Orthognathic surgical procedures are common surgical interventions in the field of maxillofacial surgery that allow the correction of skeletal malocclusion to improve occlusal function, facial harmony, and aesthetics.1Wallach M. Cuéllar J. Verdugo-Paiva F. Alarcón A. Long-term antibiotic prophylaxis regimen compared to short-term antibiotic prophylaxis regimen in patients undergoing orthognathic surgery. Orthognathic surgery is generally considered safe, however it continues to be associated with numerous complications. What is more, postoperative wound infections are amongst the most common and most severe sequelae that may potentially impair a patient’s wellbeing and jeopardize the surgical outcome. These wound infections particularly occur with intraoral surgical approaches used in orthognathic surgery.2Davis C.M. Gregoire C.E. Steeves T.W. Demsey A. Prevalence of surgical site infections following orthognathic surgery: a retrospective cohort analysis. The advantages of intraoral approaches include the avoidance of extraoral scarring while maintaining adequate visibility and surgical access to the operating area. Additionally, the risk of injury to the facial nerve and regional blood vessels is minimized. However, the oral cavity is densely populated with bacteria, which may favour the occurrence of surgical site infections (SSIs). This issue has been highlighted by the American Society of Health System Pharmacists (ASHP), and as a result, orthognathic surgery has been categorized as clean-contaminated surgery.3A systematic review of latest evidence for antibiotic prophylaxis and therapy in oral and maxillofacial surgery.The SSI rate reported in orthognathic surgery ranges from 1.4% to 33.4%.5Cousin A.S. Bouletreau P. Giai J. Ibrahim B. Louvrier A. Sigaux N. Severity and long-term complications of surgical site infections after orthognathic surgery: a retrospective study. Peterson6Antibiotic prophylaxis against wound infections in oral and maxillofacial surgery. estimated the rate of SSIs to amount to 10–15% without antibiotic prophylaxis. This rate was reduced to 1% when perioperative antibiotic prophylaxis was administered. These results correspond to those of Flynn and Lawrence,7Antimicrobial prophylaxis. who reported that a lower incidence of SSIs may be achieved when using standard aseptic techniques and antibiotic prophylaxis. According to Cousin et al.,5Cousin A.S. Bouletreau P. Giai J. Ibrahim B. Louvrier A. Sigaux N. Severity and long-term complications of surgical site infections after orthognathic surgery: a retrospective study. SSIs following orthognathic surgery occurred in 8% of cases. Antibiotic prophylaxis was administered in both studies. The importance of antibiotics was further demonstrated by Zijderveld et al.,8Zijderveld S.A. Smeele L.E. Kostense P. Bram D. Preoperative antibiotic prophylaxis in orthognathic surgery: a randomized, double-blind, and placebo-controlled clinical study. who described a significantly increased risk of SSIs after orthognathic surgery without antibiotic prophylaxis. This is consistent with other research on this topic, which has shown a reduction in the infection rate when antibiotic prophylaxis was used, regardless of the regimen applied.4Tan S.K. Lo J. Zwahlen R.A. Perioperative antibiotic prophylaxis in orthognathic surgery: a systematic review and meta-analysis of clinical trials., 9Oomens M.A.E.M. Verlinden C.R.A. Goey Y. Forouzanfar T. Prescribing antibiotic prophylaxis in orthognathic surgery: a systematic review., 10Kreutzer K. Storck K. Weitz J. Current evidence regarding prophylactic antibiotics in head and neck and maxillofacial surgery.Hence, the clinical guidelines published by the American and British associations of oral and maxillofacial surgeons (AAOMS, BAOMS) recommend the judicious use of antibiotic prophylaxis to reduce the risk of postoperative complications.1Wallach M. Cuéllar J. Verdugo-Paiva F. Alarcón A. Long-term antibiotic prophylaxis regimen compared to short-term antibiotic prophylaxis regimen in patients undergoing orthognathic surgery. However, no consensus has yet been reached regarding the type, dose, interval, and duration of prophylactic antibiotics.1Wallach M. Cuéllar J. Verdugo-Paiva F. Alarcón A. Long-term antibiotic prophylaxis regimen compared to short-term antibiotic prophylaxis regimen in patients undergoing orthognathic surgery., 4Tan S.K. Lo J. Zwahlen R.A. Perioperative antibiotic prophylaxis in orthognathic surgery: a systematic review and meta-analysis of clinical trials., 11Danda A.K. Wahab A. Narayanan V. Siddareddi A. Single-dose versus single-day antibiotic prophylaxis for orthognathic surgery: a prospective, randomized, double-blind clinical study. Numerous different prophylactic antibiotic regimens are currently in use, but none have proven to be superior in reducing SSIs.4Tan S.K. Lo J. Zwahlen R.A. Perioperative antibiotic prophylaxis in orthognathic surgery: a systematic review and meta-analysis of clinical trials. Moreover, the use of antibiotics should be minimized to prevent antimicrobial resistance and side effects (e.g. anaphylaxis and serum sickness), while ensuring the optimal efficacy for the prevention of SSIs.4Tan S.K. Lo J. Zwahlen R.A. Perioperative antibiotic prophylaxis in orthognathic surgery: a systematic review and meta-analysis of clinical trials., 5Cousin A.S. Bouletreau P. Giai J. Ibrahim B. Louvrier A. Sigaux N. Severity and long-term complications of surgical site infections after orthognathic surgery: a retrospective study., 12Van Camp P. Verstraete L. Van Loon B. Scheerlinck J. Nout E. Antibiotics in orthognathic surgery: a retrospective analysis and identification of risk factors for postoperative infection., 13Tan S.K. Lo J. Zwahlen R.A. Are postoperative intravenous antibiotics necessary after bimaxillary orthognathic surgery? A prospective, randomized, double-blind, placebo-controlled clinical trial. Antibiotic resistance, a major global health threat, needs highlighting in this context.14Bengtsson-Palme J. Kristiansson E. Larsson D.G.J. Environmental factors influencing the development and spread of antibiotic resistance.

The purpose of this study was to compare two common antibiotic regimens for the prevention of postoperative SSIs in orthognathic surgery. The aim is to reduce the antibiotic medication to a necessary minimum while still guaranteeing optimal SSI prophylaxis.

Materials and methodsStudy design

This retrospective study was conducted in the Division of Oral and Maxillofacial Surgery at the Medical University of Graz in 2017 as part of a quality improvement project that aims to reduce the amount of prophylactic antibiotics administered in orthognathic surgery (ethical approval, 30–356 ek17/18). In this regard, the standard perioperative antibiotic regimen deployed in the study department was changed from a prolonged 5-day antibiotic prophylaxis regimen to a single-dose regimen.

To identify possible differences in the efficacy of prophylactic antibiotics in preventing SSIs, these antibiotic regimens were compared by means of well-defined primary and secondary outcome measures. Patients who met defined inclusion criteria and who had received single-dose antibiotic prophylaxis (SDAP group) were matched to a control group of patients who had received prolonged antibiotic prophylaxis (PAP group); the groups were similar in sample size and surgical techniques applied.

Patients

Male and female patients who underwent bilateral sagittal split ramus osteotomy (BSSO) or bimaxillary surgery (BIMAX) during the 5 months before or after the change in antibiotic protocol were screened for eligibility. Only patients who were classified as either ASA I or ASA II according to the physical status classification of the American Society of Anesthesiologists (ASA), were included in the study. Reasons for patient exclusion included the following: incomplete follow-up (less than 6 months), additional surgical procedures performed in the same operative session (e.g. genioplasty, rhinoplasty), systemic diseases associated with reduced immunity (e.g. lupus erythematosus or HIV), and diabetes mellitus.

Perioperative management and surgical procedureIn both the PAP and SDAP groups, intravenous (IV) antibiotic prophylaxis was started within 60 min before mucosal incision. Further information on the regimens applied is given in Table 1.

Table 1The antibiotic regimens used in the two study groups. The first dose was given within 60 min before mucosal incision in both groups.

AMC, amoxicillin–clavulanate; IV, intravenous; PAP, prolonged-antibiotic prophylaxis; SAM, ampicillin–sulbactam; SDAP, single-dose antibiotic prophylaxis.

Preparation of the intraoral surgical site was performed using chlorhexidine gluconate 0.1%; for extraoral prepping, octenidine dihydrochloride was used.

All operations were performed by experienced maxillofacial surgeons in accordance with the standard operating procedures established in the department. The Le Fort I osteotomy was performed as described by Bell and Schendel.15Biologic basis for modification of the sagittal ramus split operation. Four miniplates (MODUS_orthognathics 1.5; Medartis AG, Basel, Switzerland) were used to stabilize the maxillary osteotomy. The BSSO was performed according to Hunsuck.16A modified intraoral sagittal splitting technic for correction of mandibular prognathism. Mandibular fixation involved the placement of three bicortical screws on each side via an extraoral (transmasseteric) approach using a trocar. Wound closure was achieved with resorbable sutures; no tissue glue or surgical drains were used.

Specific instructions on how to maintain adequate postoperative oral hygiene were given to each patient (e.g. the use of antiseptic mouthwash (chlorhexidine gluconate 0.1%), a soft toothbrush etc.). Pain management included ibuprofen IV and oral metamizole as basic analgesia and piritramide IV as an add-on for 3 days.

The patients were examined on a daily basis during their inpatient stay. Once discharged, weekly follow-up appointments were arranged over a period of 6 weeks to check healing, signs of infection, oral hygiene, and occlusion.

Outcome measuresThe primary outcome measure was the overall SSI rate over a period of 6 months. Furthermore, the severity of the SSIs was quantified using the Clavien–Dindo classification.17The Clavien–Dindo classification of surgical complications. This well-validated tool defines complications as any deviation from the normal postoperative course. Depending on the need for a therapeutic intervention and the level of that intervention, the classification differentiates five grades, of which grades III and IV are each divided into subgrades a and b (Table 2).Table 2The Clavien–Dindo classification,17The Clavien–Dindo classification of surgical complications. which was used to categorize surgical site infections that occurred in the study cohort.

Secondary outcomes included the localization of the SSI, duration of surgery, length of in-hospital stay (LOS), and time to onset of infection.

Statistical analysis

The statistical analysis was conducted using IBM SPSS Statistics software version 26 (IBM Corp., Armonk, NY, USA). Fisher’s exact test and the Mann–Whitney U-test were applied to compare the demographic data between the PAP and SDAP groups and to investigate potential differences in the rate and severity of SSIs. Parameters such as the operation time needed and the localization of the SSIs were also analysed using these tests. The χ2 test was used to analyse the SSI rate in relation to the various antibiotic agents used.

ResultsPatientsA total of 99 patients (68 female, 31 male; mean age 30.1 ± 8.6 years) were included in the final analysis, 50 of whom received single-dose antibiotic prophylaxis (SDAP group) and 49 of whom received a prolonged 5-day antibiotic prophylaxis regimen (PAP group). There was no significant difference between the two groups in terms of age, sex, the duration of surgery, or the length of inpatient stay (Table 3, Table 4). In terms of the surgical techniques applied, 55 of the 99 study patients underwent BIMAX and 44 received a BSSO. BIMAX was performed in 27 patients in the PAP group and 28 patients in the SDAP group, while 22 patients in each group underwent BSSO.

Table 3Relevant patient data for the study cohort. There was no statistically significant difference between the PAP and SDAP groups for any of the parameters assessed.

BIMAX, bimaxillary surgery; BSSO, bilateral sagittal split osteotomy; LOS, length of stay; PAP, prolonged-antibiotic prophylaxis; SD, standard deviation; SDAP, single-dose antibiotic prophylaxis.

Table 4Duration of the surgery according to the study group, type of surgery performed, and occurrence of surgical site infection.

BIMAX, bimaxillary surgery; BSSO, bilateral sagittal split osteotomy; PAP, prolonged-antibiotic prophylaxis; SD, standard deviation; SDAP, single-dose antibiotic prophylaxis; SSI, surgical site infection.

Primary outcome—the SSI rate

Overall, 12 infections were observed when analysing the data without subgrouping patients according to the antibiotic regimen applied. This equates to an SSI rate of 12.1%. When comparing the SSI rate between the PAP group and SDAP group, no statistically significant difference was observed between the two antibiotic regimens (P = 0.380): five infections (10.2%) occurred in the PAP group, while seven infections (14%) occurred in the SDAP group.

SSI rate according to the antibiotic agent

Amoxicillin–clavulanate was the most common antibiotic administered (80/99: 35/49 in the PAP group, 45/50 in the SDAP group). Ampicillin–sulbactam was given to 11 patients (10/49 in the PAP group, 1/50 in the SDAP group) and eight patients were given clindamycin (four patients in each group). Ten of the 12 SSIs occurred in patients on amoxicillin–clavulanate (10/80, 12.5%). Two infections were found in patients on clindamycin (2/8, 25%). There was no statistically significant difference in the occurrence of SSIs between the antibiotics used (P = 0.215).

Within the PAP group, four SSIs occurred in patients on amoxicillin–clavulanate (4/35, 11.4%) and one SSI in a patient on clindamycin (1/4, 25%). Regarding the SDAP group, six SSIs were seen in patients who had received amoxicillin–clavulanate (6/45, 13.3%) and one SSI in a patient on clindamycin (1/4, 25%).

Severity of the SSIsThe 12 SSIs included three cases of persistent swelling (25%), one sinusitis (8.3%), four cases of wound dehiscence (33.3%), and four abscesses (33.3%) (Fig. 1).

Fig. 1The numbers and types of surgical site infections that occurred.

Regarding the Clavien–Dindo classification, three complications (3/12) were rated as mild and were categorized as grade I; a further three complications (3/12) were classified as grade II. No surgical intervention was required with regard to any of these SSIs. However, systemic antibiotics had to be re-introduced as a therapeutic measure in the grade II cases. Six SSIs (6/12, 50%) met the criteria for grade IIIa of the Clavien–Dindo classification, as surgical treatment under local anaesthesia was deemed necessary: an intraoral mucosal incision was required to ensure adequate drainage of the surgical site.

The prevalence of grade I and grade II complications within the entire study population was 3.0% and 3.0%, respectively, while the prevalence of grade IIIa complications was 6.1%.

The severity of the SSIs did not differ significantly between the PAP and SDAP groups (P = 0.842).

Secondary outcomes—the SSI rate according to the localization of the SSI, surgical procedure, and duration of surgery

Regarding the localization of the 12 SSIs, nine (75%) were located in the lower jaw and three were situated in the upper jaw (25%). This disparity in the SSI rate between mandibular and maxillary surgical sites was not statistically significant (P = 0.583). In the PAP group, four of the five SSIs (80%) were located in the mandible and one (20%) was located in the maxilla. In the SDAP group, five of the seven SSIs (71.4%) affected the mandible and two (28.6%) were located in the maxilla.

Nine of the 12 SSIs (75%) occurred in patients who underwent BIMAX and three (25%) occurred in individuals who received a BSSO. Within the PAP group, all five SSIs (100%) were associated with BIMAX. Regarding the SDAP group, four of seven infections (57.1%) occurred following BIMAX and three (42.9%) following BSSO.

The average duration of surgery amounted to 117.4 ± 69.8 min. No statistically significant difference in operating time was seen when comparing the PAP group with the SDAP group: 125.2 ± 79.3 min vs 111.7 ± 59.0 min, respectively (P = 0.353). Unsurprisingly, BIMAX was associated with a significantly longer operating time in comparison to BSSO: 149.6 ± 73.9 min vs 80.7 ± 39.0 min, respectively (P P = 0.088) (Table 4). However, within the PAP group, a significantly longer operating time was detected in cases where SSIs were observed in comparison to those where no infection was reported: 200.2 ± 79.2 min vs 115.6 ± 75.0 min (P = 0.023).Onset of the SSIsThe SSIs occurred on average 37.4 ± 42.6 days after surgery. In the PAP group, SSIs were found to occur 23.1 ± 30.5 days postoperatively, whereas in the SDAP group the SSIs were noted to occur 57.4 ± 52.3 days after surgery. No statistically significant difference was observed when comparing the two groups (P = 0.181) (Fig. 2).

Fig. 2The mean time period between orthognathic surgery and the onset of infection: 57.4 ± 52.3 days in the prolonged-antibiotic prophylaxis (PAP) group vs 23.1 ± 30.5 days in the single-dose antibiotic prophylaxis (SDAP) group. No statistically significant difference was detected (P = 0.181).

Duration of hospitalization (LOS)LOS amounted to an average of 5.4 ± 1.1 days in the PAP group and 5.3 ± 1.2 days in the SDAP group (Fig. 3). No statistically significant difference was found with respect to this parameter (P = 0.863). Patients with SSIs had a mean LOS of 5.9 days, whereas patients without SSIs were hospitalized for a mean 5.3 days (P = 0.251).

Fig. 3The mean length of inpatient stay. No statistically significant difference was found when comparing the prolonged-antibiotic prophylaxis (PAP) group with the single-dose antibiotic prophylaxis (SDAP) group (P = 0.863).

DiscussionDue to the highly elective nature of orthognathic surgery, reducing the rate of complications to a minimum is paramount. Besides haemorrhage, nerve transection, and nasal septum deviations, SSIs are amongst the most frequent complications.1Wallach M. Cuéllar J. Verdugo-Paiva F. Alarcón A. Long-term antibiotic prophylaxis regimen compared to short-term antibiotic prophylaxis regimen in patients undergoing orthognathic surgery., 18Effectiveness of postoperative antibiotics in orthognathic surgery: a meta-analysis. Among other reasons, this can be attributed to the use of intraoral surgical approaches in orthognathic surgery, which may result in contamination with endogenous bacteria. The prevalence of SSIs ranges between 1% and 33.4%.5Cousin A.S. Bouletreau P. Giai J. Ibrahim B. Louvrier A. Sigaux N. Severity and long-term complications of surgical site infections after orthognathic surgery: a retrospective study., 6Antibiotic prophylaxis against wound infections in oral and maxillofacial surgery. The SSI rate of 12.1% found in this study is within this range.In a clinical trial performed in 1999, Bentley19Antibiotic prophylaxis in orthognathic surgery: a l-day versus 5-day regimen. found that a 5-day antibiotic regimen was significantly more effective in preventing postoperative infection when compared to a 1-day regimen. Davis et al.20Davis C.M. Gregoire C.E. Davis I. Steeves T.W. Prevalence of surgical site infections following orthognathic surgery: a double-blind, randomized controlled trial on a 3-day versus 1-day postoperative antibiotic regimen. described a significant reduction in SSIs with a 3-day regimen when compared to a 1-day regimen. Moreover, prolonged antibiotic prophylaxis has been described as advantageous in reducing the infection rate compared to preoperative single-dose antibiotic prophylaxis.1Wallach M. Cuéllar J. Verdugo-Paiva F. Alarcón A. Long-term antibiotic prophylaxis regimen compared to short-term antibiotic prophylaxis regimen in patients undergoing orthognathic surgery., 18Effectiveness of postoperative antibiotics in orthognathic surgery: a meta-analysis. Furthermore, numerous others have successfully shown the benefit of long-term antibiotic prophylaxis over short-term use in the prevention of SSI.1Wallach M. Cuéllar J. Verdugo-Paiva F. Alarcón A. Long-term antibiotic prophylaxis regimen compared to short-term antibiotic prophylaxis regimen in patients undergoing orthognathic surgery., 18Effectiveness of postoperative antibiotics in orthognathic surgery: a meta-analysis. Danda et al.11Danda A.K. Wahab A. Narayanan V. Siddareddi A. Single-dose versus single-day antibiotic prophylaxis for orthognathic surgery: a prospective, randomized, double-blind clinical study. even described the clinical advantage of a 1-day regimen compared to a single-dose antibiotic prophylaxis; however, no statistical difference was found.In contrast, Ghantous et al.21Ghantous Y. Araidy S. Yaffe V. Mirochnik R. El-Raziq M.A. El-Naaj I.A. The efficiency of extended postoperative antibiotic prophylaxis in orthognathic surgery: a prospective, randomized, double-blind, placebo-controlled clinical trial. compared a prolonged 5-day regimen to single-dose antibiotic prophylaxis, which yielded no statistically significant differences between the two groups. As a result, their study group cautiously proposed a reduction in antibiotic administration in healthy patients. Lindeboom et al.22Lindeboom J.A.H. Baas E.M. Kroon F.H.M. Prophylactic single-dose administration of 600 mg clindamycin versus 4-time administration of 600 mg clindamycin in orthognathic surgery: a prospective randomized study in bilateral mandibular sagittal ramus osteotomies. found no significant difference either, when comparing a single-dose and four-time administration of clindamycin. In addition, several other authors have noted no benefit for extended postoperative antibiotic prophylaxis.8Zijderveld S.A. Smeele L.E. Kostense P. Bram D. Preoperative antibiotic prophylaxis in orthognathic surgery: a randomized, double-blind, and placebo-controlled clinical study., 11Danda A.K. Wahab A. Narayanan V. Siddareddi A. Single-dose versus single-day antibiotic prophylaxis for orthognathic surgery: a prospective, randomized, double-blind clinical study. With regard to the incidence of SSIs in clean-contaminated wounds in maxillofacial surgery, Villanueva et al.23Villanueva M.J. Araya C.I. Yanine M.N. Short-term antibiotic prophylaxis versus long-term antibiotic prophylaxis in major clean-contaminated maxillofacial surgery. reported no significant difference between single-dose antibiotic prophylaxis and prolonged application of prophylactic antibiotics. Similarly, no statistically significant difference in the occurrence of SSIs was found in the present study when comparing a prolonged 5-day regimen to single-dose antibiotic prophylaxis.Van Camp et al.12Van Camp P. Verstraete L. Van Loon B. Scheerlinck J. Nout E. Antibiotics in orthognathic surgery: a retrospective analysis and identification of risk factors for postoperative infection. argue against the need for prolonged antibiotic prophylaxis as it is associated with numerous drawbacks, such as disruption of the patient microbial flora, pharmacological adverse events, economic consequences, and, particularly, antibiotic resistance. In fact, multiple trials have shown that even single-dose or short-term application (3 days) of amoxicillin increases the load of resource-resistant viridans streptococci in saliva.24Khalil D. Hultin M. Rashid M.U. Lund B. Oral microflora and selection of resistance after a single dose of amoxicillin., 25Antibiotic prophylaxis in intraoral orthognathic surgery. Against growing global concerns about antibiotic resistance, Van Camp et al.12Van Camp P. Verstraete L. Van Loon B. Scheerlinck J. Nout E. Antibiotics in orthognathic surgery: a retrospective analysis and identification of risk factors for postoperative infection. specifically advocate the use of single-dose regimens for antibiotic prophylaxis in maxillofacial surgery.In the current study, antibiotics were administered prior to mucosal incision to ensure an adequate tissue concentration at the time of surgery. According to Classen et al.,26Classen D.C. Evans R.S. Pestotnik S.L. Horn S.D. Menlove R.L. Burke J.P. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. the lowest postoperative infection rate is possible when antibiotics are given within 2 h prior to the skin incision. The World Health Organization guidelines from 2016 recommend performing antimicrobial shielding 120 min before mucosal incision. For antibiotics with a short half-life (cephalosporins, penicillins), which are often used in maxillofacial surgery, administration less than 60 min before the start of the procedure is recommended.27Allegranzi B. Zayed B. Bischoff P. Kubilay N.Z. de Jonge S. de Vries F. Gomes S.M. Gans S. Wallert E.D. Wu X. Abbas M. Boermee