4 Clinical Trials for Various Conditions
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: 1. Determine the proportion of persons whose pharyngeal gonococcal infections are cured with a single dose of 2g aztreonam intramuscularly. 2. Determine the proportion of persons with urethral and/or rectal gonorrhea whose infections are cured with a single dose of 2g aztreonam IM. 3. Evaluate the tolerability of 2g IM of aztreonam . 4. 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. 5. 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
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 gentamicin 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 gentamicin is 91% efficacious for genital NG, its efficacy at the pharynx may be less since streptomycin, another aminoglycoside previously used to treat gonorrhea, was not effective for pharyngeal NG. It is unknown if streptomycin's poor efficacy is indicative of limitations of aminoglycosides as a class. We plan to enroll 60 men who have sex with men in a demonstration study to be conducted at the Seattle \& King County STD Clinic to test the efficacy of 360 mg of gentamicin given intramuscularly for pharyngeal gonorrhea. Secondary objectives include determining the ideal pharmacodynamic criterion (comparing in vitro minimal inhibitory concentrations (MIC) of NG to peak gentamicin serum levels), estimating resistance induction among treatment failures, and assessing the tolerability of 360 mg of IM gentamicin. Objectives The proposed study aims to evaluate the efficacy of a single intramuscular (IM) dose of gentamicin in the treatment of pharyngeal gonorrhea. Secondary objectives include documenting the efficacy stratified by minimal inhibitory concentration (MIC) compared with the gentamicin peak level in order to estimate a pharmacodynamic criterion. We will also attempt to determine whether gentamicin monotherapy induces antimicrobial resistance among treatment failures. Lastly, we will evaluate the tolerability of 360 mg of IM gentamicin, stratified by subject weight (i.e. weight based dosing). The specific aims are: 1. Determine the proportion of persons whose pharyngeal gonococcal infections are cured with a single dose of 360mg gentamicin intramuscularly alone. 2. Evaluate the renal safety and tolerability of 360mg IM of gentamicin. 3. Document mean peak gentamicin levels following 360mg IM of gentamicin stratified by weight. 4. Estimate the best pharmacodynamics criterion (i.e. peak/MIC ratio) for pharyngeal gonorrhea treated with gentamicin using individual and mean peak gentamicin levels and NG isolate MIC. 5. Among treatment failures, conduct exploratory analyses comparing pre- and post-treatment MIC for evidence of induced resistance.
Investigators at the University of Alabama in Birmingham in collaboration with investigators from the Centers for Disease Control in Atlanta are evaluating the performance of three commercial nucleic acid amplification tests for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae in pharyngeal and rectal swab specimens. Cultures for C. trachomatis and N. gonorrhoeae are performed as additional reference tests. Study subjects are men and women attending sexually transmitted disease (STD) and HIV care clinics in Birmingham, Alabama, who report sexual behaviors that place them at risk for pharyngeal or rectal sexually transmitted infections.
Julius Schachter, PhD, from the Department of Laboratory Medicine at UCSF, and Jeffrey Klausner, MD, from the Department of Public Health, are conducting a study to evaluate a type of test (nucleic acid amplification test) for the detection of two sexually transmitted diseases, Chlamydia trachomatis and Neisseria gonorrhoeae, in men who have sex with men (MSM), using urine samples and swabs taken from the throat (pharynx), tip of penis (glans), and rectum. The use of nucleic acid amplification tests on these swabs is experimental, which means that the use of the tests for this purpose have not been approved by the Food \& Drug Administration.