Clinical Trials Logo

Clinical Trial Summary

The goal of this study is to figure out the best doses for two antibiotics (called cefadroxil and cephalexin) when they are used to treat bone, joint, or muscle infections in children. In order to do this, the study will collect data about children admitted to Children's Hospital Colorado who have these types of infections. During the study, these patients will receive doses by mouth of each of these antibiotics, in addition to an IV antibiotic (given through a vein) used to treat their infection. After the dose of the first antibiotic, blood samples will be drawn every few hours to measure how much of the drug is still in their body, until it is all gone. After the first antibiotic is out of the patient's body, the same will be done for the second antibiotic. Measurements, in the lab, of how much of these antibiotics are needed to kill the most common bacteria causing these infections, which is a type of "Staph" bacteria called "MSSA", will be taken. Finally, the blood levels of the antibiotics and the information from the lab tests about the Staph bacteria will be used to calculate how much and how often of the antibiotic should be given to children with bone, joint, or muscle infections. Currently, these types of infections are treated with an antibiotic that children have to take four times every day. The goal of this study is to find an antibiotic that children can take only two or three times per day.


Clinical Trial Description

This study aims to shift the current treatment paradigm for the use of oral first-generation cephalosporins in pediatric musculoskeletal (MSK) infections. Optimizing treatment for MSK infections is particularly important, as osteomyelitis is one of the most common severe infections affecting children. Treatment for these infections has markedly improved over the last few decades, but significant morbidity is still seen, including the possibility of permanent disability due to pathologic fracture, growth arrest, and joint destruction. To avoid these long term sequelae and recrudescent infection, early diagnosis, appropriate therapy, and prolonged treatment courses (typically 4-6 weeks, or longer) are essential. The most commonly used antibiotic for MSK infections is cephalexin, a first-generation cephalosporin. It is well tolerated, provides good tissue penetration, and has a preferred spectrum of activity for typical MSK pathogens, including methicillin susceptible Staphylococcus aureus (MSSA). Despite cephalexin's widespread use, its most significant disadvantage is its short plasma half-life. Because of this, cephalexin is traditionally dosed four times daily (QID) for serious infections like osteomyelitis. However, this dosing frequency, especially for prolonged treatment courses, proves difficult for both patients and their families. Concern about poor adherence drives some providers to prolong IV therapy or dose cephalexin three times daily (TID), though there are insufficient pharmacokinetic/pharmacodynamic (PK/PD) or outcome data to support TID dosing. Cefadroxil, another first-generation cephalosporin, is an appealing alternative to cephalexin due to its longer half-life. Because of this, the investigators hypothesize that cefadroxil could be used effectively in pediatric patients with MSK infections with a more convenient dosing schedule than cephalexin. While cephalexin is typically dosed 3-4 times per day, cefadroxil could likely be dosed 2-3 times per day, even for serious infections like osteomyelitis. However, cefadroxil is rarely prescribed to children due to a lack of pediatric PK/PD data to guide dosing. Our study aims to address this unmet need and help physicians use these existing drugs in smarter and more effective ways in pediatric MSK infections. The specific aims of this study are to: 1. Use a Population PK approach to define comparative PK parameters of cefadroxil and cephalexin in pediatric patients with MSK infections (osteomyelitis, septic arthritis, pyomyositis). 2. Establish reference MIC ranges for both cefadroxil and cephalexin against MSSA isolates. 3. Perform pharmacodynamic modeling (Monte Carlo simulation) based on the above PK parameters and MIC data to evaluate the expected PK/PD target attainment of cefadroxil and cephalexin at different dosing intervals: cephalexin given as 3 vs. 4 divided doses per day; cefadroxil given as 2 vs. 3 doses against a range of MICs. To answer these questions, patients with MSK infections admitted to Children's Hospital Colorado (CHCO) will be enrolled in this study and sequentially given doses of both cefadroxil and cephalexin. After each oral dose, serum levels of the antibiotic will be measured at set time points until the drug is expected to be fully cleared. They will then receive the second antibiotic after a 24-hour washout period. MIC ranges will be measured based on banked MSSA isolates. Based on these study-derived PK and MIC data, adequacy of the studied cephalexin and cefadroxil dosing regimens will be analyzed. If the study is able to confirm a favorable PK/PD profile for twice daily (BID) and/or three times daily (TID) cefadroxil dosing in children, even for severe infections, it could have an immediate impact on prescribing habits. Less frequent dosing would be an improvement over the current standard of care, allowing for easier medication administration, improved adherence, and increased provider confidence for early transition to oral therapy, which are all essential for optimal treatment of pediatric MSK infections. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03802552
Study type Interventional
Source University of Colorado, Denver
Contact
Status Completed
Phase Phase 1
Start date May 1, 2019
Completion date April 30, 2021

See also
  Status Clinical Trial Phase
Active, not recruiting NCT04563325 - Oral-only Antibiotics for Bone and Joint Infections in Children Phase 4
Not yet recruiting NCT06402292 - Surgical Treatment of Osteoarticular Infections Using Bioactive Bone Substitute N/A
Completed NCT03846804 - Next-Generation Sequencing for Pathogen Detection and Quantification in Children With Musculoskeletal Infections N/A
Active, not recruiting NCT04945434 - Clinical Effectiveness of S53P4 Bioactive Glass in Treatment of Long-bone Chronic Osteomyelitis N/A
Recruiting NCT06084754 - Effect of Pulsed Electromagnetic Field Stimulation on Localized Pediatric Osteomyelitis N/A
Recruiting NCT05177107 - Bacteriophage Therapy in Patients With Diabetic Foot Osteomyelitis Phase 2
Recruiting NCT04554108 - Acute Non-severe Osteomyelitis in Children - Outpatient Management Strategy With Oral Antibiotic Therapy Compared to a Standard Strategy With Conventional Hospitalization and Intravenous Antibiotic Therapy: a Randomized Open-label Non-inferiority Study With Bayesian and Medical-economic Analyses. N/A
Recruiting NCT02128256 - CERAMENTâ„¢|G - Bone Healing and Re-infection Prophylaxis Phase 4
Terminated NCT01612962 - Diagnostic Tests to Help Determine Osteomyelitis N/A
Terminated NCT03091439 - Safety and Efficacy of Dalbavancin Versus Active Comparator in Adult Patients With Osteomyelitis Phase 2
Recruiting NCT04936958 - RETR(Osteomyelitis)
Completed NCT03559530 - Acinetobacter Baumannii-related Osteomyelitis: Clinical and Epidemiological Characterization
Completed NCT00324922 - Vancomycin Or Trimethoprim/Sulfamethoxazole for Methicillin-resistant Staphylococcus Aureus Osteomyelitis Phase 3
Completed NCT02084147 - PET-MRI in Diagnosing Patients With Cancer, Cardiac Diseases, or Neurologic Diseases N/A
Terminated NCT02099240 - Patients Response to Early Switch To Oral:Osteomyelitis Study Early Phase 1
Withdrawn NCT02344511 - Dalbavancin vs Comparator in Pediatric Subjects With Acute Hematogenous Osteomyelitis Phase 3
Completed NCT00402064 - The Influence of Bisphosphonates in the Oral Cavity in Children N/A
Terminated NCT02168816 - Efficacy of Oral Antibiotic Therapy Compared to Intravenous Antibiotic Therapy for Osteomyelitis Phase 2
Completed NCT02685033 - Study on the Safety and Efficacy of Dalbavancin Versus Active Comparator in Adult Participants With Osteomyelitis Phase 2
Completed NCT02335905 - Ceftaroline for Treatment of Hematogenously Acquired Staphylococcus Aureus Osteomyelitis in Children Phase 1/Phase 2