hr-810 and Pseudomonas-Infections

A novel VIM-type metallo-β-lactamase variant, VIM-60, was identified in multidrug-resistant

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cefpirome; Cephalosporins; Humans; Hydrolysis; Japan; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

A Pseudomonas aeruginosa isolate recovered in Belgium produced a novel extended-spectrum ss-lactamase, BEL-2, differing from BEL-1 by a single Leu162Phe substitution. That modification significantly altered the kinetic properties of the enzyme, increasing its affinity for expanded-spectrum cephalosporins. The bla(BEL-2) gene was identified from a P. aeruginosa isolate clonally related to another bla(BEL-1)-positive isolate.

Topics: Belgium; beta-Lactamases; Cephalosporinase; Cephalosporins; Cross Infection; Escherichia coli; Genes, Bacterial; Humans; Kinetics; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

A detailed biochemical characterization of the Pseudomonas aeruginosa VIM-11 metallo-beta-lactamase (MbetaL) is reported. The only substitution differentiating VIM-11 from VIM-2 (N165S) promoted a slightly improved catalytic efficiency of the former on 3 out of 12 substrates, notably the bulky cephalosporins. Thus, MbetaL-mediated resistance also may be modulated by remote mutations.

Topics: beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Binding Sites; Escherichia coli; Humans; Kinetics; Microbial Sensitivity Tests; Models, Molecular; Plasmids; Pseudomonas aeruginosa; Pseudomonas Infections

The conditions for the emergence of resistance to cefpirome and ceftazidime were studied in rabbits with experimental aortic endocarditis due to Pseudomonas aeruginosa. The MIC of cefpirome was 16 mg/L and that of ceftazidime was 4 mg/L. Resistant mutants with MICs of > or = 64 mg/L were obtained in vitro to cefpirome after a single passage and to ceftazidime after five passages. A single dose of 50 mg/kg intramuscularly gave mean peak serum concentrations of 110.0 +/- 31.7 mg/L for cefpirome compared with 67.7 +/- 21.4 mg/L for ceftazidime and the half-lives were 1.2 +/- 0.1 h and 2.1 +/- 0.4 h, respectively. After treating infected rabbits for 4 days with various dosing regimens, resistant strains were only detected in those animals in which the time that the serum concentration exceeded the MIC was less than half of the dosing interval. There was no evidence of emergent resistance when the serum concentrations exceeded the MIC for a longer period nor when amikican was combined with the cephalosporins on the first day of therapy. Moreover, once differences in MICs and pharmacokinetics were taken into account, both antibiotics had a similar propensity to induce resistance.

Topics: Animals; Cefpirome; Ceftazidime; Cephalosporins; Drug Resistance, Microbial; Endocarditis, Bacterial; Female; Microbial Sensitivity Tests; Pseudomonas Infections; Rabbits

Treatment of disseminated Pseudomonas aeruginosa infection in leukopenic mice was evaluated using cefpirome alone and in combination with gentamicin and/or rifampin. Mice were made leukopenic with cyclophosphamide and infected through a skin incision with an inoculum of 1250 organisms (13 LD50). Antibiotics were administered subcutaneously for 48 h. Although the addition of cefpirome to gentamicin and/or rifampin improved survival significantly at 48 h compared with untreated controls (84.6%-100% vs. 38.5%), therapy with these combinations did not improve survival significantly from that achieved with cefpirome alone. Quantitative blood and tissue (liver, spleen, kidney, lung) cultures in mice treated with cefpirome alone or including rifampin were lower than in infected controls or groups receiving therapy that excluded cefpirome. Highest counts were observed in mice receiving cefpirome plus gentamicin. Except for the cefpirome plus gentamicin group, which demonstrated areas of acute tubular necrosis, the cefpirome group had less tissue pathology than infected controls.

Topics: Animals; Cefpirome; Cephalosporins; Drug Therapy, Combination; Gentamicins; Kidney; Leukopenia; Liver; Lung; Male; Mice; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Spleen

Cefpirome (HR 810) is a new cephalosporin with a 2,3-cyclopentenopyridine group in the 3-position side chain. It was compared with other cephem antibiotics in protective and therapeutic effects on various experimental infections, systemic and local, in mice and rats. HR 810 had more potent protective effect than ceftazidime (CAZ), cefoperazone (CPZ), and cefotaxime (CTX) on systemic infections induced by Escherichia coli Ec-31, Staphylococcus aureus SMITH, and Serratia marcescens Sm-6 in mice. Against systemic infection with Pseudomonas aeruginosa HR 810 was as effective as CAZ. Mice with leukopenia induced by cyclophosphamide were systemically infected with methicillin-resistant S. aureus (MRSA), methicillin-susceptible S. aureus (MSSA), Enterobacter cloacae, Acinetobacter calcoaceticus, and Enterococcus faecalis. HR 810 was superior to cefuzonam (CZON) and cefmetazole against MRSA and MSSA and was much more active than any other antibiotics tested against E. cloacae and A. calcoaceticus. In the activity against E. faecalis, HR 810 was inferior to ampicillin but superior to CZON. In mice with pyelonephritis caused by E. coli Ec-7, the rank order of activities was HR 810 greater than CAZ greater than CTX greater than CPZ. HR 810 was more effective than latamoxef, CAZ, CTX, and CPZ in improving lung infections induced by Streptococcus pneumoniae HL 438 and Klebsiella pneumoniae Kp-51 in mice. HR 810 was superior to CTX and CPZ and comparable to cefazolin in therapeutic effects on intrauterine infections with E. coli Ec-89 and S. aureus SMITH in rats.

Topics: Animals; Cefpirome; Cephalosporins; Escherichia coli; Female; Klebsiella Infections; Klebsiella pneumoniae; Lung Diseases; Male; Methicillin; Mice; Penicillin Resistance; Pseudomonas Infections; Pyelonephritis; Rats; Staphylococcal Infections; Staphylococcus aureus; Uterine Diseases

HR 810 or cefpirome is a new amino thiazole cephalosporin whose specific characteristic is a cyclopentenopyridinium group in position 3 of the cephem nucleus. This structure is responsible for a broad spectrum of activity, covering Enterobacteriaceae, including cephalosporinase-producing Enterobacter spp. and Citrobacter spp., Staphylococcus aureus, Pseudomonas aeruginosa and group D Streptococci.

Topics: Animals; Bacterial Infections; Cefpirome; Cephalosporins; Citrobacter; Enterobacter; Enterobacteriaceae; Enterococcus faecalis; Klebsiella Infections; Male; Mice; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Salmonella Infections, Animal; Salmonella typhimurium; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus pyogenes