No abstract

Doripenem showed excellent activity against Gram-negative isolates; generally it was more active than imipenem and at least as good as meropenem. Against Pseudomonas species, doripenem was more active than both imipenem and meropenem, with doripenem susceptibility observed for some imipenem- and/or meropenem-resistant isolates.

The outer membrane protein (OMP) OprD is the major channel through which carbapenems permeate the outer membrane of Pseudomonas aeruginosa. In this study, we analyzed the OMP profiles of several P. aeruginosa clinical isolates showing diminished susceptibility to imipenem while remaining susceptible to meropenem. All these isolates lacked OprD or showed a reduced expression of this porin. Susceptibility to meropenem was thus independent of the level of OprD expression, indicating that the antimicrobial could be taken up via an alternative route. The level of expression of OprC (70 kD) was also unrelated to meropenem susceptibility. Nevertheless, OMPs OprF and OprE were expressed by all isolates, suggesting that in the absence of OprD, these porins might be involved in the permeation of meropenem.

ceftobiprole exhibits in vitro activity against a wide range of Gram-positive and Gram-negative pathogens, including multidrug-resistant strains. No changes in its known susceptibility profile were identified.

The use of different breakpoints and devices, the complexity of mutation-driven resistance mechanisms and the lack of unequivocal tests to detect ESBLs or carbapenemases in P. aeruginosa leads to extraordinary variability and low accuracy in susceptibility testing, which may have consequences for the treatment and control of nosocomial infections.