Cloxacillin : Serum Level

Recommended Plasma Concentration

• According to the European Committee on Antimicrobial Susceptibility Testing (EUCAST), the MIC threshold to determine the strain sensitivity is 2 mg/L for cloxacillin.
• Until now, the optimal plasma concentration target in order to achieve the best cure rate remains undefined, but as oxa- and cloxacillin are time-dependent antibiotics, a time of 100% above the minimum inhibitory concentration (MIC) was considered to be optimal for efficacy.
• Considering that oxa- and cloxacillin are highly bound to albumin and that their unbound fraction—the available fraction for antibiotic efficacy—in healthy patients is known to be 10%,
• Previous study indicated that a dosing regimen of 1 g dicloxacillin every 6 hours should be effective for S. aureus infections with a mean MIC value of 0.125 µg·mL⁻¹ (achieving 67%T > MIC) (higher bioavailability compared to cloxacillin, 48.8% versus 36.9%)

Population: severe infections treated in ICU

• Defined a target range of total antibiotic concentration of 20–50 mg/L to reach the 100% T > MIC
• At a Median Daily Dosing of 105.5mg/kg [75; 150] produced a median plasma concentration of 134.3mg/L  [65.3; 201].
• Using a percentage of 10% to estimate the unbound fraction of oxa- or cloxacillin, all patients would have had a trough unbound fraction concentration superior or equal to the maximum MIC for oxa- or cloxacillin sensitivity, i.e. 2 mg/L

1. https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-017-0255-8

Oral Cloxacillin

• At a dose of 2g, average calculated dose based on serum concentration was 649mg (32.9%).
• Oral dose of 500mg cloxacillin produced a peak serum level of 8mcg/ml in adults
• After an oral dose of 500 mg, a peak plasma concentration of 7 to 14 μg per mL is attained in fasting subjects in 1 to 2 hours.
• After an oral dose of 500mg cloxacillin, a peak serum level of about 8 micrograms/mL is reached in about 1 hour.

1. PHARMACOKINETICS OF FLUCLOXACILLIN AND CLOXACILLIN IN HEALTHY SUBJECTS AND PATIENTS ON CHRONIC INTERMITTENT HAEMODIALYSIS. Br. J. clin. Pharmac. (1975), 2, 111-121
2. Infectious Diseases of the Female Genital Tract. By Richard L. Sweet, Ronald S. Gibbs
3. Cloxigen Product Information Leaflet

Intramuscular

• serum level after i.m. cloxacillin is approximately twice that obtained when the same dose is given orally to fasting adults

Concentration in Synovial tissue

• After a 30 min i.v. infusion of 1 g cloxacillin, the concentrations of this antibiotic were measured in plasma and synovial tissue samples from 11 patients undergoing total hip replacement.
• The concentration of free drug in synovial tissue was estimated to be 77% of the total tissue concentration.
• The maximum tissue drug concentration after an i.v. bolus dose is predicted to occur at about 37 min.
• it can be predicted that after an i.v. bolus injection of 1 g cloxacillin the maximum synovial tissue concentration will be reached at 37 min after administration. At this time the estimated free drug concentrations in plasma and tissue should be 0.9 mg/l.

1. Diffusion of cloxacillin into synovial tissue. Br. J. clin. Pharmac. (1992), 34, 275-277