Aztreonam for Pharyngeal Gonorrhea

Study Overview
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Brief Summary
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The Centers for Disease Control and Prevention has identified antimicrobial-resistant (AMR) Neisseria gonorrhoeae (NG) as one of the nation's top three urgent AMR threats. Since the advent of antibiotics in the 1930s, NG has developed resistance to every first-line antibiotic. Parenteral third-generation cephalosporins are now the only class of drug with consistent efficacy against NG. New therapies are urgently needed. Although some novel antimicrobials are under development, reevaluating older drugs is another option for quickly identifying additional treatments for gonorrhea. We propose a demonstration study to test a single dose of aztreonam for the treatment of pharyngeal gonorrhea. We chose to focus on pharyngeal gonorrhea because these infections are common, play an important role in fostering gonococcal resistance, and are harder to eradicate than genital infections. Although aztreonam appears to be >98.6% efficacious for anogenital NG, its efficacy at the pharynx may be less. Only 8 cases of pharyngeal gonorrhea have been documented to be treated with aztreonam, but of those, only 5 (62.5%) were cured. The dose used in those studies was 1g of aztreonam. Most antibiotics have a lower efficacy at the pharynx than anogenital sites, which is likely due to drug pharmacokinetics, i.e. difficulty in penetrating pharyngeal tissue. Thus, in the proposed study, we plan to treat 50 subjects with untreated pharyngeal gonorrhea with 2g IM Aztreonam. Objectives: The proposed study aims to evaluate the efficacy of a single 2g intramuscular (IM) dose of aztreonam in the treatment of pharyngeal gonorrhea. Secondary objectives include documenting the efficacy stratified by minimal inhibitory concentration (MIC) compared with the previously document area under the curve (AUC) in order to estimate a pharmacodynamic criterion. We will also attempt to determine whether aztreonam monotherapy induces antimicrobial resistance among treatment failures. Lastly, we will evaluate the tolerability of 2g of IM aztreonam. The specific aims are: Determine the proportion of persons whose pharyngeal gonococcal infections are cured with a single dose of 2g aztreonam intramuscularly. Determine the proportion of persons with urethral and/or rectal gonorrhea whose infections are cured with a single dose of 2g aztreonam IM. Evaluate the tolerability of 2g IM of aztreonam . Estimate the best pharmacodynamics criterion (i.e. AUC/MIC ratio) for pharyngeal gonorrhea treated with aztreonam using previously published AUC for 2g aztreonam and NG isolate MIC. Among treatment failures, conduct exploratory analyses comparing pre- and post-treatment MIC for evidence of induced resistance. Study Design: Prospective cohort Study Population & Inclusion Criteria: Persons diagnosed with pharyngeal gonorrhea or gonococcal urethritis who are undergoing pharyngeal gonorrhea testing, who are not yet treated. Intervention: 2g IM aztreonam x 1 Primary Outcome: Negative gonorrhea culture 4-7 days (+/- 1 day) after treatment Sample Size: 50 persons

Official Title
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Aztreonam for Pharyngeal Gonorrhea: A Demonstration Study

Conditions
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Gonorrhea of Pharynx, Gonorrhea

Intervention / Treatment
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* Drug: Aztreonam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Persons diagnosed with pharyngeal gonorrhea or gonococcal urethritis who are undergoing pharyngeal gonorrhea testing, who are not yet treated. Exclusion Criteria: Age less than 16 years Receipt of antibiotics in ≤30 days Known allergy to aztreonam History of renal disease (including diagnosis of solitary kidney, chronic renal insufficiency, renal cell carcinoma etc.) Concurrent infection with syphilis or chlamydia Pregnancy and/or nursing Unable to return for a follow-up visit 4-7 days (+/- 1 day). Study team's discretion

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Demonstration Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2g Aztreonam<br>Subjects to receive 2g Aztreonam IM for the treatment of gonorrhea | Drug: Aztreonam<br>* 2g IM Aztreonam<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Efficacy of Pharyngeal Gonorrhea as Defined as the Proportion of Study Participants With Positive Pharyngeal Gonorrhea Culture at of Enrollment Whose Test of Cure Pharyngeal Culture is Negative | Negative Test of Cure (i.e. Pharyngeal Gonorrhea Culture) after Treatment | 4-7 days following treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of 2 g Aztreonam for N. Gonorrhoeae at Anogenital Sites | Number of individuals with a negative N. gonorrhoeae culture at an anogenital site at test of cure among those who were N. gonorrhoeae culture positive at the respective anatomic site at the enrollment visit. | Test of Cure 4-7 days following treatment | 
| Tolerability of 2g Aztreonam IM | Subjects' self-report of injection related pain on a scale from 0 - 10 where 0 is no pain and 10 is the worst pain ever. | Immediately following injection | 
| Side Effects of 2g Aztreonam IM | Subject's report of perceived side effects related to study drug based on responses to standard side effect questionnaire. | assessed immediately following injection and 4-7 days after injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aztreonam, treatment study