American Journal of Infection Control 42 (2014) 311-5
Contents lists available at ScienceDirect
American Journal of Infection Control
American Journal of Infection Control
journal homepage: www.ajicjournal.org
Major article
Prevention of Clostridium difficile infection in rural hospitals Nicholas Haun MD a, Adam Hofer a, M. Todd Greene PhD, MPH b, c, Gwen Borlaug CIC, MPH d, Jenny Pritchett MPH, RN, CIC e, Tina Scallon RN f, Nasia Safdar MD, PhD a, g, * a
University of Wisconsin School of Medicine and Public Health, Madison, WI Division of General Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI c Ann Arbor VA Medical Center, Ann Arbor, MI d Wisconsin Division of Public Health, Madison, WI e Grant Regional Health Center, Lancaster, WI f Sauk Prairie Memorial Hospital, Sauk Prairie, WI g William S. Middleton Memorial Veterans Hospital, Madison, WI b
Key Words: Health care-associated Survey Evidence-based practices
Background: Prevention of Clostridium difficile infection (CDI) remains challenging across the spectrum of health care. There are limited data on prevention practices for CDI in the rural health care setting. Methods: An electronic survey was administered to 21 rural facilities in Wisconsin, part of the Rural Wisconsin Health Cooperative. Data were collected on hospital characteristics and practices to prevent endemic CDI. Results: Fifteen facilities responded (71%). Nearly all respondent facilities reported regular use of dedicated patient care items, use of gown and gloves, private patient rooms, hand hygiene, and room cleaning. Facilities in which the infection preventionist thought the support of his/her leadership to be “Very good” or “Excellent” employed significantly more CDI practices (13.3 2.4 [standard deviation]) compared with infection preventionists who thought there was less support from leadership (9.8 3.0, P ¼ .033). Surveillance for CDI was highly variable. The most frequent barriers to implementation of CDI prevention practices included lack of adequate resources, lack of a physician champion, and difficulty keeping up with new recommendations. Conclusion: Although most rural facilities in our survey reported using evidence-based practices for prevention of CDI, surveillance practices were highly variable, and data regarding the impact of these practices on CDI rates were limited. Future efforts that correlate CDI prevention initiatives and CDI incidence will help develop evidence-based practices in these resource-limited settings. Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc.
Clostridium difficile (C difficile) is the most common bacterial cause of health care-associated diarrhea, accounting for 15% to 25% of antibiotic-associated diarrhea.1 Recent years have witnessed a rapid increase in the incidence of C difficile infection (CDI) with recognition of a new highly virulent strain that has caused global outbreaks.2-6 Each year, CDI affects an estimated 500,000 persons, accounting for over $1 billion in costs and contributing to up to 20,000 deaths.7 Prevention of CDI in health care institutions is essential. Whereas recent studies have examined CDI prevention practices,8-10 * Address correspondence to Nasia Safdar, MD, PhD, MFCB 5221, University of Wisconsin Hospital and Clinics, Madison, WI 53705. E-mail address: [email protected] (N. Safdar). Conflicts of interest: None to report.
data on institutions other than acute care facilities are limited.11-13 As the spectrum of health care expands beyond traditional acute care settings, it is important to examine all types of health care settings regarding prevention of CDI because prevention efforts may need to be tailored to the type of health care setting. Small rural hospitals are one such setting where data regarding the incidence of C difficile and current infection control efforts are scarce. Aspects unique to small rural health care facilities such as patient census, interfacility movement, length of stay, and resources may impact the dynamics of C difficile transmission and infection as well as application of infection control practices. To explore this, we undertook a survey to evaluate infection control practices relevant to CDI that are currently in use in rural acute care and critical access facilities in the state of Wisconsin and to evaluate the perceptions of lead infection preventionists (IPs) for potential
0196-6553/$00.00 - Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc. http://dx.doi.org/10.1016/j.ajic.2013.09.011
312
N. Haun et al. / American Journal of Infection Control 42 (2014) 311-5
facilitators of and barriers to implementation of prevention practices for CDI. METHODS Data collection The study was conducted in May 2012 as a collaborative effort between the University of Wisconsin and the Rural Wisconsin Health Cooperative (RWHC), a coalition of 35 rural Wisconsin health care facilities that provides services such as networking and advocacy for member facilities in many aspects of care including infection control. The study was submitted to the Institutional Review Board and deemed exempt. The survey instrumentd adapted from prior research14,15dwas pilot tested by 4 IPs: 3 at the University of Wisconsin and 1 at RWHC and modified to incorporate feedback. The final version of the survey was administered electronically to lead IPs at the 21 health care facilities that are voluntary participants in the RWHC infection control roundtable. There are no appreciable differences between roundtable participant facilities and nonparticipant facilities. The final survey population included 4 acute care hospitals and 17 critical access hospitals. The primary respondent for the survey was an IP employed by the participating facility; however, consultation with physicians and other infection control staff was encouraged to ensure accurate responses. The survey was administered electronically using Select Survey software (Optimal Solutions Group LLC, College Park, MD). A cover letter with instructions and a uniform resource locator (URL, ie, Internet address) to access the survey was e-mailed to all facilities in the RWHC infection control roundtable. Study measures The survey assessed basic information of the facility including location, type of facility (acute care or critical access hospital), bed count, and average daily census. In addition, we asked respondents how frequently certain CDI prevention practices (as recommended by national guidelines16,17 were employed in their facilities. Respondents were asked to estimate the frequency of practice on a Likert scale of 1 (never) to 5 (always). We defined responses of 4 (almost always) or 5 (always) as regular use of the respective prevention practice. The practices examined included the use of dedicated patient care items, use of gowns/gloves for contact precautions, placement of patients with CDI in private rooms, hand hygiene practices, education of staff and patients regarding CDI, avoidance of treatment of asymptomatic carriers, environmental services practices, and use of chlorine-based products during outbreaks. For each prevention practice, respondents were asked to indicate whether or not the facility has a written policy and, if so, whether the written policy is monitored for adherence. Respondents were asked to rank the strength of evidence supporting these recommended practices on a Likert scale of 1 (no evidence) to 5 (extremely strong evidence). Respondents were also asked to identify the most important perceived barriers to implementing evidence-based practices by ranking from a preselected list of potential barriers and by indicating their agreement with a series of statements on a Likert scale of 1 (strongly agree) to 5 (strongly disagree). For analysis purposes, responses of 1 (strongly agree) or 2 (agree) were used to define agreement. Additional information obtained included rates of CDI and information regarding the structure of the current infection control program including whether the facility has an epidemiologist, whether IPs are certified in clinical infection control, the number of full-time equivalent IPs on staff, time invested in surveillance, types of health care-
Table 1 Characteristics of respondent facilities and infection control programs General facility information Capacity (beds) Average daily census % Of private rooms Presence of house staff trainees Use of electronic medical record Infection control program Surveillance conducted for HAI? CDI CLABSI Surgical site infection CAUTI VAP % Of time spent on surveillance Antibiotic stewardship program Participation in HAI prevention collaboratives Hospital epidemiologist employed Number of IP full-time equivalents IP certified in infection control Use of data-mining software CDI-related information Duration of contact precautions 48 Hours after asymptomatic Duration of hospitalization Method of environmental decontamination Use of chlorine solution during outbreaks Use of detergent for surface cleaning Use of sporicidal agent Method of environmental monitoring Fluorescence marker Bioluminescence assay Observation Report CDI to NHSN Use of probiotic for prevention or treatment
30; 25-73 8.9; 3-18.3 84; 20-100 3/15 (20) 13/15 (87)
15/15 (100) 10/15 (67) 15/15 (100) 15/15 (100) 3/15 (20) 45; 10-90 4/15 (27) 11/15 (73) 3/15 (20) 0.6; 0-1.3 2/14 (14) 1/15 (7)
6/15 (40) 8/15 (53) 14/15 (93) 13/15 (87) 13/15 (87) 3/15 1/15 8/15 1/15 2/13
(20) (7) (53) (7) (15)
CAUTI, catheter-associated urinary tract infection; CDI, Clostridium difficile infection; CLABSI, central line-associated bloodstream infection; HAI, health care-associated infection; IP, infection preventionist; NHSN, National Health Safety Network; VAP, ventilator-associated pneumonia. NOTE. Data are combined responses for both acute care hospitals and critical access hospitals. Aside from hospital capacity and average daily census, there were no apparent differences in facility characteristics between acute care hospitals and critical access hospitals. Continuous variables are expressed as averages with range. Binary variables are expressed as number of positive responses over total responses (including both negative and uncertain responses) with percentages in parentheses.
associated infection that are monitored, and whether an antibiotic stewardship program is employed. Statistical analysis Data were reviewed and analyzed for response frequency. For comparison of 2 binary variables, Fisher exact test was used, with significance defined as P < .05. Analysis of variance was used to compare means of continuous variables. Linear regression was used to examine correlation between 2 continuous variables. Because of the small sample size, multivariate analysis was not performed. All analyses were conducted using EpiInfo statistical software (Centers for Disease Control and Prevention, Atlanta, GA). RESULTS The survey response rate was 71% (15/21). Twelve of 17 critical access hospitals and 3 of 4 acute care hospitals responded. There were no appreciable differences between respondent and nonrespondent facilities with respect to facility characteristics. Respondents were clustered in West-Central, Southwest, and South-Central Wisconsin, with 1 respondent facility each in the Northwest and Northeast. General facility and infection control program characteristics are summarized in Table 1. Each critical
N. Haun et al. / American Journal of Infection Control 42 (2014) 311-5
313
Table 2 Frequency of regular use, prevalence of specific written policies, and frequency of monitoring written policy for adherence for selected CDI-related infection control practices Number of facilities Practice
Regular use
Use of dedicated patient care items and equipment Use of gowns and gloves for contact with patients with CDI Placement of patients with CDI in private rooms Avoid the use of electronic thermometers Perform meticulous hand hygiene based on CDC or WHO guidelines Educate health care staff about CDI Educate patients and family about CDI Perform testing for C difficile only on unformed stools Avoid use of prophylactic antimicrobial CDI therapy Avoid treatment or decolonization of asymptomatic carriers Use of chlorine-based products for environmental cleaning in outbreaks Monitoring decontamination of rooms housing patients with CDI Provide resources/training for environmental services employees Provide performance feedback to environmental services staff Perform terminal room cleaning with detergent-disinfectant Perform terminal room cleaning with sporicidal disinfectant
14/15 14/15 15/15 5/15 13/15 11/15 8/15 12/15 6/14 7/14 14/15 7/15 11/15 9/15 13/15 13/15
(93) (93) (100) (33) (87) (73) (53) (80) (43) (50) (93) (47) (73) (60) (87) (87)
Written policy 13/15 15/15 14/15 6/15 15/15 10/15 12/15 9/15 1/14 1/15 12/15 6/15 8/14 4/14 13/15 13/15
Monitored adherence
(87) (100) (93) (40) (100) (67) (80) (60) (7) (6) (80) (40) (57) (29) (87) (87)
9/13 13/15 11/14 2/6 12/15 7/10 9/12 6/9 1/1 1/1 10/12 6/6 6/8 4/4 10/13 10/13
(69) (87) (79) (33) (80) (70) (67) (67) (100) (100) (83) (100) (75) (100) (77) (77)
CDI, Clostridium difficile infection; WHO, World Health Organization. NOTE. “Regular use” is defined as a rating of 4 or 5 on a scale from 1 to 5 with 1 representing “Never” and 5 representing “Always.” Data are expressed as positive responses over total responses (including both negative and uncertain responses). Percent of respondents is in parentheses. Monitored adherence of written policy is conditional on having a written policy in place.
access hospital had a capacity of 25 beds, whereas the acute care hospitals’ capacities ranged from 36 to 73 beds. The average daily census for critical access hospitals was 7.1 (range, 3-14) and 15.7 (range, 14.5-18.3) for acute care hospitals. Aside from these variables, there were no other apparent differences between critical access and acute care hospital respondents in terms of facility characteristics. Regarding their respective infection control programs, all respondents reported that they performed surveillance for CDI. Four of the 15 facilities had antibiotic stewardship programs of some type in place. CDI rates were provided for 8 hospitals, with an average of 2.7 cases per 10,000 patient-days and a range of 0 to 13.8. Given the low frequency of CDI rate reporting, statistical analysis for correlation of rates with particular aspects of infection control was not performed. Among facilities that reported their rate of CDI, the majority of respondents (6/8) did not know whether their facility’s rate was increasing or decreasing. No facility identified outbreaks or clusters of CDI. Table 2 shows the prevalence of specific CDI-related recommended infection control practices. Nearly all facilities reported regular use of dedicated patient care items, use of gown and gloves, placement of patients with CDI in private rooms, hand hygiene, use of chorine-based solutions during outbreaks, and terminal cleaning with detergent and sporicidal agents. When asked their level of agreement with a series of statements regarding implementation of CDI-related infection control practices, 60% of respondents thought that they receive a great deal of support from leaders in the hospital when they want to implement a change and 33% agreed with the statement that “financial constraints are a significant barrier that prevents implementing CDI prevention practices.” When asked to identify perceived barriers to the implementation of evidence-based practices from a list of potential barriers, several different challenges were identified (Table 3). The most frequent barriers identified included insufficient resources to adequately implement recommended practices, lack of a physician champion, and difficulty keeping up with new recommendations. Lack of supportive hospital leadership and costeffectiveness were also cited by multiple respondents. All responding IPs thought that the strength of evidence is strong for the following practices: use of dedicated patient care equipment, use of gowns and gloves for care of patients with CDI, placement of patients with CDI in private rooms, meticulous hand hygiene,
Table 3 Perceived barriers to implementation of evidence-based recommendations to reduce CDI, by number of respondents: n ¼ 15 Barrier Not enough resources to implement recommended practices adequately Too difficult to keep up with all of the new recommendations Lack of a physician champion who will help advocate for change Hospital leadership is ineffective Most recommended practices are not cost-effective Local clinical culture distrusts outside recommendations Lots of committees but no communication
Rated among 3 most important
Rated most important
9
3
7
4
7
3
4 3
1 1
1
0
0
0
CDI, Clostridium difficile infection.
education of hospital personnel about CDI, decontamination of rooms of patients with CDI with chlorine-based products, education and training of environmental services staff, providing feedback for environmental services, and terminal room cleaning with a detergent. The remainder of recommendations had less perceived support, with 93% thinking there is strong evidence for education of the patient and their family about CDI and the use of a sporicidal agent for terminal cleaning, 86% for performing tests only on unformed stools, 79% for avoidance of the use of prophylactic antibiotics for CDI, 71% for avoidance of treatment or decolonization of asymptomatic carriers, and 36% for avoidance of electronic thermometers. In comparing an IP’s perception of the strength of data in support of a particular practice compared with the self-reported prevalence of that practice in their facility, IPs in facilities where avoiding treatment of asymptomatic colonized patients is a regular practice were more likely to rate the evidence in favor of this practice as stronger (4.7 0.5 [standard deviation] on a 5-point scale) compared with their counterparts in facilities where this was not a regular practice (3.3 0.5, P value < .005). There was no such association for the remainder of practices studied. Statistical analysis of the survey data found no significant correlation between many facility characteristics of interest (critical access vs acute care hospital, use of electronic medical record, employment of hospital epidemiologist, number of full-time
314
N. Haun et al. / American Journal of Infection Control 42 (2014) 311-5
equivalent IPs employed, presence of antibiotic stewardship program, and site of house staff training) and the total number of recommended CDI prevention practices employed. Facilities in which the IP thought the support of his/her leadership to be “Very good” or “Excellent” had employed significantly more CDI prevention practices of interest (13.3 2.4 [standard deviation]) compared with IPs who thought they received less support from leadership (9.8 3.0, P ¼ .033). The lack of consistent reporting of CDI rates prevented statistical analysis of this variable. DISCUSSION In our survey of a subset of rural health care facilities in Wisconsin, we noted a number of key findings. First, whereas most rural facilities reported that adoption of infection control practices for prevention of CDI was common, a number of challenges persisted, hampering prevention and surveillance activities. Second, leadership support was an important organizational factor, the lack of which hindered progress in infection control practices for CDI prevention. Third, lack of resources was a major barrier to implementation of prevention practices for CDI. Fourth, respondents also cited difficulty with keeping up with new, and often extensive, guideline recommendations. Finally, we noted that very few facilities had antibiotic stewardship programs, and the ones that did exist were highly variable in the extent of stewardship and the resources devoted to the program. There are a number of reasons why small rural facilities may differ from nonrural acute care facilities with regards to CDI prevention. Smaller facilities may have a lower disease burden and overall decreased incidence.18 However, rural facilities may face unique barriers to implementing infection control practices. For example, with lower census, the anticipated benefit of systematic infection control reforms may be perceived to be low. Differences in the use of antibiotics or in the degree or type of antibiotic stewardship programs may also impact transmission.19,20 Lack of specialist input may be a barrier for the development of antibiotic stewardship programs. Critical access hospitals, of which a considerable portion are rural, are not required to report health careassociated infection data to Centers for Medicare and Medicaid Services, which also may affect the resources dedicated to infection control and prevention practices. Laboratory facilities are highly variable, and increased turnaround time for send-out tests may delay the diagnosis of CDI. Given the short patient stay prior to discharge or transfer, patients with CDI may not be symptomatic until leaving the facility, making the true burden of disease invisible to that facility. Many of the previous studies of infection control in rural hospitals predate the rise of C difficile as an important cause of nosocomial infection. In the 1980s, RWHC hospitals participated in a 6-month surveillance study on nosocomial infections.21 Notably, in that study, C difficile or pseudomembranous colitis was not even listed by name in the 11 categories of infection undergoing surveillance. There were 2 reported isolates of Clostridium from sources other than urine, sputum, or surgical sites, but species and location were not reported. A more recent study also analyzed infection control practices in small rural hospitals in the western United States.22 They found that the majority of these facilities were working to enact recommended infection control practices. This survey advances on this work by focusing specifically on CDI and examining perceptions of IPs working in those facilities. Our findings have implications for IPs, clinicians, facility executive leadership, and patients. Given the relatively small sizes of rural facilities in our study population, whether critical access or acute care, dedicated resources for infection control may be difficult to obtain. This is not a challenge unique to rural hospitals. However,
because patient movement across rural and urban facilities is widespread, efforts on infection control must be focused on preventing transmission across settings. This is particularly relevant for CDI where many cases may arise after discharge. Mechanisms to ensure effective interfacility communication regarding movement of patients infected or colonized with multidrug-resistant bacteria must be a priority. Another important area of intervention is in the development of antibiotic stewardship programs for rural health care facilities. In case studies of antibiotic stewardship programs, Ohl and Luther noted that, in some rural facilities, the lack of specialist input in the development of a stewardship program may a significant barrier to the implementation of such a program.20 Taking advantage of mechanisms such as e-consults or telecommunication with other facilities may be one possibility to surmount such obstacles and promote judicious antibiotic use. Our study has a number of limitations. First, because the response rate was less than 100%, our results have some susceptibility to nonresponse bias. Second, our survey was limited only to rural facilities within RWHC that were part of an infection control roundtable. Although we did not find major differences between facilities that were or were not part of the infection control roundtable, data on facilities that did not participate in our survey are very limited. It is certainly possible that facilities already part of an infection control roundtable may be more likely to examine infection control literature and implement prevention initiatives for CDI as early adopters. Third, most facilities did not provide CDI rates, which prevented us from analyzing the relationship between prevention practices and CDI rates. These limitations notwithstanding, our study provides a baseline for CDI prevention practices in rural facilities in Wisconsin. Our findings serve as a call to action to the health care system to systematically collect incidence and surveillance data on CDI. This will allow institutions to more effectively devise interventions for prevention and to examine the impact of prevention practices on the incidence of CDI in the rural health care setting.
Acknowledgments The authors thank Dr Sanjay Saint for input regarding study design and analysis.
References 1. Bartlett JG. Antibiotic-associated diarrhea. Clin Infect Dis 1992;15:573-81. 2. Warny M, Pepin J, Fang A, Killgore G, Thompson A, Brazier J, et al. Toxin production by an emerging strain of Clostridium difficile-associated with outbreaks of severe disease in North America and Europe. Lancet 2005;366:1079-84. 3. Pepin J, Valiquette L, Alary ME, Villemure P, Pelletier A, Forget K, et al. Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. CMAJ 2004;171:466-72. 4. McDonald LC, Killgore GE, Thompson A, Owens RC Jr, Kazakova SV, Sambol SP, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005;353:2433-41. 5. Bartlett JG. Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med 2006;145:758-64. 6. Cherifi S, Delmee M, Van Broeck J, Beyer I, Byl B, Mascart G. Management of an outbreak of Clostridium difficile-associated disease among geriatric patients. Infect Control Hosp Epidemiol 2006;27:1200-5. 7. Kyne L, Hamel MB, Polavaram R, Kelly CP. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. Clin Infect Dis 2002;34:346-53. 8. Gravel D, Gardam M, Taylor G, Miller M, Simor A, McGeer A, et al. Infection control practices related to Clostridium difficile infection in acute care hospitals in Canada. Am J Infect Control 2009;37:9-14. 9. Power M, Wigglesworth N, Donaldson E, Chadwick P, Gillibrand S, Goldmann D. Reducing Clostridium difficile infection in acute care by using an improvement collaborative. BMJ 2010;341:c3359. 10. Gamage B, Varia M, Litt M, Pugh S, Bryce E, Group PINAW. Finding the gaps: an assessment of infection control surveillance needs in British Columbia acute care facilities. Am J Infect Control 2008;36:706-10.
N. Haun et al. / American Journal of Infection Control 42 (2014) 311-5 11. Wilkinson K, Gravel D, Taylor G, McGeer A, Simor A, Suh K, et al. Infection prevention and control practices related to Clostridium difficile infection in Canadian acute and long-term care institutions. Am J Infect Control 2011;39: 177-82. 12. Brakovich B, Bonham E, Vanbrackle L. War on the spore: Clostridium difficile disease among patients in a long-term acute care hospital. J Healthc Qual 2013; 35:15-21. 13. Simor AE, Bradley SF, Strausbaugh LJ, Crossley K, Nicolle LE, Committee SL-T-C. Clostridium difficile in long-term-care facilities for the elderly. Infect Control Hosp Epidemiol 2002;23:696-703. 14. Krein SL, Kowalski CP, Hofer TP, Saint S. Preventing hospital-acquired infections: a national survey of practices reported by US hospitals in 2005 and 2009. J Gen Intern Med 2012;27:773-9. 15. Saint S, Greene MT, Olmsted RN, Chopra V, Meddings J, Safdar N, et al. Perceived strength of evidence supporting practices to prevent health careassociated infection: results from a national survey of infection prevention personnel. Am J Infect Control 2013;41:100-6. 16. 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
17.
18.
19.
20. 21.
22.
315
Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 2010;31: 431-55. Rebmann T, Carrico RM. Association for Professionals in Infection Control and Epidemiology. Preventing Clostridium difficile infections: an executive summary of the Association for Professionals in Infection Control and Epidemiology’s elimination guide. Am J Infect Control 2011;39:239-42. Alfa MJ, Du T, Beda G. Survey of incidence of Clostridium difficile infection in Canadian hospitals and diagnostic approaches. J Clin Microbiol 1998;36: 2076-80. Kuntz JL, Cavanaugh JE, Becker LK, Ward MA, Appelgate DM, Herwaldt LA, et al. Clostridium difficile-associated disease in patients in a small rural hospital. Infect Control Hosp Epidemiol 2007;28:1236-9. Ohl CA, Luther VP. Antimicrobial stewardship for inpatient facilities. J Hosp Med 2011;6(Suppl 1):S4-15. Scheckler WE, Peterson PJ. Nosocomial infections in 15 rural Wisconsin hospitals: results and conclusions from 6 months of comprehensive surveillance. Infect Control 1986;7:397-402. Stevenson KB, Murphy CL, Samore MH, Hannah EL, Moore JW, Barbera J, et al. Assessing the status of infection control programs in small rural hospitals in the western United States. Am J Infect Control 2004;32:255-61.
Contents lists available at ScienceDirect
American Journal of Infection Control
American Journal of Infection Control
journal homepage: www.ajicjournal.org
Major article
Prevention of Clostridium difficile infection in rural hospitals Nicholas Haun MD a, Adam Hofer a, M. Todd Greene PhD, MPH b, c, Gwen Borlaug CIC, MPH d, Jenny Pritchett MPH, RN, CIC e, Tina Scallon RN f, Nasia Safdar MD, PhD a, g, * a
University of Wisconsin School of Medicine and Public Health, Madison, WI Division of General Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI c Ann Arbor VA Medical Center, Ann Arbor, MI d Wisconsin Division of Public Health, Madison, WI e Grant Regional Health Center, Lancaster, WI f Sauk Prairie Memorial Hospital, Sauk Prairie, WI g William S. Middleton Memorial Veterans Hospital, Madison, WI b
Key Words: Health care-associated Survey Evidence-based practices
Background: Prevention of Clostridium difficile infection (CDI) remains challenging across the spectrum of health care. There are limited data on prevention practices for CDI in the rural health care setting. Methods: An electronic survey was administered to 21 rural facilities in Wisconsin, part of the Rural Wisconsin Health Cooperative. Data were collected on hospital characteristics and practices to prevent endemic CDI. Results: Fifteen facilities responded (71%). Nearly all respondent facilities reported regular use of dedicated patient care items, use of gown and gloves, private patient rooms, hand hygiene, and room cleaning. Facilities in which the infection preventionist thought the support of his/her leadership to be “Very good” or “Excellent” employed significantly more CDI practices (13.3 2.4 [standard deviation]) compared with infection preventionists who thought there was less support from leadership (9.8 3.0, P ¼ .033). Surveillance for CDI was highly variable. The most frequent barriers to implementation of CDI prevention practices included lack of adequate resources, lack of a physician champion, and difficulty keeping up with new recommendations. Conclusion: Although most rural facilities in our survey reported using evidence-based practices for prevention of CDI, surveillance practices were highly variable, and data regarding the impact of these practices on CDI rates were limited. Future efforts that correlate CDI prevention initiatives and CDI incidence will help develop evidence-based practices in these resource-limited settings. Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc.
Clostridium difficile (C difficile) is the most common bacterial cause of health care-associated diarrhea, accounting for 15% to 25% of antibiotic-associated diarrhea.1 Recent years have witnessed a rapid increase in the incidence of C difficile infection (CDI) with recognition of a new highly virulent strain that has caused global outbreaks.2-6 Each year, CDI affects an estimated 500,000 persons, accounting for over $1 billion in costs and contributing to up to 20,000 deaths.7 Prevention of CDI in health care institutions is essential. Whereas recent studies have examined CDI prevention practices,8-10 * Address correspondence to Nasia Safdar, MD, PhD, MFCB 5221, University of Wisconsin Hospital and Clinics, Madison, WI 53705. E-mail address: [email protected] (N. Safdar). Conflicts of interest: None to report.
data on institutions other than acute care facilities are limited.11-13 As the spectrum of health care expands beyond traditional acute care settings, it is important to examine all types of health care settings regarding prevention of CDI because prevention efforts may need to be tailored to the type of health care setting. Small rural hospitals are one such setting where data regarding the incidence of C difficile and current infection control efforts are scarce. Aspects unique to small rural health care facilities such as patient census, interfacility movement, length of stay, and resources may impact the dynamics of C difficile transmission and infection as well as application of infection control practices. To explore this, we undertook a survey to evaluate infection control practices relevant to CDI that are currently in use in rural acute care and critical access facilities in the state of Wisconsin and to evaluate the perceptions of lead infection preventionists (IPs) for potential
0196-6553/$00.00 - Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc. http://dx.doi.org/10.1016/j.ajic.2013.09.011
312
N. Haun et al. / American Journal of Infection Control 42 (2014) 311-5
facilitators of and barriers to implementation of prevention practices for CDI. METHODS Data collection The study was conducted in May 2012 as a collaborative effort between the University of Wisconsin and the Rural Wisconsin Health Cooperative (RWHC), a coalition of 35 rural Wisconsin health care facilities that provides services such as networking and advocacy for member facilities in many aspects of care including infection control. The study was submitted to the Institutional Review Board and deemed exempt. The survey instrumentd adapted from prior research14,15dwas pilot tested by 4 IPs: 3 at the University of Wisconsin and 1 at RWHC and modified to incorporate feedback. The final version of the survey was administered electronically to lead IPs at the 21 health care facilities that are voluntary participants in the RWHC infection control roundtable. There are no appreciable differences between roundtable participant facilities and nonparticipant facilities. The final survey population included 4 acute care hospitals and 17 critical access hospitals. The primary respondent for the survey was an IP employed by the participating facility; however, consultation with physicians and other infection control staff was encouraged to ensure accurate responses. The survey was administered electronically using Select Survey software (Optimal Solutions Group LLC, College Park, MD). A cover letter with instructions and a uniform resource locator (URL, ie, Internet address) to access the survey was e-mailed to all facilities in the RWHC infection control roundtable. Study measures The survey assessed basic information of the facility including location, type of facility (acute care or critical access hospital), bed count, and average daily census. In addition, we asked respondents how frequently certain CDI prevention practices (as recommended by national guidelines16,17 were employed in their facilities. Respondents were asked to estimate the frequency of practice on a Likert scale of 1 (never) to 5 (always). We defined responses of 4 (almost always) or 5 (always) as regular use of the respective prevention practice. The practices examined included the use of dedicated patient care items, use of gowns/gloves for contact precautions, placement of patients with CDI in private rooms, hand hygiene practices, education of staff and patients regarding CDI, avoidance of treatment of asymptomatic carriers, environmental services practices, and use of chlorine-based products during outbreaks. For each prevention practice, respondents were asked to indicate whether or not the facility has a written policy and, if so, whether the written policy is monitored for adherence. Respondents were asked to rank the strength of evidence supporting these recommended practices on a Likert scale of 1 (no evidence) to 5 (extremely strong evidence). Respondents were also asked to identify the most important perceived barriers to implementing evidence-based practices by ranking from a preselected list of potential barriers and by indicating their agreement with a series of statements on a Likert scale of 1 (strongly agree) to 5 (strongly disagree). For analysis purposes, responses of 1 (strongly agree) or 2 (agree) were used to define agreement. Additional information obtained included rates of CDI and information regarding the structure of the current infection control program including whether the facility has an epidemiologist, whether IPs are certified in clinical infection control, the number of full-time equivalent IPs on staff, time invested in surveillance, types of health care-
Table 1 Characteristics of respondent facilities and infection control programs General facility information Capacity (beds) Average daily census % Of private rooms Presence of house staff trainees Use of electronic medical record Infection control program Surveillance conducted for HAI? CDI CLABSI Surgical site infection CAUTI VAP % Of time spent on surveillance Antibiotic stewardship program Participation in HAI prevention collaboratives Hospital epidemiologist employed Number of IP full-time equivalents IP certified in infection control Use of data-mining software CDI-related information Duration of contact precautions 48 Hours after asymptomatic Duration of hospitalization Method of environmental decontamination Use of chlorine solution during outbreaks Use of detergent for surface cleaning Use of sporicidal agent Method of environmental monitoring Fluorescence marker Bioluminescence assay Observation Report CDI to NHSN Use of probiotic for prevention or treatment
30; 25-73 8.9; 3-18.3 84; 20-100 3/15 (20) 13/15 (87)
15/15 (100) 10/15 (67) 15/15 (100) 15/15 (100) 3/15 (20) 45; 10-90 4/15 (27) 11/15 (73) 3/15 (20) 0.6; 0-1.3 2/14 (14) 1/15 (7)
6/15 (40) 8/15 (53) 14/15 (93) 13/15 (87) 13/15 (87) 3/15 1/15 8/15 1/15 2/13
(20) (7) (53) (7) (15)
CAUTI, catheter-associated urinary tract infection; CDI, Clostridium difficile infection; CLABSI, central line-associated bloodstream infection; HAI, health care-associated infection; IP, infection preventionist; NHSN, National Health Safety Network; VAP, ventilator-associated pneumonia. NOTE. Data are combined responses for both acute care hospitals and critical access hospitals. Aside from hospital capacity and average daily census, there were no apparent differences in facility characteristics between acute care hospitals and critical access hospitals. Continuous variables are expressed as averages with range. Binary variables are expressed as number of positive responses over total responses (including both negative and uncertain responses) with percentages in parentheses.
associated infection that are monitored, and whether an antibiotic stewardship program is employed. Statistical analysis Data were reviewed and analyzed for response frequency. For comparison of 2 binary variables, Fisher exact test was used, with significance defined as P < .05. Analysis of variance was used to compare means of continuous variables. Linear regression was used to examine correlation between 2 continuous variables. Because of the small sample size, multivariate analysis was not performed. All analyses were conducted using EpiInfo statistical software (Centers for Disease Control and Prevention, Atlanta, GA). RESULTS The survey response rate was 71% (15/21). Twelve of 17 critical access hospitals and 3 of 4 acute care hospitals responded. There were no appreciable differences between respondent and nonrespondent facilities with respect to facility characteristics. Respondents were clustered in West-Central, Southwest, and South-Central Wisconsin, with 1 respondent facility each in the Northwest and Northeast. General facility and infection control program characteristics are summarized in Table 1. Each critical
N. Haun et al. / American Journal of Infection Control 42 (2014) 311-5
313
Table 2 Frequency of regular use, prevalence of specific written policies, and frequency of monitoring written policy for adherence for selected CDI-related infection control practices Number of facilities Practice
Regular use
Use of dedicated patient care items and equipment Use of gowns and gloves for contact with patients with CDI Placement of patients with CDI in private rooms Avoid the use of electronic thermometers Perform meticulous hand hygiene based on CDC or WHO guidelines Educate health care staff about CDI Educate patients and family about CDI Perform testing for C difficile only on unformed stools Avoid use of prophylactic antimicrobial CDI therapy Avoid treatment or decolonization of asymptomatic carriers Use of chlorine-based products for environmental cleaning in outbreaks Monitoring decontamination of rooms housing patients with CDI Provide resources/training for environmental services employees Provide performance feedback to environmental services staff Perform terminal room cleaning with detergent-disinfectant Perform terminal room cleaning with sporicidal disinfectant
14/15 14/15 15/15 5/15 13/15 11/15 8/15 12/15 6/14 7/14 14/15 7/15 11/15 9/15 13/15 13/15
(93) (93) (100) (33) (87) (73) (53) (80) (43) (50) (93) (47) (73) (60) (87) (87)
Written policy 13/15 15/15 14/15 6/15 15/15 10/15 12/15 9/15 1/14 1/15 12/15 6/15 8/14 4/14 13/15 13/15
Monitored adherence
(87) (100) (93) (40) (100) (67) (80) (60) (7) (6) (80) (40) (57) (29) (87) (87)
9/13 13/15 11/14 2/6 12/15 7/10 9/12 6/9 1/1 1/1 10/12 6/6 6/8 4/4 10/13 10/13
(69) (87) (79) (33) (80) (70) (67) (67) (100) (100) (83) (100) (75) (100) (77) (77)
CDI, Clostridium difficile infection; WHO, World Health Organization. NOTE. “Regular use” is defined as a rating of 4 or 5 on a scale from 1 to 5 with 1 representing “Never” and 5 representing “Always.” Data are expressed as positive responses over total responses (including both negative and uncertain responses). Percent of respondents is in parentheses. Monitored adherence of written policy is conditional on having a written policy in place.
access hospital had a capacity of 25 beds, whereas the acute care hospitals’ capacities ranged from 36 to 73 beds. The average daily census for critical access hospitals was 7.1 (range, 3-14) and 15.7 (range, 14.5-18.3) for acute care hospitals. Aside from these variables, there were no other apparent differences between critical access and acute care hospital respondents in terms of facility characteristics. Regarding their respective infection control programs, all respondents reported that they performed surveillance for CDI. Four of the 15 facilities had antibiotic stewardship programs of some type in place. CDI rates were provided for 8 hospitals, with an average of 2.7 cases per 10,000 patient-days and a range of 0 to 13.8. Given the low frequency of CDI rate reporting, statistical analysis for correlation of rates with particular aspects of infection control was not performed. Among facilities that reported their rate of CDI, the majority of respondents (6/8) did not know whether their facility’s rate was increasing or decreasing. No facility identified outbreaks or clusters of CDI. Table 2 shows the prevalence of specific CDI-related recommended infection control practices. Nearly all facilities reported regular use of dedicated patient care items, use of gown and gloves, placement of patients with CDI in private rooms, hand hygiene, use of chorine-based solutions during outbreaks, and terminal cleaning with detergent and sporicidal agents. When asked their level of agreement with a series of statements regarding implementation of CDI-related infection control practices, 60% of respondents thought that they receive a great deal of support from leaders in the hospital when they want to implement a change and 33% agreed with the statement that “financial constraints are a significant barrier that prevents implementing CDI prevention practices.” When asked to identify perceived barriers to the implementation of evidence-based practices from a list of potential barriers, several different challenges were identified (Table 3). The most frequent barriers identified included insufficient resources to adequately implement recommended practices, lack of a physician champion, and difficulty keeping up with new recommendations. Lack of supportive hospital leadership and costeffectiveness were also cited by multiple respondents. All responding IPs thought that the strength of evidence is strong for the following practices: use of dedicated patient care equipment, use of gowns and gloves for care of patients with CDI, placement of patients with CDI in private rooms, meticulous hand hygiene,
Table 3 Perceived barriers to implementation of evidence-based recommendations to reduce CDI, by number of respondents: n ¼ 15 Barrier Not enough resources to implement recommended practices adequately Too difficult to keep up with all of the new recommendations Lack of a physician champion who will help advocate for change Hospital leadership is ineffective Most recommended practices are not cost-effective Local clinical culture distrusts outside recommendations Lots of committees but no communication
Rated among 3 most important
Rated most important
9
3
7
4
7
3
4 3
1 1
1
0
0
0
CDI, Clostridium difficile infection.
education of hospital personnel about CDI, decontamination of rooms of patients with CDI with chlorine-based products, education and training of environmental services staff, providing feedback for environmental services, and terminal room cleaning with a detergent. The remainder of recommendations had less perceived support, with 93% thinking there is strong evidence for education of the patient and their family about CDI and the use of a sporicidal agent for terminal cleaning, 86% for performing tests only on unformed stools, 79% for avoidance of the use of prophylactic antibiotics for CDI, 71% for avoidance of treatment or decolonization of asymptomatic carriers, and 36% for avoidance of electronic thermometers. In comparing an IP’s perception of the strength of data in support of a particular practice compared with the self-reported prevalence of that practice in their facility, IPs in facilities where avoiding treatment of asymptomatic colonized patients is a regular practice were more likely to rate the evidence in favor of this practice as stronger (4.7 0.5 [standard deviation] on a 5-point scale) compared with their counterparts in facilities where this was not a regular practice (3.3 0.5, P value < .005). There was no such association for the remainder of practices studied. Statistical analysis of the survey data found no significant correlation between many facility characteristics of interest (critical access vs acute care hospital, use of electronic medical record, employment of hospital epidemiologist, number of full-time
314
N. Haun et al. / American Journal of Infection Control 42 (2014) 311-5
equivalent IPs employed, presence of antibiotic stewardship program, and site of house staff training) and the total number of recommended CDI prevention practices employed. Facilities in which the IP thought the support of his/her leadership to be “Very good” or “Excellent” had employed significantly more CDI prevention practices of interest (13.3 2.4 [standard deviation]) compared with IPs who thought they received less support from leadership (9.8 3.0, P ¼ .033). The lack of consistent reporting of CDI rates prevented statistical analysis of this variable. DISCUSSION In our survey of a subset of rural health care facilities in Wisconsin, we noted a number of key findings. First, whereas most rural facilities reported that adoption of infection control practices for prevention of CDI was common, a number of challenges persisted, hampering prevention and surveillance activities. Second, leadership support was an important organizational factor, the lack of which hindered progress in infection control practices for CDI prevention. Third, lack of resources was a major barrier to implementation of prevention practices for CDI. Fourth, respondents also cited difficulty with keeping up with new, and often extensive, guideline recommendations. Finally, we noted that very few facilities had antibiotic stewardship programs, and the ones that did exist were highly variable in the extent of stewardship and the resources devoted to the program. There are a number of reasons why small rural facilities may differ from nonrural acute care facilities with regards to CDI prevention. Smaller facilities may have a lower disease burden and overall decreased incidence.18 However, rural facilities may face unique barriers to implementing infection control practices. For example, with lower census, the anticipated benefit of systematic infection control reforms may be perceived to be low. Differences in the use of antibiotics or in the degree or type of antibiotic stewardship programs may also impact transmission.19,20 Lack of specialist input may be a barrier for the development of antibiotic stewardship programs. Critical access hospitals, of which a considerable portion are rural, are not required to report health careassociated infection data to Centers for Medicare and Medicaid Services, which also may affect the resources dedicated to infection control and prevention practices. Laboratory facilities are highly variable, and increased turnaround time for send-out tests may delay the diagnosis of CDI. Given the short patient stay prior to discharge or transfer, patients with CDI may not be symptomatic until leaving the facility, making the true burden of disease invisible to that facility. Many of the previous studies of infection control in rural hospitals predate the rise of C difficile as an important cause of nosocomial infection. In the 1980s, RWHC hospitals participated in a 6-month surveillance study on nosocomial infections.21 Notably, in that study, C difficile or pseudomembranous colitis was not even listed by name in the 11 categories of infection undergoing surveillance. There were 2 reported isolates of Clostridium from sources other than urine, sputum, or surgical sites, but species and location were not reported. A more recent study also analyzed infection control practices in small rural hospitals in the western United States.22 They found that the majority of these facilities were working to enact recommended infection control practices. This survey advances on this work by focusing specifically on CDI and examining perceptions of IPs working in those facilities. Our findings have implications for IPs, clinicians, facility executive leadership, and patients. Given the relatively small sizes of rural facilities in our study population, whether critical access or acute care, dedicated resources for infection control may be difficult to obtain. This is not a challenge unique to rural hospitals. However,
because patient movement across rural and urban facilities is widespread, efforts on infection control must be focused on preventing transmission across settings. This is particularly relevant for CDI where many cases may arise after discharge. Mechanisms to ensure effective interfacility communication regarding movement of patients infected or colonized with multidrug-resistant bacteria must be a priority. Another important area of intervention is in the development of antibiotic stewardship programs for rural health care facilities. In case studies of antibiotic stewardship programs, Ohl and Luther noted that, in some rural facilities, the lack of specialist input in the development of a stewardship program may a significant barrier to the implementation of such a program.20 Taking advantage of mechanisms such as e-consults or telecommunication with other facilities may be one possibility to surmount such obstacles and promote judicious antibiotic use. Our study has a number of limitations. First, because the response rate was less than 100%, our results have some susceptibility to nonresponse bias. Second, our survey was limited only to rural facilities within RWHC that were part of an infection control roundtable. Although we did not find major differences between facilities that were or were not part of the infection control roundtable, data on facilities that did not participate in our survey are very limited. It is certainly possible that facilities already part of an infection control roundtable may be more likely to examine infection control literature and implement prevention initiatives for CDI as early adopters. Third, most facilities did not provide CDI rates, which prevented us from analyzing the relationship between prevention practices and CDI rates. These limitations notwithstanding, our study provides a baseline for CDI prevention practices in rural facilities in Wisconsin. Our findings serve as a call to action to the health care system to systematically collect incidence and surveillance data on CDI. This will allow institutions to more effectively devise interventions for prevention and to examine the impact of prevention practices on the incidence of CDI in the rural health care setting.
Acknowledgments The authors thank Dr Sanjay Saint for input regarding study design and analysis.
References 1. Bartlett JG. Antibiotic-associated diarrhea. Clin Infect Dis 1992;15:573-81. 2. Warny M, Pepin J, Fang A, Killgore G, Thompson A, Brazier J, et al. Toxin production by an emerging strain of Clostridium difficile-associated with outbreaks of severe disease in North America and Europe. Lancet 2005;366:1079-84. 3. Pepin J, Valiquette L, Alary ME, Villemure P, Pelletier A, Forget K, et al. Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. CMAJ 2004;171:466-72. 4. McDonald LC, Killgore GE, Thompson A, Owens RC Jr, Kazakova SV, Sambol SP, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005;353:2433-41. 5. Bartlett JG. Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med 2006;145:758-64. 6. Cherifi S, Delmee M, Van Broeck J, Beyer I, Byl B, Mascart G. Management of an outbreak of Clostridium difficile-associated disease among geriatric patients. Infect Control Hosp Epidemiol 2006;27:1200-5. 7. Kyne L, Hamel MB, Polavaram R, Kelly CP. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. Clin Infect Dis 2002;34:346-53. 8. Gravel D, Gardam M, Taylor G, Miller M, Simor A, McGeer A, et al. Infection control practices related to Clostridium difficile infection in acute care hospitals in Canada. Am J Infect Control 2009;37:9-14. 9. Power M, Wigglesworth N, Donaldson E, Chadwick P, Gillibrand S, Goldmann D. Reducing Clostridium difficile infection in acute care by using an improvement collaborative. BMJ 2010;341:c3359. 10. Gamage B, Varia M, Litt M, Pugh S, Bryce E, Group PINAW. Finding the gaps: an assessment of infection control surveillance needs in British Columbia acute care facilities. Am J Infect Control 2008;36:706-10.
N. Haun et al. / American Journal of Infection Control 42 (2014) 311-5 11. Wilkinson K, Gravel D, Taylor G, McGeer A, Simor A, Suh K, et al. Infection prevention and control practices related to Clostridium difficile infection in Canadian acute and long-term care institutions. Am J Infect Control 2011;39: 177-82. 12. Brakovich B, Bonham E, Vanbrackle L. War on the spore: Clostridium difficile disease among patients in a long-term acute care hospital. J Healthc Qual 2013; 35:15-21. 13. Simor AE, Bradley SF, Strausbaugh LJ, Crossley K, Nicolle LE, Committee SL-T-C. Clostridium difficile in long-term-care facilities for the elderly. Infect Control Hosp Epidemiol 2002;23:696-703. 14. Krein SL, Kowalski CP, Hofer TP, Saint S. Preventing hospital-acquired infections: a national survey of practices reported by US hospitals in 2005 and 2009. J Gen Intern Med 2012;27:773-9. 15. Saint S, Greene MT, Olmsted RN, Chopra V, Meddings J, Safdar N, et al. Perceived strength of evidence supporting practices to prevent health careassociated infection: results from a national survey of infection prevention personnel. Am J Infect Control 2013;41:100-6. 16. 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
17.
18.
19.
20. 21.
22.
315
Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 2010;31: 431-55. Rebmann T, Carrico RM. Association for Professionals in Infection Control and Epidemiology. Preventing Clostridium difficile infections: an executive summary of the Association for Professionals in Infection Control and Epidemiology’s elimination guide. Am J Infect Control 2011;39:239-42. Alfa MJ, Du T, Beda G. Survey of incidence of Clostridium difficile infection in Canadian hospitals and diagnostic approaches. J Clin Microbiol 1998;36: 2076-80. Kuntz JL, Cavanaugh JE, Becker LK, Ward MA, Appelgate DM, Herwaldt LA, et al. Clostridium difficile-associated disease in patients in a small rural hospital. Infect Control Hosp Epidemiol 2007;28:1236-9. Ohl CA, Luther VP. Antimicrobial stewardship for inpatient facilities. J Hosp Med 2011;6(Suppl 1):S4-15. Scheckler WE, Peterson PJ. Nosocomial infections in 15 rural Wisconsin hospitals: results and conclusions from 6 months of comprehensive surveillance. Infect Control 1986;7:397-402. Stevenson KB, Murphy CL, Samore MH, Hannah EL, Moore JW, Barbera J, et al. Assessing the status of infection control programs in small rural hospitals in the western United States. Am J Infect Control 2004;32:255-61.
