Travel Medicine and Infectious Disease (2010) 8, 373e376
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Clostridium difficile-associated disease among patients in Dhahran, Saudi Arabia Jaffar A. Al-Tawfiq a,*, Mahmoud S. Abed b a
Specialty Internal Medicine Unit, Dhahran Health Center, P.O. Box 76, Room A-428-2, Building 61, Saudi Aramco Medical Services Organization, Saudi Aramco, Dhahran 31311, Saudi Arabia b Infection Control Unit, Dhahran Health Center, Saudi Aramco Medical Services Organization, Saudi Aramco, Dhahran, Saudi Arabia Received 17 February 2010; received in revised form 2 October 2010; accepted 6 October 2010 Available online 27 October 2010
KEYWORDS Clostridium difficile; Colitis; Saudi Arabia; Epidemiology
Summary Clostridium difficile-associated diarrhea (CDAD) is an important healthcare-associated infection. However, there are no data from Saudi Arabia on this disease. A two-year prospective, observational study on the incidence of CDAD in a hospital in Saudi Arabia was carried out. Stool analysis for C. difficile toxins A and B was carried out by an enzyme-linked immunosorbent assay. Medical and laboratory records were reviewed. Of the total number of patients, there were 53.3% male and the mean age was 44.6 27.2 years. Of the 913 specimens, only 42 (4.6%) were positive for C. difficile toxins. The annual incidence rates of C. difficile were 1.2 and 0.9 per 1000 discharges, and 2.4 and 1.7 per 10,000 patient days in 2007 and 2008, respectively. Of the total number of cases, 52.4% were with onset in the hospital, 38.1% were with onset in the community and 9.5% were community-onset but healthcare facilityassociated CDAD. Of the cases, 16 (39%) patients did not have exposure to antimicrobial drugs in the 3 months prior to the test date. The remaining patients received antimicrobial drug therapy. Cephalosporin and fluroquinolone were the most common antimicrobial drugs used. Overall, the prevalence of C. difficile-associated diarrhea was low; further studies are required in Saudi Arabia to elucidate the true prevalence of the disease. ª 2010 Elsevier Ltd. All rights reserved.
Introduction Clostridium difficile colitis is an important healthcareassociated gastrointestinal infection in the United States
* Corresponding author. Tel.: þ966 3 877 3524; fax: þ966 3 877 3790. E-mail addresses:
[email protected], jaffar.tawfiq@aramco. com (J.A. Al-Tawfiq).
and an important cause of morbidity.1,2 The disease has a major cost impact with an estimated annual cost of U.S. $3.2 billion.3 C. difficile infection also caused major outbreaks in many medical centers.4 In a study from the USA, the incidence of adult CDAD hospital admissions doubled from 5.5 cases per 10,000 population in 2000 to 11.2 in 2005.5 There are no data from Saudi Arabia on the incidence or prevalence of this disease. In a study of the causes of gastroenteritis at a major referral center in Saudi Arabia,
1477-8939/$ - see front matter ª 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tmaid.2010.10.003
374 C. difficile toxin was found in 9.5% of patients.6 However, the study was published in 1994, and did not look at C. difficile-associated disease specifically. Therefore, we undertook this study to determine the prevalence of C. difficile infections in a hospital in Saudi Arabia.
Materials and methods Saudi Aramco Medical Services Organization (SAMSO) provides medical care for Saudi Aramco employees and their dependents. Approximately 370,000 individuals are eligible for medical care at SAMSO. The main hospital is a 380-bed referral and the hospital has five intensive care units (cardiac, medical, surgical, pediatric, and neonatal). Admissions to the hospital cover a whole range of patients and include general admissions, intensive care, and patients receiving chemotherapy for hematological and solid organ malignancy. However, SAMSO does not have solid organ or bone marrow transplant services. On average, there are 36,426 admissions annually with an average length of stay of 5.3 days. Case finding involved reviewing positive C. difficile toxin assays from SAMSO infection control database and the microbiology laboratory. Medical and laboratory records were reviewed from January, 2007 to December, 2008.Data were abstracted from both electronic and paper medical records using standardized forms. We collected the following data: demographics, laboratory results, prior hospitalization, risk factors, use of antimicrobial agents, and underlying conditions. All patients with positive stool for C. difficile toxins were included in our study. However, only one positive specimen per patient was included in the analysis. The Meridian Premier (enzyme-linked immunosorbent assay [ELISA]; Meridian Bioscience Inc., Cincinnati, Ohio, USA), was used for the detection of C. difficile toxin A and B. The procedure was carried out according to the manufacturer’s instructions.
Definitions C. difficile-Associated Disease (CDAD) was defined as a diarrheal disease (loose or watery stools generally three or more times per day) and/or abdominal discomfort with a positive enzyme-linked immunosorbent assay (ELISA) for C. difficile toxins A and B (Premier Toxins A&B EIA; Meridian Bioscience).7,8 Healthcare facility onset, healthcare facility-associated disease was defined as any patient with the onset of CDAD symptoms more than 48 h after admission. Community-onset, healthcare facility-associated disease was considered when CDAD symptoms occurred in the community, if symptoms occurred 48 h or less after admission to the hospital, or if symptom onset was less than 4 weeks after the last discharge from the hospital. A community-associated CDAD was defined as patients with symptoms occurring in the community or 48 h or less after admission, if the onset of symptoms was more than 12 weeks after the last hospital discharge.8
Results During the study period from January 2007 to December 2008, there were a total of 913 non-repetitive specimens
J.A. Al-Tawfiq, M.S. Abed from different patients. Of the 913 specimens, only 42 (4.6%) were positive for C. difficile toxins. Of the positive results, 23 (54.8%) were in males and 19 (45.2%) were in females. The mean age (SD) was 48 (31.8) years with a median age of 52 years. There were only 10 (23.8%) pediatric cases and 19 (45.2%) were in patients aged 65 years or older. The annual positivity rates were 4.8% (24 out of 492) in 2007 and 4.2% (18 of 421) in 2008. The annual prevalence rates of C. difficile infection were 1.2 and 0.9 per 1000 discharges and 2.4 and 1.7 per 10,000 patient days in 2007 and 2008, respectively. Patients in the medical ward constituted 21.4%. Of the positive patients, 16.8% were from intensive care units and 8 (19%) were outpatient cases. Of the total number of cases, 52.4% were with onset in the hospital, 38.1% were with onset in the community and 9.5% were with the onset in the community but were healthcare facility-associated CDAD. Of the cases, 16 (39%) patients did not have exposure to antimicrobial drugs during the 3 months prior to the test. The remaining patients received antimicrobial drug therapy. Cephalosporins were the most common antimicrobial drugs (n Z 8; 30.6%), fluroquinolone (n Z 4; 15.3%) and a combination of these two drugs in another 3 (11.5%) patients. Other risk factors for C. difficile infection include certain chronic diseases. Of all the positive cases, four (9.7%) had malignancy, three were fed by tube, three had gastroesophageal reflux and two patients had cirrhosis. However, nine patients (22%) did not have any significant underlying medical conditions.
Discussion In the current study, the prevalence of CDAD was 2.4 and 1.7 per 10,000 patient days in 2007 and 2008, respectively. This rate is lower than the prevalence rates reported from the USA. In a pediatric study of C. difficile disease, the annual incidence of C. difficile-associated disease increased from 2.6 to 4.0 cases per 1000 admissions and from 4.4 to 6.5 cases per 10,000 patient days.9 In a Spanish study, the mean annual incidence rate was 41.2 per 100,000 discharges.10 In the APIC surveillance of C. difficile infection, the overall C. difficile rate was 13.1/1000 inpatients.11 However, the rate of C. difficile varies from one hospital to another and from one region to another. In a study on the prevalence of C. difficile in the USA, the prevalence rate varied from zero in Hawaii to 28.9/1000 inpatients in Rhode Island.11 The prevalence in our hospital is low and this could be related to under detection due to the lack of the availability of cell cytotoxicity assay or toxigenic culture. Comparing our results to the few studies from the same region showed some variation. In one study, 9.5% of 263 hospitalized patients acquired C. difficile during their hospital saty.12 In a recent study from Jordan, 13.7% of 300 stool specimens were positive for C. difficile by cultures.13 However, the latter study used culture method for the detection of C. difficile14 in contrast to the present study where EIA was used and thus a head-to-head comparison is not possible. In the APIC study, 73% of reported C. difficile infection patients were classified as healthcare-associated (with
C. difficile-associated disease in Dhahran either the onset in the hospital or the community).11 Similarly, 61.9% of the patients in the current study were healthcare-associated-associated (with either the onset in the hospital or the community). Additionally, we found that 45.2% of cases were inpatients aged 65 years or older, similar to the APIC study.11 However, one of the interesting finding is that 38.1% of the cases were community-associated CDAD. C. difficile is becoming an increasingly important community pathogen.15 Similarly, in recent studies from USA and Sweden 20e28% of cases of C. difficile were reported.16e18 In addition, in a study from Canada, community-associated C. difficile infection constituted about 20% of all cases.19 Thus, C. difficile infection in the community may have serious public health impact and should be targeted for future surveillance and studies. One of the risk factors for the acquisition of C. difficile infection was thought to be age, especially more than 65 years.20,21 However, the mean age of the patients in the current study was much lower at 44 years. This is an interesting age group in the light of recently described community-acquired cases. In a recent study, patients with community-associated infection were younger than those with healthcare facility-associated infection.22 It is thought that the incidence might be increasing among persons living in the community, including, but not limited to, healthy persons without recent healthcare contact.23 Thus, further studies are imperative to identify unrecognized risk factors of CDAD in the community and plan possible interventions. Our study had some limitations. First, the study was limited only to one center. The small number of infections and limitation to one center make generalizations to other centers in Saudi Arabia difficult. Second, we used EIAs to detect C. difficile and did not use culture methods. It was shown that about 75% of patients with C. difficile would be detected with a single EIA test, and that the positive predictive value of one EIA test is only 50%.24 Repeating assays on different stool samples from patients with initial negative samples improves the sensitivity of an assay but reduces the specificity of most tests to unacceptable levels.24 Third, it is possible that not all patients with diarrhea were tested for C. difficile and therefore, the true C. difficile prevalence could be higher. However, it is usual in our hospital that all patients with diarrhea have stool tests for C. difficile. Since, toxin testing is hampered by lack of sensitivity, it was suggested to overcome this problem by using a twostep method that uses EIA detection of glutamate dehydrogenase (GDH) for initial screening and then the cell cytotoxicity assay or toxigenic culture as the confirmatory test for GDH-positive stool specimens only.15 However, these two tests are not available in our institute. Despite these limitations, we consider that this study sheds light on this problem in Saudi Arabia and calls for further studies to identify the true prevalence rate of CDI in multiple hospitals. In conclusion, the prevalence of C. difficile-associated disease was low and 22% of the patients had no known underlying chronic medical conditions. The presence of community-associated infection in 38% of the patients calls for further studies in Saudi Arabia to elucidate the true prevalence of C. difficile infection.
375
Financial support None.
Conflict of interests Neither of the authors have conflict of interests to declare.
Acknowledgment The authors wish to acknowledge the use of Saudi Aramco Medical Services Organization (SAMSO) facilities for the data and study, which resulted in this paper. Opinions expressed in this article are those of the authors and not necessarily of SAMSO.
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