Population-Level Provider Compliance With Provincial Treatment Guidelines for the Management of Gonorrhea in Adolescents and Adults in Alberta, Canada; 2000 to 2019

Abstract

Background 

Appropriate antimicrobial therapy is one of the essential strategies in the global control of gonorrhea. We sought to determine the provider compliance with provincial treatment guidelines for gonococcal infections in Alberta, Canada, and to identify characteristics associated with provider noncompliance.

Methods 

A retrospective population-based analysis of gonorrhea treatment from January 1, 2000, to December 31, 2019, using data extracted from a communicable disease database was performed. Prevalence ratios were calculated for provider compliance to treatment guidelines of patient, infection, and treating provider characteristics.

Results 

We identified a total of 42,875 cases of gonorrhea, 58.3% were men, 40.3% were White, 28.2% were First Nations, and 16% were “unknown ethnicity.” Most cases were treated by family physicians (43.4%), sexually transmitted infection (STI) clinics (31.9%) and urgent care centers/hospitals (10%). Overall, there was 80.3% provider compliance with treatment guidelines. Provider compliance to treatment guidelines had the highest rates of compliance when treatment was provided by STI nurses in correctional facilities, STI clinics, and treatment of men having sex with men (94.7%, 91.7%, and 87.5%, respectively). Provider compliance to treatment guidelines was lowest when treating women (75.5%), pregnancy status (68.4), individuals of “unknown race/ethnicity” (74.8%), and those treated in urgent care centers and emergency department (66.7%).

Conclusions 

Delivery of STI care by nurse-led models had the highest level of compliance with treatment guidelines. Our study informs areas for targeted interventions to improve the uptake of treatment guidelines, including the provision of treatment in urgent care centers and among women.

In Brief

A population-based study found that treatment of gonorrhea among women compared with men, and in urgent care centers compared with outpatient settings, was less likely to follow the treatment guideline recommendations.

Gonorrhea is the second most common notifiable infection in the Canadian province of Alberta.¹ From 2000 to 2019, the incidence of cases of gonorrhea increased 7-fold.¹ Gonorrhea is a major public health concern because of its possible complications and sequelae, the increased risk of transmission and acquisition of HIV, and the increasing antimicrobial resistance to drugs previously and currently recommended for its treatment.² The control of gonorrhea has relied on measures of primary prevention, screening, and management with an effective, accessible, and inexpensive antimicrobial, partner notification, and active surveillance.³

Alberta's sexually transmitted infection (STI) treatment guidelines provide recommendations for screening, diagnosis, and treatment of STIs including gonococcal infection in adolescents and adults.⁴ These guidelines have been updated over time in response to the emergence of antimicrobial resistance and the availability of antimicrobials with activity against Neisseria gonorrhoeae. Since the introduction of the first provincial treatment guideline in 1995, there have been 5 new updates. The present study aimed to examine the provider compliance to provincial gonorrhea treatment guidelines in Alberta from 2000 to 2019 and to identify possible patient, infection, or health care provider characteristics associated with lower provider compliance to treatment guidelines.

METHODS

Study Design

This is a retrospective population-based study of the provider compliance with Alberta treatment guidelines for the management of gonococcal infections from January 1, 2000, to December 31, 2019, in individuals 16 years and older. In Alberta, all positive gonorrhea results are reported to the provincial STI program according to the Public Health Act. Oral treatment is dispensed for free to patients at the time of the encounter and is recommended as observed therapy. In 2012, prepackaged oral antibiotics started to be distributed to clinics and hospitals to treat chlamydia and gonorrhea. When injectable drugs are required, these are administered during the clinic visit or hospital stay free of cost. Treating providers are required to submit a Notification of STI form with the treatment information. All cases not meeting treatment guidelines are referred to the provincial team of Partner Notification Nurses (PNNs) who follow up with the treating provider and patient to ensure retreatment according to guidelines or a test of cure. We obtained deidentified data from the Communicable Disease Reporting System for cases from 2000 to 2016 and the Communicable Disease and Outbreak Management system for 2017 to 2019. Both reporting systems compiled data from the Notification STI form, containing the same variables.

A unique case of gonorrhea was defined as an individual with one or multiple sites of gonococcal infection (genital and extragenital) identified on the same date. Infection with gonorrhea was defined as a positive nucleic acid amplification test result and positive N. gonorrhoeae culture from urogenital (vaginal, cervical, urine, urethra), rectal, or pharyngeal sites. Provider compliance with treatment guidelines was defined as the selection and administration of preferred or alternative antibiotics recommended by treatment guidelines, and the dose was the same or higher as the guideline recommendation. Provider noncompliance with treatment guidelines was defined as treatment with drugs not listed in the guideline, or the dose of the recommended or alternative drugs used was lower than the dose listed in the current guideline, as summarized in Table 1. During the study period, 5 different treatment guidelines were released (1998, 2003, 2008, 2012, and 2018). In these guidelines, the recommended treatment for gonorrhea has been a combination of 2 different drugs with different mechanisms of action to prevent the emergence of antimicrobial resistance. The second drug is also active for the management of chlamydial infections.

TABLE 1 - Summary of Alberta Treatment Guidelines for Gonorrhea, 2000 to 2019

Guideline Year	Population Anatomic Site	Population Anatomic Site	Pregnancy
1998	Adolescents/adults* Urethral, cervical, rectal, pharyngeal (all sites)
Recommended	Ciprofloxacin 500 mg po SD or Cefixime 400 mg po SD or Ceftriaxone 250 mg IM SD plus Azithromycin 1 g po SD or Doxycycline 100 mg po bid × 7 d		Cefixime 400 mg po SD or Ceftriaxone 250 mg IM SD plus Azithromycin 1 g po SD or Erythromycin 250 mg qid × 14 d or Erythromycin 500 mg qid × 7 d
Alternative	N/A
2003	Adolescents/adults* Urogenital, rectal sites	Adolescents/adults* Pharyngeal site	Pregnancy
Recommended plus coverage against chlamydia	Ciprofloxacin 500 mg po SD* or Cefixime 400 mg po SD	Ciprofloxacin 500 mg po SD or Cefixime 400 mg po SD	Cefixime 400 mg po SD
Alternative plus coverage against chlamydia	Ceftriaxone 125 mg IM SD	Ceftriaxone 250 mg IM SD	Ceftriaxone 125 mg IM SD or Spectinomycin 2 g IM SD
2008	Adolescents/adults* Urethral, cervical, rectal, pharyngeal (all sites)		Pregnancy
Recommended	Cefixime 400 mg po SD or Ceftriaxone 125 mg IM SD	All patients should be also treated for CT: azithromycin 1 g po SD or Doxy 100 mg po bid × 7 d	Ciprofloxacin contraindicated Co-Rx for CT: amoxicillin 500 mg tid po × 7 d
Alternative	Spectinomycin 2 g IM SD
2012	Adolescents/adults† Heterosexual, pregnant Urethral, cervical, rectal	Adolescents/adults† MSM/pharyngeal
Recommended	Cefixime 800 mg po SD plus Azithromycin 1 g po SD	Ceftriaxone 250 mg IM SD plus Azithromycin 1 g po
Alternative	Spectinomycin 2 g IM SD plus Azithromycin 1 g po SD† or Azithromycin 2 g SD†	Cefixime 800 mg po SD plus Azithromycin 1 g po SD
2018	Adolescents/adults Heterosexual/pregnant Urethral, cervical, rectal	Adolescents/adults MSM/pharyngeal	Pregnancy
Recommended	Cefixime 800 mg po SD plus Azithromycin 1 g po SD	Ceftriaxone 250 mg IM SD plus Azithromycin 1 g po SD
Alternative	Ceftriaxone 250 mg IM SD plus Azithromycin 1 g po SD or Azithromycin 2 g po SD plus Gentamicin 240 mg IM SD† or Azithromycin 2 g po SD plus Gemifloxacin 320 mg po SD†	Cefixime 800 mg po SD plus Azithromycin 1 g po SD or Azithromycin 2 g po SD plus Gentamicin 240 mg IM SD or Azithromycin 2 g po SD plus Gemifloxacin 320 mg po SD	Gentamicin or gemifloxacin not recommended

*Only to be used if susceptibility testing is available.

^†Only for penicillin/cefixime allergy.

bid indicates twice a day; IM, intramuscularly; po, orally; qid, 4 times a day; tid, 3 times a day.

Data extracted from the Communicable Disease Reporting System and Communicable Disease and Outbreak Management included age, sex, partners' sex, race/ethnicity, pregnancy status, infection site(s), testing modality (molecular testing, culture), coinfection with chlamydia, date of diagnosis, gonococcal complications (epididymo-orchitis, pelvic inflammatory disease, disseminated disease), and geographic area where treatment was provided (metro center, metro influenced, urban, and moderate urban-influenced were grouped as urban areas; rural, rural center, and remote areas were grouped as rural areas), as defined by Alberta Health⁵; treating provider setting was categorized as STI clinic, community-based general practitioner, community-based specialist, hospital, acute care center, reproductive health clinic, and correctional facilities, based on the information of location (hospital vs. community) and credentials of treating provider entered in the reportable form. This study was approved by the Research Ethics Board of the University of Alberta (REB-Pro00026513).

Statistical Analysis

Provider compliance with treatment guidelines was coded using a stepwise procedure. First, cases were categorized based on the drugs used (guideline-recommended drugs vs. drugs not listed in guidelines), those cases treated with guideline-recommended drugs were further categorized based on the treatment dose (recommended dose and higher dose vs. lower dose), and finally, the cases treated with the drugs and dose according to guidelines were categorized based on the duration of treatment (recommended duration vs. shorter duration). We coded cases that were treated according to treatment guidelines (drugs, dose, and duration) versus those cases who did not (provider-noncompliant). Only cases with full information on treatment including drugs, dose, and duration of treatment were included in the analysis to ascertain compliance with treatment guidelines.

Patients, infections, and health care providers' characteristics were described using percentages for categorical data, and median and SD for continuous data. Time to treatment was calculated based on the difference in days from the date the sample was collected to the time of the administration of the treatment.

Effect measurement was reported with prevalence ratios (PRs). Prevalence difference (PD) of provider compliance was calculated for all the patient, infection, and provider characteristics. Complicated gonococcal infections were not included in the analysis because of a lack of specific recommendations for the management of these infections in the treatment guidelines where it is suggested to consult an infectious disease specialist. Statistical analysis was done on STATA version 14.2 (StataCorp, College Station, TX).

RESULTS

A total of 58,742 specimens of confirmed gonorrhea were identified during the study period. A total of 15,867 specimens were excluded: 13,500 because of duplication of samples of the same anatomical site collected simultaneously for culture and nucleic acid amplification test, 560 specimens corresponded to individuals younger than 16 years, and 1800 specimens had missing treatment information (drug, dose, and duration). We included 42,875 unique cases of gonorrhea in the study analysis (Fig. 1). The cases excluded had no significant differences in patient, provider, and infection characteristics compared with the cases included in the study (data not shown).

Figure 1: Flow diagram of gonorrhea cases included in the study.

During the 20-year study period, an overall average of 80.3% of provider compliance with Alberta treatment guidelines was achieved. There was variability in the uptake of the guidelines throughout the studied years. The average uptakes for the guidelines released in 1998, 2003, 2008, 2012, and 2018 were 80.5% (range, 76.6%–83.5%), 78.2% (77.1%–83.4%), 67.8% (65.9%–68.5%), 82.7% (54.7%–89.7%), and 87.2% (85.9%–88.4%), respectively. Interestingly, the first quarter of 2012, after the introduction of the updated guideline, had the lowest compliance rate at 32%. In general, the average time to reach the previous average compliance to treatment guidelines after the introduction of an updated guideline was 1 year (Fig. 2). Throughout the study period, 964 cases labeled as provider-compliant with treatment guidelines were treated with a higher dose of antibiotic(s) than the recommended dose at the time of the guideline. Cefixime was given in higher doses in 515 cases, ceftriaxone in 32 cases, azithromycin (in combination with other recommended agent) in 406 cases, and ciprofloxacin in 11 cases.

Figure 2: Percentage of compliance to Alberta treatment guidelines for the management of gonorrhea cases by quarters of the year from 2000 to 2019.

Patient Characteristics

A total of 24,979 patients were men (58.3%; Table 2). The mean ± SD age was 29 ± 9.8 years, and 95.6% of the cases were between the ages of 16 to 49 years. A majority of cases were diagnosed among individuals self-identifying as White (17,258 cases; 40.3%), followed by First Nations (12,085 cases; 28.2%) and Afro-Caribbean Black (2,481 cases; 5.8%).

TABLE 2 - Provider Compliance With Provincial Treatment Guidelines for Gonorrhea, Alberta, 2000 to 2019

	Provider- compliant (n = 34,411)		Provider-noncompliant (n = 8464)		Total (N = 42,875)		Prevalence Ratio	Prevalence Difference (Per 100)
	n	%	n	%	n	%	0.8
Patient's characteristics
Sex
Male	21,107	84.5	3872	15.5	24,979	58.3	1.2	9
Female	13,517	75.5	4379	24.5	17,896	41.6
Pregnant (yes)*	849	68.4	393	31.6	1242	6.9	0.89	−8
Age group, y
16–19	5122	77.3	1506	22.7	6628	15.5	0.90	−8
20–29	16,294	80	4072	20	20,366	47.5	1	0
30–39	8458	81.9	1876	18.2	10,334	24.1	1.02	2
40–49	2966	81.7	665	18.3	3631	8.5	1.01	2
50–59	1190	81.8	265	18.2	1455	3.4	1.01	2
60–69	335	82.9	69	17.1	404	1	1.03	3
70–79	41	82	9	18	50	0.1	1.03	3
>80	5	71.4	2	28.6	7	0.02	0.89	−9
Sexual behavior†
Heterosexual	14,001	80.3	3445	19.8	17,446	53.2	0.92	−7
MSM	5105	87.5	729	12.5	5834	15.4	1.08	7
Bisexual	395	90.4	42	9.6	437	1.2	1.09	8
WSW	111	74	39	26	150	4.9	0.9	−8
Race/Ethnicity
White	14,176	82.1	3082	17.9	17,258	40.3	1.03	3
Afro-Caribbean Black	2090	84.2	391	15.8	2481	5.8	1.05	4
Asian	1470	82.5	312	17.5	1782	4.2	1.03	3
First Nations	9774	80.1	2311	19.9	12,085	28.2	1	0
Metis	1608	80.9	378	19.1	1986	4.6	1	0
Inuit	48	84.2	9	15.8	57	0.1	1.05	4
Middle East	153	89.5	18	10.5	171	0.4	1.11	9
Hispanic	179	88.2	24	11.8	203	0.5	1.1	8
Unknown	5126	74.8	1726	25.2	6852	15.9	0.91	−7
Gonococcal infection characteristics
Site of infection
Cervical	5343	68.9	2409	31.1	7752	18.1	0.84	−13
Vaginal	853	75.6	275	24.4	1128	2.6	0.95	−4
Pharynx	3284	86.7	503	13.3	3787	9.9	1.08	7
Rectum	2102	83.9	402	16.1	2504	5.9	1.05	4
Urine	15,030	80.6	3616	19.4	18,646	45.4	1.01	1
Urethra	7730	86.4	1212	13.6	8944	21.6	1.02	2
Reason for visit‡
Symptomatic	14,359	85.2	2492	14.8	16,851	49.3	1.09	9
Contact	3449	87.0	515	12.9	3964	13.8	1.1	10
STI screening	7177	85.4	1224	14.6	8401	29.7	1.1	10
Sexual assault	223	90.6	23	9.4	245	1	1.17	17
Therapeutic abortion	214	68.2	100	31.9	314	1.4	0.86	−11
Presenting symptoms§
Dysuria	8673	86.5	1353	13.9	10,026	23.4	1.04	4
Rectal symptoms¶	658	84.1	125	15.9	783	1.8	1.01	1
Physical examination
Vaginal discharge	3429	75.4	1121	25.6	4550	57.1	0.91	−8
Cervical discharge	961	73.9	339	26.1	1300	20.1	0.88	−14
Friable cervix	424	76.5	130	23.5	554	9.0	0.92	−6
Urethral discharge	8857	87.6	1256	12.4	10,113	46.9	1.1	6
Chlamydia coinfection	3158	84.5	579	15.5	3737	8.7	1.05	5
Treatment provider's characteristics
Geographic area∥
Urban	27,856	80.7	6655	19.28	34,511	80.5	1	0
Rural	6768	80.9	1596	19.1	8364	19.3
Treating HCP setting**
Community general	5388	84.4	993	15.6	6381	43.4	1.03	3
Community specialist	136	83.4	27	16.6	163	1.2	1.03	3
STI clinic	4026	91.7	367	8.4	4393	31.9	1.14	12
Hospital/Acute care/ED	917	66.7	458	33.3	1375	10	0.75	−21
Reproductive health clinic	596	86.1	96	13.9	692	5	1.02	1
Correctional facility	643	94.7	36	5.3	679	4.9	1.11	10
Same-day treatment	16,961	84.8	3030	15.2	19,991	46.8	1.09	8
Treatment from time of diagnosis, mean ± SD, d	6.6	17.2	8.1	17.5	6.9	17.3

*Percentage of self-reported pregnancy status (out of the total women).

^†Information was available only in 23,868 cases.

^‡Data only available in 34,197 cases.

^§Data only available in 27,297 cases.

^¶May include rectal pain, rectal discharge, and rectal bleeding. Data only available in 26,721 cases.

^∥Geographic area where the patient was treated. Data available on 42,712 cases.

**Data were only available on 13,754 cases, including cases from 2000, 2010, 2011, and 2017 to 2019.

HCP indicates health care provider; WSW, women having sex with women.

Women self-reported being pregnant in 6.8% of cases. Men were more likely to be treated by providers with regimens recommended by the guidelines as compared with women (PR of 1.2, PD of 9), meaning that, among men, there were 9 excess cases of provider compliance per 100 compared with women. Only 31.6% of self-reported pregnant women received guideline-recommended treatment compared with 68.4% of nonpregnant women (PR 0.89, PD −8). In addition, providers showed lower uptake of compliance to guidelines among individuals of extremes of age, age group 16 to 19 years (77.3%; PR, 0.90; PD, −8) and older than 80 years (71.4%; PR, 0.89; PD, −9) compared with the overall provider-compliance rate of 80.3%. In contrast, treatment provided to men having sex with men (MSM; 87.5%; PR, 1.08; PD, 7) and bisexual men (90.4%; PR, 1.09; PD, 8) had the highest rates of provider compliance to treatment guidelines. Provider compliance with treatment guidelines was greater than 80% for all race/ethnicity groups except for individuals reported as “unknown” race/ethnicity (74.8%; PR, 0.91; PD, −7). Provider compliance to treatment guidelines rates was lower among women from all race/ethnicities compared with men except those from the Middle East (89.5% vs. 89.5%, respectively; PR, 1) as shown in Table 3.

TABLE 3 - Provider Compliance with Provincial Treatment Guidelines for Gonorrhea by Sex, Alberta, 2000 to 2019

Patient's Characteristics	Provider Compliant (n = 34,411)				Provider Noncompliant (n = 8464)				Prevalence Ratio	Prevalence Difference
	Women %		Men		Women		Men
	N	%	N	%	N	%	N	%
	13,517	75.5	21,107	84.5	4379	24.5	3872	15.5	0.9	−9
Age group, y
16–19	3355	75.9	1803	81.7	1067	24.1	403	18.3	0.92	−6
20–29	6731	75.4	9680	84.7	2200	24.6	1753	15.3	0.89	−9
30–39	2556	75.7	5951	85.5	819	24.3	1008	14.5	0.88	−10
40–49	678	75.5	2297	84.1	220	24.5	436	15.9	0.89	−9
50–59	166	73.8	1024	83.3	59	26.2	206	16.8	0.88	−8
60–69	29	69.1	306	84.5	13	30.9	56	15.5	0.81	−15
70–79	1	50	40	83.3	1	50	8	16.7	0.6	−33
>80	0	0	5		0	0	2	28.6	—	—
Sexual behavior*
Heterosexual	10,156	77.1	3845	89.9	3017	22.9	428	10	0.86	−13
Race/Ethnicity
White	4365	75.5	9811	85.5	1417	24.5	1665	14.5	0.88	−10
Afro-Caribbean Black	377	75	1713	86.6	126	25	265	13.4	0.86	−12
Asian	314	74.7	1156	84.9	106	25.3	206	15.1	0.88	−10
First Nations	5687	77.6	4087	85.9	1641	22.4	670	14.1	0.9	−8
Metis	859	77.3	749	85.6	252	22.7	126	14.4	0.9	−8
Inuit	28	77.8	20	95.2	8	22.2	1	4.8	0.82	−17
Middle East	17	89.5	136	89.5	2	10.5	16	10.5	1	0
Hispanic	21	84	158	88.8	4	16	20	11.2	0.95	−5
Unknown	1823	69	3303	78.4	818	30.9	908	21.6	0.88	−9
Site of infection
Throat	977	86.7	2324	87.4	150	13.3	336	12.4	0.99	−1
Rectum	671	80.8	1441	86.1	159	19.2	233	13.9	0.93	−5.3
Urine	5451	78.7	9628	82.2	1477	21.3	2089	17.8	0.96	−3
Reason for testing†
Symptomatic	3848	80.1	10,511	87	924	19.4	1568	13	0.92	−7
Contact a case	1144	82.4	2308	89.6	244	17.6	268	10.4	0.92	−7
Screening	1972	77.5	5222	89.2	573	22.5	634	10.8	0.88	−12
Sexual assault	207	91.6	18	94.7	19	8.4	1	5.26	0.96	−3
Presenting symptoms
Rectal symptoms‡	148	76.7	510	86.4	45	23.3	80	13.6	0.89	−9.7
Chlamydia coinfection	1553	84	1605	85.1	297	16.1	282	14.9	0.99	−1
Multisite infection	1402	85.1	1596	90.6	245	14.9	165	9.4	0.94	−6
Geographic area
Urban	10,177	74.7	17,679	84.7	3450	25.3	3205	15.3	0.88	−10
Rural	3314	78.2	3454	83.7	924	21.8	672	16.2	0.93	−6
Treating HCP setting§
Community general	2500	83.9	2914	85.7	481	16.1	486	14.3	0.98	−2
Community specialist	75	77.3	61	92.4	22	22.7	5	7.5	0.84	−15
STI clinic	1096	90.8	2944	92.4	111	9.2	242	7.5	0.98	−2
Hospital/Acute care/ED	380	60.8	589	78.5	245	39.2	161	21.5	0.77	−18
Sexual and reproductive health clinic	398	89	224	91.4	49	11	21	8.5	0.97	−2
Correctional facility	272	95.1	371	94.4	14	4.9	22	5.1	1.01	1
Same-day treatment	3862	76.4	13,099	87.7	1195	23.6	1835	12.3	0.87	−11
Treatment from time of diagnosis (IQR), d	9.7	0–10	4.5	0–5	9.9	0–10	6.3	0–7

*Data available only in 23,868 cases.

^†Data available only in 31,197 cases.

^‡May include rectal pain, rectal discharge, and rectal bleeding.

^§Data available only in 13,754 cases, including cases from 2000, 2010, 2011, and 2017 to 2019.

HCP indicates health care provider; IQR, interquartile range.

Infection Characteristics

Of 42,875 unique cases, a similar proportion of cases corresponding to urogenital sites were collected for women and men (88.6% vs. 82.3%, respectively; Table 2). Specimens from extragenital sites (throat and rectal) represented almost 16% of the total samples collected; they were more commonly collected in men (68%) than women (32%). Provider compliance with treatment guidelines was lower for women compared with men for infections at any anatomic site, except for the throat (86.7 vs. 87.4, respectively; PR, 0.99).

The majority of infections were symptomatic (49.3%), and they had higher rates of provider compliance with guideline recommendations compared with asymptomatic cases (85.2% vs. 77.8%; PR, 1.09; PD, 9). Women with abnormal vaginal discharge, cervical discharge, or friable cervix on physical examination had lower rates of provider compliance with treatment guidelines (75.4% [PR 0.9; PD, −8], 73.9% [PR 0.88; PD, −14], and 76.5% [PR, 0.92; PD, −6], respectively). Complications of N. gonorrhoeae including pelvic inflammatory disease (n = 545), epididymo-orchitis (n = 200), and disseminated gonorrhea (n = 9) were uncommon, representing 1.75% of the total cases.

Treatment Provider's Characteristics

Treating provider setting information was only available for 13,754 cases; Supplementary Table (https://links.lww.com/OLQ/A871) shows the characteristics of these cases, showing similar trends of rates of provider compliance with guidelines compared with the cases with treating setting data. Eighty-one percent of cases included in the analysis, were treated in urban areas. Overall, the rates of provider compliance with the treatment guidelines were similar among rural and urban areas (80.7% vs. 80.9%, respectively; PR, 1; Table 2).

Overall, provider compliance with treatment guidelines was higher in settings with STI nurse-led programs: STI clinics (91.7%; PR, 1.14; PD, 12) and correctional facilities (94.7%; PR, 1.11; PD, 10). In contrast, management of gonorrhea in hospitals, emergency departments (EDs), or urgent care centers was associated with lower rates of provider compliance (66.7%; PR, 0.75; PD, −21). Gonococcal infections among women were more likely to have lower rates of provider compliance to treatment guidelines throughout all treatment settings compared with men, especially in hospitals and urgent care centers (60.8%; PR, 0.77; PD, −18), and community specialists (77.3%; PR, 0.84; PD, −15), except in corrections facilities where the compliance was exceptionally high and similar to men (95.1% vs. 94.4%, respectively; PR, 1.01; PD, 1), as shown in Table 3.

Antimicrobial Use Patterns

From 2000 to 2006, the guideline-preferred antibiotic to treat gonorrhea was ciprofloxacin in combination with a second drug, followed by cefixime (range, 15%–22%) with <5% of ceftriaxone use. In 2008, cefixime was introduced as the preferred agent, it took 9 years to fully stop using ciprofloxacin. Since 2012, with the introduction of specific recommendations for the management of infections in MSM and pharyngeal infections, the usage of ceftriaxone increased from 5% to up to 35% in 2014. From 2012 to 2019, there has been a slow but steady increase in the use of azithromycin monotherapy from 3.5% to 6% (Fig. 3).

Figure 3: Antimicrobial usage trend for the treatment of gonorrhea in Alberta from 2000 to 2019.

DISCUSSION

This retrospective population-based study found high rates of provider compliance with the treatment guidelines for the management of gonococcal infections of 80.3% among individuals 16 years and older over 20 years in Alberta, Canada. We surmise that this level of compliance was achieved owing to the role of the PNNs in the centralized STI program following up on all cases that did not meet treatment based on guidelines, allowing the PNN to inform providers on appropriate management and availability of prepackaged STI medications for the treatment of gonorrhea and chlamydia provided by the provincial health program.

The goal of treatment guidelines is to provide recommendations on treatment based on a review of evidence and the assessment of the benefits and harms of alternative care options, to optimize patient care and reduce medical errors.^6,7 In the case of gonorrhea, it also provides evidence-based recommendations for the appropriate management of these infections based on local susceptibility data and the availability of antibiotics. Previous studies addressing compliance with treatment guidelines for gonorrhea are scarce. A similar population-based study conducted in England from 2001 to 2011 found that 40% of gonococcal infections received treatment according to guidelines.⁸ Similarly, a small study conducted in Estonia identified levels of compliance of 62% among 451 episodes.⁹ A large Canadian population-based study reported rates of compliance to treatment guidelines dropped below 30% within the first year of the release of new guidelines, and it took 2 years to reach 60% uptake.¹⁰

Our study found significant variation in the time to uptake of the new guideline after its introduction. On average, it took 1 year to reach the compliance rate observed before the release of the new guideline. Compliance was lowest (32%) after the introduction of the 2012 guideline, which incorporated multiple changes including specific recommendations for the treatment of pharyngeal infections and infections in MSM, increased doses of cefixime and ceftriaxone, and high-dose azithromycin as a single agent in case of allergy to cephalosporins. It is interesting that, despite the multiple changes in this guideline, compliance improved in less than a year to more than 82%, which exceeded the previous (54.7%) rate of compliance. This rapid uptake was due likely to several factors: there was wide dissemination of the guidelines via a letter to all health care providers in the province highlighting the change of preferred treatment, and all cases that were not treated according to guidelines were reviewed by a PNN who reached out to testing providers to ensure guideline-compliant treatment. In addition, in response to rising rates of gonorrhea, a provincial STI services nurse-led test and treat program was implemented in September 2014 creating more opportunities for case management.

Similar studies focused on compliance to treatment guidelines after the removal of ciprofloxacin, as the recommended treatment, have found that the time to adoption of changes has ranged from 2 to 5 years after the release of new treatment guidelines,^9,11 but none of these studies reached an adherence level greater than 70% at the end of the study period. In a retrospective study in Belgium, Schweikardt et al.¹² found that it took 5 years to reach 50% compliance with the new recommendations after the removal of ciprofloxacin.

We identified several characteristics associated with low provider compliance with guidelines based on patient sex, patient race/ethnicity, and treatment provider setting. First, provider compliance was lower when treating women with a PR of 0.89 compared with men; men had 9 excess cases of provider compliance per 100 compared with women. This lower level of provider compliance when treating women compared with men was present in all the characteristics analyzed. Other studies have reported similar findings; for example, Tisler-Sala and colleagues⁹ found that treatment of gonococcal infections among women, compared with men, was significantly less likely to be guideline adherent (30.1% vs. 73.9%, respectively). Some possible explanations for this finding could be that gonorrhea in women is less likely to be accurately diagnosed based on a syndromic approach (including clinical symptoms or physical examination) without a point-of-care test to distinguish gonorrhea from bacterial vaginosis, vaginal candidiasis, trichomoniasis, or other causes of cervicitis. Gaydos and colleagues¹³ found that 57% of women with gonorrhea diagnosed with a syndromic approach in an ED in the United States were not treated according to the Centers for Disease Control and Prevention (CDC) guidelines. Similarly, Kane et al.¹⁴ found that women were more likely to be treated with regimens noncompliant with CDC guidelines compared with men (38% vs. 42%).

Pregnant women also had a lower rate of provider-guideline compliant treatment of 68.4% compared with the overall uptake of 80.3%, likely secondary to concerns about adverse effects on mother and infant. In contrast, the addition of specific treatment recommendations for MSM in 2012 may have simplified the selection of antibiotics to treat gonorrhea in this group and thus increased the likelihood of adherence to the recommendations. Our findings are similar to other studies that highlight a sex disparity in the medical management of women relative to men. For example, women are less likely to receive guideline-based diagnosis and treatment for myocardial infarction,^15,16 heart failure, and anticoagulation for atrial fibrillation.^17–19 These findings collectively support the need for accurate diagnostic tools to decrease this sex disparity.

It is interesting that we found differences in provider compliance with the treatment guidelines among those classified as race/ethnicity unknown, but not among Afro-Caribbean Black or First Nations peoples. People with unknown race/ethnicity represented almost 16% of our study population, and they had a PD of provider compliance of 7 less cases per 100, compared with the rest of the race/ethnicities. Race/ethnicity data collection may not have been accurate; it is also possible that other factors, for example, language barrier, may have contributed to difficulties in ascertaining symptoms, in addition to possible implicit bias and even racism resulting in incorrect clinical diagnosis and treatment. There are no studies that have examined the role of ethnicity in the treatment of gonorrhea, but non-English language concordance is well recognized to be a barrier to quality of care and clinical outcomes.²⁰

We found that gonococcal infections treated in hospitals, urgent care centers, or EDs had a PD of provider compliance of 21 less cases per 100 compared with any other treating provider setting. Adherence to guidelines in EDs has been explored in several studies. In a small retrospective study in a single ED in the United States, Kane et al.¹⁴ found even lower rates of adherence to treatment guidelines for the management of gonococcal infections of 40%. Other studies have shown that management and documentation of sexual histories are suboptimal for cases that present to ED.^21,22 Merchant et al.,²³ in a retrospective study of male adult patients attending the ED with a clinical diagnosis of gonorrhea urethritis, found that 87% received a CDC-recommended empiric treatment for gonorrhea, likely representing the study with the highest compliance to treatment guidelines. Settings with computerized decision support systems may facilitate the management of conditions based on guideline recommendations.²⁴

An important finding from our study was that nurse-led programs were associated with the highest provider compliance with treatment guidelines. In the 3 STI clinics, initial assessment, testing, and treatment are provided by registered nurses using a standardized medical directive of STI best practice with support from an STI physician. In addition, the province has a team of PNNs who provide similar assessment, testing, and treatment in several provincial correctional facilities. This may have contributed to knowledge translation and standardized management of STIs.

Monitoring the trends in the selection of antibiotics for the treatment of gonococcal infections allows for the surveillance of appropriate usage of medications as a strategy to prevent the emergence of resistance. We found a slow increase in the use of azithromycin as monotherapy. By 2016, gonococcal resistance to azithromycin at a national level was reported to be 7%,²⁵ above the World Health Organization threshold recommended of less than 5% resistance.²⁶ Because azithromycin is one of the most common antibiotics prescribed in the community in Canada,²⁷ monitoring of azithromycin resistance in gonorrhea is imperative. At present, ceftriaxone and cefixime resistance remain low (no isolates with ceftriaxone minimum inhibitory concentration ≥0.125 mg/L and 0.1% of isolates with cefixime minimum inhibitory concentration ≥0.25 mg/L) were found in Alberta in 2021, thus allowing continued use of both agents at currently recommended doses in our setting (unpublished data, Alberta STI services, June 20, 2022).

One of the main strengths of our study is that it is the largest population-based study reported to date examining provider compliance with provincial treatment guidelines for gonorrhea in a Canadian province for 20 years. Our study does have several limitations. First, given the retrospective nature of the study, there was a significant amount of missing data including health providers setting in 67.9% of cases, sexual behavior was not reported in 55.6% of cases, and there was no follow-up of data. Despite a large amount of lack of data about the treating provider, the rates of provider compliance with treatment guidelines were similar to the cases included in the analysis. Even more, the trend of lower provider compliance was similar to the cases included in the analysis, specifically when treating women, heterosexual individuals, women having sex with women, and individuals labeled as unknown race/ethnicity and vaginal or cervical infection sites. Thus, we believe that given these similar trends in provider-compliance rates, there was no bias in the analysis. Second, pregnancy status was self-reported. Likely pregnancy status and race/ethnicity may not have been collected appropriately possibly overemphasizing the racial disparities. Another limitation of this study is that we only assessed the antimicrobial treatment recommendations of the guidelines, and did not explore screening practices, counseling, and education about safe sex, abstinence recommendations after treatment, partner notification, and test of cure.

Compliance with treatment guidelines should be monitored on an ongoing basis as part of a broader strategy to control the ongoing rising rates of gonorrhea in our province. There are several innovative ways to facilitate the distribution and usage of treatment guidelines, and we anticipate that our findings will be used to plan the implementation of some of these strategies in our province. The incorporation of guideline-based management into electronic medical records for treatment pathways and decision support systems has been shown to increase adherence to treatment guidelines.^28,29 In more recent years, the use of smartphone applications has facilitated access to treatment information and has been used by health care providers to support antimicrobial stewardship and reduce antimicrobial resistance³⁰ and improve the accessibility to gonorrhea treatment guidelines in Alberta.

Our study found the highest rates of provider compliance (80%) with treatment guidelines for gonorrhea of any population-based study to date. We attribute this to a combination of public health initiatives in our province, of which the most important was nurse-led programs. However, we identified disparities in guideline provider compliance for women and in settings that were not nurse-led, highlighting areas that can be targeted for additional interventions to improve compliance.