Prophylactic antibiotics in septoplasty with intranasal septal splints: A comparative analysis

Postoperative antibiotic therapy is a common practice following septoplasty with intra‐septal splints placement (ISS), even though there is a lack of evidence to support it. We sought to investigate the role of antibiotic therapy in septal surgeries with the placement of ISS.

Intranasal septal splints (ISS) are commonly used in septoplasty to stabilise the reconstructed septum and prevent the formation of synechia during early mucosal healing. 1,2The effectiveness of ISS, when compared to nasal packing, has been well-established in improving nasal airflow and enhancing patient comfort, thereby driving its widespread acceptance and implementation in clinical practice. 3Nonetheless, the introduction of nasal foreign bodies has raised concerns regarding the potential risk of developing local nasal infections and even toxic shock syndrome. 4,5To minimise the risk of postoperative infections, the practice of prescribing postoperative antibiotic therapy following septoplasty with ISS placement has become increasingly common. 6However, the available data on the efficacy of prophylactic antibiotic therapy in the presence of ISS are limited, leaving uncertainty about its true benefits.
The risk of post-septoplasty infection is estimated at less than 5%. 7,8Notably, even in cases involving nasal foreign bodies such as ISS, the incidence of postoperative infection remains remarkably low. 9,10These findings raise important considerations about the need for routine antibiotic administration in all cases.Furthermore, research studies have revealed that prophylactic antibiotics often fail to effectively prevent bacterial colonisation and biofilm formation on ISS. 11,12ofilm formation, in particular, poses a significant challenge in the treatment of infections, as it enhances bacterial resistance to antibiotics and contributes to the persistence of the infection. 13Therefore, the indiscriminate use of antibiotics may not only be unnecessary but could also contribute to the development of bacterial resistance, which is a growing concern in the medical field.
5][16] Studies investigating ISS cultures in patients treated with prophylactic antibiotics have revealed the growth of bacterial isolates with acquired antibiotic resistance, including multidrug-resistant gram-negative bacteria. 10These findings highlight the potential risks associated with antibiotic therapy and suggest that the practice of routine prophylactic antibiotic administration in septal surgeries with ISS placement may have unintended consequences.
Considering the limited evidence on the efficacy of prophylactic antibiotics, the potential for bacterial resistance development, and the increasing prevalence of multidrug-resistant infections, it is crucial to conduct further research to investigate the role of antibiotic therapy in septal surgeries with the placement of ISS.The aim of the present study was to address this gap in knowledge and provide valuable insights into the appropriate use of antibiotics in this specific clinical scenario.

| Study design and subjects
The study protocol was approved by the Institutional Research Ethics Committee.Inclusion criteria for the study were adult patients (≥18 years) who had septoplasty with the placement of ISS with or without turbinate reduction, with a minimum follow-up period of 1 month.Patients were excluded from the study in the following cases: Evidence of chronic rhinosinusitis, immunosuppression, or autoimmune diseases, and when septoplasty was performed in addition to sinus surgery or rhinoplasty.The electronic records of all patients who had septoplasty between March 2015 and April 2020 were screened.

| Surgical procedure
All surgeries were carried out under general anaesthesia and performed in an endonasal approach.Deviated nasal septum was treated via submucosal resection, with or without bilateral inferior turbinate reduction.
The initial surgical incision was a standard hemitransfixation or Killian, chosen according to the septal pathology and location of maximal deviation.Polyglactin 910 suture (Vicryl Rapide™; Ethicon-CA, United States) was used to close the mucosal incision lines.Intranasal silicone splints (Mackay/Grimaldi Nasal Splint; Exmoor-United Kingdom) were inserted bilaterally in the nasal cavity at the end of surgery.Transseptal silk suture 2-0 (Perma-Hand Silk ® ; Ethicon-CA, United States) was used to attach the splints to the septum.Nasal packing (Merocel ® ; Medtronic-MN, United States) was inserted at the discretion of the operating surgeon.

| Prophylactic antibiotic therapy and postoperative care
Prophylactic antibiotic therapy was administered at the discretion of the operating surgeon.Three antibiotic treatment groups were identified: (1) a preoperative single-dose IV prophylaxis (group AB-1) was given cefazolin (Cefamezin ® once 1000 mg; Teva Pharmaceutical

Key points
• Patients undergoing septoplasty with the placement of ISS are at increased risk of gram-negative bacterial colonisation, and development of postoperative nasal infection.
• A single preoperative dose of IV antibiotic therapy should be considered the prophylactic treatment of choice for septoplasty with ISS.
• Diabetes is associated with an increased risk of postoperative infection following septoplasty, regardless of antibiotic regimen.
• The detection of Klebsiella pneumonia before surgery was associated with an increased rate of postoperative infection.
• An increase in the rates of bacterial resistance was recorded post-operatively mainly in patients who were treated with antibiotics for 7 days after surgery.Industries-Israel).Clindamycin was used in patients with suspected beta-lactam allergy; (2) daily oral antibiotics until removal of the ISS on postoperative day (POD) 8 (group AB-7) were given cephalexin (Ceforal ® TID 500 mg; Teva Pharmaceutical Industries-Israel) and amoxicillinclavulanate (Augmentin™ BID 875/125 mg; GlaxoSmithKline-United Kingdom), according to the surgeon's preference; and (3) no antibiotic therapy (group AB-0).Nasal packing with Merocel ® when inserted was removed on POD-1.ISS was removed on POD-8.All patients were instructed to perform nasal irrigations using a 10 cc syringe, rinsing each nostril with 0.9% saline solution three times daily for a duration of 3 weeks in the postoperative period.During the initial post-operative visit for splint removal, patients were asked to adhere to the treatment regimen meticulously.
Postoperative local infection was characterised by the presence of nasal cellulitis, vestibulitis, vestibular abscess, septal cellulitis, or septal abscess.

| Bacterial cultures
Bacterial cultures were taken routinely as part of the department's protocol for monitoring infectious diseases.Septal swabs were taken before surgery under sterile conditions.Samples were cultivated in chocolate agar, McConkey agar, TSA with 5% sheep blood agar and thioglycolate medium, and were incubated at 37 C and 5% CO 2 under aerobic conditions.Cultures were evaluated after 24 h.In cases of microbial growth only in thioglycolate medium, subcultures were transferred to agar plates for further incubation under aerobic and anaerobic conditions.Bacterial identification and susceptibility were performed for positive cultures using conventional methods.Positive cultures did not alter prophylactic antibiotic therapy unless clinical signs of infection were observed.Silicone splints were examined for the presence of bacteria after their removal.The splints were removed under sterile conditions and were incubated in a thioglycolate medium for 24 h.Subcultures were transferred to agar plates at 37 C under aerobic and anaerobic conditions and were evaluated after 24 h.

| Statistical analysis
All statistical analyses were conducted using IBM SPSS Statistics for Windows, Version 27.0 (IBM Corp, Armonk, NY, USA).Associations between nominal variables were assessed using Pearson chi-square (χ2), McNemar, and Fisher's exact tests.Odds ratios with 95% confidence intervals were reported to estimate the strength of the associations.
Effect size (φ) was calculated using Cramer's V test.Associations between continuous and quantitative variables were examined using the Mann-Whitney U-Test.Univariate analysis was performed to test potential confounding variables, and multivariate logistic regression was used to assess their associations.A two-sided p-value of < .05 was considered statistically significant for all analyses.
An a priori power analysis was conducted using G*Power version 3.1.9.7 (Faul et al. 17 ) for sample size estimation.The analysis was based on previous studies that reported post-septoplasty infection rates as low as 0.5% in patients treated with antibiotics and up to 13% in non-treated patients. 18,19With a significance criterion of α = .05and power = 0.80, a minimum sample size of 147 patients was calculated: 49 patients in the AB-0 group and 98 patients in the antibiotic-treatment groups (AB-1 and AB-7).

| RESULTS
The study included 146 patients.The main indication for surgery in all patients was nasal airway obstruction due to septal deviation.Group AB-0 (no antibiotic treatment) included 48 patients, group AB-1 (single-dose IV prophylaxis) included 43 patients, and group AB-7 (daily oral antibiotics until removal of the ISS) included 55 patients.Patient characteristics and details of the three treatment groups are pre- Group AB-0 patients were more likely to develop postoperative infection compared to antibiotic-treated patients (OR = 8.2, 95%CI: 1.63-41.1;p = .01,φ = 0.04).Infection rates did not differ significantly between the two antibiotic treatment groups AB-1 and AB-7.An analysis of the association between different demographic and clinical variables and postoperative infection was performed.Diabetes was associated with an increased risk of postoperative infection in all groups (OR = 5.2, 95%CI: 1.15-23.5;p = .032,φ = 0.04).Smoking status, obstructive sleep apnea, allergies, and history of sinusitis were not associated with infection.Nasal packing, which was placed in 15% of patients (all in group AB-7), was also not associated with postoperative infection.A post hoc analysis was conducted to determine the achieved power.With the given groups sizes and infection rates, and a significance criterion of α = .05,an adequate power of 0.80 was determined.
The detection of Klebsiella pneumonia before surgery was associated with an increased postoperative infection rate (p = .017).Seven patients (5%) were found to carry K. pneumonia in their nasal cavities before surgery.Three of these patients developed postoperative  Data on bacterial cultures and resistance were analysed and are presented in Table 3 and Figure 1.Overall, gram-positive bacteria (52% of patients) were more prevalent before surgery than gram-negative bacteria (38%), and S. aureus was the most common isolate (30%).
Postoperative cultures grew 182 isolates in 132 patients (90%).Interestingly, the bacterial detection rate increased postoperatively in groups AB-0 and AB-7 by 13% and 26%, respectively, but did not change in group AB-1.The detection rate of gram-positive bacteria decreased from 52% before surgery to 40% postoperatively.A corresponding increase in the rate of gram-negative bacteria (a 'Gram-negative shift') was documented, from 38% before surgery to 63% postoperatively.This trend was observed in all three treatment groups.
Resistant bacterial strains, excluding coagulase-negative Staphylococcus and Streptococcus Viridans which were considered contaminants, were identified in 8 patients (5%) before surgery.None of the patients had clinical signs of nasal infection prior to surgery.Acquired antimicrobial resistance was documented postoperatively in 14 patients (10%).Cultures from these patients grew gram-negative bacteria with increased resistance to beta-lactam antibiotics; three strains acquired ESBL or AmpC (plasmid-mediated AmpC enzymes) resistance.The rate of acquired resistance was highest among patients who were treated with one-week oral antibiotics, although this difference did not reach statistical significance (+10% in group AB-7, +5% in group AB-1, À2% in group AB-0) (Table 3).

| DISCUSSION
Septoplasty in general is defined as a clean-contaminated procedure, in which prophylactic antibiotics should be considered before first incision. 20,21However, due to the low risk of postoperative infection, a panel of experts of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) reconsidered the role of routine perioperative antibiotics in septoplasty.In a clinical statement published in 2015, the panel reached a consensus that antibiotics have no benefit in routine septoplasty in patients without nasal packing or splint placement. 22However, no conclusion was reached concerning prophylactic antibiotic treatment following septoplasty with ISS.Our study provides a comprehensive analysis of the effects of prophylactic antibiotic therapy following septoplasty with ISS.In the present study, the rate of infection in patients after septoplasty with ISS was low at 6%, which is consistent with previously published rates of 0.5%-12%. 18,23All cases of infection were resolved after a 7 to 10-day course of antibiotics without further complications.

| Antibiotic prophylaxis for septoplasty with ISS
Thus far, large prospective studies have reported no significant differences in post-septoplasty infection rates between patients given prophylactic antibiotic therapy and placebo groups.In these studies, Ricci et al. 8 did not use ISS, and Lilja et al. 24 reported using ISS only in a minority of cases (57/188 subjects).Other studies have examined the rate of postoperative infection in the presence of septal splints.Two prospective studies reported no infections in patients with ISS who were treated with prophylactic antibiotics. 13,25Other studies reported low rates of postoperative infection (1%-2%) following septoplasty with ISS without prophylactic treatment. 10None of these studies compared patients who received antibiotic therapy with those who did not.The present study, to the best of our knowledge, is the first to compare different antibiotic treatment groups.
The rate of postoperative infection was significantly higher in patients who were not treated with antibiotics (group AB-0).Patients in this group were up to 8 times more likely to develop postseptoplasty infection compared to patients treated with antibiotics.
The rate of infection in the AB-7 and AB-1 antibiotic treatment groups was 4% and 0%, respectively.These findings suggest a F I G U R E 1 Alteration in bacterial growth and resistance following septoplasty.
potential role for prophylactic antibiotics in the prevention of infections in patients undergoing septoplasty with ISS placement.

| Additional risk factors for postoperative infection
Diabetes was associated with an increased risk of postoperative infection regardless of prophylactic antibiotic therapy.Diabetes in general is considered a risk factor for development of surgical site infections, supposably due to the effects of hyperglycemia on immune system function. 26A recently published population-based Taiwanese study reported an association between type-2 diabetes mellitus and development of septal abscess after septoplasty. 27These findings support the need for close monitoring and further research on prophylactic antibiotic treatment in diabetic patients undergoing nasal surgery.
Interestingly, non-resistant K. pneumonia carriers were up to 16.5 times more likely to develop postoperative infection, regardless of antibiotic prophylaxis.K. pneumonia has previously been described as a pathogen involved in infections after nasal surgeries. 28However, to our knowledge, this is the first report of a significant association between the detection of the bacteria preoperatively and a higher risk of infection in patients after septoplasty with ISS.The significantly higher infection rate in carriers suggests a potential role for nasal screening for K. pneumonia before surgery.The reported susceptibility of K. pneumonia to cefazolin is >80%, 29 and patients with nonresistant strains are expected to respond well to antibiotic prophylaxis given before incision.

| Gram-negative shift and bacterial resistance
The overall rate of positive cultures increased after surgery by 13%.
Interestingly, the increase in bacterial growth was limited to the oraltreatment and no-treatment groups only (by 39% and 16%, respectively).Conversely, the rate of bacterial growth in patients treated with antibiotic prophylaxis before first incision did not change after surgery.The increase in bacterial colonisation after surgery may be explained by several mechanisms, including disruption of the mucosal lining with migration of pathogens, 30 and formation of biofilm on ISS. 13,31Thus, providing antibiotic protection before disrupting the mucosal lining in the clean-contaminated nasal environment is deemed necessary to decrease the rate of bacterial colonisation during and after surgery, and reduce the risk of postoperative infection.
As expected, gram-positive bacteria were more commonly identified before surgery (52%), and S. aureus was the most frequently isolated bacterial species (30%), in agreement with previous studies. 25e proportion of gram-negative bacteria increased substantially after surgery in all three treatment groups (overall from 38% to 63%), indicating a violation of the normal nasal flora regardless of antibiotic treatment.Not surprisingly, gram-negative pathogens were involved in 78% of postoperative infections.
In contrast to the increase in gram-negative bacteria in all treatment groups, an increase in the rate of bacterial resistance was recorded after surgery mainly in patients treated with antibiotics (group AB-7 by 10% and group AB-1 by 5%).Conversely, the rate of resistant strains decreased postoperatively in patients not treated with antibiotics (group AB-0, by 2%).These findings support the theories according to which the emergence of antibiotic resistance is a direct result of selective pressure exerted by antimicrobial agents. 11e emergence of resistance, particularly ESBL or AmpC, puts patients at risk of difficult-to-treat infections.According to a recent Centers for Disease Control and Prevention report, E. coli, K. pneumonia, and S.
aureus are among the leading causes of resistance-related mortality. 32ese pathogens were detected in the present study in approximately 80% of postoperative infections.

| Final considerations
4][35] However, direct comparisons between transseptal sutures and ISS, independent of other packing methods, remain limited.
Undoubtedly, adopting techniques that eliminate foreign bodies from the nasal cavity holds the potential to significantly reduce the risk of postoperative infection and eliminate the need for antibiotic prophylaxis.However, additional evidence is necessary to substantiate this assertion.Moreover, given the ongoing prevalent use of ISS, whether routinely or selectively, particularly in cases like septal perforations, our study's findings offer valuable potential insights into the risk of ISS-related infections, its impact on microbiology, and the potential advantages of prophylactic therapy.

| Study limitations
The major limitation of this study stems from its retrospective design and potential selection bias.Specifically, the decision to administer antibiotics, as determined by the operating surgeon, may have been impacted by the severity of the septal disease and the complexity of the surgical procedure.Additionally, the disturbance of the microbiome could potentially vary depending on the extent of the disease and the scope of the surgery.Different surgical techniques and surgeon preferences should also be considered potential sources of bias.
In addition, the study was limited to patients with ISS, and may not be applied to septoplasty without the placement of septal splints.Nevertheless, the findings of the study provide an insight into the effects of prophylactic antibiotic therapy on bacterial colonisation and resistance patterns after septoplasty with ISS.The ability to compare between treatment and control groups allowed us to demonstrate a significant association between different treatment protocols and the risk of postoperative infections.

| CONCLUSIONS
Septoplasty with ISS increases the risk of gram-negative bacterial colonization and postoperative nasal infection.Antibiotic therapy administered at the time of induction of anesthesia may be more effective in reducing bacterial load and antibiotic resistance than a one-week oral regimen.The study suggests that preoperative single-dose IV prophylaxis may also be effective in reducing the risk of postoperative infection, although larger studies are necessary to reinforce the findings and guide clinical decisions.Finally, special consideration should be given to diabetic patients undergoing nasal surgery, and further research is recommended to determine the role of preoperative nasal screening for K. pneumonia.
infection (43%) compared with a 3% infection rate in Klebsiella-negative patients (OR = 16.6, 95%CI: 3.02-91.54;p = .001,φ = 0.12).None of the K. pneumonia species detected before surgery was antibioticresistant.Detection of other bacterial species, as well as bacterial resistance before and after surgery, and identification of multiple bacterial species, were not associated with postoperative infection.Antibiotic treatment (IV prophylaxis or one-week oral therapy) was independently associated with a reduced likelihood of developing postoperative infection (p = .02).
Clinical characteristics of study population.Two patients had their ISS removed.Postoperative cultures from the nasal cavity and the ISS identified Staphylococcus aureus in 4 patients, and various types of Enterobacteriaceae in 5 patients (Table2).All patients were treated with a 7-10-day course of antibiotics.No systemic complications, including sepsis, toxic shock syndrome, or meningitis, were observed in any of the patients.
T A B L E 3 Bacterial cultures and resistance.