Alterations in transmembrane pressures during continuous venovenous haemofiltration significantly contribute to the pharmacokinetic variability of meropenem: a case series of three patients

Jos L M L le Noble, Sjoerd D Meenks, Norbert Foudraine, Paddy K C Janssen
2018 Journal of Antimicrobial Chemotherapy  
pronounced permeabilizing effect of tobramycin in combination with imipenem leading to extensive outer membrane disruption, higher periplasmic imipenem concentrations and rapid upregulation of inducible AmpC b-lactamase in P. aeruginosa. 8 While ceftolozane/tazobactam has shown much higher stability against AmpC hydrolysis and slower development of resistance compared with other antibacterials, including carbapenems, 1,9 our case adds to the few documented clinical cases of the development of
more » ... he development of ceftolozane/tazobactam resistance upon exposure to ceftolozane/tazobactam. 1,10 The high level of resistance observed in our isolate is likely driven by multiple mutations in the AmpC region causing structural changes, along with AmpD-associated derepression of AmpC. While the development of high-level resistance to ceftolozane/tazobactam after exposure is worrisome, our severely neutropenic patient rapidly cleared bacteraemia on a combination of a pharmacodynamically driven dose of ceftolozane/ tazobactam 7 and tobramycin with resultant synergy. It emphasizes the importance of strategic dosing and the potential benefit of combination therapy when combating refractory cases of MDR P. aeruginosa infection.
doi:10.1093/jac/dky411 pmid:30295774 fatcat:anfrgsktorapvigeo64ge42dhe