Impact of targeted interventions on healthcare-acquired infection prevention and control of Clostridium difficile infections 

Impact of targeted interventions on healthcare-acquired infection prevention and control of Clostridium difficile infections | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of targeted interventions on healthcare-acquired infection prevention and control of Clostridium difficile infections Sisi Zhang, Juping Duan, Lina Zhang, Sidi Liu, Xiujuan Meng, Xiaobei Peng, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4976901/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Oct, 2025 Read the published version in Antimicrobial Resistance & Infection Control → Version 1 posted 9 You are reading this latest preprint version Abstract Background Clostridium difficile infection (CDI) is one of the major causative factors leading to antibiotic-associated hospital-acquired and infectious diarrhea. Because C. difficile spores can be transmitted between healthcare systems, healthcare workers have become a key target for preventing and controlling C. difficile infection. Methods We conducted a 6-month intervention and collected 776 patients with diarrhea and 72 cases with hospital-onset C. difficile infection (HO-CDI) in Xiangya Hospital’s intensive care units (ICU). We created a questionnaire on prevention and control knowledge of C. difficile infection, investigated the correctness of healthcare workers' answers before and after the training, statistically described the use of antimicrobial drugs, and judged the validity of this study as a result of the rates of C. difficile infection and morbidities in the three phases. Results The rates of three-stage C. difficile infection (13.3%vs.8.79%vs.6.5%) and morbidities rate/10,000 hospital days (117.14%vs.99.30%vs.71.63%) decreased gradually. After the training, the knowledge, attitude, and practice on prevention and control of C. difficile infection among healthcare workers were much improved. Among all diarrhea patients, there was a decreasing trend in the utilization of cefoperazone sulbactam (P < 0.001), imipenem (P = 0.047), tigecycline (P = 0.044) in all three phases, and an increase in cefoxitin (P < 0.001). There was no statistical difference between the three phases of antimicrobial utilization among hospital-onset C. difficile infection patients. Conclusions This study demonstrated that our training of healthcare workers on C. difficile infection was effective, enhancing healthcare workers' prevention and control awareness of C. difficile infection effectively reducing incidences and morbidities of C. difficile infection, and emphasizing the importance of healthcare workers in the healthcare process. Clostridium difficile (CDI)、healthcare-associated infection (HAI)、healthcare worker、antimicrobial usage、knowledge attitude and practice (KAP) Figures Figure 1 Figure 2 Figure 3 Introduction Clostridium difficile is a toxin-producing, Gram-positive, anaerobic, spore-producing bacillus, and C. difficile infection (CDI) is a gastrointestinal bacterial disease caused by C. difficile [ 1 ]. C. difficile spores persist and remain viable in the environment, including healthcare facilities, thus facilitating the spread of this pathogen to patients. Once ingested by susceptible patients, C. difficile spores germinate, produce toxins, and induce intestinal epithelial damage, inflammation, and mucosal pathology [ 2 ]. C. difficile is one of the leading causes of hospital-acquired diarrhea [ 3 ]. Hospital-acquired diarrhea (HAD) is an acute diarrheal episode after ≥ 3 days of hospitalization [ 4 ]. The most important risk factor for C. difficile-associated diarrhea is prior use of broad-spectrum antibiotics, i.e. antibiotic-associated diarrhea [ 5 ]. Broad-spectrum antibiotics may disrupt the microbial community in the gut, allowing C. difficile to grow and produce toxins [ 6 ]. Therefore, rational use of antibiotics may reduce the incidence of antibiotic-associated diarrhea due to CDI [ 7 , 8 ]. CDI is prevalent in healthcare settings in several developed countries, including Europe and the U.S [ 9 , 10 ]. The Centers for Disease Control and Prevention (CDC) in the United States defined healthcare-associated infection (HAI) as an infection acquired in a healthcare setting (e.g., inpatient hospitals, hemodialysis units, or same-day surgery) [ 11 ]. To date, CDI has placed a significant burden on the healthcare system [ 12 ]. This is reflected not only in higher morbidity and mortality rates but also in high medical costs [ 13 – 16 ]. We carried out a study on the burden of disease and risk factors for CDI in two intensive care units (ICUs) at Xiangya Hospital in 2013 [ 17 ]. The data showed that the incidence of CDI in the two ICUs at Xiangya Hospital was 14.08/10,000 patient-days (95% CI: 10.47–18.57), which was higher than that reported by the CDC in 2010 of 7.4/10,000 patient days [ 18 ]. All 47 patients with laboratory-confirmed CDI identified in this study had used antimicrobials before admission or during hospitalization. In addition, we monitored one clustered case. These findings suggested that infection control measures regarding CDI in the ICUs of Xiangya Hospital were still inadequate. Given the increase of hospital-acquired CDI and community-acquired CDI globally, the study of CDI had become a hot topic in epidemiological research. Therefore, integrating antimicrobial stewardship programs that encourage the rational use of antimicrobials with environmental and infection control-related efforts is particularly salient in targeting nosocomial CDI. Strengthening the management of healthcare infections is also a crucial step forward [ 19 , 20 ]. The main population to reach this goal consists of healthcare workers in the healthcare system. Our objectives of this study are to describe the incidence of CDI in Xiangya Hospital statistically and to evaluate and develop a set of interventions designed to reduce the burden of CDI in the ICUs of Xiangya Hospital. This intervention should standardize the management of CDI patients in the hospital and provide targeted training to healthcare workers on the prevention and control of CDI, to raise their awareness of prevention and control and to reduce the use of broad-spectrum antimicrobials. Methods 1. Study design This study addressed the knowledge, attitudes and practices of healthcare workers regarding HO-CDI, adherence to infection control measures for CDI, and antimicrobial use in a prospective intervention program conducted in the 2 ICUs of Xiangya Hospital of Central South University, a tertiary teaching hospital in Changsha, Hunan Province of China, over 6 months, from January 2019 to June 2019, with 2 months as a phase, divided into a total of 3 phases. In addition to this, we described the incidence, strain distribution and antibiotic resistance pattern of C. difficile toxin-positive isolates. 2. Study population and collection of data Our test subjects were inpatients aged 18 years or older, including Xiangya comprehensive ICU and neurological ICU patients. We selected all patients with diarrhea and CDI admitted to these two ICUs during the study period initially. Next, we conducted an intervention with healthcare workers that consisted of four main components as illustrated in (Fig. 1 ). 3. Design of the training questionnaire We designed a total of fourteen questions, including single-multiple-choice questions, categorized as objective and subjective. The specific items were shown in (Supplementary Table 1). We used this one questionnaire to assess the correctness of the questions before and after the training of the healthcare workers. 4. Statistics and calculation We first counted the number of diarrhea and CDI cases in the 2 ICUs. Next, we used GraphPad Prism 9.5.0 to make line graphs of infection rate and morbidity. We then applied SPSS 27.0 to examine the changes in knowledge, attitudes, and practices of healthcare workers before and after training on CDI prevention and control, and the use of different antimicrobials in the three phases. For this study. p < 0.05 was used as the criterion for statistical differences. Results 1. Cases of patients and length of ICU hospitalization We divided the process into three phases and registered the number of HO-CDI cases (n = 72), diarrhea patients (n = 776), and ICU hospital days in each phase. The results of this section were given in (Table 1 ). 2. Changes in C. difficile incidence infection rates Both the HO-CDI infection rate and the morbidity rate/10,000 hospital days were shown in (Fig. 2 a -b) exhibited a prominent downward trend in the first, second, and third intervention phases, with a P value of 0.032 for the HO-CDI infection rate. 3. Changes in healthcare workers' knowledge level, attitudes and practice of CDI We conducted the correct rate of each question for healthcare workers in the six months from 2019.01-2019.06, as illustrated in (Fig. 3 a-e). In addition to this, we also counted the correct rate of a total 3 trainings, the results in (Fig. 3 f). These results demonstrated that the each and average correctness of C. difficile prevention and control knowledge quiz after training mostly was significantly higher than that before training. 4. Use of broad-spectrum antimicrobial Our preliminary study found that CDI occurrence was closely connected to the use of broad-spectrum antibiotics. We mainly studied the use of broad-spectrum antibiotics in patients with diarrhea and patients with HO-CDI at three distinct stages. As shown in (Table 2 ), among diarrhea patients, the usage of cefoperazone sulbactam, imipenem, tigecycline and cefoxitin in the three phases were divided into (39.82% vs 34.80% vs 20.94%, p < 0.001 * ), (22.12% vs 13.92% vs 19.86%, p = 0.047 * ), (15.49% vs 12.09% vs 8.303%, p = 0.044 * ) and (2.212% vs 6.227% vs 10.83%, p = 0.001 * ). However, among HO-CDI patients, none of the antimicrobials studied had a statistically significant difference in utilization rates across the three phases. Table 1 Cases and ICU durations of HO-CDI and diarrhea patients in the three stages Intervention stage HO-CDI patients cases (n = 72) Diarrhea patients cases (n = 776) ICU duration(days) Phase I 30 226 2561 Phase II 24 273 2417 Phase III 18 277 2513 HO-CDI Hospital-onset C. difficile infection. ICU Intensive care unit. Table 2 Three-stage broad-spectrum antimicrobial use in patients with diarrhea and HO-CDI patients Antibacterial Phase I (n = 226) Phase II(n = 273) Phase III(n = 277) P -value Cases Utilization (%) Cases Utilization (%) Cases Utilization (%) Diarrhea patients (n = 77) Piperacillin tazobactam 82 36.28 101 37 101 36.46 0.985 Cefoperazone sulbactam 90 39.82 95 34.8 58 20.94 0.000 * Meropenem 69 30.53 58 21.25 60 21.66 0.270 Moxifloxacin 15 6.637 17 6.227 18 6.498 0.982 Ceftazidime 25 11.06 25 9.158 28 10.11 0.780 Imipenem 50 22.12 38 13.92 55 19.86 0.047 * Ceftriaxone 33 14.6 29 10.62 38 13.72 0.366 Radox cephalosporin 22 9.735 29 10.62 27 9.747 0.927 Cefotiari 4 1.77 1 0.366 4 1.444 0.330 Tigecycline 35 15.49 33 12.09 23 8.303 0.044 * Levofloxacin 25 11.06 21 7.692 25 9.025 0.428 Cefoxitin 5 2.212 17 6.227 30 10.83 0.001 * Aggregation 455 464 467 HO-CDI patients (n = 70) Piperacillin tazobactam 13 41.94 10 47.62 9 50 0.843 Cefoperazone sulbactam 9 29.03 10 47.62 4 22.22 0.202 Meropenem 11 35.48 7 33.33 3 16.67 0.354 Moxifloxacin 5 16.13 1 4.762 3 16.67 0.482 Ceftazidime 3 9.677 2 9.524 5 27.78 0.796 Imipenem 5 16.13 4 19.05 8 44.44 0.67 Ceftriaxone 6 19.35 5 23.81 4 22.22 0.933 Radox cephalosporin 1 3.226 4 19.05 4 22.22 0.800 Cefotiari 2 6.452 1 4.762 1 5.556 1.000 Tigecycline 3 9.677 2 9.524 3 16.67 0.796 Aggregation 58 46 44 HO-CDI Hospital-onset C. difficile infection. Discussion C. difficile infection (CDI) and healthcare-associated infection (HAI) have long been a major concern for healthcare organizations [ 21 ]. One study tallied the distribution of pathogens infecting patients with all HAI and found that CDI was the most common, accounting for more than a quarter of all infections [ 22 ]. C. difficile could survive in the environment for up to 140 days in the form of spores, which cannot be inactivated by common detergents, making it a formidable cause of hospital-acquired infection [ 23 ]. In a study on the causes of HAI, it was found that the misuse of antimicrobials accounted for nearly 20% [ 24 ]. Judicious use of antimicrobials is the most effective intervention to reduce C. difficile colonization and CDI cases [ 25 ]. The intervention in this study also included the judicious use of antimicrobials. Secondly, careful cleaning and disinfection of environmental components are essential elements of effective hospital infection prevention programs. However, it is not feasible to achieve the desired results by purely chemical-physical disinfection methods alone [ 26 ]. Since this aspect of the problem is often due to poor prevention and control awareness or inadequate implementation by healthcare workers, the outcome is poor [ 27 ]. Therefore, we also need to implement interventions to improve healthcare workers' awareness of CDI prevention and control, to achieve the effect of “double insurance”. Finally, the results showed that after our standardized process, the knowledge and attitude of healthcare workers towards the diagnosis, treatment, prevention and control of CDI before and after the training were notably improved, as well as their ability to perform Clostridium difficile isolation and prevention and control. A high-quality systematic review concluded that reducing antibacterial use may not increase mortality and may shorten the length of hospitalization [ 28 ].This study found a statistically significant downward trend in the use of cefoperazone sulbactam and tigecycline in all patients with diarrhea. A prospective study found that exposure to fluoroquinolones or cephalosporins was a risk factor for outbreaks of C. difficile-associated diarrhea [ 29 ]. However, there was no statistically significant difference in the use of all antimicrobials in patients with HO-CDI, the reason for which may be linked to the small sample size, which could be expanded before continuing the study in future experiments. The definition of CDI surveillance given by healthcare professionals had led to a better understanding of the epidemiology of CDI and had helped to best protect at-risk patients [ 30 ]. This speaked volumes about the need and importance of raising awareness of prevention and control among healthcare workers. As early as 2017, a study found that daily cleaning with sporicidal disinfectants and C. difficile screening on admission were the most effective single intervention strategies, while contact precautions for healthcare workers were the most effective interventions to reduce hospital-onset colonization and infection [ 31 ]. Our study attached great importance to the awareness of CDI prevention and control among healthcare workers, not only at the observational level, but also through targeted interventions for them, and demonstrated that our interventions had achieved significant results through the fact that the rates of CDI infections and morbidities gradually declined during the study period, which fully justified the necessity and clinical significance of the study. Undeniably, this study also had shortcomings. Because we only carried out all the activities in one hospital and the study lasted only six months, there was no later consolidation of healthcare workers' awareness of prevention and control. It is desirable for later researchers can continue the experiment in a multi-center manner to expand the sample size and extend the study period. Conclusions In conclusion, it is of great clinical significance to strengthen the awareness of CDI prevention and control among healthcare workers and the rational use of antimicrobials through intervention methods to reduce CDI's prevalence and infection rate. Abbreviations CDI Clostridium difficile infection HO-CDI hospital-onset C. difficile infection ICU intensive care unit HAI healthcare-associated infection KAP knowledge, attitude and practice CDC Centers for Disease Control and Prevention Declarations Consent for publication Not applicable. Availability of data and materials Not applicable. Acknowledge We would like to thank everyone who took part in this study. Conflict of interest statement None declared. Funding statement Funding. This work was supported by National Key Research and Development Program of China [No. 2022YFC2009801; No. 2022YFC2009805], the Natural Science Foundation of Hunan Province [No. 2021JJ31071], the Project program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital)[No. 2021KFJJ05], Health Development Research Center of the National Health Commission, "Evidence-based Evaluation and Demonstration Base Construction Project of Infection Control Measures in Healthcare Institutions"[No. CNHDRC-KJ-L-2020-53-04375], Changsha science and technology plan project (NO. kq2202059) and Scientific and technological personnel lifting Project in Hunan Province [No. 2023TJ-Z11]. Ethical approval The Ethics Committee of the Xiangya Hospital of Central South University and the United States Centers for Disease Control and Prevention IRB authorization agreement approved the study protocol (CGH #2014-047). Since the study involved the collection and testing of stool specimens for CDI, only verbal consent from the patient (or a family member) was required for enrollment. Author contributions Sisi Zhang conceived the project and designed all experiments and wrote the manuscript independently, and Juping Duan guided the statistical analyses. While Lina Zhang, Xiaobei Peng and Wei Liu assisted with data collection. Sidi Liu and Xiujuan Meng supervised the completion of the manuscript. All authors read and approved the final manuscript. References Akoghlanian G, Lakshmi S. The difficile in Clostridium difficile infection. Int J Infect Dis. 2018;77:14–5. Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol. 2009;7(7):526–36. Barbut F, Corthier G, Charpak Y, Cerf M, Monteil H, Fosse T, Trévoux A, De Barbeyrac B, Boussougant Y, Tigaud S, et al. Prevalence and pathogenicity of Clostridium difficile in hospitalized patients. A French multicenter study. Arch Intern Med. 1996;156(13):1449–54. Mawer D, Byrne F, Drake S, Brown C, Prescott A, Warne B, Bousfield R, Skittrall JP, Ramsay I, Somasunderam D, et al. Cross-sectional study of the prevalence, causes and management of hospital-onset diarrhoea. J Hosp Infect. 2019;103(2):200–9. Petrof EO, Gloor GB, Vanner SJ, Weese SJ, Carter D, Daigneault MC, Brown EM, Schroeter K, Allen-Vercoe E. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: 'RePOOPulating' the gut. Microbiome. 2013;1(1):3. Owens RC Jr., Donskey CJ, Gaynes RP, Loo VG, Muto CA. Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect Dis. 2008;46(Suppl 1):S19–31. Tamma PD, Avdic E, Li DX, Dzintars K, Cosgrove SE. Association of Adverse Events With Antibiotic Use in Hospitalized Patients. JAMA Intern Med. 2017;177(9):1308–15. Feuerstadt P, Louie TJ, Lashner B, Wang EEL, Diao L, Bryant JA, Sims M, Kraft CS, Cohen SH, Berenson CS, et al. SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection. N Engl J Med. 2022;386(3):220–9. Bauer MP, Notermans DW, van Benthem BH, Brazier JS, Wilcox MH, Rupnik M, Monnet DL, van Dissel JT, Kuijper EJ. Clostridium difficile infection in Europe: a hospital-based survey. Lancet. 2011;377(9759):63–73. Anderson DJ, Chen LF, Weber DJ, Moehring RW, Lewis SS, Triplett PF, Blocker M, Becherer P, Schwab JC, Knelson LP, et al. Enhanced terminal room disinfection and acquisition and infection caused by multidrug-resistant organisms and Clostridium difficile (the Benefits of Enhanced Terminal Room Disinfection study): a cluster-randomised, multicentre, crossover study. Lancet. 2017;389(10071):805–14. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36(5):309–32. Dubberke ER, Olsen MA. Burden of Clostridium difficile on the healthcare system. Clin Infect Dis. 2012;55(Suppl 2):S88–92. Boven A, Vlieghe E, Engstrand L, Andersson FL, Callens S, Simin J, Brusselaers N. Clostridioides difficile infection-associated cause-specific and all-cause mortality: a population-based cohort study. Clin Microbiol Infect. 2023;29(11):1424–30. 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(3):346–53. Oyaro MO, Plants-Paris K, Bishoff D, Malonza P, Gontier CS, DuPont HL, Darkoh C. High rate of Clostridium difficile among young adults presenting with diarrhea at two hospitals in Kenya. Int J Infect Dis. 2018;74:24–8. Goyal A, Chatterjee K, Yadlapati S, Rangaswami J. Impact of end stage kidney disease on costs and outcomes of Clostridium difficile infection. Int J Infect Dis. 2017;62:8–9. Li C, Li Y, Huai Y, Liu S, Meng X, Duan J, Klena JD, Rainey JJ, Wu A, Rao CY. Incidence and Outbreak of Healthcare-Onset Healthcare-Associated Clostridioides difficile Infections Among Intensive Care Patients in a Large Teaching Hospital in China. Front Microbiol. 2018;9:566. McDonald LC, Lessa F, Sievert D, Wise M, Herrera R, Gould C, Malpiedi P, Dudeck M, Srinivasan A, Fridkin S, et al. Vital Signs: Preventing Clostridium difficile Infections. Jama-Journal Am Med Association. 2012;307(16):1684–7. Krein SL, Mayer J, Harrod M, Weston LE, Gregory L, Petersen L, Samore MH, Drews FA. Identification and Characterization of Failures in Infectious Agent Transmission Precaution Practices in Hospitals: A Qualitative Study. JAMA Intern Med. 2018;178(8):1016–57. Casari E, De Luca C, Calabrò M, Scuderi C, Daleno C, Ferrario A. Reducing rates of Clostridium difficile infection by switching to a stand-alone NAAT with clear sampling criteria. Antimicrob Resist Infect Control. 2018;7:40. Thomas RE, Thomas BC, Lorenzetti D, Conly J. Hospital and long-term care facility environmental service workers' training, skills, activities and effectiveness in cleaning and disinfection: a systematic review. J Hosp Infect. 2022;124:56–66. Santino I, Teggi A, Marangi M, Montesano M, Petrucca A, Bertamino E, Zerbetto A, Sandorfi F, Iachini M, Orsi GB. Surveillance of healthcare acquired infections by alert microorganisms: preliminary results. Ann Ig. 2019;31(5):414–22. Porter L, Sultan O, Mitchell BG, Jenney A, Kiernan M, Brewster DJ, Russo PL. How long do nosocomial pathogens persist on inanimate surfaces? A scoping review. J Hosp Infect. 2024;147:25–31. Lukasewicz Ferreira SA, Franco Meneses AC, Vaz TA, da Fontoura Carvalho OL, Hubner Dalmora C, Pressotto Vanni D, Ribeiro Berti I. Pires Dos Santos R: Hospital-acquired infections surveillance: The machine-learning algorithm mirrors National Healthcare Safety Network definitions. Infect Control Hosp Epidemiol. 2024;45(5):604–8. Stephenson B, Lanzas C, Lenhart S, Ponce E, Bintz J, Dubberke ER, Day J. Comparing intervention strategies for reducing Clostridioides difficile transmission in acute healthcare settings: an agent-based modeling study. BMC Infect Dis. 2020;20(1):799. Ray AJ, Deshpande A, Fertelli D, Sitzlar BM, Thota P, Sankar CT, Jencson AL, Cadnum JL, Salata RA, Watkins RR, et al. A Multicenter Randomized Trial to Determine the Effect of an Environmental Disinfection Intervention on the Incidence of Healthcare-Associated Clostridium difficile Infection. Infect Control Hosp Epidemiol. 2017;38(7):777–83. Boyce JM. Modern technologies for improving cleaning and disinfection of environmental surfaces in hospitals. Antimicrob Resist Infect Control. 2016;5:10. Davey P, Marwick CA, Scott CL, Charani E, McNeil K, Brown E, Gould IM, Ramsay CR, Michie S. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Reviews 2017(2). Loo VG, Poirier L, Miller MA, Oughton M, Libman MD, Michaud S, Bourgault AM, Nguyen T, Frenette C, Kelly M, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med. 2005;353(23):2442–9. Skally M, Bennett K, Humphreys H, Fitzpatrick F. Rethinking Clostridioides difficile infection (CDI) surveillance definitions based on changing healthcare utilisation and a more realistic incubation period: reviewing data from a tertiary-referral hospital, Ireland, 2012 to 2021. Euro Surveill 2024, 29(6). Barker AK, Alagoz O, Safdar N. Interventions to Reduce the Incidence of Hospital-Onset Clostridium difficile Infection: An Agent-Based Modeling Approach to Evaluate Clinical Effectiveness in Adult Acute Care Hospitals. Clin Infect Dis. 2018;66(8):1192–203. Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterials.docx Cite Share Download PDF Status: Published Journal Publication published 01 Oct, 2025 Read the published version in Antimicrobial Resistance & Infection Control → Version 1 posted Editorial decision: Revision requested 12 Dec, 2024 Reviews received at journal 06 Dec, 2024 Reviewers agreed at journal 30 Nov, 2024 Reviewers agreed at journal 28 Oct, 2024 Reviewers agreed at journal 23 Oct, 2024 Reviewers invited by journal 23 Sep, 2024 Editor assigned by journal 31 Aug, 2024 Submission checks completed at journal 26 Aug, 2024 First submitted to journal 26 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4976901","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":358191437,"identity":"81226416-a2c3-4f32-8338-9111d479b99a","order_by":0,"name":"Sisi Zhang","email":"","orcid":"","institution":"Department of Infection Control Center, Xiangya Hospital Central South University","correspondingAuthor":false,"prefix":"","firstName":"Sisi","middleName":"","lastName":"Zhang","suffix":""},{"id":358191438,"identity":"7a678469-20b5-42d7-9bad-54bd7ea52121","order_by":1,"name":"Juping Duan","email":"","orcid":"","institution":"Department of Infection Control Center, Xiangya Hospital Central South University","correspondingAuthor":false,"prefix":"","firstName":"Juping","middleName":"","lastName":"Duan","suffix":""},{"id":358191439,"identity":"05af724d-f7f3-4d8a-a155-a6a3040a4b94","order_by":2,"name":"Lina Zhang","email":"","orcid":"","institution":"Department of Critical Care Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University","correspondingAuthor":false,"prefix":"","firstName":"Lina","middleName":"","lastName":"Zhang","suffix":""},{"id":358191440,"identity":"ce137199-97fe-468c-965f-0a3e561672d6","order_by":3,"name":"Sidi Liu","email":"","orcid":"","institution":"Department of Infection Control Center, Xiangya Hospital Central South University","correspondingAuthor":false,"prefix":"","firstName":"Sidi","middleName":"","lastName":"Liu","suffix":""},{"id":358191441,"identity":"6fa8c9e5-41c2-4d25-9f44-5a781a98e9bd","order_by":4,"name":"Xiujuan Meng","email":"","orcid":"","institution":"Department of Infection Control Center, Xiangya Hospital Central South University","correspondingAuthor":false,"prefix":"","firstName":"Xiujuan","middleName":"","lastName":"Meng","suffix":""},{"id":358191442,"identity":"23a278e3-4591-469b-b07a-c57a1e7e5442","order_by":5,"name":"Xiaobei Peng","email":"","orcid":"","institution":"Department of Critical Care Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University","correspondingAuthor":false,"prefix":"","firstName":"Xiaobei","middleName":"","lastName":"Peng","suffix":""},{"id":358191443,"identity":"7f0d35a3-b0d6-40e0-acf4-6c9778fc9fa5","order_by":6,"name":"Wei Liu","email":"","orcid":"","institution":"Department of Critical Care Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Liu","suffix":""},{"id":358191444,"identity":"6ef7897a-f1b0-48be-8133-e8ba71a8acea","order_by":7,"name":"Anhua Wu","email":"","orcid":"","institution":"Department of Infection Control Center, Xiangya Hospital Central South University","correspondingAuthor":false,"prefix":"","firstName":"Anhua","middleName":"","lastName":"Wu","suffix":""},{"id":358191445,"identity":"ae9e4f41-d07f-4a2f-b1cb-9c2630f77180","order_by":8,"name":"Chunhui Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYBACPmYGNiB1gIGNvQEswNhASAsbXAvPAWK1MEC1MEgkEKuFnfnZY94ddxL7JB8//szDYCO74QDzswf4HcZmbsx75llim3SamTQPQ5rxhgNs5gb4tfCwSfO2HQZqyQGyGQ4nbjjAwyZBnBbJM8xAh/0nRYsEDwPQYQeI0cJmJjm37bBxG0+ameQcg2TjmYfZzPBq4ec//Ezibdth2fnthx9/eFNhJ9t3vPkZXi1oABRUzCSoHwWjYBSMglGAHQAAcDQ9ORvIkiYAAAAASUVORK5CYII=","orcid":"","institution":"Department of Infection Control Center, Xiangya Hospital Central South University","correspondingAuthor":true,"prefix":"","firstName":"Chunhui","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2024-08-26 09:32:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4976901/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4976901/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13756-025-01616-4","type":"published","date":"2025-10-01T15:57:56+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":66793312,"identity":"6006fc21-e392-4ad6-b368-23a29c79efa9","added_by":"auto","created_at":"2024-10-16 13:51:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":114053,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eInterventions targeting increased awareness of CDI prevention and control among healthcare workers. \u003c/strong\u003eFirst, healthcare workers were trained on knowledge, attitudes and practices regarding C. difficile transmission and infection control measures in three sessions covering glove use, hand hygiene and equipment cleaning. Second, infection control measures for suspected and confirmed CDI patients were assessed using a daily surveillance tool, and a daily infection control checklist was drawn up and implemented by project staff. Third, antimicrobial stewardship was strengthened through training and feedback to reduce the use of certain antibiotics, with a focus on training ICU clinicians and nursing staff about the rational use of antimicrobials such as fluoroquinolones and amoxicillin clavulanate. Fourth, the use of WeChat reminded clinicians of the judicious use of antimicrobials, especially when prescribing broad-spectrum antimicrobials, and reminded them to reduce empirical antimicrobial therapy within 48 hours.\u003c/p\u003e","description":"","filename":"floatimage143.png","url":"https://assets-eu.researchsquare.com/files/rs-4976901/v1/ea907665982c18e2c434c526.png"},{"id":66793313,"identity":"de20c8ef-83d4-4885-b38c-4eea74623855","added_by":"auto","created_at":"2024-10-16 13:51:18","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":106927,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChanges in HO-CDI infection rates and morbidity rate/10,000 hospital days in three phases\u003c/strong\u003e(a) The infection rate in Phase I was 13.30%, in Phase II was 8.79%, and in Phase III was 6.5%. In the three phases, the average infection rate was 9.28%. (b) The morbidity rate/10,000 hospital days in Phase I was 117.14%, in Phase II was 99.30%, and in Phase III was 71.63%. In the three phases, the average morbidity rate/10,000 hospital days was 96.12%.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4976901/v1/5392d1b03f68499a735bbc4b.jpeg"},{"id":66793309,"identity":"56e4a5e1-4b84-4114-85d0-e8f7ab9c3cdd","added_by":"auto","created_at":"2024-10-16 13:51:17","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":241364,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChanges in healthcare workers' knowledge level, attitudes and practice of CDI \u003c/strong\u003e(a-e) Changes in per accuracy of Q＆A before and after training for healthcare workers. Correctness before and after training for each question was: 2nd (95.20% vs 100%), 3rd (38.1% vs 81.80%), 7th (95.20% vs 100%), 1st (85% vs 90.90%), 5th (50% vs 68.20%), 6th (95% vs 100%), 8th (95% vs 100%), 4th (80% vs 65.20%), 9th (47.5% vs 100%), 10th (57.10% vs 95.60%), 11th (80% vs 95.80%), 12th (50% vs 90.90%), 13th (65% vs 95.50%), 14th (52.40% vs 87%). (f) Changes in the average accuracy of Q＆A before and after training. The types of knowledge points in the questionnaire mainly included: risk factors (76.20% vs. 93.90%), preventive measures (76.70% vs. 86.30%), prognosis (47.50% vs. 100.00%), and practice (60.90% vs. 92.96%). While the correctness rate of the one knowledge point of diagnosis (87.50% vs 82.60%) was slightly lower after the training than before. Q＆A includes questions and answers.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4976901/v1/f505cdb98b86c3b05989c157.jpeg"},{"id":92884472,"identity":"daf24df7-9857-4aef-bb41-3aef81466a6a","added_by":"auto","created_at":"2025-10-06 16:13:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1254125,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4976901/v1/b73ae3ac-95cd-4947-a6c4-d4fb604b044d.pdf"},{"id":66795021,"identity":"91d52236-a811-48f4-923f-00457ade7e19","added_by":"auto","created_at":"2024-10-16 13:59:18","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":13904,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-4976901/v1/1f867528a138c082b0d03369.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of targeted interventions on healthcare-acquired infection prevention and control of Clostridium difficile infections ","fulltext":[{"header":"Introduction","content":"\u003cp\u003eClostridium difficile is a toxin-producing, Gram-positive, anaerobic, spore-producing bacillus, and C. difficile infection (CDI) is a gastrointestinal bacterial disease caused by C. difficile [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. C. difficile spores persist and remain viable in the environment, including healthcare facilities, thus facilitating the spread of this pathogen to patients. Once ingested by susceptible patients, C. difficile spores germinate, produce toxins, and induce intestinal epithelial damage, inflammation, and mucosal pathology [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. C. difficile is one of the leading causes of hospital-acquired diarrhea [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Hospital-acquired diarrhea (HAD) is an acute diarrheal episode after ≥ 3 days of hospitalization [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The most important risk factor for C. difficile-associated diarrhea is prior use of broad-spectrum antibiotics, i.e. antibiotic-associated diarrhea [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Broad-spectrum antibiotics may disrupt the microbial community in the gut, allowing C. difficile to grow and produce toxins [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Therefore, rational use of antibiotics may reduce the incidence of antibiotic-associated diarrhea due to CDI [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCDI is prevalent in healthcare settings in several developed countries, including Europe and the U.S [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The Centers for Disease Control and Prevention (CDC) in the United States defined healthcare-associated infection (HAI) as an infection acquired in a healthcare setting (e.g., inpatient hospitals, hemodialysis units, or same-day surgery) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. To date, CDI has placed a significant burden on the healthcare system [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. This is reflected not only in higher morbidity and mortality rates but also in high medical costs [\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e–\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. We carried out a study on the burden of disease and risk factors for CDI in two intensive care units (ICUs) at Xiangya Hospital in 2013 [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The data showed that the incidence of CDI in the two ICUs at Xiangya Hospital was 14.08/10,000 patient-days (95% CI: 10.47–18.57), which was higher than that reported by the CDC in 2010 of 7.4/10,000 patient days [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. All 47 patients with laboratory-confirmed CDI identified in this study had used antimicrobials before admission or during hospitalization. In addition, we monitored one clustered case. These findings suggested that infection control measures regarding CDI in the ICUs of Xiangya Hospital were still inadequate. Given the increase of hospital-acquired CDI and community-acquired CDI globally, the study of CDI had become a hot topic in epidemiological research. Therefore, integrating antimicrobial stewardship programs that encourage the rational use of antimicrobials with environmental and infection control-related efforts is particularly salient in targeting nosocomial CDI.\u003c/p\u003e \u003cp\u003eStrengthening the management of healthcare infections is also a crucial step forward [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The main population to reach this goal consists of healthcare workers in the healthcare system. Our objectives of this study are to describe the incidence of CDI in Xiangya Hospital statistically and to evaluate and develop a set of interventions designed to reduce the burden of CDI in the ICUs of Xiangya Hospital. This intervention should standardize the management of CDI patients in the hospital and provide targeted training to healthcare workers on the prevention and control of CDI, to raise their awareness of prevention and control and to reduce the use of broad-spectrum antimicrobials.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003e1. Study design\u003c/p\u003e\u003cp\u003eThis study addressed the knowledge, attitudes and practices of healthcare workers regarding HO-CDI, adherence to infection control measures for CDI, and antimicrobial use in a prospective intervention program conducted in the 2 ICUs of Xiangya Hospital of Central South University, a tertiary teaching hospital in Changsha, Hunan Province of China, over 6 months, from January 2019 to June 2019, with 2 months as a phase, divided into a total of 3 phases. In addition to this, we described the incidence, strain distribution and antibiotic resistance pattern of C. difficile toxin-positive isolates.\u003c/p\u003e\u003cp\u003e2. Study population and collection of data\u003c/p\u003e\u003cp\u003eOur test subjects were inpatients aged 18 years or older, including Xiangya comprehensive ICU and neurological ICU patients. We selected all patients with diarrhea and CDI admitted to these two ICUs during the study period initially. Next, we conducted an intervention with healthcare workers that consisted of four main components as illustrated in (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e3. Design of the training questionnaire\u003c/p\u003e\u003cp\u003eWe designed a total of fourteen questions, including single-multiple-choice questions, categorized as objective and subjective. The specific items were shown in (Supplementary Table\u0026nbsp;1). We used this one questionnaire to assess the correctness of the questions before and after the training of the healthcare workers.\u003c/p\u003e\u003cp\u003e4. Statistics and calculation\u003c/p\u003e\u003cp\u003eWe first counted the number of diarrhea and CDI cases in the 2 ICUs. Next, we used GraphPad Prism 9.5.0 to make line graphs of infection rate and morbidity. We then applied SPSS 27.0 to examine the changes in knowledge, attitudes, and practices of healthcare workers before and after training on CDI prevention and control, and the use of different antimicrobials in the three phases. For this study. p \u0026lt; 0.05 was used as the criterion for statistical differences.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e1. Cases of patients and length of ICU hospitalization\u003c/p\u003e \u003cp\u003eWe divided the process into three phases and registered the number of HO-CDI cases (n\u0026thinsp;=\u0026thinsp;72), diarrhea patients (n\u0026thinsp;=\u0026thinsp;776), and ICU hospital days in each phase. The results of this section were given in (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e2. Changes in C. difficile incidence infection rates\u003c/p\u003e \u003cp\u003eBoth the HO-CDI infection rate and the morbidity rate/10,000 hospital days were shown in (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea -b) exhibited a prominent downward trend in the first, second, and third intervention phases, with a P value of 0.032 for the HO-CDI infection rate.\u003c/p\u003e \u003cp\u003e3. Changes in healthcare workers' knowledge level, attitudes and practice of CDI\u003c/p\u003e \u003cp\u003eWe conducted the correct rate of each question for healthcare workers in the six months from 2019.01-2019.06, as illustrated in (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea-e). In addition to this, we also counted the correct rate of a total 3 trainings, the results in (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ef). These results demonstrated that the each and average correctness of C. difficile prevention and control knowledge quiz after training mostly was significantly higher than that before training.\u003c/p\u003e \u003cp\u003e4. Use of broad-spectrum antimicrobial\u003c/p\u003e \u003cp\u003eOur preliminary study found that CDI occurrence was closely connected to the use of broad-spectrum antibiotics. We mainly studied the use of broad-spectrum antibiotics in patients with diarrhea and patients with HO-CDI at three distinct stages. As shown in (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), among diarrhea patients, the usage of cefoperazone sulbactam, imipenem, tigecycline and cefoxitin in the three phases were divided into (39.82% vs 34.80% vs 20.94%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e), (22.12% vs 13.92% vs 19.86%, p\u0026thinsp;=\u0026thinsp;0.047\u003csup\u003e*\u003c/sup\u003e), (15.49% vs 12.09% vs 8.303%, p\u0026thinsp;=\u0026thinsp;0.044\u003csup\u003e*\u003c/sup\u003e) and (2.212% vs 6.227% vs 10.83%, p\u0026thinsp;=\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e). However, among HO-CDI patients, none of the antimicrobials studied had a statistically significant difference in utilization rates across the three phases.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCases and ICU durations of HO-CDI and diarrhea patients in the three stages\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntervention stage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHO-CDI patients\u003c/p\u003e \u003cp\u003ecases (n\u0026thinsp;=\u0026thinsp;72)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDiarrhea patients\u003c/p\u003e \u003cp\u003ecases (n\u0026thinsp;=\u0026thinsp;776)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eICU duration(days)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhase I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e226\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2561\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhase II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e273\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2417\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhase III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e277\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2513\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eHO-CDI Hospital-onset C. difficile infection.\u003c/p\u003e \u003cp\u003eICU Intensive care unit.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThree-stage broad-spectrum antimicrobial use in patients with diarrhea and HO-CDI patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAntibacterial\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003ePhase I\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;226)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003ePhase II(n\u0026thinsp;=\u0026thinsp;273)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003ePhase III(n\u0026thinsp;=\u0026thinsp;277)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUtilization\u003c/p\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUtilization\u003c/p\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eUtilization\u003c/p\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"12\" rowspan=\"13\"\u003e \u003cp\u003eDiarrhea patients\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePiperacillin tazobactam\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e36.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.985\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCefoperazone sulbactam\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e34.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e20.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.000\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMeropenem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e21.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.270\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMoxifloxacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.637\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.227\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.498\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.982\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCeftazidime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.158\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.780\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eImipenem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e19.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.047\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCeftriaxone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e13.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.366\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRadox cephalosporin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.735\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9.747\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.927\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCefotiari\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.366\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.444\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.330\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTigecycline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8.303\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.044\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLevofloxacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.692\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.428\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCefoxitin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.227\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAggregation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e455\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e464\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e467\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"10\" rowspan=\"11\"\u003e \u003cp\u003eHO-CDI patients\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePiperacillin tazobactam\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.843\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCefoperazone sulbactam\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e22.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.202\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMeropenem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e33.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.354\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMoxifloxacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.762\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.482\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCeftazidime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.677\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.524\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e27.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.796\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eImipenem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e44.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCeftriaxone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e22.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.933\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRadox cephalosporin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.226\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e22.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.800\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCefotiari\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.452\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.762\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.556\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTigecycline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.677\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.524\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.796\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAggregation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cp\u003eHO-CDI Hospital-onset C. difficile infection.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eC. difficile infection (CDI) and healthcare-associated infection (HAI) have long been a major concern for healthcare organizations [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. One study tallied the distribution of pathogens infecting patients with all HAI and found that CDI was the most common, accounting for more than a quarter of all infections [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. C. difficile could survive in the environment for up to 140 days in the form of spores, which cannot be inactivated by common detergents, making it a formidable cause of hospital-acquired infection [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In a study on the causes of HAI, it was found that the misuse of antimicrobials accounted for nearly 20% [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Judicious use of antimicrobials is the most effective intervention to reduce C. difficile colonization and CDI cases [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The intervention in this study also included the judicious use of antimicrobials.\u003c/p\u003e \u003cp\u003eSecondly, careful cleaning and disinfection of environmental components are essential elements of effective hospital infection prevention programs. However, it is not feasible to achieve the desired results by purely chemical-physical disinfection methods alone [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Since this aspect of the problem is often due to poor prevention and control awareness or inadequate implementation by healthcare workers, the outcome is poor [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Therefore, we also need to implement interventions to improve healthcare workers' awareness of CDI prevention and control, to achieve the effect of \u0026ldquo;double insurance\u0026rdquo;. Finally, the results showed that after our standardized process, the knowledge and attitude of healthcare workers towards the diagnosis, treatment, prevention and control of CDI before and after the training were notably improved, as well as their ability to perform Clostridium difficile isolation and prevention and control.\u003c/p\u003e \u003cp\u003eA high-quality systematic review concluded that reducing antibacterial use may not increase mortality and may shorten the length of hospitalization [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].This study found a statistically significant downward trend in the use of cefoperazone sulbactam and tigecycline in all patients with diarrhea. A prospective study found that exposure to fluoroquinolones or cephalosporins was a risk factor for outbreaks of C. difficile-associated diarrhea [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. However, there was no statistically significant difference in the use of all antimicrobials in patients with HO-CDI, the reason for which may be linked to the small sample size, which could be expanded before continuing the study in future experiments.\u003c/p\u003e \u003cp\u003eThe definition of CDI surveillance given by healthcare professionals had led to a better understanding of the epidemiology of CDI and had helped to best protect at-risk patients [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. This speaked volumes about the need and importance of raising awareness of prevention and control among healthcare workers. As early as 2017, a study found that daily cleaning with sporicidal disinfectants and C. difficile screening on admission were the most effective single intervention strategies, while contact precautions for healthcare workers were the most effective interventions to reduce hospital-onset colonization and infection [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Our study attached great importance to the awareness of CDI prevention and control among healthcare workers, not only at the observational level, but also through targeted interventions for them, and demonstrated that our interventions had achieved significant results through the fact that the rates of CDI infections and morbidities gradually declined during the study period, which fully justified the necessity and clinical significance of the study.\u003c/p\u003e \u003cp\u003eUndeniably, this study also had shortcomings. Because we only carried out all the activities in one hospital and the study lasted only six months, there was no later consolidation of healthcare workers' awareness of prevention and control. It is desirable for later researchers can continue the experiment in a multi-center manner to expand the sample size and extend the study period.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, it is of great clinical significance to strengthen the awareness of CDI prevention and control among healthcare workers and the rational use of antimicrobials through intervention methods to reduce CDI's prevalence and infection rate.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7414%;\"\u003e\n \u003cp\u003eCDI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69.2586%;\"\u003e\n \u003cp\u003eClostridium difficile infection\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7414%;\"\u003e\n \u003cp\u003eHO-CDI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69.2586%;\"\u003e\n \u003cp\u003ehospital-onset C. difficile infection\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7414%;\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69.2586%;\"\u003e\n \u003cp\u003eintensive care unit\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7414%;\"\u003e\n \u003cp\u003eHAI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69.2586%;\"\u003e\n \u003cp\u003ehealthcare-associated infection\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7414%;\"\u003e\n \u003cp\u003eKAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69.2586%;\"\u003e\n \u003cp\u003eknowledge, attitude and practice\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 30.7414%;\"\u003e\n \u003cp\u003eCDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69.2586%;\"\u003e\n \u003cp\u003eCenters for Disease Control and Prevention\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eAcknowledge\u003c/h2\u003e\n\u003cp\u003eWe would like to thank everyone who took part in this study.\u003c/p\u003e\n\u003ch2\u003eConflict of interest statement\u003c/h2\u003e\n\u003cp\u003eNone declared.\u003c/p\u003e\n\u003ch2\u003eFunding statement\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eFunding. This work was supported by National Key Research and Development\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Program of China [No. 2022YFC2009801; No. 2022YFC2009805], the Natural Science Foundation of Hunan Province [No. 2021JJ31071], the Project program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital)[No. 2021KFJJ05], Health Development Research Center of the National Health Commission, \u0026quot;Evidence-based Evaluation and Demonstration Base Construction Project of Infection Control Measures in Healthcare Institutions\u0026quot;[No. CNHDRC-KJ-L-2020-53-04375], Changsha science and technology plan project (NO. kq2202059) and Scientific and technological personnel lifting Project in Hunan Province [No. 2023TJ-Z11].\u003c/p\u003e\n\u003ch2\u003eEthical approval\u003c/h2\u003e\n\u003cp\u003eThe Ethics Committee of the Xiangya Hospital of Central South University and the United States Centers for Disease Control and Prevention IRB authorization agreement approved the study protocol (CGH #2014-047). Since the study involved the collection and testing of stool specimens for CDI, only verbal consent from the patient (or a family member) was required for enrollment.\u003c/p\u003e\n\u003ch2\u003eAuthor contributions\u003c/h2\u003e\n\u003cp\u003eSisi Zhang conceived the project and designed all experiments and wrote the manuscript independently, and Juping Duan guided the statistical analyses. While Lina Zhang, Xiaobei Peng and Wei Liu assisted with data collection. Sidi Liu and Xiujuan Meng supervised the completion of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAkoghlanian G, Lakshmi S. The difficile in Clostridium difficile infection. Int J Infect Dis. 2018;77:14\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol. 2009;7(7):526\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarbut F, Corthier G, Charpak Y, Cerf M, Monteil H, Fosse T, Tr\u0026eacute;voux A, De Barbeyrac B, Boussougant Y, Tigaud S, et al. Prevalence and pathogenicity of Clostridium difficile in hospitalized patients. A French multicenter study. Arch Intern Med. 1996;156(13):1449\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMawer D, Byrne F, Drake S, Brown C, Prescott A, Warne B, Bousfield R, Skittrall JP, Ramsay I, Somasunderam D, et al. Cross-sectional study of the prevalence, causes and management of hospital-onset diarrhoea. J Hosp Infect. 2019;103(2):200\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePetrof EO, Gloor GB, Vanner SJ, Weese SJ, Carter D, Daigneault MC, Brown EM, Schroeter K, Allen-Vercoe E. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: 'RePOOPulating' the gut. Microbiome. 2013;1(1):3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOwens RC Jr., Donskey CJ, Gaynes RP, Loo VG, Muto CA. Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect Dis. 2008;46(Suppl 1):S19\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTamma PD, Avdic E, Li DX, Dzintars K, Cosgrove SE. Association of Adverse Events With Antibiotic Use in Hospitalized Patients. JAMA Intern Med. 2017;177(9):1308\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeuerstadt P, Louie TJ, Lashner B, Wang EEL, Diao L, Bryant JA, Sims M, Kraft CS, Cohen SH, Berenson CS, et al. SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection. N Engl J Med. 2022;386(3):220\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBauer MP, Notermans DW, van Benthem BH, Brazier JS, Wilcox MH, Rupnik M, Monnet DL, van Dissel JT, Kuijper EJ. Clostridium difficile infection in Europe: a hospital-based survey. Lancet. 2011;377(9759):63\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAnderson DJ, Chen LF, Weber DJ, Moehring RW, Lewis SS, Triplett PF, Blocker M, Becherer P, Schwab JC, Knelson LP, et al. Enhanced terminal room disinfection and acquisition and infection caused by multidrug-resistant organisms and Clostridium difficile (the Benefits of Enhanced Terminal Room Disinfection study): a cluster-randomised, multicentre, crossover study. Lancet. 2017;389(10071):805\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoran TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36(5):309\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDubberke ER, Olsen MA. Burden of Clostridium difficile on the healthcare system. Clin Infect Dis. 2012;55(Suppl 2):S88\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoven A, Vlieghe E, Engstrand L, Andersson FL, Callens S, Simin J, Brusselaers N. Clostridioides difficile infection-associated cause-specific and all-cause mortality: a population-based cohort study. Clin Microbiol Infect. 2023;29(11):1424\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKyne 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(3):346\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOyaro MO, Plants-Paris K, Bishoff D, Malonza P, Gontier CS, DuPont HL, Darkoh C. High rate of Clostridium difficile among young adults presenting with diarrhea at two hospitals in Kenya. Int J Infect Dis. 2018;74:24\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoyal A, Chatterjee K, Yadlapati S, Rangaswami J. Impact of end stage kidney disease on costs and outcomes of Clostridium difficile infection. Int J Infect Dis. 2017;62:8\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi C, Li Y, Huai Y, Liu S, Meng X, Duan J, Klena JD, Rainey JJ, Wu A, Rao CY. Incidence and Outbreak of Healthcare-Onset Healthcare-Associated Clostridioides difficile Infections Among Intensive Care Patients in a Large Teaching Hospital in China. Front Microbiol. 2018;9:566.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcDonald LC, Lessa F, Sievert D, Wise M, Herrera R, Gould C, Malpiedi P, Dudeck M, Srinivasan A, Fridkin S, et al. Vital Signs: Preventing\u0026thinsp;\u0026lt;\u0026thinsp;i\u0026thinsp;\u0026gt;\u0026thinsp;Clostridium difficile\u0026thinsp;Infections. Jama-Journal Am Med Association. 2012;307(16):1684\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKrein SL, Mayer J, Harrod M, Weston LE, Gregory L, Petersen L, Samore MH, Drews FA. Identification and Characterization of Failures in Infectious Agent Transmission Precaution Practices in Hospitals: A Qualitative Study. JAMA Intern Med. 2018;178(8):1016\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCasari E, De Luca C, Calabr\u0026ograve; M, Scuderi C, Daleno C, Ferrario A. Reducing rates of Clostridium difficile infection by switching to a stand-alone NAAT with clear sampling criteria. Antimicrob Resist Infect Control. 2018;7:40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThomas RE, Thomas BC, Lorenzetti D, Conly J. Hospital and long-term care facility environmental service workers' training, skills, activities and effectiveness in cleaning and disinfection: a systematic review. J Hosp Infect. 2022;124:56\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSantino I, Teggi A, Marangi M, Montesano M, Petrucca A, Bertamino E, Zerbetto A, Sandorfi F, Iachini M, Orsi GB. Surveillance of healthcare acquired infections by alert microorganisms: preliminary results. Ann Ig. 2019;31(5):414\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePorter L, Sultan O, Mitchell BG, Jenney A, Kiernan M, Brewster DJ, Russo PL. How long do nosocomial pathogens persist on inanimate surfaces? A scoping review. J Hosp Infect. 2024;147:25\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLukasewicz Ferreira SA, Franco Meneses AC, Vaz TA, da Fontoura Carvalho OL, Hubner Dalmora C, Pressotto Vanni D, Ribeiro Berti I. Pires Dos Santos R: Hospital-acquired infections surveillance: The machine-learning algorithm mirrors National Healthcare Safety Network definitions. Infect Control Hosp Epidemiol. 2024;45(5):604\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStephenson B, Lanzas C, Lenhart S, Ponce E, Bintz J, Dubberke ER, Day J. Comparing intervention strategies for reducing Clostridioides difficile transmission in acute healthcare settings: an agent-based modeling study. BMC Infect Dis. 2020;20(1):799.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRay AJ, Deshpande A, Fertelli D, Sitzlar BM, Thota P, Sankar CT, Jencson AL, Cadnum JL, Salata RA, Watkins RR, et al. A Multicenter Randomized Trial to Determine the Effect of an Environmental Disinfection Intervention on the Incidence of Healthcare-Associated Clostridium difficile Infection. Infect Control Hosp Epidemiol. 2017;38(7):777\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoyce JM. Modern technologies for improving cleaning and disinfection of environmental surfaces in hospitals. Antimicrob Resist Infect Control. 2016;5:10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDavey P, Marwick CA, Scott CL, Charani E, McNeil K, Brown E, Gould IM, Ramsay CR, Michie S. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Reviews 2017(2).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLoo VG, Poirier L, Miller MA, Oughton M, Libman MD, Michaud S, Bourgault AM, Nguyen T, Frenette C, Kelly M, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med. 2005;353(23):2442\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSkally M, Bennett K, Humphreys H, Fitzpatrick F. Rethinking Clostridioides difficile infection (CDI) surveillance definitions based on changing healthcare utilisation and a more realistic incubation period: reviewing data from a tertiary-referral hospital, Ireland, 2012 to 2021. Euro Surveill 2024, 29(6).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarker AK, Alagoz O, Safdar N. Interventions to Reduce the Incidence of Hospital-Onset Clostridium difficile Infection: An Agent-Based Modeling Approach to Evaluate Clinical Effectiveness in Adult Acute Care Hospitals. Clin Infect Dis. 2018;66(8):1192\u0026ndash;203.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"antimicrobial-resistance-and-infection-control","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aric","sideBox":"Learn more about [Antimicrobial Resistance and Infection Control](http://aricjournal.biomedcentral.com/)","snPcode":"13756","submissionUrl":"https://submission.nature.com/new-submission/13756/3","title":"Antimicrobial Resistance \u0026 Infection Control","twitterHandle":"@ARICJournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Clostridium difficile (CDI)、healthcare-associated infection (HAI)、healthcare worker、antimicrobial usage、knowledge, attitude and practice (KAP)","lastPublishedDoi":"10.21203/rs.3.rs-4976901/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4976901/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eClostridium difficile infection (CDI) is one of the major causative factors leading to antibiotic-associated hospital-acquired and infectious diarrhea. Because C. difficile spores can be transmitted between healthcare systems, healthcare workers have become a key target for preventing and controlling C. difficile infection.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a 6-month intervention and collected 776 patients with diarrhea and 72 cases with hospital-onset C. difficile infection (HO-CDI) in Xiangya Hospital\u0026rsquo;s intensive care units (ICU). We created a questionnaire on prevention and control knowledge of C. difficile infection, investigated the correctness of healthcare workers' answers before and after the training, statistically described the use of antimicrobial drugs, and judged the validity of this study as a result of the rates of C. difficile infection and morbidities in the three phases.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe rates of three-stage C. difficile infection (13.3%vs.8.79%vs.6.5%) and morbidities rate/10,000 hospital days (117.14%vs.99.30%vs.71.63%) decreased gradually. After the training, the knowledge, attitude, and practice on prevention and control of C. difficile infection among healthcare workers were much improved. Among all diarrhea patients, there was a decreasing trend in the utilization of cefoperazone sulbactam (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), imipenem (P\u0026thinsp;=\u0026thinsp;0.047), tigecycline (P\u0026thinsp;=\u0026thinsp;0.044) in all three phases, and an increase in cefoxitin (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There was no statistical difference between the three phases of antimicrobial utilization among hospital-onset C. difficile infection patients.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis study demonstrated that our training of healthcare workers on C. difficile infection was effective, enhancing healthcare workers' prevention and control awareness of C. difficile infection effectively reducing incidences and morbidities of C. difficile infection, and emphasizing the importance of healthcare workers in the healthcare process.\u003c/p\u003e","manuscriptTitle":"Impact of targeted interventions on healthcare-acquired infection prevention and control of Clostridium difficile infections ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-16 13:51:10","doi":"10.21203/rs.3.rs-4976901/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-12-13T04:21:43+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-06T17:42:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"230452861430079182654887106128023832748","date":"2024-11-30T15:39:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"166207031824331719401026635512890769175","date":"2024-10-28T12:24:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"249332439986691212947902772387945922036","date":"2024-10-23T13:33:22+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-24T01:27:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-31T13:33:41+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-27T03:38:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"Antimicrobial Resistance \u0026 Infection Control","date":"2024-08-26T09:31:07+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"antimicrobial-resistance-and-infection-control","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aric","sideBox":"Learn more about [Antimicrobial Resistance and Infection Control](http://aricjournal.biomedcentral.com/)","snPcode":"13756","submissionUrl":"https://submission.nature.com/new-submission/13756/3","title":"Antimicrobial Resistance \u0026 Infection Control","twitterHandle":"@ARICJournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a68eb8de-9396-43d1-bbba-9c822e988852","owner":[],"postedDate":"October 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-06T16:09:58+00:00","versionOfRecord":{"articleIdentity":"rs-4976901","link":"https://doi.org/10.1186/s13756-025-01616-4","journal":{"identity":"antimicrobial-resistance-and-infection-control","isVorOnly":false,"title":"Antimicrobial Resistance \u0026 Infection Control"},"publishedOn":"2025-10-01 15:57:56","publishedOnDateReadable":"October 1st, 2025"},"versionCreatedAt":"2024-10-16 13:51:10","video":"","vorDoi":"10.1186/s13756-025-01616-4","vorDoiUrl":"https://doi.org/10.1186/s13756-025-01616-4","workflowStages":[]},"version":"v1","identity":"rs-4976901","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4976901","identity":"rs-4976901","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}