Cefadroxil Comparable to Cephalexin: Minimum Inhibitory Concentrations among Methicillin-Susceptible Staphylococcus aureus Isolates from Pediatric Musculoskeletal Infections

Haynes, Andrew S; Prinzi, Andrea; Silveira, Lori; Parker, Sarah K.; Lampe, Jed N.; Kavanaugh, J.S.; Horswill, Alexander R.; Fish, Douglas N.

doi:10.1128/spectrum.01039-22

Cited by 4 publications

(2 citation statements)

References 16 publications

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“…Other studies have demonstrated success in use of cefadroxil for treatment of AHO in children [ 19 ]. Previous recommendations have suggested cefadroxil dosing of 100 to 150 mg/kg/d divided 2 or 3 times per day, for treatment of osteomyelitis, though more recent literature has demonstrated success with much lower doses (30 mg/kg/d divided twice per day) [ 20 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

First-Generation Cephalosporins for Treatment of Acute Hematogenous Osteomyelitis in Children: A Study of Efficacy and Adverse Effects

Hiskey,

Saifuddin,

Levy

et al. 2023

Open Forum Infectious Diseases

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Background Acute hematogenous osteomyelitis (AHO) is a relatively infrequent but significant infection in pediatric patients. As Staphylococcus aureus is the most common cause of AHO, intravenous and oral first-generation cephalosporins are common therapies. Cephalexin is a commonly prescribed oral therapy for pediatric AHO, although it requires frequent dosing that may affect adherence. Cefadroxil is a comparable oral first-generation cephalosporin with a more desirable dosing schedule. Methods We reviewed pediatric patients admitted to Mayo Clinic between March 2002 and September 2020 for management of AHO who received treatment with a first-generation cephalosporin. We reviewed timing of oral therapy transition, therapy-associated adverse effects, and recurrence of disease after completion of therapy. Results There were 59 patients included in the study. There was similar occurrence of adverse effects in patients receiving cefadroxil and cephalexin, although use of cefadroxil coincided with more gastrointestinal adverse effects and leukopenia and use of cephalexin with more rash and neutropenia. One secondary treatment failure occurred in our study, in a patient receiving cephalexin for treatment of septic arthritis. Conclusions Cefadroxil may be a reasonable alternative oral therapy for methicillin-susceptible S aureus or culture-negative AHO in pediatric patients, particularly when a less frequent dosing schedule is desired. Future study with a larger sample size is warranted.

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Section: Discussionmentioning

confidence: 99%

First-Generation Cephalosporins for Treatment of Acute Hematogenous Osteomyelitis in Children: A Study of Efficacy and Adverse Effects

Hiskey,

Saifuddin,

Levy

et al. 2023

Open Forum Infectious Diseases

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“…From the release studies, it can be inferred that the concentrations exceed the limit needed for the effective inhibition of clinically relevant, infection-causing pathogens. For example, the minimum inhibitory concentration (MIC) of cephalexin required to treat methicillin-sensitive Staphylococcus aureus (MSSA) infections is 2 µg mL −1 [55]. For Met, an effective MIC against many anaerobic bacterial strains ranges between 0.125 µg mL −1 and 1 µg mL −1 indicating the potential application of these composites for biomedical applications, such as in developing antimicrobial gauze and disinfectant surfaces [11,56,57].…”

Section: Drug Release Profilementioning

confidence: 99%

Biodegradable Polymer Composites of Metal Organic Framework-5 (MOF-5) for the Efficient and Sustained Delivery of Cephalexin and Metronidazole

Anim,

Mahmoud,

Kelly

et al. 2023

Applied Sciences

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The sustained and controlled delivery of antimicrobial drugs has been largely studied using nanomaterials, like metal organic frameworks (MOFs), and various polymers. However, not much attention has been given to combining MOFs and biodegradable polymers towards the potentially more sustained release of active pharmaceutical ingredients. Herein, we report a comparative study of two widely used antimicrobial drugs, cephalexin and metronidazole, from zinc-based MOF-5 incorporated into biodegradable polycaprolactone (PCL) and poly-lactic glycolic acid (PLGA) composites. Cephalexin and metronidazole were separately loaded into MOF-5 post-synthetically, followed by their integration into biodegradable PLGA and PCL composites. The pristine MOF-5 and the loaded MOFs were thoroughly characterised using Fourier-transformed infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and powder X-ray diffraction (PXRD). Ultraviolet-visible (UV-Vis) spectroscopy studies were carried out to assess the release of the drugs in PBS for up to 72 h, showing a cumulative release of 24.95 wt% and 27.84 wt% for cephalexin and metronidazole, respectively. The antibacterial properties of the pristine MOF, pure drugs, drug-loaded MOFs and the loaded composites were assessed against Gram-positive and Gram-negative bacterial strains, Staphylococcus aureus or Staphylococcus epidermidis and Escherichia coli or Acinetobacter baumanii, respectively. A cephalexin-loaded MOF-5 composite of PCL (PCL-ceph@MOF-5) showed the best efficiency for the controlled release of drugs to inhibit the growth of the bacteria compared to the other composites. This study demonstrates that the combination of MOFs with biodegradable polymers can provide an efficient platform for the sustained release of antimicrobial drugs and can be a promising tool to manage antimicrobial resistance (AMR).

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Cefadroxil and cephalexin pharmacokinetics and pharmacodynamics in children with musculoskeletal infections

Haynes,

Wei,

Anderson

et al. 2024

Antimicrob Agents Chemother

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Cephalexin, a first-generation cephalosporin, is the first-line oral therapy for children with musculoskeletal infections due to methicillin-susceptible Staphylococcus aureus (MSSA). Cefadroxil, a similar first-generation cephalosporin, is an attractive alternative to cephalexin given its longer half-life. In this study, we describe the comparative pharmacokinetics (PK) and pharmacodynamics (PD) of cephalexin and cefadroxil in children with musculoskeletal infections. Children aged 6 months to 18 years with a musculoskeletal infection were enrolled in a prospective, open-label, crossover PK study and given single oral doses of cefadroxil (50–75 mg/kg up to 2,000 mg) and cephalexin (50 mg/kg up to 1,375 mg). Population PK models were developed and used for dosing simulations. Our primary PD target was the achievement of free antibiotic concentrations above the minimum inhibitory concentration ( f T >MIC) for 40% of the day for MICs ≤ 4 mg/L. PK of cephalexin ( n = 15) and cefadroxil ( n = 14) were best described using a one-compartment, first-order absorption model, with a lag time component for cefadroxil. PK parameters were notable for cefadroxil’s longer half-life (1.61 h) than cephalexin’s (1.10 h). For pediatric weight bands, our primary PD target was achieved by cephalexin 25 mg/kg/dose, maximum 750 mg/dose, administered three times daily and cefadroxil 40 mg/kg/dose, maximum 1,500 mg/dose, administered twice daily. More aggressive dosing was required to achieve higher PD targets. Among children with musculoskeletal infections, oral cephalexin and cefadroxil achieved PD targets for efficacy against MSSA. Given less frequent dosing, twice-daily cefadroxil should be further considered as an alternative to cephalexin for oral step-down therapy for serious infections due to MSSA.

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Cefadroxil Comparable to Cephalexin: Minimum Inhibitory Concentrations among Methicillin-Susceptible Staphylococcus aureus Isolates from Pediatric Musculoskeletal Infections

Abstract: Cephalexin and cefadroxil are oral antibiotics that are used to treat serious infections due to the bacteria MSSA. While cephalexin is used more commonly, cefadroxil is excreted from the body more slowly; this generally allows patients to take cefadroxil less frequently than cephalexin.

Cited by 4 publications

References 16 publications

First-Generation Cephalosporins for Treatment of Acute Hematogenous Osteomyelitis in Children: A Study of Efficacy and Adverse Effects

First-Generation Cephalosporins for Treatment of Acute Hematogenous Osteomyelitis in Children: A Study of Efficacy and Adverse Effects

Biodegradable Polymer Composites of Metal Organic Framework-5 (MOF-5) for the Efficient and Sustained Delivery of Cephalexin and Metronidazole

Cefadroxil and cephalexin pharmacokinetics and pharmacodynamics in children with musculoskeletal infections

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