Experimental Human Infection With Neisseria Gonorrhoeae
Condition: Gonococcal Infection
MeSH terms: Infections; Communicable Diseases; Gonorrhea
Intervention: Cefixime; Ceftriaxone; Ciprofloxacin; Neisseria gonorrhoeae strain FA1090 A26; Neisseria gonorrhoeae strain FA7537
Intervention description: Mandatory rescue therapy consisting of cefixime 400 mg orally in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.; Mandatory rescue therapy consisting of ceftriaxone 250 mg intramuscularly in a single dose: on patient request, at the onset of symptoms or on the 5th study day after inoculation.; Mandatory antibiotic treatment failure therapy: Ciprofloxacin 500 mg orally in a single dose: if the subject has a positie test of cure 1 week post initial antibiotic treatment; 0.4 mL of a suspension containing 10^5 - 10^6 CFU of Neisseria gonorrhoeae, in phosphate-buffered saline, delivered to the anterior urethra through a No.8 pediatric French catheter.; 0.4 mL of a suspension containing 10^5 - 10^6 CFU of Neisseria gonorrhoeae, in phosphate-buffered saline, delivered to the anterior urethra through a No.8 pediatric French catheter
Intervention MeSH terms: Ciprofloxacin; Ceftriaxone; Cefixime
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: Male
Minimum age: 18 Years
Maximum age: 36 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: ceftriaxone; challenge; ciprofloxacin; males; Neisseria gonorrhoeae

Summary:

      This is a Phase 1, interventional, non-randomized, experimental infection model study with
      healthy adult males adults (N=32) between the ages of 18-36 at study enrollment. The study is
      designed to test the requirements of predicted N. gonorrhoeae virulence determinants for
      gonococcal infection in the male urethra. The duration for all participants will be about 3
      weeks. Study duration will be approximately about 18 months for implementation and
      enrollment. The primary objectives of the present study are to: (1) compare infectivity of
      different isogenic mutants with wild-type (WT) N. gonorrhoeae in noncompetitive infections
      and to (2) assess relative fitness of the mutant in competitive infections initiated by
      inocula containing equivalent numbers of both WT and mutant strains for mutants with WT
      infectivity.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy man > / = 18 and < 36 years old

          2. Able and willing to be located easily by providing street address and telephone number
             (land line and/or cell phone number)

          3. Willingness to provide written informed consent

          4. Able and willing to attend all study visits including 6-day stay in the Clinical
             Translational Research Center (CTRC) during the trial (with ability to leave the unit
             during the day) and follow-up visit during the week after treatment

          5. Able and willing to abstain from all sexual activity until completion of the study and
             the follow-up test for gonorrhea is negative

          6. Acceptable medical history by screening evaluation

          7. No clinically significant abnormalities on physical exam

          8. Urinalysis: leukocyte esterase, and White Blood Cell (WBC) values within normal limits
             (WNL)

          9. CH50 WNL

         10. Urine negative for chlamydia, gonorrhea, and trichomonas

         11. Negative Human Immunodeficiency Virus (HIV), syphilis, and Hepatitis C (HCV) test
             results

         12. Negative Hepatitis B (HBV) core and surface antibodies or results consistent with
             immunization (negative HBV core antibody/positive HBV surface antibody)

         13. Denies history of Sexually Transmitted Infections (STIs) including gonorrhea,
             chlamydia, syphilis, HIV, HBV, and HCV

         14. Denies history of bleeding diathesis

         15. Denies history of seizures (due to reports of seizures with ciprofloxacin)

         16. Denies history of cancer, except basal cell carcinoma of the skin > 5 years ago

         17. Denies history of drug abuse

         18. Denies history of genitourinary surgery

        Exclusion Criteria:

          1. Student or employee under the direct supervision of any of the study investigators

          2. Any known immunodeficiencies including complement deficiency, antibody deficiency,
             chronic granulomatous disease or Human Immunodeficiency Virus (HIV) infection

          3. Psychiatric disorders that, in the opinion of the physician, would interfere with the
             integrity of the data or volunteer safety

          4. Unstable depression (defined as receiving either < 3 months of the same medication
             (and dose) or a decompensating event during the previous 3 months) or depression that,
             in the opinion of the investigator, will compromise the subject's ability to comply
             with protocol requirements

          5. Heart murmur or heart disease

          6. Anatomic abnormality of the urinary tract

          7. Any antibiotic treatment in the past 30 days, or azithromycin in the past 60 days

          8. Self-reported chemotherapy within the past year

          9. Current steroid use, except for topical application

         10. Allergy to penicillin, cephalosporins or ciprofloxacin or to lidocaine

         11. Treatment with medications in the previous month that are contraindicated with
             cefixime, ceftriaxone or ciprofloxacin and that cannot be withheld for the single
             doses given in this study

         12. Serum creatinine level < 0.7 or > 1.75 mg/dL and deemed clinically significant by the
             study physician

         13. Serum ALT level < LLN or > 105 U/L and deemed clinically significant by the study
             physician

         14. WBC count < 2.5 or > 15.0 x 10^9/L and deemed clinically significant by the study
             physician

         15. Absolute neutrophil count (ANC) < 1.5 or > 7.5 x 10^9/L and deemed clinically
             significant by the study physician Exception: For African Americans, ANC values as low
             as 1.3 x 10^9/L will be allowed (25)

         16. Hemoglobin level < 12.0 g/dL or above ULN and deemed clinically significant by the
             study physician

         17. Urinalysis: Qualitative protein level > 1+ or RBC count > 10/hpf

        Medications not permitted with cefixime or ceftriaxone:

          1. Warfarin

          2. Probenecid

          3. Aspirin

          4. Diuretics such as furosemide

          5. Aminoglycoside antibiotics

          6. Chloramphenicol

        Medications not permitted with ciprofloxacin:

          1. Tizanidine

          2. Theophylline

          3. Warfarin

          4. Glyburide

          5. Cyclosporine

          6. Probenecid

          7. Phenytoin

          8. Methotrexate

          9. Antacids, multivitamins, and other dietary supplements containing magnesium, calcium,
             aluminum, iron or zinc

         10. Caffeine-containing medications

         11. Sucralfate or didanosine chewable or buffered tablets