To devise an individualized dosing regimen of flucloxacillin and cefazolin that ensures optimal therapy for the individual patient. It is important to define the optimal exposure – where the probability of efficacy is maximized and the risk of toxicity is minimized. Prospective research on this subject and target exposures are lacking, but highly needed.
Furthermore, SAB patients with infected prosthetic implants have a less favourable prognosis and generally receive combination therapy of flucloxacillin or cefazolin with rifampicin, which is a known inducer of many enzymes and transporters. Rifampicin most likely increases the clearance of flucloxacillin, which may result in a diminished flucloxacillin exposure and possible reduced efficacy. Yet the extent of this pharmacokinetic drug-drug interaction and the clinical consequence are unknown. The effect of rifampicinon cefazolin exposure has not been investigated before.
Objective: To investigate the association between flucloxacillin or cefazolin exposure and efficacy and toxicity, and the effect of co-treatment with rifampicin on flucloxacillin and cefazolin exposure.
This substudy is funded by the ZonMw Rational Pharmacotherapy program and is conducted in the Netherlands.
Coordinating investigator: Fleur Sinkeler, PharmD – Radboud Umc, Nijmegen, the Netherlands
Principal investigator: Dr. Nynke Jager, PharmD –Radboud Umc, Nijmegen, the Netherlands
Blood samples will be drawn at day 2, day 5, day 8 and day 14. If possible, blood will be drawn through a pre-existent catheter or with minimal additional venipuncture. In these samples, the amount of antibiotic in your blood (drug concentration) and the amount of Staphylococcus aureus in your blood will be measured.
All S. aureus bacteraemia patients (≥ 18 years) treated with flucloxacillin or cefazolin included in the SNAP platform in the Netherlands are eligible for this substudy.
The collection of blood samples may cause some discomfort. It may cause possible bruising, redness, and swelling around the site, bleeding at the site, feeling of light-headedness when the blood is taken, and rarely, an infection at the site of the blood test or fainting. You may have none, some, or all of these, and they may be mild, moderate or severe. If you have any of these side effects or are worried about them, you can talk with the study investigators or your doctor.
The extra intervention compared to routine care consist of sampling a minimum amount of extra blood (maximum 6 samples of 4 ml per patient). If possible, blood will be drawn through a pre-existent catheter to minimize the burden.
You may not benefit from this study, but it is possible that the results from this study will help us better understand the relationship between the amount of antibiotic in your body and the chance of treatment success and risk of toxicity. Research like this may also help us to improve the care, by optimized dosing, of S. aureus bacteremia patients in the future.
All data obtained during this substudy will be recorded pseudonymized, therefore the your identity cannot be deduced from the database. Only the local investigators will have access to this secured database and they will be the only ones able to add, change, or delete data.
You can leave the study at any time for any reason if you wish to do so without any consequences. If you withdraw, we will keep any information we have collected about you up until you withdraw.
Name: Fleur Sinkeler