HR 810 and BMY-28142, two new cephalosporins with broad-spectrum activity:an <i>in-vitro</i> comparison with other β-lactam antibiotics

107

Cefquinome is a new injectable aminothiazolyl cephalosporin derivative. It is stable against chromosomally and plasmid-encoded I8-lactamases and has a broad antibacterial spectrum. Staphylococcus aureus, streptococci, Pseudomonas aeruginosa, and members of the family Enterobacteriaceae (Escherichia coli, Salmonella spp., Klebsiella spp., Enterobacter spp., Citrobacter spp., and Serratia marcescens) are inhibited at low concentrations. Cefquinome is also active against many strains of methicillin-resistant staphylococci and enterococci. Its in vitro activity against gram-negative anaerobes is very limited. The high in vitro activity of cefquinome is reflected by its high in vivo efficacy against experimental septicemia due to different gram-positive and gram-negative bacteria. We studied the pharmacokinetic properties of cefquinome in mice, dogs, pigs, and calves. After single parenteral administrations, cefquinome displayed high peak levels, declining with half-lives of about 0.5, 0.9, 1.2, and 1.3 h, respectively. The areas under the concentration-time curve determined for dogs and mice showed linear correlations to the given doses. In dogs the urinary recovery was more than 70% within 24 h of dosing.

Section: Discussionmentioning

confidence: 56%

“…Owing to its resistance to various plasmid-encoded or chromosomally encoded P-lactamases, cefquinome is also active against bacteria that are resistant to earlier cephalosporins. Its action against gramnegative strict anaerobic bacteria (e.g., Bacteroidesfragilis) is limited, as is that of cefpirome and cefepime (2,4).…”

Section: Discussionmentioning

confidence: 99%

Antibacterial activities in vitro and in vivo and pharmacokinetics of cefquinome (HR 111V), a new broad-spectrum cephalosporin

Limbert¹,

Isert²,

Klesel³

et al. 1991

107

“…E. coli Kl and H. influenzae type b are the two most important gram-negative pathogens isolated from infants and children with bacterial meningitis. Cefpirome has excellent antibacterial activity against these two organisms, with reported MICs for 90% of organisms tested of 0.06 and 0.015 jxg/ml, respectively (1,2,13).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and antibacterial efficacy of cefpirome (HR 810) in experimental Escherichia coli and Haemophilus influenzae type b meningitis

Jafari

Sáez-Llorens

Ramilo

et al. 1991

Cefpirome (HR 810) is a new cephalosporin related to cefotaxime that has potent bactericidal activity against a broad spectrum of gram-negative and gram-positive organisms. The pharmacokinetics and bacteriological efficacy of cefpirome administered as a single intravenous dose were assessed in rabbits with experimental Haemophilus influenzae type b and Escherichia coli Kl meningitis. The mean penetrations into the cerebrospinal fluid (CSF) in relation to the amount of drug in serum of animals infected with H. influenzae and E. coli were 25 and 54%, respectively. The median CSF bactericidal titers were 1:128 against both organisms at 1 h after the dose and 1:32 and 1:16 against H. influenzae and E. coli, respectively, at 8 h after the dose. In CSF of uninfected animals, the mean penetration was 4.5%. There was a significant reduction in the concentrations of bacteria in CSFs of both groups of animals treated with cefpirome compared with that in untreated groups. Mortality was also significantly lower in treated animals than it was in untreated animals. Intravenous administration of dexamethasone before the cefpirome dose did not compromise penetration, bactericidal titers, or antibacterial activity of cefpirome in CSF.Cefpirome (HR 810) is a new cephalosporin related to cefotaxime that has potent bactericidal activity against a broad range of gram-negative and gram-positive organisms including Pseudomonas aeruginosa and methicillin-susceptible Staphylococcus spp. It is also highly active against Haemophilus influenzae type b and many members of the family Enterobacteriaceae (1, 2, 13). Escherichia coli Kl and H. influenzae type b are the two most important gramnegative pathogens involved in bacterial meningitis affecting infants and children.The objectives of the present study were (i) to determine the concentrations of cefpirome, after a single intravenous (i.v.) dose, in the sera and cerebrospinal fluid (CSF) of rabbits with experimental E. coli Kl and H. influenzae type b meningitis; (ii) to evaluate the penetration and bacteriologic efficacy of this investigational cephalosporin in CSF of infected and uninfected animals; and (iii) to assess the effects of dexamethasone, administered i.v. before the antibiotic dose, on penetration, bacteriostatic and bactericidal titers, and antibacterial activity of cefpirome in CSF of infected animals. MATERIALS AND METHODSSix rabbits in each of the following groups of animals were used to study cefpirome pharmacokinetics: (i) E. coli meningitis, (ii) H. influenzae meningitis, (iii) uninfected controls, and (iv) H. influenzae meningitis with dexamethasone therapy. Because of the higher mortality in untreated animals, up to 18 animals had to be used in all groups in order to compare the antibacterial activities between the treated and untreated groups.Experimental meningitis model. New Zealand White male rabbits (weight, 2 to 3 kg) were prepared as described * Corresponding author. previously (3). Briefly, a dental acrylic helmet was attached to the skull of each rabbit, and ...

“…Cefepime (CP; BMY-28142) is a new broad-spectrum parenteral, so-called "fourth-generation" cephalosporin antibiotic with significant in vitro antimicrobial advantages over other 3-lactam antibiotics (3,5,15,21,27). In addition to a broad antimicrobial spectrum, CP has a low binding affinity for the major inducible chromosomally mediated 3-lactamases and can resist hydrolysis by 3-lactamases (5,14,21,23).…”

mentioning

confidence: 99%

“…and other members of the family Enterobacteriaceae. It also has corresponding potency against gram-positive bacteria such as Staphylococcus aureus and streptococci (1,3,5,15,21,23). The in vitro advantages of CP have been reproduced in several in vivo infection models and have the potential to provide improved antimicrobial therapy, especially against infections caused by bacteria that are resistant to other antibiotics (15,16,26).…”

mentioning

confidence: 99%

Cefepime compared with ceftazidime as initial therapy for serious bacterial infections and sepsis syndrome

Kieft¹,

Hoepelman²,

Rozenberg-Arska³

et al. 1994

In an open randomized multicenter comparative study, we evaluated the safety and efficacy of cefepime (CP; 2.0 g given intravenously every 12 h) and ceftazidime (CZ; 2.0 g given intravenously every 8 h) as initial treatment for adult patients with suspected serious bacterial infections. A total of 133 patients entered the study, of whom 114 were evaluable for clinical and microbiological response assessment: 56 received CP and 58 received CZ. About 50%o (30 who received CP and 25 who received CZ) fulfilled the criteria of the sepsis syndrome. The treatment groups were comparable with respect to sex distribution, mean age, underlying diseases, treatment duration, APACHE II score, and type of infection. The most commonly cultured microorganisms were members of the family Enterobacteriaceae, Streptococcus pneumoniae, and Staphylococcus aureus. The causative microorganisms were eradicated from 92% (37 of 40) of patients with a microbiologically documented infection who underwent treatment with CP; they were eradicated from 86% (42 of 49) of patients who received CZ. The responses of only clinically documented infections in the CP group were 90% (27 of 30 patients); in the CZ group they were 87% (26 of 30 patients). When patients fulfilled the criteria of the sepsis syndrome (septic shock excluded), the causative microorganisms were eradicated from 89%o (16 of 18) of CP-treated patients and 86% (12 of 14) of CZ-treated patients. None of these differences was statistically significant. Mortality was the same in both groups (four patients in each group) and was not attributable to the study medication. In conclusion, CP is at least as effective and as safe as CZ as initial antimicrobial therapy for suspected serious bacterial infections in nonneutropenic patients with or without the sepsis syndrome. CP has the additional advantage in that it can be given twice daily, which may lead to a decrease in hospital costs.