Indian Journal of Cancer
Home  ICS  Feedback Subscribe Top cited articles Login 
Users Online :1332
Small font sizeDefault font sizeIncrease font size
Navigate here
  Search
 
  
Resource links
 »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
 »  Article in PDF (399 KB)
 »  Citation Manager
 »  Access Statistics
 »  Reader Comments
 »  Email Alert *
 »  Add to My List *
* Registration required (free)  

 
  In this article
 »  Abstract
 » Introduction
 » Patients and Methods
 » Results
 » Discussion
 » Conclusion
 »  References
 »  Article Figures
 »  Article Tables

 Article Access Statistics
    Viewed1832    
    Printed87    
    Emailed0    
    PDF Downloaded171    
    Comments [Add]    

Recommend this journal

 

  Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 54  |  Issue : 1  |  Page : 39-42
 

A study of changes in the oral fungal flora of patients on radiotherapy for head and neck malignancies and their correlation with funguria and fungemia


1 Department of Radiotherapy, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
2 Department of Microbiology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India

Date of Web Publication1-Dec-2017

Correspondence Address:
Dr. S Raj
Department of Radiotherapy, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_155_17

Rights and Permissions

 » Abstract 

BACKGROUND: Patients of head and neck malignancies often develop oral mucositis and invite various pathogens to colonize over it. OBJECTIVES: The objective of this study is to identify the fungi isolated from patients undergoing radiotherapy (RT) for head and neck cancer, to determine the antifungal susceptibility of these isolates and to determine the time and week of fungal colonization. PATIENTS AND METHODS: Three specimens (throat, urine, and blood) were collected from each of the head and neck cancer patients, who were advised RT. These specimens, which were collected before the start of RT, during RT (2nd and 6th week), and post-RT (8th week) were inoculated into fungal culture media. Candida species were identified by standard methods and antifungal susceptibility of the candidal isolates was done. RESULTS: Candida infection was found in 24/42 patients (57.14%) out of which Candida albicans was isolated in 14.28%, Candida tropicalis (28.57%) and Candida parapsilosis (14.28%). Maximum isolation of yeast was in the 6th week of RT. Fungemia was found in 3/42 patients. All the yeast isolates were sensitive to fluconazole except two. CONCLUSION: Prophylactic antifungal therapy in patients undergoing RT for head and neck malignancy is particularly important to prevent intraoral colonization and infection by Candida. Screening of such patients on RT for fungal infections can prevent fatal mold infections.


Keywords: Antifungal resistance, Ca oral cavity, Ca oropharynx, Candida spp, colonization, head and neck malignancy, oropharyngeal candidiasis, radiotherapy


How to cite this article:
Raj S, Sharma D, Mate P, Capoor M R, Bhowmik K T. A study of changes in the oral fungal flora of patients on radiotherapy for head and neck malignancies and their correlation with funguria and fungemia. Indian J Cancer 2017;54:39-42

How to cite this URL:
Raj S, Sharma D, Mate P, Capoor M R, Bhowmik K T. A study of changes in the oral fungal flora of patients on radiotherapy for head and neck malignancies and their correlation with funguria and fungemia. Indian J Cancer [serial online] 2017 [cited 2020 Apr 6];54:39-42. Available from: http://www.indianjcancer.com/text.asp?2017/54/1/39/219542



 » Introduction Top


Under normal conditions, the Candida species are very often present in the oral flora. However, under certain physiological and pathological conditions, the yeast may transform from a commensal to a pathogen, particularly in patients with malignancies. The incidence of head and neck malignancy is on the rise due to escalating practices such as smoking, tobacco chewing, and alcohol consumption. Worldwide, the estimated number of new patients of oral and pharyngeal malignancies in the year 2017 is 49,670 and that of laryngeal malignancies is 13,360.[1] Head and neck cancers are very common in India and account for about 23% of cancers in males and about 6.2% in females.[2] About 90%–95% of the head and neck malignancies are oral squamous cell carcinomas.[3] Radiotherapy (RT) administered to patients with head and neck malignancy make them particularly susceptible to oropharyngeal candidiasis.[4],[5],[6] These patients are commonly subject to oral mucosal colonization (up to 93%) and infection (17%–29%) with Candida.[5],[7],[8] Direct mucosal toxicity caused by cytotoxic drugs and radiation, and indirect mucosal damage caused by the inflammatory reaction, leads to Oral mucositis which is exacerbated by neutropenia and provides an opportunity for the emergence of the bacterial, viral, and fungal infections.[9] This process is facilitated by resulting xerostomia due to the destruction of glandular tissue by radiation.[5],[10] Patients with oropharyngeal candidiasis suffer from oral pain and burning which has a major effect on the quality of life.[5]Candida albicans has been found to be the most preponderant organism in these patients receiving cancer therapies. However, of late, non-albicans Candida species has been seen to be an emerging cause of oropharyngeal candidiasis and these organisms are found to exhibit increased resistance to antifungal drugs. The objectives of this study were (1) identification of the fungal agent isolated from various sites in the mouth from patients undergoing radiation therapy for the treatment of oral, oropharyngeal, and laryngeal neoplasm, (2) determination of antifungal susceptibility of the various fungi isolated, and (3) to know the time and week of candidal colonization so as to prevent fungal infections.


 » Patients and Methods Top


The study was a 1-year prospective cohort study. The study group included patients of oral, oropharyngeal, and laryngeal cancer who were advised Radical RT as a primary treatment. A written informed consent was taken from all the eligible patients. Exclusion criteria were (1) other risk factors for candidiasis such as diabetes, corticosteroids, recent use of antibiotics (at least 2 weeks before the start of irradiation therapy), (2) patients with intraoral prostheses, and (3) patients receiving antifungal therapy. Detailed clinical history of the patients was taken, and thorough clinical examination was done.

Radiotherapy methods

Radical RT up to 66 Gy/33# was administered over 6½ weeks by telecobalt therapy machine, along with concomitant chemotherapy with weekly CISPLATIN 30 mg/m 2. The dose per fraction was 2 Gy, and RT was administered 5 days a week. The patients were evaluated before the start of RT (week 0), during RT (week 2 and week 6), and post-RT (8 weeks). Symptomatic treatment was given to all patients, as and when required. Oral hygiene measures comprising Betadine gargles, high protein, diet and plenty of fluids was routinely recommended to each patient. Edentulous patients were not allowed to wear their dentures during RT.

Microbiological methods

At each visit, three samples were taken from each patient, that of throat, urine, and blood. Throat samples were collected by plain cotton swabs by collecting as much exudate as possible from the visible growth or ulcer, tonsils, posterior pharyngeal wall, and any other inflamed or exudate-bearing area. Urine samples were collected using the midstream, clean-catch method. These samples were inoculated into sabouraud dextrose agar (SDA) within 2 h of sampling by a standardized technique, and the plates were incubated at 37°C for 72 h. Blood samples were inoculated into biphasic brain heart infusion agar broth and incubated at 37°C. Subcultures into SDA plates were done after 2 days and 7 days. Candida species was identified using hicrome agar, cornmeal agar, germ tube test, tetrazolium reduction test and carbon, and nitrogen assimilation tests using API 20 yeast identification kit (Biomerieux, France). Antifungal susceptibility of the candidal isolates was done by the E-test against three drugs amphotericin B, fluconazole, and voriconazole and their MICs were noted. The results were evaluated according to Clinical and Laboratory Standards Institute guidelines.

Once the samples were positive for fungal infection, specific antifungal treatment (a/c to sensitivity) was given to the patients, till 2 weeks after the culture became negative. To begin the treatment empirically, tablet fluconazole 50 mg BD was given.

Statistical analysis

The data were analyzed using Epi info 7.1.4 version (CDC, Atlanta, USA). The descriptive statistics was used to present the demographic variables. Proportions were used to show the sites of carcinoma, types of fungal infections, and sources of culture positive for fungal infections. Z- test for proportion and Chi-square statistics were applied to assess the difference and association between various variables, respectively.


 » Results Top


A total of 42 patients were included in the study. The ages of these patients ranged from 23 to 75 years (median age = 53) [Figure 1]. The male-female ratio was 9.5:1 with male preponderance (90.47%) which is statistically significant. The demographic characteristics of the patients are shown in [Table 1]. Out of these 42 patients, 18 had laryngeal, and 24 had oropharyngeal carcinoma. Different sites of carcinoma are not statistically significant (P = 0.200). All the oral, as well as laryngeal neoplasms were squamous cell carcinomas. The oral and oropharyngeal carcinomas involved the (a) base of the tongue, (b) vallecula, (c) floor of the mouth, (d) tonsils, (e) soft palate, and (f) buccal mucosa. The laryngeal group included both supraglottic and glottic neoplasms. The major risk factors for carcinoma were found to be narcotic use in various forms (Bidi, Khaini, Gutka) which was seen in 66.66% of the patients [Table 1] and [Figure 2], which is statistically significant (P = 0.001) and denture use seen in 9.5% of the patients [Figure 3]. None of the patients had positive fungal culture in the pre-RT period. In the 2nd week of RT, 14 patients had throat cultures positive for fungus, out of which 6 isolates were Candida tropicalis and 4 each were C. albicans and Candida parapsilosis, respectively. Furthermore, fungus was isolated from urine samples of six patients out of which 4 isolates were C. tropicalis and 2 isolates were C. albicans. However, in the 6th week of RT, fungus was isolated from the throat cultures of 18 patients (12 = C. tropicalis, 4 = C. albicans, and 2 = C. parapsilosis) and from the urine cultures of 12 patients (6 isolates each of C. tropicalis and C. albicans, respectively). The difference of proportion of patients having positive fungal cultures after 2nd and 6th week of RT is statistically significant (P = 0.002). At post-RT 8th week, throat samples of 8 patients were positive for Candida (5 = C. tropicalis, 3 = C. albicans) [Table 2] and [Figure 4]. Out of the total 42 patients, fungemia was found in three patients (7.14%). The fungi isolated from these 3 patients were Fusarium oxysporum, Acremonium kiliense, and C. Tropicalis, respectively. Fungemia was seen in the 6th week of RT. Candida infection occurred in 24 out of 42 patients (57.14%). Out of these, C. albicans was isolated in 6/42 patients (14.28%). The non-albicans Candida spp. which were isolated were C. tropicalis (28.57%) and C. parapsilosis (14.28%). Besides Candida spp., some other fungi were also isolated. These were F. oxysporum and Acremonium kiliense which were isolated in 1 patient each. The spectrum of fungi isolated from the patients is shown in [Table 3].
Figure 1: Age composition

Click here to view
Figure 2: Exposure to risk factors

Click here to view
Figure 3: Use of denture use

Click here to view
Figure 4: Percentage of patients with fungal colonization

Click here to view
Table 1: Clinical and demographic characteristics of the 42 patients

Click here to view
Table 2: Number of patients with positive fungal cultures according to weeks of radiotherapy

Click here to view
Table 3: Spectrum of fungi isolated from the patients

Click here to view


Maximum quantitative rise in the oral fungi (yeast spp.) and followed by fungemia was seen in the 6th week of RT. Mortality was seen in 2 patients from whom molds were isolated.

Antifungal susceptibility: all the yeast isolates were sensitive to fluconazole except 2 (1 isolate each of C. albicans and C. tropicalis) isolated from 2 different patients which were found to be resistant. All the yeast isolates were, however, sensitive to Amphotericin B and Voriconazole.


 » Discussion Top


Patients with head and neck malignancy undergoing RT and/or chemotherapy are at increased risk of developing oral mucositis and colonization as well as infection with Candida spp. despite routine oral hygiene measures. Several studies report up to 86% of oral mucosa yeast colonization in patients treated with ionizing radiation.[11],[12],[13] There is a wide contradistinction (from 17% to 52.5%) in the epidemiology of oral candidiasis in different studies.[14],[15],[16] In this study, Candida infection occurred in 24 out of 42 patients (57.14%). The prime reason for this wide variability is that it is difficult to distinguish oral candidiasis (especially oral pseudomembranous candidiasis) from the radiation–induced mucosal reaction, and also because oral candidiasis may be superimposed on radiation-induced mucosal reactions, thus making differential diagnosis all the more challenging.[14] RT has deleterious effect on the salivary function thus leading to favorable conditions for opportunistic fungal overgrowth. This, in turn, leads to easy detection thus increasing the rate of a positive culture.[17] In this study, a quantitative rise in oral fungi (especially yeasts) and fungemia was found during RT with peak being in the 6th week, but it persisted during post-RT. C. tropicalis was found to be the predominant yeast isolated in our study. C. tropicalis is commonly isolated from clinical specimens, and in one survey, it accounted for 18% of laboratory growths.[18] In the past, C. albicans has been the major yeast isolated.[8] In one study, C. albicans was isolated in 78.57%.[19] Another study showed that Candida infections occurred in 27% of the patients receiving RT for head and neck cancer.[4] But of late, an increasing incidence of non-albicans Candida spp. has been found in the patients receiving RT.[20] The other non-albicans Candida spp. isolated in our study was C. parapsilosis (11.1%). Acremonium kiliense and F. oxysporum were isolated from one patient each. Fungal organisms other than Candida spp. are increasingly being associated with oral infections in immunocompromised patients.[21],[22]

The principal antifungal used for the treatment of oropharyngeal candidiasis is fluconazole. In our study, resistance to fluconazole was seen in two patients from whom the respective isolates were C. parapsilosis and C. albicans. All the other patients responded to fluconazole at the standard dosage of 100 mg/day. Fluconazole resistance has become a growing concern in patients with oropharyngeal candidiasis and usually is correlated with the degree of immunosuppression and the total dose of the drug. A study showed that fluconazole 100 mg was effective in the treatment of all Candida spp. except Candida rugosa.[4] Yeasts other than C. albicans are less susceptible to fluconazole. All of the yeast isolates were sensitive to amphotericin B. In this study, high incidence of mold fungemia without prior colonization especially Fusarium spp. and Acremonium spp is a cause of concern. These molds were resistant to amphotericin B and voriconazole and were fatal despite timely diagnosis and therapy.


 » Conclusion Top


Fungal colonization enhances by 2nd week and peaks at 6th week in patients undergoing RT in head and neck cancers. The addition of appropriate antifungal treatment prophylactically during the 2nd week of RT is to be strongly considered to prevent the dissemination of local fungal flora to cause fungemia. Furthermore, screening of RT patients for fungal infections can prevent fatal mold infections in such patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 » References Top

1.
SEER Cancer Statistics Factsheets: Oral Cavity and Pharynx. Bethesda, MD: National Cancer Institute. Available from: http://www.seer.cancer.gov/statfacts/html/oralcav.html. [Last accessed on 2017 Apr 23].  Back to cited text no. 1
    
2.
Available from: http://www.globocan.iarc.fr/Pages/fact_sheets_population.aspx. [Last accessed on 2017 Apr 23].  Back to cited text no. 2
    
3.
Wang CC. Radiotherapy for Head and Neck Neoplasms: Indications, Technique and Results. Boston: John Wright PSG Inc.; 1983. p. 155-64.  Back to cited text no. 3
    
4.
Redding SW, Zellars RC, Kirkpatrick WR, McAtee RK, Caceres MA, Fothergill AW, et al. Epidemiology of oropharyngeal Candida colonization and infection in patients receiving radiation for head and neck cancer. J Clin Microbiol 1999;37:3896-900.  Back to cited text no. 4
[PUBMED]    
5.
Fotos PG, Hellstein JW. Candida and candidosis. Epidemiology, diagnosis and therapeutic management. Dent Clin North Am 1992;36:857-78.  Back to cited text no. 5
[PUBMED]    
6.
Ramirez-Amador V, Silverman S Jr., Mayer P, Tyler M, Quivey J. Candidal colonization and oral candidiasis in patients undergoing oral and pharyngeal radiation therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;84:149-53.  Back to cited text no. 6
    
7.
Just-Nübling G, Gentschew G, Meissner K, Odewald J, Staszewski S, Helm EB, et al. Fluconazole prophylaxis of recurrent oral candidiasis in HIV-positive patients. Eur J Clin Microbiol Infect Dis 1991;10:917-21.  Back to cited text no. 7
    
8.
Silverman S Jr., Luangjarmekorn L, Greenspan D. Occurrence of oral Candida in irradiated head and neck cancer patients. J Oral Med 1984;39:194-6.  Back to cited text no. 8
    
9.
Ferretti GA, Raybould TP, Brown AT, Macdonald JS, Greenwood M, Maruyama Y, et al. Chlorhexidine prophylaxis for chemotherapy- and radiotherapy-induced stomatitis: A randomized double-blind trial. Oral Surg Oral Med Oral Pathol 1990;69:331-8.  Back to cited text no. 9
[PUBMED]    
10.
Haveman CW, Redding SW. Dental management and treatment of xerostomic patients. Tex Dent J 1998;115:43-56.  Back to cited text no. 10
[PUBMED]    
11.
Belazi M, Velegraki A, Koussidou-Eremondi T, Andreadis D, Hini S, Arsenis G, et al. Oral Candida isolates in patients undergoing radiotherapy for head and neck cancer: Prevalence, azole susceptibility profiles and response to antifungal treatment. Oral Microbiol Immunol 2004;19:347-51.  Back to cited text no. 11
[PUBMED]    
12.
Jham BC, França EC, Oliveira RR, Santos VR, Kowalski LP, da Silva Freire AR. Candida oral colonization and infection in Brazilian patients undergoing head and neck radiotherapy: A pilot study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:355-8.  Back to cited text no. 12
    
13.
Thaweboon S, Thaweboon B, Srithavaj T, Choonharuangdej S. Oral colonization of Candida species in patients receiving radiotherapy in the head and neck area. Quintessence Int 2008;39:e52-7.  Back to cited text no. 13
[PUBMED]    
14.
Nicolatou-Galitis O, Sotiropoulou-Lontou A, Velegraki A, Pissakas G, Kolitsi G, Kyprianou K, et al. Oral candidiasis in head and neck cancer patients receiving radiotherapy with amifostine cytoprotection. Oral Oncol 2003;39:397-401.  Back to cited text no. 14
[PUBMED]    
15.
Nicolatou-Galitis O, Dardoufas K, Markoulatos P, Sotiropoulou-Lontou A, Kyprianou K, Kolitsi G, et al. Oral pseudomembranous candidiasis, herpes simplex virus-1 infection, and oral mucositis in head and neck cancer patients receiving radiotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwash. J Oral Pathol Med 2001;30:471-80.  Back to cited text no. 15
[PUBMED]    
16.
Makkonen TA, Minn H, Jekunen A, Vilja P, Tuominen J, Joensuu H. Granulocyte macrophage-colony stimulating factor (GM-CSF) and sucralfate in prevention of radiation-induced mucositis: A prospective randomized study. Int J Radiat Oncol Biol Phys 2000;46:525-34.  Back to cited text no. 16
[PUBMED]    
17.
Chen TY, Webster JH. Oral monilia study on patients with head and neck cancer during radiotherapy. Cancer 1974;34:246-9.  Back to cited text no. 17
[PUBMED]    
18.
Walker LJ, Luecke MR. The identification of yeasts from clinical material. Proc Iowa Acad Sci1974;81:14.  Back to cited text no. 18
    
19.
Suryawanshi H, Ganvir SM, Hazarey VK, Wanjare VS. Oropharyngeal candidosis relative frequency in radiotherapy patient for head and neck cancer. J Oral Maxillofac Pathol 2012;16:31-7.  Back to cited text no. 19
  [Full text]  
20.
Kurtzman PC, Fell JW. The Yeasts: A Taxonomic Study. 4th ed. New York: Elsevier; 1998.  Back to cited text no. 20
    
21.
Schubert MM, Peterson DE. Oral complications of hematopoietic cell transplantation. In: Appelbaum FR, Forman SJ, Negrin RS, Blume KG, editors. Thomas' Hematopoietic Cell Transplantation: Stem Cell Transplantation. 4th ed. Oxford, UK: Wiley-Blackwell; 2009. p. 1589-607.  Back to cited text no. 21
    
22.
Ellis ME, Clink H, Ernst P, Halim MA, Padmos A, Spence D, et al. Controlled study of fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies and bone marrow transplant recipients. Eur J Clin Microbiol Infect Dis 1994;13:3-11.  Back to cited text no. 22
[PUBMED]    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
Print this article  Email this article
 

    

  Site Map | What's new | Copyright and Disclaimer
  Online since 1st April '07
  © 2007 - Indian Journal of Cancer | Published by Wolters Kluwer - Medknow