Ceftizoxime: A Beta‐Lactamase‐Stable, Broad‐Spectrum Cephalosporin

Neu, Harold C.

doi:10.1002/j.1875-9114.1984.tb03313.x

Cited by 26 publications

(13 citation statements)

References 80 publications

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“…Levels in serum reached after i.v. administration of 2 g of CZX or CTX and pharmacokinetic parameters were usually similar to those found in other studies (8,10,27,33). In contrast, CTX elimination half-life and blister fluid penetration by CZX and dCTX were slightly superior to those in the references cited.…”

Section: In Fresh Resultssupporting

confidence: 46%

Comparative study of pharmacokinetics and serum bactericidal activity of ceftizoxime and cefotaxime

Vallée

LeBel

1991

Antimicrob Agents Chemother

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Single 2-g intravenous doses of ceftizoxime (CZX) and cefotaxime (CTX) were given over 30 min to 10 adult volunteers in a crossover manner on two separate occasions. Concentrations of CZX, CTX, and the primary metabolite of CTX, desacetylcefotaxime (dCTX), in serum, suction-induced-blister fluid, and urine were determined by high-pressure liquid chromatography. Pharmacokinetic parameters were estimated by using an extended least-squares modeling program (MKMODEL). CZX exhibited a half-life in serum (2.05 h) longer than that of CTX (1.43 h) but comparable to that of dCTX (2.02 h). The percentage of penetration in blister fluid, estimated by area under the curve ratios, was significantly higher for CZX (164.4%) than for CTX (60.8%). Serum bactericidal activity, determined for volunteer samples at 1, 6, 8, and 12 h after patients were dosed, against clinical isolates of the Bacteroides fragilis group, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and MorganeUa morganii were significantly higher for CZX than those for CTX against members of the family Enterobacteriaceae at all times. Serum bactericidal titers against B. fragilis were also

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Section: In Fresh Resultssupporting

confidence: 46%

Comparative study of pharmacokinetics and serum bactericidal activity of ceftizoxime and cefotaxime

Vallée

LeBel

1991

Antimicrob Agents Chemother

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“…The pharmacokinetics of ceftizoxime have been studied in Japanese children (Neu, 1984;Richards and Heel, 1985). The serum concentrations and half-life of the drug are similar to those achieved in adults.…”

Section: Cejiizoximementioning

confidence: 92%

“…No metabolites with antibacterial activity were detected in the urine. The pharmacokinetics of ceftazidime have been reviewed by Neu (1984) and by Richards and Heel (1985).…”

Section: Cejtazidimementioning

confidence: 99%

Clinical Pharmacokinetics of the Third Generation Cephalosporins

Balant

Dayer

Auckenthaler

1985

Clinical Pharmacokinetics

106

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At the present time, the third generation cephalosporins that are already on the market or close to this point include cefsulodin, cefotaxime, cefoperazone, latamoxef, ceftriaxone, ceftazidime, ceftizoxime and cefotetan. Other newer compounds are also under development but have not been included in this review. None of the third generation compounds is suitable for oral administration and, accordingly, their pharmacokinetics have been studied only after intravenous and intramuscular administration. Microbiological assays and HPLC methods have been used for the measurement of plasma/serum, urine, bile and cerebrospinal fluid (CSF) concentrations. As found with cefotaxime, microbiological assays should only be used when the full metabolite spectrum of a particular drug is known, as otherwise, the presence of microbiologically active metabolites may lead to erroneous conclusions. Under normal conditions, the major route of elimination is via the kidneys for cefsulodin, latamoxef, ceftazidime, ceftizoxime and cefotetan. In contrast, cefoperazone is mainly eliminated in the bile, whereas cefotaxime and ceftriaxone depend both on the liver and the kidneys for their elimination. With the exception of ceftriaxone, which has a longer elimination half-life (i.e. around 8 hours), all the other third generation cephalosporins have a t1/2 ranging between 1.5 and 2.5 hours. Plasma protein binding is variable from one compound to another. However, the clinical relevance of this parameter is not clearly established since tissue penetration also depends on the relative affinity of the drug for tissue components. Third generation cephalosporins seem to penetrate adequately into the CSF and, thus pharmacokinetically appear to be appropriate agents for the treatment of meningitis. The degree of modification of pharmacokinetic parameters by renal insufficiency or hepatic diseases depends, as for other drugs, on the extent to which the compound is excreted via the kidneys or the liver. The third generation cephalosporins have been extensively studied under these conditions and recommendations for dosage modification in special circumstances are available for most of them. The pharmacokinetics of some third generation cephalosporins may be modified in neonates and elderly patients. Accordingly, their use at the extremes of age must be accompanied by a closer than usual clinical monitoring of the patient. From a clinical point of view, the third generation cephalosporins possess reliable pharmacokinetic properties.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…Figure 1 is a typical time-kill curve, utilizing an isolate of S. faecalis. In this example, cefotaxime plus gentamicin was the only combination that caused a 2 log10 decrease in colony count at 20 h. 100 ,ug/ml (0); amikacin, 20 pLg/ml, plus cefotaxime, 100 ,ug/ml (U); amikacin, 20 ,ug/ml (A); gentamicin, 5 ,ug/ml (A); tobramycin, 5 ,Lg/ml (O); tobramycin, 5 ,ug/ml, plus cefotaxime, 100 ,ug/ml (*); and gentamicin, 5 ,ug/ml, plus cefotaxime, 100 ,ug/ml (0). Only gentamicin plus cefotaxime (0) produced a greater than 2 log1o decrease in colony counts at 20 h and therefore fulfilled the criteria for synergy.…”

Section: Resultsmentioning

confidence: 93%

Interaction of cefotaxime and aminoglycosides against enterococci in vitro

Elliott¹,

Karam²,

Cobbs³

1983

Antimicrob Agents Chemother

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The antibacterial activities of cefotaxime, gentamicin, tobramycin, and amikacin as well as the combinations of cefotaxime and aminoglycosides were tested against 50 strains of enterococci. Synergy studies were performed by the time-kill method, and with this technique the combination of cefotaxime plus gentamicin appeared to be more active than the combination of cefotaxime plus tobramycin or cefotaxime plus amikacin. Results of this in vitro study suggest cefotaxime and gentamicin may provide some activity against enterococci, although not sufficient to substitute for proven therapy such as penicillin-ampicillin and gentamicin.Enterococci have emerged as important bacterial pathogens that are frequently resistant to the new cephalosporin antimicrobial agents. Because these new agents are often utilized in combination with aminoglycosides, we thought it would be interesting to determine the in vitro activity of combinations of cefotaxime, the first third-generation agent available in the United States, and the three most commonly used aminoglycosides, gentamicin, tobramycin, and amikacin, to determine whether cefotaxime plus these agents might be reasonable candidates for use in patients with enterococcal disease. MATERIALS AND METHODSFifty strains of enterococci were obtained from 24 urine cultures, 20 wound cultures, 2 sputum cultures, 2 bronchial washings, and 2 bile cultures performed in the Clinical Microbiology Laboratory at the University of Alabama Medical Center during November and December 1982.All strains grew in 6.5% NaCl heart infusion broth and as brownish-black colonies surrounded by a black zone on bile esculin agar. Precise determination of species was performed by the API 20S Streptococcus System (Analytab Products, Plainview, N.Y.). There were 46 strains of Streptococcus faecalis and 4 strains of Streptococcus faecium.Antimicrobial agents used in this study were kindly supplied as sterile standard reference powders by the following companies: cefotaxime by Hoechst-Roussell Pharmaceuticals, Inc., Somerville, N.J.; gentamicin by Schering Corp., Kenilworth, N.J.; tobramycin by Eli Lilly & Co., Indianapolis, Ind.; and amikacin by Bristol Laboratories, Syracuse, N.Y.The minimal inhibitory concentration (MIC) was determined for each isolate for cefotaxime, gentamicin, tobramycin, and amikacin by both agar dilution and broth dilution techniques. In the broth dilution technique, five colonies of each strain were picked to 2 ml of Mueller-Hinton broth (BBL Microbiology Systems, Cockeysville, Md.), which were incubated overnight at 37°C and then diluted to a final inoculum of 5 x 10' CFU/ml. Serial twofold dilutions were made in Mueller-Hinton broth, using borosilicate tubes with loose-fitting metal caps with a total volume of 1 ml. The MIC was defined as the lowest concentration of the antimicrobial agent causing no visible growth after incubation at 37°C for 18 h.From each clear tube and the cloudy tube with the least antimicrobial concentration, 0.01 ml was subcultured onto 5% sheep blood agar. The ...

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Ceftizoxime: A Beta‐Lactamase‐Stable, Broad‐Spectrum Cephalosporin

Cited by 26 publications

References 80 publications

Comparative study of pharmacokinetics and serum bactericidal activity of ceftizoxime and cefotaxime

Comparative study of pharmacokinetics and serum bactericidal activity of ceftizoxime and cefotaxime

Clinical Pharmacokinetics of the Third Generation Cephalosporins

Interaction of cefotaxime and aminoglycosides against enterococci in vitro

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