%0 Electronic Article
%A Mushtaq, Shazad and Ge, Yigong and Livermore, David M.
%I American Society for Microbiology
%D 2004
%D 2004
%G English
%@ 0066-4804
%@ 1098-6596
%~ Katalog der Westsächsischen Hochschule Zwickau
%T Doripenem versus Pseudomonas aeruginosa In Vitro: Activity against Characterized Isolates, Mutants, and Transconjugants and Resistance Selection Potential
%V 48
%J Antimicrobial Agents and Chemotherapy
%V 48
%N 8
%P 3086-3092
%U http://dx.doi.org/10.1128/aac.48.8.3086-3092.2004
%X ABSTRACT
Doripenem is a broad-spectrum parenteral carbapenem under clinical development in Japan and North America. Its activities against (i)
Pseudomonas aeruginosa
isolates with graded levels of intrinsic efflux-type resistance, (ii) mutants with various combinations of AmpC and OprD expression, (iii) PU21 transconjugants with class A and D β-lactamases, and (iv)
P. aeruginosa
isolates with metallo-β-lactamases were tested by the agar dilution method of the National Committee for Clinical Laboratory Standards. Selection of resistant
P. aeruginosa
mutants was investigated in single- and multistep procedures. Doripenem MICs for isolates without acquired resistance mostly were 0.12 to 0.5 μg/ml, whereas meropenem MICs were 0.25 to 0.5 μg/ml and imipenem MICs were 1 to 2 μg/ml. The MICs of doripenem, meropenem, ertapenem, and noncarbapenems for isolates with increased efflux-type resistance were elevated, whereas the MICs of imipenem were less affected. The MICs of doripenem were increased by the loss of OprD but not by derepression of AmpC; nevertheless, and as with other carbapenems, the impermeability-determined resistance caused by the loss of OprD corequired AmpC activity and was lost in OprD
−
mutants also lacking AmpC. The TEM, PSE, PER, and OXA enzymes did not significantly protect
P. aeruginosa
PU21 against the activity of doripenem, whereas MICs of ≥16 μg/ml were seen for clinical isolates with VIM and IMP metallo-β-lactamases. Resistant mutants seemed to be harder to select with doripenem than with other carbapenems (or noncarbapenems), and the fold increases in the MICs were smaller for the resistant mutants. Single-step doripenem mutants were mostly resistant only to carbapenems and had lost OprD; multistep mutants had broader resistance, implying the presence of additional mechanisms, putatively including up-regulated efflux. Most mutants selected with aminoglycosides and quinolones had little or no cross-resistance to carbapenems, including doripenem.
%Z https://www.katalog.fh-zwickau.de/Record/ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTEyOC9hYWMuNDguOC4zMDg2LTMwOTIuMjAwNA
%U https://www.katalog.fh-zwickau.de/Record/ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTEyOC9hYWMuNDguOC4zMDg2LTMwOTIuMjAwNA