Antibiotics and Bleach Baths for Eczema

Overseen By Monica E Taylor, R.N.

Age: < 65

Sex: Any

Trial Phase: Phase 2

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 This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how antibiotics and bleach baths affect the bacteria on the skin of people with eczema, a chronic skin condition often accompanied by bacterial infections. Researchers will divide participants into groups to test different combinations of antibiotics (such as Cephalexin, Doxycycline, and Trimethoprim/sulfamethoxazole) and bleach treatments. Those with moderate to severe eczema or healthy individuals without a history of eczema might be suitable candidates. The study seeks to determine if these treatments can change the type and number of bacteria living on the skin. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

Research shows that the treatments in this trial have been used before and have different safety records. Cephalexin, an antibiotic often used for skin infections, including those in people with eczema, is generally safe, though some may experience stomach upset or allergic reactions.

Doxycycline, another antibiotic, can reduce inflammation, aiding skin conditions. However, in rare cases, it may cause serious skin reactions like Stevens-Johnson syndrome, a severe skin condition.

Trimethoprim/sulfamethoxazole (TMP/SMZ) also treats bacterial infections. While effective, it can sometimes lead to serious allergic reactions or skin issues.

Lastly, dilute bleach baths are considered safe and can help improve eczema symptoms. Studies have shown they are usually well-tolerated, with minor side effects like skin stinging in some cases.

Overall, each treatment carries risks, but most people tolerate them well. It is important to discuss possible side effects with a doctor before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for eczema because they combine the use of antibiotics with bleach baths, which is not a standard approach. Typically, eczema treatments focus on topical steroids or moisturizers. However, this trial explores whether systemic antibiotics like Cephalexin, Doxycycline, and TMP/SMZ, combined with dilute bleach baths, can reduce skin inflammation more effectively. The unique aspect is the potential of bleach baths to decrease bacterial load on the skin, offering a novel method to enhance the effectiveness of antibiotics. This combination might offer a dual approach to managing eczema by both directly targeting infection and reducing inflammation.

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

Research has shown that the antibiotic cephalexin, which participants in this trial may receive, can reduce skin infections in people with eczema by lowering harmful bacteria like S. aureus. One study found that combining cephalexin with topical treatments improved infected eczema. Doxycycline, another treatment option in this trial, is known for its anti-inflammatory and healing effects, which can lessen eczema severity. Trimethoprim/sulfamethoxazole (TMP/SMZ), also studied in this trial, has effectively treated skin infections, suggesting it could help manage eczema-related bacterial issues. Additionally, various studies have shown that diluted bleach baths, part of some treatment arms in this trial, significantly improve skin conditions and reduce eczema severity. These findings suggest a promising way to manage skin bacteria and relieve eczema symptoms. ^{1 2 6 7 8}

Who Is on the Research Team?

Heidi H Kong, M.D.

Principal Investigator

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

Are You a Good Fit for This Trial?

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.

My eczema is moderate to severe, with a SCORAD score of 15 or more.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

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

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.

How Is the Trial Designed?

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 United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Keflex for:

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

Approved in European Union as Cefalexin for:

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

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

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Randomized, Double-Blind, Placebo-Controlled Trial of ... The 90.5% cure rate observed in the placebo arm and 84.1% cure rate observed in the cephalexin arm provide strong evidence that antibiotics may be unnecessary ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1081120625002650

Infectious complications of atopic dermatitis: An update Invasive complications are rare; however, they can include bacteremia, osteomyelitis, septic arthritis endocarditis and viremia.

3. publications.aap.org publications.aap.org/aapgrandrounds/article/28/4/43/90745/Treatment-of-Infected-Eczema

Treatment of Infected Eczema | AAP Grand Rounds A 2-week treatment course of topical corticosteroids and oral cephalexin results in clinical improvement and lower levels of S aureus and proinflammatory ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7411503/

The infectious complications of atopic dermatitis - PMC Infectious complications are a comorbidity of AD. Although not common, systemic bacterial infections and eczema herpeticum can be life-threatening.

5. annals.edu.sg annals.edu.sg/systemic-antibiotic-prophylaxis-for-recurrent-infective-flares-in-children-and-adolescents-with-atopic-dermatitis/

Systemic antibiotic prophylaxis for recurrent infective flares ... The results of our study suggest that cephalexin prophylaxis may be a useful and safe adjunct to reduce the frequency of infective flares in patients with ...

6. aap.org aap.org/en/patient-care/atopic-dermatitis/treatment-of-atopic-dermatitis/?srsltid=AfmBOor5KGuwIDVH4O0IavKs4n8iXMMrl9jMJsUH5aH-4sFFLTQIgG9v

Treatment of Atopic Dermatitis Cephalexin (7- to 10-day course) is a common first-choice when MRSA is not suspected. Simultaneously treat for repair of skin barrier. Eczema ...

7. go.drugbank.com go.drugbank.com/drugs/DB00567

Cephalexin: Uses, Interactions, Mechanism of Action The oral LD50 in a monkey is >1g/kg and the lowest dose causing a toxic effect in humans is 14mg/kg. Cephalexin has not been shown to be harmful in pregnancy ...

8. emedicine.medscape.com emedicine.medscape.com/article/1049085-medication

Atopic Dermatitis Medication: Anti-inflammatory agents ... Cephalexin is a first-generation cephalosporin that arrests bacterial growth by inhibiting bacterial cell wall synthesis. It has bactericidal activity against ...