HR 756, a New Cephalosporin Active Against Gram-Positive and Gram-Negative Aerobic and Anaerobic Bacteria

Neu, Harold C.; Aswapokee, Nalinee; Aswapokee, P; Fu, Kwung P.

doi:10.1128/aac.15.2.273

Cited by 152 publications

(68 citation statements)

References 15 publications

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“…Cefamandole, in this and other studies (3,13), has been shown to have good in vitro activity against gram-positive cocci VOL. 19,1981 on April 7, 2019 by guest http://aac.asm.org/ Downloaded from (2,14,26) and moxalactam (7,15,25). Ro and cefotaxime were approximately equal in activity, with moxalactam being only slightly less active.…”

Section: Discussionmentioning

confidence: 98%

Comparative in vitro studies of Ro 13-9904, a new cephalosporin derivative

Eickhoff¹,

Ehret²

1981

Antimicrob Agents Chemother

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The in vitro activity of Ro 13-9904, a new cephalosporin derivative, was compared with the activities of cephalothin, cefamandole, cefoxitin, cefotaxime, and moxalactam against 591 clinical isolates of gram-negative and gram-positive organisms. The spectra of activity and potency of Ro and cefotaxime were quite similar; they were the most active agents against Enterobacteriaceae, Streptococcus pyogenes, Haemophilus influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis. Moxalactam was only slightly less active against these organisms. Ro 13-9904, cefotaxime, and moxalactam were approximately equal in activity against Pseudomonas aeruginosa; concentrations of 50 to 100 ,Ig/ml inhibited over 90% of the strains tested. Cefamandole and cephalothin were the most active drugs tested against staphylococci. Moxalactam demonstrated the highest intrinsic activity against Bacteroides fragilis; a concentration of 1.6 yg/ ml inhibited over 50% of the strains. All six of the antibiotics were essentially inactive against group D streptococci. The action of all of the antibiotics was bactericidal, with minimal bactericidal concentrations generally being no more than twofold greater than miniimal inhibitory concentrations. The only exception to this was found when large inocula of Staphylococcus aureus were tested. Increased inoculum size generally sharply reduced the activity of Ro 13-9904, cefotaxime, and moxalactam against Enterobacteriaceae and P. aeruginosa.The chemotherapy of serious bacterial infections, particularly those which are hospital acquired, is a continuing clinical challenge. Organisms such as Serratia, Acinetobacter, Pseudomonas cepacia, and others once thought to cause disease only rarely, if at all, are now recognized as common pathogens. The need for antimicrobial agents with broad spectra of activity and resistance to the /3-lactamases of gramnegative organisms associated with nosocomial infection has motivated research resulting in the development of a great number of cephalosporin derivatives. Since the discovery of the fungus Cephalosporium acremonium in Sardinian sewage in 1945 (1), the cephalosporins have evolved into a complex group of antibiotics with significant differences in potency and antibacterial spectrum. Ro 13-9904 (Fig. 1) is a new product of the chemical manipulation of side chains joined to the 7-amino-cephalosporanic acid nucleus. It has been reported to be highly active against common gram-negative organisms and relatively resistant to inactivation by cephalosporinases; preliminary data also suggest that the expanded spectrum of activity includes Pseudomonas aeruginosa, Serratia marcesens, and most strains of Enterobacter (compound Ro 13-9904 preliminary data, Hoffmann-La Roche, Inc., 1979).The purpose of this study was to compare the in vitro activity of Ro 13-9904 with the activities of other drugs representing the three major generations of cephalosporin development. The first generation was represented by cephalothin, the second was represented by cefamandole and cefoxit...

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Section: Discussionmentioning

confidence: 98%

Comparative in vitro studies of Ro 13-9904, a new cephalosporin derivative

Eickhoff¹,

Ehret²

1981

Antimicrob Agents Chemother

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“…Much effort has been expended in an attempt to develop broad-spectrum antibiotics with resistance to the enzyme. As a result, recently introduced cephalosporins, such as cefoxitin, cefotiam, and cefuroxime, have possessed some in vitro activity against isolates of Enterobeter and indole-positive Proteus, but not Pseudomonas (13,14,17,26,27 CE.…”

Section: Discussionmentioning

confidence: 99%

“…(13,15,17,26,27). Cefotaxime, a new cephalosporin, has been reported to have a broad antimicrobial spectrum (1, 2, 4, 6,7,14,23,24,28,29) and to be a potent inhibitor of ,B-lactamase and stable in the presence of the enzyme (5). The present study deals with the in vitro antimicrobial activity and ,B-lactamase stability of the compound using clinical isolates stocked in this laboratory.…”

mentioning

confidence: 99%

In vitro antimicrobial activity of cefotaxime, a new cephalosporin

Masuyoshi¹,

Arai²,

Miyamoto³

et al. 1980

Antimicrob Agents Chemother

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Laboratories, Hoechst Japan Limited, Saitama,2 Japan Cefotaxime, a new semisynthetic cephalosporin derivative, showed a broad spectrum of antibacterial activity against clinically isolated strains of grampositive and gram-negative bacteria. This cephalosporin was slightly less active than cefazolin against Staphylococcus aureus but 4 to 300 times as active as carbenicillin against gram-negative organisms, including Pseudomonas aeruginosa, Pseudomonas cepacia, Enterobacter cloacae, and Serratia marcescens. Cefotaxime was the most active compound against members of the Enterobacteriaceae and 20-to 100-fold more active than cefoxitin against the indole-positive Proteus group. The minimal bactericidal concentrations of the compound were identical to, or two times higher than, the minximal inhibitory concentrations against Escherichia coli and P. aeruginosa and four times higher against S. marcescens. A reduction of inoculum size decreased greatly the miniimal inhibitory and bactericidal concentrations of cefotaxime against E. coli, P. aeruginosa, and S. marcescens. The antibiotic was very stable to penicillinase and cephalosporinase produced by gram-negative bacteria, including Proteus vulgaris.Many cephalosporins with broad antibacterial spectra have been in clinical use for the treatment of a wide range of bacterial infections. Recently, however, the effectiveness of the existing cephalosporins has been shown to be limited; there has been a steady increase in clinical infections caused by gram-negative bacteria resistant to 8l-lactam antibiotics, e.g., Pseudomonas spp., Enterobacter spp., Serratia marcescens, and indole-positive Proteus spp., which have been reported to produce ,B-lactamase (11,12,25). Much effort has been expended in developing broad-spectrum antibiotics with resistance to the enzyme. Cefoxitin, cefotiam, and cefuroxime have been semisynthesized, but they are still ineffective against some strains of Enterobacter spp. and Pseudomonas spp. (13,15,17,26,27). Cefotaxime, a new cephalosporin, has been reported to have a broad antimicrobial spectrum (1, 2, 4,6,7,14,23,24,28,29) Table 1 were shown to be standard strains by the Japan Society of Chemotherapy; other strains were isolated from patients in several hospitals in Japan between 1977 and 1978. We selected the strains at random.Media. Heart infusion (HI) agar and brain heart infusion (BHI) agar were used. BHI broth and antibiotic medium 3 (ABM 3) were used. Other media used were medium B, peptone water, and nutrient agar containing bromothymol blue and lactose. Medium B consisted of 2 g of yeast extract, 10 g of polypeptone, 8 g of Na2HPO4 12H20, 2 g of KH2PO4,1.2 g of (NH4)2SO4, 2 g of glucose, 0.4 g of MgSO4.7H20, and 1,000 ml of purified water, and the medium was adjusted to pH 7.4. Peptone water consisted of 10 g of polypeptone, 5 g of NaCl, and 1,000 ml of purified water. For the dilution of cell suspensions, ABM 3 and buffered saline containing gelatin (3)

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“…At the beginning of the 1980's, Stoutenbeek, in designing the selective digestive decontamination (SDD) protocol, searched for a parenteral antimicrobial with adequate spectrum and pharmacokinetic properties to be included in a prophylaxis for critically ill patients requiring treatment on ICU. Cefotaxime was chosen because: Its spectrum included both 'normal' and most 'abnormal' bacteria: (10) Its pharmacokinetic properties included a high level of excretion in saliva and bile, associated with eradication of overgrowth. (11) Salivary and biliary samples were obtained from adult patients requiring biliary surgery and receiving 1g of cefotaxime intravenously four times daily.…”

Section: Surveillance Cultures Required To Identify Overgrowthmentioning

confidence: 99%

Gut overgrowth harms the critically ill patient requiring treatment on the intensive care unit

2012

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HR 756, a New Cephalosporin Active Against Gram-Positive and Gram-Negative Aerobic and Anaerobic Bacteria

Cited by 152 publications

References 15 publications

Comparative in vitro studies of Ro 13-9904, a new cephalosporin derivative

Comparative in vitro studies of Ro 13-9904, a new cephalosporin derivative

In vitro antimicrobial activity of cefotaxime, a new cephalosporin

Gut overgrowth harms the critically ill patient requiring treatment on the intensive care unit

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