International Journal of Surgery 54 (2018) 170–175

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International Journal of Surgery

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Original Research

Perioperative antibiotic prophylaxis in open tracheostomy: A preliminary T

randomized controlled trial
Pichit Sittitraia,∗, Chatmanee Siriwittayakornb
a
Department of Otolaryngology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
b
Otolaryngology Unit, Nakornping Hospital, Chiang Mai, 50180, Thailand

A R T I C LE I N FO A B S T R A C T

Keywords: Background: The efficacy of perioperative antibiotic prophylaxis for prevention of wound infection in open
Tracheostomy tracheostomy has been minimally studied and remains controversial.
Surgical wound infection Methods: A preliminary double-blind, randomized, placebo-controlled trial was conducted. A total of 159 pa-
Antibiotic prophylaxis tients who underwent open tracheostomy were enrolled, and 88 patients were excluded because of lack of desire
Clindamycin
to participate in research, emergency condition, administration of other antibiotics, immunocompromise, or
cervical skin infection. The remainings were randomly assigned to an antibiotic group or a control group.
Another 11 patients were excluded after the randomization due to intraoperative contamination, death from the
underlying disease, receiving other antibiotics, or lost to the follow-up. A total of 30 patients in each group were
qualified for analysis. In the antibiotic group, clindamycin was intravenously administered 30 min before the
incision and every 8 h after the operation for 24 h. In the control group, an equal volume of sterile saline was
administered.
Results: Wound infection developed in 2 patients (6.7%) in the antibiotic group and 7 patients (23.3%) in the
control group (p = 0.08). In multivariate analysis, smoking and previous neck irradiation were the significant
risk factors for wound infection (p = 0.042 and 0.019, respectively). The mean length of hospital stay after
tracheostomy in patients with and without wound infection were 17 ± 2 days and 4 ± 2 days, respectively
(p = 0.013).
Conclusion: The result of this preliminary study reveals that antibiotic prophylaxis reduced tracheostomy wound
infection rate from 23.3% to 6.7% although it was not statistically significant. However, wound infection may
lead to serious complications and prolonged postoperative length of hospital stay, and therefore proper perio-
perative antibiotics should be considered in patients who are not receiving other antibiotics, and particularly in
patients with risk factors for wound infection.

1. Introduction
Tracheostomy is one of the most common operations performed in
the hospital [1,2]. It has been done as an emergency or elective pro-
cedure [1,2]. Initially, tracheostomy was performed for upper airway
obstruction and later the indications were extended to include re-
spiratory failure, prolonged endotracheal intubation and ventilation,
pulmonary toilet, and as an adjunct to surgery [1–3]. Open or surgical
tracheostomy has been widely accepted as the standard of care for a
long period of time and mostly performed in the operating room [1].
Since 1985, when percutaneous dilatational tracheostomy was in-
troduced by Ciaglia [4], the procedure has been rapidly adopted and
has increased in popularity because of its safety, convenience, and
technical advantages of bedside procedure [1]. However, open
tracheostomy still has a main role for emergency situations, difficult
neck anatomy, previous tracheostomy, patients with comorbidities, and
failure of percutaneous tracheostomy [1].
The incidence of complications associated with open tracheostomy
has been reported between 5% and 40% which include hemorrhage,
apnea, adjacent tissue injury, tube displacement, subcutaneous em-
physema, pneumothorax, and infection [5–7]. The incidence of infec-
tion following elective open tracheostomy has been reported up to 33%
[8–10]. Tracheotomy is considered a clean-contaminated wound as the
procedure enters the upper aerodigestive tract which has bacterial co-
lonization and may also become contaminated by the bacterial flora of
the skin especially in urgent or emergency tracheostomy [5,9]. Wound
infection may produce serious complications such as tracheitis, med-
iastinitis, clavicular osteomyelitis, and necrotizing fasciitis [5–7].

∗
Corresponding author.
E-mail addresses: psittitrai@yahoo.com (P. Sittitrai), chatmaneesiri@gmail.com (C. Siriwittayakorn).

https://doi.org/10.1016/j.ijsu.2018.04.047
Received 17 January 2018; Received in revised form 6 April 2018; Accepted 24 April 2018
Available online 02 May 2018
1743-9191/ © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
P. Sittitrai, C. Siriwittayakorn
However, perioperative antibiotics to prevent surgical site infection in
tracheostomy have not been generally considered because of minimal
evidence of their effectiveness [11,12].
The purpose of this randomized controlled trial was to clarify
whether antibiotic prophylaxis for open tracheostomy would reduce
infection rate and to identify risk factors for tracheostomy wound in-
fection.
2. Materials and methods
2.1. Study design
The preliminary prospective randomized controlled trial was con-
ducted in the Department of Otolaryngology, Faculty of Medicine, be-
tween February 2015 and January 2017. The study protocol was per-
formed in compliance with the guidelines for Good Clinical Practice and
the Declaration of Helsinki and approved by the institutional ethics
committee. All the subjects signed an informed consent form prior to
enrollment.
The inclusion criteria were patients between 18 and 85 years of age
who had open tracheostomy performed with the following indications:
1) upper airway obstruction from tumor, airway edema or stenosis,
neck or maxillofacial trauma, or foreign body, 2) prolonged en-
dotracheal intubation, and 3) facilitating pulmonary toilet.
The exclusion criteria were patients who had immunosuppressive
conditions, allergy to clindamycin, diagnosis of cervical skin infection
or tracheobronchopulmonary infection, administration of other anti-
biotics within 7 days before tracheostomy or within 14 days after tra-
cheostomy, and patients who were deceased or unavailable for follow-
up in the 30 days after tracheostomy.
The randomization process was carried out using the CONSORT
statement 2010 checklist for randomized controlled clinical trials.
Patients were assigned in a double-blinded method to either an anti-
biotic group or a control group. A randomized block design by a com-
puter-generated list was used to allocate patients into the two groups.
The surgery team, the surgeon who instructed patients regarding the
intravenous injection and the surgeon who evaluated the wound were
all blinded to the allocation group. In addition, the patients were not
informed about the contents of injection.
2.2. Surgical technique
Tracheostomy was generally performed in the operating room under
general anesthesia or monitored anesthesia care. The patient was po-
sitioned with the neck extended. An aqueous solution of 10% povidone-
iodine was used for skin disinfection before the operation. A 3–4 cm
transverse skin incision was made midway between the sternal notch
and cricoid cartilage or two fingerbreadths above the sternal notch. The
strap muscles were separated along midline and retracted laterally. The
thyroid isthmus was retracted superiorly, inferiorly, or divided. A
cruciate incision was made at the second and third tracheal rings. Two
stay sutures were used to secure the tracheal opening. The plastic cuffed
tracheostomy tube was inserted. The skin incision was not sutured
unless it was larger than 5 cm. The tracheostomy tube tape was placed
and secured around the neck. A 4x4-inch sterile gauze was cut to allow
placement under the tracheostomy tube. In postoperative care, the
wound and surrounding skin were cleaned with 70% ethyl alcohol and
the sterile gauze was changed twice daily.
2.3. Intervention
Because the common pathogens responsible for tracheostomy
wound infection were reported as Staphylococcus spp. and Streptococcus
spp [5,11,13], the selected antibiotic in the study was clindamycin.
Patients in the antibiotic prophylaxis group received 100 mL of sterile
saline with 600 mg of clindamycin by continuous intravenous infusion
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International Journal of Surgery 54 (2018) 170–175
30 min before the surgical incision and every 8 h after the operation for
24 h for a total of 4 doses. An equal volume of sterile saline was ad-
ministered to the control group in the same manner.
2.4. Follow-up
Surgical site infection is classified as wound infection which occurs
within 30 days after the operation [14]. The wounds were carefully
examined every day for 30 days by surgeons who were blinded to the
randomization. Patients who were discharged from the hospital earlier
than day 30 would be instructed to record wound characteristics, and
follow-up at day 30 after the operation. The criteria of wound infection
included: 1) purulent drainage, 2) identification of organisms, 3) in-
flammation accompanied by fever or tenderness, 4) abscess or other
evidence of infection around the wound detected on gross anatomical
or histopathological exam, or imaging test, or 5) diagnosis of a wound
infection by the surgeon [14]. Wound discharge was sent for aerobic
bacterial culture and sensitivity. Anaerobic bacterial culture was not
done because the tracheostomy wound is an open wound and no pus
collection in the deep tissues was detected in any patients. The infected
wound was managed with intensive local wound dressing, daily tra-
cheostomy tube change, and antibiotics change based on the culture
results.
Selected demographic data (sex, age, history of smoking, diabetes
mellitus, previous neck irradiation, preoperative albumin level, pre-
operative hemoglobin level), indication for tracheostomy, and pre-
operative length of hospital stay were documented and compared be-
tween study groups. The outcomes including infection rate, causative
organism, duration of postoperative hospitalization, and surgical com-
plication were recorded.
2.5. Statistical analysis
Statistical analyses were performed using SPSS (version 22) for
Windows (IBM Corporation, Armonk, NY, USA). Continuous variables
were compared using Student's t tests or Mann–Whitney U tests, and
categorical variables were compared using chi-square tests or Fisher's
exact tests as appropriate. For analysis of risk factors, the chi-square
association test was used. Then, a logistic regression model was out-
lined based on a stepwise forward method testing the significant vari-
ables at univariate and multivariate analysis. The risk measure used was
the odds ratio (OR), and its respective 95% confidence interval was
calculated. Statistical significance was considered for p values less than
0.05.
3. Results
There were 159 eligible patients during the study period. Before
randomization, 88 patients were excluded because of lack of desire to
participate in research, emergency condition, administration of other
antibiotics, immunocompromise, or cervical skin infection. The re-
maining 71 patients were randomly assigned to either antibiotic group
(n = 36) or control group (n = 35). Six patients in the antibiotic group
and five patients in the control group were excluded after randomiza-
tion because of intraoperative contamination, death due to underlying
diseases, receipt of other antibiotics during the postoperative period,
and loss to follow-up. Therefore, data from 30 patients in each group
were analyzed (Fig. 1).
There were no statistically significant intergroup differences in de-
mographic parameters and indication for tracheostomy which con-
firmed the correct selection of the subjects and randomization of the
groups and enabled further analyses (Table 1). Because of the exclusion
criteria of no other perioperative antibiotics, the only indication for
tracheostomy in this study was upper airway obstruction from tumor or
stenosis.
Wound infection was detected in 9 patients with the overall
P. Sittitrai, C. Siriwittayakorn International Journal of Surgery 54 (2018) 170–175

Fig. 1. Flowchart of participants in randomized controlled trial of perioperative antibiotic prophylaxis versus placebo in open tracheostomy.

Table 1
Comparison of demographic data between the study groups.
Variables Antibiotic group Control group p value
N = 30 (%) N = 30 (%)

Age, year (mean ± SD) 49.9 ± 11.9 48.8 ± 9.5 0.66

Sex
M 23 (76.7) 25 (83.3) 0.75
F 7 (23.3) 5 (16.7)
Cause of airway obstruction
Laryngohypopharyngeal cancer 20 (66.7) 19 (63.3) 0.72
Thyroid cancer 2 (6.7) 4 (13.3)
Tracheal tumor 1 (3.3) 2 (6.7)
Laryngotracheal stenosis 7 (23.3) 5 (16.7)
Smoking
Yes 5 (16.7) 6 (20) 1.0
Diabetes mellitus
Yes 4 (13.3) 3 (10) 1.0
Previous neck irradiation
Yes 2 (6.7) 4 (13.3) 0.67
Albumin level, g/dl (mean ± SD) 3.5 ± 0.1 3.6 ± 0.2 0.46
Hemoglobin level, g/dl (mean ± SD) 12.9 ± 0.6 12.7 ± 0.5 0.17
Preoperative hospitalization
< 6h 1 (3.3) 4 (13.3) 0.5
6–24 h 14 (46.7) 11 (36.7)
24–72 h 12 (40) 11 (36.7)
> 72 h 3 (10) 4 (13.3)

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Table 2
Comparison of outcomes between the study groups.
Outcomes Antibiotic group Control group p value
N = 30 (%) N = 30 (%)

Infection
Yes 2 (6.7) 7 (23.3) 0.08
Time to infection, day (mean ± SD) 3.0 ± 1.4 3.7 ± 0.9 0.42
Postoperative hospitalization, day (mean ± SD) 5.1 ± 3.9 7.1 ± 5.9 0.13
Bleeding
Yes 3 (10) 5 (16.7) 0.71
Pneumothorax
Yes 2 (6.7) 1 (3.3) 1.0

Table 3 Table 4
Univariate analysis of risk factors for tracheostomy wound infection. Details of preoperative hospitalization duration and bacterial pathogens in nine
patients who developed wound infection.
Variables Infection No infection p value
N = 9 (%) N = 51 (%) Patient group Preoperative hospitalization Pathogen
duration (h)
Antibiotic
Yes 2 (22.2) 28 (54.9) 0.18 Antibiotic > 72 Pseudomonas aeruginosa
Age, year Klebsiella pneumoniae
< 60 8 (90) 42 (82.4) 0.45 Antibiotic > 72 Pseudomonas aeruginosa
≥ 60 1 (10) 9 (17.6) Proteus mirabilis
Sex Control <6 Staphylococcus aureus
M 9 (100) 39 (76.5) 0.99 Control <6 Staphylococcus aureus
F 0 12 (23.5) Streptococcus viridans
Cause of airway obstruction Control <6 Streptococcus viridans
Laryngohypopharyngeal cancer 8 (88.9) 31 (60.8) 0.99 Control <6 Streptococcus pyogenes
Thyroid cancer 0 6 (11.8) 0.99 Control > 72 Pseudomonas aeruginosa
Tracheal tumor 1 (11.1) 2 (3.9) 1.0 Proteus mirabilis
Laryngotracheal stenosis 0 12 (23.5) 0.99 Streptococcus viridans
Smoking Control > 72 Klebsiella pneumoniae
Yes 8 (88.9) 7 (13.7) < 0.001 Proteus mirabilis
Diabetes mellitus Control > 72 Proteus mirabilis
Yes 5 (55.6) 2 (3.9) 0.09
Previous radiation
Yes 6 (66.7) 1 (2) < 0.001
bacterial infection were hospitalized for less than 6 h (Table 4). The
Albumin level, g/dl
< 3.5 7 (77.8) 6 (11.8) 0.001 mean length of hospital stay after the operation in patients with and
≥ 3.5 2 (22.2) 45 (88.2) without wound infection were 17 ± 2 days and 4 ± 2 days, respec-
Hemoglobin level, g/dl tively which was significantly different (p = 0.013).
< 12.5 1 (11.1) 13 (25.5) 0.36
Regarding the bacteriology results, the isolated Gram-positive bac-
≥ 12.5 8 (88.9) 38 (74.5)
Preoperative hospitalization
teria were Staphylococcus aureus, Streptococcus viridans, and
< 6h 3 (33.3) 2 (3.9) 0.81 Streptococcus pyogenes while the isolated Gram-negative bacteria were
6–24 h 0 25 (49) 0.33 Pseudomonas aeruginosa, Klebsiella pneumonia, and Proteus mirabilis.
24–72 h 0 23 (45.1) 0.99 Other complications noted in the study were minor bleeding and
> 72 h 6 (66.7) 1 (1.9) 0.99
pneumothorax, with no significant difference noted between groups for
either complication (Table 2). Minor bleeding was observed in eight
infection rate of 15%, and two patients were in the antibiotic group patients, three in the antibiotic group and five in the control group. All
(infection rate, 6.7%) and seven patients in the control group (infection patients with bleeding were detected within two days after the opera-
rate, 23.3%) (p = 0.08). Characteristics of wound infection were de- tion, and were treated successfully with packing. All three patients with
tected as cellulitis with turbid discharge or with purulent discharge. All pneumothorax were detected during or within one hour of the opera-
wound infection occurred during day two to day five after the operation tion, and were managed with tube drainage. There was no record of any
(Table 2). major complication or perioperative mortality related to the procedure.
In univariate analysis, eight variables were analyzed to determine
the risk factors for wound infection (Table 3). History of smoking,
4. Discussion
previous neck irradiation, and albumin level < 3.5 g/dl were associated
with the development of infection (p < 0.001, p < 0.001, and
Complications of open tracheostomy are consistent, in terms of type,
p = 0.001, respectively). When using multivariate analysis, only
frequency, and severity, with wound infection is second in incidence
smoking (p = 0.042, 95% CI = 22, [1.1–46.7]) and previous neck ir-
only to bleeding [6,15]. Exposure to contaminated oral secretions, in-
radiation (p = 0.019, 95% CI = 31.5, [1.7–65.9]) had a significant ef-
fected sputum, and the colonizing flora of skin provide favorable con-
fect on wound infection while albumin level did not (p = 0.051).
ditions for tracheotomy infection [5–7,9]. Wound infection includes
Both infected patients in the antibiotic group were hospitalized
local tissue inflammation, cellulitis, and abscess which may progress to
longer than 72 h (6 days, and 7 days) before having tracheostomy and
the serious conditions such as mediastinitis and necrotizing fasciitis
the causative organisms were Gram-negative bacteria. Of the seven
[5–7].
infected patients in the control group, three patients who had either
Antibiotic prophylaxis initiated prior to skin incision and continued
pure Gram-negative (2 patients) or mixed Gram-positive and Gram-
over the period of 24 h after surgery has been documented to reduce
negative (1 patient) bacterial infection were hospitalized longer than
surgical site infection in clean-contaminated head and neck surgery
72 h preoperatively. The other four patients with pure Gram-positive
[16]. Clindamycin was selected for antibiotic prophylaxis in this study

173
P. Sittitrai, C. Siriwittayakorn
because of its effectiveness in preventing head and neck surgical site
infection [16,17] and because the causative organisms of tracheostomy
wound infection are considered to be Staphylococcus spp. and Strepto-
coccus spp. [5,11,13].
All nine patients with wound infection in this study developed the
infection within five days after the operation with an overall infection
rate of 15%. This is consistent with the rates reported in a meta-analysis
(range, 0%–33.3%) [9]. The wound infection rate was reduced from
23.3% (seven patients) in the control group to 6.7% (two patients) in
the antibiotic group although it was close, it was not statistically sig-
nificant (p = 0.08).
It should be noted that the four infected patients in the control
group with Gram-positive bacterial infection were hospitalized less
than 6 h before the operation and all of them were sensitive to clin-
damycin. The other five infected patients in both groups who were
hospitalized longer than 72 h had either pure Gram-negative or mixed
Gram-positive and Gram-negative organisms, and these pathogens are a
common cause of hospital-acquired infection. According to this finding,
the causative organisms in patients who were recently hospitalized
before tracheostomy were most likely to be Gram-positive bacteria,
while the possible causative organisms in patients who were hospita-
lized longer than 72 h were either pure Gram-negative or mixed Gram-
positive and Gram-negative bacteria.
The risk factors for wound infection in head and neck surgery have
been reported to include smoking, alcohol, albumin, hemoglobin, dia-
betes mellitus, previous neck irradiation, chemotherapy, and poor oral
hygiene [18]. In this study, smoking, previous neck irradiation, and
albumin level < 3.5 g/dl were identified as factors increasing risk of
wound infection in univariate analysis while only smoking and previous
radiotherapy were revealed as risk factors in multivariate analysis.
Based on these findings, the use of antibiotic prophylaxis to prevent
tracheostomy wound infection should be considered in high risk pa-
tients who have history of smoking or previous neck irradiation. Based
on the culture results in the study, antibiotics which include Gram-
positive bacterial coverage such as clindamycin, antistaphylococcus
penicillins, or first-generation cephalosporins are the suitable anti-
biotics in patients who are hospitalized within 6 h prior to the tra-
cheostomy and antibiotics which cover both Gram-positive and Gram-
negative bacteria such as clindamycin combined with third-generation
cephalosporin are the preferred choice in patients who are hospitalized
longer than 72 h.
There are limitations in the study. First, this is a single-center ran-
domized study with a rather small sample size. Second, our study did
not include emergency or urgent tracheostomy which may have a high
rate of wound infection without antibiotic prophylaxis because of the
inability to obtain informed consent for the study with this specific si-
tuation.
In conclusion, this preliminary study reveals that the tracheostomy
wound infection rate was reduced from 23.3% to 6.7% with perio-
perative clindamycin although it was not statistically significant.
However, with the possible serious complications and prolonged post-
operative length of hospital stay, antibiotic prophylaxis should be
considered in patients who are currently not receiving other antibiotics,
and particularly in patients who are at risk of wound infection such as a
history of smoking or previous neck irradiation. Perioperative anti-
biotics which cover Gram-positive bacteria should be selected in pa-
tients who are hospitalized less than 6 h prior to the tracheostomy and
antibiotics which cover both Gram-positive and Gram-negative bacteria
for patients who are hospitalized longer than 72 h. With the trend to-
ward decreasing tracheostomy wound infection rate with perioperative
antibiotics, this warrants further investigation in a larger study.
Ethical approval
The study was approved by the institutional ethics committee of
Faculty of Medicine, Chiang Mai University.
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International Journal of Surgery 54 (2018) 170–175
Study code: 2556-01852.
ID: 01852.
Funding
None.
Author contribution
Pichit Sittitrai designed the study, developed the methodology,
collected the data, performed the analysis, and wrote the manuscript.
Chatmanee Siriwittayakorn designed the study, collected the data,
and wrote the manuscript.
Conflicts of interest
The authors declare no competing financial interests exist.
Research registration Unique Identifying Number (UIN)
UIN3575.
Guarantor
Pichit Sittitrai.
Saisaward Chiyasate.
Department of Otolaryngology, Faculty of Medicine, Chiang Mai
University.
Author disclosure statement
No competing financial interests exist.
Acknowledgments
The authors would like to thank Dr. for assistance in statistical
analysis.
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