HRE 664, a new parenteral penem. I. Antibacterial activity in vitro.

Seibert, Gerhard; Isert, D.; Klesel, N; Limbert, M.; Pries, Alexandra; Schrinner, E; Cooke, Marylyn; Walmsley, John; Ph, Bentley

doi:10.7164/antibiotics.40.660

Cited by 11 publications

(4 citation statements)

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“…It was also more active than broad-spectrum cephalosporins, except for isolates of Shigella sonnei, Proteus mirabilis, and Providencia alcalifaciens. This degree of activity is also improved over those of penems CGP-31608, FCE-22101, and HRE-664 reported in the literature (8,9,15,18). Like other penems (15), CP-65,207 shows high affinity for PBP 2 in cell-free studies with E. coli.…”

Section: Discussionsupporting

confidence: 55%

“…This degree of activity is also improved over those of penems CGP-31608, FCE-22101, and HRE-664 reported in the literature (8,9,15,18). Like other penems (15), CP-65,207 shows high affinity for PBP 2 in cell-free studies with E. coli. This high affinity for PBPs, combined with its stability to hydrolysis by a wide variety of P-lactamases, may explain the high antibacterial activity of CP-65,207 against members of the Enterobacteriaceae.…”

Section: Discussionsupporting

confidence: 55%

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In vitro activity of CP-65,207, a new penem antimicrobial agent, in comparison with those of other agents

Gootz

Retsema

Girard

et al. 1989

Antimicrob Agents Chemother

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CP-65,207 is a new parenteral penem antibiotic with a broad spectrum that includes gram-positive, gram-negative, and anaerobic microorganisms, with MICs for 90% (MIC90s) of the majority of 1,101 clinical pathogens tested being '1 ,ig/ml. The compound was from 10-to 100-fold more active than cefoxitin and broad-spectrum cephalosporins against gram-positive bacteria and anaerobes. CP-65,207 was less active than imipenem for staphylococci, group A streptococci, and Enterococcus faecalis. Against members of the family Enterobacteriaceae, CP-65,207 was in general 100-fold more active than cefoxitin, 5-to 10-fold more active than broad-spectrum cephalosporins, and 2-fold more active than imipenem. Fresh clinical isolates that were resistant to broad-spectrum cephalosporins were highly susceptible to 207 and imipenem (MIC90,1 ,ug/ml). Isolates of Enterococcusfaecalis, Serratia marcescens, and anaerobic Peptococcus spp. had MIC9,s of 8, 2, and 3.12 ,ug/mI, respectively. CP-65,207 was not very active against methicillin-resistant staphylococci or Pseudomonas aeruginosa. Killing kinetics showed that against some strains CP-65,207 is rapidly bactericidal at concentrations well below those required to achieve a similar degree of killing with cefotaxime, ceftazidime, and ceftriaxone. CP-65,207 was only slightly susceptible to hydrolysis by type I cephalosporinases and TEM-1, SHV-1, and PSE-2 plasmid-encoded enzymes. It had the highest affinity for penicillin-binding proteins 2, 1A, 1B, and 3 in cell-free preparations of Escherichia coli W-7.Penems are synthetic beta-lactams that, as a class, possess a number of interesting properties which include a broad antibacterial spectrum and low susceptibility to hydrolysis by ,B-lactamases but, at the same time, are inactivated by renal dipeptidases found in the brush border of the kidney (20). A number of novel penems have been evaluated in the past decade; SCH-29482 and SCH-34343 (2, 10, 11) have rivaled carbapenems like imipenem in antibacterial activity, yet in clinical trials they were found to have undesirable side effects. The broad antibacterial spectrum of penems, however, has encouraged continued research in order to find clinically useful compounds. Two of these penems, FCE-22101 and SUN-5555, are in clinical trials (20). 207 ( Fig. 1) is a new parenteral penem that demonstrates high activity against gram-positive, gram-negative, and anaerobic bacteria that in some itistances is significantly imtproved over cefoxitin and the broad-spectrum cephalosporins. The current study characterizes the in vitro activity of CP-65,207 compared with those of both cephalosporins and imipenem.( Susceptibility studies. Antibiotic susceptibility studies were performed in microdilution trays containing 0.2 ml of unsupplemented Mueller-Hinton broth (MHB) per well with twofold dilutions of antibiotic (3). Inocula were grown overnight in MHB and diluted in broth to give a final inoculum of approximately 7.5 x 105 CFU/ml. Inoculated plates were incubated at 37°C in air for 18 h.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionsupporting

confidence: 55%

In vitro activity of CP-65,207, a new penem antimicrobial agent, in comparison with those of other agents

Gootz

Retsema

Girard

et al. 1989

Antimicrob Agents Chemother

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“…At present, there is some confusion as to whether [I-lactamase inhibitors owe induc tion potency, thus resulting in a possible antagonism instead of the expected syner gism [7], It is evident that clavulanic acid as well as sulbactam exhibit induction po- Consequently, there is no close relation between the induction potency and a pos sible antagonism, presumably due to the formation of an enzymatically inactive complex which is stable for several hours [15]. A comment should be made on the new penem compound H RE 664 [ 18]. This agent is a by far less potent inducer as compared to the related compound Sch 34343, in spite of common structural fea tures and properties.…”

Section: Discussionmentioning

confidence: 99%

Induction Potency of Various Beta-Lactam Derivatives in Gram-Negative Rods

Cullmann

Dick²

1989

Chemotherapy

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The induction potency of various (3-lactams as well as that of ‘nonspecific’ inducers such as the media employed or body fluids were studied in gram-negative clinical isolates and in their resistant corresponding counterparts. In all wild-type isolates quite a few (3-lactams (mainly cefoxitin and imipenem) shared the ability to induce the chromosomal ^-lactamase, whereas all (3-lactams – including 6-APS and 7-CPS clavu-lanic acid, and sulbactam (both (3-lactamase inhibitors), exhibited strong induction potency in their corresponding resistant counterparts. Moreover, all resistant counterparts exhibited the phenomenon of ‘nonspecific’ induction, whereas the wild-type strains did not. Interestingly, in both Proteus vulgaris 4917 W and Providencia rettgeri 862 W wild-type strains most P-lactam compounds were potent inducers, thus providing an explanation for resistance against P-lactamase-unstable compounds. The addition of subinhibitory concentrations of the quinolone compound enoxacin or chloramphenicol did not influence the phenotypic (3-lactamase expression, neither in wild-type strains nor in their resistant counterparts, whereas the addition of clindamycin or gentamicin resulted in a marked decrease of enzyme production in cephalosporinase overproducers, the P. vulgaris and the P. rettgeri isolates.

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“…Such compounds exhibit good antibacterial activity against gram-positive and gram-negative species, on the one hand, and stability to a variety of beta-lactamases, on the other (6,8,10,11). However, with the exception of the penem compound CGP 31608 (CIBA-GEIGY Corp., Summit, N.J.), they are not active against Pseudomonas aeruginosa (6,7,9,11). In this study the antibacterial effect of a new penem compound (HRE 664) was evaluated against clinical isolates; and the results were compared with those obtained with broad-spectrum penicillins, cephalosporins, and structurally related agents (Fig.…”

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confidence: 99%

Antibacterial activity of HRE 664, a new parenteral penem

Cullmann

Stieglitz

1988

Antimicrob Agents Chemother

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The antibacterial activity of the new penem compound HRE 664 was evaluated in 451 clinical isolates, including ampiciflin-resistant members of the family Enterobacteriaceae, Acinetobacter spp., Haemophilus influenzae, Staphylococcus aureus, and beta-hemolytic streptococci, and compared with those of piperacillin, ceftazidime, ceftriaxone, aztreonam, imipenem, and the penem compound Sch 34343. The new agent HRE 664 exhibited antibacterial activity comparable to that of the penem Sch 34343 and imipenem. The MICs of the new agent HRE 664 for 90% of the strains tested ranged from 1 to 4 ,ug/ml against Enterobacteriaceae and were 0.06

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HRE 664, a new parenteral penem. I. Antibacterial activity in vitro.

Cited by 11 publications

References 0 publications

In vitro activity of CP-65,207, a new penem antimicrobial agent, in comparison with those of other agents

In vitro activity of CP-65,207, a new penem antimicrobial agent, in comparison with those of other agents

Induction Potency of Various Beta-Lactam Derivatives in Gram-Negative Rods

Antibacterial activity of HRE 664, a new parenteral penem

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