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

doi:10.21203/rs.3.rs-4976901/v1

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

https://doi.org/10.21203/rs.3.rs-4976901/v1

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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)

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.

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.

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. 2a -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. 3a-e). In addition to this, we also counted the correct rate of a total 3 trainings, the results in (Fig. 3f). 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
	Antibacterial	Cases	Utilization (%)	Cases	Utilization (%)	Cases	Utilization (%)	P-value
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.

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.

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.

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

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.

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No competing interests reported.

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You are reading this latest preprint version

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

Status:

Version 1

Abstract

Background

Methods

Results

Conclusions

Figures

Introduction

Methods

Results

Discussion

Conclusions

Abbreviations

Declarations

Consent for publication

Availability of data and materials

Acknowledge

Conflict of interest statement

Funding statement

Ethical approval

Author contributions

References

Additional Declarations

Supplementary Files

Status:

Version 1