We investigated the mechanisms involved in imipenem resistance in 23 clinical strains of Acinetobacter baumannii. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed the presence of a 30-kDa protein in imipenem-intermediate A. baumannii (IIAB) and imipenem-resistant A. baumannii (IRAB) strains; this protein was almost undetectable in imipenem-susceptible A. baum...

The mechanism of interaction between imipenem and HSA was investigated by various techniques like fluorescence, UV.vis absorbance, FRET, circular dichroism, urea denaturation, enzyme kinetics, ITC, and molecular docking. We found that imipenem binds to HSA at a high affinity site located in subdomain IIIA (Sudlow's site I) and a low affinity site located in subdomain IIA.IIB. Electrostatic inte...

Carbapenem-resistant bacteria represent a significant treatment challenge due to the lack of active antimicrobials available. MK-7655 is a novel β-lactamase inhibitor under clinical development. We investigated the combined killing activity of imipenem and MK-7655 against four imipenem-resistant bacterial strains, using a mathematical model previously evaluated in our laboratory. Time-kill stud...

A recent multicentre clinical study evaluated the safety and efficacy of i.v. ciprofloxacin therapy compared with imipenem-cilastatin in hospitalized patients with severe pneumonia. Monotherapy with i.v. ciprofloxacin was at least equivalent to imipenem in terms of bacteriological eradication and clinical response. In a single-centre, retrospective, post-therapy evaluation of persistent and sub...

Acinetobacter baumannii is among the most dangerous pathogens and emergence of resistance is highly problematic. Our objective was to identify and rationally optimize β-lactam-plus-aminoglycoside combinations via novel mechanism-based modeling that synergistically kill and prevent resistance of carbapenem-resistant A. baumannii. We studied combinations of 10 β-lactams and three aminoglycosides ...

OBJECTIVES Previous studies have demonstrated that a combination of levofloxacin with imipenem could prevent the emergence of resistance during the treatment of susceptible Pseudomonas aeruginosa isolates in a two-compartment pharmacodynamic model of infection. In this study, the efficacy of levofloxacin/imipenem was further evaluated against a panel of characterized P. aeruginosa strains that ...

Eight unrelated clinical Acinetobacter baumannii isolates resistant to all commonly used antibiotics were subjected to three-dimensional checkerboard microtiter plate dilution and time-kill studies at one-fourth of their MICs of polymyxin B, imipenem, and rifampin. Synergy was demonstrated with combinations of polymyxin B and imipenem, polymyxin B and rifampin, and polymyxin B, imipenem, and ri...

Imipenem and cilastatin concentrations in serum were determined by using reverse-phase high-pressure liquid chromatography. Serum samples were stabilized with 0.5 M morpholineethanesulfonic acid buffer (pH 6.0) and subjected to ultrafiltration before chromatography. The elution solvent consisted of water or potassium phosphate buffered to pH 2.5 and methanol. The imipenem and cilastatin peaks w...

The activities of meropenem, imipenem, ceftriaxone, and vancomycin were evaluated against 80 penicillin-susceptible and -resistant Streptococcus pneumoniae strains. Meropenem, imipenem, ceftriaxone, and vancomycin MICs at which 90% of the isolates are inhibited were 0.5, 0.25, 1, and 0.25 microg/ml, respectively. Against penicillin-resistant strains, the best killing activity at cerebrospinal f...

The in vitro susceptibility of 157 anaerobic bacteria to imipenem was compared with that to cefoxitin, latamoxef (moxalactam) and clindamycin. The isolates were cultured from clinical specimens submitted to Tufts Anaerobic Laboratory between January 1981 and March 1983. Two strains of Bacteroides fragilis only, were highly resistant to imipenem. The incidence of cefoxitin resistance in the Bact...