Serine deamination by human serine racemase synergizes with antibiotics to curtail the replication of Chlamydia trachomatis.

The obligate intracellular bacterium, Chlamydia trachomatis, has evolved to depend on its human host for many metabolites, including most amino acids and three of the four nucleotides. Given this, it is not surprising that depletion of a single amino acid in the host cell growth medium blocks chlamydial replication. Paradoxically, supra-normal levels of some amino acids also block productive replication of Chlamydia. Here, we have determined how elevated serine levels, generated by exogenous supplementation, impede chlamydial inclusion development and reduce the generation of infectious progeny. Our findings reveal that human serine racemase, which is broadly expressed in multiple tissues, potentiates the anti-chlamydial effect of elevated serine concentrations. In addition to reversibly converting l-serine to d-serine, serine racemase also deaminates serine via ß-elimination. We have determined that d-serine does not directly impact Chlamydia; rather, ammonia generated by serine deamination limits the productive chlamydial replication. Our findings imply that ammonia produced within host cells can traverse the chlamydial inclusion membrane. Further, this property of serine deaminase can be exploited to sensitize Chlamydia to concentrations of doxycycline that are otherwise not bactericidal. Because exogenously elevated levels of serine can be tolerated over extended periods, the broad expression pattern of serine racemase indicates it to be a host enzyme whose activity can be directed against multiple intracellular bacterial pathogens. From a therapeutic perspective, demonstrating host metabolism can be skewed to generate an anti-bacterial metabolite that synergizes with antibiotics, we believe our results provide a new approach to target intracellular pathogens.

Metabolic dormancy in Chlamydia trachomatis treated with different antibiotics.

Diseases caused by Chlamydia spp. are often associated with persistent infections. Chlamydial persistence is commonly associated with a unique non-infectious intracellular developmental form, termed an aberrant form. Although infectious chlamydiae can be cultured consistently in cells stressed to aberrancy, their role in persistence is not clear. Recovery from antibiotic stress was explored as a model to determine how survival of non-aberrant chlamydiae, in the presence of fully inhibitory drug concentrations, may participate in persistence. Assays included incubation in quinolones, tetracyclines, or chloramphenicol for differing lengths of time, followed by an extended recovery period in antibiotic-free media. Culturable elementary bodies were not detected during treatment with each antibiotic, but viable and culturable Chlamydia trachomatis emerged after the drug was removed. Time-lapse imaging of live, antibiotic-treated infected cells identified metabolically dormant developmental forms within cells that emerged to form typical productive inclusions. The effects of the increasing concentration of most tested antibiotics led to predictable inhibitory activity, in which the survival rate decreased with increasing drug concentration. In contrast, in fluoroquinolone-treated cells, there was a paradoxical increase in productive development that was directly correlated with drug concentration and inversely associated with aberrant form production. This model system uncovers a unique chlamydial persistence pathway that does not involve the chlamydial aberrant form. The association between productive latency and metabolic dormancy is consistent with models for many bacterial species and may lead to a different interpretation of mechanisms of chlamydial persistence in patients.IMPORTANCEThe life history of most pathogens within the genus Chlamydia relies on lengthy persistence in the host. The most generally accepted model for Chlamydia spp. persistence involves an unusual developmental stage, termed the aberrant form, which arises during conditions that mimic a stressful host environment. In this work, we provide an alternate model for chlamydial persistence in the face of antibiotic stress. This model may be relevant to antibiotic treatment failures in patients infected with C. trachomatis.

Azithromycin or Doxycycline for Asymptomatic Rectal Chlamydia trachomatis.

BACKGROUND: Rectal chlamydia is a common bacterial sexually transmissible infection among men who have sex with men. Data from randomized, controlled trials are needed to guide treatment. METHODS: In this double-blind trial conducted at five sexual health clinics in Australia, we randomly assigned men who have sex with men and who had asymptomatic rectal chlamydia to receive doxycycline (100 mg twice daily for 7 days) or azithromycin (1-g single dose). Asymptomatic chlamydia was selected as the trial focus because more than 85% of men with rectal chlamydia infection are asymptomatic, and clinical guidelines recommend a longer treatment course for symptomatic infection. The primary outcome was a negative nucleic acid amplification test for rectal chlamydia (microbiologic cure) at 4 weeks. RESULTS: From August 2016 through August 2019, we enrolled 625 men (314 in the doxycycline group and 311 in the azithromycin group). Primary outcome data were available for 290 men (92.4%) in the doxycycline group and 297 (95.5%) in the azithromycin group. In the modified intention-to-treat population, a microbiologic cure occurred in 281 of 290 men (96.9%; 95% confidence interval [CI], 94.9 to 98.9) in the doxycycline group and in 227 of 297 (76.4%; 95% CI, 73.8 to 79.1) in the azithromycin group, for an adjusted risk difference of 19.9 percentage points (95% CI, 14.6 to 25.3; P<0.001). Adverse events that included nausea, diarrhea, and vomiting were reported in 98 men (33.8%) in the doxycycline group and in 134 (45.1%) in the azithromycin group (risk difference, -11.3 percentage points; 95% CI, -19.5 to -3.2). CONCLUSIONS: A 7-day course of doxycycline was superior to single-dose azithromycin in the treatment of rectal chlamydia infection among men who have sex with men. (Funded by the National Health and Medical Research Council; RTS Australian New Zealand Clinical Trials Registry number, ACTRN12614001125617.).

STI pathogens in the oropharynx: update on screening and treatment.

PURPOSE OF REVIEW: The rise in antimicrobial resistance in several STI pathogens such as Neisseria gonorrhoeae has become a public health threat as only one first-line treatment remains. Reducing screening interval for gonorrhoea and chlamydia in high-prevalence populations has been proposed to address antimicrobial stewardship, but this remains controversial. This review aimed to revisit the epidemiology of infections at the oropharynx and review the current screening recommendations and treatment guidelines in different populations. RECENT FINDINGS: Emerging evidence suggests that the oropharynx is the primary anatomical site for gonorrhoea transmission but maybe not for chlamydia transmission. Most international guidelines recommend 3-monthly oropharyngeal gonorrhoea and chlamydia screening for high-prevalence populations (e.g. men who have sex with men) but not low-prevalence populations (e.g. heterosexuals) given the clinical and public health benefits of screening in low-prevalence populations are still unclear. Doxycycline remains the first-line treatment for oropharyngeal chlamydia in most guidelines. However, some countries have moved from dual therapy (ceftriaxone and azithromycin) to monotherapy (ceftriaxone) for oropharyngeal gonorrhoea treatment to address antimicrobial stewardship. SUMMARY: The transmission of gonorrhoea and chlamydia is still not fully understood. Further work will be required to evaluate the benefits and harms of reducing screening in high-prevalence populations.

Expedited Partner Therapy: A Multicomponent Initiative to Boost Provider Counseling.

BACKGROUND: Expedited partner therapy prescription remains low and highly variable throughout the United States, leading to frequent reinfections with Chlamydia trachomatis and Neisseria gonorrhoeae . We examined provider counseling on expedited partner therapy before and after an electronic smart tool-based initiative. METHODS: In this quasi-experimental interrupted time-series study, we implemented an initiative of electronic smart tools and education for expedited partner therapy in March 2020. We reviewed the records of patients with chlamydia and/or gonorrhea at an urban, academic obstetrics and gynecology clinic in the preimplementation (March 2019-February 2020) and postimplementation (March 2020-February 2021) groups. Descriptive statistics and an interrupted time-series model were used to compare the percent of expedited partner therapy offered by clinicians to patients in each group. RESULTS: A total of 287 patient encounters were analyzed, 155 preintervention and 132 postintervention. An increase in expedited partner therapy counseling of 13% (95% confidence interval [CI], 2%-24%) was observed before the intervention (27.1% [42 of 155]) versus after the intervention (40.2% [53 of 132]). Significant increases in provider counseling were seen for patients who were single (15%; 95% CI, 3%-26%), 25 years or older (21%; 95% CI, 6%-37%), receiving public insurance (15%; 95% CI, 3%-27%), seen by a registered nurse (18%; 95% CI, 4%-32%), or seen for an obstetrics indication (21%; 95% CI, 4%-39%). No difference was seen in patients' acceptance of expedited partner therapy ( P = 1.00). CONCLUSIONS: A multicomponent initiative focused on electronic smart tools is effective at increasing provider counseling on expedited partner therapy. Further research to understand patient perceptions and acceptance of expedited partner therapy is critical.

Trends in Chlamydia trachomatis Treatment Prescribing Practices in King County, Washington, 2010-2018.

BACKGROUND: In 2021, national Chlamydia trachomatis (CT) treatment guidelines changed from recommending either azithromycin (1 g; single dose) or doxycycline (100 mg twice daily for 7 days) to recommending only doxycycline as first-line treatment. The distribution and trends in CT prescribing practices before the guidelines change is largely unknown. METHODS: We conducted a trends analysis using Washington STD surveillance data. We included all female cases of urogenital CT 15 years or older who resided in King County and were diagnosed between 2010 and 2018. Surveillance data included information on demographics, sexual history, clinical features, diagnosing facility (eg, emergency department, family planning), and treatment regimen. We conducted descriptive analyses to examine trends in prescribing practices over time and by facility type. We used Poisson regression to examine the association between CT case characteristics and receipt of receipt of azithromycin. RESULTS: There were 36,830 cases of female urogenital CT during the study period. The percent of cases receiving azithromycin increased significantly from 86% in 2010 to 94% in 2018; the percent receiving doxycycline decreased from 13% to 5%. Five of the 8 facility types prescribed azithromycin to >95% of CT cases by 2018. Cases who were younger or cases of color were more likely to receive azithromycin (versus doxycycline) compared with older and White cases, respectively. CONCLUSIONS: A substantial shift in CT prescribing practices will be needed to adhere to new CT treatment guidelines. Our findings highlight the need for targeted provider education and training to encourage the transition to doxycycline use.

Treatment Rates for Chlamydia trachomatis and Neisseria gonorrhoeae in a Metropolitan Area: Observational Cohort Analysis.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are the 2 most common sexually transmitted infections (STIs) in the United States. The Centers for Disease Control and Prevention regularly publishes and updates STI Treatment Guidelines. The purpose of this study was to measure and compare treatment rates for CT and GC among public and private providers. METHODS: Data from multiple sources, including electronic health records and Medicaid claims, were linked and integrated. Cases observed during 2016-2020 were defined based on positive laboratory results. We calculated descriptive statistics and odd ratios based on characteristics of providers and patients, stratifying by public versus private providers. Univariate logistic regression models were used to examine the factors associated with recommended treatment. RESULTS: Overall, we found that 82.2% and 63.0% of initial CT and GC episodes, respectively, received Centers for Disease Control and Prevention-recommended treatment. The public STI clinic treated more than 90% of CT and GC cases consistently across the 5-year period. Private providers were significantly less likely to treat first episodes for CT (79.6%) and GC (53.3%; P < 0.01). Other factors associated with a higher likelihood of recommended treatment included being male, being HIV positive, and identifying as Black or multiracial. Among GC cases, 10.8% received nonrecommended treatment; all CT cases with treatment occurred per guidelines. CONCLUSIONS: Although these treatment rates are higher than previous studies, there remain significant gaps in STI treatment that require intervention from public health.

Use of Expedited Partner Therapy for Pregnant Women Treated for Sexually Transmitted Infections in Gaborone, Botswana.

BACKGROUND: Partner notification and treatment for sexually transmitted infections are critical to prevent reinfection and reduce transmission. However, partner treatment rates are low globally. Expedited partner therapy (EPT), in which the patient delivers treatment directly to their partner, may result in more partners treated. We assessed partner notification and treatment outcomes among pregnant women in Gaborone, Botswana, including EPT intent, uptake, and effectiveness. METHODS: The Maduo study was a cluster-controlled trial evaluating the effect of antenatal Chlamydia trachomatis and Neisseria gonorrhoeae infection screening in pregnant women. The intervention arm received screening at first antenatal care (ANC), third-trimester, and postnatal care visits. The standard-of-care arm received screening postnatally. Participants screening positive were given options for partner treatment: contact slips, in-clinic treatment, or EPT. Self-reported partner notification and treatment outcomes were assessed at test-of-cure visit. RESULTS: Of 51 women who screened positive for C. trachomatis / N. gonorrhoeae at first ANC and returned for test of cure, 100% reported notifying their partner and 48 (94.1%) reported their partner received treatment. At third trimester 100% (n = 5), reported partners were treated. Before testing, EPT intent was lower than EPT uptake at all time points (first ANC: 17.9% vs. 80.4%; third-trimester: 57.1% vs. 71.4%; postnatal care: 0% vs. 80.0%). Partner treatment success was 100% among EPT users compared with 70% among nonusers ( P = 0.006). CONCLUSIONS: Partner notification and treatment success was high in this population. Despite low pretest intent to use EPT, uptake was high and associated with greater partner treatment success. Our findings suggest that EPT may be a successful partner treatment strategy to pursue in low- and middle-income countries.

Reducing Barriers for Expedited Partner Treatment in Adolescents and Young Adults: A Quality Improvement Initiative.

BACKGROUND: Adolescents and young adults (AYAs) face significant barriers to screening, testing, and treatment of sexually transmitted infections (STIs). Expedited partner therapy (EPT) streamlines partner treatment of STIs, but use among adolescents is low. We aimed to increase EPT offering and provision at 2 adolescent medicine clinics (AMCs) and the emergency department (ED) in an urban children's hospital. We addressed barriers at provider, pharmacy, and patient levels. We compared EPT offering and provision for chlamydia ( Chlamydia trachomatis [CT]) and trichomonas ( Trichomonas vaginalis [TV]) infection at baseline and across 2 intervention cycles. METHODS: Baseline data were collected from July 2019 to March 2020 and our intervention time frame spanned from April 2020 to October 2021. Laboratory codes identified patients with CT or TV infections. Cycle 1 allowed providers to order EPT within a patient's chart. The second cycle targeted education and standardization for STI/EPT notification and counseling. During this cycle, notification of ED patients was centralized to the AMC nurses. RESULTS: A total of 747 CT and TV cases were identified. In the AMC, EPT offering increased from 77.3% to 87.7% ( P = 0.01). Expedited partner therapy provision increased from 32.3% to 69.9% ( P < 0.001). Expedited partner therapy offering for ED patients increased by 82.3%. Retesting rates remained consistent, with a significant drop in reinfection rates ( P = 0.003) within patients seen in the AMC. CONCLUSIONS: This quality improvement initiative successfully increased EPT offering and provision among the cases identified. Future cycles may include longer-term follow-up to confirm partner treatment and testing per guidelines.

Should We Be Testing for Mycoplasma genitalium on Initial Presentation? Trends in Persistent/Recurrent Urethritis Among Men Presenting for Care in STD Clinics, 2015-2019, STD Surveillance Network.

BACKGROUND: Mycoplasma genitalium is a major contributor to persistent/recurrent urethritis cases. However, there are limited published studies on recent trends of persistent/recurrent urethritis. METHODS: A retrospective analysis was conducted of men presenting with symptomatic urethritis in 16 sexually transmitted disease (STD) clinics from 2015 to 2019. Poisson regression was used to assess trends in the annual proportions of urethritis episodes with follow-up (FU) characterized with persistent/recurrent urethritis symptoms. Results were also stratified by results of chlamydia (CT) and gonorrhea (NG) testing and treatment prescribed. RESULTS: There were 99,897 urethritis episodes, from 67,546 unique men. The proportion of episodes with persistent/recurrent symptomatic FU visits increased 50.8% over a 4-year period (annual percentage change [APC], 11.3%; 95% confidence interval [CI], 6.5-16.3). Similar trends were observed in nonchlamydial nongonococcal urethritis episodes (APC, 12.7%; 95% CI, 6.8-18.9) but increases among those positive for NG (APC, 12.1%; 95% CI, -2.3 to -28.5) or for CT (APC, 7.3%; 95% CI, -6.7 to 23.5) were not statistically significant. Among episodes who received azithromycin as first-line treatment, increases in the proportion of persistent/recurrent FU visits were observed (APC, 12.6%; 95% CI, 8.6-16.7). For episodes where first-line treatment was doxycycline, no significant increases were detected (APC, 4.3%; 95% CI, -0.3 to 9.2). CONCLUSIONS: We found an increase in the proportion of urethritis episodes with persistent or recurrent symptoms over time. Given these observed trends in episodes negative for NG or CT, an etiology not detectable by routine diagnostics was a likely factor in increased persistence, suggesting patients with urethritis may benefit from diagnostic testing for M. genitalium during an initial symptomatic presentation.

Analysis of Patient Adherence to Filling Emergency Department Discharge Prescriptions for Empiric Treatment of Chlamydia.

PURPOSE: Sexually transmitted infections (STIs) represent an enormous public health burden in the United States. Emergency departments (EDs) are a significant source of medical care, particularly for vulnerable patient populations. Guidelines for the treatment of Chlamydia trachomatis have evolved and now recommend doxycycline 100 mg orally twice daily for 7 days as the primary regimen for adults. However, the single-dose azithromycin regimen can be given during the ED visit, while the new regimen has nonadherence hurdles. The purpose of this study will be determining the rate of ED discharge prescription pick ups of doxycycline for Chlamydia trachomatis infection at two discharge pharmacies. METHODS: This is a retrospective chart review of information contained in the electronic medical record (EMR) from August 1st, 2021 - July 31st, 2022. Adult patients who present to the two EDs in the healthcare system and those who received empiric antibiotic treatment for Chlamydia trachomatis infection prior to, or at, ED discharge will be included. Patients who are pregnant, less than 18 years old, those without a Chlamydia trachomatis nucleic acid amplification test during their ED visit, or patients whose antibiotic treatment prescription was sent to a pharmacy other than the two primary discharge pharmacies at the respective medical centers will be excluded. The primary outcome of this study will be determining the rate of emergency department (ED) discharge prescription pick ups of doxycycline for empiric treatment of Chlamydia trachomatis infection at two discharge pharmacies. The secondary outcomes will include the incidence of repeat positive tests between four weeks and 90 days, risk of repeat positive tests in those who do not fill doxycycline, number of positive and negative test results, rate of prescribing adherence to 2021 Centers for Disease Control and Prevention (CDC) Sexually Transmitted Infections Treatment Guidelines regimens for empiric treatment, and insurance status at the time of discharge fill. RESULTS: Seven hundred and thirty patients were pulled from the EMR. One hundred of the patients were excluded from the study as they did not receive empiric antibiotic treatment for Chlamydia trachomatis infection prior to, or at, ED discharge leaving 630 participants. Among this group, 369 patients were excluded as their discharge prescription was not sent to the discharge pharmacies within the medical system, leaving 261 individuals in the study. Per chart review, 215 of the patients picked up their doxycycline prescription (82.4%) and 46 (17.6%) patients failed to pick up their prescription. Additionally, 43 (16.5) of the patients who were prescribed empiric therapy had a positive chlamydia trachomatis test, while 209 (83.5%) of those had a negative test. This study also showed 188 (72%) patients received treatment according to the current CDC recommendations. CONCLUSION: Majority of patients who received prescriptions from the in-hospital discharge pharmacy picked up their prescriptions.

Doxycycline adherence for the management of Chlamydia trachomatis infections.

BACKGROUND: The updated 2021 CDC treatment guidelines recommend a single dose of 500 mg intramuscular ceftriaxone for Neisseria gonorrhea and doxycycline 100 mg by mouth twice daily for 7 days for Chlamydia trachomatis coinfection. However, there is a significant public health concern regarding patient non-adherence to the 7-day course of doxycycline. To date, there are no studies assessing this concern. Therefore, the objective of this study was to evaluate a patient's adherence to doxycycline for chlamydial infections after discharge from the Emergency Department (ED). METHODS: This was an IRB-approved, single-center, retrospective cohort study evaluating the adherence to doxycycline for Chlamydia trachomatis infections. Patients who received treatment and were discharged from the ED with a doxycycline e-prescription between May 2021 and September 2022 were included. Patients were excluded if <18 years of age, pregnant, a sexual assault victim, or admitted inpatient. The primary endpoint was the incidence of doxycycline prescription pick-up after discharge from the ED. The secondary endpoint was the incidence of repeat ED visits for the same chief complaint within 28 days. Descriptive statistics were computed for all study variables and Fisher's Exact tests were used to assess the outcomes. RESULTS: A review of 144 patients who tested positive for chlamydia and were discharged from the ED with an e-prescription for doxycycline revealed that 18% of patients did not pick up their prescription (N = 26). Non-adherent patients were more likely to return to the ED with the same chief complaint within 28 days (23.1% vs 7.6%, OR 3.6 [1.2-11.3], p = 0.026). No differences were detected in baseline demographics, housing status, insurance type, sexual orientation, or Sexually Transmitted Infection history. CONCLUSION: For patients with a positive chlamydia infection who were discharged from the ED on doxycycline, an 18% non-adherence rate was found and a 3.6-fold higher likelihood of returning to the ED with the same chief complaint if the prescription was not picked up.

Impact of point-of-care gonorrhea and chlamydia testing in the emergency department on reducing overtreatment rates.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections continue to increase in the United States. Advancement in technology with point-of-care (POC) testing can improve the overall treatment of sexually transmitted infections (STI) in the emergency department (ED) by shortening the time to test result and administration of accurate treatment. The purpose of this study was to assess if the POC test reduced the rate of overtreatment for CT and/or NG compared to the standard-of-care (SOC) test. METHODS: This retrospective cohort study included adult patients tested for CT and NG at two urban EDs between August 2020 and October 2022. This cohort excluded hospital admissions, elopement, pregnancy, rectal and oral samples, victims of sexual assault, and diagnoses for which antimicrobial treatment overlapped that of CT/NG. The primary outcome assessed overtreatment, defined as receiving treatment in the ED or a prescription prior to discharge for patients who tested negative for CT and/or NG. Secondary outcomes included undertreatment rates, overtreatment rates in select populations, test turnaround time, and ED length of stay (LOS). RESULTS: Of 327 patients screened, 97 patients were included in the SOC group and 100 in POC. Overtreatment for CT was provided in zero POC patients and 29 (29.9%) SOC patients (p < 0.001). NG was overtreated in 1 (1%) POC and 23 (23.7%) SOC (p < 0.001). POC was associated with undertreatment of CT and/or NG in two patients, compared to four patients tested with SOC. Overall, treatment was deemed inappropriate for 5 (5%) of those tested with POC, compared to 35 (36%) tested with SOC (p < 0.001). There was no difference in ED LOS (2.7 vs 3.01 h, p = 0.41). CONCLUSIONS: POC testing facilitated the return of results prior to patients being discharged from the ED. Compared to standard testing, POC improved appropriateness of CT and NG treatment by reducing the rates of overtreatment.

Patient-delivered partner therapy for chlamydia: health practitioner views on updated guidance in Victoria, Australia.

Background Patient-delivered partner therapy (PDPT) involves providing a prescription or medication to a patient diagnosed with chlamydia to pass to their sexual partner/s. Barriers to PDPT include uncertainty about its integration into clinical practice and permissibility. In Victoria, Australia, the Department of Health provides clinical guidance for PDPT (updated in 2022). We explored health practitioner views on the usefulness of the updated guidance for providing PDPT. Methods We conducted an online survey (12 December 2022 to 2 May 2023) of health practitioners who primarily work in Victoria and can prescribe to treat chlamydia. The survey displayed excerpts from the guidance, and asked closed and free-text questions about its ability to address barriers to PDPT. Quantitative data were descriptively analysed, complemented by conventional content analysis of qualitative data. Results Of a total of 49 respondents (66.7% general practitioners), 74.5% were aware of PDPT, and 66.7% had previously offered PDPT. After viewing excerpts of the guidance, >80% agreed it could support them to identify patients eligible/ineligible for PDPT, and 66.7% indicated they would be comfortable to offer PDPT. The guidance was viewed as helpful to address some barriers, including complicated documentation (87.7%) and medico-legal concerns (66.7%). Qualitative data highlighted medico-legal concerns by a minority of respondents. Some raised concerns that the guidance recommended prescribing azithromycin, despite doxycycline being first-line chlamydia treatment. Conclusions The guidance was largely viewed as supportive for PDPT decision-making. There is scope for further refinements and clarifications, and wider dissemination of the guidance.

Impact of Point-of-Care Testing on the Management of Sexually Transmitted Infections in South Africa: Evidence from the HVTN702 Human Immunodeficiency Virus Vaccine Trial.

BACKGROUND: Alternative approaches to syndromic management are needed to reduce rates of sexually transmitted infections (STIs) in resource-limited settings. We investigated the impact of point-of-care (POC) versus central laboratory-based testing on STI treatment initiation and STI adverse event (STI-AE) reporting. METHODS: We used Kaplan-Meier and Cox regression models to compare times to treatment initiation and STI-AE reporting among HVTN702 trial participants in South Africa. Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) were diagnosed POC at eThekwini clinic and in a central laboratory at Verulam/Isipingo clinics. All clinics used POC assays for Trichomonas vaginalis (TV) testing. RESULTS: Among 959 women (median age, 23 [interquartile range, 21-26] years), median days (95% confidence interval [95%CI]) to NG/CT treatment initiation and NG/CT-AE reporting were 0.20 (.16-.25) and 0.24 (.19-.27) at eThekwini versus 14.22 (14.12-15.09) and 15.12 (13.22-21.24) at Verulam/Isipingo (all P < .001). Median days (95%CI) to TV treatment initiation and TV-AE reporting were 0.17 (.12-.27) and 0.25 (.20-.99) at eThekwini versus 0.18 (.15-.2) and 0.24 (.15-.99) at Verulam/Isipingo (all P > .05). Cox regression analysis revealed that NG/CT treatment initiation (adjusted hazard ratio [aHR], 39.62 [95%CI, 15.13-103.74]) and NG/CT-AE reporting (aHR, 3.38 [95%CI, 2.23-5.13]) occurred faster at eThekwini versus Verulam/Isipingo, while times to TV treatment initiation (aHR, 0.93 [95%CI, .59-1.48]) and TV-AE reporting (aHR, 1.38 [95%CI, .86-2.21]) were similar. CONCLUSIONS: POC testing led to prompt STI management with potential therapeutic and prevention benefits, highlighting its utility as a diagnostic tool in resource-limited settings.

Spontaneous clearance of asymptomatic anogenital and pharyngeal Neisseria gonorrhoeae: a secondary analysis from the NABOGO trial.

INTRODUCTION: Spontaneous clearance of asymptomatic Neisseria gonorrhoeae (NG) does occur, but data are scarce. We aimed to assess spontaneous clearance among patients with asymptomatic anal, pharyngeal, vaginal and urethral NG infections who participated in the New AntiBiotic treatment Options for uncomplicated GOnorrhoea (NABOGO) trial. In addition, we assessed the determinants associated with spontaneous clearance. METHODS: The NABOGO trial (Trial registration number: NCT03294395) was a randomised controlled, double-blind, single-centre trial assessing non-inferiority of ertapenem, gentamicin and fosfomycin to ceftriaxone for treatment of uncomplicated gonorrhoea. For asymptomatic NABOGO participants, we collected pre-enrolment and enrolment visit samples before trial medication was given. Spontaneous clearance was defined as a positive pre-enrolment nucleic acid amplification test (NAAT) result, followed by a negative NAAT at enrolment. We compared the median time between pre-enrolment and enrolment visits for patients who cleared spontaneously and for those who did not. Determinants of spontaneous clearance were assessed using logistic regression. RESULTS: Thirty-two of 221 (14.5%) anal NG infections cleared spontaneously, 17 of 91 (18.7%) pharyngeal, 3 of 13 (23.1%) vaginal and 9 of 28 (32.1%) urethral NG infections. The median time between the pre-enrolment and enrolment visit was longer for patients who cleared their pharyngeal infection spontaneously compared with those who did not (median 8 days (IQR=7-11) vs 6 days (IQR=4-8), p=0.012); no determinants of clearance at other sites were identified. Overall, patients with more days between the pre-enrolment and enrolment visit were more likely to clear spontaneously (adjusted OR=1.06 per additional day, 95% CI 1.01 to 1.12). No association between location of NG infection and spontaneous clearance was found. CONCLUSIONS: A significant proportion of asymptomatic patients cleared their NG infections spontaneously. Given these results, treatment of all NG infections after a one-time NAAT may be excessive, and more research on the natural history of NG is needed to improve antibiotic stewardship.

Non-empirical management of asymptomatic chlamydia and gonorrhoea reduces unnecessary antibiotic use fivefold: a before and after study.

OBJECTIVES: In 2019, informed by favourable patient and provider acceptability surveys and concerns about antimicrobial resistance, Sydney Sexual Health Centre stopped routinely providing empirical antibiotic treatment to asymptomatic contacts of Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoea (gonorrhoea). We aimed to assess if this policy change had any negative impact on patient outcomes. METHODS: A retrospective file review of people who presented as asymptomatic contacts of chlamydia and gonorrhoea cases before and after the policy change was conducted. Data on infection type, test results and treatment were extracted. For contacts who tested positive and were treated non-empirically, additional data were reviewed including sexual activity and symptom or complication development between testing and treatment, time from testing to notification and treatment and loss to follow-up. RESULTS: Of 1194 asymptomatic sexual contacts of chlamydia or gonorrhoea, most tested negative to both infections (814, 68%). All contacts with a positive result who were not treated empirically were notified of their result and 173 (99%) were treated within a mean time of 5 days. More contacts were overtreated in 2018 (n=355, 58%) under the empirical treatment model compared with 2019 (n=58, 11%, p≤0.001). There was no significant difference in the proportion of contacts who tested positive and were treated (p=0.111) or developed symptoms (p=0.413) before and after the policy change and no contacts who were treated non-empirically developed complications of pelvic inflammatory disease, epididymitis or proctitis between testing and treatment. CONCLUSION: In this population, a switch from empirically treating all asymptomatic contacts to treating only those who tested positive significantly reduced antibiotic overuse with minimal adverse outcomes. Our findings support results-directed treatment for asymptomatic sexual contacts of chlamydia and gonorrhoea.

Measuring quality STI care among adolescent female primary care patients in Philadelphia.

OBJECTIVES: Engagement in guideline-recommended sexually transmitted infection (STI) care is fundamental to ending the STI epidemic in the USA. However, the US 2021-2025 STI National Strategic Plan and STI surveillance reports do not include a framework to measure quality STI care delivery. This study developed and applied an STI Care Continuum that can be used across settings to improve STI care quality, assess adherence to guideline-recommended care and standardise the measurement of progress towards National Strategic goals. METHODS: Review of the Centers for Disease Control and Prevention STI Treatment guidelines identified seven distinct steps of STI care for gonorrhoea, chlamydia and syphilis: (1) STI testing indication, (2) STI test completion, (3) HIV testing, (4) STI diagnosis, (5) partner services, (6) STI treatment and (7) STI retesting. Steps 1-4, 6 and 7 for gonorrhoea and/or chlamydia (GC/CT) were measured among females aged 16-17 years with a clinic visit at an academic paediatric primary care network in 2019. We used Youth Risk Behavior Surveillance Survey data to estimate step 1, and electronic health record data for steps 2, 3, 4, 6 and 7. RESULTS: Among 5484 female patients aged 16-17 years, an estimated 44% had an STI testing indication. Among those patients, 17% were tested for HIV, of whom none tested positive, and 43% were tested for GC/CT, 19% of whom were diagnosed with GC/CT. Of these patients, 91% received treatment within 2 weeks and 67% were retested within 6 weeks to 1 year after diagnosis. On retesting, 40% were diagnosed with recurrent GC/CT. CONCLUSIONS: Local application of an STI Care Continuum identified STI testing, retesting and HIV testing as areas for improvement. The development of an STI Care Continuum identified novel measures for monitoring progress towards National Strategic indicators. Similar methods can be applied across jurisdictions to target resources, standardise data collection and reporting and improve STI care quality.

Factors Associated With Chlamydia and Gonorrhea Treatment Completion Among Sexual Health Clinic Patients, Baltimore City, Maryland; 2018 to 2019.

BACKGROUND: Prompt and appropriate treatment of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is critical to prevent transmission and serious sequelae. The objectives were to determine the prevalence of CT/NG treatment completion and identify demographic, behavioral, and clinical factors associated with treatment completion at sexual health clinics in Baltimore City, Maryland. METHODS: Electronic health record data from patients diagnosed with CT/NG during 2018-2019 were analyzed. Treatment completion was defined as documentation of Centers for Disease Control and Prevention-recommended treatment ≤30 days after testing. Regression was used to assess differences in treatment completion across groups; analyses were stratified by birth sex. RESULTS: Most of the 2426 male (86%) and 754 (72%) female patients diagnosed with CT/NG completed treatment in ≤30 days; 74% of male and 36% of female patients were treated same-day. Among 890 male patients not treated same-day, treatment completion was associated with other same-day antimicrobial treatments (adjusted prevalence ratio, 0.76 [95% confidence interval, 0.61-0.94]), longer test processing times (≥10 days; 0.78 [0.65-0.95]) infection at multiple anatomic sites (1.49 [1.25-1.76]), and patients with previous clinic visits (1.16 [1.03-1.31]). Among 483 female patients not treated same-day, treatment completion was associated with diagnosis year (2019 vs. 2018; 1.23 [1.05-1.43]) and residential addresses 2 to 5 miles (vs. <2 miles) from clinic (1.25 [1.02-1.53]). Demographic and behavioral characteristics were not associated with treatment completion. CONCLUSIONS: Substantial proportions of male and female sexual health clinic patients did not complete treatment. Our findings underscore the need for implementation of highly sensitive and specific point-of-care (POC) CT/NG testing to improve treatment completion in this setting.

The Relationship Between Directly Observed Therapy for Chlamydia Infections and Retesting Rates in an Adolescent Population.

BACKGROUND: Chlamydia trachomatis is the most common reportable sexually transmitted infection in the United States, with >60% of reported cases occurring in individuals aged 15 to 24 years. US practice guidelines recommend directly observed therapy (DOT) for the treatment of chlamydia in adolescents, but almost no research has been done to evaluate whether DOT results in improved outcomes. METHODS: We conducted a retrospective cohort study of adolescents who sought care at 1 of 3 clinics within a large academic pediatric health system for a chlamydia infection. The study outcome was return for retesting within 6 months. Unadjusted analyses were performed using χ2 , Mann-Whitney U , and t tests, and adjusted analyses were performed using multivariable logistic regression. RESULTS: Of the 1970 individuals included in the analysis, 1660 (84.3%) received DOT and 310 (15.7%) had a prescription sent to a pharmacy. The population was primarily Black/African American (95.7%) and female (78.2%). After controlling for confounders, individuals who had a prescription sent to a pharmacy were 49% (95% confidence interval, 31%-62%) less likely than individuals who received DOT to return for retesting within 6 months. CONCLUSIONS: Despite clinical guidelines recommending the use of DOT for chlamydia treatment in adolescents, this is the first study to describe the association between DOT and an increase in the number of adolescents and young adults who return for sexually transmitted infection retesting within 6 months. Further research is needed to confirm this finding in diverse populations and explore nontraditional settings for the provision of DOT.