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[Shanghai, China, September 20, 2025] During the 10th HUAWEI CONNECT, Kang Ning, President of Huawei Cloud Global Ecosystem delivered a keynote titled “Empowering AI Pioneers in Industries to Build Success with Developers.” Mr. Kang detailed the latest advancements in the Huawei Cloud ecosystem and unveiled a comprehensive upgrade to Huawei Developer Space.

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Introduction

Antimicrobial resistance (AMR) has emerged as a global public health threat, and infections caused by resistant bacteria increase patient mortality and treatment costs.^1–4 It is estimated that in 2021, the burden of bacterial AMR has led to approximately 1.14 million attributable deaths and about 4.71 million associated deaths. Without intervention, deaths are projected to increase substantially by 2050.⁵ Consequently, the World Health Organization(WHO) has developed a global action plan against AMR, and 178 countries (including China) have formulated national action plans to curb AMR.^6–8 Studies have shown that the irrational use of antibiotics is the primary cause of AMR, a problem prevalent in developing countries. Additionally, data from the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2022 have also indicated that reducing antibiotics consumption can lower AMR.^9,10 It has been confirmed and widely used in international countries that implementing antimicrobial stewardship programs (ASPs) can improve patient outcomes, reduce AMR, and lower healthcare costs.^11,12 Microbiological diagnostic testing is a core component of ASPs, and using antibiotics based on microbiological testing and antibiotic susceptibility results can provide a basis for precise clinical treatment, as well as reduce the occurrence of multidrug-resistant organisms (MDRO).^13,14 Despite the widespread recognition of the importance of microbiological testing, its application in clinical practice remains insufficient. During the COVID-19 pandemic, physicians still used a large number of antimicrobial agents empirically. Multiple studies have emphasized the need to strengthen antimicrobial stewardship through microbiological testing and the use of biomarkers to aid decision-making.^12,15,16

Pathogen submission before antimicrobial therapy refers to the initiation of pathogen testing and completion of relevant specimen collection before the administration of antimicrobial therapy. Specifically, pathogen testing includes microbiological culture and biomarkers such as procalcitonin. The pathogen submission rate before antimicrobial therapy has been proven to be a key indicator for the rational use of antibiotics and the containment of AMR.^13,14 From 2009 to 2010, the pathogen submission rate in 6 emergency care hospitals in the United States reached 79.10% (the highest reported rate in the literature, but specimens collected on the same day as the initiation of antimicrobial therapy were also included).¹⁷ Moreover, accumulating studies have shown that comprehensive intervention measures (such as information systems, training and education, performance assessment, and feedback follow-up) can effectively improve the pathogen submission rate before antimicrobial therapy and guide rational clinical medication use.^18–22 China has included “improving the pathogen submission rate before antimicrobial therapy” in hospital infection management quality control objectives and national medical quality and safety improvement objectives. Since 2021, a special improvement action (hereinafter referred to as the special action) has been launched to “increase the pathogen submission rate before antimicrobial therapy”, proposing that the pathogen submission rate before antimicrobial therapy should not be less than 50%, the pathogen submission rate related to hospital-acquired infections (HAIs) should not be less than 90%, and the pathogen submission rate before the combined use of key antibiotics should be 100%. With the government as the leading force, the rational use of antibiotics and the AMR control system have been continuously optimized, and some achievements have been made in curbing bacterial resistance.²³ However, the irrational use of antibiotics still exists in medical institutions at all levels, and the increase in bacterial resistance has not been effectively controlled.^24,25 The situation remains severe, and the management of submission rates requires not only national policy support but also administrative intervention from hospitals.²⁶ Therefore, from the perspective of hospital management, It is of great significance to adopt a scientific quality improvement method to enhance the pathogen submission rate before antimicrobial therapy.

The Find-Organize-Clarify-Understand-Select (FOCUS)-Plan-Do-Check-Act (PDCA) model is a comprehensive quality management tool, which is divided into 9 steps: Find, Organize, Clarify, Understand, Select, Plan, Do, Check, and Act. Originating in the United States, it has been widely used at national and international levels in recent years. This model emphasizes data-driven decision-making and multi-department collaboration to break down departmental barriers, as well as continuous quality improvement targeting the root causes of problems to adapt to the ever-changing medical environment and patient needs. Huang et al have applied the FOCUS-PDCA model to the management of sterile packages in the disinfection supply center, effectively reducing the occurrence rate of distribution defects and lowering the risk of hospital infections.²⁷ Xu et al have applied the FOCUS-PDCA model to central venous catheter management, significantly reducing the incidence of catheter-related bloodstream infections (CR-BSI).²⁸ Therefore, the FOCUS-PDCA model has been successfully used in the medical industry, especially in medical quality management, patient safety, and optimization of medical processes.

Currently, there is research on the application of the FOCUS-PDCA model in hospital infection management, and there are few reports on its application in antimicrobial stewardship. This study innovatively applied the FOCUS-PDCA model to the management of pathogen submission before antimicrobial therapy from the perspective of hospital management. Using fishbone diagrams and Pareto analysis, we identified the weak links in the management of pathogen submission before antimicrobial therapy. Through information technology and multi-department collaboration, we significantly improved the pathogen submission rate and specimen quality before antimicrobial therapy, thereby reducing the detection rate of MDRO and providing new ideas and methods for antimicrobial stewardship.

Materials and Methods

Study Setting and Patient Population

This study was conducted in a tertiary general hospital in Zhejiang Province, China, with 2560 open beds, nearly 140,000 patient admissions, and more than 50,000 surgeries performed annually. The study population included hospitalized patients who received antimicrobial therapy from January 1, 2021, to December 31, 2024. Based on whether the FOCUS-PDCA model was implemented for pathogen submission management before antimicrobial therapy, patients were assigned to the control group (admitted from January 1, 2021 to December 31, 2021) and intervention group (admitted from January 1, 2022, to December 31, 2024). The pathogen submission rates before antimicrobial therapy from 2022 to 2024 were continuously tracked to evaluate the improvement effects of the FOCUS-PDCA model. The inclusion criteria were: hospitalized patients receiving systemic antimicrobial therapy. The exclusion criteria were: (1) Patients receiving prophylactic antimicrobial drugs. (2) patients receiving topical antimicrobial treatment.

Study Design and Intervention

In 2021, the state introduced new benchmarks and target values for the pathogen submission rate before antimicrobial therapy. According to data analysis, our hospital achieved a pathogen submission rate before antimicrobial therapy of 55.51% for inpatients. However, 26 departments (47% of all departments, mainly surgical wards) had submission rates below 50%. Moreover, these departments had a high number of patients receiving antimicrobial drugs, with large amounts of usage and significant irrational use. Neurosurgery, Hepatobiliary and Pancreatic Surgery, General Surgery, Orthopedics, Colorectal and Anal Surgery, Cardiothoracic Surgery, Vascular Surgery, and Trauma Surgery were selected as key departments for improvement. Meanwhile, we continued to improve the pathogen submission rate before antimicrobial therapy for all hospitalized patients.

At the end of 2021, a special improvement team was established, coordinated by the vice president, led by the Hospital Infection Management Department, and supported by multiple departments (including the Medical Affairs Office, Laboratory Department, Pharmacy Department, Information Center, Nursing Department, and General Affairs Department). Quarterly meetings were held.

A form was designed to retrospectively analyze data from hospitalized patients in the fourth quarter of 2021, focusing on those with low pathogen submission rates before antimicrobial therapy. The reasons were categorized as follows: (1) failure to order pathogen tests: physicians did not issue order pathogen tests when prescribing antimicrobials simultaneously; (2) post-antimicrobial specimen collection: the time of pathogen specimen collection occurred after the time of antibiotic administration; (3) failure to collect available specimens: physicians ordered the pathogen tests, and patients receiving antimicrobial therapy had pathogen specimens available for collection, but medical staff did not collect them; (4) incorrect ONCE medical order: the ONCE order did not have correct frequency designation; (5) no specimen available for collection: patients had indications for antimicrobial use, but no pathogen specimen was available for collection (eg patients with cholecystitis and appendicitis); (6) other reasons: patients receiving antimicrobial therapy did not have pathogen specimens submitted due to reasons such as transfer to another department or emergency surgery.

Pareto analysis was performed on the non-compliant data. According to the 80/20 rule, failure to order pathogen tests and post-antimicrobial specimen collection accounted for 48.73% and 33.21%, respectively, which was the primary reason for the low pathogen submission rate before antimicrobial therapy (Figure 1). The fishbone diagram was employed to analyze the primary reasons. During the verification of true causes, the team analyzed the reasons from 4 aspects (personnel, equipment, work procedure, and environment). Finally, 4 specific causes were determined, including incomplete information system construction, inefficient specimen submission processes, insufficient supervision and assessment efforts by administrative departments, and insufficient training (Figures 2 and 3).

Figure 2 Roots cause of failuring to order pathogen tests.

Figure 3 Roots cause of post-antimicrobial specimen collection.

Specific improvement measures were listed as follows:

Establishing a Diversified Training System

A hospital-wide survey on the knowledge of pathogen submission before antimicrobial therapy was conducted to develop a targeted training plan. The whole hospital was organized to study the relevant specifications of antimicrobial drug management, interpret national policy documents, and hold training courses on a standardized collection of microbiological specimens (eg video recordings on correct blood, urine, and sputum culture collection) with assessments. Joint training at both hospital and department levels was conducted to reinforce physicians’ awareness of active and standardized specimen submission. Hospital infection specialists provided specialized lectures for key monitoring departments, analyzed reasons for failure to conduct pathogen tests before antimicrobial therapy, and assisted with departmental improvements.

Improving Information Technology Monitoring

An information monitoring module was established within the real-time hospital infection surveillance system to clearly define the capture points for antimicrobial administration and pathogen specimen collection times. It required that specimens should be collected before the initiation of therapeutic antimicrobial therapy, enabling real-time monitoring and querying of submission rate indicators by both administrative departments and clinical departments. A pop-up reminder for pathogen testing was added when physicians ordered antimicrobial agents, with medication options for preventive or therapeutic use. For therapeutic use, physicians could choose empirical or sensitivity-guided treatment, with reminders to conduct pathogen testing before treatment and options for pathogen tests. Specimens that have already been submitted could be linked to sensitivity results. Moreover, as some specimens (such as cerebrospinal fluid and blood cultures) are difficult to obtain, specimens submitted within 72 hours before admission for outpatients and emergency patients were included in the statistics. The information department increased the number of PDAs available for clinical use and ensured full network coverage in all departments.

Optimizing Specimen Collection and Submission Processes

To reduce delays and errors in specimen collection, transport, and testing, multiple departments (including the Medical Affairs Office, General Affairs Office, Nursing Department, and Laboratory Department) collaborated to optimize the specimen submission process. The Medical Affairs Office coordinated with the microbiology laboratory to operate 24 hours for microbiological specimen receipt, with night shifts covered by the emergency laboratory and specimen inoculation performed by qualified physicians. The specimen submission processes for microbiological specimens collected during surgery and endoscopy were optimized. Instead, specimens were directly transported by logistics workers to the laboratory to shorten transport times. Meanwhile, the Nursing Department led efforts to improve the quality of specimen collection for sputum, blood, and urine cultures. The General Affairs Office focused on shortening specimen transport times.

Increasing Regulatory and Assessment Efforts

A supervision plan was developed, linking performance to clinical department evaluations. The pathogen submission rate was included as a hospital-level quality assessment indicator; clinical departments were assessed monthly, which was integrated into the annual performance assessment of department heads. Monthly statistical analyses of antimicrobial use and pathogen submission rates were published in the Medical Quality and Safety Newsletter, with department rankings. The top 10 departments with substandard submission rates were publicly notified at the Hospital Infection Management Committee and Antimicrobial Management meetings. Monthly drug newsletters published antimicrobial use data and conducted antimicrobial prescription reviews. The use of special-use antimicrobial agents was strictly regulated, requiring prescriptions by physicians with appropriate prescription rights and online consultation approval from infectious disease specialists. The Antimicrobial Management Team developed a “penalty plan for typical irrational antimicrobial use cases”, which listed cases of combined key antimicrobial use without prior pathogen testing as typical irrational cases, with penalties applied to both the department head and the responsible physician (with double penalties for department heads).

Definitions of Terms

HAIs were diagnosed by the Hospital Infection Management Department according to the diagnostic criteria issued by the National Health Commission of China in 2001. The pathogen submission rate before antimicrobial therapy in inpatients is defined according to the document issued by China’s National Health Commission (Guiding Opinions on the Special Action to Improve the Pathogen submission Rate Before Antimicrobial Therapy in Hospitalized Patients).

Targeted pathogen submission rate before antimicrobial therapy (%) = the number of cases with targeted pathogen submission before antimicrobial therapy/total number of cases receiving antimicrobial therapy × 100% (Note: targeted pathogen submission includes microbiological culture and sensitivity testing, microscopic examination, immunological submission, and molecular rapid diagnostic tests).

Pathogen submission rate before antimicrobial therapy (%) = the number of cases with pathogen submission before antimicrobial therapy/total number of cases receiving antimicrobial therapy × 100% (Note: including both targeted and non-targeted pathogen submission; non-targeted pathogen submission refers to related biomarkers such as procalcitonin, interleukin-6, fungus(1-3)-β-D-glucantests, and galactomannan antigen submission).

Pathogen submission rate related to HAIs (%) = the number of cases with pathogen submission related to HAIs/total number of cases with HAIs × 100% (Note: related biomarkers are excluded).

Pathogen submission rate before the combined use of key antibiotics (%) = the number of cases with pathogen submission before combined use of two or more key antibiotics/total number of cases receiving combined therapy with two or more key antibiotics × 100% [Note: key drugs include carbapenems (imipenem, meropenem, panipenem, biapenem, and ertapenem), glycopeptides (vancomycin and teicoplanin), tigecycline, linezolid, polymyxin, cefoperazone sulbactam, and antifungals (voriconazole, itraconazole, and caspofungin)].

The proportion of sterile specimens (%) = the number of sterile specimens for microbiological culture/total number of microbiological specimens × 100% [Note: sterile specimens include blood, cerebrospinal fluid, synovial fluid (joint fluid), pleural effusion (pleural fluid), peritoneal fluid (peritoneal fluid), pericardial effusion, blind tube fluid (pelvic effusion), amniotic fluid, bone marrow, and tissues].

The proportion of microbiological specimens (%) = the number of specific microbiological specimens/total number of all microbiological specimens × 100%.

The detection rate of MDRO (%) = the number of cases with specific multidrug-resistant bacteria detected in hospitalized patients/total number of cases with specific bacteria detected in hospitalized patients×100%. [Note: target multidrug-resistant bacteria include methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Escherichia coli (CREC)].

Microbial Identification

Bacteria were cultured and isolated according to the standard microbiological procedures, the strain identification was carried out using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDITOF/MS, Bruker, America), and the quality control strains were provided by the Clinical Laboratory Center of the Ministry of Health. The antibiotic sensitivity testing was performed using the Kirby-Bauer disk diffusion technique, E-test or Minimum inhibitory concentrations (MICs), and the MICS was tested via the VITEK2-Compact system (bioMérieux, France). The interpretation criteria and quality control followed the 2023 recommendations of the Clinical and Laboratory Standards Institute (CLSI).

Data Collection and Analysis

Relevant data were collected via the Xingling Real-Time Hospital Infection Surveillance System and the Laboratory Information Management System (LIS). Data on bacterial isolation and antimicrobial susceptibility test results from the microbiology laboratory were collected, excluding duplicate strains from the same patient and the same site. These data were collected by microbiology laboratory staff, while other data were collected by hospital infection management specialists. Data analysis was performed using R software (version 4.4.2). The count data were expressed as percentages, and trend analysis over different years was conducted using the Cochran-Armitage trend test, with a statistical significance level set at p < 0.05.

Results

Antibiotics-Related Pathogen Submission

The pathogen submission rate before antimicrobial therapy increased from 64.99% in 2021 to 76.40% in 2024 (Z = 31.992, p < 0.001), and the targeted pathogen submission rate before antimicrobial therapy increased from 55.51% in 2021 to 69.48% in 2024 (Z = 36.727, p < 0.001). Additionally, the pathogen submission rates in key departments also showed significant improvement, with an increasing trend year by year. The increase was primarily driven by targeted pathogen submission projects. In the pathogen submission rate before antimicrobial therapy, the Hepatobiliary and Pancreatic Surgery Ward 1 and the Vascular Surgery Ward showed the most substantial improvements in the pathogen submission rate before antimicrobial therapy, as evidenced by an increase of 171.11% and 117.00%, respectively. Moreover, the targeted pathogen submission rate before antimicrobial therapy also increased significantly by 144.34% and 142.16% in these wards, respectively (p < 0.001) (Tables 1 and 2).

Table 1 The Pathogen Submission Rate Before Antimicrobial Therapy From 2021 to 2024 (%)

Table 2 The Targeted Pathogen Submission Rate Before Antimicrobial Therapy From 2021 to 2024 (%)

The pathogen submission rate related to HAIs increased from 95.16% in 2021 to 99.62% in 2024, consistently remaining above 95% and reaching the national requirement (Z = 8.877, p < 0.001) (Table 3).

Table 3 Therapy-Related Pathogen Submission Rates Before Antimicrobial Therapy From 2021 to 2024 (%)

The pathogen submission rate before the combined use of key antibiotics increased from 94.38% in 2021 to 99.44% in 2024, showing statistically significant differences (Z = 7.742, p < 0.001) (Table 3).

Microbiological Specimen Structure

The total number of microbiological specimens submitted for testing increased yearly from 2021 to 2024. The proportion of sterile specimens increased from 38.07% in 2021 to 43.24% in 2024 (Z = 27.497, p < 0.001). The proportion of blood cultures increased from 35.13% in 2021 to 38.49% in 2024 (Z = 15.863, p < 0.001). However, the proportion of sputum cultures decreased from 31.99% to 29.90% (Z = −10.848, p < 0.001), and that of urine cultures decreased from 10.74% to 9.63% (Z = −8.535, p < 0.001) (Table 4).

Table 4 Analysis of Microbiological Specimen Composition Proportions From 2021 to 2024 (%)

Detection Rate of MDRO

The overall detection rate of MDRO showed a downward trend from 17.19% in 2021 to 15.36% in 2024 (Z = −2.733, p < 0.05). Specifically, from 2021 to 2024, the detection rates of MRSA, CRPA, and CRKP decreased from 32.42%, 20.57%, and 14.19% to 27.50%, 12.66%, and 12.23%, respectively. However, the detection rate of CRAB showed an increasing trend (30.96% in 2021 to 41.78% in 2023) before dropping to 33.04% in 2024. The detection rate of CREC showed an upward trend, which increased from 1.40% in 2021 to 2.09% in 2024 (Z = 3.161, p < 0.05) (Table 5).

Table 5 The Detection Rate of MDRO From 2021 to 2024 (%)

Discussion

The management of pathogen submission before antimicrobial therapy involves multiple aspects, including enhancing the professional capabilities of medical staff, optimizing the specimen submission process, and improving information system construction. Specifically, the process includes the clinical physician’s specimen submission request, patient specimen collection, specimen transportation, and feedback from the microbiology laboratory, involving clinical physicians, nurses, specimen transporters, and laboratory personnel. From the perspective of hospital management, this study applied the FOCUS-PDCA model to effectively improve the pathogen submission rate and specimen quality before antimicrobial therapy and reduce the detection rate of MDRO, providing a sustainable management mechanism.

FOCUS-PDCA Model-Driven Continuous Quality Improvement Promotes Special Action

Compared with traditional management methods, the FOCUS-PDCA model has the following advantages. It is data-driven, allowing for precise problem identification through the collection and analysis of large amounts of data, avoiding the shortcomings of relying on experience-based judgments. It promotes multi-department collaboration, enhancing management efficiency and effectiveness. It emphasizes continuous improvement through the PDCA cycle, continuously enhances antimicrobial management levels.

This study applied the FOCUS-PDCA model and kept the pathogen submission process efficient and rational by integrating quality management concepts into improving pathogen submission rates. After the improvement, the pathogen submission rate before antimicrobial therapy for hospitalized patients increased from 64.99% to 76.40%, and the targeted pathogen submission rate increased from 55.51% to 69.48%, with significant growth in surgical departments. These data are higher than the results reported by Lao et al and Zheng et al.^18,21 Measures such as training, performance assessment, and information technology can effectively improve the pathogen submission rate before antimicrobial therapy and enhance physicians’ willingness to submit specimens. Zheng et al have reported consistent results.²⁹ From a hospital management perspective, this study proved that applying the FOCUS-PDCA model is beneficial for the advancement of special action measures.

FOCUS-PDCA Model-Driven Information Management Significantly Improves Submission Rates

Currently, hospital infection information management has become an essential tool for reducing hospital infection rates and antimicrobial usage. Information technology helps increase microbiological testing submission rates and facilitates timely communication between departments.^{20,22,29–31} Physicians play a central role in antimicrobial use, as they are the ones who order pathogen tests. Studies have shown that information system decision-making is a key factor influencing physicians’ intentions to conduct pathogen testing, especially for special-use antibiotics.²⁹ Antimicrobial drugs have high usage rates in surgical departments. This is because surgeons often use antimicrobial agents for the long term to prevent surgical site infections. They may have insufficient awareness of the importance of pathogen diagnosis and may prefer empirical treatment due to the long turnaround time for antimicrobial susceptibility testing (AST).^32–34 In this study, rigid rules were designed based on information technology. When physicians ordered antimicrobial agents, a pop-up reminder for pathogen testing was displayed, with pathogen test options provided for selection. Additionally, Personal Digital Assistants (PDAs) were used to scan and match antimicrobial administration times with pathogen specimen collection times, which directly intervened in physicians’ diagnostic behaviors and improved their compliance with pathogen testing before therapeutic antimicrobial use. The combined use of key antibiotics is mostly used for patients with severe conditions and long hospital stays. In this study, the pathogen submission rate before the combined use of key antibiotics was slightly lower than the 100% target set by the National Health Commission, which will be a key area for improvement in the next phase.

High-quality monitoring is the foundation for controlling drug-resistant bacteria. Inaccurate or erroneous monitoring results can mislead clinical practice and are not conducive to resistance control. This study showed that the submission rate and quality were increased. The proportion of sterile specimens in microbiological specimens increased by 5.17%, and the proportion of blood cultures increased by 3.36%. However, the proportion of sputum and urine cultures decreased by 2.09% and 1.11%, respectively. In foreign countries, blood and urine cultures are the most common microbiological specimens, while sputum is the most frequently collected specimen in China. Although sputum and urine cultures are easily obtained in clinical practice, they are also more prone to contamination. Blood and other sterile specimens should be preferred.^35,36 In this study, it was found through PDA specimen collection times that many departments still collected morning sputum and urine, which violated the principle of specimen submission before antimicrobial therapy. The awareness of medical staff was gradually changed through a cycle of training, inspection feedback, retraining, and re-inspection feedback. The increase in sterile specimens (such as blood cultures) reduced the risk of specimen contamination, improved the reliability of antimicrobial susceptibility results, shortened the duration of empirical treatment, and thus encouraged clinical physicians to shift from empirical to evidence-based treatment, curbing the development of multidrug resistance.

FOCUS-PDCA Model-Driven Antimicrobial Management Contributes to Lowering MDRO Detection Rates

The 2022 Global Burden of Disease study identified 6 major pathogens responsible for AMR-related deaths in 2019, including Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, accounting for 73.4% of attributable deaths.^37,38 The management of antibiotics is crucial to curb the trend of MDRO.^39,40 After improvements, the detection rate of MRSA, CRPA, and CRKP decreased from 32.42% to 27.50%, from 20.57% to 12.66%, and from 14.19% to 12.23%, respectively. The analysis suggests that submitting relevant biomarkers and targeted pathogen specimens can maximize the use of empirical antibiotics without indication and prevent prolonged antimicrobial courses.^15,16 For patients with confirmed pathogen diagnoses, physicians can select antimicrobial agents to which the pathogens are susceptible for targeted treatment, avoiding the use of broad-spectrum or combination therapy to reduce the selective pressure of resistance. Timely adjustment of treatment regimens based on AST results could improve treatment efficacy and reduce the development of resistance. Therefore, it’s believed that the decline in MRSA/CRPA/CRKP detection rates is directly related to the reduction of antimicrobial selective pressure due to precise medication use.

However, in this study, CRAB and CREC showed a fluctuating upward trend, which requires attention. The detection rate of CRAB increased from 30.96% in 2021 to 41.78% in 2023, and then dropped to 33.04% in 2024. The detection rate of CREC slowly rose from 1.40% in 2021 to 2.09% in 2024, which is consistent with global data.¹⁰ The analysis indicates that MDRO mainly originate from the ICU, where carbapenem antimicrobial agents are used at a high rate for treating severe bacterial infections or MDRO infections, leading to an increasing trend in the detection rate of carbapenem-resistant Enterobacteriaceae. Moreover, the medical environment is conducive to the growth of resistant bacteria. CRAB can survive for a long time on dry and inanimate surfaces, and E.coli is ubiquitous in the environment,⁴¹ making them unresponsive to single antimicrobial management strategies. This suggests that controlling multidrug-resistant bacteria requires joint environmental cleaning and disinfection, hand hygiene, and active surveillance, in addition to rational antimicrobial use.^42,43 Although the detection rate of CREC is still relatively low, its upward trend is concerning and warrants continued monitoring. In the next phase, we will strengthen bacterial resistance surveillance and promote multi-disciplinary collaboration.

This study has some limitations. First, some patients may have used antimicrobial agents before admission, and it is currently impossible to screen out patients who have already used antimicrobial agents in other hospitals or outpatient clinics through information technology. Therefore, the impact of pre-hospital antimicrobial use on pathogen specimens cannot be completely ruled out. Second, the detection rate of CREC shows an overall upward trend in this study, which requires further improvement. Third, this study fails to further investigate whether the specimen collection sites match the infection sites for HAIs. In future research, we will focus on matching the infection sites with the submitted specimens.

Conclusion

In summary, this study implemented the FOCUS-PDCA model, adopting a metrics-driven and problem-oriented approach to enhance multi-disciplinary team collaboration and communication. Strengthening intelligent regulatory systems using information technology reinforced the awareness of clinical medical staff in pathogen submission before antimicrobial therapy. These measures effectively promoted rational clinical antimicrobial use and reduced the detection rate of MDRO. Furthermore, through multiple measures (including establishing a diversified training system, analyzing representative cases of inappropriate antimicrobial use, implementing departmental and individual performance evaluations, and ensuring follow-up by dedicated infection control personnel), the study strictly monitored every step of antimicrobial prescribing and specimen submission management. This approach not only increased the pathogen submission rate but also improved the submission quality, providing practical experience for clinical healthcare institutions seeking to enhance the pathogen submission rate before antimicrobial therapy. In the future, we aim to accelerate information system development, promote clinical rapid diagnostic technologies, and uphold the principle of “collecting specimens whenever necessary; performing pathogen testing before administering therapeutic antimicrobials for infections”, thereby better supporting clinical practice.

Ethics Statement

This study was conducted in accordance with the Declaration of Helsinki. The research design was reviewed and approved by the Ethics Committee of Affiliated Jinhua Hospital, Zhejiang University School of Medicine. The hospital’s Ethics Committee approved the waiver of informed consent. We guarantee the privacy, confidentiality, or anonymity of the participants at any stage of this study. The anonymous indirect data of the participants will be collected, analyzed, and presented in the research.

Acknowledgments

We would like to thank Affiliated Jinhua Hospital, Zhejiang University School of Medicine for its approval and support for this large-scale research project, and we thank all the medical staff involved in this project.

Funding

This work was supported by the Youth and Middle-aged Scientific Research Start-up Fund Project of Affiliated Jinhua Hospital, Zhejiang University School of Medicine (Approval No. JY2022-2-02).

Disclosure

The authors have declared that no competing interests exist in this work.

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Introduction

In 1874, James Paget first reported Paget’s disease (PD), a rare form of intraepithelial adenocarcinoma predominantly affecting skin regions containing apocrine glands.¹ Based on the primary lesion location of PD, the disease is categorized into two types: mammary Paget’s disease (MPD) and extramammary Paget’s disease (EMPD).² In 1893, perianal Paget’s disease (PPD), a subtype of EMPD, was first described by Darier and Couillaud.³ Owing to the limited number of cases, our understanding of this disease remains incomplete and necessitates further investigation. In this report, we present a case of secondary PPD which is associated with adenocarcinoma of the anorectal junction.

Case Presentation

A 67-year-old Chinese male patient presented with a one-year history of perianal rash. Three months prior to presentation, the patient experienced worsening perianal pruritus accompanied by perianal pain and exudation, hematochezia, and increased stool frequency. In January 2020, the patient sought medical attention at our hospital. His medical history was significant for prostatic hyperplasia, with no documented history of cancer or other malignancy-related conditions. Physical examination revealed symmetrically distributed lichenoid lesions extending from the perianal region into the anal canal, measuring approximately 15 cm in diameter. The well-demarcated erythematous lesion exhibited crusts, scales, and erosions (Figure 1A). A comprehensive diagnostic evaluation was performed. Digital rectal examination and colonoscopy identified a mass involving the anterior side of the anorectal junction (Figure 1B). Abdominopelvic computed tomography (CT) and contrast-enhanced pelvic magnetic resonance imaging (MRI) demonstrated thickening and enhancement of the tissues in the perianal region and the junction of the rectum and anal canal. Biopsies of the perianal skin and anal canal mass confirmed EMPD and adenocarcinoma of the anorectal junction, respectively. Staging investigations, including chest and brain CT scans as well as an abdominal enhanced CT scan, did not reveal any evidence of distant metastasis. Subsequently, the case was reviewed at a multidisciplinary team (MDT) comprising surgeons, dermatologists, pathologists, oncologists, and radiologists. Full-thickness skin mapping biopsies were recommended to delineate the resection margins of the cutaneous lesion prior to surgery. Mapping biopsies were conducted at a 1-cm margin around the lesion, with sampling performed at 1-cm intervals (Figure 1A). The resection margin was determined based on the distribution of negative biopsy sites. Where biopsy results were positive, additional biopsies were performed 1 cm beyond the positive sites until all biopsy sites were negative for tumor involvement. The preoperative full-thickness mapping biopsy results confirmed negativity across all sites. Fine-needle aspiration biopsy of the inguinal lymph nodes was also performed, with no evidence of carcinoma cells detected.

Ultimately, the patient underwent laparoscopic abdominoperineal resection combined with permanent colostomy and bilateral V-Y flap reconstruction. The proximal edge of the tumor was located approximately 4 cm from the anal verge. The tumor was situated at the anterior anorectal junction, occupying more than half of the luminal circumference. Continuity was observed between the primary lesion at the left quadrant and a secondary perianal lesion. In contrast, portions of apparently normal tissue were observed between the primary lesion and the secondary perianal lesion in the right quadrant. Preoperative and postoperative images of the patient are shown in Figure 1A–F and Supplementary Figure 1.

Histopathology revealed a moderately differentiated anorectal adenocarcinoma (pT2N0M0), involving the internal sphincter, with negative surgical margins and no lymph node metastasis (0/23). Hematoxylin-eosin staining revealed the presence of epidermal pagetoid cells, characterized by atypical large cells with abundant, pale cytoplasm, sometimes eosinophilic (Figure 2A and B). Immunohistochemical staining of the perianal skin lesion showed positivity for cytokeratin 7 (CK-7), cytokeratin 20 (CK-20) and caudal-related homeobox gene nuclear transcription factor 2 (CDX-2), but negativity for gross cystic disease fluid protein-15 (GCDFP-15) in the pagetoid cells (Figure 2C and F). The patient was ultimately diagnosed with adenocarcinoma of the anorectal junction combined with secondary PPD. For various reasons, the patient refused further radiotherapy and chemotherapy. During a 2-year follow-up, the patient survived without local recurrence or metastasis but was later lost to follow-up.

Figure 2 Histopathology and immunohistochemistry images. (A) Hematoxylin and eosin staining of the skin lesion reveals pagetoid spread of atypical cells forming solid clusters that infiltrate the dermis (×10); (B) Higher magnification highlights the details of Paget cells: large cells with abundant, pale cytoplasm, sometimes exhibiting eosinophilic features (×20); (C) Immunohistochemical staining demonstrates positive expression of CK-7 in Paget cells (×10); (D) Immunohistochemical staining confirms positive expression of CK-20 in Paget cells (×10); (E) Immunohistochemical staining indicates negative expression of GCDFP-15 in Paget cells (×10); (F) Immunohistochemical staining verifies positive expression of CDX-2 in Paget cells (×10).

Discussion

The etiology of EMPD remains incompletely understood. EMPD is prone to occur in areas where apocrine glands are distributed. It is most commonly found in the scrotum and penis in men and the external genitalia in women. It can also affect the perianal area, groin, axilla and other parts.^4,5 As a subtype of EMPD, PPD can be categorized into two distinct types: primary and secondary.^6,7 The former may be attributed to the abnormal proliferation of hair follicle stem cells that differentiate into sebaceous glands, while the latter represents a primary EMPD-like lesion resulting from the cutaneous invasion of malignant cells, such as those associated with colorectal carcinoma or urothelial carcinoma.^8–10 Tumor cells may spread and extend to the epidermis through blood vessels or lymphatic vessels.¹⁰ Despite their distinct origins, the local manifestations are remarkably similar. A slowly progressive lesion in the perianal region, characterized by erythema, scaling, or hypopigmentation with well-demarcated borders, is commonly observed.¹¹ Patients with this disease often experience symptoms such as itching, exudation, bleeding, a burning sensation, or pain.^12,13 The clinical features of PPD may closely resemble those of inflammatory dermatological conditions, such as psoriasis, eczema, and fungal infections, which can be effectively managed with topical corticosteroids or other therapeutic interventions in the short term.¹⁴ Therefore, PPD should be considered in the differential diagnosis for patients exhibiting resistance to long-term topical corticosteroid or other drug therapy.¹⁵

In order to reduce diagnostic delay, examinations such as dermoscopy, reflectance confocal microscopy, and full-thickness skin biopsy are recommended for suspicious lesions.^16–18 Generally, an accurate diagnosis requires the combination of histopathology and immunohistochemistry. The histopathological hallmark of EMPD is the presence of Paget cells infiltrating the epidermis. These cells can be categorized into two main types: classic and signet ring. The classic type is distinguished by large, bubble-like nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm. In contrast, the signet ring type exhibits eccentric displacement of the nucleus and an increased amount of acidic mucin within the cytoplasm.¹⁸ Immunohistochemistry plays a crucial role in the differential diagnosis of EMPD. CK7 is stably expressed in EMPD.¹⁹ Trichorhinophalangeal syndrome type 1 (TRPS1) and CK20 serves as a reliable method to distinguish primary EMPD from secondary EMPD. Recent studies indicate that primary EMPD consistently exhibits diffuse and strong TRPS1 immunoreactivity, whereas the majority of secondary EMPD cases lack TRPS1 expression.²⁰ In addition, it should be noted that most primary PPD is also negative for TRPS1. Although CK20 can serve as an adjunct differential diagnostic marker, it should be noted that primary PPD cases may also express CK20.²¹ Other pagetoid intraepithelial lesions, including melanoma in situ and pagetoid squamous cell carcinoma in situ, should be considered in the histopathologic differential diagnosis, as they typically show SOX10 (SRY-Box Transcription Factor 10) and tumor protein p63 expression, respectively.^22,23 In patients with PPD who are negative for GCDFP-15 staining, the possibility of an underlying visceral malignancy, such as rectal carcinoma, should be carefully considered.^20,21 Additionally, positivity for NKX3.1 (NK3 Homeobox 1), uroplakin, or CDX2 should raise suspicion for an underlying malignancy, such as prostate carcinoma, urothelial carcinoma, or colorectal carcinoma.^24–26 Based on the finding of cancer at the anorectal junction, this patient was diagnosed with PPD of anorectal origin. Based on the reported case, patient with PPD may present symptoms directly associated with the primary disease, including increased bowel frequency, rectal bleeding, and other alterations in bowel habits. Laboratory tests (eg, CEA), digital rectal examination, colonoscopy, cystoscopy, and imaging evaluations should also be included in the diagnostic process for PPD. In female patients, colposcopy may also be necessary to exclude gynecological causes.

Although there are various treatment options, surgery remains the primary treatment for EMPD. In light of the potential diffuse spread of EMPD, wide local excision (WLE) with a 2–5 cm margin of normal skin has been a popular surgical option for a long time.^13,27 However, in patients undergoing WLE, the resulting large skin defects can pose significant challenges for reconstruction. Studies have shown that when combined with mapping biopsy, resection margins of 1 cm around well-demarcated lesions are reliable.^28–30 In the present case, the lesion margins were relatively clear. Combined with the negative result of preoperative mapping biopsy, a 1 cm margin resection was finally performed. Since the patient presented with secondary PPD originating at the anorectal junction, the therapeutic principles for anorectal adenocarcinoma were followed. No signs of local recurrence were observed during the 2-year follow-up period. In recent years, Mohs micrographic surgery (MMS) has also been applied in the treatment of EMPD.^31–33 However, due to the high time and labor costs associated with MMS, its use in EMPD treatment has not yet become widespread. Compared with MMS, combining preoperative mapping biopsy significantly reduces the duration of surgery while maintaining an equivalent local recurrence rate.³⁰ Prolonged operative time has been shown to be positively associated with a variety of postoperative complications, including surgical site infection, intraoperative or postoperative bleeding, and deep venous thrombosis.³⁴ Therefore, compared to intraoperative frozen section biopsy, preoperative mapping biopsy allows for more efficient intraoperative management and significantly reduces the duration of definitive surgery, which may help enhance patient tolerance and minimize surgical risks. Additionally, alternative treatments such as topical imiquimod cream, photodynamic therapy, radiotherapy, chemotherapy and targeted therapy are available for EMPD.^35–39

Although this report documents the patient’s treatment process and short-term outcome in detail, long-term follow-up was interrupted two years after surgery. As a result, long-term prognosis could not be assessed. In the future, studies involving more patients and long-term follow-ups should be conducted.

Conclusions

In conclusion, PPD secondary to adenocarcinoma of the anorectal junction is relatively uncommon in clinical practice. Early diagnosis and treatment of secondary PPD are critical for prognosis. Biopsy of the perianal lesion and conducting examinations, including digital rectal examination and colonoscopy, should be performed appropriately to avoid delaying diagnosis or misdiagnosis. Additionally, preoperative mapping biopsy may serve as an alternative technique for margin assessment.

Data Sharing Statement

The data involved in this study are available from the corresponding author upon reasonable request.

Ethics Approval and Consent to Participate

Written informed consent was obtained from the patient for the publication of this case report and the accompanying images. Institutional approval for the publication of anonymized case details was granted by the Ethics Committee of Hangzhou Third People’s Hospital. This study was performed in accordance with the Declaration of Helsinki.

Consent Statement

The authors confirm that they have obtained all necessary patient consent forms. Additionally, the patient provided written consent for the publication of both the case details and associated images.

Acknowledgments

Jun He and Rong-Chao He are co-first authors for this study. The authors would like to thank all the people involved in this work.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This work was funded by the Zhejiang Medical Health Science and Technology Project (Grant No. 2023KY922), Zhejiang Basic Public Welfare Research Project (Grant No. LY24H03005), General Project of Zhejiang Administration of Traditional Chinese Medicine (Grant No. 2024ZL734), Hangzhou Sciensuppce and Technology Bureau General Project (Grant No. 20220919Y011).

Disclosure

The authors declare no conflicts of interest in this work.

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