Cefixime vs. Penicillin for Syphilis

Overseen By Jeffrey D Klausner

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Southern California

Must be taking: HIV treatment

Must not be taking: Azithromycin, Doxycycline, Ceftriaxone, others

Disqualifiers: Pregnancy, Neurosyphilis, Allergy to penicillin, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 10 days

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, cefixime and penicillin, to determine which is more effective for treating syphilis, a sexually transmitted infection. Participants take cefixime as a pill twice a day for ten days, while penicillin (Benzathine Penicillin G) is administered as a one-time injection. The trial seeks volunteers diagnosed with early-stage syphilis who have a specific blood test result (RPR titer of 1:8 or more). Individuals with well-managed HIV can also participate. This trial may suit those with syphilis who can attend regular follow-up visits. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you have not taken certain antibiotics like azithromycin, doxycycline, ceftriaxone, or other beta-lactam antibiotics (like amoxicillin) in the past 7 days. If you are on HIV treatment, you must continue it and be virologically suppressed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Past studies have used cefixime to treat many bacterial infections, and it is generally safe. Available since 1989, it has FDA approval for other infections. Common side effects include upset stomach and diarrhea, but serious issues are rare. Research shows that cefixime is safe for most people.

Benzathine penicillin G is a well-known treatment for syphilis and other infections. It is considered safe, with the main side effect being an allergic reaction in some individuals. Most people tolerate it well with few problems.

Both treatments in this trial are generally safe based on past use and studies. Always consult a doctor about any concerns before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for syphilis?

Researchers are excited about cefixime as a potential treatment for syphilis because it offers a non-injection alternative to the standard treatment, benzathine penicillin G. Unlike the traditional single intramuscular injection of penicillin, cefixime is taken orally, which could make it more accessible and preferable for people who are needle-averse. Additionally, cefixime's 10-day oral regimen might offer more convenient treatment options for patients, especially in areas with limited healthcare access where follow-up for injections might be challenging. These features make cefixime a promising new option in the fight against syphilis.

What evidence suggests that this trial's treatments could be effective for syphilis?

Research has shown that cefixime might effectively treat early syphilis. One study found that cefixime successfully treated 87% of people with early syphilis. Another study demonstrated that cefixime was as effective as a single penicillin shot for treating early syphilis. In this trial, participants will receive either cefixime or benzathine penicillin G, a well-known and commonly used treatment for syphilis, to compare their effectiveness. ^{2 6 7 8 9}

Who Is on the Research Team?

Jeffrey D Klausner, MD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

This trial is for adults diagnosed with primary, secondary, or early latent syphilis who have an RPR titer of at least 1:8. People with HIV can join if they're on treatment and either have a low viral load or a CD4 count over 350. You can't join if you're pregnant, show signs of neurosyphilis, recently took certain antibiotics, are allergic to cephalosporins/penicillin, or can't make follow-up visits.

Inclusion Criteria

I have been diagnosed with syphilis and my recent test shows a high level of infection.

I have HIV, am on treatment, and my viral load is under control or my CD4 count is above 350.

Able to provide informed consent

Exclusion Criteria

Self-reported allergy to cephalosporins or penicillin

Individuals with HIV infection who report HIV treatment interruption for more than 4 weeks since their most recent viral load or CD4 test

I am showing signs of a brain or nerve condition caused by syphilis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either cefixime (400mg orally, twice a day, for 10 days) or a single intramuscular injection of benzathine penicillin G

10 days

Follow-up

Participants are monitored for clinical outcomes and serological response (RPR titer) every 3 months for 9 months

9 months

3 visits (in-person) every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Benzathine Penicillin G
• Cefixime

Trial Overview The study compares the effectiveness of two treatments for syphilis: Cefixime (400mg) versus benzathine penicillin G. It aims to determine which medication works better in curing the infection.

How Is the Trial Designed?

Group I: Cefixime Experimental Treatment 1 Intervention

Oral cefixime 400mg, taken twice a day for 10 days

Group II: Benzathine Penicillin G Active Control 1 Intervention

Single intramuscular injection of 2.4 million units of benzathine penicillin G

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

AIDS Healthcare Foundation

Collaborator

Trials

19

Recruited

147,000+

Universidad Peruana Cayetano Heredia

Collaborator

Trials

80

Recruited

62,300+

Published Research Related to This Trial

Cefixime (CFIX) was highly effective in treating acute uncomplicated cystitis, with an overall clinical efficacy of 80.8% in a study of 94 patients, and it successfully eradicated 97.9% of the bacterial strains isolated from patients.

The treatment was well-tolerated, with only one patient (0.7%) reporting mild side effects, and no significant drug-related laboratory abnormalities were observed, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical evaluation of cefixime in the treatment of acute uncomplicated cystitis]. Togashi, M., Kubota, M., Nagamori, S., et al.[2013]

Cefixime (CFIX) demonstrated a high overall clinical effectiveness rate of 98% in treating acute uncomplicated cystitis among 92 female patients, while showing a 57% effectiveness rate in complicated urinary tract infections (UTIs) among 42 patients.

The safety profile of CFIX was favorable, with only 1.7% of patients experiencing subjective adverse reactions, and any abnormal laboratory findings resolved after stopping the medication, indicating it is a clinically useful oral antibiotic for UTIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical evaluation of cefixime (CFIX) in the treatment of urinary tract infection]. Sonoda, T., Matsuda, M., Nakano, E., et al.[2013]

SY5555, a new oral penem antibiotic, demonstrated superior antibacterial activity against several common bacteria, including methicillin-susceptible Staphylococcus aureus and Streptococcus pneumoniae, compared to cefaclor, cefixime, and cefteram.

Unlike many beta-lactam antibiotics, SY5555 was not hydrolyzed by various beta-lactamases, suggesting it may have a more targeted action against certain bacterial strains, although it was still susceptible to specific beta-lactamases from Xanthomonas maltophilia and Pseudomonas aeruginosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro antibacterial activity and beta-lactamase stability of SY5555, a new oral penem antibiotic. Inoue, E., Mitsuhashi, S.[2021]

Cefixime (CFIX) demonstrated high therapeutic effectiveness in treating urinary tract infections, achieving a 100% clinical efficacy rate in women with acute uncomplicated cystitis and a 63% efficacy rate in patients with complicated UTIs, based on a study of 129 cases.

The treatment was generally safe, with only 3.1% of patients experiencing mild adverse reactions, all of which resolved after stopping the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical experience with cefixime in urinary tract infections]. Kameoka, H., Takano, Y., Miyoshi, S., et al.[2016]

Cefixime demonstrated a high clinical success rate of 94% in treating community-acquired acute lower respiratory tract infections, which is comparable to other antibiotics, with eradication rates reaching 92%.

The safety profile of cefixime was similar to that of other antibiotics, with adverse experiences reported in 34% to 50% of patients across treatment groups, primarily mild to moderate gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cefixime in the treatment of patients with lower respiratory tract infections: results of US clinical trials. Quintiliani, R.[2019]

Cefixime was tested in multicenter trials involving 406 patients (137 children and 269 adults) with respiratory and urinary tract infections, showing positive clinical and bacteriological outcomes in 76-90% of cases.

The medication had a low incidence of adverse reactions, such as skin eruptions and dyspepsia, which were rare and did not necessitate specific treatment, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical efficacy of cefixime (results of multicenter trials)]. Sereda, EV., Gusel', VA., Feshchenko, IuI., et al.[2016]

In a trial involving 40 children with culture-positive typhoid fever, cefixime demonstrated a significantly higher clinical cure rate of 90% compared to 45% for chloramphenicol after 14 days of treatment.

Cefixime proved to be highly effective, curing 93.3% of all cases when including patients who switched from chloramphenicol to cefixime, highlighting its potential as a preferred treatment option for typhoid fever in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of cefixime and chloramphenicol in children with typhoid fever. Rabbani, MW., Iqbal, I., Malik, MS.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8423500/

Clinical Efficacy of Cefixime for the Treatment of Early ... In this randomized noncomparative clinical study, 87% of participants with early syphilis who received cefixime were treated successfully. The study included an ...

2. academic.oup.com academic.oup.com/ofid/article/12/Supplement_1/ofae631.075/7988391

217. Preliminary Results from a Clinical Trial Comparing the ... A previous pilot study showed cefixime was likely efficacious in treating early syphilis. This study aims to evaluate the efficacy of cefixime in comparison to ...

3. jwatch.org jwatch.org/na59090/2025/09/12/cefixime-might-it-be-option-treating-early-syphilis

Cefixime: Might It Be an Option for Treating Early Syphilis? In a small randomized open-label trial, oral cefixime was as effective as a single injection of penicillin for treating early syphilis. Along ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03752112

Study Details | NCT03752112 | Trial Evaluating the ... Hypotheses The antibiotic, Cefixime, for use in non-pregnant women with early syphilis will be efficacious and safe. Primary Objective The primary objective ...

5. link.springer.com link.springer.com/article/10.1007/s11904-025-00725-4

Expanding Horizons in Syphilis Treatment: Challenges ... The most robust evidence supports penicillin use in early syphilis, but data for late-stage syphilis, neurosyphilis, and congenital syphilis ...

6. rxlist.com rxlist.com/suprax-drug.htm

Suprax (Cefixime): Side Effects, Uses, Dosage, Interactions ... Suprax (cefixime) for Oral Suspension is a cephalosporin antibiotic used to treat many different types of infections caused by bacteria.

7. reference.medscape.com reference.medscape.com/drug/suprax-cefixime-342503

Suprax (cefixime) dosing, indications, interactions, adverse ... Indicated in the treatment of uncomplicated urinary tract infections caused by susceptible isolates of Escherichia coli and Proteus mirabilis.

8. drugs.com drugs.com/cefixime.html

Cefixime: Uses, Dosage, Side Effects & Warnings Cefixime is an antibiotic that may be used to treat many different types of infections caused by bacteria. It was FDA approved in 1989.

9. cdc.gov cdc.gov/std/treatment-guidelines/gonorrhea-adults.htm

Gonococcal Infections Among Adolescents and Adults Furthermore, as cefixime becomes less effective, continued used of cefixime might hasten the development of resistance to ceftriaxone, a safe, well-tolerated, ...