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Abstract
Background The indiscriminate use of antibiotics has accelerated antimicrobial resistance (AMR) in Neisseria gonorrhoeae (NG), emphasising the need to follow treatment guidelines. This study aimed to assess the rate of adherence to standard treatment among patients with gonorrhoea and identify influencing factors.
Methods A survey was conducted in Guangdong province, China, involving uncomplicated gonorrhoea cases registered in the Chinese Information System for Disease Control and Prevention. Data on demographic characteristics and medical information were collected to determine the standard treatment rate, defined as the proportion of patients receiving treatment according to national guidelines (ie, a single dose of ceftriaxone 250 mg, spectinomycin 2 g, cefotaxime 1 g or other third-generation cephalosporins). Medication choices were documented. χ² tests and multilevel logistic regression were used to analyse factors associated with standard treatment.
Results The survey included 2424 patients with gonorrhoea from 59 hospitals. The standard treatment rate was 30.7% (743/2424), with 36.2% for females and 29.6% for males. Common reasons for substandard treatment included the use of non-guideline medications (42.3%, 710/1681) and incorrect dosing (36.2%, 605/1681). Factors associated with the standard treatment rate included gender, address, educational level, department, physicians’ training, number of diagnosed gonorrhoea cases and hospital level.
Conclusion The standard treatment rate for gonorrhoea in Guangdong province, China, is below expectations. Comprehensive measures, such as establishing a goal-directed monitoring system and implementing promotional activities, are needed to improve adherence to treatment guidelines.
- infection control
- public health
- epidemiology
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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STRENGTHS AND LIMITATIONS OF THIS STUDY
The study encompassed 15 cities, covering approximately 93.1% of the reported gonorrhoea cases in Guangdong province in 2019.
Comprehensive data from patients, physicians and hospitals were collected to analyse factors influencing adherence to standard treatment.
Sample bias may be present as the study did not include patients with gonorrhoea who did not visit the hospital or were misdiagnosed.
Some critical factors affecting whether patients with gonorrhoea received standard treatment may have been overlooked.
Background
Gonorrhoea, caused by the bacterium Neisseria gonorrhoeae (NG), is a significant global public health concern. It ranks as the second most common bacterial sexually transmitted disease (STD), with 87 million new cases reported worldwide in 2016 among individuals aged 15 to 49 years.1 In China alone, 117 938 new cases were reported in 2019,2 with Guangdong province accounting for over 23.7% (28 010 cases).3 Inadequate control and treatment of gonorrhoea can result in severe complications, including pelvic inflammatory disease, infertility, ectopic pregnancy, neonatal infections causing blindness and increased HIV transmission.1 These consequences place a substantial burden on both patients and public health systems.
The emergence of antimicrobial resistance (AMR) in NG has worsened the gonorrhoea epidemic. Over the years, the bacterium has developed resistance to many commonly used antibiotics,4 posing significant challenges for disease control. Surveillance data from 77 countries in 2014 revealed that NG exhibited resistance to ciprofloxacin in 70 countries (97%), azithromycin in 47 countries (81%) and extended-spectrum cephalosporins (ESCs) in 51 countries.5
The substandard treatment is a major driver of AMR in NG. To address this issue, countries and organisations regularly update gonorrhoea treatment guidelines based on surveillance data. In 2016, the WHO recommended two regimens: a single intramuscular (IM) dose of 250 mg ceftriaxone combined with a single oral dose of 1 g azithromycin and a single oral dose of 400 mg cefixime combined with a single oral dose of 1 g azithromycin.6 In 2020, the Centres for Disease Control and Prevention (CDC) in the USA and the European Centre for Disease Prevention and Control (ECDC) updated their guidelines.7 8 Concurrently, the latest Chinese guidelines recommended either a single dose of 1 g ceftriaxone (IM or oral) or a single dose of 2 g spectinomycin (4 g for cervicitis) for uncomplicated gonorrhoea.9 Despite these guidelines, a national survey revealed that only 37.8% of physicians adhered to standard treatment protocols.10
Guangdong Province, in southern China, accounts for nearly 9% of the country’s population and over 20% of reported gonorrhoea cases in the past decade.2 Between 2013 and 2020, high resistance levels to penicillin, tetracycline, ciprofloxacin, cefixime and azithromycin were documented, with resistance rates to spectinomycin and ceftriaxone reaching 7.63% and 16.18%, respectively.11 Previous studies have not evaluated adherence to treatment protocols at the provincial level. Therefore, we conducted a cross-sectional study to assess compliance with national treatment guidelines and identify influencing factors in Guangdong, China.
Methods
Study sites and population
The study covered 15 of Guangdong province’s 21 cities, representing about 93.1% of the province’s reported gonorrhoea cases in 2019. At least two hospitals per city were selected for the survey. The anticipated standard treatment rate (p) for patients with gonorrhoea, based on previous studies, was 37.8%.10 The allowable error was set at 0.1*p, with a significance level (α) of 0.05. Thus, a minimum of 1035 participants was required for the cross-sectional survey. The minimum sample size for each hospital was determined based on the ratio of reported gonorrhoea cases from 2017 to 2019. Cases were randomly selected from the Chinese Information System for Disease Control and Prevention (CISDCP), with a sampling ratio of 1:1:1 for 2017, 2018 and 2019. All cases were diagnosed by physicians in STD-related clinics according to the National Guideline of Diagnosis for gonorrhoea. Each diagnosis required exposure to a potential infection source, positive test results (gram stain smear, bacterial culture or nucleic acid testing method) and corresponding clinical symptoms. Eligible participants were individuals diagnosed with gonorrhoea between 2017 and 2019 at the selected study sites who received treatment at the corresponding hospitals. Patients with complications related to gonorrhoea were excluded from the study.
Data collection
Investigators from STD control institutions underwent comprehensive training for data collection. Participant information, including demographic data, was retrospectively gathered from the CISDCP. Diagnosis and treatment details were retrieved from the Hospital Information System of the respective hospitals (figure 1). The collected information comprised three components: (1) participant demographic and medical data, including age, marital status, educational level, occupation, place of residence, history of previous gonorrhoea infection, test method and time to onset of symptoms; (2) information regarding the diagnosing physicians, including professional title, department, recent training in STD treatment, number of gonorrhoea cases diagnosed in the past 6 months and receipt of the annual AMR test report; and (3) details about the diagnosing hospitals, including location, hospital level, STD laboratory level, types of gonorrhoea tests conducted and ability to provide drug susceptibility reports. All investigators were authorised by the local health bureau to manage clinical information of STD patients.
The flow chart of survey (with the number of resident populations in each region).
Measures
This study focused on the standard treatment rate, which is the proportion of patients with gonorrhoea receiving treatment according to the National STD Guidelines. These guidelines recommend ceftriaxone 250 mg IM or intravenous (IV) as a single dose, spectinomycin 2 g IM as a single dose, cefotaxime 1 g IM as a single dose or other effective third-generation cephalosporins. The investigators systematically assessed the dosage, frequency, duration and administration route (IM, IV or oral) for ceftriaxone, spectinomycin and cefotaxime to ensure compliance with Chinese guidelines. They also compared usage of other third-generation cephalosporins with provided instructions.
Statistical analysis
The database was created using Epidata 3.0, with all data entries double-checked for consistency. Data analysis was conducted using R Software (version 4.2.0). The χ² test was used to examine the associations between receiving standard treatment and various variables of patients with gonorrhoea. Prescriptions deviating from guidelines were analysed to speculate on potential reasons for non-compliance. Furthermore, multilevel logistic regression modelling was employed to assess the relationships between standardised treatment and the selected variables, with ORs and 95% CIs calculated and reported. A p value below 0.05 was considered statistically significant.
Patient and public involvement
None.
Results
Demographic characteristics of patients with gonorrhoea
Data were collected from a total of 2424 patients with gonorrhoea, with 743 (30.7%, 743/2424) receiving treatment according to guidelines. Most patients were male (84.3%), aged 21–30 years (43.3%) and over half were married (51.3%). Regarding education, 27.8% had completed junior high school, while 31.6% had completed high school. The most common occupations were in business services (29.3%) and as workers (23.7%) (table 1).
Demographic characteristics of participants
Medication choices and applications
Among the 743 patients receiving standard treatment, most (66.8%) were treated with ceftriaxone, followed by cefixime (19.8%). However, a substantial proportion of patients (69.3%, 1681/2424) did not receive the recommended treatment according to current Chinese guidelines. Of these, 42.3% (710/1681) received medications not aligned with the guidelines, 36.2% (605/1681) received inappropriate doses and 21.5% (362/1681) had improper treatment durations. The most commonly misused drugs were second-generation cephalosporins (27.5%) and azithromycin (25.9%). Among those receiving inappropriate doses, the majority (60.4%) were due to overdosing (table 2).
Medication choices and applications of the prescription against the guideline
Factors associated with the standard treatment rate
The multilevel logistic regression analysis revealed several factors associated with receiving the standard treatment among patients with gonorrhoea. Male patients (OR: 0.73, 95% CI: 0.57 to 0.92), those in urban areas (OR: 0.55, 95% CI: 0.36 to 0.83) and those with a middle school education (OR: 0.63, 95% CI: 0.46 to 0.85) were more likely to receive standard treatment. Among physicians, those in the gynaecology and obstetrics department (OR: 1.46, 95% CI: 1.13 to 1.89), those who received internal training (OR: 3.38, 95% CI: 2.12 to 5.38) or external training (OR: 3.74, 95% CI: 2.42 to 5.79) in the past 3 months, those who diagnosed fewer than five gonorrhoea cases (OR: 0.52, 95% CI: 0.34 to 0.79) in the past 6 months and those using the gram stain smear method (OR: 0.78, 95% CI: 0.62 to 0.92) were more likely to have patients receive the standard treatment. Patients treated in municipal-level hospitals (OR: 1.47, 95% CI: 1.16 to 1.88) were more likely to receive standard treatment, whereas those treated in provincial-level hospitals (OR: 0.12, 95% CI: 0.02 to 0.92) were less likely (table 3).
Factors associated with the compliance rate of patients with gonorrhoea
Discussion
This study identified a low standard treatment rate among patients with gonorrhoea in Guangdong province, including an analysis of medication choices and prescription practices. Factors associated with the standard treatment rate were also identified, providing compelling evidence to support the promotion of the standard treatment among patients with gonorrhoea.
In comparison to the national survey in China (37.8%)10 and two studies in Shenzhen (66.4% and 76.3%, respectively),12 13 our study found a lower standard treatment rate. The national survey determines the standard treatment rate based on physician questionnaires, while our research assesses it by collecting patient prescriptions, which may explain the difference in rates. Shenzhen, as the leading economy in South China, has superior medical institutions and higher medical standards than the regional average in Guangdong,14 possibly contributing to the higher prevalence of the standard treatment in Shenzhen. Additionally, developed countries such as the USA and Europe demonstrate greater adherence to recommended regimens15 16 compared with China.
Some studies suggest that performing antimicrobial susceptibility testing (AST) of NG to guide individualised prescriptions may be more effective than relying solely on guidelines.17 However, the gold standard methods for AST of NG are laborious and time-consuming,18 highlighting the need to promote novel AST methods for routine clinical use.19 20 While two-thirds of the surveyed hospitals are capable of providing drug susceptibility tests for patients, specific application data for NG-positive patients were not collected in this survey. Considering the periodic revision of gonorrhoea treatment guidelines to incorporate the latest evidence on emerging trends in antimicrobial susceptibility, raising awareness about the increasing antibiotic resistance of NG and promoting the adoption of national gonorrhoea treatment guidelines are crucial to control the gonorrhoea epidemic.
In most cases, physicians determined treatment prescriptions, limiting patients' options due to their lack of professional treatment knowledge. Over 60% of patients in the compliance group received ceftriaxone as the first-line drug, aligning with preferences observed in other studies.15 21 Incorrect drug selection and dosage accounted for approximately three-quarters of cases not receiving the standard treatment. Physicians may have overlooked the possibility of treatment failure when prescribing second-generation cephalosporins, azithromycin and other antimicrobials.10 Moreover, many physicians tend to base antimicrobial doses and treatment durations on their experience rather than following national guidelines, often opting for higher doses or longer courses to ensure effectiveness.22 However, insufficient clinical data supported the effectiveness of overdose and longer-course treatment, which could contribute to AMR of NG and lead to adverse reactions in patients.
Based on the findings of this study, several actions should be considered. First, although the Gonococcal Resistance to Antimicrobials Surveillance Programme has been active for over four decades, there is currently no monitoring mechanism for gonorrhoea treatment in China. Implementing such a mechanism can help identify intervention opportunities and improve provider adherence.15 Furthermore, since even the latest guideline may not fully reflect the real drug resistance trends in a patient with gonorrhoea, drug susceptibility testing is recommended for each patient whenever the service is available. Physicians who received training were more likely to adhere to guidelines, underscoring the importance of regular STD gonorrhoea treatment training for physicians, particularly those with less experience in diagnosing gonorrhoea. Lastly, many individuals infected with gonorrhoea remain undiagnosed due to asymptomatic infections and misdiagnoses in hospitals.23 To address this, increased testing should be provided to populations at high risk of NG infection, particularly among young individuals.
This study has limitations. Patients with gonorrhoea who did not visit the hospital or were misdiagnosed may introduce sample bias. Various factors can influence whether patients receive the standard treatment, such as the availability of guidelines and medication, hospital double-check procedures for prescriptions and physician work experience, which may have been overlooked. Moreover, patients detected by routine screening without symptoms were more or less likely to be underdosed than those presenting with symptoms, while patient symptoms were unavailable in this survey. Lastly, recall bias may exist in the questionnaire survey for physicians.
Conclusion
Adherence to gonorrhoea guidelines in Guangdong province, China, is suboptimal. Addressing this requires implementing comprehensive measures, including establishing a robust monitoring system to ensure guideline compliance and enhancing training programmes for physicians specialising in STDs to promote the standard treatment for patients with gonorrhoea.
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
Ethics statements
Patient consent for publication
Ethics approval
This study involved human participants and was approved by the Ethics Review Committee of Dermatology Hospital of Southern Medical University (2022019). Participants gave informed consent to participate in the study before taking part.
Acknowledgments
We would like to thank all the investigators from STD control institutions and physicians at the selected hospitals who contributed to the completion of this study.
Footnotes
Contributors HZ and CW were responsible for the study conception and design and critically reviewed the final manuscript. MX curated the data with input from MY. MX conducted the data analysis and drafted the manuscript with inputs from CW. SH, PZ and XW provided iterative reviews and critical comments. HZ and CW acted as guarantors of the work, accepted full responsibility for the work, had access to the data and controlled the decision to publish. All the authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Funding This research has been funded by Basic and Applied Basic Research Fund of Guangdong Province (No. 2022A1515110895) and Guangdong University Youth Innovation Talent Project (No. 2021KQNCX011).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.