 16 were included in this scoping review (Table 1 and Table 2), 13 of which were published in the last decade. Fifteen of the included studies evaluated perioperative antibiotic prophylaxis (PAP) for surgically treated maxillofacial fractures [4,24,25,26,27,28,29,30,31,32,33,34,35,36,37] and one study evaluated systemic antibiotic prophylaxis for conservatively treated fractures [38].
Upper and lower facial fractures were discussed separately because significantly more infections are seen in fractures of the tooth-bearing area of the mandible, which is frequently argued to be due to the proximity to the oral cavity [39]. Table 1 provides an overview of the 11 included studies on lower facial fractures (mandibular fractures) [24,25,26,27,28,29,30,31,32,34,37], and Table 2 provides an overview of the ten studies on midface and upper facial fractures [4,25,26,27,31,33,35,36,37,38]. Five studies included both mandibular as well as midface and upper facial fractures; these results were included in both tables [25,26,27,31,37]. Since the exact type of antibiotic therapy, in relation to the outcome, was not described in most studies, a separate column was provided for the generic names of the administered antibiotics.
In total, we included ten randomized controlled trials (RCT) [4,24,25,26,27,30,32,34,35,36] and six retrospective cohort studies (RCS) [28,29,31,33,37,38], with a total of 2430 patients. For fractures of the lower facial third (Table 1), six studies reported on both open and closed mandibular fractures [24,27,28,29,30,37] and the remaining five studies failed to report if the fractures were open or closed [25,26,31,32,34]. For fractures of the midface and upper facial third (Table 2), two studies only included patients with closed fractures [4,38], one reported on both open and closed fractures [37], and seven studies failed to report if the fractures were open or closed [25,26,27,31,33,35,36].

3.1. Study Design and Research Aims

Included studies showed a considerable variability in their design and research aims, which rendered them difficult to compare. Chole et al. compared antibiotic prophylaxis of one hour preoperatively and eight hours postoperatively, to no antibiotic prophylaxis at all [27]. Campos et al. evaluated prolonging antibiotic prophylaxis until 24 h postoperatively to a single-dose administration at the time of induction (20 min before surgery) [26]. Eight studies compared either less than one day (no [25,30], a single-dose [32] or 12 h [24]) or up to 24 h of postoperative antibiotic prophylaxis [31,34,35,36]), to five or more days of postoperative antibiotic prophylaxis [24,25,30,31,32,34,35,36]. Moreover, six studies were included that presented different study designs. Jang et al. compared four days of postoperative antibiotic prophylaxis to one dose at induction [4]. Lovato et al. and Zosa et al. grouped all patients who received antibiotic prophylaxis for less than 24 h and compared them to patients receiving more than 24 h of antibiotic prophylaxis [29,37]. Finally, Domingo et al., Reiss et al., and Malekpour et al. compared antibiotic prophylaxis for variable durations [28,33,38].

3.2. Study Outcomes

Infection rates varied from 0% to 43.9% for all included studies in this review [4,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38].

3.2.1. Fractures of the Lower Facial Third

Infection rates for mandibular fractures varied from 3.3% to 43.9% (Table 1). None of the included studies found a statistically significant benefit of prolonging antibiotic prophylaxis over 24 h [24,25,28,29,30,31,32,34,37]. Campos et al. illustrated a significant benefit of continuing antibiotic prophylaxis until 24 h postoperatively [26]; infection rates were almost seven times higher for patients who received only a single dose at the time of induction. Chole et al. could only establish a significant benefit of antibiotic prophylaxis (one hour preoperatively and eight hours postoperatively) for fractures of the mandibular angle or parasymphyseal region treated with open reduction and internal fixation (ORIF) [27]. However, for condylar fractures and for all mandibular fractures treated with closed reduction (CR), no significant reduction was seen in infection rates for patients receiving antibiotic prophylaxis compared to no antibiotic prophylaxis at all [27]. Furthermore, Zosa et al. noted a significantly increased infection rate for patients who received antibiotic prophylaxis over 24 h [37], and Miles et al. described an increased late-onset infection in patients who received antibiotic prophylaxis for five to seven days [30].

3.2.2. Fractures of the Midface and Upper Facial Third

Infection rates for fractures of the midface and upper facial third varied from 0% to 12.5% (Table 2). None of the included studies found a significant benefit in prolonging antibiotic prophylaxis over 24 h [4,25,31,33,35,36,37]. Furthermore, Campos et al. even suggested that a single-dose administration at the time of induction (20 min before surgery) suffices and found no significant benefit of prolonging antibiotic prophylaxis for 24 h [26]. Finally, two studies on surgically treated fractures [27,33] and one study on conservatively treated fractures [38] reported an infection rate of 0% without antibiotic prophylaxis.

3.2.3. Antibiotic Type

All included studies administered β-lactam antibiotics. Nine studies used cephalosporins, including first (cefazolin, cefalexin, cefadroxil, and cefazedone), second (cefotetan), third (ceftriaxone, cefotaxime, and cefdinir), and fourth (cefepime) generation cephalosporins [4,25,26,27,28,29,30,33,37]. Twelve studies used penicillins, including amoxicillin—often co-administered with clavulanic acid or sulbactam—and penicillin G or penicillin VK [24,28,29,30,31,32,33,34,35,36,37,38]. In three studies, the penicillins or cephalosporins were combined with metronidazole [25,30,32]. Clindamycin was the antibiotic of choice in case of a penicillin allergy [29,30,31,38].
Furthermore, four retrospective cohort studies used a wide variety of antibiotics or combinations, without specifying the reasoning for administering different antibiotic types to different patients [28,29,33,37]. Next to cephalosporins and penicillins, fluoroquinolones (moxifloxacin, levofloxacin, and ciprofloxacin), carbapenems (imipenem), cotrimoxazole (sulfamethoxazole and trimethoprim), tetracyclines (doxycycline), and vancomycin were administered [28,29,33,37].
Since none of the included studies compared the different types of antibiotics, and data on pathogens identified by culture at the time of the diagnosis of infection were lacking across studies, no statement could be made about the most suitable antibiotic type used for antibiotic prophylaxis in maxillofacial fracture treatment.

3.3. Outcome Description

Infection was the primary outcome measure in all included studies. Lovato et al. and Reiss et al. failed to describe the applied criteria for infection [29,33]. For the included studies that did describe their outcome parameters, there was considerable variation in the definition of infection (Table 3). Six studies referred to the criteria for surgical site infection (SSI) as described by the Centers for Disease Control and Prevention (CDC) [28,31,32,34,35,36]. The remaining studies formulated their own criteria without providing a reference or substantiating the reasoning for the stated criteria [4,24,25,26,27,30,32,38]. Miles et al. [30] described local clinical and radiological criteria for infection, which were subsequently adopted by Perepa et al. [32]. Abubaker et al. [24] described local and systemic clinical criteria, which were subsequently adopted by Baliga et al. and Campos et al. [25,26].

3.4. Follow-Up Period

Follow-up periods varied widely and ranged from less than one week to six months, with a median follow-up of six weeks [4,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38]. Two studies (one RCT and one RCS) provided a follow-up of less than one month [25,38]. Reiss et al. included patients with a variable follow-up of less than one month to more than three months [33]. Three more studies (two RCTs and one RCS) provided a follow-up of just one month for all patients [4,27,28]. The RCT by Miles et al. had a follow-up of five weeks [30]. The RCS by Lovato et al. and the RCTs by Campos et al. and Abubaker et al. had a follow-up of six weeks [24,26,29]. Most patients included in the RCS by Zosa et al. were followed for a variable duration of one to eight months [37]. The RCT by Perepa et al. had a follow-up of three months [32]. Only four studies (two RCTs and two RCS) provided a follow-up of six months [31,34,35,36].

4. Discussion

This scoping review included ten RCTs and six RCS investigating the effect of systemic antibiotic prophylaxis duration on the infection rate after treatment of maxillofacial fractures [4,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38].

4.1. Duration of Systemic Antibiotic Prophylaxis

Based on the included studies, prolonged antibiotic prophylaxis does not appear to be beneficial in the prevention of infection. None of the studies comparing an antibiotic prophylaxis duration of up to 24 h with longer durations found a significant difference in infection rates [4,24,25,28,29,30,31,32,33,34,35,36,37,38].
The results of this scoping review are consistent with the most recent recommendations, which support discontinuing antibiotic prophylaxis after 24 h for all fracture types [10]. For mandibular fractures, continuing antibiotic prophylaxis for 24 h after wound closure is advised, but not beyond this time frame [24,25,26,28,29,30,31,32,34,37]. For upper and midface fractures, the benefit of continuing antibiotic prophylaxis for 24 h is questioned [26].
For conservatively treated fractures of the middle and upper facial third, there is no evidence for the use of systemic antibiotic prophylaxis at all [38].

4.2. Clinical Heterogeneity and the Limited Number of High-Quality Studies

Our initial literature search revealed 29 studies on the type and duration of systemic antibiotic prophylaxis with infection as the primary outcome measure [4,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51] (Figure 1). Compared to previous systematic reviews, we excluded multiple studies due to the fact that their primary aim was not to investigate the type and duration of systemic antibiotic prophylaxis, due to a lack of comparison group, or due to unclear reporting of the antibiotic prophylaxis duration [39,40,41,42,43,44,45,46,47,48,49,50,52,53,54,55,56,57,58]. One more study was excluded because it unclearly described which fractures were treated surgically and which were treated non-surgically [51]. Previously published systematic reviews included these studies [1,3,7,12,13,14,16,17] and even performed a meta-analysis [1,7,14]. In our opinion, the strict inclusion criteria enhanced the strength of our study and led to a more appropriate representation of available evidence. However, even for the included studies, variability in study design, antibiotic type, surgical treatment, fracture type and location, follow-up period and outcome caused significant heterogeneity.

4.2.1. Patient Characteristics

Eleven of the studies in this scoping review included patients under the age of 18 years [25,26,27,28,29,30,31,33,34,35,36]. The youngest patient, included by Domingo et al., was only 2 years old [28]. Moreover, two studies failed to report the age of the included patients [4,32]. Skeletally immature patients have a superior ability for soft-tissue recovery and infection resistance [59]. As the inclusion of these patients can potentially lead to an underestimation of the actual number of infectious complications, future trials should exclude skeletally immature patients.

4.2.2. Antibiotic Type and Duration

Although all studies administered β-lactam antibiotics, the antibiotic agents that were prescribed varied widely. In retrospective studies, a wide variety of antibiotics or combinations was often administered without specifying the reasoning for administering the different antibiotic types to different patients [28,29,33,37]. Future trials should be based on a single regimen to avoid possible confounding.
Furthermore, the duration of antibiotic prophylaxis varied and none of the studies had the same research question. Of the included prospective studies, one administered antibiotic prophylaxis one hour preoperatively and eight hours postoperatively [27], one evaluated prolonging antibiotic prophylaxis until 24 h postoperatively [26], and ten administered antibiotic prophylaxis for four days [4] or five or more days postoperatively [24,25,29,30,31,32,34,35,36]. Comparison groups received either no dose [4,25,27,29,30], a single dose [26,32], 12 h [24] or up to 24 h [31,34,35,36] of antibiotic prophylaxis. In addition, both treatment arms often received variable preoperative and intraoperative antibiotic prophylaxis, which possibly confounded the study results. Of the included retrospective studies, Domingo et al. and Reiss et al. reported variable and unknown postoperative durations, while patients received variable or no preoperative antibiotics [28,33]. Zosa et al. and Lovato et al. attempted to solve this heterogeneity by grouping all patients receiving antibiotic prophylaxis for less than 24 h and patients receiving antibiotic prophylaxis for more than 24 h [29,37]. Malekpour et al. compared non-surgically treated patients who did not receive antibiotic prophylaxis to those receiving either 1 to 5 days, or more than 5 days of antibiotic prophylaxis [38]. Only Mottini et al. prescribed the same type of antibiotic to all patients (except for patients with a penicillin allergy) and was able to provide a delineated comparison group [31].

4.2.3. Causal Pathogens

The selection of prophylactic antibiotics for infection prevention should consider the susceptibility of potential pathogens to these antibiotics [60]. Therefore, knowledge of the type of causative pathogens in infection related to the treatment of maxillofacial trauma is required. When the source of pathogens is skin flora, cefazolin is the antibiotic of choice as it covers Gram-positive cocci (i.e., Staphylococcal species) [60]. In maxillofacial trauma surgery, where pathogens may include oropharyngeal flora (Streptococcal species; oropharyngeal anaerobes (i.e., Peptostreptococcus species)), broad-spectrum antibiotics may be indicated (amoxicillin with clavulanic acid, or cephazolin with metronidazole) [61]. Data on pathogens identified by culture at the time of diagnosis of infection are lacking in the currently available literature.
The gold standard for a diagnosis of infection remains the deep tissue cultures, obtained from intraoperative samples [62]. Data on other techniques, such as a culture of sonication fluid from hardware, polymerase chain reaction (PCR), and histopathology (i.e., the presence of polymorphonuclear neutrophils (PMNs)) have not been described with respect to the diagnosis of infection after a maxillofacial trauma. For long-bone fractures, sonication of the osteosynthesis material and subsequent inoculation of sonication fluid has already proven to be useful in diagnosing infection [62]. Using low-intensity ultrasound, sonication is deployed to dislodge the biofilm from the osteosynthesis material. The sonication fluid is then cultured onto bacterial media for further analysis [62]. Sonication may be a way to avoid the contamination of tissue cultures with oral flora, and high-quality studies are needed to substantiate the utility of sonication in the treatment of infection after maxillofacial fractures.
Included studies showed considerable variability in their antibiotic type, with varying specificity against the presumed bacterial flora. This is a significant limitation, as the use of an effective antibiotic agent is essential to validate study outcomes. Abubaker et al. administered penicillin G and penicillin VK—narrow-spectrum antibiotics that only cover Streptococcal species—which could be a possible cause of their insignificant study results [24]. Furthermore, four retrospective studies administered a wide variety of antibiotic regimens in the intervention arm, resulting in insufficient sample sizes and therefore conclusions that should be interpreted with caution [28,29,33,37].
Future trials should thoroughly describe the causal pathogens related to infection after maxillofacial trauma, identified by culture. High quality, uncontaminated, deep tissue and implant samples are essential to validate culture outcomes [63]. Furthermore, to avoid false-negative culture results, it is generally advised to stop antimicrobial therapy two weeks before sampling [63].

4.2.4. Fracture Type

Five included studies on mandibular fractures failed to report whether they included open or closed fractures [25,26,31,32,34]. A mandibular fracture is considered open when the fracture site communicates either intraorally through the mucosa or extraorally through a laceration or avulsive injury of the overlying skin. Therefore, all fractures involving the tooth-bearing areas of the jaws are regarded as open fractures [64]. Any mandibular fracture that does not have extraoral communication and/or involves the tooth-bearing area is considered a closed fracture (e.g., condylar fracture) [64]. Numerous studies have shown that an open fracture is considered a significant risk for infection [27,28,39]. Therefore, not reporting whether the included fractures are open or closed makes the interpretation of the study results almost impossible. As most open fractures are contaminated with microorganisms, immediate antibiotic administration, wound debridement, soft-tissue coverage, and fracture stabilization are necessary [65]. While an immediate antibiotic administration at admission is the standard of care for long-bone open fractures [65], evidence is lacking for maxillofacial fractures and studies have not been able to objectify this benefit [47], possibly due to the limited number of included patients and insufficient follow-up. There is a need for high-quality studies evaluating the benefit of starting antibiotic prophylaxis at admission for open maxillofacial fractures.

4.2.5. Surgical Treatment

Fracture stability is of the utmost importance in the prevention of infection. Instability leads to ongoing soft-tissue trauma, interruption of neo-vascularity and osteolysis of bone, which creates a supportive environment for bacterial proliferation [66]. However, in most studies included in this review, both surgical therapy (e.g., fracture stability) and the timing of fracture fixation were poorly described [24,26,27,28,29,30,31,32,33,37,38].
Surgical treatment of mandibular fractures is performed using ORIF or CR and maxillomandibular fixation (MMF). Standard MMF methods are either tooth-supported (arch bars, interdental wires, or Ernst ligatures), or bone-supported devices such as intermaxillary fixation (IMF) screws [64]. Out of 11 included studies on surgically treated mandibular fractures, only Chole et al. and Domino et al. report separate infection rates for CR-MMF and ORIF [27,28]. These data are important as an open procedure may lead to a four-fold higher rate of infection [28,67]. As the type and timing of fracture fixation can have an influence on the outcome, future trials should develop protocols that clearly take these aspects into account.
Only one study on non-surgically treated maxillofacial fractures met our inclusion criteria [38]. The study by Malekpour et al. included 289 patients with maxillary and orbital fractures. They compared no antibiotic prophylaxis to 1 to 5 days, or more than 5 days of antibiotic prophylaxis, and showed an infection rate of 0% for all three comparison groups [38]. Based on the available literature, there is no evidence of the utility of systemic antibiotic prophylaxis in conservatively treated maxillofacial fractures [38,40,51,55,56]. However, due to the considerable risk of bias, it is not possible to withhold guidelines based on these studies. High-quality studies are needed to clarify the role of antibiotic use with respect to infection prevention and treatment in conservatively treated maxillofacial fractures.

4.2.6. Outcome Description

The lack of a uniform definition for infection after maxillofacial trauma also contributed to the scarcity of comparable data. Using inadequate outcome parameters risks underestimating or overestimating the actual number of complications, resulting in misleading study conclusions [5]. The absence of a universally accepted definition of infection after maxillofacial trauma mirrors the situation for fracture-related infection (FRI) in long-bone fractures and prosthetic joint infection (PJI) identified many years ago [68].
To date, the term FRI has not been used to describe infection following maxillofacial trauma. Although general treatment principles may differ, and significant differences exist with respect to the blood supply at the fracture site and the bacterial flora present at the site of injury, the basic diagnostic principles are similar. The definition of FRI is based on clinical, laboratory and radiological features that confirm or exclude the presence of infection. The described confirmatory and suggestive criteria could also apply to maxillofacial trauma and possibly be utilized to diagnose (and define) infection [5]. The term FRI covers both surgically treated as well as conservatively treated fractures, which is why we prefer to use the standardized term of FRI even though it has not yet been widely accepted within oral and maxillofacial surgery practice.

4.2.7. Follow-Up Period

In this review, follow-up periods were mostly short with only four studies reaching six months [31,34,35,36]. This suggests that late-onset infections were probably missed in most studies. The CDC currently advocates a surveillance period of 90 days after fracture fixation [69]. In clinical studies on maxillofacial trauma, a follow-up over 90 days is rare. A recent retrospective study on the timing of infection onset in patients with long-bone fractures illustrated that in a follow-up period of 90 days, only 64% of infections were diagnosed, while after one year of follow-up this percentage increased to 89% [70]. Of course, we should be careful with extrapolating these results to patients with maxillofacial fractures. Since failure to diagnose late-onset infections may lead to misrepresentation of study results, a minimum follow-up period of one year is recommended to ensure a correct representation of the study outcome [70].

4.3. Discrepancy between Guidelines and Clinical Practice

To the best of our knowledge, 11 systematic reviews on systemic antibiotic prophylaxis in maxillofacial fracture treatment were published over the past 15 years [1,3,6,7,11,12,13,14,15,16,17]. The first systematic review by Andreasen et al., in 2006, already demonstrated that 24 h of antibiotic prophylaxis suffices as antimicrobial prophylaxis in all maxillofacial fractures [6]. These findings were confirmed in all subsequent systematic reviews [1,3,7,11,12,13,14,15,16,17].
Recent surveys have confirmed that surgeons do not always adhere to these recommendations, and a high percentage still prolong the use of antibiotic prophylaxis [16,17]. A survey on systemic antibiotic prophylaxis in patients undergoing ORIF for mandibular fractures, where 687 surgeons responded, showed that 75% of surgeons stated that they administer antibiotics for up to 3 days (44.1%), 1 week (54.8%), and more than 1 week (1.1%) in the case of open fractures. Furthermore, 51% of surgeons administer antibiotics for up to 3 days (50.5%), 1 week (48.6%), and more than 1 week (1%) in the case of closed fractures [17].
The question arises as to why the above-mentioned recommendations have not yet been implemented in our daily clinical practice. Existing guidelines are mainly based on only a handful of clinical studies which still leads to uncertainty regarding the optimal type and duration of systemic antibiotic prophylaxis. Therefore, worldwide heterogeneity in prevention protocols still exists. Because of the microbiome present in the oral cavity and sinuses, maxillofacial surgeons fear contamination of the fracture site with commensal flora leading to infection [17] and intuitively assume that there may be a benefit to prolonged antibiotic administration. Since high-quality data for procedures that involve clean-contaminated procedures are lacking, controversy related to this topic remains within the maxillofacial community. There is a need for large, multicentric, well designed, double-blind RCTs, with sufficient follow-up, that can contribute to the guidelines with respect to the diagnosis and treatment of FRI in maxillofacial trauma.

4.4. Implications of Antibiotic Overuse

Antibiotics are a worldwide leading cause of adverse drug reactions and emergency department visits [71]. Prolonged systemic antibiotic prophylaxis can be associated with, rash, diarrhea and Clostridioides difficile infection, nausea, vomiting and abdominal pain, malaise, and fatigue [72,73].
Furthermore, prolonged antibiotic prophylaxis could possibly contribute to delayed infectious complications. Zosa et al. described a significantly increased infection risk for patients receiving prolonged antibiotic prophylaxis over seven days [37], and Miles et al. found that patients who received extended antibiotic prophylaxis developed late infectious complications [30]. A recent systematic review by Delaplain et al. confirmed a higher rate of surgical site infection for more than 72 h of antibiotic prophylaxis [7]. This issue has also been an issue encountered in long-bone fractures [74]. To the best of our knowledge, a possible cause for this phenomenon has not yet been described in the current literature and further research is required to validate these findings.
Finally, the overuse and improper use of antibiotics are considered important drivers for the emergence and spread of AMR [75]. AMR occurs as a natural evolutionary response to antimicrobial exposure, whereby microorganisms acquire the ability to withstand antimicrobial drugs via mutations in chromosomal genes and by horizontal gene transfer [75]. The global spread of AMR may compromise our ability to treat existing and emerging common infectious diseases, as well as undermining many other improvements in health care. Maxillofacial surgeons, like all healthcare workers, should realize that AMR is a global health problem. Antimicrobial stewardship promotes the appropriate use of antibiotics based on internationally accepted guidelines, leading to effective prevention and treatment of infections while avoiding the harmful effects of antibiotic use [75].

5. Limitations

The main limitation of this scoping review is the limited quality and heterogeneity of evidence available in the literature. In our opinion, none of the current studies provides sufficient evidence to serve as a starting point for future RCTs. Variability in study design, antibiotic type and duration, treatment, fracture type and location, renders existing studies difficult to evaluate and compare. Outcome measurements were mostly determined using unclear criteria and inadequate follow-up periods. Therefore, this review only provides limited evidence, and the results should be interpreted with caution.

6. Conclusions

This scoping review demonstrates the lack of well-constructed studies investigating the association between the type and duration of systemic antibiotic prophylaxis and infection in the treatment of maxillofacial fractures. All current available studies with respect to this topic showed a significant risk of bias. The considerable variability in antibiotic duration seen throughout the literature highlights the need for further research and guidelines for the use of antibiotic prophylaxis in maxillofacial trauma. Based on currently available evidence, shortening the duration of antibiotic prophylaxis to one day or less for all operatively treated facial fractures should be sufficient. Furthermore, there is no evidence for the use of systemic antibiotic prophylaxis in conservatively treated fractures. In fact, overprescribing practices may contribute to increased long-term infectious complications and AMR. Furthermore, although multiple guidelines have been developed to prevent infections after maxillofacial trauma over recent years, worldwide heterogeneity still exists with respect to the implementation of these guidelines in our daily clinical practice. High-quality studies are needed to clarify the optimal duration of antibiotic prophylaxis in the management of maxillofacial fractures.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/antibiotics11040483/s1. Search strings for each database are provided as Supplementary Data.

Author Contributions

Conceptualization, F.G. and R.C.; methodology, F.G., R.C. and M.V.; formal analysis, F.G. and M.V.; writing—original draft preparation, F.G.; writing—review and editing, R.C., R.W., I.S. and C.P.; supervision, C.P. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Acknowledgments

The authors wish to thank Eline Vancoppenolle, biomedical information specialist (KU Leuven Libraries–2Bergen–Learning Centre Désiré Collen, Belgium), for her help in conducting the systematic literature search.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Dawoud, B.E.S.; Kent, S.; Henry, A.; Wareing, J.; Chaudry, H.; Kyzas, P. Use of antibiotics in traumatic mandibular fractures: A systematic review and meta-analysis. Br. J. Oral Maxillofac. Surg. 2021. [Google Scholar] [CrossRef] [PubMed]
  2. Badia, J.M.; Casey, A.L.; Petrosillo, N.; Hudson, P.M.; Mitchell, S.A.; Crosby, C. Impact of surgical site infection on healthcare costs and patient outcomes: A systematic review in six European countries. J. Hosp. Infect. 2017, 96, 1–15. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Kyzas, P.A. Use of antibiotics in the treatment of mandible fractures: A systematic review. J. Oral Maxillofac. Surg. 2011, 69, 1129–1145. [Google Scholar] [CrossRef] [PubMed]
  4. Jang, N.; Shin, H.W. Are postoperative prophylactic antibiotics in closed reduction of nasal bone fracture valuable?: Prospective study of 30 cases. Arch. Craniofac. Surg. 2019, 20, 89–93. [Google Scholar] [CrossRef]
  5. Metsemakers, W.J.; Morgenstern, M.; McNally, M.A.; Moriarty, T.F.; McFadyen, I.; Scarborough, M.; Athanasou, N.A.; Ochsner, P.E.; Kuehl, R.; Raschke, M.; et al. Fracture-related infection: A consensus on definition from an international expert group. Injury 2018, 49, 505–510. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  6. Andreasen, J.O.; Jensen, S.S.; Schwartz, O.; Hillerup, Y. A systematic review of prophylactic antibiotics in the surgical treatment of maxillofacial fractures. J. Oral Maxillofac. Surg. 2006, 64, 1664–1668. [Google Scholar] [CrossRef] [PubMed]
  7. Delaplain, P.T.; Phillips, J.L.; Lundeberg, M.; Nahmias, J.; Kuza, C.M.; Sheehan, B.M.; Murphy, L.S.; Pejcinovska, M.; Grigorian, A.; Gabriel, V.; et al. No Reduction in Surgical Site Infection Obtained with Post-Operative Antibiotics in Facial Fractures, Regardless of Duration or Anatomic Location: A Systematic Review and Meta-Analysis. Surg. Infect. 2020, 21, 112–121. [Google Scholar] [CrossRef]
  8. Djulbegovic, B.; Guyatt, G.H. Progress in evidence-based medicine: A quarter century on. Lancet 2017, 390, 415–423. [Google Scholar] [CrossRef]
  9. Murray, C.J.; Ikuta, K.S.; Sharara, F.; Swetschinski, L.; Aguilar, G.R.; Gray, A.; Han, C.; Bisignano, C.; Rao, P.; Wool, E.; et al. Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet 2022, 399, 629–655. [Google Scholar] [CrossRef]
  10. Anderson, D.J.; Sexton, D.J.; Post, T. Antimicrobial Prophylaxis for Prevention of Surgical Site Infection in Adults. UpToDate. 2016. Available online: https://www.uptodate.com/contents/antimicrobial-prophylaxis-for-prevention-of-surgical-site-infection-in-adults (accessed on 17 January 2022).
  11. Asokan, C.; Ebenezer, V.; Ramalingam, B. Role of prophylactic antibiotics in the surgical treatment of maxillofacial fractures. Indian J. Public Health Res. Dev. 2019, 10, 2848–2852. [Google Scholar] [CrossRef]
  12. Blatt, S.; Al-Nawas, B. A systematic review of latest evidence for antibiotic prophylaxis and therapy in oral and maxillofacial surgery. Infection 2019, 47, 519–555. [Google Scholar] [CrossRef] [PubMed]
  13. Chaudhry, H.; Hennedige, A.; Patel, M. Review of prophylactic prescribing of antibiotics during the management of fractured mandibles. Surgeon 2021, 19, e519–e525. [Google Scholar] [CrossRef]
  14. Habib, A.M.; Wong, A.D.; Schreiner, G.C.; Satti, K.F.; Riblet, N.B.; Johnson, H.A.; Ossoff, J.P. Postoperative prophylactic antibiotics for facial fractures: A systematic review and meta-analysis. Laryngoscope 2019, 129, 82–95. [Google Scholar] [CrossRef] [PubMed]
  15. Milic, T.; Raidoo, P.; Gebauer, D. Antibiotic prophylaxis in oral and maxillofacial surgery: A systematic review. Br. J. Oral Maxillofac. Surg. 2020, 59, 633–642. [Google Scholar] [CrossRef] [PubMed]
  16. Mundinger, G.S.; Borsuk, D.E.; Okhah, Z.; Christy, M.R.; Bojovic, B.; Dorafshar, A.H.; Rodriguez, E.D. Antibiotics and facial fractures: Evidence-based recommendations compared with experience-based practice. Craniomaxillofac. Trauma Reconstr. 2014, 8, 64–78. [Google Scholar] [CrossRef] [Green Version]
  17. Shridharani, S.M.; Berli, J.; Manson, P.N.; Tufaro, A.P.; Rodriguez, E.D. The Role of Postoperative Antibiotics in Mandible Fractures: A Systematic Review of the Literature. Ann. Plast. Surg. 2015, 75, 353–357. [Google Scholar] [CrossRef]
  18. Puetzler, J.; Zalavras, C.; Moriarty, T.F.; Verhofstad, M.H.J.; Kates, S.L.; Raschke, M.J.; Rosslenbroich, S.; Metsemakers, W.J. Clinical practice in prevention of fracture-related infection: An international survey among 1197 orthopaedic trauma surgeons. Injury 2019, 50, 1208–1215. [Google Scholar] [CrossRef]
  19. Declercq, P.; Zalavras, C.; Mertens, B.; Van der Linden, L.; Nijs, S.; Spriet, I.; Metsemakers, W.J. Perioperative antibiotic prophylaxis in long bone open fractures: The need for randomized controlled trials. Arch. Orthop. Trauma. Surg. 2021. epub ahead of print. [Google Scholar] [CrossRef]
  20. Tricco, A.C.; Lillie, E.; Zarin, W.; O’Brien, K.K.; Colquhoun, H.; Levac, D.; Moher, D.; Peters, M.D.J.; Horsley, T.; Weeks, L.; et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann. Intern. Med. 2018, 169, 467–473. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  21. Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021, 372, n71. [Google Scholar] [CrossRef] [PubMed]
  22. Sterne, J.A.; Hernán, M.A.; Reeves, B.C.; Savović, J.; Berkman, N.D.; Viswanathan, M.; Henry, D.; Altman, D.G.; Ansari, M.T.; Boutron, I.; et al. ROBINS-I: A tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016, 355, i4919. [Google Scholar] [CrossRef] [Green Version]
  23. Higgins, J.P.T.; Altman, D.G.; Gøtzsche, P.C.; Jüni, P.; Moher, D.; Oxman, A.D.; Savović, J.; Schulz, K.F.; Weeks, L.; Sterne, J.A.C.; et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011, 343, d5928. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  24. Abubaker, A.O.; Rollert, M.K. Postoperative antibiotic prophylaxis in mandibular fractures: A preliminary randomized, double-blind, and placebo-controlled clinical study. J. Oral Maxillofac. Surg. 2001, 59, 1415–1419. [Google Scholar] [CrossRef] [PubMed]
  25. Baliga, S.D.; Bose, A.; Jain, S. The evaluation of efficacy of post-operative antibiotics in the open reduction of the zygomatic and mandibular fracture: A prospective trial. J. Maxillofac. Oral Surg. 2014, 13, 165–175. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  26. Campos, G.B.; Lucena, E.E.; da Silva, J.S.; Gomes, P.P.; Germano, A.R. Efficacy assessment of two antibiotic prophylaxis regimens in oral and maxillofacial trauma surgery: Preliminary results. Int. J. Clin. Exp. Med. 2015, 8, 2846–2852. [Google Scholar]
  27. Chole, R.A.; Yee, J. Antibiotic prophylaxis for facial fractures: A prospective, randomized clinical trial. Arch. Otolaryngol.—Head Neck Surg. 1987, 113, 1055–1057. [Google Scholar] [CrossRef]
  28. Domingo, F.; Dale, E.; Gao, C.; Groves, C.; Stanley, D.; Maxwell, R.A.; Waldrop, J.L. A single-center retrospective review of postoperative infectious complications in the surgical management of mandibular fractures: Postoperative antibiotics add no benefit. J. Trauma Acute Care Surg. 2016, 81, 1109–1114. [Google Scholar] [CrossRef] [PubMed]
  29. Lovato, C.; Wagner, J.D. Infection rates following perioperative prophylactic antibiotics versus postoperative extended regimen prophylactic antibiotics in surgical management of mandibular fractures. J. Oral Maxillofac. Surg. 2009, 67, 827–832. [Google Scholar] [CrossRef] [PubMed]
  30. Miles, B.A.; Potter, J.K.; Ellis, E., III. The efficacy of postoperative antibiotic regimens in the open treatment of mandibular fractures: A prospective randomized trial. J. Oral Maxillofac. Surg. 2006, 64, 576–582. [Google Scholar] [CrossRef] [PubMed]
  31. Mottini, M.; Wolf, R.; Soong, P.L.; Lieger, O.; Nakahara, K.; Schaller, B. The role of postoperative antibiotics in facial fractures: Comparing the efficacy of a 1-day versus a prolonged regimen. J. Trauma Acute Care Surg. 2014, 76, 720–724. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  32. Perepa, A.; Sinha, R.; Agarwal, A.; Khan, T.A. Protocol for Antibiotic Administration in Mandibular Trauma: A Prospective Clinical Trial. J. Maxillofac. Oral Surg. 2018, 17, 19–23. [Google Scholar] [CrossRef] [PubMed]
  33. Reiss, B.; Rajjoub, L.; Mansour, T.; Chen, T.; Mumtaz, A. Antibiotic Prophylaxis in Orbital Fractures. Open Ophthalmol. J. 2017, 11, 11–16. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Schaller, B.; Soong, P.L.; Zix, J.; Iizuka, T.; Lieger, O. The role of postoperative prophylactic antibiotics in the treatment of facial fractures: A randomized, double-blind, placebo-controlled pilot clinical study. Part 2: Mandibular fractures in 59 patients. Br. J. Oral Maxillofac. Surg. 2013, 51, 803–807. [Google Scholar] [CrossRef] [PubMed]
  35. Soong, P.L.; Schaller, B.; Zix, J.; Iizuka, T.; Mottini, M.; Lieger, O. The role of postoperative prophylactic antibiotics in the treatment of facial fractures: A randomised, double-blind, placebo-controlled pilot clinical study. Part 3: Le Fort and zygomatic fractures in 94 patients. Br. J. Oral Maxillofac. Surg. 2014, 52, 329–333. [Google Scholar] [CrossRef] [PubMed]
  36. Zix, J.; Schaller, B.; Iizuka, T.; Lieger, O. The role of postoperative prophylactic antibiotics in the treatment of facial fractures: A randomised, double-blind, placebo-controlled pilot clinical study. Part 1: Orbital fractures in 62 patients. Br. J. Oral Maxillofac. Surg. 2013, 51, 332–336. [Google Scholar] [CrossRef] [PubMed]
  37. Zosa, B.M.; Ladhani, H.A.; Sajankila, N.; Elliott, C.W.; Claridge, J.A. Pre-Operative Antibiotic Agents for Facial Fractures: Is More than One Day Necessary? Surg. Infect. 2021, 22, 516–522. [Google Scholar] [CrossRef] [PubMed]
  38. Malekpour, M.; Bridgham, K.; Neuhaus, N.; Widom, K.; Rapp, M.; Leonard, D.; Baro, S.; Dove, J.; Hunsinger, M.; Blansfield, J.; et al. Utility of Prophylactic Antibiotics in Nonoperative Facial Fractures. J. Craniofac. Surg. 2016, 27, 1677–1680. [Google Scholar] [CrossRef] [PubMed]
  39. Zallen, R.D.; Curry, J.T. A study of antibiotic usage in compound mandibular fractures. J. Oral Surg. 1975, 33, 431–434. [Google Scholar] [PubMed]
  40. Esce, A.R.; Chavarri, V.M.; Joshi, A.B.; Meiklejohn, D.A. Evaluation of Antibiotic Prophylaxis for Acute Nonoperative Orbital Fractures. Ophthalmic Plast. Reconstr. Surg. 2021, 37, 462–464. [Google Scholar] [CrossRef] [PubMed]
  41. Gaal, A.; Bailey, B.; Patel, Y.; Smiley, N.; Dodson, T.; Kim, D.; Dillon, J. Limiting Antibiotics When Managing Mandible Fractures May Not Increase Infection Risk. J. Oral Maxillofac. Surg. 2016, 74, 2008–2018. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  42. Gutta, R.; Tracy, K.; Johnson, C.; James, L.E.; Krishnan, D.G.; Marciani, R.D. Outcomes of mandible fracture treatment at an academic tertiary hospital: A 5-year analysis. J. Oral Maxillofac. Surg. 2014, 72, 550–558. [Google Scholar] [CrossRef] [PubMed]
  43. Hindawi, Y.H.; Oakley, G.M.; Kinsella, C.R., Jr.; Cray, J.J.; Lindsay, K.; Scifres, A.M. Antibiotic duration and postoperative infection rates in mandibular fractures. J. Craniofac. Surg. 2011, 22, 1375–1377. [Google Scholar] [CrossRef] [PubMed]
  44. Huang, W.; Lynham, A.; Wullschleger, M. Orbitozygomatic Fracture Repairs: Are Antibiotics Necessary? Craniomaxillofac. Trauma Reconstr. 2015, 8, 271–276. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  45. Lauder, A.; Jalisi, S.; Spiegel, J.; Stram, J.; Devaiah, A. Antibiotic prophylaxis in the management of complex midface and frontal sinus trauma. Laryngoscope 2010, 120, 1940–1945. [Google Scholar] [CrossRef] [PubMed]
  46. Linkugel, A.D.; Odom, E.B.; Bavolek, R.A.; Snyder-Warwick, A.K.; Patel, K.B. Systemic Preoperative Antibiotics with Mandible Fractures: Are They Indicated at the Time of Injury? Craniomaxillofac. Trauma Reconstr. 2018, 11, 35–40. [Google Scholar] [CrossRef] [PubMed]
  47. Mamthashri, V.; Reddy, B.P. Comparison of Preoperative and Perioperative Antibiotic Prophylaxis Regimen in Compound Facial Fractures. J. Contemp. Dent. Pract. 2018, 19, 214–220. [Google Scholar] [CrossRef]
  48. Schaefer, E.H.; Caterson, E.J. Antibiotic selection for open reduction internal fixation of mandible fractures. J. Craniofac. Surg. 2013, 24, 85–88. [Google Scholar] [CrossRef] [PubMed]
  49. Sethi, A.; Van Huekelom, E.; Mehra, P. Outcomes following use of a standard antibiotic protocol in the management of maxillofacial trauma patients. J. Oral Biol. Craniofacial Res. 2020, 10, 519–522. [Google Scholar] [CrossRef] [PubMed]
  50. Wladis, E.J. Are post-operative oral antibiotics required after orbital floor fracture repair? Orbit 2013, 32, 30–32. [Google Scholar] [CrossRef]
  51. Zosa, B.M.; Elliott, C.W.; Kurlander, D.E.; Johnson, F.; Ho, V.P.; Claridge, J.A. Facing the facts on prophylactic antibiotics for facial fractures: 1 day or less. J. Trauma Acute Care Surg. 2018, 85, 444–450. [Google Scholar] [CrossRef]
  52. Adalarasan, S.; Mohan, A.; Pasupathy, S. Prophylactic antibiotics in maxillofacial fractures: A requisite? J. Craniofac. Surg. 2010, 21, 1009–1011. [Google Scholar] [CrossRef]
  53. Hammond, D.; Parmar, S.; Whitty, J.; McPhillips, M.; Wain, R. Prescription of antibiotics: Does it alter the outcome for patients who have fractures of the angle of the mandible? Br. J. Oral Maxillofac. Surg. 2017, 55, 958–961. [Google Scholar] [CrossRef]
  54. Knepil, G.J.; Loukota, R.A. Outcomes of prophylactic antibiotics following surgery for zygomatic bone fractures. J. Craniomaxillofac. Surg. 2010, 38, 131–133. [Google Scholar] [CrossRef] [PubMed]
  55. Pessino, K.; Cook, T.; Layliev, J.; Bradley, J.P.; Bastidas, N. Excluding Antibiotics in the Management of Nonoperative Orbital and Zygomatic Fractures. Ann. Plast. Surg. 2021, 86, 424–427. [Google Scholar] [CrossRef] [PubMed]
  56. Schmidt, R.S.; Dodson, K.M.; Goldman, R.A. Prophylactic antibiotic therapy for fractures of the maxillary sinus. Ear Nose Throat J. 2015, 94, 170–177. [Google Scholar] [PubMed]
  57. Wick, E.H.; Deutsch, B.; Kallogjeri, D.; Chi, J.J.; Branham, G.H. Effectiveness of Prophylactic Preoperative Antibiotics in Mandible Fracture Repair: A National Database Study. Otolaryngol.–Head Neck Surg. 2021, 165, 798–808. [Google Scholar] [CrossRef]
  58. Eddine, S.B.Z.; Cooper–Johnson, K.; Ericksen, F.; Brookes, C.C.; Peppard, W.J.; Revolinski, S.L.; Carver, T.W. Antibiotic Duration and Outcome Complications for Surgical Site Infection Prevention in Traumatic Mandible Fracture. J. Surg. Res. 2020, 247, 524–529. [Google Scholar] [CrossRef] [PubMed]
  59. Chen, H.; Chen, S.; Shi, Y.; Lu, Y.; Yu, B. Children with open tibial fractures show significantly lower infection rates than adults: Clinical comparative study. Int. Orthop. 2019, 43, 713–718. [Google Scholar] [CrossRef]
  60. Leekha, S.; Terrell, C.L.; Edson, R.S. General principles of antimicrobial therapy. Mayo Clin. Proc. 2011, 86, 156–167. [Google Scholar] [CrossRef] [Green Version]
  61. Mangram, A.J.; Horan, T.C.; Pearson, M.L.; Silver, L.C.; Jarvis, W.R. Guideline for Prevention of Surgical Site Infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am. J. Infect. Control. 1999, 27, 97–132. [Google Scholar] [CrossRef]
  62. Onsea, J.; Depypere, M.; Govaert, G.; Kuehl, R.; Vandendriessche, T.; Morgenstern, M.; McNally, M.; Trampuz, A.; Metsemakers, W.J. Accuracy of Tissue and Sonication Fluid Sampling for the Diagnosis of Fracture-Related Infection: A Systematic Review and Critical Appraisal. J. Bone Jt. Infect. 2018, 3, 173–181. [Google Scholar] [CrossRef]
  63. Trampuz, A.; Zimmerli, W. Diagnosis and treatment of infections associated with fracture-fixation devices. Injury 2006, 37 (Suppl. 2), S59–S66. [Google Scholar] [CrossRef]
  64. AO Surgery Reference—CMF—Trauma—Mandible. Available online: https://surgeryreference.aofoundation.org/cmf/trauma/mandible (accessed on 16 January 2022).
  65. Zalavras, C.G.; Marcus, R.E.; Levin, L.S.; Patzakis, M.J. Management of open fractures and subsequent complications. Instr. Course Lect. 2008, 57, 51–63. [Google Scholar] [CrossRef] [PubMed]
  66. Foster, A.L.; Moriarty, T.F.; Zalavras, C.; Morgenstern, M.; Jaiprakash, A.; Crawford, R.; Burch, M.A.; Boot, W.; Tetsworth, K.; Miclau, T.; et al. The influence of biomechanical stability on bone healing and fracture-related infection: The legacy of Stephan Perren. Injury 2021, 52, 43–52. [Google Scholar] [CrossRef]
  67. Andreasen, J.O.; Storgård Jensen, S.; Kofod, T.; Schwartz, O.; Hillerup, S. Open or closed repositioning of mandibular fractures: Is there a difference in healing outcome? A systematic review. Dent. Traumatol. 2008, 24, 17–21. [Google Scholar] [CrossRef] [PubMed]
  68. Metsemakers, W.J.; Moriarty, T.F.; Morgenstern, M.; Kuehl, R.; Borens, O.; Kates, S.; Richards, R.G.; Verhofstad, M. Letter to the Editor: New Definition for Periprosthetic Joint Infection: From the Workgroup of the Musculoskeletal Infection Society. Clin. Orthop. Relat. Res. 2016, 474, 2726–2727. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  69. Centers for Disease Control and Prevention, National Healthcare Safety Network. Surveillance for Surgical Site Infection Events. 2022. Available online: https://www.cdc.gov/nhsn/pdfs/pscmanual/9pscssicurrent.pdf (accessed on 10 March 2022).
  70. Zalavras, C.G.; Aerden, L.; Declercq, P.; Belmans, A.; Metsemakers, W.J. Ninety-Day Follow-up Is Inadequate for Diagnosis of Fracture-related Infections in Patients with Open Fractures. Clin. Orthop. Relat. Res. 2022, 480, 139–146. [Google Scholar] [CrossRef]
  71. Geller, A.I.; Lovegrove, M.C.; Shehab, N.; Hicks, L.A.; Sapiano, M.R.P.; Budnitz, D.S. National Estimates of Emergency Department Visits for Antibiotic Adverse Events Among Adults—United States, 2011–2015. J. Gen. Intern. Med. 2018, 33, 1060–1068. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  72. Branch-Elliman, W.; O’Brien, W.; Strymish, J.; Itani, K.; Wyatt, C.; Gupta, K. Association of Duration and Type of Surgical Prophylaxis with Antimicrobial-Associated Adverse Events. JAMA Surg. 2019, 154, 590–598. [Google Scholar] [CrossRef]
  73. Oppelaar, M.C.; Zijtveld, C.; Kuipers, S.; Oever, J.T.; Honings, J.; Weijs, W.; Wertheim, H.F.L. Evaluation of Prolonged vs. Short Courses of Antibiotic Prophylaxis Following Ear, Nose, Throat, and Oral and Maxillofacial Surgery: A Systematic Review and Meta-analysis. JAMA Otolaryngol.—Head Neck Surg. 2019, 145, 610–617. [Google Scholar] [CrossRef] [PubMed]
  74. Declercq, P.; Zalavras, C.; Nijssen, A.; Mertens, B.; Mesure, J.; Quintens, J.; De Ridder, T.; Belmans, A.; Nijs, S.; Spriet, I.; et al. Impact of duration of perioperative antibiotic prophylaxis on development of fracture-related infection in open fractures. Arch. Orthop. Trauma. Surg. 2021, 141, 235–243. [Google Scholar] [CrossRef] [PubMed]
  75. Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States. 2019. Available online: https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf (accessed on 17 January 2022).
Antibiotics 11 00483 g001 550
Figure 1. PRISMA 2020 flow diagram [21].
Figure 1. PRISMA 2020 flow diagram [21].
Antibiotics 11 00483 g001
Table
Table 1. Characteristics of included studies: Lower facial third (mandibular) fractures.
Table 1. Characteristics of included studies: Lower facial third (mandibular) fractures.
AuthorRisk of Bias *Open or Closed FracturesTreatmentNAntibiotic TypeComparison
Antibiotic Regimen for All Patients		Outcome
(IR = Infection Incidence Rate)		Follow-Up
Randomized controlled trials
Surgically treated fractures
Campos
2015
(Part I)		High risk of biasNRSurgical (NS)31cefazolinPostoperative Ab every 6 h for 24 h vs. no postoperative Ab
All patients received Ab 20 min before surgery.		IR: 24 h postoperative Ab 5.6%,
no postoperative Ab 38.5%
Significant difference between the regimens.		6 w
Chole
1987
(Part I)		High risk of biasOpen and closedORIF and CR-MMF79cefazolinAb 1 h preoperatively and 8 h later vs. no AbIR: Ab 13.2 %, no Ab 43.9%
Significant difference between the regimens.		30 d
Baliga
2014
(Part I)		High risk of biasNRORIF30cefotaxime,
metronidazole		5 d postoperative Ab vs. no postoperative Ab
All patients received Ab pre- and intra-operatively		IR: Ab group 3.3%; no Ab group 3.3%
No significant difference between the regimens.		3 w
Abubaker 2001High risk of biasOpen and closedORIF and CR-MMF30penicillin G and
penicillin VK		5 d postoperative Ab vs. no prolonged postoperative Ab
All patients received Ab every 4 h preoperatively, intraoperatively and 12 h postoperatively		IR: 5 d postoperative Ab 14.3%,
no prolonged postoperative Ab 12.5%
No significant difference between the regimens.		6 w
Perepa
2018		High risk of biasNRORIF144amoxicillin/
clavulanic acid, metronidazole		5 d postoperative Ab vs. no prolonged postoperative Ab
All patients received preoperative Ab and 1 dose iv postoperative		IR: 5 d postoperative Ab 20.5%,
no prolonged postoperative Ab 20%
No significant difference between the regimens.		3 m
Schaller
2013		High risk of biasNRORIF59amoxicillin/
clavulanic acid		5 d postoperative Ab vs. no prolonged postoperative Ab
All patients received Ab from admission until 24 h postoperatively		IR: 5 d postoperative Ab 20%,
no prolonged postoperative Ab 21%
No significant difference between the regimens.		6 m
Miles
2006		High risk of biasOpen and closedORIF181penicillin G,
metronidazole,
cephalosporins,
cefazolin,
clindamycin		5–7 d postoperative Ab
vs. no postoperative Ab
All patients received Ab from diagnosis until surgery and intraoperatively		IR: 5–7 d postoperative Ab 9.9%,
no postoperative Ab 14.0%
No significant difference between the regimens.		5 w
Retrospective cohort studies
Surgically treated fractures
Lovato
2009		Serious risk of biasOpen and closedORIF and CR-MMF150cefazolin, cefalexin, cefepime, cefotetan, clindamycin, doxycycline, imipenem, penicillin, amoxicillin/clavulanic acid, amoxicillin/sulbactam,
piperacillin/tazobactam,
unknown (18%)		≤24 h postoperative Ab vs. >24 h postoperative Ab (24 h–10 d)
All patients received perioperative Ab for ≤24 h		IR: <24 h postoperative Ab 13.33%,
>24 h postoperative Ab 10.67%
No significant difference between the regimens.		6 w
Mottini
2014
(Part I)		Serious risk of biasNRNR115amoxicillin/
clavulanic acid or clindamycin		≥5 d postoperative Ab vs. no prolonged postoperative Ab
All patients received Ab from admission until 24 h postoperatively.		IR: ≥5 d postoperative Ab 9.59%,
no prolonged postoperative Ab 11.90%
No significant difference between the regimens.		6 m
Domingo 2016Critical risk of biasOpen and closedORIF and CR-MMF359cefazolin, cefalexin, cefadroxil, cefepime ceftriaxone, amoxicillin, amoxicillin/clavulanic acid, amoxicillin/sulbactam, moxifloxacin, levofloxacin, ciprofloxacin, bactrim, clindamycin, combinationsPostoperative Ab (1–3 d, 4–7 d, >7 d, or unknown)
vs. no postoperative Ab
Patients received variable or no preoperative Ab.		IR: postoperative Ab 14.7%,
no postoperative Ab 9.6%
No significant difference between the regimens.		4 w
Zosa
2021
(Part I)		Serious risk of biasOpen and closedNR42First- generation cephalosporins,
β-lactam antibiotics with β-lactamase inhibitors, clindamycin, penicillin, vancomycin, tetracycline, and combinations.		<24 h Ab (incl. single-dose or no Ab) vs. >24 h Ab (median 4 d (range 1–14 d))IR: <24 h Ab 4.0%, >24 h Ab 29.4%
Significantly higher infection rates for longer courses.		1–30 m
(8 m)
(Follow-up rate 93.6%)
Abbreviations: N: number of patients; IR: infection incidence rate; RCT: randomized controlled trial; RCS: retrospective cohort study; NR: not reported; NS: not specified; ORIF: open reduction and internal fixation; CR-MMF: closed reduction–maxillomandibular fixation; Ab: antibiotics; min: minutes, h: hours, w: weeks; m: months; incl.: including. * As evaluated by the Risk Of Bias In Non-Randomized Studies assessment tool (ROBINS-I) [22], or the revised Cochrane Risk-of-Bias tool for randomized trials (RoB 2) [23].
Table
Table 2. Characteristics of included studies: Middle and upper facial third fractures.
Table 2. Characteristics of included studies: Middle and upper facial third fractures.
AuthorRisk of Bias *Fracture LocationOpen or Closed FracturesNAntibiotic TypeComparison
Antibiotic Regimen for All Patients		Outcome
(IR = Infection Incidence Rate)		Follow-Up
Randomized controlled trials
Surgically treated fractures
Campos
2015
(Part II)		High risk of biasMidface, upper faceNR44cefazolinPostoperative Ab every 6 h for 24 h vs. no postoperative Ab
All patients received Ab 20 min before surgery.		IR: 24 h postoperative Ab 0%,
no postoperative Ab Ab 3.3%
No significant difference between the regimens		6 w
Chole
1987
(Part II)		High risk of biasZygoma,
Le Fort		NR101cefazolin1 h preoperative and 8 h later vs. no AbIR: 0%
No significant difference between the regimens.		30 d
Baliga
2014
(Part II)		High risk of biasZygomaNR30cefotaxime, metronidazole5 d postoperative Ab vs. no postoperative Ab
All patients received Ab pre- and intra-operatively		IR: 0.00%
No significant difference between the regimens.		3 w
Jang
2019		High risk of biasNasal boneClosed30cefazedone, cephalexinAb 4 d postoperatively vs. no postoperative Ab
All patients received one dose of Ab at induction.		IR: 0%
No significant difference between the regimens.		30 d
Zix
2013		High risk of biasOrbitNR62amoxicillin/
clavulanic acid		5 d postoperative Ab vs. no prolonged postoperative Ab
All patients received Ab from admission until 24 h postoperatively.		IR: 5 d postoperative Ab 6.8%,
no prolonged postoperative Ab 3.2%
No significant difference between the regimens.		6 m
Soong
2014		High risk of biasLe Fort, zygomaNR94amoxicillin/
clavulanic acid		5 d postoperative Ab vs. no prolonged postoperative Ab
All patients received Ab from admission until 24 h postoperatively.		IR: 5 d postoperative Ab 4.4%,
no prolonged postoperative Ab 4.1%
No significant difference between the regimens.		6 m
Retrospective cohort studies
Surgically treated fractures
Reiss
2017		High risk of biasOrbitNR172cefazolin, cephalexin, cefdinir, ceftriaxone, penicillin, amoxicillin, amoxicillin/clavulante, ampicillin/sulbactam,
piperacillin/tazobactam, clindamycin ciprofloxacin, levofloxacin, azithromycin, vancomycin		No Ab,
vs. one dose of Ab,
vs. 5–7 days of Ab,
vs. 10–14 d of Ab		IR: 0.00%
No significant difference between the regimens.		<1 w–>3 m
Mottini
2014
(Part II)		Serious risk of biasZygoma, orbit, Le FortNR339amoxicillin/
clavulanic acid or clindamycin		≥5 d postoperative Ab vs. no prolonged postoperative Ab
All patients received Ab from admission until 24 h postoperatively.		IR: ≥5 d postoperative Ab 0.4%,
no prolonged postoperative Ab 0%,
No significant difference between the regimens.		6 m
Zosa
2021
(Part II)		Serious risk of biasMidfaceOpen and closed49First- generation cephalosporins,
β-lactam antibiotics with β-lactamase inhibitors, clindamycin, penicillin, vancomycin, tetracycline, and combinations.		<24 h Ab (incl. single-dose or no Ab) vs. >24 h Ab (median 4 d (range 1–14 d))IR: <24 h Ab 7.3%, >24 h Ab 12.5%
No significant difference between the regimens.		1–30 m
(8 m)
(Follow-up rate 93.6%)
Conservatively (non-surgically) treated fractures
Malekpour
2016		High risk of biasMaxilla,
orbit		Closed289ampicillin/sulbactam, amoxicillin/clavulanate, or combinations,
clindamycin		No Ab,
vs. 1–5 d of Ab,
vs. >5 days of Ab		IR: 0.00%
No significant difference between the regimens.		2 w
Abbreviations: N: number of patients; IR: infection incidence rate; RCT: randomized controlled trial; RCS: retrospective cohort study; NR: not reported; NS: not specified; Ab: antibiotics; min: minutes, h: hours, w: weeks; m: months; incl.: including. * As evaluated by the Risk Of Bias In Non-Randomized Studies assessment tool (ROBINS-I) [22], or the revised Cochrane Risk-of-Bias tool for randomized trials (RoB 2) [23].
Table
Table 3. Outcome description: definition of infection.
Table 3. Outcome description: definition of infection.
AuthorOutcome Description: Definition of Infection
Lovato 2009
Reiss 2017		Not reported
Domingo 2016
Perepa 2018
Schaller 2013
Mottini 2014
Soong 2014
Zix 2013		CDC guidelines
Miles 2006
Perepa 2018		Clinical criteria: Grade I: Erythema around suture line < 1 cm; Grade II: 1–5 cm of erythema; Grade III: > 5 cm of erythema and induration; Grade IV: Purulent drainage spontaneously or by incision; Grade V: Fistulae
Radiological criteria: Grade I: Ossification of fracture site/no change from initial injury; Grade II: Radiolucenties localized to hardware or necrotic tooth; Grade III: Generalized radiolucenties of fracture or hardware
Abubaker 2001
Baliga 2014
Campos 2015		Purulent drainage from the surgical or fracture site, increased facial Swelling beyond postoperative day 7, fistula formation at the surgical or fracture site, with evidence of drainage, fever associated with local evidence of infection (swelling, erythema, or tenderness).
Jang 2019Nasal bone infection: Heating sensation, swelling, persistent pain, purulent nasal drainage, septal abscess, vital sign showing general signs of infection (not specified).
Malekpour 2016Warmth, redness, abscess, fever, purulent drainage, or patients who were started on antibiotics at follow-up.
Chole 1987The fracture site, incision, or adjacent area showed clinical signs of infection, including purulent drainage, abscess formation, or cellulitis.
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Goormans, F.; Coropciuc, R.; Vercruysse, M.; Spriet, I.; Willaert, R.; Politis, C. Systemic Antibiotic Prophylaxis in Maxillofacial Trauma: A Scoping Review and Critical Appraisal. Antibiotics 2022, 11, 483. https://doi.org/10.3390/antibiotics11040483

AMA Style

Goormans F, Coropciuc R, Vercruysse M, Spriet I, Willaert R, Politis C. Systemic Antibiotic Prophylaxis in Maxillofacial Trauma: A Scoping Review and Critical Appraisal. Antibiotics. 2022; 11(4):483. https://doi.org/10.3390/antibiotics11040483

Chicago/Turabian Style

Goormans, Femke, Ruxandra Coropciuc, Maximilien Vercruysse, Isabel Spriet, Robin Willaert, and Constantinus Politis. 2022. "Systemic Antibiotic Prophylaxis in Maxillofacial Trauma: A Scoping Review and Critical Appraisal" Antibiotics 11, no. 4: 483. https://doi.org/10.3390/antibiotics11040483

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