Cefuzonam

Abstract: The effect of protein binding in serum of eight cephem antibiotics (ceftazidime, ceftizoxime, cefotiam, cefmetazole, cefpiramide, cefazolin, cefuzonam, ceftriaxone) on their therapeutic efficacies was examined in mice with experimentally induced intraperitoneal infections or pneumonia. The relationship among therapeutic activity, in vitro antibacterial activity, total or free (unbound) levels in serum, and homogenized whole lung levels was investigated. In the intraperitoneal infection caused by Staphylococcus aureus or Klebsiella pneumoniae, the 50% effective doses (ED50s) of the cephem antibiotics correlated with the area under the concentration-time curve (AUC) values of free levels in serum and the MICs but not with those of total levels in serum. A linear relationship was seen between 1/ED50 values and AUC of free levels in serum/MIC values. On the other hand, in mice with pneumonia caused by K. pneumoniae, the number of bacteria in the lung closely correlated with the AUC of the antibiotic concentration in lung tissue. There was a direct correlation between the levels in lung tissue and total levels in serum but not free levels in serum. The cephem antibiotics tested in this study were bound only slightly to homogenates of mouse lung. These results indicate that the effect of protein binding in serum on therapeutic efficacy against intraperitoneal infection differs from that against pulmonary infection.

Abstract: Infections caused by resistant bacterial pathogens such as Citrobacter freundii, Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa have become an increasing problem with respect to therapy in large medical centres in Korea. The MICs of cefepime for aerobic Gram-negative bacilli isolated during 1991, mostly from in-patients in a hospital in Seoul, were determined by the agar dilution method and compared with those of several other antimicrobials. Of the agents tested, cefepime had the lowest MIC90s for C. freundii and E. cloacae (0.12 and 8 mg/L, respectively). The MIC90s of cefepime and amikacin (both 8 mg/L) were the lowest for S. marcescens. The MIC90s of cefepime, ceftazidime and doxycycline (all 32 mg/L) were the lowest for Acinetobacter anitratus. For P. aeruginosa, the MIC90 was relatively high (32 mg/L) but still the lowest of the antimicrobials tested. Of the cefotaxime-resistant E. cloacae isolates studied, only 7% were resistant to cefepime, while 100%, 96% and 89% were resistant to ceftazidime, ceftizoxime and cefuzonam, respectively. Similarly, only 6% of gentamicin-resistant isolates were resistant to cefepime, compared with 91%, 72%, 69% and 63% to ceftazidime, ceftizoxime, cefuzonam and cefotaxime, respectively. In conclusion, isolates from Korean patients are often resistant to several antimicrobial agents. However, based on the results of this study, cefepime may be very useful as treatment for patients with nosocomial infections caused by aerobic Gram-negative bacilli, including those which are resistant to most of the third-generation cephalosporins and gentamicin.

Abstract: A novel 4-halo-2-oxyimino-3-oxo butyric acid-N, N-dimethyl formiminium chloride chlorosulfate of formula (I) useful in the preparation of cephalosporin antibiotics, wherein X is chlorine or bromine; R is hydrogen, C1-4 alkyl group, an easily removable hydroxyl protective group, -CH2COOR5, or -C(CH3)2COOR5, wherein R5 is hydrogen or an easily hydrolysable ester group. The compound of formula (I) is prepared by reacting 4-halo-2-oxyimino-3-oxobutyric acid of formula (IV1), wherein X, R and R5 are as defined above, with N, N-dimethylformiminium chloride chlorosulphate of formula (VII), in an organic solvent at a temperature ranging from -30 °C to -15 °C. The cephalosporins that may be prepared from the intermediate include cefdinir, cefditoren pivoxil, cefepime, cefetamet pivoxil, cefixime, cefmenoxime, cefodizime, cefoselis, cefotaxime, cefpirome, cefpodoxime proxetil, cefquinome, ceftazidime, cefteram pivoxil, ceftiofur, ceftizoxime, ceftriaxone and cefuzonam.

Abstract: The in vitro and in vivo antibacterial activities of meropenem were compared with those of imipenem, ceftazidime, flomoxef, cefuzonam and cefotiam. Meropenem showed a broad antibacterial spectrum against clinical isolates of Gram-positive and Gram-negative bacteria. Against Gram-negative bacteria, with the exception of Acinetobacter calcoaceticus, meropenem exhibited the most potent activity among the drugs tested. It inhibited all 330 strains of Enterobacteriaceae at 0.78 mg/l. Meropenem was sensitive against several cephem-resistant strains of Enterobacteriaceae. Against Pseudomonas aeruginosa, meropenem was four-fold more active than imipenem and eight-fold more active than ceftazidime, with an MIC90 of 0.78 mg/l. The therapeutic effect of meropenem on systemic infection in mice was ten to twenty-fold less than that of imipenem against Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae. However, meropenem was as effective as imipenem on infections of Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Acinetobacter calcoaceticus and Pseudomonas aeruginosa. Meropenem was eliminated from mice plasma two-fold faster than imipenem, with a plasma half-life of 7.6 min. From the above results the authors concluded that meropenem is a promising drug for clinical use.