Efficacy of topical antibiotic administration on the inhibition of perioperative oral bacterial growth in oral cancer patients: a preliminary study

Abstract

Parenteral antibiotic prophylaxis is the current standard of therapy in clean-contaminated oral cancer surgery. Nevertheless, the incidence of surgical site infection (SSI) in oral oncological surgery is relatively high, especially in major surgery with reconstruction and tracheotomy. The aims of this study were to investigate the perioperative condition related to microorganisms in the oral cavity and to examine the efficacy of the topical administration of tetracycline in reducing the number of bacteria in the oropharyngeal fluid during intubation. The number of oral bacteria was measured during intubation in patients undergoing major oral cancer surgery. The efficacy of the topical administration of tetracycline or povidone iodine gel in reducing the bacteria was then investigated. Bacteria in the oropharyngeal fluid grew from 10 6 CFU/ml to 10 8 CFU/ml during the 3 h after intubation (CFU, colony-forming units). When tetracycline was applied to the dorsum of the tongue, oral bacteria decreased immediately to 10 5 CFU/ml, and the number of bacteria in the oropharyngeal fluid was maintained below 10 7 CFU/ml for 7 h. The concentration of tetracycline in the oropharyngeal fluid was extremely high for several hours after topical administration. The topical administration of tetracycline could reduce oral bacteria in patients undergoing clean-contaminated oral cancer surgery. This method is expected to be effective in the prevention of SSI.

Postoperative infection, including surgical site infection (SSI) or remote infection, occurs frequently after head and neck cancer surgery, causing not only a prolonged hospital stay and decrease in quality of life, but also a poorer prognosis due to the delay in postoperative treatment. According to the guidelines for the prevention of SSI published by the US Centers for Disease Control and Prevention (CDC) in 1999, various factors such as age, nutritional status, diabetes, smoking, and obesity are thought to be related to the occurrence of SSI. The CDC guidelines state that the risk of SSI can be conceptualized as a level of bacterial contamination × virulence/resistance of the host patient, and that if a surgical site is contaminated with >10 5 microorganisms per gram of tissue, the risk of SSI is markedly increased.

The number of microorganisms in the saliva usually exceeds 10 5 CFU/ml (CFU, colony-forming units). The CDC guidelines classify surgical wounds by degree of contamination as follows: class 1, clean; class 2, clean-contaminated; class 3, contaminated; and class 4, dirty-infected. According to the CDC guidelines, wounds in the oral cavity and oropharynx are included in the class 2 category, and the leading cause of the development of SSI in oral cancer surgery appears to be perioperative contamination by microorganisms in the saliva.

Parenteral antibiotic prophylaxis is the current standard of therapy in clean-contaminated oncological head and neck surgery. Nevertheless, the reported incidence of SSI in head and neck surgery is relatively high, ranging from 10.9% to 45.0%. Some studies in normal, healthy volunteers have documented the efficacy of a single dose of antibiotic mouthwash in quantitatively reducing aerobic and anaerobic bacteria in the oral cavity for 4 h. However, in a study on head and neck surgery with flap reconstruction, Simons et al. reported that the additional use of topical piperacillin/tazobactam administered as a mouthwash immediately before surgery, and once a day for 2 days postoperatively, did not appear to enhance the prophylactic benefit of parenteral antibiotics alone.

The objectives of the present study were to investigate the perioperative condition related to microorganisms in the oral cavity and to examine the efficacy of the topical administration of tetracycline ointment and iodine gel in reducing the number of bacteria in the oral fluid.

Materials and methods

A total of 25 subjects were recruited into this study ( Table 1 ).

Table 1
Patient characteristics in the three studies.
Study 1 (during surgery) Study 2 (during surgery) Study 3 (in the ICU)
Age, mean (range), years 76.2 (67–93) 65.2 (52–75) 66.2 (51–76)
Gender
Male 3 7 8
Female 2 3 2
Primary site
Tongue 1 5 5
Mandibular gingiva 2 0 1
Maxillary gingiva 1 2 1
Buccal mucosa 1 0 0
Floor of the mouth 0 3 3
Stage
Stage II (late neck metastasis) 1 2 0
Stage III 0 4 2
Stage IV 4 4 8
Surgery
Neck dissection 1 2 0
Neck dissection + tumour resection 3 2 2
Neck dissection + tumour resection + reconstruction 1 6 8
Tracheotomy
Yes 3 8 10
No 2 2 0
Total 5 10 10

ICU, intensive care unit.

Number of bacteria in the oral cavity during surgery

After intubation, the oral cavities of five patients who were to undergo neck dissection were irrigated with 500 ml of saline. Ampicillin/sulbactam (1500 mg) was administered parenterally at the start of surgery. The number of bacteria on the surfaces of the dorsum of the tongue, buccal mucosa, and hard palate, and in the oropharyngeal fluid, was measured every 15 min until the neck dissection had been completed and resection of the intraoral tumour was started. The number of bacteria was measured with a rapid oral bacteria quantification system (Panasonic Healthcare Co. Ltd., Osaka, Japan) using the dielectrophoresis and impedance measurement method. Because the detection limit of this machine is 10 5 CFU/ml, actual bacterial counts less than this limit were displayed as 10 5 CFU/ml.

Efficacy of the topical administration of povidone iodine gel or tetracycline ointment on the inhibition of bacterial growth in the oral cavity during surgery

The oral cavities of 10 patients undergoing neck dissection were irrigated with saline, as described above, after intubation. Patients were divided randomly into two treatment groups: (1) parenteral ampicillin/sulbactam plus topical administration of 10 g of 10% povidone iodine gel on the dorsum of the tongue (five patients), and (2) parenteral ampicillin/sulbactam plus topical administration of 10 g of 3% tetracycline ointment on the tongue (five patients). The number of bacteria on the surface of the tongue and in the oropharyngeal fluid was measured every 15 min until the neck dissection had been completed.

Efficacy of topical tetracycline ointment on the inhibition of bacterial growth in the oral cavity after surgery

Ten patients who underwent oral cancer surgery with flap reconstruction and were managed under intubation by tracheotomy, had their oral cavity irrigated with 200 ml of water and were divided randomly into two treatment groups: (1) parenteral administration of 1500 mg of ampicillin/sulbactam three times a day (five patients), and (2) parenteral ampicillin/sulbactam plus topical administration of 10 g of 3% tetracycline ointment on the tongue on the day after surgery (five patients). The number of bacteria on the surface of the tongue and in the oropharyngeal fluid was measured every 30 min for 8 h.

The concentration of tetracycline in the oropharyngeal fluid was measured in a patient undergoing neck dissection during surgery, before topical administration, and at 5 min, 1, 2, and 5 h after topical administration, with a bioassay.

This study was approved by the university ethics committee.

Results

Number of bacteria in the oral cavity during surgery ( Fig. 1 )

The bacterial count on the tongue and in the oropharyngeal fluid increased gradually. The number of bacteria in the oropharyngeal fluid exceeded 10 7 CFU/ml after 30 min, while on the tongue the number exceeded 10 7 CFU/ml after 2 h. In contrast, the number of bacteria on the buccal mucosa and the hard palate did not increase within the measurement time.

Fig. 1
Growth of oral bacteria during surgery. Bacteria in the oropharyngeal fluid and on the tongue increased rapidly after intubation, whereas bacteria on the buccal mucosa and the palate did not.

Efficacy of the topical administration of povidone iodine gel or tetracycline ointment on the inhibition of bacterial growth in the oral cavity during surgery ( Fig. 2 )

In patients administered topical povidone iodine, the number of bacteria on the tongue remained below 10 7 CFU/ml for approximately 150 min. However, bacteria in the oropharyngeal fluid multiplied at a rate similar to the control group, which indicated that topical povidone iodine did not inhibit the growth of oral bacteria.

Fig. 2
Efficacy of topical povidone iodine gel and tetracycline ointment on the reduction of oral bacterial growth during intubation. The growth of bacteria on the tongue was slightly suppressed by the topical administration of iodine, and markedly suppressed by tetracycline ointment (A). In the oropharyngeal fluid, there was no inhibition of bacterial growth by topical povidone iodine gel, while after the topical administration of tetracycline ointment, oral bacteria decreased markedly, and this was maintained for at least 165 min after intubation (B).

In contrast, after the topical administration of tetracycline ointment, the number of oral bacteria remained below baseline both on the tongue and in the oropharyngeal fluid throughout the operation. The efficacy of topical tetracycline on the inhibition of oral bacteria was apparent for up to 150 min.

Efficacy of topical tetracycline ointment on the inhibition of bacterial growth in the oral cavity after surgery ( Fig. 3 )

In the control group, oral bacteria increased rapidly after irrigation of the oral cavity. The number of bacteria in the oropharyngeal fluid reached 10 8 CFU/ml approximately 150 min later, and the number on the tongue was more than 10 7 CFU/ml 2 h later. It was thought that the level of oral bacteria in the control group had increased to a level high enough to represent a great risk of SSI, so measurements were stopped and irrigation was performed.

Fig. 3
Efficacy of topical tetracycline ointment on the reduction of oral bacterial growth after surgery during respiratory management by tracheotomy. The number of oral bacteria was less than baseline both on the tongue and in the oropharyngeal fluid 30 min after the topical administration of tetracycline ointment. The bacterial count on the tongue was maintained at below 10 6 CFU/ml for up to 7 h, while that in the oropharyngeal fluid was maintained at below 10 6 CFU/ml for up to 5 h and at below 10 7 CFU/ml for up to 7 h after topical administration.

In contrast, the number of oral bacteria was reduced to less than baseline both on the tongue and in the oropharyngeal fluid at 30 min after the topical administration of tetracycline ointment. The number of bacteria on the tongue remained below 10 6 CFU/ml for up to 7 h after the topical administration of tetracycline ointment. The bacterial count in the oropharyngeal fluid increased gradually, but remained below 10 6 CFU/ml for up to 5 h and below 10 7 CFU/ml for up to 7 h after topical administration.

The concentration of tetracycline in the oropharyngeal fluid was 1.70 μg/ml at 5 min, 89.3 μg/ml at 1 h, and 183.4 μg/ml at 2 h after application, and was maintained at 89.3 μg/ml up to 5 h after application.

A SSI occurred in a patient in the control group, but there was no case of SSI in those receiving topical tetracycline.

Results

Number of bacteria in the oral cavity during surgery ( Fig. 1 )

The bacterial count on the tongue and in the oropharyngeal fluid increased gradually. The number of bacteria in the oropharyngeal fluid exceeded 10 7 CFU/ml after 30 min, while on the tongue the number exceeded 10 7 CFU/ml after 2 h. In contrast, the number of bacteria on the buccal mucosa and the hard palate did not increase within the measurement time.

Jan 17, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Efficacy of topical antibiotic administration on the inhibition of perioperative oral bacterial growth in oral cancer patients: a preliminary study
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