Interaction of Ro 17–2301 (AMA-1080) with &lt;i&gt;β&lt;/i&gt;-Lactamases

Rl, Then

doi:10.1159/000238300

Cited by 10 publications

(13 citation statements)

References 11 publications

(14 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most antibiotics and fine chemicals were supplied by commercial sources. Ceftriaxone, carumonam (20,23), aztreonam, norfloxacin, trimethoprim, and brodimoprim (22) f8-Lactamase assays. ,B-Lactamase was assayed at 37°C in crude sonicated bacterial extracts, using nitrocefin as the substrate (21).…”

Section: And Methodsmentioning

confidence: 99%

“…,B-Lactamase was assayed at 37°C in crude sonicated bacterial extracts, using nitrocefin as the substrate (21). Hydrolysis of various P-lactams was measured by a spectroscopic method (20). Isoelectric points were determined in crude extracts on PAG plates (LKB Instruments, Inc., Rockville, Md.)…”

Section: And Methodsmentioning

confidence: 99%

“…The conditions for the isolation of membranes, the binding assay, and polyacrylamide gel electrophoresis were described recently (23). Penicillin- (20). The Sarkosyl (CIBA-GEIGY Corp., Summit, N.J.) insoluble fraction, obtained essentially as described previously (6), was analyzed on 12% acrylamide gels, containing 0.1% sodium dodecyl sulfate (SDS).…”

Section: And Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Multiply resistant mutants of Enterobacter cloacae selected by beta-lactam antibiotics

Then¹,

Angehrn²

1986

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Mutants of Enterobacter cloacae, selected in vitro with ceftriaxone, ceftazidime, carumonam, or aztreonam, fell into several distinct classes. Three mutants highly resistant to nearly all beta-lactam antibiotics were stably derepressed for beta-lactamase production. Although no other changes could be detected, virulence in a mouse septicemia model was decreased in two of these mutants. One mutant, 908-Ssi, showed selectively decreased susceptibility to ampicillin and cefotetan. A change in beta-lactamase expression was thought to be responsible for this. Alterations in the production of two outer membrane proteins with molecular sizes of 36.5 and 39 kilodaltons were responsible for multiple antibiotic resistance in two mutants, both of which acquired a low level of resistance to beta-lactam antibiotics. Whereas one of the mutants, AMA-R, simultaneously acquired resistance to chloramphenicol and trimethoprim, the other, AZT-R, became hypersusceptible to these and other hydrophobic agents. Both strains had drastically reduced virulence in mice.

show abstract

Section: And Methodsmentioning

confidence: 99%

Section: And Methodsmentioning

confidence: 99%

Section: And Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Multiply resistant mutants of Enterobacter cloacae selected by beta-lactam antibiotics

Then¹,

Angehrn²

1986

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Samples (0.01 ml) from clear wells were transferred to antibiotic-free I"-Lactamase assays. The stabilities of compounds to ,-lactamases were determined by spectrophotometric assay at 37°C (13). The assay contained 100 ,uM substrate in 100 mM phosphate buffer.…”

mentioning

confidence: 99%

“…The rate of cephaloridine hydrolysis was set at 100. The inhibitory properties for 1-lactamases were determined by testing P-lactams at several concentrations with 100 ,uM nitrocefin as the substrate, at 37°C with 1-ml volume, and starting the reaction with the addition of enzyme (13 MIC90s of c0.39 ,ug/ml. Morganella morganii, Providencia rettgeri, C. freundii, H. influenzae, methicillin-susceptible S.…”

mentioning

confidence: 99%

In vitro and in vivo evaluation of Ro 09-1428, a new parenteral cephalosporin with high antipseudomonal activity

Arisawa

Sekine

Shimizu

et al. 1991

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Ro 09-1428, a new parenteral cephalosporin with a catechol moiety attached at position 7 of the cephalosporin ring, showed high in vitro activity against Escherichia coli, Kkbsielia pneumoniae, Proteus mirabilis, Proteus vulgaris, and Streptococcus pyogenes, with MICs for 90% of strains tested (MIC9s) of c0.39 ,ug/ml.MorganeUa morganii, Providencia reftgeri, Citrobacterfreundii, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae were inhibited with MIC90s of <3.13 ,ug/mi. Serratia marcescens was less susceptible to Ro 09-1428, with a MICg of 25 ,ug/ml. The most distinctive feature of Ro 09-1428 was its potent activity against Pseudomonas aeruginosa and Acinetobacter caloaceticus, with MIC90s of 0.39 and 6.25 ,Ig/ml, respectively. Most of the ceftazidime-resistant strains of P. aeruginosa, E. cloacae, and C. freundii were inhibited by Ro 09-1428, while those of S. marcescens were resistant at a concentration of 12.5 ,ug/ml. Ro 09-1428 was more active than ceftazidime against staphylococci. PBP 3 was the most sensitive target in E. coli and P. aeruginosa. The response to ferric iron in growth medium suggests that Ro 09-1428 may be taken up by transport mechanisms similar to those of other catechol cephalosporins. In accordance with its in vitro activity, Ro 09-1428 activity was equal to or greater than ceftazidime activity in efficacy against experimental septicemias in mice. The results indicate that Ro 09-1428 is a broad-spectrum cephalosporin with advantages over ceftazidime in its activity against P. aeruginosa, staphylococci, and ceftazidime-resistant strains of C. freundii and E. cloaceae.In spite of a considerable number of cephalosporins on the market, few compounds have useful activity against Pseudomonas aeruginosa. Although ceftazidime and cefpiramide are cephalosporins which inhibit the growth of P. aeruginosa at therapeutically attainable concentrations in blood, this activity leaves room for improvement. Recently, several cephalosporins containing catechol substituents have been reported as having superior antipseudomonal activities compared with those of other P-lactam antibiotics (1-9, 16).Ro 09-1428, (6R, (Fig. 1), is a parenteral cephalosporin that has a catechol moiety in the 7-acylamino side chain and showed high activity against gram-negative rods, particularly P. aeruginosa. Furthermore, the compound was found to be active against strains refractory to broad-spectrum cephalosporins. In this paper, we evaluated the in vitro and in vivo activities of Ro 09-1428 compared with those of ceftazidime. In addition, stability to ,-lactamases and affinity for penicillin-binding proteins (PBPs) are described.(This work was presented in part at the 29th Interscience Conference on Antimicrobial Agents and Chemotherapy, Houston, Tex., 17 to 20 September 1990.) MATERIALS AND METHODS Antibiotics. Ro 09-1428 and ceftriaxone were synthesized in the research laboratory of Nippon Pharmaceutical Devel-* Corresponding author. opment Institute, Hokkaido, Japan, and F. Hoffmann-La Roche A...

show abstract

β‐Lactamase Inhibitors

Stam

2000

Kirk-Othmer Encyclopedia of Chemical Technology

View full text Add to dashboard Cite

The antibacterial effectiveness of penicillins, cephalosporins, and other β‐lactam antibiotics depends on the inactivation of transpeptidases involved in bacterial cell wall synthesis. Bacteria that are resistant to β‐lactam antibiotics often produce enzymes called β‐lactamases that inactivate the antibiotics by catalyzing the hydrolytic opening of the β‐lactam ring to give products devoid of antibacterial activity. One approach to combating antibiotic resistance caused by β‐lactamase is to inhibit the enzyme. Effective combinations of enzyme inhibitors with β‐lactam antibiotics such as penicillins or cephalosporins result in a synergistic response, lowering the minimal inhibitory concentration (MIC) by a factor of four or more for each component. However, pharmacokinetics, stability, ability to penetrate bacteria, cost, and other factors are also important in determining whether an inhibitor is suitable for therapeutic use. The most important β‐lactamases to inhibit clinically are the gram‐positive penases, the gram‐negative TEM, which are Richmond‐Sykes type III, and the gram‐negative chromosomal cephalosporinases–cephases which are Richmond‐Sykes type I. These enzymes may be referred to as penase, TEM(III), and cephase(I). These clinically important β‐lactamases are serine proteases that form an acyl enzyme intermediate with β‐lactam substrates and β‐lactam‐derived β‐lactamase inhibitors. A number of β‐lactamase‐resistant penicillins and cephalosporins were found to be β‐lactamase inhibitors. No clinically useful inhibitors have been identified from this class. Clavulanic acid has only weak antibacterial activity, but is a potent irreversible inhibitor for many clinically important β‐lactamases, including penases and Richmond‐Sykes types II, III, IV, V, VI ( Bacteroides ). Carbapenems are another class of natural product β‐lactamase inhibitors. Many penem β‐lactamase inhibitors are potent antibacterials. Penicillanic acid sulfone, (2( S )‐ cis )‐3,3‐dimethyl‐7‐oxo‐4,4‐dioxide‐4‐thia‐1‐azabicyclo [3.2.0]heptane‐2‐carboxylic acid (sulbactam) ( , ), C 8 H 11 NO 5 S, is a weak antibacterial, but is a potent irreversible inactivator of many β‐lactamases, including penases and Richmond‐Sykes type II, III, IV, V, and VI ( Bacteroides ) β‐lactamases. Sulbactam is better than clavulanic acid against type I cephases, and synergy is observed for combinations of many penicillins and cephalosporins. Because sulbactam is not well absorbed orally, prodrug forms have been developed. Numerous other penicillin sulfones have been reported to be β‐lactamase inhibitors. Among penam β‐lactamase inhibitors, of 6‐β‐bromopenicillanic acid, a potent inhibitor, has progressed to clinical trials. Although a broad range of β‐lactamase inhibitors has been discovered, only clavulanic acid and sulbactam have been commercialized. Clavulanic acid manufactured by SmithKline Beecham is sold as an oral and parenteral product in combination with amoxicillin under the trade name Augmentin. A parenteral product in combination with ticarcillin, C 15 H 16 N 2 O 6 S, has the trade name, Timentin. The oral version of sulbactam in combination with ampicillin, produced by Pfizer is called Unasyn Oral, which is the mutual prodrug sultamicillin. Two sulbactam parenteral products are sold, a combination product with ampicillin called Unasyn and a combination with cefoperazone called Sulperazon. In addition, sulbactam is sold alone for parenteral use with any β‐lactam antibiotic as Betamaze.

show abstract

Interaction of Ro 17–2301 (AMA-1080) with <i>β</i>-Lactamases

Cited by 10 publications

References 11 publications

Multiply resistant mutants of Enterobacter cloacae selected by beta-lactam antibiotics

Multiply resistant mutants of Enterobacter cloacae selected by beta-lactam antibiotics

In vitro and in vivo evaluation of Ro 09-1428, a new parenteral cephalosporin with high antipseudomonal activity

β‐Lactamase Inhibitors

Contact Info

Product

Resources

About