NOCARDICIN A, a NEW MONOCYCLIC Β-Lactam ANTIBIOTIC. III

Mine, Yasuhiro; Nonoyama, Shigeo; Kojo, Hitoshi; Fukada, Shigemi; Nishida, Motohiro; Goto, Shinichi; Kuwahara, Shōgo

doi:10.7164/antibiotics.30.917

Cited by 36 publications

(16 citation statements)

References 7 publications

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“…Another explanation o;f the observed synergy could have been the inhibition of 13-lactamase action by the phosphonopeptide. We have confirmed that this does not occur, and furthermore, the high stability of nocardicin A to these enzymes is well known (15).…”

Section: Methodssupporting

confidence: 67%

“…Nocardicin A has been shown to stimulate phagocytic function of polymorphonuclear leukocytes (7,15), and it has been suggested that this effect enhances its therapeutic efficacy (7,14). It is unlikely that this property accounts for the in vivo synergy between Nva-Ala(P) and nocardicin A, as the phosphonopeptide has no effect on polymorphonuclear leukocytes or on nocardicin A stimulation of phagocyte activity (unpublished data).…”

Section: Methodsmentioning

confidence: 99%

“…When clinical isolates of species reported to be especially susceptible to nocardicin A in vitro (15) as well as to Nva-Ala(P) (3) were tested for activity of the agents alone and in combination, synergy was most frequently observed against P. aeruginosa (Table 2). Eighty-five percent of P. aeruginosa strains gave an FICI of less than 0.5 at the majority of ratios examined, with an optimum ratio of 8:1 Nva-Ala(P) to nocardicin A (Table 2).…”

Section: Methodsmentioning

confidence: 99%

“…We have studied combinations of Nva-Ala(P) with various 3-lactam antibiotics, including the monocyclic agent nocardicin A, with a view to improving its antipseudomonal activity. Nocardicin A is reported to have an unusually restricted spectrum of activity in vitro and in vivo but includes organisms such as P. aeruginosa, Proteus spp., and Serratia marcescens (14,15) which are often refractory to treatment. In this paper, we have identified nocardicin A as an especially useful partner for Nva-Ala(P), giving synergy in several species, including P. aeruginosa, and a broad spectrum of activity against gram-negative bacterial infections in an animal model.…”

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confidence: 99%

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Synergistic antibacterial activity between L-norvalyl-L-1-aminoethylphosphonic acid and nocardicin A

Angehrn¹,

Hall²,

Lloyd³

et al. 1984

Antimicrob Agents Chemother

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The phosphonopeptide L-norvalyl-L-1-aminoethylphosphonic acid [Nva-Ala(P)] has been studied in combination with 12 r-lactam antibiotics for activity against Pseudomonas aeruginosa. Nocardicin A was found to give the most potent synergistic combination with Nva-Ala(P). This interaction was widely observed in clinical isolates of P. aeruginosa in vitro and in a mouse septicemia model. Synergy was also observed in vitro and in vivo in several other species, including Proteus mirabilis, indole-positive Proteus spp., and Serratia marcescens. The interaction between Nva-Ala(P) and nocardicin A involved a strongly bacteriolytic mechanism. In addition, the individual components were complementary to one another in their action against organisms not showing synergy. These properties resulted in a broad spectrum of activity of the combination Nva-Ala(P) plus nocardicin A when used to treat experimental gram-negative bacterial infections.A synergistic antibacterial interaction between the phosphonopeptide alafosfalin (L-alanyl-L-1-aminoethylphosphonic acid) and other inhibitors of cell wall biosynthesis, such as ampicillin, cephalexin, mecillinam, and D-cycloserine, has been reported previously (1, 2). This property was also displayed by related phosphonopeptides derived from aminomethylphosphonic acid (5) Agents Chemother. 19th, Boston, Mass., abstr. no. 238, 1979). Of the latter, L-norvalyl-L-1-aminoethylphosphonic acid [Nva-Ala(P)] was of particular interest, as it possessed a broad antibacterial spectrum, including activity against Pseudomonas aeruginosa (3). We have studied combinations of Nva-Ala(P) with various 3-lactam antibiotics, including the monocyclic agent nocardicin A, with a view to improving its antipseudomonal activity. Nocardicin A is reported to have an unusually restricted spectrum of activity in vitro and in vivo but includes organisms such as P. aeruginosa, Proteus spp., and Serratia marcescens (14, 15) which are often refractory to treatment. In this paper, we have identified nocardicin A as an especially useful partner for Nva-Ala(P), giving synergy in several species, including P. aeruginosa, and a broad spectrum of activity against gram-negative bacterial infections in an animal model. MATERIALS AND METHODSCompounds. Nva-Ala(P) was synthesized by R. W. Lambert by the methods described previously (6). Samples of apalcillin (Sumitomo Chemical Co., Osaka, Japan), azlocillin

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Section: Methodssupporting

confidence: 67%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Synergistic antibacterial activity between L-norvalyl-L-1-aminoethylphosphonic acid and nocardicin A

Angehrn¹,

Hall²,

Lloyd³

et al. 1984

Antimicrob Agents Chemother

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“…The nocardicins were the first ^la c tam antibiotics found to lack the bicyclic structural principle of the classical /¡-lac tams [2], Contrary to expectation, the an tibacterial properties of the natural com pounds which showed rather weak in vitro activities and somewhat more pro nounced in vivo efficacy [8,9] could not be improved by structural modification. However, the isolation and characteriza tion of monocyclic N-sulfonated /¡-lac tam antibiotics some years ago [5,11] greatly revived the interest in monocyclic /8-lactam derivatives.…”

Section: Introductionmentioning

confidence: 99%

Antibacterial Properties of Carumonam (Ro 17–2301, AMA-1080), a New Sulfonated Monocyclic <i>β</i>-Lactam Antibiotic

Angehrn¹

1985

Chemotherapy

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The in vitro and in vivo activity of carumonam was tested in comparison with that of aztreonam and other β-lactam antibiotics. With the exception of a few isolates that were overproducers of cephalosporinase, Enterobacteriaceae were highly susceptible to carumonam, 90% of the isolates being inhibited at 0.5 μg/ml. Aztreonam, ceftriaxone and ceftazidime were overall slightly less active than carumonam against Enterobacteriaceae. Carumonam was intermediate between ceftazidime and aztreonam as to the activity against Pseudomonas aeruginosa. Staphylococci were resistant to the monocyclic β-lactams. In accordance with the in vitro data, carumonam was effective against experimental septicemias and infections of the thigh and the kidney that were caused by gram-negative pathogens.

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β‐Lactam Antibiotics

Andreotti

Biondi

Modugno

2003

Burger's Medicinal Chemistry and Drug Discovery

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This chapter reviews the history of β‐lactams from the discovery of penicillin in 1928 to the more recently studied and the current trends in the field. The most relevant aspects related to the mechanism of action of β‐lactams are covered, and the various mechanisms of resistance to currently available β‐lactams that bacteria have adopted since the introduction of penicillin are described. A classification of β‐lactamases and their relevance in clinics is also provided. Applications of β‐lactams both in the hospital and in the community are reported, with particular attention to their pharmacokinetic properties, related side effects, and their therapeutic indications. The history and discovery of β‐lactams are described and all major classes are covered: penicillins, cephalosporins, oxacephems, carbacephems, penems, monobactams and nocardicins, carbapenems and trinems, classical (e.g., clavulanic acid, sulbactam, tazobactam), and the more recently disclosed β‐lactamase inhibitors. Several aspects related to the most recent developments in β‐lactams are also covered: new molecules active against difficult Gram‐positive strains or endowed with an antibacterial broad spectrum of action; potent orally active β‐lactams; injectable β‐lactams; and β‐lactamase inhibitors. The chapter concludes with a continuing analysis of the industry‐driven trends and the most recent new application of β‐lactams as inhibitors of protein export in bacteria. Finally, a few very interesting Web addresses and a comprehensive reference list are also provided.

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NOCARDICIN A, a NEW MONOCYCLIC Β-Lactam ANTIBIOTIC. III

Cited by 36 publications

References 7 publications

Synergistic antibacterial activity between L-norvalyl-L-1-aminoethylphosphonic acid and nocardicin A

Synergistic antibacterial activity between L-norvalyl-L-1-aminoethylphosphonic acid and nocardicin A

Antibacterial Properties of Carumonam (Ro 17–2301, AMA-1080), a New Sulfonated Monocyclic <i>β</i>-Lactam Antibiotic

β‐Lactam Antibiotics

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