Cephalexin for Kidney Infection

Recruiting at 1 trial location

Overseen By Brett Faine, PharmD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Brett A Faine

Must be taking: Antimicrobials

Must not be taking: Antibiotics, Cephalosporins

Disqualifiers: Diabetes, Liver disease, Pregnancy, others

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

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 10 days

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot study will randomize 40 female patients with acute uncomplicated pyelonephritis to receive standard duration of therapy versus patient-directed antimicrobial duration (PDAD). The primary objectives of this pilot trial are to determine the feasibility and safety of conducting a full-scale multi-center randomized controlled trial.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have taken antibiotics in the last 48 hours, you cannot participate.

Is cephalexin safe for humans?

Cephalexin is generally considered safe for humans, with common side effects including skin rashes, itching, and mild stomach issues. Serious allergic reactions are rare, and it is less likely to cause kidney problems compared to some other antibiotics. ^{1 2 3 4 5}

How does the drug Cephalexin differ from other treatments for kidney infections?

Cephalexin is unique because it is a cephalosporin antibiotic that is well absorbed from the gastrointestinal tract and achieves high concentrations in the urine, making it effective against common urinary tract infection bacteria. It is also known for its low incidence of side effects and can be used in patients with impaired kidney function, with dosage adjustments based on renal status. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for women aged 18-55 with a kidney infection called acute uncomplicated pyelonephritis. They must be able to go home on oral antibiotics, understand English or Spanish, and have started antibiotics in the last 48 hours. It's not for those with insulin-dependent diabetes, end-stage liver disease, serious allergies to cephalosporins or penicillins, or certain kidney complications.

Inclusion Criteria

You have a serious allergic reaction to the study medication or a similar type of medication called a cephalosporin.

You have a known blockage or infection in your kidneys found by a hospital ultrasound.

My liver is in its final stage of disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants are randomized to receive either 10 days of cephalexin or patient-directed antimicrobial duration (PDAD) with a minimum of 3 days of cephalexin followed by placebo once symptom resolution is reported.

10 days

1 visit (in-person), daily assessments (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with urine samples collected at in-person visits.

90 days

3 visits (in-person) at day 1, 3 weeks, and 4 weeks

Treatment Details

Interventions

• Cephalexin

Trial Overview The study tests if letting patients decide how long they take Cephalexin (an antibiotic) is safe and feasible compared to a standard treatment duration. This pilot will help determine if a larger trial should be conducted.

Participant Groups

Group I: Patient-directed antimicrobial duration (PDAD) Experimental Treatment 1 Intervention

Group II: Standard Duration Treatment Active Control 1 Intervention

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?

Brett A Faine

Lead Sponsor

Trials

2

Recruited

60+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

Findings from Research

In two randomized studies involving 343 patients, cephalexin hydrochloride was found to be as effective as cephalexin monohydrate for treating skin and soft tissue infections, with high response rates of 95.7% and 96.5% respectively.

Both formulations demonstrated a similar safety profile, with only 4.95% of patients experiencing adverse events, indicating that cephalexin hydrochloride is a safe and effective option for these infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study of cephalexin hydrochloride and cephalexin monohydrate in the treatment of skin and soft tissue infections. Kumar, A., Murray, DL., Hanna, CB., et al.[2021]

Cephalosporins are generally safe with fewer side effects compared to penicillins, and recent studies suggest that cross-reactivity in patients with penicillin allergies may not be a significant concern.

While modern cephalosporins have low nephrotoxicity, some can cause bleeding risks and gastrointestinal issues, particularly ceftriaxone and cefoperazone, which can lead to high biliary concentrations and potential Clostridium difficile infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of cephalosporins. Norrby, SR.[2018]

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]

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]

A study reviewing 325 patient charts found that adjusting electronic medical record alerting rules for β-lactam antibiotics resulted in no cases of anaphylaxis (0%) among patients who received these medications after being documented as allergic to penicillins.

The new alerting rules, which only flagged similar side chain antibiotics, effectively reduced unnecessary alerts for prescribers while maintaining patient safety, although some patients did experience non-anaphylactic delayed reactions like rashes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β-lactam exposure outcome among patients with a documented allergy to penicillins post-implementation of a new electronic medical record system and alerting rules. Buffone, B., Lin, YC., Grant, J.[2022]

Cephalexin is effectively absorbed and excreted in high concentrations in urine, making it suitable for treating urinary tract infections caused by common bacteria like E. coli, even in patients with impaired kidney function.

In anephric patients, cephalexin can achieve high serum concentrations after doses of 250 or 500 mg, although absorption may be delayed in some cases, and hemodialysis significantly reduces its serum levels by 58%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cephalexin: absorption and excretion as related to renal function and hemodialysis. Reisberg, BE., Mandelbaum, JM.[2021]

Cephalexin is an effective oral antibiotic for treating urinary tract infections, achieving high concentrations in urine where it effectively targets the bacteria responsible for these infections.

It has a strong safety profile, being essentially nontoxic at recommended doses, and its clinical efficacy has been consistently supported by studies since 1971.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cephalexin in the therapy of infections of the urinary tract. Weinstein, AJ.[2013]

Cephalexin is effective against common pathogens causing infections in the respiratory tract, skin, and urinary tract, and can be taken in high oral doses without causing gastrointestinal irritation.

It has a low incidence of allergies and side effects due to its rapid absorption in the upper intestine and minimal metabolism in the body, making it a safe option for many patients, although dosage adjustments are necessary for those with reduced kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of cephalexin. Griffith, RS.[2013]

Cephalosporins, despite being more expensive, are still commonly used for urinary tract infections due to their high urinary concentrations, which can exceed 1000 mg/L after small doses, making them effective in treating these infections.

While single-dose oral cephalosporins like cephalexin and cefaclor are less effective than other antibiotics for uncomplicated lower urinary tract infections, they are still utilized, and newer cephalosporins like cefuroxime axetil show promise for short-term therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cephalosporins in urinary tract infection. Gentry, LO.[2018]

In normal subjects, a single 500-mg dose of cefalexin resulted in peak serum levels of 12.0 mcg/ml after 2 hours, with a serum half-life of approximately 1.03 hours, indicating effective absorption and elimination in healthy individuals.

In patients with renal impairment and those on hemodialysis, the elimination of cefalexin was significantly slower, with a serum half-life potentially reaching 8.47 hours, highlighting the need for adjusted dosing based on kidney function to ensure safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of cefalexin pharmacokinetics and dosage adjustments in relation to renal function. Brogard, JM., Pinget, M., Dorner, M., et al.[2019]

References

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

Comparative study of cephalexin hydrochloride and cephalexin monohydrate in the treatment of skin and soft tissue infections. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Side effects of cephalosporins. [2018]

3. England pubmed.ncbi.nlm.nih.gov

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

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

[Clinical efficacy of cefixime (results of multicenter trials)]. [2016]

5. Canada pubmed.ncbi.nlm.nih.gov

β-lactam exposure outcome among patients with a documented allergy to penicillins post-implementation of a new electronic medical record system and alerting rules. [2022]

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

Cephalexin: absorption and excretion as related to renal function and hemodialysis. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Cephalexin in the therapy of infections of the urinary tract. [2013]

8. England pubmed.ncbi.nlm.nih.gov

The pharmacology of cephalexin. [2013]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Cephalosporins in urinary tract infection. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Determination of cefalexin pharmacokinetics and dosage adjustments in relation to renal function. [2019]