Cefuroxime, a New Cephalosporin Antibiotic: Activity In Vitro

Cefotaxime is more active than six other cephalosporins against 150 cephalothin-resistant Enterobacteriaceae strains and is the only drug which is more active than ampicillin against Haemophilus. It shows a potentially useful activity against Pseudomonas.Cefotaxime is the sodium salt of 7-[(2-(2-amino-4-thiazolyl)-2(z)-methoxy-imino) acetamido] cephalosporanic acid. The antibacterial spectrum of the compound is considerably broader than that of known cephalosporins (8). The increase in resistance among the Enterobacteriaceae against cephalothin (11) and the emergence of ,B-lactamase-producing Haemophilus strains (9) has increased the demand for new antibiotics. Among the newer cephalosporin-like antibiotics, the most promising are cefamandole and cefuroxime with good activity on Haemophilus and most of the Enterobacteriaceae (5, 12) and cefoxitin with good activity on Bacteroides fragilis (13) and on the Enterobacteriaceae, with the exception of Enterobacter (3, 15); finally, cefazaflur was shown to be very active against the Enterobacteriaceae with the exception of Serratia (14).Cefotaxime has several advantages over the other newer cephalosporins. It has been shown by others to be more active than previous cephalosporins, including cefuroxime and cefoxitin, against cephalothin-susceptible strains and Haemophilus influenzae (1,7). Its stability against ,8-lactamase hydrolysis is comparable to that of cefuroxime and cefoxitin, but cefotaxime is the most active inhibitor of type 1 ,B-lactamase (6).In contrast, it seems to be less active than cefoxitin against Bacteroides fragilis (1).In accordance with these publications, it is clear from this study that cefotaxime is also very active against cephalothin-resistant Enterobacteriaceae with an activity that is at least 21 times greater than that of the second most active drug and the only drug with excellent activity against one of the most resistant species, namely, Serratia. It is also at least 45 times more active than the other cephalosporins against Haemophilus strains and the only one which is even

mentioning

confidence: 99%

In Vitro Activity of Cefotaxime Against Cephalothin-Resistant Clinical Isolates

Landuyt

Pyckavet

1979

“…Recently, naturally occurring inhibitors of ,B-lactamases produced by streptomyces have been discovered (1,14). Cefoxitin and cefuroxime, two new fi-lactam compounds, have been reported to be resistant to B8-lactamases of gram-negative bacilli (3,12).…”

mentioning

confidence: 99%

Beta-Lactamase Stability of HR 756, a Novel Cephalosporin, Compared to That of Cefuroxime and Cefoxitin

Neu

1978

122

The stability to β-lactamase hydrolysis of HR 756, a new cephalosporin antibiotic, was compared to the β-lactamase stability of cefoxitin and cefuroxime. HR 756, cefoxitin, and cefuroxime were not hydrolyzed by Richmond type I, III, IV, and V β-lactamases. Antibacterial activity of HR 756 correlated well with resistance to β-lactamase hydrolysis except against Pseudomonas aeruginosa . HR 756, cefoxitin, and cefuroxime inhibited type I β-lactamases, but not type III, IV, or V enzymes. HR 756 was the most active inhibitor.

“…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%

“…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.…”

mentioning

confidence: 99%

In vitro antimicrobial activity of cefotaxime, a new cephalosporin

Masuyoshi¹,

Arai²,

Miyamoto³

et al. 1980

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)