meropenem and flomoxef

The study aimed to characterize the genetic basis of flomoxef and collateral ertapenem resistance in a clinical isolate of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) after flomoxef exposure.. Four ESBL-KP isolates (Lkp11-14) were recovered sequentially from four episodes of bacteraemia in an elderly patient. Laboratory investigations included genotyping by PFGE, resistance gene analysis by PCR and sequencing, and outer membrane protein analysis by SDS-PAGE. Plasmid analysis by DNA-DNA hybridization, electroporation and conjugation was also performed.. Lkp14 was recovered after 21 days of flomoxef therapy. It demonstrated an indistinguishable PFGE pattern when compared with those produced by Lkp11-13. However, resistance to both flomoxef and ertapenem emerged in Lkp14. Molecular characterization revealed that, in addition to the pre-existing ESBL production (CTX-M-3 and SHV-5) and OmpK35 deficiency found in Lkp11-13, Lkp14 had acquired an extra plasmid-mediated AmpC beta-lactamase gene (blaDHA-1) and failed to express OmpK36, because of insertional inactivation by an insertion sequence IS5. Other resistance mechanisms, such as production of carbapenem-hydrolysing enzymes or expression of chromosomal efflux, were apparently not involved. Conjugational transfer of the plasmid-mediated blaDHA-1 gene into Lkp11 resulted in a significant increase in the MICs of cephamycins and beta-lactamase inhibitors, but not in those of carbapenems.. Lkp14 was apparently derived from the previously flomoxef-susceptible isolates, Lkp11-13. After flomoxef exposure, the in vivo acquisition of the plasmid-mediated blaDHA-1 gene has led to flomoxef resistance in Lkp14, and the concomitant depletion of OmpK36 expression has resulted in a collateral effect of ertapenem resistance and diminished susceptibilities to imipenem and meropenem.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Cephalosporins; Conjugation, Genetic; DNA, Bacterial; Drug Resistance, Bacterial; Electroporation; Ertapenem; Female; Genotype; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Molecular Sequence Data; Plasmids; Porins; Reverse Transcriptase Polymerase Chain Reaction; Thienamycins

To screen effective useful drugs for disease due to M. abscessus, we determined MIC of 3 cephems [ceftazidime (CAZ), cefoxitin (CFX), flomoxef (FMOX)] and 3 carbapenems [imipenem (IPM), panipenem (PAPM), meropenem (MEPM)] for 8 strains of clinically isolated M. abscessus by micro-dilution method using MGIT system. In all the 8 strains, MICs of CAZ are higher than 32 micrograms/ml. MIC50, MIC90, MIC range of CFX are 32 micrograms/ml, > 32 micrograms/ml and 16- > 32 micrograms/ml respectively, and for FMOX, 16 micrograms/ml, 32 micrograms/ml and 16-32 micrograms/ml; for IPM, 8 micrograms/ml, 16 micrograms/ml and 8-16 micrograms/ml; for PAPM, 4 micrograms/ml, 16 micrograms/ml and 4-16 micrograms/ml; for MEPM, 8 micrograms/ml, 16 micrograms/ml and 8-16 micrograms/ml. From this study, it is concluded that FMOX, IPM, PAPM and MEPM can be clinically useful drugs in the treatment of the disease due to M. abscessus.

Topics: Carbapenems; Cefoxitin; Ceftazidime; Cephalosporins; Drug Resistance, Bacterial; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Mycobacterium chelonae; Mycobacterium Infections, Nontuberculous; Thienamycins; Tuberculosis, Pulmonary

The in vitro and in vivo antibacterial activities of sulopenem, a new penem, were evaluated in comparison with imipenem (IPM), meropenem (MEPM), ceftazidime (CAZ) and flomoxef (FMOX). Sulopenem had broad and potent antibacterial spectra against Gram-positive and Gram-negative bacteria, including Enterococcus faecalis, Proteus vulgaris, Morganella morganii, Enterobacter spp. and Citrobacter freundii. Sulopenem showed concentration-dependent bactericidal activities against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Acinetobacter calcoaceticus. Morphological observation using phase-contrast microscope revealed that sulopenem induced spherical cell formation with E. coli and K. pneumoniae at lower concentrations and bacteriolysis at higher concentrations. Therapeutic efficacies of sulopenem against systemic infections in mice were almost equal to those of imipenem against Streptococcus pneumoniae. While its therapeutic efficacies were superior to those of meropenem, ceftazidime and flomoxef against S. aureus and S. pneumoniae, they were inferior to those of imipenem/cilastatin against S. aureus, K. pneumoniae and A. calcoaceticus.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Ceftazidime; Cephalosporins; Gram-Negative Bacteria; Gram-Positive Bacteria; Imipenem; Lactams; Male; Meropenem; Mice; Thienamycins