ChemInform Abstract: HR 810, a New Parenteral Cephalosporin with a Broad Antibacterial Spectrum.

Seibert, Gerhard; KIESEL, N.; Limbert, M.; Schrinner, E; Seeger, K.; Winkler, Irvin; Lattrell, Rudolf; Blumbach, J.; Duerckheimer, W.; Fleischmann, Klaus; Kirrstetter, R. G. H.; Mencke, Burkhard; Ross, Barry C.; Scheunemann, Karl Heinz; Schwab, Wilfried; Wieduwilt, Manfred

doi:10.1002/chin.198350201

Cited by 28 publications

(14 citation statements)

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“…The ,B-lactams examined were cefpirome (20) and flomoxef (21), which have strong antimicrobial activities against S. aureus as well as gram-negative bacteria; five other cephalosporins (cefotaxime, moxalactam, cefmetazole, cefotiam, and cefazolin); and two penicillins (penicillin G and methicillin). Interestingly, we found that the activities of some ,-lactamase-stable cephalosporins and methicillin were markedly improved when these drugs were combined with sulbactam but that no such synergy occurred when they were combined with clavulanic acid.…”

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confidence: 99%

In vitro effects of beta-lactams combined with beta-lactamase inhibitors against methicillin-resistant Staphylococcus aureus

Kobayashi¹,

Arai²,

Hayashi³

et al. 1989

Antimicrob Agents Chemother

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The effects of combinations of 13-lactams with two P-lactamase inhibitors, sulbactam and clavulanic acid, were determined in vitro against 22 clinical isolates of methicillin-resistant Staphylococcus aureus. Combinations of cefpirome, cefotaxime, and cefazolin with sulbactam (10 ,ug/ml) showed synergistic effects against more than 70% of the strains. Combinations of methicillin and penicillin G with sulbactam also showed synergistic effects against 50 and 68% of the strains, respectively, while cefotiam, moxalactam, flomoxef, and cefmetazole in combination with sulbactam showed such effects against only 40% or fewer. Clavulanic acid was synergistic only when combined with penicillin G, the effect probably being due to the 1-lactamase inhibition by the inhibitor. Sulbactam did not improve the antimicrobial activities of the 1-lactams against methicillinsusceptible S. aureus strains. At 42°C the MICs of cefotaxime, methicillin, and flomoxef alone were markedly decreased from the values at 35°C, and no synergy between these P-lactams and sulbactam appeared. The resistance to penicillin G was not inhibited by incubation at 42°C, and combinations of penicillin G with sulbactam and clavulanic acid showed synergy. The amounts of 13-lactamase produced were not related to the decreases in the MICs of the I-lactams, except for penicillin G combined with sulbactam. Clavulanic acid showed slightly stronger ,3-lactamase-inhibiting activity than sulbactam did. These results suggest that the synergy between sulbactam and the 13-lactams, except for penicillin G, may not be due to 13-lactamase inhibition but to suppression of the methicillin-resistant S. aureus-specific resistance based on other factors.Recently, reports have been made on the isolation of and infections with methicillin-resistant Staphylococcus aureus (MRSA) (1,5,9,25,26). The resistance of these strains is associated with the presence of a low-affinity penicillinbinding protein, PBP 2' (23) or PBP 2a (10), and the protein has been suggested to be inducible by ,-lactams (7, 18, 22). The role of ,B-lactamase in the resistance has also been examined with the ,B-lactamase inhibitors clavulanic acid (17, 18) and sulbactam (3,8), and it has been reported that staphylococcal P-lactamase may be the cause of decreased antimicrobial activities of drugs such as penicillin G and cefazolin, which are relatively susceptible to 1-lactamase hydrolysis (4, 15). There has also been a report that drug inactivation by penicillinase is the main possible mechanism of resistance to cefazolin, cephaloridine, and cephalothin in S. aureus (14).To determine the role of ,-lactamase in the resistance to more antimicrobial agents, we determined the effects of combinations of nine 3-lactams with the two 3-lactamase inhibitors in vitro against clinically isolated MRSA strains. The ,B-lactams examined were cefpirome (20) and flomoxef (21), which have strong antimicrobial activities against S. aureus as well as gram-negative bacteria; five other cephalosporins (cefotaxime, moxalactam, cefmetazo...

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confidence: 99%

In vitro effects of beta-lactams combined with beta-lactamase inhibitors against methicillin-resistant Staphylococcus aureus

Kobayashi¹,

Arai²,

Hayashi³

et al. 1989

Antimicrob Agents Chemother

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“…Cefpirome (HR 810) is a new cephalo sporin derivative of the third generation with an extremely broad antibacterial spectrum [1], including bacterial strains re sistant to cefotaxime and ceftazidime [2]. The pharmacokinetic behaviour of single doses of cefpirome up to 2.0 g has been in vestigated in earlier studies [3].…”

Section: Introductionmentioning

confidence: 99%

Safety, Tolerance and Pharmacokinetics of 2.0 g Cefpirome (HR 810) after Single and Multiple Dosing

Badian¹,

Malerczyk

Collins³

et al. 1988

Chemotherapy

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After intravenous injection of a single dose of 2.0 g cefpirome (HR 810) and multiple doses of 2.0 g b.i.d. (11 doses) to 10 healthy male volunteers in an open design, concentrations of unchanged drug were measured at various times in serum and urine over 24 and 96 h, respectively. Cefpirome concentrations were determined using high-pressure liquid chromatography (HPLC). The biological half-life (t_½,β) found by fitting a two-compartment open model to the data was 2 h. No accumulation of the serum levels could be detected during the multiple-dose phase. Urinary concentrations of unchanged cefpirome effective against most clinically relevant bacteria were detected for at least 36 h. The drug was safe and well tolerated. No drug-related changes were observed for blood pressure, heart rate, ECG, haematology, clinical chemistry or urinalysis, including β₂-microglobulin in serum and creatinine clearance.

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“…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

Antimicrob Agents Chemother

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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 ...

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ChemInform Abstract: HR 810, a New Parenteral Cephalosporin with a Broad Antibacterial Spectrum.

Abstract: Durch Alkylierung des Cyclopentanopyridins (II) mit den β‐Lactam‐Derivaten (I) erhält man das Antibioticum (III).

Cited by 28 publications

References 0 publications

In vitro effects of beta-lactams combined with beta-lactamase inhibitors against methicillin-resistant Staphylococcus aureus

In vitro effects of beta-lactams combined with beta-lactamase inhibitors against methicillin-resistant Staphylococcus aureus

Safety, Tolerance and Pharmacokinetics of 2.0 g Cefpirome (HR 810) after Single and Multiple Dosing

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

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