Ceftaroline pharmacokinetics/pharmacodynamics in the hollow-fibre model of Mycobacterium abscessus lung disease
Year: 2025
Type: article
Abstract: SUMMARY BACKGROUND Guideline-based therapy (GBT) of Mycobacterium abscessus (MAB) lung disease (LD) achieves a sputum culture conversion rate in ∼35% of patients. The β-lactam antibiotics, imipenem and cefoxitin, are the cornerstone of GBT. However, a 1-h half-life means multiple infusions per day, which is difficult for months-long therapy. METHODS As an alternative, we tested ceftaroline–avibactam, with a 3-h half-life, in the hollow-fibre model system of MAB-LD (HFS-MAB). Eight ceftaroline–avibactam exposures were administered twice daily based on human intrapulmonary pharmacokinetics. Next, we compared GBT (cefoxitin–clarithromycin–amikacin) to standard-dose and to high-dose ceftaroline–avibactam–tigecycline–moxifloxacin regimens, in the HFS-MAB, mimicking the intrapulmonary pharmacokinetics of all drugs. RESULTS Ceftaroline–avibactam maximal microbial kill was 0.72 log 10 colony-forming units (CFUs) per millilitre below day 0 burden (stasis). The ceftaroline pharmacokinetic–pharmacodynamic parameter linked to microbial kill and anti-microbial resistance was 0–24-h area under the concentration–time curve (AUC 0–24 ) to minimum inhibitory concentration. GBT killed 1.21 ± 0.25 log 10 CFU/mL versus 0.45 ± 0.42 log 10 CFU/mL below stasis for high-dose ceftaroline combination ( P = 0.20). In combination regimens, proportion of the ceftaroline-resistant subpopulation was 41.22 ± 13.11 times lower than the cefoxitin-resistant subpopulation ( P = 0.002). CONCLUSION Ceftaroline–avibactam administered twice a day would be an adequate replacement for the four-times-a-day cefoxitin treatments for MAB-LD.
Source: IJTLD OPEN
Authors: B.E. Ferro, S. Srivastava, T. Gumbo
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4414146374