A highly cephem-resistant Escherichia coli strain, FP1546, isolated from the fecal flora of laboratory dogs previously administered 1-lactam antibiotics was found to produce a P-lactamase, FEC-1, of 48-kilodalton size and pl 8.2. FEC-1 hydrolyzed cefuroxime, cefotaxime, cefmenoxime, and ceftriaxone, as well as the enzymatically less-stable antibiotics cephaloridine, cefotiam, and cefpiramide. Of the oxyimino-cephalosporins, ceftizoxime was fairly stable to FEC-1. FEC-1 differed notably from chromosomal E. coli cephalosporinase, especially in its broad-spectrum substrate profile and its high inhibition by clavulanic acid, sulbactam, and imipenem. A conjugation study revealed that FEC-1 was encoded by a 74-megadalton plasmid, pFCX1. This may be the first instance of a plasmid-mediated oxyimino-cephalosporinase from E. coli.Over 30 plasmid-mediated f-lactamases (mostly penicillinases) have been found in gram-negative bacteria and classified according to characteristics such as substrate specificity, isoelectric point, and molecular weight. Common are the TEM, OXA, SHV, and PSE types (10,(17)(18)(19)24), with the TEM type of penicillinase being the most frequently isolated plasmid P-lactamase from such gram-negative bacteria as members of the family Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenzae, and Neisseria gonorrhoeae. On the other hand, there have been only two reports of plasmid-mediated cephalosporinases, from Proteus mirabilis (2) and Achromobacter spp. (14).We evaluated the possible resistance mechanisms of oxyimino-cephalosporin-resistant Escherichia coli isolated from the fecal flora of laboratory dogs, and we identified a 3-lactamase which hydrolyzes oxyimino-cephalosporins such as cefuroxime, cefotaxime, cefmenoxime, and ceftriaxone in addition to cephaloridine. The physiological properties of this enzyme were quite distinct from those of chromosomal cephalosporinases from E. coli (20,23). We confirmed that this enzyme was plasmid mediated and had properties similar to those of oxyimino-cephalosporinase type I (7). MATERIALS AND METHODSBacterial strains. E. coli FP1546 was isolated from the fecal flora of a laboratory dog being used for pharmacokinetic studies of P-lactam antibiotics. The nalidixic acidresistant derivative of E. coli CSH2 (metB F-) was kindly provided by T. Yokota of Juntendo University.Antibiotics. Commercially available cephaloridine, cephalothin, cefamandole, cefotiam, cefmetazole, cefsulodin, cefuroxime, cefotaxime, cefmenoxime, ceftriaxone, ceftazidime, cefoperazone, cefpiramide, cefoxitin, moxalactam, and imipenem were used. Cefazolin and ceftizoxime were from Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan. * Corresponding author.Clavulanic acid, sulbactam, and nitrocefin were synthesized in our laboratories.Susceptibility testing. Antibacterial activity of test antibiotics was determined by the agar dilution method. Hundredfold dilutions of overnight cultures in Mueller-Hinton broth (Difco Laboratories, Detroit, Mich.) were inoculated with a multipoint replic...

Background Two major definitions exist for presenteeism: sickness presenteeism and impaired work function. The evidence for comparing previous studies on presenteeism is insufficient because of the different definitions of presenteeism used. Aims To assess the relationship between the two major definitions of presenteeism. Methods This cross-sectional study analysed secondary data on 5334 respondents to an employee survey administered in a construction company in Japan. Impaired work function was measured using the Work Functioning Impairment Scale (WFun). Multiple logistic regression was performed. Results A strong linear association was observed between the number of days of sickness presenteeism and impaired work function (all P < 0.001). In contrast, the number of days of sickness absence was only partially positively associated with impaired work function. All choices for most frequent health problem were positively associated with impaired work function, beginning with mental problems (adjusted odds ratio [OR] = 20.45, 95% confidence interval [CI]: 14.94–28.01), followed by malaise (adjusted OR = 11.91, 95% CI: 9.08–15.62) and sleeping problems (adjusted OR = 8.62, 95% CI: 6.57–11.33). Conclusions A strong relationship was observed between the two major definitions of presenteeism, even after adjusting for a variety of chronic health conditions. Although a consensus on the definition of presenteeism is yet to be reached, this study provides insight on comparing existing studies on presenteeism.

FK 749 is a new parenteral cephalosporin derivative which is more active against various gram-negative bacilli, including the opportunistic pathogens such as Enterobacter, Citrobacter species, and Serratia marcescens, than cephalosporins and cephamycins such as cefotiam, cefamandole, cefuroxime, cefotaxime, and cefmetazole. FK 749 was especially active against gram-negative organisms resistant to these related antibiotics. FK 749 was more potent in bactericidal activity than the other antibiotics, and the activity was clearly enhanced in the presence of 90% defibrinated rabbit blood. The therapeutic effect of subcutaneously injected FK 749 in mice infected with various gram-negative bacilli was far superior to that of cefotiam, cefamandole, cefuroxime, and cefmetazole and was almost the same as that of cefmetazole in mice infected with Staphylococcus aureus and that of ticarcillin in mice infected with Pseudomonas aeruginosa. FK 749 has, in general, nearly the same in vitro and in vivo antibacterial activities as cefotaxime. The former had more potent bactericidal activity in the presence of the blood than the latter and showed more excellent therapeutic effect than cefotaxime against infections caused by large inoculum sizes.The cephalosporins cefazolin (4) and ceftezole (5) resulted from our drug development program. In the continuing search for new cephalosporins with even greater antibacterial activity against a wide variety of gram-positive and gram-negative organisms, including the opportunistic pathogens, FK 749, a distinctive new parenteral cephalosporin derivative, was recently developed (Fig. 1) Bacterial strains. Standard strains from the culture collection of this laboratory were used in the study. Clinical isolates of various species of bacteria were obtained from several hospitals in Japan.Antibiotic susceptibility. Minimum inhibitory concentrations (MICs) were determined by the agar dilution method using heart infusion agar (HI agar, Difco Laboratories, Detroit, Mich.), unless otherwise specified. For testing Haemophilus influenzae, Neisseria species, and streptococcal species, except Streptococcus faecalis, the medium was supplemented with 5% defibrinated horse blood. The inoculum was grown in Trypticase soy broth (BBL Microbiology Systems, Cockeysville, Md.) overnight at 37°C. The broth was supplemented with 10% Fildes enrichment (Difco) for H. influenzae and with 5% defibrinated horse blood for Neisseria species and streptococcal species. An overnight broth culture and decimal dilutions thereof were streaked or spot-inoculated onto the agar media containing graded concentrations of the test antibiotics. MICs were read after incubation at 37°C for 20 h. For testing anaerobic bacteria, incubation was performed by the GasPak method (BBL) at 37°C; GAM broth (Nissui, Tokyo) and GAM agar (Nissui) were used for the preculture and test culture, respectively.

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FK 027 was more active than cefaclor, cephalexin, and amoxicillin against stock strains of a wide variety of gram-negative bacteria, including such opportunistic pathogens as Citrobacter and Enterobacter species and Serratia marcescens. FK 027 was significantly more active than the three reference drugs against clinical isolates of Escherichia coli, Klebsiella pneumoniae, indole-positive and -negative Proteus species, Providencia species, Haemophilus influenzae, and Neisseria gonorrhoeae. It was less active than cefaclor, cephalexin, and amoxicillin against staphylococci, but it was similar to cefaclor in its activity against streptococci. With few exceptions, FK 027 was active against strains of E. coli, K. pneumoniae, and Proteus mirabilis that were resistant to the reference agents. The bactericidal activity of FK 027 against various gram-negative bacteria, including Proteus species, Citrobacterfreundii, Enterobacter aerogenes, and S. marcescens, was greater than that of cefaclor, cephalexin, and amoxicillin. The therapeutic activities of FK 027 in mice infected with gram-negative bacilli were far superior to the activities of cefaclor, cephalexin, and amoxicillin, but they were inferior to the activities of these reference drugs against infection with Staphylococcus aureus.Various orally active cephem antibiotics with broad antibacterial spectra have been developed (1,3,5,7,8,10,12) and used extensively in the treatment of bacterial infections. The clinical usefulness of these agents is limited, however, because of their relatively low activity against infections with gram-negative bacilli. We recently succeeded in developing FK 027 (Fig. 1) Gani agar (Nissui, Tokyo, Japan) was used for testing anaerobic bacteria. Nonfastidious aerobic organisms were prectiltured in Mueller-Hinton broth (Difco), streptococci were precultured in Mueller-Hinton broth plus 1O0o horse serum, H. influenzae was precultured in Mueller-Hinton broth plus 5% Fildes enrichment, Neisseria species were precultured in Trypticase soy broth (BBL Microbiology Systems, Cockeysville, Md.), and anaerobic bacteria were precultured in Gam broth (Nissui). Overnight cultures of these organisms were diluted 100-fold with the respective medium, and 0.025 ml of an inoculum containing 104 CFU was applied with a multipoint replicating apparatus to agar plates containing serial 2-fold dilutions of each antibiotic. For the testing of N. gonorrhoeae, 0.025 ml of an overnight culture was applied to agar plates. These plates were incubated at 37°C for 18 h. For streptococci, Haemophilus influenzae, and Neisseria species, incubation was carried out in an atmosphere of 5% C02, and.for anaerobic bacteria, incubation was carried out at 37°C for 24 h by the GasPak method (BBL). The MIC was the lowest antibiotic concentration that inhibited macroscopic colonial growth during this incubation. Broth dilution MICs were determined with overnight broth cultures of the test strains in Mueller-Hinton broth (Difco). The cultures were diluted in this broth to give an inocu...