Keywords
head and neck Cancer - surgical site infection - multi-drug resistance - MRSA
Introduction
Head and neck cancers are of very much public health importance, accounting for more
than 650,000 cases around 330,000 deaths annually.[1] The head and neck cancers are the cancers that are occurring in the oral cavity,
pharynx, nasal cavities, and paranasal sinuses, ears, eyes, and orbit, scalp, and
salivary glands.[2] The site of occurrence of these cancers interferes with some of the basic functions
of life such as swallowing, breathing, and higher functions such as speech, hearing,
vision, smelling and taste.[3]
There is gender predisposition toward men in head and neck cancers. The major pre-disposing
factors being excess consumption of alcohol and tobacco, were postulated more than
two and half decade ago.[4] This causes cancer to be from diverse origin such as epithelium, especially squamous
cell carcinoma, others being lymphocytes (lymphoma), soft tissue (sarcoma), and endocrine
tumors.[5] Thus requires a multidisciplinary approach with surgery, radiotherapy, chemotherapy,
reconstructive surgery, speech therapy, psychological support.[6]
For improved curative rates, wide resection and reconstruction are the most accepted
mode of treatment.[7] However, the prognosis is greatly affected when the surgical site gets infected,
causing increased treatment cost, prolonged length of stay in hospital, and delayed
in other treatments such as chemo- or radiotherapy.[8]
The surgical site infections (SSIs) can be prevented with appropriate pre-surgical
antimicrobial prophylaxis, following aseptic precautions during the surgery and postoperative
care. Thus, to initiate appropriate antimicrobial prophylaxis, the flora causing SSIs
has to be known with its antimicrobial resistance pattern. So, this study was undertaken
to study the pathogens causing SSI and their antimicrobial resistance pattern.
Materials and Methods
This is a retrospective study carried out in the department of Microbiology/Infection
control of Fr Muller Medical College Hospital, Mangalore, India. The data on the antibiotic
sensitive pattern of the aerobic bacteria isolated from the wound infection in the
patients undergoing surgery for head and neck cancer, admitted from January 2017 to
December 2018, were collected. The demographic details were collected from the medical
records departments, and microbiological data were collected from the clinical laboratory,
after obtaining permission from the Institutional Ethics Committee.
The culture of the pus sample was done on sheep blood agar and MacConkey agar and
pathogens isolated were identified according to the standard microbiological procedure.
Antimicrobial susceptibility test was done as per the Clinical Laboratory Standard
Institute (CLSI) guidelines.[9] The antimicrobial susceptibility was tested against ampicillin (10 μg), ceftriaxone/ceftazidime/cefoxitin
(30 μg), cotrimoxazole (25 μg), gentamicin (10 μg), amikacin (30 μg), ciprofloxacin
(5 μg), and levofloxacin (5 μg). Additionally, piperacillin/tazobactam (100/10 μg),
meropenem (10 μg) for gram-negative pathogens and erythromycin (15 μg), clindamycin
(2 μg), vancomycin (30 μg), linezolid (30 μg), teicoplanin (30 μg) for gram-positive
pathogens were tested. The collected data were entered into Microsoft Excel, and statistical
analysis was done as per percentage of isolates and drug resistance.
Results
A total of 130 culture-positive pus samples were detected during the study period.
The majority of the samples were from males (71.5%) and one-third of the patients
belonged to the sixth decade of their life ([Table 1]). Most patients included in the study had cancer of buccal mucosa (46, 35.38%),
followed by tongue (27, 20.77%). From the 130 exudate samples, 235 pathogens were
isolated. The gram-negative pathogens accounted for 158 (67.23%) and gram-positive
pathogens (77, 32.77%). Klebsiella sp. outnumbered among the gram-negative pathogens followed by Acinetobacter sp. ([Table 2]). Among the gram-positive, Staphylococcus aureus was the commonest followed by Enterococcus sp.([Table 2]). Methicillin-resistance isolation was noted to be as high as 64.28% and 63.9% among
coagulase-negative Staphylococcus (9/14) and S. aureus (23/36), respectively. The study of antimicrobial susceptibility revealed a high
level of resistance to aminopenicillins, third-generation cephalosporins, co-trimoxazole,
and fluoroquinolones among the gram-negative pathogens. The high-end antimicrobials
such as β lactam-β lactamase inhibitor combination, carbapenems, and aminoglycosides
were sensitive to around 45% of the Klebsiella isolates. However, in case of Acinetobacter sp., resistance to high-end antimicrobials is more than 80% ([Table 3]). Among E. coli and other gram-negative pathogens more than 55% were susceptible to high-end antimicrobials.
Only Acinetobacter sp. isolates were the difficult to be treated among the gram-negative pathogens.
Among the gram-positive pathogens, MRCoNS and MRSA isolation rate was high. The penicillin,
3GC, fluoroquinolones resistance was very high. Anti-MRSA drugs such as vancomycin,
linezolid, and teicoplanin resistance was not seen among S. aureus and Enterococcus sp. isolated, but resistance to linezolid was emerging among the CoNS ([Table 4]).
Table 1
Demographic details of head and neck cancer patients
|
Parameters
|
No. of patients (n = 130)
|
%
|
|
Age
|
<30
|
3
|
2.31
|
|
31–40
|
19
|
14.62
|
|
41–50
|
24
|
18.46
|
|
51–60
|
43
|
33.08
|
|
61–70
|
31
|
23.85
|
|
71–80
|
6
|
4.62
|
|
81–90
|
4
|
3.08
|
|
Gender
|
Male
|
93
|
71.54
|
|
Female
|
37
|
28.46
|
|
Site of tumor
|
Buccal mucosa
|
46
|
35.38
|
|
Tongue
|
27
|
20.77
|
|
Oral cavity
|
14
|
10.77
|
|
Alveolus
|
12
|
9.23
|
|
Larynx
|
11
|
8.46
|
|
RMT
|
5
|
3.85
|
|
Maxilla
|
3
|
2.31
|
|
Thyroid
|
3
|
2.31
|
|
Floor of mouth
|
3
|
2.31
|
|
Glottis
|
2
|
1.54
|
|
Pharynx
|
2
|
1.54
|
|
PFS
|
1
|
0.77
|
|
Metastasis of unknown origin
|
1
|
0.77
|
Table 2
Distribution of pathogens isolated from SSI of head and neck cancer patients
|
Gram-negative
|
158
|
67.23
|
|
Klebsiella sp
|
56
|
23.83
|
|
Acinetobacter sp
|
36
|
15.32
|
|
Escherichia coli
|
30
|
12.77
|
|
Pseudomonas aeruginosa
|
19
|
8.09
|
|
Citrobacter sp.
|
9
|
3.83
|
|
Proteus sp.
|
8
|
3.40
|
|
Gram-positive
|
77
|
32.77
|
|
Staphylococcus aureus
|
36
|
15.32
|
|
Enterococcus sp.
|
16
|
6.81
|
|
Coagulase-negative Staphylococcus (CoNS)
|
14
|
5.96
|
|
Corynebacterium sp.
|
11
|
4.68
|
|
235
|
100.00
|
Table 3
Antimicrobial resistance pattern among gram-negative pathogens isolated from SSI
|
Klebsiella sp.
(56)
|
Acinetobacter sp.
(36)
|
Escherichia coli
(30)
|
Pseudomonas aeruginosa (19)
|
Citrobacter sp.
(9)
|
Proteus sp.
(8)
|
|
Ampicillin
|
−
|
100.00
|
93.33
|
−
|
100.00
|
100.00
|
|
3GC
|
98.21
|
97.22
|
90.00
|
21.05
|
77.78
|
62.50
|
|
Cotrimoxazole
|
69.64
|
75.00
|
80.00
|
−
|
88.89
|
62.50
|
|
Gentamicin
|
42.86
|
91.67
|
43.33
|
15.79
|
22.22
|
75.00
|
|
Amikacin
|
41.07
|
80.56
|
6.67
|
15.79
|
11.11
|
37.50
|
|
Ciprofloxacin
|
75.00
|
94.44
|
86.67
|
15.79
|
88.89
|
50.00
|
|
Levofloxacin
|
53.57
|
72.22
|
83.33
|
10.53
|
55.56
|
37.50
|
|
Piptaz
|
75.00
|
91.67
|
40.00
|
15.79
|
33.33
|
0.00
|
|
Meropenem
|
53.57
|
83.33
|
23.33
|
5.26
|
0.00
|
25.00
|
Table 4
Antimicrobial resistance pattern among the Gram positive pathogens isolated from SSI
|
Staphylococcus aureus
(36)
|
Enterococcus sp.
(16)
|
Coagulase-negative Staphylococcus
(14)
|
|
Ampicillin
|
94.44
|
43.75
|
100.00
|
|
3GC
|
63.89
|
–
|
71.43
|
|
Cotrimoxazole
|
41.67
|
–
|
35.71
|
|
Gentamicin
|
50.00
|
68.75
|
50.00
|
|
Amikacin
|
27.78
|
0.00
|
14.29
|
|
Ciprofloxacin
|
91.67
|
68.75
|
50.00
|
|
Levofloxacin
|
69.44
|
62.50
|
35.71
|
|
Erythromycin
|
52.78
|
0.00
|
71.43
|
|
Clindamycin
|
41.67
|
0.00
|
57.14
|
|
Vancomycin
|
0.00
|
0.00
|
0.00
|
|
Teicoplanin
|
0.00
|
0.00
|
0.00
|
|
Linezolid
|
0.00
|
0.00
|
7.14
|
Discussion
Surgical site infection is one of the important nosocomial infections, which is caused
by highly antimicrobial-resistant bacteria. In turn, it causes prolonged hospital
stay, increased antimicrobial therapy, medical costs, comorbidity, emotional trauma,
further reducing the immune status of the cancer patients, leading to further delay
in other adjuvant therapies.[10] In Mexico, around 8% of SSI was reported among 23,421 surgeries performed in a 7
years retrospective study. In another study on 110 oral cancer patterns, SSI rate
was noted as 22.7%.[11] Similarly, in 260 French patients with head and neck squamous cell carcinomas undergoing
surgical procedure, 117 (45%) were infected.[8] The males were more prone to wound infection compared to females in head and neck
cancers in the French population,[8] similar trend is found in our study.
Various studies have reported different bacterial flora causing SSI in cancer patients,
depending on the age of patient, population treated, and site of cancer. Among the
pathogens isolated, gram-negative E. coli accounted for (27.5%), followed by gram-positive, S. aureus (16.3%).[12] Similarly, an Indian study reported E. coli being the predominant pathogen causing SSI.[13] However, in our study, even though gram-negative bacilli outnumbered, Klebsiella sp. was as the predominant pathogen. This emphasis the flora causing SSI can vary
among the hospitals. In developed countries such as the USA, gram-positive pathogen,
S. aureus continues to be the leading causing of SSI in cancer patients irrespective of site
of infection.[14]
The study of resistance pattern among gram-negative pathogens revealed a high level
of resistance to commonly used antimicrobials such as aminoglycosides, fluoroquinolones
were ineffective in the study, similar to our isolates.[12] In an Indian study, high level of resistance, i.e., around 63% to third-generation
cephalosporins such as cefotaxime and ceftazidime were observed among the gram-negative
pathogens in SSI in cancer patients.[13] The predominant gram-negative pathogens such as Klebsiella, Acinetobacter, and E. coli had resistance to a range of 90 to 98% to 3GC in our patients. The resistance to
β lactam-β lactamase inhibitor and carbapenems was reported to as high as 85% in pathogens
causing SSI an Egyptian patients[15]; similarly, we reported a resistance range from 75 to 92% in various isolates. Among
the gram-positive isolates, Staphylococcus sp. and Enterococcus sp. are the common pathogens causing SSI in cancer patients.[13]
[15] The methicillin resistance have be reported as high as 40%. We had MRSA isolation
rate (64.28%) among S. aureus higher than other studies[12]
[13]
[16]
[17] but higher rates are been reported in Egyptian patients.[15]
Conclusion
In the present study, we have studied the pathogens causing SSI in head and neck cancer
patients. This study has helped to identify resistance patterns in both gram-negative
and gram-positive pathogens causing SSI and highlights that the antimicrobial resistance
among these pathogens is occurring at a very alarming rate. So, the infection control
practices need to be implemented strictly in these immunocompromised cancer patients.
The SSI in the cancer patients studied denotes that the pathogens are predominantly
gram-negative Klebsiella sp. and Acinetobacter sp., which are multi-drug resistant. Among gram-positive, MRSA and Enterococcus sp. are of concern, the treatment option available is very less. So, greater responsibilities
lies on the health care workers on implementation of strict infection control practices
to prevent SSI rather than treating them.
