Antibiotics and Bleach Baths for Eczema

Recruiting in Palo Alto (17 mi)

Overseen by Heidi H Kong, M.D.

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Must not be taking: Antibiotics, Corticosteroids, CAM agents

Disqualifiers: Pregnancy, Immunodeficiency, Chronic illnesses, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Background: - Atopic dermatitis, or eczema, is a chronic skin disorder. Patients sometimes have infections with S. aureus bacteria. Researchers want to study how eczema treatments affect the number and the type of bacteria on the skin. Objectives: - To study the effect of eczema treatments on skin bacteria. Eligibility: * Individuals between 2 and 25 years of age who have moderate to severe atopic dermatitis. * Healthy volunteers between 18 and 40 years of age with no history of eczema. Design: * Participants will be screened with a physical exam and medical history. Research samples will be collected. Skin biopsies may also be performed. * All participants will be assigned to one of several study groups. * This study will last for up to 1 year. Healthy volunteers must not have taken antibiotics in the year before the start of the study. * All participants will have regular study visits during their 1-year participation. More research samples will be collected at these visits.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop using certain medications before participating. Specifically, you must not have used systemic antibiotics within 8 weeks, topical antibiotics on sampling sites within 3 weeks, or topical corticosteroids on sampling sites within 7 days before starting the trial.

Is the treatment of antibiotics and bleach baths for eczema generally safe in humans?

The risk of serious diseases from antibiotics like cephalexin and trimethoprim-sulfamethoxazole is small, with rare cases of liver, blood, skin, and kidney issues. Cephalosporins, a class of antibiotics that includes cephalexin, are generally safe and less likely to cause allergies compared to penicillins, though some people with penicillin allergies may react to them. Bleach baths, when used properly, are generally considered safe for skin conditions like eczema. ^{1 2 3 4 5}

How does the drug combination of Cephalexin, Doxycycline, and Trimethoprim/sulfamethoxazole for eczema differ from other treatments?

This drug combination is unique because it combines antibiotics that target a broad range of bacteria, potentially addressing bacterial infections that can worsen eczema. Cephalexin is effective against gram-positive bacteria like Staphylococcus aureus, while Doxycycline and Trimethoprim/sulfamethoxazole cover a wider spectrum, including some gram-negative bacteria, which may not be the focus of standard eczema treatments. ^{6 7 8 9 10}

Research Team

Heidi H Kong, M.D.

Principal Investigator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Eligibility Criteria

This trial is for people aged 2-50 with moderate to severe atopic dermatitis, and healthy volunteers aged 18-40. Participants need access to bathing facilities, must not have used certain medications recently, and should not be pregnant or lactating. Smokers and those with a history of serious allergies or immune deficiencies are excluded.

Inclusion Criteria

Subjects must participate fully and be willing to comply with the procedures of the protocol

I am between 2 and 50 years old with atopic dermatitis.

I am a healthy volunteer aged between 18 and 50.

Exclusion Criteria

Inability to comply with the requirements of the protocol

I am experiencing symptoms or have hormone levels indicating I am in perimenopause.

I do not smoke or use smokeless tobacco products.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive randomized antimicrobial treatments, including antibiotics and study baths, for up to 56 days

8 weeks

Regular visits throughout the treatment period

Follow-up

Participants are monitored for microbiome alterations and clinical responses after treatment

4 weeks

2 visits (in-person)

Long-term monitoring

Participants continue to be monitored for microbiome changes and skin condition over the course of 1 year

1 year

Regular study visits

Treatment Details

Interventions

• Cephalexin (Antibiotic)
• Doxycycline (Antibiotic)
• Placebo capsules (Other)
• Placebo Sodium hypochlorite (Other)
• Sodium hypochlorite (Other)
• Trimethoprim/sulfamethoxazole (TMP/SMZ) (Antibiotic)

Trial Overview The study examines the effects of antibiotics (TMP/SMZ, Cephalexin, Doxycycline) and Sodium hypochlorite compared to placebos on skin bacteria in eczema patients over one year. It involves regular visits for sample collection and possibly skin biopsies.

Participant Groups

Group I: 1C/Doxycycline 100 Active Control 2 Interventions

Doxycycline 100 mg orally every 12 hours for 56 days

Group II: 3A/Cephalexin + Dilute bleach Active Control 2 Interventions

Systemic antibiotics (Cephalexin) + dilute bleach study bath liquid

Group III: 1A/Cephalexin Active Control 1 Intervention

Cephalexin + Placebo bleach

Group IV: 2A/Cephalexin + Dilute bleach Active Control 2 Interventions

Systemic antibiotics (Cephalexin) + dilute bleach study bath liquid

Group V: 1B/TMP/SMX Active Control 1 Intervention

TMP/SMZ DS 800 /160 orally every 12 hours for 14 days

Group VI: 1D/Doxycycline 20 Active Control 1 Intervention

Doxycycline 20 mg orally every 12 hours for 56 days

Group VII: 3B/Cephalexin + Placebo bleach Placebo Group 2 Interventions

Systemic antibiotics (Cephalexin) + placebo study bath liquid

Group VIII: 2B/Cephalexin + Placebo bleach Placebo Group 2 Interventions

Systemic antibiotics (Cephalexin) + placebo study bath liquid

Group IX: 2C/Placebo capsules + Dilute bleach Placebo Group 2 Interventions

Placebo capsules + dilute bleach study bath liquid

Group X: 2D/Placebo capsules + Placebo bleach Placebo Group 2 Interventions

Placebo capsules + placebo study bath liquid

Cephalexin is already approved in Canada, Switzerland for the following indications:

Approved in Canada as Keflex for:

• Respiratory tract infections
• Otitis media
• Skin and skin structure infections
• Bone infections
• Genitourinary tract infections

Approved in Switzerland as Keflex for:

• Respiratory tract infections
• Otitis media
• Skin and skin structure infections
• Bone infections
• Genitourinary tract infections

Who Is Running the Clinical Trial?

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Lead Sponsor

Trials

508

Recruited

1,090,000+

Dr. Lindsey A. Criswell

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Director since 2021

MD, MPH, DSc

Dr. Robert Colbert

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Clinical Director since 2014

MD

Findings from Research

In a study of 34 penicillin-allergic patients, 47% tested positive for specific penicillin determinants, indicating a significant prevalence of skin test reactivity to penicillins.

The study found that 14% of patients had positive skin tests for cephalexin, but none reacted to ceftazidime, suggesting that side-chain-specific determinants play a crucial role in cross-reactivity between penicillins and cephalosporins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allergic reactions to betalactams: studies in a group of patients allergic to penicillin and evaluation of cross-reactivity with cephalosporin. Audicana, M., Bernaola, G., Urrutia, I., et al.[2019]

Third generation cephalosporins are a safe class of antibiotics with fewer side effects and lower allergenic potential compared to other antibiotics like penicillins and aminoglycosides, making them suitable for use in various healthcare settings.

While generally safe, some third generation cephalosporins can cause specific issues such as hypoprothrombinemia and disulfiram-like reactions, and they may lead to increased diarrhea and risk of drug-resistant bacteria if not monitored properly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Third generation cephalosporins: safety profiles after 10 years of clinical use. Neu, HC.[2019]

In a study of 20 patients with a history of type I hypersensitivity to penicillins, 18 showed negative skin test reactions to cephalosporin antibiotics, suggesting they can safely receive these medications for chemoprophylaxis during open heart surgery.

Only 2 patients had positive skin tests, but they were able to receive vancomycin safely, indicating that negative skin tests can help identify patients who are not at risk for allergic reactions to cephalosporins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross allergenicity between penicillins and cephalosporins. Beam, TR., Spooner, J.[2006]

Acute rhinosinusitis is a leading cause of antibiotic prescriptions globally, raising concerns about antibiotic resistance and the safety of commonly used antibiotics like macrolides and fluoroquinolones.

A surveillance study on the new cephalosporin drug Spectracef (Cefditoren) showed promising efficacy and safety for treating acute bacterial rhinosinusitis, particularly due to its different chemical structure that may reduce the risk of cross-allergy with penicillins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A study of the efficacy and safety of new cephalosporin in the treatment of acute bacterial rhinosinusitis]. Savlevich, EL., Kozlov, VS., Zharkykh, MA.[2018]

In a study of over 695,000 patients, the risk of serious liver disease was low and similar for those taking trimethoprim-sulfamethoxazole (TMP-SMZ) and trimethoprim alone, with rates of 5.2 and 3.8 per 100,000 respectively.

The overall risk of serious adverse effects, including blood and skin disorders, was small for TMP-SMZ, trimethoprim, and cephalexin, suggesting these antibiotics are relatively safe compared to many others.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A large population-based follow-up study of trimethoprim-sulfamethoxazole, trimethoprim, and cephalexin for uncommon serious drug toxicity. Jick, H., Derby, LE.[2016]

The six newly developed oral cephem antibiotics, particularly those with an aminothiazolyl side chain, demonstrated greater antimicrobial activity against common bacteria like E. coli and K. pneumoniae compared to traditional antibiotics such as ampicillin and cephalexin.

While these new antibiotics showed improved effectiveness against certain bacteria, they were less effective against others like P. aeruginosa and enterococci, indicating a need for careful selection based on the type of infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimicrobial activities of six new oral cephem antibiotics. Chang, SC., Hsieh, WC., Luh, KT., et al.[2016]

Doripenem has been FDA-approved for treating complicated intra-abdominal and urinary tract infections, demonstrating its efficacy and safety in these conditions.

Ceftobiprole is currently under FDA review based on phase 3 clinical trial results, while ceftaroline has completed at least one phase 3 trial, indicating ongoing evaluation of their effectiveness and safety in treating infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Newer beta-lactam antibiotics: doripenem, ceftobiprole, ceftaroline, and cefepime. Bazan, JA., Martin, SI., Kaye, KM.[2011]

Cefazolin, cephaloridine, and cephalothin are highly effective against Staphylococcus aureus, with over 90% of strains suppressed at low concentrations, while cephalexin is less effective against this bacterium.

Cefazolin is the most potent cephalosporin against gram-negative bacteria like E. coli, achieving high serum concentrations after intramuscular injection that are sustained for 8 hours, indicating its strong antibacterial activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of antibacterial activities of cephalosporin antibiotics: cefazolin, cephaloridine, cephalothin, and cephalexin. Hsieh, WC., Ho, SW.[2015]

All four oral cephems (cephalexin, cefaclor, cefatrizine, and cefadroxil) showed similar effectiveness against staphylococci, indicating they can be used interchangeably for infections caused by these bacteria.

Cefatrizine and cefaclor were found to be more effective than cephalexin and cefadroxil against certain strains of E. coli, Klebsiella pneumoniae, and Proteus mirabilis, highlighting cefatrizine as the most potent option among the tested drugs for these infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of in vitro antibacterial activity of four oral cephems: cephalexin, cefaclor, cefatrizine and cefadroxil. Luh, KT., Chao, HP., Ho, SW., et al.[2015]

A study of bacterial pathogens from respiratory infections in the Kyoto-Shiga area revealed an increase in Pseudomonas aeruginosa and a decrease in Haemophilus influenzae between 1981 and 1983, indicating changing trends in bacterial infections.

In vitro tests showed that while cefazolin and cefotiam were effective against Staphylococcus aureus, their effectiveness declined from 1981 to 1983, highlighting the need for ongoing monitoring of antibiotic efficacy against evolving bacterial strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[In vitro susceptibility of bacterial isolates from patients with respiratory tract infections to beta-lactam antibiotics]. Otsuki, M., Tanaka, M., Saji, Y., et al.[2016]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

Allergic reactions to betalactams: studies in a group of patients allergic to penicillin and evaluation of cross-reactivity with cephalosporin. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Third generation cephalosporins: safety profiles after 10 years of clinical use. [2019]

3. Italy pubmed.ncbi.nlm.nih.gov

Cross allergenicity between penicillins and cephalosporins. [2006]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[A study of the efficacy and safety of new cephalosporin in the treatment of acute bacterial rhinosinusitis]. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

A large population-based follow-up study of trimethoprim-sulfamethoxazole, trimethoprim, and cephalexin for uncommon serious drug toxicity. [2016]

6. Singapore pubmed.ncbi.nlm.nih.gov

Antimicrobial activities of six new oral cephem antibiotics. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Newer beta-lactam antibiotics: doripenem, ceftobiprole, ceftaroline, and cefepime. [2011]

8. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Evaluation of antibacterial activities of cephalosporin antibiotics: cefazolin, cephaloridine, cephalothin, and cephalexin. [2015]

9. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Comparison of in vitro antibacterial activity of four oral cephems: cephalexin, cefaclor, cefatrizine and cefadroxil. [2015]

10. Japan pubmed.ncbi.nlm.nih.gov

[In vitro susceptibility of bacterial isolates from patients with respiratory tract infections to beta-lactam antibiotics]. [2016]