[Sensitivity of bacteria to therapeutic drugs (Zurich 1996)]. / Die Empfindlichkeit von Bakterien gegen Chemotherapeutika (Zürich, 1996).

This paper describes the frequency of susceptibility of Gram-negative and Gram-positive bacteria against antibacterial agents. The data are based on all susceptibility tests performed in 1996 at the Department of Medical Microbiology of the University of Zurich and at the private medical laboratory "medica" in Zurich. The evaluation of the results from 1975 to 1996 shows that susceptibilities against the antimicrobial agents tested have not changed markedly in this period with few exceptions. The tables may be a help for the physician in his decision for a "calculated chemotherapy" of bacterial infections.

In vitro activity of cefpodoxime in comparison with other oral beta-lactam antibiotics.

The aim of our study was to re-evaluate the in vitro activity of cefpodoxime in comparison with other oral beta-lactam antibiotics against bacteria causing respiratory tract infections. The study drugs were cefpodoxime, cefaclor, cefixime, cefuroxime, cefetamet, cefprozil, and the combination of amoxicillin and clavulanic acid (= augmentin). In addition, cefotaxime as the standard agent of parenteral third generation cephalosporins was examined. The organisms tested were Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, streptococci of serogroups C and G, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae and Proteus mirabilis. Minimal inhibitory concentrations of the antimicrobials were determined with the agar dilution procedure. Cefpodoxime showed the broadest spectrum and generally also the highest activity of the oral beta-lactam antibiotics examined. The drug was equally active against the major groups of beta-lactamase negative and positive bacteria causing respiratory tract infections. Against penicillin-resistant pneumococci, all beta-lactam agents exhibited reduced activity comparable to the reduced activity of penicillin.

Prevalence of fluoroquinolone resistance in Europe. Study Group 'Bacterial Resistance' of the Paul-Ehrlich-Society for Chemotherapy e. V.

Since 1984, when the first fluoroquinolone, norfloxacin, was marketed in Europe, there has been a marked increase in the usage of this class of drugs. In order to evaluate the influence of this drug usage on the prevalence of resistance to fluoroquinolones in clinical isolates of the family Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus, coagulase-negative staphylococci and Enterococcus faecalis we reviewed the susceptibility data from four collaborative surveys conducted between 1983 and 1990 by the Study Group 'Bacterial Resistance' of the Paul-Ehrlich-Society for Chemotherapy. All participating laboratories used the same standardized methods. Minimal inhibitory concentrations were determined by the broth microdilution method. More than 20,000 bacterial strains were tested. The results are presented for ciprofloxacin, which is regarded as the representative of the fluoroquinolones. Using > or = 4 mg/l as a breakpoint for resistance to ciprofloxacin, the prevalence of resistant strains of the family Enterobacteriaceae in Central Europe between 1983 and 1990 remained below 1%. In contrast, the resistance rates in P. aeruginosa were 0.7%, 1.0%, 3.8% and 7.0%, in S. aureus 0%, 0.5%, 6.6% and 6.8%, and in E. faecalis 2.2%, 0.7%, 4.9% and 7.7% in 1983, 1986, 1989 and 1990, respectively. The latest study carried out in cooperation with 78 laboratories from 12 European countries revealed great differences in the prevalence of resistance to fluoroquinolones from one species to another ranging from 0% with Proteus vulgaris and Salmonella spp. to 26.7% with Providencia stuartii.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of imipenem resistance acquired by three Pseudomonas aeruginosa strains during imipenem therapy.

Imipenem sensitive pretherapy isolates (MICs 1-2 mg/l) and the corresponding resistant posttherapy isolates (MICs 16 mg/l) of Pseudomonas aeruginosa from three patients undergoing imipenem treatment were analyzed to establish the resistance mechanism. The identity of pyocin types, serotypes, DNA restriction endonuclease profiles and plasmid profiles strongly suggested isogenicity of pre- and posttherapy isolates. The imipenem resistant posttherapy isolates showed cross-resistance only to another carbapenem, meropenem. There were neither qualitative nor quantitative differences between pre- and posttherapy isolates in beta-lactamase production. Affinity of the penicillin-binding proteins 1A, 1B, 2, 3, 4,4' and 5 for [14C]imipenem was the same in pre- and posttherapy isolates. One-dimensional and two-dimensional gel electrophoresis of outer membrane protein preparations showed diminished expression of an outer membrane protein of about 46.5 and 47.5 kilodaltons, respectively, in the posttherapy isolates. This protein had an apparent isoelectric point of about pH 5.2 in two-dimensional gel electrophoresis. Growth in proteose peptone no. 2 broth did not reduce expression of this outer membrane protein, which spoke against its identity with the outer membrane protein D1. The permeability of the outer membrane for imipenem was reduced in the posttherapy isolates, since addition of 0.5 or 0.25 of the MIC of the permeabilizing agent ethylene-diaminetetraacetate reduced the MICs of imipenem for all isolates from each patient to the same (susceptible) level. The diminished expression of one of the outer membrane proteins might be the reason for this reduced permeability.

[Antibiotic resistance and serotypes of Streptococcus pneumoniae in Zurich (1984-1985)]. / Antimikrobielle Resistenz und Serotypen von Streptococcus pneumoniae in Zürich (1984/1985).

We have investigated the serotypes and sensitivity of 133 pneumococci against 11 antimicrobial agents in the agar dilution test. The strains had been isolated from clinical specimens sent to the Department of Medical Microbiology of the University of Zurich during 1984 and 1985. - Three strains (2.3%) had reduced sensitivity to penicillin G. 23 strains (17.3%) showed resistance or reduced susceptibility to tetracycline, one strain each (0.8%) to amoxycillin and cefaclor, and two strains each (1.5%) to erythromycin and sulfamethoxazole/trimethoprim. All pneumococcal strains investigated were susceptible to ceftazidime, ceftriaxone, chloramphenicol, vancomycin and ciprofloxacin. In view of this situation, routine testing of all clinically significant pneumococci is to be recommended. However, in the agar diffusion test the use of a penicillin G disk is unreliable and may give results with false sensitivity. Therefore, the susceptibility test should be performed with a disk containing oxacillin. - The prevalent capsular serotypes were - in descending order - types 3, 6, 23, 19, 14, 7, 8, 9, 1, and 17. 90.2% of the isolated pneumococci belonged to serotypes which are contained in the new vaccine "Pneumovax-23".

Antimicrobial activity of econazole and miconazole in vitro and in experimental candidiasis and aspergillosis.

The antibacterial and antimycotic activity of econazole base, an imidazole derivative, was examined in vitro and in experimental infections of mice. Comparative minimal inhibitory concentration (MIC) determinations indicate econazole as well as miconazole to be of moderate activity against gram-positive bacteria (MICs: 0.78-25mug/ml) and yeasts (MICs: 1.56-25 mug/ml). Against filamentous fungi, econazole exhibits better in vitro activity than miconazole and - with the exception of Rhizopus oryzae and Absidia corymbifera - MICs are markedly lower than against yeasts. No effect of nutrient media and no effect of the inoculum were observed with the four drugs. A strong influence of bovine serum on MIC values, however, suggested a strong protein binding. In experimental candidiasis of mice, no therapeutic effect with econazole base administered orally or intraperitoneally could be observed (ED50 and 'minimum life-prolonging dose': great than 200 mg/kg). In experimental aspergillosis of mice, a slight effect, as demonstrated by the 'minimum life-prolonging dose' of 100 mg/kg, was found. The in vitro and in vivo results are discussed in the light of the available pharmacokinetic and toxicological data. It is concluded that more studies, especially on the pharmacology of econazole and about the clinical efficacy, are needed to come to a definite judgement.