[Antimicrobial sensitivity of coagulase-positive staphylococcal strains isolated from bovine mastitis in the central dairy catchment area of Argentina ]. / Susceptibilidad a antimicrobianos de cepas de estafilococos coagulasa positivos aisladas de mastitis bovina en la cuenca lechera central de la Argentina.

The activity of antimicrobial agents frequently used for treating bovine mastitis was determined against 101 coagulase-positive staphylococci isolated from bovine mammary secretion. The isolates were obtained from 39 dairy farms located in the central dairy area of Argentina. The disk diffusion method was used and the following antimicrobial agents were tested: penicillin, ampicillin, oxacillin, cephacetrile, penicillin + novobiocin, erythromycin, pirlimycin, novobiocin and neomycin. The highest levels of resistance were observed against penicillin and ampicillin (47.6%), while the lowest against erythromycin (2%), pirlimycin (4%) and neomycin (2.9%). No resistant strains against oxacillin, cephacetrile and penicillin + novobiocin were detected.

Susceptibilidad a antimicrobianos de cepas de estafilococos coagulasa positivos aisladas de mastitis bovina en la cuenca lechera central de la Argentina / Antimicrobial sensitivity of coagulase-positive staphylococcal strains isolated from bovine mastitis in the central dairy catchment area of Argentina

The activity of antimicrobial agents frequently used for treating bovine mastitis was determined against 101 coagulase-positive staphylococci isolated from bovine mammary secretion. The isolates were obtained from 39 dairy farms located in the central dairy area of Argentina. The disk diffusion method was used and the following antimicrobial agents were tested: penicillin, ampicillin, oxacillin, cephacetrile, penicillin + novobiocin, erythromycin, pirlimycin, novobiocin and neomycin. The highest levels of resistance were observed against penicillin and ampicillin (47.6), while the lowest against erythromycin (2), pirlimycin (4) and neomycin (2.9). No resistant strains against oxacillin, cephacetrile and penicillin + novobiocin were detected.(AU)

Effects of cephacetrile on reproduction cycle.

The research of possible effects of cephacetrile (Celospor) on the reproductive function was carried out on two animal species, rats and rabbits. The animals were divided into experimental groups, each treated subcutaneously with different amounts of cephacetrile (50, 100 and 500 mg/kg/die), control group receiving physiological solution. Effects of the preparation on fertility and post-natal growth in rats were analyzed, and trials were performed to test perinatal toxicity and teratogenesis in rabbits. From the observation of the experimental data collected it can be assumed that cephacetrile, administered subcutaneously in the given doses--1, 2 and 10 times, respectively, higher than the maximum therapeutic dose advisable--does not alter fertility, gestation and post-natal development of term foetuses of rats and fertility and gestation of rabbits.

Bactericidal activity and induction of cell volume alterations of cephalosporins in Escherichia coli.

The bactericidal efficacy of cefuroxime and cephacetril on Escherichia coli cultures was measured by killing curves. Simultaneously bacterial cell volumes were analysed by electronic particle counting using a Coulter Counter Channelanalyser system in order to study the relationship between bactericidal activity and bacterial cell volume alterations. Various concentrations (2-120 mg/l cefuroxime and 16-120 mg/l cephacetril) and different exposure times (over a time period of 12 h) were used. Growth medium was human plasma ultrafiltrate. The bactericidal activity of cefuroxime, as measured by the rate of killing of the E. coli culture, was independent of the concentration and constant in the range 4-120 mg/l. The characteristic cefuroxime-induced change in bacterial cell volume was a marked volume increase up to a maximum of 5-fold after 160-200 min exposure with a low-grade bacteriolysis following. The cefuroxime-induced bacterial volume changes were, in accordance with the bactericidal testing, almost independent of the concentration. In contrast, the killing curves for cephacetril strongly depended on the drug concentration. However, this effect was short-lived and regrowth of the E. coli culture followed. The typical cephacetril-induced volume distribution curves were also highly concentration-dependent. With increasing drug levels bacterial cell volume increased up to 20-fold, and regrowth of a persisting bacterial population occurred at lower antibiotic concentrations. Bacteriolysis started earlier than with cefuroxime. The relationship between loss of viability and cell volume increase was more marked with cefuroxime than with cephacetril.

In vitro evaluation of pyridine-2-azo-p-dimethylaniline cephalosporin, a new diagnostic chromogenic reagent, and comparison with nitrocefin, cephacetrile, and other beta-lactam compounds.

Pyridine-2-azo-p-dimethylanaline cephalosporin (PADAC), a chromogenic reagent which is purple and changes to yellow upon cleavage of its beta-lactam ring, was evaluated in comparison with other chromogenic cephalosporins. PADAC exhibited little antimicrobial activity against gram-negative bacteria, but did have good activity (minimum inhibitory concentration, 0.12 to 0.5 microgram/ml) against Staphylococcus aureus, a quality comparable to nitrocefin. Nitrocefin, however, demonstrated an unexpected and uniquely potent activity against Streptococcus faecalis (minimum inhibitory concentration, less than or equal to 0.06 to 0.12 microgram/ml) The relative hydrolysis rate of PADAC when subjected to six different beta-lactamases was substantially greater than that of cephacetrile, but less than that of nitrocefin. The relative hydrolysis rates of PADAC and nitrocefin were comparable with type IIIa beta lactamase and the derived from Bacillus cereus. The inhibition of beta-lactamase hydrolysis of the chromogenic cephalosporin substrates by six enzyme-stable inhibitors was generally greater with PADAC than with nitrocefin. Unlike nitrocefin, PADAC mixed with 50% human serum or various broth culture media showed no evidence of color change or degradation over several hours. The subsequent enzyme hydrolysis rates of such mixtures were the same as in phosphate buffer. Beta-lactamase-containing bacterial suspensions and clinical specimens containing such bacteria produced positive visual and spectrophotometric color changes when mixed with PADAC or nitrocefin. Although color changes occurred more slowly with PADAC than with nitrocefin, PADAC was not adversely influenced (non-enzyme-related color change) by the protein content of specimens. PADAC appears to be a promising alternative for beta-lactamase diagnostic testing in the clinical and research microbiology laboratory.

[Microbiological evaluation of the antibacterial activity of cefotaxime in comparison with other cephalosporins]. / Valutazione microbiologica dell'attività antibatterica del cefotaxime in rapporto ad altre cefalosporine.

In this study we have evaluated the antibacterial activity of six cephalosporins of the first generation (cephacetrile, cephalothin, cefazolin, cephaloridin, cephalexin, cephradine) two cephalosporin of the second generation (cefoxitin and cefuroxime) and two of the third generation (cefotaxime and cefoperazone) against 66 clinical bacterial isolates. Cefotaxime has been highly active against the strains examined in this study with low MICs.

The cephalosporins: activity and clinical use.

The cephalosporin antibiotics have been employed with increasing frequency since their introduction into clinical practice in the early 1960s. With the exception of cephaloridine, cephalosporin compounds are not associated with the production of significant untoward effects. The availability of newer cephalosporins, both oral and parenteral, with enhanced antibacterial activity, has expanded the clinical indications for administration of these antibiotics.

A comparison of the activity in vitro of different cephalosporins: cephalothin, cephradine, cephacetrile, cefaclor, cefuroxime and cefotaxime.

6-cephalosporins (cephalothin, cephradine, cephacetrile, cefaclor, cefuroxime, cefotaxime) has been tested in vitro against 212 gram negative bacteria and 60 Staphylococci. Cefuroxime and especially Cefotaxime showed the highest activity against the gram negative bacteria, with a very low MIC. Cefotaxime also acted fairly well against several strains of Pseudomonas. Of the six cephalosporins tested, cephalothin gave the best results against the Staphylococci.

[Correlation between antibacterial activity of some cephalosporins and pharmacokinetic properties "in vitro" (author's transl)]. / Correlazioni tra attività antibatterica di alcune cefalosporine e proprietà farmacocinetiche simulate "in vitro".

A new apparatus is described which can be used to investigate the in vitro antibacterial activity of antibiotics as a function of different concentration-time curves. The apparatus can be adjusted to simulate the biexponential serum level curves observed in vivo after oral or intramuscular administration. Preliminary studies were carried out with cefazolin against an E. coli strain simulating initial concentrations of 5, 10 and 20 micrograms/ml that decreased exponentially with half-lives of 30, 60 and 120 min. In all the situations tested there was an initial phase of rapid bactericidal activity followed by a phase of bacteriostatic activity, whose length depended on the drug elimination rate but was relactively independent of the initial concentrations. Bacterial regrowth occurred when the antibiotic concentration fell below the minimum inhibitory concentration (MIC) of the drug. The antibacterial activity of cefazolin, cephacetrile, and cephradine against an E. coli strains was also investigated, in a medium containing 4% human albumin, simulating the serum level curves observed in humans after an intramuscular dose of 1 g. The results obtained confirm that, for cephalosporins, the dosage schedule should be adjusted taking into account the potency of the drug (MIC) and its rate of elimination.

The assessment of interaction between drugs by the Autobac 1 system.

A study has been undertaken on the applicability of the Autobac 1 system to the checker board method to determine the interaction of combined drugs on bacterial populations. Preliminary results are reported which show that the Autobac makes easier, accurate, flexible and rapid such a method. In order to improve the significance and facilitate technical operations and data processing of this test additional equipment and device are suggested.

[Comparative study of 7 cephalosporins on "Staphylococcus aureus" by the method of population analysis (author's transl)]. / Etude comparée de l'action de 7 céphalosporines sur Staphylococcus aureus par la méthode d'analyse de population.

Miscellaneous Staphylococcus aureus populations were tested with seven commercialized cephalosporins. The strains were divided in five groups according to the following criteria: penicillinase production or not: sensitivity to methicillin and cephalosporins; RB type resistance to methicillin; RH and RO type resistance to every beta-lactamine (according to Chabbert and Baudens). For each cephalosporin studied, the population cell analysis performed with these different groups showed the constant heterogeneous arrangement of the individual MIC. However, whatever the staphylococcus group, cephaloridine remains the antibiotic that inhibits the largest number of cells at lower concentration than other cephalosporins. In vitro results were compared with pharmacokinetic data of the different cephalosporins.

[The growth curves of enterobacteriaceae and the estimation of L-forms under the influence of cephalosporin antibiotics].

The antibacterial effectiveness of cephalothin, cefazolin, cephacetrile and cephradine was investigated on growing cultures of Klebsiella pneumoniae recording the growth curves with a biophotometer. Thereby cefazolin has a greater antibacterial activity than the other cephalosporins. By raising the dose to 100 microgram/ml after initial bactericidal effect a second growth phase was observed. Phase microscopic observation showed that this was caused by an increasing number of L-forms. This phenomenon could be observed with two other strains and seems to be a strain-specific characteristic. It occurs only using cephalosporins and isotonic nutrient media. The medical importance of the described ability of some bacteria as a factor of pathogenicity is discussed.

[An investigation into the influence of human serum on the in-vitro activity of various cephalosporins (author's transl)]. / Untersuchung über den Einfluss von Humanserum auf die In-vitro-Aktivität verschiedener Cephalosporine.

Cephalosporins are being given more and more frequently empirically as initial therapy, until the bacteriological findings become available. The wide selection of cephalosporins available make the choice of the most suitable one difficult for the clinician. Cephazolin, cephradine and cephacetrile were tested against three standard bacteria strains (Escherichia coli, Staphylococcus aureus, Kelebsiella pneumoniae) in normal broth and with the addition of 30% inactivated human serum; the geometric mean of the minimum inhibitory concentration (MIC) was determined by serial dilution, and the minimum bactericidal concentration (MBC) by inoculation onto solid medium. On the addition of 30% serum, cephazolin showed a reduction in effectivity of up to 360% for the MIC and up to 74% for the MBC, cephacetril up to 250% for the MIC and 100% for the MBC, and cephradin a maximum loss of 16%. Successful treatment of a severe infection requires a high drug level or a corresponding tissue titer. Due to the high tissue concentration of cephradin and the unrivalled stable antibacterial effectivity in serum, this antibiotic can be recommended for clinical use.

[Comparative activity of 6 cephalosporin antibiotics against the causative agents of surgical infection]. / Sravnitel'naia aktivnost' 6 tsefalosporinovykh antibiotikov v otnoshenii vozbuditelei khirurgicheskoi infektsii

Activity of 6 cephalosporanic antibiotics, such as cephaloridin, cephalotin, cephradin, cephacetry1, cephamezin and cephalexin was studied on 200 strains of microorganisms causing purulent infections in surgical patients (Staphylococcus, E. coli, Proteus and Ps. aerugionsa, 50 strains of each organism). The studies showed significant differences in the activity of the above antibiotics against definite species of the pathogenes. The highest activity of the cephalosporins was observed with respect to the clinical strains of staphylococci resistant to such drugs as benzylpenicillin, tetracycline, erythromycin, kanamycin, lincomycin. A significant part of the clinical isolates of gramnegative organisms, i.e. E coli and indol-negative Proteus was characterized by sensitivity to cephalosporins. Among the cephalosporins tested cephaloridin was most active against Staphylococcus, cephacetryl and cephaloridin were most active against E. coli. With respect to the indol-negative Proteus no pronounced advantages of the separate drug were noted. All 6 cephalosporins had low activity against the indol-positive strains of Proteus and all strains of Ps. aeruginosa.

[Fundamental studies on combination of antibiotics; especially on pharmacokinetics. I. Combination of gentamicin with sulbenicillin or cephacetrile (author's transl)].

1. When gentamicin (GM) and sulbenicillin (SBPC) or cephacetrile (CEC), in combination with pre- or post-treatment, were injected intravenously to the rat, their pharmacokinetics were investigated. 2. The antibiotics in the samples were separated by paper electrophoretic technique and their concentrations were determined by cup thin layer plate method using Bacillus subtilis as the test organism. 3. The biological half-life of SBPC in the serum was shortened in pretreatment with GM and prolonged in posttreatment with GM, while that of GM did not vary in pre- or post-treatment with SBPC. 4. The half-life of CEC was prolonged in treatment with GM, while that of GM did not vary. 5. These phenomena may be considered to be produced as the results of a concentration ratio of SBPC and GM or of CEC and GM, and protein binding of these antibiotics, as far as plasma initial levels, tissue distribution, urinary excretion and protein binding of these antibiotics are concerned.

[The cephalosporins and their clinical value]. / Die cephalosporine und ihre Bedeutung für die Klinik

Up to now cephalothin was the only parenteral and cephalexin the only oral cephalosporin for clinical use in the GDR. The paper deals with several newer cephalosporins. Of these cephazolin shows some advantages, especially in antibacterial activity and serum levels. There is no metabolization and a better local tolerability compared with cephalothin. Cephapirin has no and cephacetril only inessential advantages. The antibacterial activity of the also well tolerated cephradin is less than that of cephalothin. Certain favourable pharmacokinetic properties such as high lymph and tissue levels, related to serum levels, slight protein binding, high distribution volume and a better stability against beta-lactamases lead to a superiority over cephalothin and diminish the disadvantages compared with cephazolin. The oral form of cephradin very equals to cephalexin.

The in vitro spectrum of the cephalosporins.

The cephalosporins may currently be classified according to their relative susceptibility to beta-lactamases. Cefoxitin, cefamandole, cefatrizine, and cephanone are relatively resistant to the gram-negative beta-lactamases, whereas cephalothin, cefamandole, and cefoxitin are resistant to staphylococcal beta-lactamase. Although the inhibitory activity of cephalothin is representative of that of cephaloridine, cephalexin, cefazolin, cephapirin, cephacetrile, and cephradine, there are significant differences between its activity and that of cefoxitin, cefamandole, and cefatrizine, especially against Enterobacter, Serratia, indole-positive Proteeae, Bacteroides fragilis, and ampicillin-resistant Haemophilus influenzae.