Cleansing the periurethral area, as one strategy to prevent CAUTI, has been recommended by international guidelines on the management and prevention of CAUTI [18]. Past studies have focused mainly on exploring suitable aseptic agents for periurethral cleansing, such as soapy water, chlorhexidine solution, normal saline, distilled water, sterile water and povidone-iodine [12,13,14,15,16]. However, as an important part of periurethral cleansing, the periurethral range has not been fully studied. Evidence concerning the effect of the periurethral cleansing range on CAUTI occurrence is particularly sparse. The impact of different periurethral ranges on reducing CAUTI remains unknown. To our knowledge, this is the first RCT evaluating the efficacy of expanded periurethral cleansing for the prevention of CAUTI in comatose patients. Compared with the usual periurethral cleansing protocol, we found that the expanded periurethral cleansing protocol could reduce the incidence of CAUTI in comatose patients.

The effect of expanded periurethral cleansing on reducing CAUTI is likely related to the following aspects: (i) Human skin can protect the body from pathogens, but it is also the natural reservoir of pathogenic microorganisms. Anatomically, sweat and sebaceous glands are densely distributed in the periurethral and anal skin [19], facilitating the formation of a humid environment in which microorganisms thrive [20]. Expanded periurethral cleansing can remove microorganisms from periurethral and anal skin. (ii) Comatose patients with urinary catheters usually reach a stage of immune dysfunction [21] and thus are more vulnerable to CAUTI. Expanded periurethral cleansing can reduce the burden of the fragile immune system. (iii) Comatose patients are more likely to present with stool incontinence as their gastrointestinal function and defecation become dysfunctional. One study by Karen revealed that the presence of stool incontinence was significantly associated with the occurrence of CAUTI, and more than 80% of patients with CAUTIs experienced stool incontinence [22]. The microorganisms in the intestine are excreted in the feces and contaminate the periurethral area. Expanded periurethral cleansing can decrease pathogen colonization around anal skin, thereby limiting the introduction of opportunistic pathogens into the urinary tract.

The length of catheterization was significantly associated with CAUTI. Under the usual periurethral cleansing protocol, the incidences of CAUTI in the control group on days 3, 7, and 10 were 3.17%, 8.14%and21.27%, respectively, and these results are similar to those of previous studies [8, 13, 14]. However, under the expanded periurethral cleansing protocol, the incidences of CAUTI on the 3rd, 7th and 10th day decreased to 2.22%, 5.33% and 10.22%, respectively. One study by Flores found that after the first 7 days, the risk of developing bacteriuria increases by approximately 5% every day in patients with indwelling urinary catheters. This finding was similar to our finding that the incidence of CAUTIs on day 10 increased by more than 13% with the usual periurethral cleansing protocol but increased by less than 5% with the expanded periurethral cleansing protocol. In addition, our study confirmed that polymicrobial CAUTI increased rapidly as the length of catheterization exceeded 7 days, and a similar result was reported in one study by Hiwot [23].

We selected povidone-iodine as the antiseptic substance for periurethral cleansing in this study. Many randomized controlled trials (RCTs) have confirmed that povidone-iodine is not inferior to other antiseptics for reducing the risk of CAUTI [13, 16, 24].

In our study, Escherichia coli was the most common pathogenic bacteria, followed by Enterococcus spp. Candida tropicalis and Candida albicans were the most common fungi. Similarly, one study by Jaffar reported that the common pathogen of CAUTI is Escherichia coli (37.8%), followed by Candida spp. (14.4%) and Pseudomonas aeruginosa (11.7%) [25]. A multicenter study involving 3288 patients in Turkey showed that the most common pathogens of CAUTI were Candida albicans, Pseudomonas aeruginosa, and Acinetobacter.[26] However, one study conducted in Taiwan reported that Candida spp. were the most common pathogens (25.8%), followed by Escherichia coli (15.2%) [27]. The similarities and/or differences in the spectrum of pathogens implicated in causing CAUTI in ICU patients may be mainly attributable to the regional epidemiology of pathogens, environmental conditions, patient demographic characteristics, the use of broad-spectrum antibiotics, prior antimicrobial exposure, and the organisms unique to each facility [28].

In this trial, we found that female gender was a risk factor (HR 2.01, 95% CI 1.14–3.53) for CAUTI in comatose patients. This finding is similar to that of one study by Gillen, which concluded that female gender is an independent risk factor for CAUTI [29]. One meta-analysis involving 8785 participants also revealed that the risk of CAUTI in females was 2 times higher than that in males [30]. This difference may be explained by the relatively shorter and wider urethral anatomy of the female urethra, which is closer to the anus, facilitating bacterial entry [31]. Additionally, we found that comatose patients with diabetes are4.22 times (95% CI 2.41–7.40) higher than those without diabetes after the same course of catheterization. The similar result was reported by one meta-analysis that suggested patients with diabetes had a higher risk for CAUTI than those without diabetes (HR = 1.98, 95% CI 1.31–2.99). The immunocompromised state of diabetes patients, along with glycosuria as a source of microbial growth, puts them at a high risk for developing CAUTI [32].

This study has several limitations. First, although it was randomized, our study was monocentric and single-blinded. We were unable to blind group allocation to the nurses and physicians who cared for the study subjects, which may have introduced bias. Second, the number of study subjects was limited. In the future, we will enroll more patients to assess the effectiveness of expanded periurethral cleansing. Third, our results may not apply to long-term catheterization since the duration of catheterization in this study was no more than 10 days. Third, we didn't collected catheter days and used incidences of CAUTI of different days rather than the rate of CAUTI per 1000 catheter days as epidemiological indicator in DA-HAIs surveillance in the study. Finally, the participants in our study were critically ill comatose patients in the ICU, and further studies should be conducted to determine whether common patients could benefit from expanded periurethral cleansing for the prevention of CAUTI. However, as a pilot study including different types of units, this investigation still provided useful information for establishing an infection control policy for the prevention and control of CAUTI.

In conclusion, our study was the first RCT to provide evidence supporting the effectiveness of expanded periurethral cleansing in reducing CAUTI, especially those caused by bacteria and multiple pathogens, in comatose patients with short-term catheterization (≤ 10 days). Female and diabetes patients benefit more from the expanded periurethral cleansing protocol for reducing CAUTI. Expanded periurethral cleansing could be considered an easy-to-implement and cost-effective intervention for preventing CAUTI in critical care settings.