Aims: The purpose of this paper was to investigate the impact of Methicillin Resistant Staphylococcus Aureus (MRSA) infection in the aetiology of pharyngo-cutaneous fistula (PCF) formation following total laryngectomy for advanced laryngeal cancer.Methods: This was a retrospective uncontrolled case study series of 31 consecutive patients based in a single institution tertiary referral head and neck oncology centre.Results: Pharyngo-cutaneous fistulas (PCF) following total laryngectomy occurred in 10 (32%) patients. MRSA was identified in 80% of patients with a PCF compared to 9% of patients that did not develop a fistula (p = 0.0001255 Fisher exact test). MRSA infection (p = 0.00012) and previous radiotherapy (p = 0.00025) were the only significant factors found to be important in fistula formation on multivariate analysis. Post-operative infections such as cellulitis, chest infection and carotid fistula were also associated with MRSA infections.Conclusion: MRSA infection following total laryngectomy for laryngeal cancer can lead to potential serious complications such as PCF. Patients who underwent total laryngectomy following radiotherapy failure are at a higher risk of acquiring MRSA.</p

Ahmad Orabi

Argyris Manganaris

Jean-Pierre Jeannon

Ricard Simo

PubMed

Crossref

Head & Neck Oncology

Methicillin Resistant Staphylococcus Aureus Infection as a causative agent of fistula formation following total laryngectomy for advanced head &amp; neck cancer

Jeannon, Jean-Pierre

Orabi, Ahmad

Manganaris, Argyris

Simo, Ricard

King's Research Portal

Springer - Publisher Connector

Jeannon et al. Head & Neck Oncology 2010, 2:14
http://www.headandneckoncology.org/content/2/1/14
Open AccessR E S E A R C HResearchMethicillin Resistant Staphylococcus Aureus 
Infection as a causative agent of fistula formation 
following total laryngectomy for advanced head & 
neck cancer
Jean-Pierre Jeannon*, Ahmad Orabi, Argyris Manganaris and Ricard Simo
Abstract
Aims: The purpose of this paper was to investigate the impact of Methicillin Resistant Staphylococcus Aureus (MRSA) 
infection in the aetiology of pharyngo-cutaneous fistula (PCF) formation following total laryngectomy for advanced 
laryngeal cancer.
Methods: This was a retrospective uncontrolled case study series of 31 consecutive patients based in a single 
institution tertiary referral head and neck oncology centre.
Results: Pharyngo-cutaneous fistulas (PCF) following total laryngectomy occurred in 10 (32%) patients. MRSA was 
identified in 80% of patients with a PCF compared to 9% of patients that did not develop a fistula (p = 0.0001255 Fisher 
exact test). MRSA infection (p = 0.00012) and previous radiotherapy (p = 0.00025) were the only significant factors 
found to be important in fistula formation on multivariate analysis. Post-operative infections such as cellulitis, chest 
infection and carotid fistula were also associated with MRSA infections.
Conclusion: MRSA infection following total laryngectomy for laryngeal cancer can lead to potential serious 
complications such as PCF. Patients who underwent total laryngectomy following radiotherapy failure are at a higher 
risk of acquiring MRSA.
Introduction
Total laryngectomy is a major surgical procedure used to
treat advanced cancer of the larynx.
Pharyngo-cutaneous fistula (PCF) is a complex type of
wound dehiscence and hence a potential major complica-
tion following total laryngectomy. The reported inci-
dence of this complication following laryngectomy varies
between 8-40% [1]. It results when a pathological com-
munication develops between the internal mucosa of the
pharynx and the external skin which discharges saliva
(Figure 1). The immediate sequelae of PCF is that oral
feeding has to be suspended. This delays healing in the
post-operative period and the subsequent loss of fluids,
electrolytes and proteins in the fistula further compro-
mises the patient's condition. Long-term problems fol-
lowing PCF may include aspiration, further wound
infection, chest infection and cachexia.
The aetiology of PCF is thought to be multi-factorial
[1]. Several factors have been thought to be important
and can be generally divided into patient factors and
operative factors. In particular these can include pre-
operative co-morbidity, pre-operative radiotherapy, peri-
operative wound infection, advanced T stage and closure
technique.
Methicillin Resistant Staphylococcus Aureus (MRSA)
infection in the post-surgical patient is associated with
higher post-operative morbidity including skin break-
down and cellulitis [2]. No previous study has investi-
gated MRSA infection as a causative factor in PCF
following laryngectomy.
The objective of this paper is to review our experience
of patients who have developed PCF following total
* Correspondence: jean-pierre.jeannon@gstt.nhs.uk
1 Department of Ear Nose & Throat - Head and Neck Surgery, Guy's and St 
Thomas' Hospital NHS Foundation Trust, London, UK
Full list of author information is available at the end of the article© 2010 Jeannon et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Jeannon et al. Head & Neck Oncology 2010, 2:14
http://www.headandneckoncology.org/content/2/1/14
Page 2 of 5Figure 1 Photograph showing large PCF 10 days post SL with 
heavy growth of MRSA.
 
laryngectomy and determine the influence of MRSA is a
causative factor.
'What is already known about this topic?
The aetiology of pharyngo-cutaneous fistula (PCF) is
thought to be multifactorial. MRSA infection is associ-
ated with higher postoperative morbidity including skin
breakdown and fistula formation. No previous study has
investigated MRSA infection as a causative factor in PCF
following laryngectomy.
'What does this article add?
This is the first study to identify MRSA as a possible caus-
ative agent in PCF following laryngectomy. Implementa-
tion of MRSA eradication protocol is recommended in
every patient undergoing laryngectomy.
Material and Methods
This is a retrospective review of 31 consecutive patients
who underwent total laryngectomy at Guy's & St Thomas
NHS Foundation Trust London, which is the tertiary
regional cancer centre for the South East London Head
and Neck Cancer Network (SELCN). The study period
ran from January 2004 until January 2007. From January
2004 all patients undergoing treatment for head and neck
cancer have been entered prospectively on a database.
All patients with a diagnosis of head and neck cancer
were discussed in the regional head and neck oncology
multidisciplinary team (MDT) meeting prior to definitive
treatment being commenced.
Patients underwent elective pre-admission MRSA
screening upon admission through swab taking. Subse-
quent screening continued throughout the in patient stay
in hospital. Therefore all new MRSA acquisitions were
therefore detected prospectively. During their inpatient
stay as a routine protocol, patients were screened for
MRSA twice weekly.
Patient data including MRSA swab results and post-
operative water soluble swallow tests were retrieved from
the electronic patient record.
All patients undergoing head and neck surgery were
given peri-operative antibiotic prophylaxis and post-
operative gastro-oesophageal reflux medication as a pro-
tocol.
For the purpose of this study a pharyngo-cutaneous fis-
tula was defined as a clinically detected fistula or radio-
logically identified leak that delayed the onset of oral
feeding after laryngectomy.
Multivariate analysis was performed using STATA sta-
tistical software to analyse the data. The following factors
were analysed to determine their effect on fistula forma-
tion: T stage, previous radiotherapy and MRSA infection.
Ethical Considerations
Data was retrieved from the database using medical
record numbers hence patients remained anonymous.
Ethical approval was not needed for this study.
Results
During the study period (2004 to 2007 inclusive), 31 total
laryngectomies were performed for advanced laryngeal
cancer.
The patient demographic data were illustrated in Table
1. The mean patient age was 65 years (range 37 to 86).
15 patients underwent primary laryngectomy for
advanced laryngeal cancer and 16 patients had salvage
laryngectomy for recurrence after previous failed radio-
therapy.
A pharyngo-cutaneous fistula (PCF) occurred in 10
(32%) patients, MRSA was identified in 8 of these
patients. Of the 21 patients that did not develop a PCF, 2
were found to acquire MRSA infection (in the tracheal
stoma). This difference reached statistical significance p =
0.0001255 Fisher exact test (Table 2).
None of these 31 patients were found to be carriers of
MRSA on pre-operative screening. Therefore from this
Jeannon et al. Head & Neck Oncology 2010, 2:14
http://www.headandneckoncology.org/content/2/1/14
Page 3 of 5group of 31 patients, 10 (32%) were seen to acquire
MRSA during their hospital stay.
Using multivariate analysis, previous radiotherapy (p =
0.00025) and MRSA infection (p = 0.00012) were identi-
fied as significant risk factors for PCF (Table 3).
MRSA was cultured from the tracheostomy stoma site
in 5 patients, in 3 patients it was detected in the fistula
site, from the surgical drain 1 and from the gastrostomy
site in 1 patient (Figure 2).
The 2 patients that did acquire MRSA but did not
develop PCF did however suffer significant morbidity. 1
patient developed a significant cellulitis infection and 1
had a carotid fistula that required return to the operating
theatre to arrest the bleeding.
Discussion
MRSA may reside in healthy individuals and not cause
any health problems. However hospital acquired infec-
tion can result in significant morbidity and mortality. The
first case of MRSA was identified as early as 1961- 1962
shortly after introduction of Methicillin in 1960 [2-4].
MRSA has caused particular concern due to the resis-
tance to standard antibiotics caused by gene mecA and
the rapidity with which it spreads [2-5]. MRSA arose as a
hospital based infection but has steadily spread to the
community [4,5]. Hospital acquired MRSA infection has
been steadily increasing and in some reports infection
rates have reached over 60% [4]. In this series we have
identified an acquisition rate of 30% which is high. We
believe this is because head and neck patients undergoing
major surgery particularly at risk of this infection.
Head and neck cancer patients are prone to MRSA
infection due to a number of factors such as: prolonged
hospitalization, intravascular catheterization, compro-
mised host immunity, malignancy, chemotherapy, radio-
therapy surgery, prior antibiotic therapy and prolonged
operative time [2-7]. Many of these factors were present
in our series of patients. Following total laryngectomy,
the mucosa of the trachea is permanently directly
exposed to room air and we feel this site is particularly
prone to MRSA infection. This is why the tracheal stoma
was shown to be the commonest site of infection.
Serious postoperative complications related to MRSA
infection have been identified in head and neck surgery
patients with significant increase in morbidity [8,9] num-
ber of surgical procedures and prolonged hospitalization
time [10]. One of our patients had a carotid fistula or
'blow out' which is a life threatening complication. Colo-
nisation of the tracheostomy site appeared to be the most
important site of MRSA infection. The creation of a per-
manent tracheostomy following total laryngectomy may
significantly reduce the patient's local defence mecha-
nism allowing a conduit of infection to the aero-digestive
tract.
PCF following laryngectomy constitutes a particularly
serious complication with subsequent devastating medi-
cal, functional, psychological and economical effects. The
rate ranges considerably from 8% to 40%, according to the
literature [11-17]. A recently published meta-analysis of
previously published studies on post-laryngectomy PCF
concluded that the following four factors were thought to
be significant: a) preoperative radiotherapy, b) postopera-
tive haemoglobin level below 12.5 g/dl, c) prior tracheos-
tomy, and d) preoperative radiotherapy and concurrent
neck dissection [1]. Our study also has identified pre-
operative radiotherapy as an important risk factor for
PCF.
To our knowledge this is the first study to investigate
and suggest a potential causal relationship between PCF
and MRSA in patients undergoing total laryngectomy for
laryngeal cancer. Whilst we have found a significantly
higher MRSA infection rate in patients that have devel-
oped PCF following laryngectomy compared to those
that did not, this association only implicates MRSA as a
possible causative factor in. We recognise the limitations
of this paper in that the design is retrospective and sam-
ple size small, however we feel the high incidence of
MRSA infection seen in the PCF patients warrants fur-
ther study.
The incidence of PCF in our laryngectomy patients was
high (32%) compared to previously published series. The
focus of future study in our institution is aimed at reduc-
ing this PCF rate.
MRSA principal mode of transmission is through direct
contact via hospital personnel and by airborne transmis-
sion particularly from patients with tracheostomies [2-6].
Many strategies have been advocated to prevent MRSA
infection with variable degree of evidence based, includ-
ing search and destroy policy, restrictive antibiotic pre-
scribing policy [12], hand hygiene with the use of alcohol-
based solutions, isolation measures [13]. The high inci-
dence of MRSA infection seen in this patient group
obliged us to upgrade our infection control protocols and
Figure 2 Sites where MRSA was isolated.
 
0
1
2
3
4
5
Fistula site Stoma Drain site PEG
N
u
m
b
e
r
Jeannon et al. Head & Neck Oncology 2010, 2:14
http://www.headandneckoncology.org/content/2/1/14
Page 4 of 5we have subsequently seen a dramatic reduction in
MRSA infection rates.
There is some controversy regarding treating MRSA
colonization versus infection particularly in hospital staff
carriers and in endemic areas like UK, which can be
proved to be difficult. However because of the particular
risks associated with head and neck cancer patients, colo-
nized patients should be eradicated prior to major sur-
gery [10]. The current approach is to carry out
preoperative screening and appropriate treatment by
antiseptic skin washes, nasal mupirocin and chlorhexa-
dine mouthwashes, isolation or barrier nursing and peri-
Table 1: Patient Demographic Data
Patient TNM PREVIOUS RADIOTHERAPY MRSA FISTULA
1 T4N0M0 N X X
2 T2N0M0 Y √ √
3 T4N1M0 N X X
4 T2N0M0 Y √ X
5 T4N0M0 Y X X
6 T3N2BM0 N X X
7 T4N1M0 N X X
8 T3N2BM0 N X X
9 T4N0M0 N √ √
10 T4N0M0 N √ √
11 T3N1M0 N X X
12 T4N2CM0 N X X
13 T3N2CM0 Y √ √
14 T4N0M0 N X X
15 T3N0M0 Y √ √
16 T2N0M0 Y X √
17 T2N0M0 Y X X
18 T4N0M0 N X X
19 T3N0M0 Y √ √
20 T4N1M0 Y √ √
21 T2N0M0 Y X X
22 T4N0M0 Y X √
23 T4N2BM0 N X X
24 T3N0M0 Y X X
25 T3N1M0 N X X
26 T2N0M0 Y X X
27 T2N2BM0 N √ √
28 T2N0M0 Y X X
29 T2N0M0 Y X X
30 T3N2BM0 N √ X
31 T2N0M0 Y X X
Table 2: MRSA Infection and Fistula Formation
FISTULA +VE NO FISTULA TOTAL
MRSA +VE 8 2 10
MRSA -VE 2 19 21
TOTAL 10 21 31
(p = 0.0001255 Fisher exact test)
Jeannon et al. Head & Neck Oncology 2010, 2:14
http://www.headandneckoncology.org/content/2/1/14
Page 5 of 5operative anti MRSA antibiotic in carrier patients, and
judicious antibiotic prescription practice.
Having carried out this study, we have implemented an
MRSA eradication protocol in all patients undergoing
laryngectomy even if they are not colonized with MRSA
in order to reduce infection rates. We have also seen a
significant overall reduction in MRSA infection rates
across the hospital due to strict hand hygiene, screening
and MRSA eradication protocols being implemented.
MRSA will continue to pose a challenge because of ris-
ing incidence not only in hospitals and nursing homes but
also in the outpatient community. The emergence of
increasingly resistant staph. aureus organisms and the
demand to treat patients with more and more complex
medical conditions will continue to test medical and
nursing staff in the future.
Conclusion
This is the first study to identify MRSA as a possible caus-
ative agent in pharyngo-cutaneous fistula (PCF) follow-
ing total laryngectomy for laryngeal cancer. Patients who
underwent laryngectomy following radiotherapy failure
and acquired MRSA were at higher risk of PCF. MRSA
infection post laryngectomy can lead to significant mor-
bidity. A multidisciplinary approach is essential for effec-
tive management. Implementation of MRSA eradication
protocol is recommended in every patient undergoing
salvage laryngectomy.
Conflict of interest
The authors declare that they have no competing inter-
ests.
Authors' contributions
JPJ conceived the study and wrote the manuscript, AO and AM participated in
the design of the study and performed the statistical analysis and RS revised
the manuscript. All authors read and approved the final manuscript.
Acknowledgements
None
Disclosure
The authors state that they have no interests which might be perceived as pos-
ing a conflict or bias.
Author Details
Department of Ear Nose & Throat - Head and Neck Surgery, Guy's and St 
Thomas' Hospital NHS Foundation Trust, London, UK
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doi: 10.1186/1758-3284-2-14
Cite this article as: Jeannon et al., Methicillin Resistant Staphylococcus 
Aureus Infection as a causative agent of fistula formation following total 
laryngectomy for advanced head & neck cancer Head & Neck Oncology 2010, 
2:14
Received: 24 February 2010 Accepted: 28 June 2010 
Published: 28 June 2010
This article is available from: http://www.headandneckoncology.org/content/2/1/14© 2010 Jeannon et a ; licensee BioMed Central Lt . is an Open Access articl  distributed under he terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Head & Neck Oncology 2010, 2:14
Table 3: Multivariate analysis of Risk Factors for PCF
p VALUE ODDS RATIO CONFIDENCE INTERVAL
T STAGE p = 0.054 1.15 0.4 - 4.5
MRSA INFECTION p = 0.00012 9.2 2.36-35.8
PREVIOUS RADIOTHERAPY p = 0.00025 8.6 1.24-27.9
(Log rank test)
