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ORIGINAL ARTICLE
Year : 2018  |  Volume : 36  |  Issue : 3  |  Page : 381-384
 

Incidence, epidemiology and control of Clostridium difficile infection in a tertiary care private hospital in India


Department of Infection Prevention and Control, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, Maharashtra, India

Date of Web Publication14-Nov-2018

Correspondence Address:
Dr. Tanu Singhal
Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Four Bungalows, Andheri West, Mumbai - 53, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmm.IJMM_18_340

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 ~ Abstract 

Purpose: Clostridium difficile infection (CDI) is a serious healthcare-associated infection (HAI) now being increasingly reported from hospitals across India. However, there is a paucity of data on the incidence of and impact of control measures on CDI in India. Materials and Methods: This is a retrospective study conducted at a tertiary care hospital in Mumbai from January 2016 to December 2017. All patients with healthcare-onset diarrhoea were tested for C. difficile by glutamate dehydrogenase (GDH)/toxin assay or nucleic acid amplification test (NAAT). CDI was defined as either GDH and toxin positive or NAAT positive. The incidence of CDI was calculated per 1000 patient days. Demographic features of patients with CDI including age, sex, duration of hospitalisation before onset of CDI, antibiotic use and treatment administered were summarised. Results: A total of 67 patients had CDI in the study period with a mean incidence of 0.2/1000 patient days. A halving of the CDI incidence was seen after intensification of the CDI prevention bundle. The mean age of affected patients was 64 years and CDI occurred at a median duration of 2 weeks after hospitalisation. Eighty-seven per cent of the patients were on antibiotics at the time of diagnosis of CDI. The crude mortality rate was 22%. Conclusions: CDI is an emerging HAI in India. All hospitals need to set up policies for surveillance, testing, treatment and prevention of CDI based on recent international guidelines and local infrastructure/logistics.


Keywords: Clostridium difficile, control, glutamate dehydrogenase and toxin, incidence, nucleic acid amplification test


How to cite this article:
Singhal T, Shah S, Tejam R, Thakkar P. Incidence, epidemiology and control of Clostridium difficile infection in a tertiary care private hospital in India. Indian J Med Microbiol 2018;36:381-4

How to cite this URL:
Singhal T, Shah S, Tejam R, Thakkar P. Incidence, epidemiology and control of Clostridium difficile infection in a tertiary care private hospital in India. Indian J Med Microbiol [serial online] 2018 [cited 2019 Dec 11];36:381-4. Available from: http://www.ijmm.org/text.asp?2018/36/3/381/245395



 ~ Introduction Top


Clostridium difficile is a spore-forming gram-positive anaerobic bacillus that exists as normal flora of the gut in around 2% of healthy individuals.[1] This rate increases to 3%–26% in those with previous or current hospitalisation, acquisition occurring from hands of healthcare personnel and the hospital environment.[2] The presence of risk factors such as advanced age, antibiotic use and colonisation leads to infection. The clinical spectrum of C. difficile infection (CDI) ranges from mild diarrhoea to severe life-threatening toxic megacolon.

C. difficile has emerged as the most common cause of healthcare-associated infection (HAI) in North America.[3] CDI among hospitalised patients is a growing concern in India. There are a handful of Indian studies that report the prevalence, epidemiology, diagnosis, molecular characterisation and risk factors of CDI in hospitalised patients with diarrhoea.[4],[5],[6],[7] However, there are no data on the incidence of CDI and impact of control and prevention measures on CDI in the Indian setting. This study is an attempt to fill these knowledge gaps.


 ~ Materials and Methods Top


This is a retrospective study conducted among hospitalised patients at a tertiary care hospital in Mumbai from January 2016 to December 2017. The hospital is accredited by National Accreditation Board for Hospitals, Joint Commission International, National Accreditation Board for Laboratories and College of American Pathologists. The study was approved by the Research and Ethics Committee of the hospital which granted waiver of informed consent. The hospital has a well-defined protocol for evaluation of patients who develop health care facility-onset (HO) diarrhoea (passage of >3 unformed stools in 24 h after 3 days of hospitalisation). As part of this protocol, all patients with HO diarrhoea or those who have a suspected toxic megacolon in the absence of diarrhoea were assessed for C. difficile infection. A two-step test protocol was followed. All liquid stool samples are screened for glutamate dehydrogenase (GDH) using enzyme-linked immunofluorescent assay (Biomerieux). When GDH is positive, the samples were further tested for C. difficile A and B (CDAB) toxin detection by the same method. In some patients, the C. difficile polymerase chain reaction (PCR) by cartridge-based nucleic acid amplification test, GeneXpert from Cepheid, was also ordered on clinician discretion. CDI was defined as patients who were both GDH positive and CDAB toxin positive or patients who were PCR positive. Treatment of CDI was as per the treating clinician and included withdrawal of antibiotics, administration of oral/IV metronidazole or oral/rectal vancomycin or both and if needed surgical intervention. A standard C. difficile prevention bundle [Table 1] was implemented for all patients with CDI. Patients who were GDH positive but toxin negative were also placed under contact isolation but treated only if clinical features were strongly suggestive of CDI.
Table 1: Clostridium difficile prevention bundle[14]

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All hospitalised patients with CDI during the study period were included in the study. The incidence of CDI was defined as a number of cases of CDI per thousand patient days. The case records of study patients were further abstracted and analysed for age and sex, duration of hospitalisation before onset of diarrhoea, duration and number of antibiotic use, severity of illness, treatment initiated and outcome of treatment.


 ~ Results Top


A total number of 62,206 patients amounting to 344,210 patient days were admitted to the hospital from January 2016 to December 2017. Of these, 1,361 (2.2%) had diarrhoea for whom stool samples were screened for C. difficile by GDH and toxin assay or NAAT. A total of 67 (4.9% of patients with diarrhoea) patients were diagnosed to have CDI. Of these, 56 were positive by the toxin assay and 11 by C. difficile PCR. One hundred and eighty patients were GDH positive with either negative/equivocal CDAB. None of the patients with a positive PCR had the hypervirulent O27/NAP1/BI strain.

The incidence of CDI per 1000 patient days for each quarter is depicted in [Figure 1]. The average incidence was 0.2/1000 patient days. The first quarter of 2016 had the highest incidence which was followed by a sustained decline. Assuming the patients who were GDH positive and toxin equivocal/negative as possible CDI, the incidence was 0.71/1000 patient days.
Figure 1: Incidence of Clostridium difficile infection/1000 patient days January 16 to December 17 (Quarter-wise)

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There were 40 male patients and 27 female patients. The age of the patients varied from 16 to 89 years with the mean age being 64 years. A total of 26 (39%) of the patients were in the age group of 70 or above. Forty-four of the patients with CDI were admitted for medical ailments (66%) while 23 (34%) were post-surgical patients. As many as 32 (48%) patients were already admitted to the critical unit when diagnosed to have CDI. The median duration of hospitalisation following which patients developed CDI in the study was 14 days (range: 4–70 days). The pattern of antibiotic use before onset of CDI is summarised in [Table 2]. As many as 50% of the patients had abdominal distension, while 9% of patients had megacolon on plain X-ray abdomen and 11% of patients required inotropic support.
Table 2: Duration of antibiotic therapy before onset of Clostridium difficile infection

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Four patients recovered without treatment, 29 (43%) patients were treated with metronidazole alone, 11 (16%) were treated with vancomycin alone, while 23 (34%) patients were treated with both metronidazole and vancomycin. Fifteen study patients with CDI died with a crude mortality rate of 22%.


 ~ Discussion Top


This is the first of its kind of study on CDI from India. The incidence of CDI seen in our study was around 0.2/1000 patient days which is significantly less than the 0.74/1000 patient days of healthcare onset (HO) reported by US hospitals in 2008.[8] A European surveillance study reported the mean CDI incidence rate as 0.41 cases/1000 patient days with rates ranging from 0 to 3.6 between countries.[9] Our study reported the prevalence of CDI in patients with HO diarrhoea to be around 5% in contrast to rates ranging from 5% to 30% in other reports.[4],[5],[6],[7],[10] Singh et al. from PGI Chandigarh reported the prevalence of CDI in 8.5% of 1110 hospitalised patients with diarrhoea where the testing method was toxigenic culture (could be an overestimate since asymptomatic carriers may also have a positive toxigenic culture).[4],[11]

This incidence of CDI in HO diarrhoea as reported in our study may be an underestimate as the sensitivity of CDAB toxin detection test is at best 70%. In addition, some patients with HO diarrhoea may have missed screening for C. difficile. On the other hand, only a positive NAAT (which we also used to define CDI) could have overestimated the incidence.[12]

The ideal testing strategy for C. difficile is fairly controversial. All available methods have their limitations. In addition, the positive predictive value heavily depends on the pre-test likelihood of CDI.[13] Hence, most experts agree that testing should be performed only in patients with diarrhoea likely to be due to C. difficile and consider excluding patients on laxatives in the past 48 h and where diarrhoea could be related to chemotherapy-induced mucositis, enteral feeding and underlying inflammatory bowel disease.[14] Sensitivity and specificity can be further improved by testing only liquid samples.[14] The available tests are summarised in [Table 3].[14] Cell cytotoxicity neutralisation assay has high sensitivity and specificity but is generally not commercially available. Toxigenic cultures and GDH have high sensitivity but poor specificity since they are also positive in asymptomatic carriers. Previous guidelines recommended NAAT as a stand-alone test for the diagnosis of CDI, but new studies indicate that diagnosis of CDI based on a positive NAAT with negative toxin leads to overdiagnosis.[12],[14],[15] There is now general consensus in both the USA and Europe that a two-step testing method should be used for diagnosis.[14],[16] The screening can be with either GDH assay or NAAT or toxigenic culture and patients testing positive with either of these methods should undergo a toxin assay for confirmation of diagnosis. However, if NAAT testing is done in carefully selected patients with strong clinical suspicion of CDI where the test has good specificity and positive predictive value, it may be used as a stand-alone test.[17] Patients with a positive screening test but negative toxin assay should be evaluated for isolation and treatment based on clinical symptomatology.[16]
Table 3: Available tests for diagnosis of Clostridium difficile infection in decreasing order of sensitivity[14]

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The observation that almost half of the cases of CDI occurred in those aged 70 or more is in agreement with the fact that advanced age is the most important risk factor for CDI.[18] The duration of hospitalisation (often a surrogate for antibiotic exposure, severity of illness and exposure to organism) is another important risk factor.[18] More than half of the study patients with CDI had received antibiotics for more than a week while a fifth more than 2 weeks. This indicates that there is considerable scope of improving antibiotic stewardship at the study site since current guidelines recommend limiting the duration of therapy to a week or less for most infections. The fact that 13% of study patients had not received any antibiotics in the week before onset of CDI is not surprising since it is well known that receipt of antibiotic at any time point within the past 3 months is sufficient to cause disruption of the intestinal microbiota.[14]

The treatment strategy employed was based on the 2010 Infectious Diseases Society of America (IDSA) recommendations which advocated oral metronidazole for mild, oral vancomycin for severe and oral vancomycin and IV metronidazole for complicated CDI.[15] The current IDSA recommendation is of using oral vancomycin for all cases irrespective of severity.[14] Notably, the 125-mg formulation of vancomycin is not available in India, and hence, study patients were treated with 250 mg three to four times daily. Likewise, the drug fidaxomicin which is currently recommended as first-line therapy at par with oral vancomycin for mild/severe/recurrent CDI is unavailable in India.

The crude mortality rate of 22% reported in the study is considerably high; however, the current study is limited by its inability to provide an attributable mortality rate. Previous studies have shown attributable mortality rates ranging widely from 2% to 15%.[14]

The crux of CDI prevention and control is contact isolation of the patient and strict environmental disinfection.[14] Although a basic CDI prevention bundle was in place in the hospital for the past few years, the outbreak in the first quarter of 2016 led to intensification of the bundle. Salient features included heightened surveillance for diarrhoea; placing patients on contact isolation immediately after onset of diarrhoea till the results of C. difficile tests were available; cleaning of high-touch surfaces (bed railing, door handle, bedside trolley, cardiac table etc.) every 2 h, use of separate colour gloves for perineal care to ensure that any touching of the environment with the same gloves could be easily detected; keeping the medical record of the patient outside the room; limiting patient transport, regular disinfection of the transport equipment and disinfection of the equipment used if patient transported to another department and maintaining a 1:1 patient ratio, especially in the critical care unit. Training was intensified for all stakeholders including doctors, nurses, technicians, physiotherapists and housekeeping staff, and regular surveillance/audit of compliance to the bundle was conducted and necessary feedback was given. Specific aspects of training for doctors included reduction of antibiotic use and management of C. difficile, for nurses' recognition of suspected CDI, sending the correct stool samples and contact precautions while for housekeeping training focused on preparation and use of disinfectants and perineal care.


 ~ Conclusions Top


C. difficile is an emerging HAI in India and causes substantial morbidity and mortality in those affected. Hence, there is a need for all healthcare institutions to put into place primary prevention measures for CDI (hand hygiene, environmental disinfection and antibiotic stewardship), surveillance/testing/treatment strategy for HO diarrhoea and finally appropriate prevention measures (contact isolation and rigorous environmental disinfection) for infected patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 ~ References Top

1.
Viscidi R, Willey S, Bartlett JG. Isolation rates and toxigenic potential of Clostridium difficile isolates from various patient populations. Gastroenterology 1981;81:5-9.  Back to cited text no. 1
    
2.
Zacharioudakis IM, Zervou FN, Pliakos EE, Ziakas PD, Mylonakis E. Colonization with toxinogenic C. difficile upon hospital admission, and risk of infection: A systematic review and meta-analysis. Am J Gastroenterol 2015;110:381-90.  Back to cited text no. 2
    
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Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med 2014;370:1198-208.  Back to cited text no. 3
    
4.
Singh M, Vaishnavi C, Kochhar R, Mahmood S. Toxigenic Clostridium difficile isolates from clinically significant diarrhoea in patients from a tertiary care centre. Indian J Med Res 2017;145:840-6.  Back to cited text no. 4
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Rituparna C, Mamatha B, Mukhyaprana PM, Manjunatha HH, Gururaja PP, Thandavarayan R, et al. Characterization of Clostridium difficile isolated from diarrheal patients in a tertiary-care hospital, Karnataka, South India. Southeast Asian J Trop Med Public Health 2016;47:1221-30.  Back to cited text no. 5
    
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Ingle M, Deshmukh A, Desai D, Abraham P, Joshi A, Gupta T, et al. Clostridium difficile as a cause of acute diarrhea: A prospective study in a tertiary care center. Indian J Gastroenterol 2013;32:179-83.  Back to cited text no. 6
    
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Chaudhry R, Joshy L, Kumar L, Dhawan B. Changing pattern of Clostridium difficile associated diarrhoea in a tertiary care hospital: A 5 year retrospective study. Indian J Med Res 2008;127:377-82.  Back to cited text no. 7
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Centers for Disease Control and Prevention (CDC). Vital signs: Preventing Clostridium difficile infections. MMWR Morb Mortal Wkly Rep 2012;61:157-62.  Back to cited text no. 8
    
9.
Bauer MP, Notermans DW, van Benthem BH, Brazier JS, Wilcox MH, Rupnik M, et al. ECDIS Study Group. Clostridium difficile infection in Europe: a hospital-based survey. Lancet 2011;377:63-73.  Back to cited text no. 9
    
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Bauer MP, Notermans DW, van Benthem BH, Brazier JS, Wilcox MH, Rupnik M, et al. Clostridium difficile infection in Europe: A hospital-based survey. Lancet 2011;377:63-73.  Back to cited text no. 10
    
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Planche TD, Davies KA, Coen PG, Finney JM, Monahan IM, Morris KA, et al. Differences in outcome according to Clostridium difficile testing method: A prospective multicentre diagnostic validation study of C. difficile infection. Lancet Infect Dis 2013;13:936-45.  Back to cited text no. 11
    
12.
Polage CR, Gyorke CE, Kennedy MA, Leslie JL, Chin DL, Wang S, et al. Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med 2015;175:1792-801.  Back to cited text no. 12
    
13.
Dubberke ER, Han Z, Bobo L, Hink T, Lawrence B, Copper S, et al. Impact of clinical symptoms on interpretation of diagnostic assays for Clostridium difficile infections. J Clin Microbiol 2011;49:2887-93.  Back to cited text no. 13
    
14.
McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the infectious diseases society of America (IDSA) and society for healthcare epidemiology of America (SHEA). Clin Infect Dis 2018;66:e1-e48.  Back to cited text no. 14
    
15.
Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 2010;31:431-55.  Back to cited text no. 15
    
16.
Crobach MJ, Planche T, Eckert C, Barbut F, Terveer EM, Dekkers OM, et al. European society of clinical microbiology and infectious diseases: Update of the diagnostic guidance document for Clostridium difficile infection. Clin Microbiol Infect 2016;22 Suppl 4:S63-81.  Back to cited text no. 16
    
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Berry N, Sewell B, Jafri S, Puli C, Vagia S, Lewis AM, et al. Real-time polymerase chain reaction correlates well with clinical diagnosis of Clostridium difficile infection. J Hosp Infect 2014;87:109-14.  Back to cited text no. 17
    
18.
Loo VG, Bourgault AM, Poirier L, Lamothe F, Michaud S, Turgeon N, et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med 2011;365:1693-703.  Back to cited text no. 18
    


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