- Email: [email protected]
Clostridioides difficile infection: Incidence and risk factors in a tertiary care facility in Riyadh, Saudi Arabia
G Model JIPH-1228; No. of Pages 6
ARTICLE IN PRESS Journal of Infection and Public Health xxx (2019) xxx–xxx
Contents lists available at ScienceDirect
Journal of Infection and Public Health journal homepage: http://www.elsevier.com/locate/jiph
Clostridioides difficile infection: Incidence and risk factors in a tertiary care facility in Riyadh, Saudi Arabia Sally Alzouby a,b , Kamran Baig b , Fahad Alrabiah c , Atef Shibl a,∗ , Daifallah Al-Nakhli b , Abiola C. Senok d a
Department of Microbiology and Immunology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia Infection Control Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia c Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia d College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates b
a r t i c l e
i n f o
Article history: Received 27 March 2018 Received in revised form 15 May 2019 Accepted 3 October 2019 Keywords: Clostridioides difficile Epidemiology Infection control Saudi Arabia
a b s t r a c t Background: Significant increase in rates of Clostridioides difficile associated diarrhea (CDI) has been reported globally but there remains a paucity of data from Saudi Arabia. Methodology: Prospective hospital-based surveillance for CDI using the Center for Disease Control (CDC) criteria was conducted from June to November 2015 in a tertiary healthcare facility in Riyadh, Saudi Arabia. Results: During the surveillance period, 106 episodes of CDI were identified among 59 patients in 137,230 patient-days. The incidence of CDI was 3.5 per 10,000 patient days. Of the 106 episodes, 58% (n = 61) were new cases, 12% (n = 13) were recurrent cases and 30% (n = 32) were duplicate cases. Majority of the new cases (n/N = 43/61; 70%) were healthcare onset, followed by community onset (21%) and 8% were community-onset healthcare associated. No statistically significant change in trend was observed during the surveillance period. The most prevalent CDI risk factor was use of proton pump inhibitor (PPI) (92%) followed by prolonged use of antibiotics (77%). Pareto-analysis indicated that controlling for PPI use, prolong and multiple antibiotic exposure and prolonged hospitalization results in 80% CDI reduction. Conclusion: The findings indicate a low incidence of CDI. Multicenter studies are needed to elucidate the burden to CDI in the country. © 2019 Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).
Introduction Clostridioides difficile-associated disease (CDI) remains an important nosocomial infection with attendant morbidity, mortality and increased healthcare cost [1]. The clinical presentation of CDI ranges from diarrhea to pseudomembranous colitis, toxic megacolon and in severe cases colon perforation. Risk factors which have been linked with CDI include older age, prolonged use of multiple, usage of proton pump inhibitors and prolonged hospitalization [2–5]. Over the past fifteen years, there has been an upward trend in the incidence of CDI. Data from the Centers for Disease Control and Prevention (CDC), indicates that almost half a million cases of CDI
infections were reported annually in the United States of America [6]. Indeed, CDI rates in the USA in 2006–2010 showed a 47% increment in comparison with 2001–2005 rates [7]. In the Middle East region, reported prevalence rates of CDI ranges from 23.8% in Jordan to 8–10% in Kuwait [8–11]. Only two studies have been reported from Saudi Arabia with both describing the prevalence rates of CDI in tertiary care facilities [12,13]. The rates ranged from 0.2 to 0.3 per 10,000 patient days across two years in one hospital [13] and 1.7–2.4 per 10,000 patient days in the second hospital [12]. However, there are no studies determining and benchmarking the incidence of CDI in Saudi Arabia with international rates. This study which was carried out to address this gap in the literature was designed to determine the incidence of CDI in a tertiary care facility in Saudi Arabia based on internationally defined definitions to enable benchmarking.
∗ Corresponding author at: College of Medicine, Alfaisal University, P.O. Box 5092, Riyadh 11533, Saudi Arabia. E-mail address: [email protected] (A. Shibl). https://doi.org/10.1016/j.jiph.2019.10.014 1876-0341/© 2019 Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article in press as: Alzouby S, et al. Clostridioides difficile infection: Incidence and risk factors in a tertiary care facility in Riyadh, Saudi Arabia. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.10.014
G Model JIPH-1228; No. of Pages 6
ARTICLE IN PRESS S. Alzouby et al. / Journal of Infection and Public Health xxx (2019) xxx–xxx
2
Methods
Community – onset – healthcare facility associated (CO-HCFA)
Study setting
CDI laboratory event collected within three days of admission but within four weeks of last discharge. Fig. 1 shows the data collection sheet which was used.
This study was carried out at Prince Sultan Military Medical City (PSMMC) in Riyadh, Saudi Arabia. This 1300 bed facility is one of the largest tertiary care facilities in the country and serves the armed forces personnel and their families. This facility provides a broad range of complex services across all clinical disciplines and the wards are multi-bedded rooms. In the ICU the nurse:patient ratio is 1:1 while it is 1:4.for the non-ICU wards. Study design and implementation This prospective study was carried out from June to November 2015. Outpatients and babies in the neonatal intensive care units (NICU), labor, delivery, recovery, post-partum units well baby nursery and well-baby clinics were excluded. All eligible hospitalized patients admitted for clinical purposes to PSMMC who developed diarrhea were included in this study. All stools samples were tested using commercial enzyme-linked immunosorbent assay (ELISA) and then confirmed by the GeneXpert PCR testing. Antimicrobial susceptibility was not included because of the lack of testing in the laboratory. The data was collected by the investigator who is a trained infection control practitioner. All definitions and other related information are based on Center for Disease Control and Prevention’s National Healthcare Safety Network (NHSN) C. difficile Laboratory-identified (labID) event reporting module, 2015 [14]. The following NHSN definitions were used: CDI — positive laboratory assay was defined as a positive laboratory test result for C. difficile toxin A and/or B (including molecular assay PCR and toxin assay) tested on unformed stool sample. Incident CDI A CDI laboratory event case from a specimen obtained for the first time or more than 8 weeks after the most recent CDI lab event case. Recurrent CDI A CDI laboratory event from a specimen obtained more than 2 weeks and less or equal than 8 weeks from the most recent event for that patient. Duplicated C. difficile positive test (duplicate cases) A C. difficile toxin-positive laboratory result from the same patient and location, following a previous C. difficile toxin positive laboratory result within the past 2 weeks (14 days). All duplicated results were excluded from the study.
Data analysis All data were entered in an electronic database created using Microsoft Access (Microsoft Inc. Redmond, USA). SPSS version 20 (IBM, Chicago, USA) was used for data analysis. CDI incidence density per 10,000 patient-days was calculated and Pareto analysis was done to identify the most common risk factors. Descriptive analysis of collected data was performed. Ethical approval The study was approved by the research ethics committee of Prince Sultan Military Medical City, Riyadh, Saudi Arabia. Results During the six-month surveillance period, a total of 106 episodes of CDI were identified among 59 patients in 137,230 patientdays. Majority of patients were males (n/N = 34/59; 58%) while 42% (n/N = 25/59) were females. Out of the 106 episodes, 58% (n = 61) were new (incident) cases, 12% (n = 13) were recurrent cases and 30% (n = 32) were duplicate cases according to NHSN definitions. Duplicate cases were excluded from further analysis. Majority of the new cases (n/N = 43/61; 70%) were healthcare onset (HO), followed by community onset (CO) (21%) and 8% were communityonset healthcare associated (CO-HAI). The incidence of CDI was 3.5 per 10,000 per patient days and only HA and CO-HAI were included in the calculation. Fig. 2 shows the trend of CDI during the six-month study period. The distribution of HO and CO-HAI CDI varied with different clinical areas and the highest number was observed in male medical ward, followed by the pediatric ward, oncology ward and accident and emergency (Fig. 3). The Pareto analysis of risk factors associated with HO and CO-HAI CDI is shown in Fig. 4. The commonest risk factor was the use of proton pump inhibitors (PPIs) (92%) followed by prolonged exposure to antimicrobial therapy (>to 10 days) in the preceding 90 days (77%) and prolonged hospitalization for more than 3 weeks (75%). Other risk factors of significance were use of multiple antibiotics which was defined as receiving more than 3 antibiotics within the last 90 days (63%), elderly patients >65years (58%) and nasogastric tubing feeding (58%). The most commonly used antibiotics were tazocin (n = 24), vancomycin (n = 21), imipenem (n = 15), meropenem (n = 14) and colistin (n = 9; 19%) (Fig. 5). No agespecific trend between CDI and the different types of antibiotics was observed. Discussion
Hospitals facility onset (HO) A CDI laboratory event sample collected more than 3 days after admission to the facility. Community onset (CO) A CDI laboratory event sample collected in an outpatient location or inpatient location less or equal 3 days after admission to the facility.
There is a paucity of data from Saudi Arabia on the incidence of CDI hence a national bench mark has hitherto not been established. Indeed, the two studies from Saudi Arabia have reported the prevalence rates of CDI. In one study, the prevalence rate was 1.7–2.4 per 10,000 patient days from 2007 to 2008 while a lower prevalence rate of 0.2–0.3 per 10,000 patient days were reported from 2011 to 2012 in another center [12,13]. In addition, there was no indication from these two reports on the use of NHSN definitions for CDI classification. We present data on CDI incidence from Saudi Arabia based on NHSN classification which enables
Please cite this article in press as: Alzouby S, et al. Clostridioides difficile infection: Incidence and risk factors in a tertiary care facility in Riyadh, Saudi Arabia. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.10.014
G Model JIPH-1228; No. of Pages 6
ARTICLE IN PRESS S. Alzouby et al. / Journal of Infection and Public Health xxx (2019) xxx–xxx
3
Fig. 1. Data collection sheet.
benchmarking with international data. The incidence rate of 3.5 per 10,000 patient days is much lower compared to the NHSN rate of 7.2 per 10,000 patient days [15]. Additionally, the number of incident CDI cases is lower while recurrent cases are at about similar levels when compared to reported literature [16,17]. It is significant that majority of cases (70%) were of hospital onset.
Although this is higher than 52.7% reported from Dhahran, Saudi Arabia [12] it is still lower in comparison to recently reported data of 81% from Japan [5]. The slight male preponderance (58%) which we observed is similar to findings by Luo et al., but sharply contrasts data from the USA, where a female preponderance has been reported [6,18].
Please cite this article in press as: Alzouby S, et al. Clostridioides difficile infection: Incidence and risk factors in a tertiary care facility in Riyadh, Saudi Arabia. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.10.014
G Model JIPH-1228; No. of Pages 6 4
ARTICLE IN PRESS S. Alzouby et al. / Journal of Infection and Public Health xxx (2019) xxx–xxx
Fig. 2. Trend of HA CDI from June to November 2015.
Fig. 3. Number of cases from different clinical areas*. *(1–2) neuro surgery ward, (1–6) step down adult surgical ICU, (2–2) urology ward, (2–4) male medical ward, (2–8) medical cardiac ward, (2N) adult and pediatric medical and surgical ward, (3–2) adult female medical ward, (3–3) pediatric ward, (3–4) surgical ward, (3N) medical and surgical ward, (4N) medical surgical ward, (5B) OB & gynecology ward, (5N) oncology ward, (6B) renal transplant ward, (7N) male medical surgical VIP ward, (CCUA) adult and pediatric surgical cardiac ICU, (CCUB) medical cardiac ICU, (PSICU) pediatric surgical ICU, (4–3) liver transplant, (AE) accident and emergency.
Fig. 4. Pareto analysis for CDAD risk factors.
Please cite this article in press as: Alzouby S, et al. Clostridioides difficile infection: Incidence and risk factors in a tertiary care facility in Riyadh, Saudi Arabia. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.10.014
G Model JIPH-1228; No. of Pages 6
ARTICLE IN PRESS S. Alzouby et al. / Journal of Infection and Public Health xxx (2019) xxx–xxx
Fig. 5. Antibiotics used by patients prior to developing CDI.
The current study determined the possible risk factors for CDI in our setting. According to our Pareto-risk analysis, if we were able to remove the following risk factors (PPIs, receiving several antibiotics (>3) for prolonged period (>10 days), prolonged hospitalization, tube feeding and older age) we will be able to decrease CDI cases by 80%. This is significant as it indicates that in our setting there is an association between these risk factors and CDI. This pattern of association has not been universally described in the literature. There are reports in the literature which have failed to find an association between PPIs and CDI [19–21]. However, other studies agreed with our findings of increased age and prolonged hospitalization being contributory factors for CDI [6,18]. In addition, tazocin, which was the most commonly used antibiotic in this study had previously been found to be associated with a CDI outbreak in Brazil [22]. Similar to our findings, Huang et. al. identified carbapenems and previous use of three antibiotics as independent risk factors for CDI [23]. These findings reinforce the call for judicious use of antimicrobials with establishment of comprehensive antimicrobial stewardship program as important measures for the prevention of CDI. A greater proportion of patients diagnosed with CDI in our facility were in the male medical ward. This is in keeping with findings from a six-year retrospective study in an Italian hospital [24]. CDI cases were more in the medical ward compared to ICU and surgical ward. Similarly, in a prospective study in Canada patients aged >65 years were more likely to acquire CDI infection in medical ward compared to other wards [25]. However, this is not surprising as patients in the medical ward might stay in the facility for prolonged lengths of time. Several factors which may be also considered as CDI associated risk factors include, hospital infrastructure (multi bedded room), lack of number of hand washing sink, patient to nurse ratio, patient placement, availability of supplies such as personnel protective equipment’s and their correct utilization, antimicrobial stewardship program, adherence to environmental measures (ex: use of sodium hypochlorite) and patient visitors/caregivers. Further work on the role of these factors in modulating CDI rates in our setting is warranted.
5
*TMZ: trimethoprim–sulfamethoxazole.
Our study has some limitations. Firstly, duration of the study is short (6 months), a longer duration of at least one year would provide better indication of the temporal trends in C. difficile infection in this facility. In addition, we were unable to assess rate of CDI episodes in outpatient clinics and accident and emergency department due to the unavailability of denominator data. Another limitation is that the microbiology laboratory has no rejection policy to reject unappropriated samples (e.g., formed samples, samples for treatment purposes and duplicated samples). This might be one explanation of the number of duplicated samples in this study. Overall, the incidence of disease in this tertiary care facility was low when compared to NHSN rates. This analysis of CDI surveillance data gives a snapshot of the incidence of disease in Riyadh, Saudi Arabia. Disclosure statement None of the authors of this manuscript has any conflict of interest to disclose. This work was presented in part as poster at the 1st GCCMID conference held in Dubai in May 2016. It is also part of the academic thesis for Sally Alzouby toward the Masters in Biomedical Science (Infection Control) awarded by Alfaisal University, Riyadh, Saudi Arabia. Funding No funding sources. Contribution of authors SA, AS, FA & ACS conceived the study. SA collected the data. SA, KB, DA and ACS analyzed the data. All authors contributed to interpretation of the data and manuscript preparation. All authors approved the final version of the manuscript. Acknowledgement None.
Please cite this article in press as: Alzouby S, et al. Clostridioides difficile infection: Incidence and risk factors in a tertiary care facility in Riyadh, Saudi Arabia. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.10.014
G Model JIPH-1228; No. of Pages 6
ARTICLE IN PRESS S. Alzouby et al. / Journal of Infection and Public Health xxx (2019) xxx–xxx
6
References [1] Depestel DD, Aronoff DM. Epidemiology of Clostridium difficile infection. J Pharm Pract 2013;26:464–75. [2] Deshpande A, Pasupuleti V, Thota P, Pant C, Rolston DD, Hernandez AV, et al. Risk factors for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol 2015;36:452–60. [3] Forster AJ, Taljaard M, Oake N, Wilson K, Roth V, van Walraven C. The effect of hospital-acquired infection with Clostridium difficile on length of stay in hospital. Can Med Assoc J 2012;184:37–42. [4] 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. [5] Ogielska M, Lanotte P, Le Brun C, Valentin AS, Garot D, Tellier AC, et al. Emergence of community-acquired Clostridium difficile infection: the experience of a French hospital and review of the literature. Int J Infect Dis 2015;37:36–41. [6] Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015;372:825–34. [7] Halabi WJ, Nguyen VQ, Carmichael JC, Pigazzi A, Stamos MJ, Mills S. Clostridium difficile colitis in the United States: a decade of trends, outcomes, risk factors for colectomy, and mortality after colectomy. J Am Coll Surg 2013;217:802–12. [8] Jamal W, Rotimi VO, Brazier J, Duerden BI. Analysis of prevalence, risk factors and molecular epidemiology of Clostridium difficile infection in Kuwait over a 3-year period. Anaerobe 2010;16:560–5. [9] Nasereddin LM, Bakri FG, Shehabi AA. Clostridium difficile infections among Jordanian adult hospitalized patients. Am J Infect Control 2009;37:864–6. [10] Rotimi VO, Jamal WY, Mokaddas EM, Brazier JS, Johny M, Duerden BI. Prevalent PCR ribotypes of clinical and environmental strains of Clostridium difficile isolated from intensive-therapy unit patients in Kuwait. J Med Microbiol 2003;52:705–9. [11] Rotimi VO, Mokaddas EM, Jamal WY, Verghese TL, el-Din K, Junaid TA. Hospitalacquired Clostridium difficile infection amongst ICU and burn patients in Kuwait. Med Princ Pract 2002;11:23–8. [12] Al-Tawfiq JA, Abed MS. Clostridium difficile-associated disease among patients in Dhahran, Saudi Arabia. Travel Med Infect Dis 2010;8:373–6. [13] Sue ES, Mohammed FH, Michael A. Prevalence of Clostridium difficile toxin in diarrhoeal stool samples of patients from a general hospital in Eastern province, Saudi Arabia. Int J Med Res Health Sci 2014;3:302–308.
[14] Prevention CfDCa. Center for Disease Control and Prevention’s National Healthcare Safety Network (NHSN) C. difficile laboratory-identified (labID) event reporting module; 2015. [15] Dudeck MA, Weiner LM, Malpiedi PJ, Edwards JR, Peterson KD, Sievert DM. Risk adjustment for healthcare facility-onset C. difficile and MRSA bacteremia laboratory-identified event reporting in NHSN; 2013. [16] Molagic V, L˘ap˘adat I, Mih˘ailescu R, Popescu C, Tilis¸can C, Jipa R, et al. Clinical and epidemiologic features of community versus hospital-acquired Clostridium difficile infection. BMC Infect Dis 2014;14:O25. [17] Kurti Z, Lovasz BD, Mandel MD, Csima Z, Golovics PA, Csako BD, et al. Burden of Clostridium difficile infection between 2010 and 2013: trends and outcomes from an academic center in Eastern Europe. World J Gastroenterol 2015;21:6728–35. [18] Luo R, Greenberg A, Stone CD. Outcomes of Clostridium difficile infection in hospitalized leukemia patients: a nationwide analysis. Infect Control Hosp Epidemiol 2015;36:794–801. [19] Freedberg DE, Salmasian H, Friedman C, Abrams JA. Proton pump inhibitors and risk for recurrent Clostridium difficile infection among inpatients. Am J Gastroenterol 2013;108:1794–801. [20] Kutty PK, Woods CW, Sena AC, Benoit SR, Naggie S, Frederick J, et al. Risk factors for and estimated incidence of community-associated Clostridium difficile infection, North Carolina, USA. Emerg Infect Dis 2010;16:197–204. [21] Naggie S, Miller BA, Zuzak KB, Pence BW, Mayo AJ, Nicholson BP, et al. A casecontrol study of community-associated Clostridium difficile infection: no role for proton pump inhibitors. Am J Med 2011;124:276 e1–7. [22] Balassiano IT, Dos Santos-Filho J, de Oliveira MP, Ramos MC, Japiassu AM, Dos Reis AM, et al. An outbreak case of Clostridium difficile-associated diarrhea among elderly inpatients of an intensive care unit of a tertiary hospital in Rio de Janeiro, Brazil. Diagn Microbiol Infect Dis 2010;68:449–55. [23] Huang H, Wu S, Chen R, Xu S, Fang H, Weintraub A, et al. Risk factors of Clostridium difficile infections among patients in a university hospital in Shanghai, China. Anaerobe 2014;30:65–9. [24] Di Bella S, Musso M, Cataldo MA, Meledandri M, Bordi E, Capozzi D, et al. Clostridium difficile infection in Italian urban hospitals: data from 2006 through 2011. BMC Infect Dis 2013;13:146. [25] Gravel D, Miller M, Simor A, Taylor G, Gardam M, McGeer A, et al. Health care-associated Clostridium difficile infection in adults admitted to acute care hospitals in Canada: a Canadian Nosocomial Infection Surveillance Program Study. Clin Infect Dis 2009;48:568–76.
Please cite this article in press as: Alzouby S, et al. Clostridioides difficile infection: Incidence and risk factors in a tertiary care facility in Riyadh, Saudi Arabia. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.10.014
ARTICLE IN PRESS Journal of Infection and Public Health xxx (2019) xxx–xxx
Contents lists available at ScienceDirect
Journal of Infection and Public Health journal homepage: http://www.elsevier.com/locate/jiph
Clostridioides difficile infection: Incidence and risk factors in a tertiary care facility in Riyadh, Saudi Arabia Sally Alzouby a,b , Kamran Baig b , Fahad Alrabiah c , Atef Shibl a,∗ , Daifallah Al-Nakhli b , Abiola C. Senok d a
Department of Microbiology and Immunology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia Infection Control Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia c Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia d College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates b
a r t i c l e
i n f o
Article history: Received 27 March 2018 Received in revised form 15 May 2019 Accepted 3 October 2019 Keywords: Clostridioides difficile Epidemiology Infection control Saudi Arabia
a b s t r a c t Background: Significant increase in rates of Clostridioides difficile associated diarrhea (CDI) has been reported globally but there remains a paucity of data from Saudi Arabia. Methodology: Prospective hospital-based surveillance for CDI using the Center for Disease Control (CDC) criteria was conducted from June to November 2015 in a tertiary healthcare facility in Riyadh, Saudi Arabia. Results: During the surveillance period, 106 episodes of CDI were identified among 59 patients in 137,230 patient-days. The incidence of CDI was 3.5 per 10,000 patient days. Of the 106 episodes, 58% (n = 61) were new cases, 12% (n = 13) were recurrent cases and 30% (n = 32) were duplicate cases. Majority of the new cases (n/N = 43/61; 70%) were healthcare onset, followed by community onset (21%) and 8% were community-onset healthcare associated. No statistically significant change in trend was observed during the surveillance period. The most prevalent CDI risk factor was use of proton pump inhibitor (PPI) (92%) followed by prolonged use of antibiotics (77%). Pareto-analysis indicated that controlling for PPI use, prolong and multiple antibiotic exposure and prolonged hospitalization results in 80% CDI reduction. Conclusion: The findings indicate a low incidence of CDI. Multicenter studies are needed to elucidate the burden to CDI in the country. © 2019 Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).
Introduction Clostridioides difficile-associated disease (CDI) remains an important nosocomial infection with attendant morbidity, mortality and increased healthcare cost [1]. The clinical presentation of CDI ranges from diarrhea to pseudomembranous colitis, toxic megacolon and in severe cases colon perforation. Risk factors which have been linked with CDI include older age, prolonged use of multiple, usage of proton pump inhibitors and prolonged hospitalization [2–5]. Over the past fifteen years, there has been an upward trend in the incidence of CDI. Data from the Centers for Disease Control and Prevention (CDC), indicates that almost half a million cases of CDI
infections were reported annually in the United States of America [6]. Indeed, CDI rates in the USA in 2006–2010 showed a 47% increment in comparison with 2001–2005 rates [7]. In the Middle East region, reported prevalence rates of CDI ranges from 23.8% in Jordan to 8–10% in Kuwait [8–11]. Only two studies have been reported from Saudi Arabia with both describing the prevalence rates of CDI in tertiary care facilities [12,13]. The rates ranged from 0.2 to 0.3 per 10,000 patient days across two years in one hospital [13] and 1.7–2.4 per 10,000 patient days in the second hospital [12]. However, there are no studies determining and benchmarking the incidence of CDI in Saudi Arabia with international rates. This study which was carried out to address this gap in the literature was designed to determine the incidence of CDI in a tertiary care facility in Saudi Arabia based on internationally defined definitions to enable benchmarking.
∗ Corresponding author at: College of Medicine, Alfaisal University, P.O. Box 5092, Riyadh 11533, Saudi Arabia. E-mail address: [email protected] (A. Shibl). https://doi.org/10.1016/j.jiph.2019.10.014 1876-0341/© 2019 Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article in press as: Alzouby S, et al. Clostridioides difficile infection: Incidence and risk factors in a tertiary care facility in Riyadh, Saudi Arabia. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.10.014
G Model JIPH-1228; No. of Pages 6
ARTICLE IN PRESS S. Alzouby et al. / Journal of Infection and Public Health xxx (2019) xxx–xxx
2
Methods
Community – onset – healthcare facility associated (CO-HCFA)
Study setting
CDI laboratory event collected within three days of admission but within four weeks of last discharge. Fig. 1 shows the data collection sheet which was used.
This study was carried out at Prince Sultan Military Medical City (PSMMC) in Riyadh, Saudi Arabia. This 1300 bed facility is one of the largest tertiary care facilities in the country and serves the armed forces personnel and their families. This facility provides a broad range of complex services across all clinical disciplines and the wards are multi-bedded rooms. In the ICU the nurse:patient ratio is 1:1 while it is 1:4.for the non-ICU wards. Study design and implementation This prospective study was carried out from June to November 2015. Outpatients and babies in the neonatal intensive care units (NICU), labor, delivery, recovery, post-partum units well baby nursery and well-baby clinics were excluded. All eligible hospitalized patients admitted for clinical purposes to PSMMC who developed diarrhea were included in this study. All stools samples were tested using commercial enzyme-linked immunosorbent assay (ELISA) and then confirmed by the GeneXpert PCR testing. Antimicrobial susceptibility was not included because of the lack of testing in the laboratory. The data was collected by the investigator who is a trained infection control practitioner. All definitions and other related information are based on Center for Disease Control and Prevention’s National Healthcare Safety Network (NHSN) C. difficile Laboratory-identified (labID) event reporting module, 2015 [14]. The following NHSN definitions were used: CDI — positive laboratory assay was defined as a positive laboratory test result for C. difficile toxin A and/or B (including molecular assay PCR and toxin assay) tested on unformed stool sample. Incident CDI A CDI laboratory event case from a specimen obtained for the first time or more than 8 weeks after the most recent CDI lab event case. Recurrent CDI A CDI laboratory event from a specimen obtained more than 2 weeks and less or equal than 8 weeks from the most recent event for that patient. Duplicated C. difficile positive test (duplicate cases) A C. difficile toxin-positive laboratory result from the same patient and location, following a previous C. difficile toxin positive laboratory result within the past 2 weeks (14 days). All duplicated results were excluded from the study.
Data analysis All data were entered in an electronic database created using Microsoft Access (Microsoft Inc. Redmond, USA). SPSS version 20 (IBM, Chicago, USA) was used for data analysis. CDI incidence density per 10,000 patient-days was calculated and Pareto analysis was done to identify the most common risk factors. Descriptive analysis of collected data was performed. Ethical approval The study was approved by the research ethics committee of Prince Sultan Military Medical City, Riyadh, Saudi Arabia. Results During the six-month surveillance period, a total of 106 episodes of CDI were identified among 59 patients in 137,230 patientdays. Majority of patients were males (n/N = 34/59; 58%) while 42% (n/N = 25/59) were females. Out of the 106 episodes, 58% (n = 61) were new (incident) cases, 12% (n = 13) were recurrent cases and 30% (n = 32) were duplicate cases according to NHSN definitions. Duplicate cases were excluded from further analysis. Majority of the new cases (n/N = 43/61; 70%) were healthcare onset (HO), followed by community onset (CO) (21%) and 8% were communityonset healthcare associated (CO-HAI). The incidence of CDI was 3.5 per 10,000 per patient days and only HA and CO-HAI were included in the calculation. Fig. 2 shows the trend of CDI during the six-month study period. The distribution of HO and CO-HAI CDI varied with different clinical areas and the highest number was observed in male medical ward, followed by the pediatric ward, oncology ward and accident and emergency (Fig. 3). The Pareto analysis of risk factors associated with HO and CO-HAI CDI is shown in Fig. 4. The commonest risk factor was the use of proton pump inhibitors (PPIs) (92%) followed by prolonged exposure to antimicrobial therapy (>to 10 days) in the preceding 90 days (77%) and prolonged hospitalization for more than 3 weeks (75%). Other risk factors of significance were use of multiple antibiotics which was defined as receiving more than 3 antibiotics within the last 90 days (63%), elderly patients >65years (58%) and nasogastric tubing feeding (58%). The most commonly used antibiotics were tazocin (n = 24), vancomycin (n = 21), imipenem (n = 15), meropenem (n = 14) and colistin (n = 9; 19%) (Fig. 5). No agespecific trend between CDI and the different types of antibiotics was observed. Discussion
Hospitals facility onset (HO) A CDI laboratory event sample collected more than 3 days after admission to the facility. Community onset (CO) A CDI laboratory event sample collected in an outpatient location or inpatient location less or equal 3 days after admission to the facility.
There is a paucity of data from Saudi Arabia on the incidence of CDI hence a national bench mark has hitherto not been established. Indeed, the two studies from Saudi Arabia have reported the prevalence rates of CDI. In one study, the prevalence rate was 1.7–2.4 per 10,000 patient days from 2007 to 2008 while a lower prevalence rate of 0.2–0.3 per 10,000 patient days were reported from 2011 to 2012 in another center [12,13]. In addition, there was no indication from these two reports on the use of NHSN definitions for CDI classification. We present data on CDI incidence from Saudi Arabia based on NHSN classification which enables
Please cite this article in press as: Alzouby S, et al. Clostridioides difficile infection: Incidence and risk factors in a tertiary care facility in Riyadh, Saudi Arabia. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.10.014
G Model JIPH-1228; No. of Pages 6
ARTICLE IN PRESS S. Alzouby et al. / Journal of Infection and Public Health xxx (2019) xxx–xxx
3
Fig. 1. Data collection sheet.
benchmarking with international data. The incidence rate of 3.5 per 10,000 patient days is much lower compared to the NHSN rate of 7.2 per 10,000 patient days [15]. Additionally, the number of incident CDI cases is lower while recurrent cases are at about similar levels when compared to reported literature [16,17]. It is significant that majority of cases (70%) were of hospital onset.
Although this is higher than 52.7% reported from Dhahran, Saudi Arabia [12] it is still lower in comparison to recently reported data of 81% from Japan [5]. The slight male preponderance (58%) which we observed is similar to findings by Luo et al., but sharply contrasts data from the USA, where a female preponderance has been reported [6,18].
Please cite this article in press as: Alzouby S, et al. Clostridioides difficile infection: Incidence and risk factors in a tertiary care facility in Riyadh, Saudi Arabia. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.10.014
G Model JIPH-1228; No. of Pages 6 4
ARTICLE IN PRESS S. Alzouby et al. / Journal of Infection and Public Health xxx (2019) xxx–xxx
Fig. 2. Trend of HA CDI from June to November 2015.
Fig. 3. Number of cases from different clinical areas*. *(1–2) neuro surgery ward, (1–6) step down adult surgical ICU, (2–2) urology ward, (2–4) male medical ward, (2–8) medical cardiac ward, (2N) adult and pediatric medical and surgical ward, (3–2) adult female medical ward, (3–3) pediatric ward, (3–4) surgical ward, (3N) medical and surgical ward, (4N) medical surgical ward, (5B) OB & gynecology ward, (5N) oncology ward, (6B) renal transplant ward, (7N) male medical surgical VIP ward, (CCUA) adult and pediatric surgical cardiac ICU, (CCUB) medical cardiac ICU, (PSICU) pediatric surgical ICU, (4–3) liver transplant, (AE) accident and emergency.
Fig. 4. Pareto analysis for CDAD risk factors.
Please cite this article in press as: Alzouby S, et al. Clostridioides difficile infection: Incidence and risk factors in a tertiary care facility in Riyadh, Saudi Arabia. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.10.014
G Model JIPH-1228; No. of Pages 6
ARTICLE IN PRESS S. Alzouby et al. / Journal of Infection and Public Health xxx (2019) xxx–xxx
Fig. 5. Antibiotics used by patients prior to developing CDI.
The current study determined the possible risk factors for CDI in our setting. According to our Pareto-risk analysis, if we were able to remove the following risk factors (PPIs, receiving several antibiotics (>3) for prolonged period (>10 days), prolonged hospitalization, tube feeding and older age) we will be able to decrease CDI cases by 80%. This is significant as it indicates that in our setting there is an association between these risk factors and CDI. This pattern of association has not been universally described in the literature. There are reports in the literature which have failed to find an association between PPIs and CDI [19–21]. However, other studies agreed with our findings of increased age and prolonged hospitalization being contributory factors for CDI [6,18]. In addition, tazocin, which was the most commonly used antibiotic in this study had previously been found to be associated with a CDI outbreak in Brazil [22]. Similar to our findings, Huang et. al. identified carbapenems and previous use of three antibiotics as independent risk factors for CDI [23]. These findings reinforce the call for judicious use of antimicrobials with establishment of comprehensive antimicrobial stewardship program as important measures for the prevention of CDI. A greater proportion of patients diagnosed with CDI in our facility were in the male medical ward. This is in keeping with findings from a six-year retrospective study in an Italian hospital [24]. CDI cases were more in the medical ward compared to ICU and surgical ward. Similarly, in a prospective study in Canada patients aged >65 years were more likely to acquire CDI infection in medical ward compared to other wards [25]. However, this is not surprising as patients in the medical ward might stay in the facility for prolonged lengths of time. Several factors which may be also considered as CDI associated risk factors include, hospital infrastructure (multi bedded room), lack of number of hand washing sink, patient to nurse ratio, patient placement, availability of supplies such as personnel protective equipment’s and their correct utilization, antimicrobial stewardship program, adherence to environmental measures (ex: use of sodium hypochlorite) and patient visitors/caregivers. Further work on the role of these factors in modulating CDI rates in our setting is warranted.
5
*TMZ: trimethoprim–sulfamethoxazole.
Our study has some limitations. Firstly, duration of the study is short (6 months), a longer duration of at least one year would provide better indication of the temporal trends in C. difficile infection in this facility. In addition, we were unable to assess rate of CDI episodes in outpatient clinics and accident and emergency department due to the unavailability of denominator data. Another limitation is that the microbiology laboratory has no rejection policy to reject unappropriated samples (e.g., formed samples, samples for treatment purposes and duplicated samples). This might be one explanation of the number of duplicated samples in this study. Overall, the incidence of disease in this tertiary care facility was low when compared to NHSN rates. This analysis of CDI surveillance data gives a snapshot of the incidence of disease in Riyadh, Saudi Arabia. Disclosure statement None of the authors of this manuscript has any conflict of interest to disclose. This work was presented in part as poster at the 1st GCCMID conference held in Dubai in May 2016. It is also part of the academic thesis for Sally Alzouby toward the Masters in Biomedical Science (Infection Control) awarded by Alfaisal University, Riyadh, Saudi Arabia. Funding No funding sources. Contribution of authors SA, AS, FA & ACS conceived the study. SA collected the data. SA, KB, DA and ACS analyzed the data. All authors contributed to interpretation of the data and manuscript preparation. All authors approved the final version of the manuscript. Acknowledgement None.
Please cite this article in press as: Alzouby S, et al. Clostridioides difficile infection: Incidence and risk factors in a tertiary care facility in Riyadh, Saudi Arabia. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.10.014
G Model JIPH-1228; No. of Pages 6
ARTICLE IN PRESS S. Alzouby et al. / Journal of Infection and Public Health xxx (2019) xxx–xxx
6
References [1] Depestel DD, Aronoff DM. Epidemiology of Clostridium difficile infection. J Pharm Pract 2013;26:464–75. [2] Deshpande A, Pasupuleti V, Thota P, Pant C, Rolston DD, Hernandez AV, et al. Risk factors for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol 2015;36:452–60. [3] Forster AJ, Taljaard M, Oake N, Wilson K, Roth V, van Walraven C. The effect of hospital-acquired infection with Clostridium difficile on length of stay in hospital. Can Med Assoc J 2012;184:37–42. [4] 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. [5] Ogielska M, Lanotte P, Le Brun C, Valentin AS, Garot D, Tellier AC, et al. Emergence of community-acquired Clostridium difficile infection: the experience of a French hospital and review of the literature. Int J Infect Dis 2015;37:36–41. [6] Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015;372:825–34. [7] Halabi WJ, Nguyen VQ, Carmichael JC, Pigazzi A, Stamos MJ, Mills S. Clostridium difficile colitis in the United States: a decade of trends, outcomes, risk factors for colectomy, and mortality after colectomy. J Am Coll Surg 2013;217:802–12. [8] Jamal W, Rotimi VO, Brazier J, Duerden BI. Analysis of prevalence, risk factors and molecular epidemiology of Clostridium difficile infection in Kuwait over a 3-year period. Anaerobe 2010;16:560–5. [9] Nasereddin LM, Bakri FG, Shehabi AA. Clostridium difficile infections among Jordanian adult hospitalized patients. Am J Infect Control 2009;37:864–6. [10] Rotimi VO, Jamal WY, Mokaddas EM, Brazier JS, Johny M, Duerden BI. Prevalent PCR ribotypes of clinical and environmental strains of Clostridium difficile isolated from intensive-therapy unit patients in Kuwait. J Med Microbiol 2003;52:705–9. [11] Rotimi VO, Mokaddas EM, Jamal WY, Verghese TL, el-Din K, Junaid TA. Hospitalacquired Clostridium difficile infection amongst ICU and burn patients in Kuwait. Med Princ Pract 2002;11:23–8. [12] Al-Tawfiq JA, Abed MS. Clostridium difficile-associated disease among patients in Dhahran, Saudi Arabia. Travel Med Infect Dis 2010;8:373–6. [13] Sue ES, Mohammed FH, Michael A. Prevalence of Clostridium difficile toxin in diarrhoeal stool samples of patients from a general hospital in Eastern province, Saudi Arabia. Int J Med Res Health Sci 2014;3:302–308.
[14] Prevention CfDCa. Center for Disease Control and Prevention’s National Healthcare Safety Network (NHSN) C. difficile laboratory-identified (labID) event reporting module; 2015. [15] Dudeck MA, Weiner LM, Malpiedi PJ, Edwards JR, Peterson KD, Sievert DM. Risk adjustment for healthcare facility-onset C. difficile and MRSA bacteremia laboratory-identified event reporting in NHSN; 2013. [16] Molagic V, L˘ap˘adat I, Mih˘ailescu R, Popescu C, Tilis¸can C, Jipa R, et al. Clinical and epidemiologic features of community versus hospital-acquired Clostridium difficile infection. BMC Infect Dis 2014;14:O25. [17] Kurti Z, Lovasz BD, Mandel MD, Csima Z, Golovics PA, Csako BD, et al. Burden of Clostridium difficile infection between 2010 and 2013: trends and outcomes from an academic center in Eastern Europe. World J Gastroenterol 2015;21:6728–35. [18] Luo R, Greenberg A, Stone CD. Outcomes of Clostridium difficile infection in hospitalized leukemia patients: a nationwide analysis. Infect Control Hosp Epidemiol 2015;36:794–801. [19] Freedberg DE, Salmasian H, Friedman C, Abrams JA. Proton pump inhibitors and risk for recurrent Clostridium difficile infection among inpatients. Am J Gastroenterol 2013;108:1794–801. [20] Kutty PK, Woods CW, Sena AC, Benoit SR, Naggie S, Frederick J, et al. Risk factors for and estimated incidence of community-associated Clostridium difficile infection, North Carolina, USA. Emerg Infect Dis 2010;16:197–204. [21] Naggie S, Miller BA, Zuzak KB, Pence BW, Mayo AJ, Nicholson BP, et al. A casecontrol study of community-associated Clostridium difficile infection: no role for proton pump inhibitors. Am J Med 2011;124:276 e1–7. [22] Balassiano IT, Dos Santos-Filho J, de Oliveira MP, Ramos MC, Japiassu AM, Dos Reis AM, et al. An outbreak case of Clostridium difficile-associated diarrhea among elderly inpatients of an intensive care unit of a tertiary hospital in Rio de Janeiro, Brazil. Diagn Microbiol Infect Dis 2010;68:449–55. [23] Huang H, Wu S, Chen R, Xu S, Fang H, Weintraub A, et al. Risk factors of Clostridium difficile infections among patients in a university hospital in Shanghai, China. Anaerobe 2014;30:65–9. [24] Di Bella S, Musso M, Cataldo MA, Meledandri M, Bordi E, Capozzi D, et al. Clostridium difficile infection in Italian urban hospitals: data from 2006 through 2011. BMC Infect Dis 2013;13:146. [25] Gravel D, Miller M, Simor A, Taylor G, Gardam M, McGeer A, et al. Health care-associated Clostridium difficile infection in adults admitted to acute care hospitals in Canada: a Canadian Nosocomial Infection Surveillance Program Study. Clin Infect Dis 2009;48:568–76.
Please cite this article in press as: Alzouby S, et al. Clostridioides difficile infection: Incidence and risk factors in a tertiary care facility in Riyadh, Saudi Arabia. J Infect Public Health (2019), https://doi.org/10.1016/j.jiph.2019.10.014