The Japanese surveillance committee conducted the first nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for female acute uncomplicated cystitis at 43 hospitals throughout Japan from April 2009 to November 2010. In this study, the causative bacteria (Escherichia coli and Staphylococcus saprophyticus) and their susceptibility to various antimicrobial agents were investigated by isolation and culturing of bacteria from urine samples. In total, 387 strains were isolated from 461 patients, including E. coli (n = 301, 77.8 %), S. saprophyticus (n = 20, 5.2 %), Klebsiella pneumoniae (n = 13, 3.4 %), and Enterococcus faecalis (n = 11, 2.8 %). S. saprophyticus was significantly more common in premenopausal women (P = 0.00095). The minimum inhibitory concentrations of 19 antibacterial agents used for these strains were determined according to the Clinical and Laboratory Standards Institute manual. At least 87 % of E. coli isolates showed susceptibility to fluoroquinolones and cephalosporins, and 100 % of S. saprophyticus isolates showed susceptibility to fluoroquinolones and aminoglycosides. The proportions of fluoroquinolone-resistant E. coli strains and extended-spectrum β-lactamase (ESBL)-producing E. coli strains were 13.3 % and 4.7 %, respectively. It is important to confirm the susceptibility of causative bacteria for optimal antimicrobial therapy, and empiric antimicrobial agents should be selected by considering patient characteristics and other factors. However, the number of isolates of fluoroquinolone-resistant or ESBL-producing strains in gram-negative bacilli may be increasing in patients with urinary tract infections (UTIs) in Japan. Therefore, these data present important information for the proper treatment of UTIs and will serve as a useful reference for future surveillance studies.

This study was conducted by the Japanese Society of Chemotherapy and is the first nationwide study on bacterial pathogens isolated from patients with urinary tract infections at 28 hospitals throughout Japan between January 2008 and June 2008. A total of 688 bacterial strains were isolated from adult patients with urinary tract infections. The strains investigated in this study are as follows: Enterococcus faecalis (n = 140), Escherichia coli (n = 255), Klebsiella pneumoniae (n = 93), Proteus mirabilis (n = 42), Serratia marcescens (n = 44), and Pseudomonas aeruginosa (n = 114). The minimum inhibitory concentrations of 39 antibacterial agents used for these strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) manual. All Enterococcus faecalis strains were susceptible to ampicillin and vancomycin. Although a majority of the E. faecalis strains were susceptible to linezolid, 11 strains (7.8%) were found to be intermediately resistant. The proportions of fluoroquinolone-resistant Enterococcus faecalis, Escherichia coli, Proteus mirabilis, and S. marcescens strains were 35.7%, 29.3%, 18.3%, and 15.2%, respectively. The proportions of E. coli, P. mirabilis, K. pneumoniae, and S. marcescens strains producing extended-spectrum β-lactamase were 5.1%, 11.9%, 0%, and 0%, respectively. The proportions of Pseudomonas aeruginosa strains resistant to carbapenems, aminoglycosides, and fluoroquinolones were 9.2%, 4.4%, and 34.8%, respectively, and among them, 2 strains (1.8%) were found to be multidrug resistant. These data present important information for the proper treatment of urinary tract infections and will serve as a useful reference for periodic surveillance studies in the future.

The pharmacokinetic profile of ceftizoxime was studied in mice, rats, dogs, and monkeys given the drug in a single parenteral dose. The serum data after an intravenous injection were analyzed by the two-compartment open model. Cefotiam, cefmetazole, cefotaxime, and cefamandole were used as reference drugs. High concentrations of ceftizoxime were attained in the sera of all test animals and in the tissues of rats after parenteral dosing. The serum concentrations of ceftizoxime were higher than those of the other antibiotics in large animals (dogs and monkeys), but were lower in small animals (mice and rats). About 80% of ceftizoxime was excreted unchanged in the 24-h urine of all species tested. The biliary excretion of ceftizoxime was low: 3.7% in rats and 0.59% in dogs. However, therapeutically significant concentrations of ceftizoxime were found in the bile of dogs. Ceftizoxime was stable in biological fluids such as serum, urine, and tissue homogenates, but cefotaxime was unstable in rat tissue homogenates. Binding of ceftizoxime to serum protein in all species was the lowest of all the antibiotics: 31% for humans, 17% for dogs, and 32% for rats.Ceftizoxime, a new parenteral cephalosporin derivative, is more active against various gramnegative bacilli, including the opportunistic pathogens such as Enterobacter, Citrobacter spp., and Serratia marcescens, than such cephalosporins as cefotiam, cefuroxime, cefotaxime, and cefmetazole (5). In the present study the pharmacokinetics, metabolism in animals, binding to serum protein, and stability of ceftizoxime were evaluated. Cefotiam, cefamandole, cefotaxime, and cefinetazole, all recently developed cephalosporins, were used as reference drugs.MATERIALS AND METHODSAntibiotics. The compounds used in this study included ceftizoxime (FK 749, Fujisawa, Japan), cefotiam (SCE 963, Takeda, Japan), cefamandole (Eli IJlly & Co., Indianapolis, Ind.), cefmetazole (CS 1170, Sankyo, Japan), and cefotaxime (HR 756, HoechstRoussel, West Germany).Animals. The animals used in this study included 6-week-old male JCL:ICR strain mice, 6-week-old male JCL:SD strain rats, 7.5-to 15.0-kg male beagle dogs, and 5.8-to 9.1-kg male rhesus monkeys. Dosing. The antibiotics for injection were dissolved in 0.9% saline. The drugs were given in a dose of 20 mg/kg to all test animals. The volumes were: 0.25 ml per animal by the intravenous (i.v.) and subcutaneous routes to mice; 5 ml/kg of body weight by the intramuscular (i.m.) and i.v. routes to rats; and 0.5 ml/kg of body weight by the i.m. and i.v. routes to dogs and monkeys.Serum sampling. Blood samples were collected: (i) from the carotid artery of mice at specified intervals after injection; (ii) by heart puncture from rats; (iii) from the antecubital veins of dogs and monkeys. The antibiotic concentrations in the serum were bioassayed using standard solutions prepared with control serum of the respective species of animals.Pharmacokinetic analysis. The serum concentration-time data were fitted to a two-compartment open model (4) using Marqu...

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A new in vitro model was devised for evaluating the bactericidal activity of antibiotics undqr dynamic conditions. This model accurately reproduced the observed serum levels of antibiotics after intravenous dosing. The apparatus consists of two vessels which correspond to the central and peripheral compartments of a two-compartment open model. The volume of medium in each vessel and flow rates of media were determined from the pharmacokinetic parameters calculated from the observed serum levels selected for simulation. The bactericidal activity of cefazolin against strains of Escherichia coli and Klebsiella pneumoniae showing different minimal inhibitory concentrations was investigated with the apparatus simulating serum levels after intravenous injection, and the bactericidal activity was evaluated with respect to the relationship between the minimal inhibitory concentration and the serum levels.Previously (10) (1) where A is the extrapolated concentration of the a phase at t = 0; B is the extrapolated concentration of the ,B phase at t = 0; C is the serum concentration at time t, a is the first-order elimination rate constant of the a phase; ,B is the first-order elimination rate constant of the f8 phase; and t is the time after injection. Serum concentrations simulated in the kinetic model were analyzed by the two-compartment open model, and the following pharmacokinetic parameters were determined by Marquardt's nonlinear leastsquares regression analysis, using a FACOM 230/38 digital computer (Fujitsu Co., Ltd., Tokyo, Japan): a