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Original article
Treatment of chlamydia and gonorrhoea, compliance with treatment guidelines and factors associatedwith non-compliant prescribing: findings form a cross-sectional study
  1. Anna Tisler-Sala1,
  2. Sven-Erik Ojavee2,
  3. Anneli Uusküla3
  1. 1 Department of Clinical Microbiology, Virology and Molecular Diagnostics, East-Viru Central Hospital, Kohtla-Jarve, Estonia
  2. 2 Department of Mathematics and Statistics, University of Tartu, Tartu, Estonia
  3. 3 Department of Family Medicine and Public Health, University of Tartu, Tartu, Estonia
  1. Correspondence to Anna Tisler-Sala, Department of Clinical Microbiology, Virology and Molecular Diagnostics, East-Viru Central Hospital, Tervise 1, 31025, Kohtla-Jarve, Estonia; annatisler{at}gmail.com

Abstract

Objectives Proper antibiotic treatment of STI reduces transmission, antimicrobial resistance and serious disease complications. In this study, we assessed compliance with STI treatment guidelines for genital gonorrhoea and chlamydia infections in Estonia.

Methods Prescription data from the Estonian Health Insurance Fund on 7556 treatment episodes of 6499 patients treated for gonorrhoea or chlamydia during 2012–2014 were analysed to assess compliance with the guidelines and factors associated with it.

Results Between 1 January 2012 and 31 December 2014, a total of 6074 patients were treated for chlamydia and 425 for gonorrhoea in Estonia. Among all prescriptions, 48.6% were non-compliant with gonorrhoea treatment guidelines and 3.8% for chlamydia. Non-compliant antibiotic treatment for gonorrhoea was associated with patient gender (female (adjusted OR (AOR)) 3.0, 95% CI 1.6 to 5.9), region (east AOR 3.3, 95% CI 1.3 to 8.2; west AOR 6.5, 95% CI 2.2 to 19.7) and prescribing physician specialty (general healthcare doctors: AOR 5.6, 95% CI 2.3 to 13.8; gynaecologists: AOR 5.9, 95% CI 2.8 to 12.4). Non-compliant antibiotic treatment for chlamydia was associated with younger patient age (15–24 AOR 0.5, 95% CI 0.4 to 0.7), region (north AOR 1.9, 95% CI 1.4 to 2.6; west AOR 2.3, 95% CI 1.5 to 3.4) and multiple treatment episodes (AOR 2.7, 95% CI 2.1 to 3.9). Approximately 14% of prescriptions were multiple treatments for the same patient for the same infection over the 3-year period (6.1% for gonorrhoea and 14.5% for chlamydia).

Conclusion There are significant differences in terms of compliance with treatment guidelines for gonorrhoea and chlamydia, and several factors associated with non-compliance that can potentially be targeted with interventions. Future research should explore reasons clinicians do not follow guidelines and examine ways to improve practice among doctors and patients and assess factors associated with multiple treatments, particularly multiple treatments for the same STI.

  • chlamydia trachomatis
  • antIbIotics
  • neisseria gonorrhoea
  • compliance
  • treatment

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Introduction

Optimal treatment for STI is a significant public health issue, given the health consequences of untreated infections which include pelvic inflammatory disease, infertility, pregnancy complications1 and facilitating HIV transmission.2 Treatment for STIs, including bacterial STIs, is an integral component of reducing STI transmission, particularly among young populations who may experience significant morbidity if left untreated.3 Non-compliant treatment, including use of the wrong antibiotics or subtherapeutic doses of antibiotics, can lead to multiple treatments for the same infection, undue burden on the healthcare system and, most importantly, the development of antibiotic resistance over time, reducing the clinical effectiveness of current treatments.4

Genital chlamydia and gonorrhoea account for nearly 95% of STIs in the European Union reported to the European Centre for Disease Prevention and Control, exclusive of HIV. Newly diagnosed cases of gonorrhoea have increased by 62% since 2010, with 52 995 cases reported in 2013. Similarly, chlamydia has increased by 7% to 384 555 cases reported in 2013.5

The European guidelines for the treatment and management of STI enable clinicians to prescribe appropriate antibiotic regimens, and provide guidance on appropriate dosages for treating specific bacterial infections.6 Several studies have evaluated physician adherence to STI guidelines in North America and Africa, and have shown gaps in doctors’ knowledge of the treatment guidelines and clear inconsistencies in prescribing patterns after STI diagnosis.7–9 However, there is a lack of research on adherence to STI treatment guidelines in Europe.

In this study, we assessed antibiotic treatment prescribed by doctors in Estonia for genital chlamydia and gonorrhoea to determine compliance with the European and Estonian STI guidelines. We also examined demographic factors and characteristics of clinicians associated with antibiotic prescribing that did not follow the guideline recommendations.

Methods

Data and data sources

Since the early 2000s, the Estonian Health Insurance Fund (EHIF) has maintained a complete record of inpatient and outpatient healthcare services provided to insured and uninsured patients. The EHIF database is a ‘reimbursement database’, and is considered to be relatively complete.10 In the EHIF, the type International Nonproprietary Name and the Anatomical Therapeutic Chemical (ATC) Classification System is used so medication can be identified as well as the amount purchased. It also identifies the date of prescription, date of purchase and details of the doctor who issued the prescription (including location and specialty). All pharmaceutical prescriptions include International Classification of Diseases (ICD-10) diagnostic codes. In Estonia, the requirement for a physician’s prescription to obtain antibiotics is strictly enforced.

The case definitions for chlamydia or gonorrhoea treatment episodes were based on identification of the infection-specific ICD-10 diagnosis codes on the prescriptions. Only urogenital chlamydia (ICD 10 codes: A56; A56.0; A56.1; A56.2; A56.8) and gonorrhoea (ICD 10 codes: A54; A54.0; A54.1; A54.2; A54.9) cases were included. We abstracted the following data from the EHIF database for each treatment episode:

  • medication (including the ATC code for the medication’s active ingredient, its trade name and the amount prescribed and purchased)

  • prescribing physician specialty; county of the healthcare institution where the prescription issuing physician was working (region)

  • prescription date (date prescription was issued) and the prescription status (filled, cancelled by the physician or not filled by the patient)

  • patient date of birth, gender and pseudoidentification code which allows for longitudinal tracking of the prescriptions issued to this person, but does not enable personal identification.

To assess compliance of STI treatment with the guidelines, the antibiotic and amount prescribed were compared with integrated recommendations from the European guideline on the diagnosis and treatment of gonorrhoea in adults11 the European guideline for the management of Chlamydia trachomatis infections12 and the Estonian guideline for STI treatment13 (see online supplementary appendices 1 and 2).

Supplementary appendix

Compliance was classified as compliant with the guidelines when the antibiotic and the amount of the recommended drug prescribed were in agreement with the guideline recommendations, or when the amount of the recommended drug prescribed exceeded the guideline recommendations. Non-compliance was classified as non-compliant with the guidelines, indicating that the prescribed drug was not listed in the guidelines for the recommended treatment of the STI, or the amount of drug prescribed was below the recommended amount.

Age groups were populated based on categories reported for STI prevalence in the Europe and the USA, and included 15–24, 25–34 and 35 and over categories.5 Doctor specialty was categorised using the three most visited doctor specialties as individual variables, and a fourth variable was generated for other specialties that saw 5% or fewer patients from the entire sample. Multiple prescriptions were defined as those given to the same patient for the treatment of the same disease during the 2012–2014 study period.

Statistical analysis

Prescription records were eligible for inclusion if the data on the name of the drug and the amount prescribed were available. Only prescriptions for antibiotics for systemic use were included in the analyses. We excluded all non-genital chlamydia and gonorrhoea treatment prescriptions and prescriptions given to patients under 15 years of age.

To describe demographic characteristics of patients (age, region and gender), we removed repeated records for individual patients (ie, repeated prescription episodes). Repeated treatment episodes for individual patients were not removed while describing doctor specialties (as we wanted to generate totals based on the number of prescriptions) and for multiple treatment episodes. 

We used univariate statistics to describe the treatments given to patients in Estonia. For continuous variables, mean and SD are presented; for categorical variables, percentages and absolute frequencies (n) are presented.

Bivariate analysis was used to explore demographic and doctor characteristics associated with treatments that did not comply with guidelines for gonorrhoea and chlamydia, and Χ2 tests were conducted to note statistically significant differences by STI. ORs and 95%CIs were calculated using reference groups based on the literature regarding STI models evaluating similar outcomes.14 Multivariable regression analysis with backwards deletion was used to examine factors from the bivariate analysis that were associated with treatments that did not comply with guidelines for gonorrhoea and chlamydia. Data were analysed using statistical packages STATA V.1215 and R V.3.0.2.16

The study procedures were in accordance with local data protection regulations. The analysis presented here is based on pre-existing records containing only non-identifiable data about individuals and was therefore exempt from ethical review.

Results

We collected all prescription records from the EHIF database for patients treated for gonorrhoea or chlamydia in Estonia from 1 January 2012 to 31 December 2014. A total of 8407 prescriptions for chlamydia or gonorrhoea treatment episodes were recorded in the database; an antibacterial drug for systemic use (oral administration or injection) was prescribed in 7556 treatment episodes. We excluded 851 prescriptions: 52 for non-urogenital chlamydia or gonorrhoea, 31 for patients under 15 years of age, 358 prescriptions that were cancelled (either by the prescribing physician or were not filled by patients, and therefore missing data on the amount of the drug prescribed), 96 prescriptions where the amount of prescribed drug was not specified and 314 prescriptions for non-systemic or non-antibacterial systemic use. Among excluded treatments (non antibacterials for systemic use), the most common were antibiotics for topical use (1.5%) or antimycotics for systemic use (ATC J02 code) (0.9%) (figure 1).

Figure 1

Flow chart showing the selection process for urogenital chlamydia and gonorrhoea treatment prescriptions included in the adherence analyses.

The subsequent analysis focuses on these 7556 prescriptions for systemic antibacterial medications that were prescribed to 6499 patients (20.3% men and 79.7% women). A significantly higher number of patients were treated for chlamydia (n=6074; 93.4%) compared with gonorrhoea (n=425; 6.6%).

Among those treated for genital chlamydia and gonorrhoea, there were significant differences (p<0.001 in all cases) in terms of gender, region, age and prescribing physicians’ specialty. Among those treated for gonorrhoea (n=425), there were similar numbers of men and women (47.3% and 52.7% respectively); the mean age of patients was 30.2 years (SD 10.5). The majority of treatments were prescribed by dermatovenereologists (42.4%) and gynaecologists (38.8%). Among those treated for chlamydia (n=6074), the majority of patients were female (81.6%), the mean age was 26.4 years (SD 8.6), and most patients were seen by gynaecologists (68.9%).

Of the 7556 prescriptions for chlamydia or gonorrhoea, 1057 (14%) were multiple prescriptions. A significantly higher proportion of multiple prescriptions were given for chlamydia (1031, 14.5%) than for gonorrhoea (26, 5.7%, p<0.001 by the Χ2 test).

Table 1 presents data on compliance with guidelines for treatments for chlamydia and gonorrhoea. Of the 451 antibiotic prescriptions issued for gonorrhoea, 48.6% (95% CI43.9% to 53.3%) did not follow treatment guidelines: in 47.9% (95% CI 43.2% to 52.6%), the antibiotics were not included in the guideline, and in 0.6% (95% CI 0.01% to 1.9%) a recommended antibiotic was prescribed but at a subtherapeutic dose. Of the 7105 antibiotic prescriptions for chlamydia, 3.8% (95% CI 3.4% to 4.3%) did not follow treatment guidelines: in 1.4% (95% CI 1.1% to 1.7%), the antibiotics prescribed were not included in the guideline, and in 2.4% (95% CI 2.1% to 2.8%) a recommended antibiotic was used, but at a subtherapeutic dose.

Table 1

Antibiotic prescriptions for urogenital gonorrhoea and chlamydia in Estonia 2012–2014

Tables 2 and 3 present bivariate and multivariate analysis of factors associated with non-compliant prescriptions for chlamydia and gonorrhoea. Non-guideline compliant antibiotic prescriptions for gonorrhoea were associated with patient gender (female adjusted OR (AOR) 3.0, 95% CI 1.6 to 5.9), region (east AOR 3.3, 95% CI 1.3 to 8.2; west AOR 6.5, 95% CI 2.2 to 19.7) and prescribing physician specialty (general healthcare doctors: AOR 5.6, 95% CI 2.3 to 13.8; gynaecologists: AOR 5.9, 95% CI 2.8 to 12.4; and other specialties AOR 10.0, 95% CI 4.6 to 21.8 compared with dermatovenereologists). For antibiotic prescriptions for chlamydia, non-guideline compliant treatment was associated with patient age (15–24 years AOR 0.5, 95% CI 0.4 to 0.7), region (north AOR 1.9, 95% CI 1.4 to 2.6; west AOR 2.3, 95% CI 1.5 to 3.4), prescribing physician specialty (other specialties: AOR 3.1, 95% CI 1.9 to 5.1 compared with dermatovenereologists) and multiple treatment episodes over the 3-year period (AOR 2.7, 95% CI 2.1 to 3.9).

Table 2

Factors associated with non-compliant antibiotic prescriptions for urogenital gonorrhoea in Estonia, 2012–2014

Table 3

Factors associated with non-compliant antibiotic prescriptions for urogenital chlamydia in Estonia, 2012–2014

Discussion

Using data from a nationwide population-based administrative database, our study documented high rates of antibiotic treatment non-compliance with guideline recommendations for gonorrhoea (48.6%) but low rates of non-compliant antibiotic prescribing for chlamydia (3.8%).

Results of the previous literature addressing physician adherence to the treatment guidelines for gonorrhoea showed that 14.9% of participants received non-recommended treatment. Therefore, our research results are not unexpected and outline the use of interventions to prove treatment adherence to the guidelines.7 The results of our study were consistent with prior studies that revealed high rates of adherence to guidelines for treating chlamydia.8

Our results differ significantly from a previous study examining prescription practices for STI treatment in Estonia published in 2004 (based on STI treatment prescription data from 2001 to 2002). The 2004 study documented non-compliant prescription rates of approximately 18% for chlamydia and 36% for gonorrhoea.17 Our results indicate that there has been a significant decrease in non-compliant prescriptions for chlamydia (from 18% to 3.8%) but a moderate increase in those for gonorrhoea (from 36.1% to 48.6%). The comparison of the two studies, one of which was conducted before and the other several years after adoption of the national evidence based/contemporary STI treatment guidelines allow us to speculate on the potential role of the guidelines on prescription practices. To our knowledge, there have been no significant changes on the system level (health insurance, healthcare organisation/provision, the numbers of healthcare specialists) or factors that may influence physicians’ STI treatment/prescription practices, and the number of STIs reported (and treated) in Estonia has declined over the past decade.18

We observed significantly different compliance rates for prescriptions for gonorrhoea and chlamydia. It may be that the route of medication administration (oral vs injection) affects physicians’ or patients’ decisions or preferences. In addition, doctors in Estonia do not dispense drugs. So, to receive the injected treatments patients have to fill the prescription and return with the medication to the doctor. Currently, the first line recommended treatment for gonorrhoea available in Estonia is a drug for parenteral use (ceftriaxone).

Additionally, frequency of a particular disease may have an effect on prescribing practices.19 Gonorrhoea is diagnosed significantly less often in Estonia than chlamydia (in 2014, the national notification rates for chlamydia and gonorrhoea were 115.8 and 10.3 per 100 000, respectively).18 In agreement with this, we found the ratio of prescriptions for chlamydia and gonorrhoea treatment to be 16 to 1 in our sample.

Multiple prescriptions (repeated treatment episodes of the same infection over the study period) made up 14% of the total number of prescriptions in the sample which is in line with other studies reporting a range of 6% to 26% multiple prescriptions for gonorrhoea and chlamydia treatment.20–22 The need for multiple treatment episodes can stem from various causes. A study that evaluated multiple treatment visits for chlamydia found that among women who made more than one visit for treatment, approximately 66% of infections were probably acquired from a new partner, 17% were re-infections from untreated or inadequately treated sexual partners, 14% were probable antibiotic treatment failures and 3% persisted without treatment.23 Our data do not allow us to distinguish between these different reasons. However, we found that among the multiple treatment episodes for gonorrhoea the proportion of prescriptions not in agreement with the guidelines was nearly 50%. Understanding the causes for multiple treatment episodes among patients with STI in Estonia is critical for informing tailored control measures.

Multiple treatment episodes of the same infection, treatment failure, treatment inconsistent with guidelines for treating the STI and lack of adherence with prescription regimens by patients are all factors that can lead to microbial resistance. This is particularly problematic in cases of gonorrhoea infections due to the high level of resistance documented with this STI.24 The results of this study clearly indicate that there is a need to ensure that treatment guidelines are followed, particularly for gonorrhoea, to reduce the development of resistance to treatments over time.

Our analysis of factors associated with prescription non-compliance with treatment guidelines for chlamydia and gonorrhoea revealed differences according to the region of the country and the prescribing physician’s specialty. Our results are consistent with previous research which suggested that patients who are diagnosed with STIs receive the most appropriate treatment from an STI specialist (ie, dermatovenereologist).25 Studies have shown that clinicians who see chlamydia and gonorrhoea cases frequently are more likely to be familiar with, and adhere to, clinical guidelines.26 These results may inform the development of a novel intervention to bridge the gap between knowledge and practice. However, this highlights the importance of continuous education of general medicine doctors, gynaecologists and other non-STI physicians who provide STI care.

Finally, we found that prescriptions for multiple treatments for chlamydia were less likely to comply with guidelines than those for single episodes. Educational efforts are needed to increase physician awareness of STI guidelines to assure optimal STI care in all settings.

Successful implementation of guidelines is a four-step process: development of evidence-based guidelines, dissemination and discussion, implementation with feedback and practitioner accountability.27 As clinical guidelines change and new management pathways are identified, national organisations should explore ways to follow the four-step implementation process more effectively. Previous studies have shown that non-adherence is multifactorial and includes lack of awareness about guideline updates, distrust and hesitancy to change, and complexity of the guidelines.28 29

Some possible ways to improve compliance with current guidelines may include use of computer-based decision support systems and guideline reminders which encourage doctors to adhere to guidelines and could motivate doctors to follow recommendations more closely.30 Future studies should evaluate the impact of different modes of communication (eg, online or in person meetings) in addition to continuous education for physicians about STI treatment.

Limitations

Several limitations to the study should be noted. First, we used administrative data from the National Health Insurance Fund; therefore, we could only assess a limited set of variables and there may have been confounding factors associated with treatments that were not included in the administrative data, such as patients’ behavioural characteristics (including number of sexual partners and use of contraception).

As we limited the data analysis to prescriptions that were filled by patients, a moderate number of prescriptions (n=358) in the sample were either cancelled (by doctors) or expired before they were filled (we were unable to discriminate between these two categories in the data). As a result, data on these prescriptions were not included in our analysis. However, we did not observe age or gender differences between patients with cancelled/expired versus their counterpart and given that the number of these prescriptions was low we speculate that there will be no major bias attached.

It is possible that errors in the database could introduce bias into the findings (such as incorrect filling of the prescriptions by the physician in terms of the diagnosis code or medication or data entry errors). However, given the database is relatively complete, and comes from official health insurance sources, these limitations are unlikely to be responsible for the overall results documented in this study.

We were unable to assess the effect of prescriptions that did not comply with guidelines as we did not have follow-up data on treatment success or failure for patients. The data collected here are cross-sectional data from yearly visits to doctors for STI treatment; for this reason, temporality cannot be established. Finally, as the prescriptions in this sample are from visits treating STIs, our findings about guideline adherence are not generalisable to other diseases and infections for which antibiotic therapy is indicated.

Conclusions

This study use a nationwide population-based administrative database in Estonia and documented high rates of non-compliant treatment for gonorrhoea and low rates of non-compliant treatment for chlamydia with several factors associated with non-compliance in multivariable analysis. Future studies should evaluate the factors among physicians that are associated with non-compliance, and qualitative data should be collected to explore these themes in greater detail. It is imperative that clinicians improve compliance with guidelines in the treatment of STIs, particularly for gonorrhoea, given the recent trends in antimicrobial resistance. Finally, organisations responsible for writing and implementing guidelines should explore new methods to disseminate their recommendations to doctors, in order to improve communication and compliance.

Key messages

  • High rates of non-compliant treatment for gonorrhoea warrant attention.

  • New methods of promoting guidelines to doctors should be explored.

  • Communication and compliance with guideline recommendations needs periodic monitoring.

Abstract translation

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

References

Footnotes

  • Handling editor Jane S Hocking

  • Contributors This paper was conceived by AT-S and AU. AT-S wrote the draft of the article with further contributions from AU and help from S-EO in carrying out statistical analysis. All authors interpreted data, reviewed successive drafts and approved the final version of the article.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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