This cohort study examines whether an association exists between the use of perioperative topical antisepsis and the development of surgical site infections during upper aerodigestive tract flap reconstruction.
Key Points
Question
Is perioperative topical antisepsis associated with a reduction in surgical site infections (SSIs) in upper aerodigestive tract flap reconstruction?
Findings
In this multi-institutional cohort study of 554 adults, preoperative topical antisepsis mucosal preparation and systemic prophylaxis with piperacillin and tazobactam were associated with decreased postoperative SSIs. Use of an osseous vascularized flap was associated with an increased risk of postoperative SSI.
Meaning
This study suggests that topical antisepsis mucosal preparation needs to be considered as part of the perioperative antisepsis protocol to reduce postoperative SSIs.
Abstract
Importance
Surgical site infections (SSIs) after vascularized reconstruction of the upper aerodigestive tract (UADT) are associated with considerable morbidity. The association between perioperative prophylaxis practices, particularly topical antisepsis, and SSIs remains uncertain.
Objective
To assess the association between perioperative topical antisepsis and SSIs in patients undergoing vascularized reconstruction of the UADT.
Design, Setting, and Participants
This cohort study included patients from 12 academic tertiary care centers over an 11-month period, from July 1, 2020, to June 1, 2021. Patients undergoing open surgical procedures requiring a communication between the UADT and cervical skin with a planned regional pedicled flap, free flap, or both were included. Patients with an active infection at the time of surgical procedure were excluded.
Main Outcomes and Measures
The primary outcome measure was an SSI within 30 days of surgery. The association of demographic characteristics, perioperative antibiotic prophylaxis, surgical technique, and postoperative care with SSIs was assessed using univariable and multivariable analyses. The relative risk ratio and 95% CIs for developing SSI were calculated for each of the variables based on predetermined categories. Variables for which the relative risk 95% CI did not include the value of zero effect (relative risk = 1.00) were included in the multivariable model.
Results
A total of 554 patients (median age, 64 years; range, 21-95 years; 367 men [66.2%]) were included. Cancer ablation was the most frequent reason for surgery (n = 480 [86.6%]). Overall, the SSI rate was 20.9% (n = 116), with most infections involving the head and neck surgical site only (91 [78.4%]). The median time to SSI diagnosis was 11 days (range, 1-28 days). Topical antisepsis mucosal preparation was performed preoperatively in 35.2% (195) and postoperatively in 52.2% (289) of cases. Ampicillin and sulbactam was the most common systemic antibiotic prophylaxis agent used (n = 367 [66.2%]), with 24 hours being the most common duration (n = 363 [65.5%]). On multivariable analysis, preoperative topical antisepsis mucosal preparation (odds ratio [OR], 0.49; 95% CI, 0.30-0.77) and systemic prophylaxis with piperacillin and tazobactam (OR, 0.42; 95% CI, 0.21-0.84) were associated with a decreased risk of a postoperative SSI. The use of an osseous vascularized flap was associated with an increased risk of postoperative SSI (OR, 1.76; 95% CI, 1.13-2.75).
Conclusions and Relevance
Findings of this study suggest that preoperative topical antisepsis mucosal preparation was independently associated with a decreased risk of SSIs in a 12-center multi-institutional cohort. Further investigation of the association between individual perioperative practices and the incidence of postoperative SSIs is necessary to develop evidence-based protocols to reduce SSIs after UADT reconstruction.
Introduction
Upper aerodigestive tract (UADT) cancer continues to be an important source of morbidity and mortality in the US with more than 66 000 new cases and 13 000 deaths estimated for 2021.1 Surgical resection is central in the therapeutic approach for many UADT cancers. This treatment includes primary ablation for oral cancer and advanced disease of the larynx and hypopharynx as well as salvage surgery after radiation failure.2 Oncologic ablative surgery can be followed by UADT defects with considerable functional and aesthetic consequences. Likewise, surgical management of complex facial trauma, osteoradionecrosis, and osteomyelitis can be followed by similar defects. Vascularized reconstruction is often necessary to restore cosmesis and physiological function while minimizing postoperative morbidity.3
Although vascularized flap failure in the UADT is now less than 3% in high-volume centers, surgical site infection (SSI) remains a pervasive perioperative problem.4 Surgical site infections represent a major contributor to postoperative morbidity in open UADT surgery; complications include increased length of hospital stay, hardware exposure, flap loss or necrosis, readmission, and death.5,6,7,8 Rates of SSI generally have been reported to be between 15% and 30% in the literature, despite the standardized use of systemic prophylactic antibiotics.9,10,11 Perioperative use of these antibiotics has been well established by landmark randomized clinical trials (RCTs) completed in the 1970s and mid-1980s, which reported SSI rates upward of 70% without antibiotic use.12,13,14 The ideal duration of prophylactic antibiotics in open UADT surgery is a debated subject, with current evidence supporting a duration of 24 hours or less as optimal.9,15 Proliferation of systemic prophylactic antibiotics is associated with a substantial decrease in SSI rates after clean-contaminated surgery compared with these early reports, yet further progress is needed.
Topical antibiotics are an appealing perioperative prophylaxis adjunct treatment and possess several advantages, including high drug concentration at the site of application and low systemic adverse effects. Although some studies have examined the use of topical antibiotic prophylaxis in head and neck surgery,16,17,18 the data remain heterogeneous and limited. This study examined current patterns in perioperative topical antibiotic and antiseptic use and evaluated their association with development of SSIs in patients undergoing vascularized reconstruction of the UADT.
Methods
Study Design and Patient Population
This prospective, observational cohort study included patients who underwent an open surgical procedure requiring communication between the UADT and cervical skin with either a regional pedicled flap, free flap, or both between July 1, 2020, and June 1, 2021. Reconstructed subsites included the oral cavity, oropharynx, hypopharynx, larynx, or cervical esophagus. Patients were excluded if evidence of an active infection was present at the time of the surgical procedure, as identified by the treating surgeon. Data from 12 academic tertiary care centers (Geisinger Medical Center; H. Lee Moffitt Cancer Center & Research Institute; Indiana University School of Medicine; Massachusetts Eye and Ear Infirmary, Harvard Medical School; Medical College of Wisconsin; Medical University of South Carolina; Oregon Health & Science University; Penn State College of Medicine; University of California, San Francisco; University of Kentucky; University of Vermont Medical Center; and Washington University School of Medicine) were collected and included patient demographic characteristics, medical history, surgical details, perioperative management, and treatment outcomes (data on race and ethnicity were not collected for the study). There were no changes in standard of care treatment and no study-specific perioperative antibiotic prophylaxis practices. Each surgeon performed surgical resection, reconstruction, and perioperative prophylaxis per their personal or institutional protocol. Occurrence of an SSI within 30 days postoperatively was recorded using the Centers for Disease Control and Prevention criteria.19 The definition of a subsite for an SSI included either the recipient or donor operative sites used during the index surgical procedure. Diagnosis for an SSI included (1) purulent drainage from the incision, (2) spontaneous incision dehiscence or an incision opened by the surgeon because of infection, (3) abscess or other evidence of infection involving a deep incision, or (4) an SSI diagnosed by the surgeon. Concurrent presence of an orocutaneous or pharyngocutaneous fistula was documented by the attending physician. A fistula without other evidence of infection was not considered to be an SSI in accordance with Centers for Disease Control and Prevention criteria. Surgical site infection characteristics, including location, method of diagnosis, culture results, and treatment, were collected when available. Complications resulting from an SSI, such as readmission, prolonged hospital stay, and reoperation, were also documented. The study was approved by the Medical College of Wisconsin Institutional Review Board, all data collection was approved by the other centers’ institutional review boards, and the requirement for patient informed consent was waived because only deidentified data were used. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Statistical Analysis
Descriptive statistics were used to summarize the characteristics of the study population. The relative risk ratio (and 95% CI) for developing SSI was calculated for each of the variables based on predetermined categories. Variables for which the relative risk 95% CI did not include the value of zero effect (relative risk = 1.00) were included in the multivariable model. Multivariable binary logistic regression was used to investigate the association between demographic characteristics, flap type, perioperative antibiotic practices, surgical technique, and postoperative outcomes. A subgroup analysis was performed for the location of the SSI. The statistical analysis was again performed as described earlier. Statistical analysis was performed with SPSS, version 26 (IBM).
Results
A total of 554 patients (367 men [66.2%] and 187 women [33.8%]) were included in the study. The median (IQR) number of patients per center ranged from 13 to 91 (32-54). The median (range) age was 64 (21-95) years. The overall SSI rate was 20.9% (n = 116), varying between centers from 6.0% to 42.9%. Table 1 shows the demographic, perioperative antibiotic prophylaxis, and surgical details of the group of patients who developed an SSI and the relative risk of SSI for each variable.
Table 1. Characteristics of the Study Population and SSI Group With Univariable Analysis.
| Variable | Patients, No. (%) (n = 554) | SSIs, No. (%) (n = 116) | RR (95% CI) |
|---|---|---|---|
| Age, y | |||
| <64 | 261 (47.1) | 58 (22.2) | 1.12 (0.81-1.55) |
| ≥64 | 293 (52.9) | 58 (19.8) | |
| Sex | |||
| Female | 187 (33.8) | 43 (23.0) | 0.86 (0.62-1.21) |
| Male | 367 (66.2) | 73 (19.9) | |
| American Society of Anesthesiologists scorea | |||
| I or II | 109 (19.7) | 20 (18.3) | 0.85 (0.55-1.32) |
| III or IV | 442 (79.8) | 95 (21.5) | |
| Past head and neck radiotherapy | |||
| Yes | 194 (35.0) | 35 (18.0) | 0.80 (0.56-1.14) |
| No | 360 (65.0) | 81 (22.5) | |
| Smokingb | |||
| <10 Pack-years | 206 (37.2) | 45 (21.8) | 1.07 (0.77-1.49) |
| ≥10 Pack-years | 343 (62.0) | 70 (20.4) | |
| Head and neck subsite | |||
| Oral cavity | 395 (71.3) | 85 (21.5) | 1.10 (0.76-1.59) |
| Otherc | 159 (28.7) | 31 (19.5) | |
| Systemic antibiotic prophylaxis | |||
| Piperacillin and tazobactam | 83 (15.0) | 10 (12.0) | 0.54 (0.29-0.98) |
| Otherd | 471 (85.0) | 106 (22.5) | |
| Preoperative topical antisepsis mucosal preparation | |||
| Yes | 195 (35.2) | 30 (15.4) | 0.64 (0.44-0.94) |
| No | 359 (64.8) | 86 (24.0) | |
| Postoperative topical antisepsis mucosal preparationa | |||
| Yes | 287 (51.8) | 61 (21.3) | 1.04 (0.75-1.44) |
| No | 264 (47.7) | 54 (20.5) | |
| Indication | |||
| Cancer ablation | 480 (86.6) | 104 (21.7) | 1.34 (0.78-2.31) |
| Othere | 74 (13.4) | 12 (16.2) | |
| Flap type | |||
| Osseous | 137 (24.7) | 40 (29.2) | 1.60 (1.15-2.23) |
| Soft tissue only | 417 (75.3) | 76 (18.2) | |
| Flap complexity | |||
| Regional pedicled | 77 (13.9) | 16 (20.8) | 0.99 (0.62-1.59) |
| Free | 477 (86.1) | 100 (21.0) | |
| Flap inset suture | |||
| 3-0 Vicryl | 367 (66.2) | 80 (21.8) | 1.13 (0.80-1.61) |
| Otherf | 187 (33.8) | 36 (19.3) | |
| Time under anesthesia, hg | |||
| <9 | 232 (41.9) | 42 (18.1) | 0.79 (0.56-1.10) |
| ≥9 | 321 (57.9) | 74 (23.1) | |
| Postoperative corticosteroids | |||
| Yes | 287 (51.8) | 66 (23.0) | 1.23 (0.89-1.70) |
| No | 267 (48.2) | 50 (18.7) | |
| Duration of postoperative systemic prophylaxis, hh | |||
| ≤24 | 392 (70.8) | 91 (23.2) | 1.49 (0.99-2.22) |
| >24 | 160 (28.9) | 25 (15.6) |
Abbreviations: RR, relative risk; SSI, surgical site infection.
Data are missing for 3 cases in the total patient cohort.
Data are missing for 5 cases in the total patient cohort.
Other included oropharynx, larynx, hypopharynx, cervical esophagus, and sinonasal or skull base.
Other included ampicillin-sulbactam, cefazolin, cefazolin and metronidazole, ceftriaxone and metronidazole, clindamycin, and vancomycin and metronidazole. Regimens with frequency of 1 not listed.
Other included cancer ablation, osteoradionecrosis, trauma, fistula repair, exposed hardware, and benign masses. Indications with frequency of 1 not listed.
Other included 2-0 Vicryl (Ethicon Inc), 2-0 PDS, 3-0 PDS, and 3-0 Biosyn (Medtronic). Suture with frequency of 1 not listed.
Data are missing for 1 case in the total patient cohort.
Data are missing for 2 cases in the total patient cohort.
The oral cavity was the most frequently involved head and neck subsite for surgery (395 [71.3%]), followed by the larynx (71 [12.8%]). Although indications for the surgical procedures varied, cancer ablation was the most frequent indication (480 [86.6%]), with osteoradionecrosis being the second most common indication (39 [7.0%]). A total of 328 surgical procedures (59.2%) included concurrent tracheotomy. Free flaps alone were used in most cases (477 [86.1%]), regional pedicled flaps alone were used in 72 cases (13.0%), and both free and regional pedicled flaps were used in 5 cases (1.0%).
Preoperative topical antisepsis mucosal preparation was performed in 35.2% of cases (195) on the day of surgery before incision—most frequently with povidone-iodine alone (99 [17.9%]), followed by chlorhexidine alone (47 [8.5%]) and both povidone-iodine and chlorhexidine (47 [8.5%]). Intraoperative antiseptic irrigations were performed in 11.0% of cases (61). Systemic antibiotic prophylaxis choices and duration varied, with ampicillin and sulbactam (367 [66.2%]) as the most common agent, followed by piperacillin and tazobactam (83 [15.0%]), cefazolin (33 [6.0%]), cefazolin and metronidazole (31 [5.6%]), and clindamycin (18 [3.2%]). The most common duration of systemic antibiotic prophylaxis was 24 hours (363 [65.5%]), followed by 48 hours (97 [17.5%]) and more than 5 days (63 [11.4%]). Postoperatively, 51.8% (287) of cases had topical antisepsis mucosal preparation. The regimen for all cases included chlorhexidine oral rinses. Oral topical tetracycline was used in addition to the chlorhexidine rinses in 24 of 289 patients (8.3%). There were no complications associated with topical antiseptic therapy.
Most of the 116 SSIs involved the head and neck surgical site only (91 [78.4%]), 25 cases (21.6%) involved the flap donor surgical site only, and 4 cases (3.4%) involved both head and neck and donor surgical sites. The median time to SSI diagnosis was 11 days (range, 1-28 days; IQR, 7-17 days). The most common method of diagnosis was by the surgeon or the surgeon’s designee (eg, nurse practitioner, resident) (55 [47.4%]), followed by wound dehiscence (39 [33.6%]) and purulent drainage from the incision (31 [26.7%]). Culture results for 49.1% (57) of SSIs were available. Most (57.9% [33]) cultured organisms were pathogens not typically found among commensal oral microbiota (Pseudomonas, Klebsiella, E coli, methicillin-resistant Staphylococcus aureus, methicillin-susceptible S aureus, and Enterobacter). A total of 53.4% of patients (62) with SSIs had outpatient antibiotic treatment, and 32.8% of SSIs (38) were associated with orocutaneous or pharyngocutaneous fistula. Complications of SSIs included extended length of hospital stay (39.7% [46]), readmission (25.0% [29]), and a return to the operating room (25.0% [29]). Seven patients (6.0%) continued to experience persistent problems for more than 6 weeks after surgery.
On multivariable analysis, preoperative topical antisepsis mucosal preparation was associated with a decreased risk of a postoperative SSI (odds ratio [OR], 0.49; 95% CI, 0.30-0.77) (Table 2). Other factors associated with a decreased risk of a postoperative SSI on multivariable analysis included antibiotic prophylaxis with piperacillin and tazobactam (OR, 0.42; 95% CI, 0.21-0.84). The use of an osseous vascularized flap was associated with an increased risk of postoperative SSI (OR, 1.76; 95% CI, 1.13-2.75).
Table 2. Multivariable Logistic Regression Analysis of Risk Factors for SSI.
| Variable | OR (95% CI) |
|---|---|
| Systemic antibiotic prophylaxis (piperacillin and tazobactam vs other) | 0.42 (0.21-0.84) |
| Preoperative topical antisepsis mucosal preparation | 0.49 (0.30-0.77) |
| Flap type (osseous vs soft tissue) | 1.76 (1.13-2.75) |
Abbreviations: OR, odds ratio; SSI, surgical site infection.
Table 3 and Table 4 show univariable and multivariable risk factors for SSIs stratified by location of infection (head and neck vs flap donor). On subgroup multivariable analysis, age older than 64 years (OR, 0.58; 95% CI, 0.37-0.92), systemic prophylaxis with piperacillin and tazobactam (OR, 0.33; 95% CI, 0.15-0.75), and preoperative topical antisepsis mucosal preparation (OR, 0.49; 95% CI, 0.29-0.82) were associated with a decreased risk of head and neck SSI. Age older than 64 years (OR, 2.59; 95% CI, 1.16-5.81) and use of an osseous vascularized flap (OR, 3.30; 95% CI, 1.56-7.00) were associated with an increased risk of flap donor SSI.
Table 3. Characteristics of SSI Cases Grouped by Location With Univariable Analysis.
| Variable | Patients, No. (%) (n = 554) | Head and neck surgical site | Flap donor site | ||
|---|---|---|---|---|---|
| SSI, No. (%) | RR (95% CI) | SSI, No. (%) | RR (95% CI) | ||
| Age, y | |||||
| <64 | 261 (47.1) | 60 (23.0) | 1.57 (1.07-2.30) | 9 (3.4) | 0.39 (0.18-0.84) |
| ≥64 | 293 (52.9) | 35 (11.9) | 21 (7.2) | ||
| Sex | |||||
| Female | 187 (33.8) | 36 (19.3) | 0.84 (0.57-1.22) | 13 (7.0) | 0.67 (0.33-1.34) |
| Male | 367 (66.2) | 59 (16.1) | 17 (4.6) | ||
| ASA scorea | |||||
| I or II | 109 (19.7) | 16 (14.7) | 0.83 (0.51-1.37) | 6 (5.5) | 1.01 (0.43-2.42) |
| III or IV | 442 (79.8) | 78 (17.6) | 24 (5.4) | ||
| Past head and neck radiotherapy | |||||
| Yes | 194 (35.0) | 33 (17.0) | 0.99 (0.67-1.45) | 7 (3.6) | 0.56 (0.25-1.29) |
| No | 360 (65.0) | 62 (17.2) | 23 (6.4) | ||
| Smokingb | |||||
| <10 Pack-years | 206 (37.2) | 36 (17.5) | 1.03 (0.71-1.51) | 13 (6.3) | 1.27 (0.63-2.57) |
| ≥10 Pack-years | 343 (62.0) | 58 (16.9) | 17 (5.0) | ||
| Head and neck subsite | |||||
| Oral cavity | 395 (71.3) | 66 (16.7) | 0.93 (0.62-1.38) | 23 (5.8) | 1.29 (0.57-2.94) |
| Otherc | 159 (28.7) | 28 (17.6) | 7 (4.4) | ||
| Systemic antibiotic prophylaxis | |||||
| Piperacillin and tazobactam | 83 (15.0) | 7 (8.4) | 0.44 (0.21-0.92) | 4 (4.8) | 0.86 (0.31-2.40) |
| Otherd | 471 (85.0) | 88 (18.7) | 26 (5.5) | ||
| Preoperative topical antisepsis mucosal preparation | |||||
| Yes | 195 (35.2) | 23 (11.8) | 0.59 (0.38-0.91) | 11 (5.6) | 1.07 (0.52-2.19) |
| No | 359 (64.8) | 72 (20.1) | 19 (5.3) | ||
| Postoperative topical antisepsis mucosal preparationa | |||||
| Yes | 287 (51.8) | 48 (16.7) | 0.94 (0.65-1.36) | 15 (5.2) | 0.92 (0.46-1.85) |
| No | 264 (47.7) | 47 (17.8) | 15 (5.7) | ||
| Indication | |||||
| Cancer ablation | 480 (86.6) | 84 (17.5) | 1.12 (0.63-2.00) | 29 (6.0) | 2.85 (0.39-20.97) |
| Othere | 74 (13.4) | 11 (14.9) | 1 (1.4) | ||
| Flap type | |||||
| Osseous | 137 (24.7) | 31 (22.6) | 1.16 (0.79-1.71) | 17 (12.4) | 3.14 (1.56-6.31) |
| Soft tissue only | 417 (75.3) | 64 (15.3) | 13 (3.1) | ||
| Flap complexity | |||||
| Regional pedicled | 77 (13.9) | 18 (23.4) | 1.45 (0.92-2.28) | 2 (2.6) | 0.82 (0.11-1.82) |
| Free | 477 (86.1) | 77 (16.1) | 28 (5.9) | ||
| Flap inset suture | |||||
| 3-0 Vicryl | 367 (66.2) | 67 (18.3) | 1.28 (0.84-1.94) | 21 (5.7) | 1.16 (0.54-2.48) |
| Otherf | 187 (33.8) | 26 (13.9) | 9 (4.8) | ||
| Anesthesia time, hg | |||||
| <9 | 232 (41.9) | 42 (18.1) | 0.88 (0.61-1.28) | 14 (6.0) | 0.98 (0.49-1.96) |
| ≥9 | 321 (57.9) | 53 (16.5) | 16 (5.0) | ||
| Postoperative corticosteroids | |||||
| Yes | 287 (51.8) | 52 (18.1) | 1.12 (0.78-1.62) | 18 (6.3) | 1.39 (0.68-2.83) |
| No | 267 (48.2) | 43 (16.1) | 12 (4.5) | ||
| Duration of postoperative systemic antibiotic prophylaxis, hh | |||||
| ≤24 | 392 (70.8) | 70 (17.9) | 1.15 (0.75-1.74) | 23 (5.9) | 1.35 (0.59-3.07) |
| >24 | 160 (28.9) | 25 (15.6) | 7 (4.4) | ||
Abbreviations: ASA, American Society of Anesthesiologists; RR, relative risk; SSI, surgical site infection.
Data are missing for 3 cases in the total patient cohort.
Data are missing for 5 cases in the total patient cohort.
Other included oropharynx, larynx, hypopharynx, cervical esophagus, and sinonasal or skull base.
Other included ampicillin-sulbactam, cefazolin, cefazolin and metronidazole, ceftriaxone and metronidazole, clindamycin, and vancomycin and metronidazole. Regimens with frequency of 1 not listed.
Other included cancer ablation, osteoradionecrosis, trauma, fistula repair, exposed hardware, and benign masses. Indications with frequency of 1 not listed.
Other included 2-0 Vicryl, 2-0 PDS, 3-0 PDS, and 3-0 Biosyn. Suture with frequency of 1 not listed.
Data are missing for 1 case in the total patient cohort.
Data are missing for 2 cases in the total patient cohort.
Table 4. Multivariable Logistic Regression Analysis of Risk Factors for SSI by SSI Location.
| Variable | OR (95% CI) |
|---|---|
| Head and neck surgical site | |
| Age, y (≥64 vs <64) | 0.58 (0.37-0.92) |
| Systemic antibiotic prophylaxis (piperacillin and tazobactam vs other) | 0.33 (0.15-0.75) |
| Preoperative topical antisepsis mucosal preparation | 0.49 (0.29-0.82) |
| Flap donor site | |
| Age, y (≥64 vs <64) | 2.59 (1.16-5.81) |
| Flap type (osseous vs soft tissue) | 3.30 (1.56-7.00) |
Abbreviations: OR, odds ratio; SSI, surgical site infection.
Discussion
To our knowledge, this study constitutes the largest observational prospective study on SSIs in clean-contaminated UADT surgery requiring flap reconstruction. We found that SSIs remain an important source of postoperative morbidity, with a substantial portion of patients with these infections requiring an increased length of hospital stay, readmission, or return to the operating room. We also found that preoperative topical antisepsis mucosal preparation may play a role in mitigating SSI risk in patients undergoing similar procedures.
The data available on preoperative topical antisepsis mucosal prophylaxis in head and neck surgery are limited and heterogeneous. Kirchner et al20 and Elledge et al21 reported rapid (less than 1 hour) and sustained (more than 4 hours) reduction in the concentration of aerobic and anaerobic oral flora with the use of a single clindamycin mouthwash in healthy volunteers. Perioperative use of topical clindamycin was examined by Grandis et al,16 with a single dose of preoperative mouthwash and intraoperative irrigation used in lieu of parenteral antibiotic prophylaxis in 10 consecutive patients undergoing total laryngectomy with neck dissection. Preoperative mouthwash was associated with a 99% reduction of both aerobic and anaerobic oral bacterial counts, and intraoperative irrigations were associated with a 90% reduction in neck wound bacterial counts. Although the sample size was small, no patients developed SSIs. Based on these promising results, Simons et al17 conducted an RCT to evaluate the use of topical and parenteral piperacillin and tazobactam prophylaxis compared with parenteral prophylaxis alone. Bacterial load was significantly decreased in both treatment groups, with certain bacterial counts significantly decreased with the addition of topical prophylaxis compared with parenteral prophylaxis alone. The study was terminated early because of intermediate analysis revealing a significantly lower SSI rate than anticipated (8.1% vs 20%-25%), requiring a prohibitively large sample size. With the relatively small number of enrolled patients (62), an absolute difference of 25% in SSI rate between study groups would have been required for adequate statistical power, which was not possible with the overall SSI rate being 8.1%. In another RCT, Funahara et al18 reported a significant reduction in SSIs (19.6% vs 36.1%) in patients undergoing oral cancer resection, neck dissection, flap reconstruction, and tracheotomy with the use of topical tetracycline for 48 hours postoperatively. The results of the present study found a similar decrease in SSIs of the head and neck surgical site associated with the use of preoperative topical antisepsis mucosal preparation. There was no change in SSI at the vascularized donor site, which is consistent with the localized treatment effects of topical antibiotic prophylaxis.
The aforementioned studies,16,17,20,21 among others,22,23 have found a significant reduction of mucosal microbial bioburden associated with the use of various topical antisepsis mucosal preparations, yet there are several remaining questions about their optimal use and implications. The full treatment effects of topical antiseptics and antibiotics on the oral microbiome and subsequent timing and sequela of bacterial recolonization remain unclear, and the implications for subsequent wound healing or development of SSI require further elucidation. An important remaining question is the source of the bacteria that lead to SSIs. Topical antisepsis is effective only if applied to the surfaces that harbor bacteria that may subsequently lead to SSI. However, UADT flap surgeries are long and complex procedures with multiple potential sites for contamination. It remains unclear whether the bacteria that lead to SSIs are opportunistic colonists present in the oral cavity preoperatively or if these bacteria are introduced intraoperatively or postoperatively from another source. Low overall concordance has been noted between preoperative oral cultures and the causative pathogen of SSIs in previous reports of UADT reconstruction.24 However, given the abundance of commensal bacteria in the oral cavity, basic microbiological oral culture may not have the sensitivity to detect and identify all potential pathogens preoperatively. A total of 58.7% of SSIs in this study were caused by pathogens not commonly found in the commensal oral microbiome, similar to findings reported by other studies.24,25 Whether these pathogens were present in small quantities in the preoperative oral cavity is uncertain, and novel methods to detect and identify the perioperative source of the infectious organism will be essential to tailoring topical therapies to the right patient at the right time.
In addition to topical antisepsis mucosal preparation, decreased risk of SSIs was associated with piperacillin and tazobactam intravenous prophylaxis, but no clinically meaningful difference was seen with a longer duration of antibiotics or systemic antibiotic therapy. Overall, the current body of literature has not found a benefit to administration of prophylactic antibiotics for longer than 24 hours in clean-contaminated head and neck surgery, with 2 recent systematic reviews and meta-analyses supporting that conclusion.9,26 It is important to note that a portion of the RCTs included in previous meta-analyses used antibiotics without considerable gram-negative coverage, such as clindamycin and cefazolin. In addition, the patient populations included in these studies varied, with some studies including less than 30% of patients with cancer.27 The evolution of the oral microbiome during progression of oral cancer has been shown to lead to distinct microbial alterations, which may make comparisons to populations without cancer less valid.28,29
Our findings may also reflect a changing microbiota among current patients with UADT cancer, including a greater percentage of gram-negative and resistant organisms. Eighty-five percent of cultured gram-negative bacilli obtained by Durand et al25 from patients with head and neck free flaps were resistant to ampicillin and sulbactam. The expanded coverage of gram-negative bacilli with piperacillin and tazobactam in this context can perhaps explain the unanticipated SSI rate (8.1%) reported by Simons et al,17 as mentioned previously.7,10 The addition of a quinolone to ampicillin and sulbactam has also been proposed as an alternative.25 Although individualizing antibiotic therapy may optimize the balance between therapeutic coverage and antibiotic stewardship in these cases, currently a biomarker or diagnostic test on which to base prophylactic choice is lacking. However, it is possible that use of expanded gram-negative coverage should be considered in cases with a high risk of SSI.
Several other key variables were associated with SSIs in this study. Osseous flaps were found to increase infection risk, consistent with previous reports.30,31,32 Hypotheses for the observed increase in SSI rates include increased operative complexity, hardware use, and dead space.6,30 However, in this study, reconstruction with an osseous flap was only independently associated with donor-site SSI. Similarly, older age was associated with flap donor SSI but not overall SSI. The cause of these donor site associations are likely multifactorial but may be related to patient comorbidities, such as vasculopathies and metabolic disorders, that more prominently affect extremity donor sites.33,34
Limitations
This study has limitations. Because of the observational study design, there was no unified protocol for perioperative prophylaxis or any placebo control. Heterogeneous antiseptic regimens were used with varying duration. In addition, there was no control over duration, frequency, or volume of topical treatments. Because of the heterogeneous perioperative practices, this study was not powered for practice-specific subset analysis (eg, 24 vs 48 hours of systemic prophylaxis or comparison of the different mucosal preparation agents). In addition, intraoperative antibiotic irrigations are a potential confounding factor. No independent analysis was performed because of the small number of cases that used intraoperative irrigations. Another limitation in this study was the failure to capture the individual severity of comorbid ailments and other factors that can lead to a predisposition to infections. Despite these limitations, this study, to our knowledge, represents the largest prospective multicenter evaluation to date of SSIs in UADT flap reconstruction, which included rigorous data collection and a consistent definition of SSI across centers.
Conclusions
Surgical site infections remain a major source of morbidity for patients undergoing flap reconstruction of UADT defects. The results of this cohort study suggest a role for preoperative topical antisepsis mucosal preparation in reducing rates of SSI. Our findings also support the high prevalence of pathogenic gram-negative bacilli and consideration of greater gram-negative coverage with perioperative prophylaxis. This study found significant heterogeneity of perioperative practices, emphasizing key areas for further study and standardization. Future RCTs are needed to evaluate individual topical and systemic prophylactic interventions that may decrease the incidence of SSIs in patients undergoing UADT resection and reconstruction.
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