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Biomedical subjects

J Sirot

Publications and source records attributed to J Sirot.

At least 109 records · Page 6Linked to original sources

[In vitro activity of combinations of cefotaxime and moxalactam with aminoglycosides on beta-lactamase-producing Enterobacteriaceae].

The in vitro synergistic activities of cefotaxime (Ctx) or moxalactam (Mox) in combination with gentamicin, amikacin, dibekacin or netilmicin were compared against 15 beta-lactamases non-producing or producing isolates of Enterobacteriaceae. The strains were classified according to their resistance to ampicillin (Am), carbenicillin (Cb) and cephalotin (Ce), but all were sensitive to the antibiotics tested in combination. In vitro checkerboard studies were performed using a microtiter technique for the selected strains. The FIC index was less than or equal to 0.62 for AmR CbR CeR strains (E. coli, E. cloacae, Serratia), for AmR CbS CeR strains (E. cloacae, Serratia, P. vulgaris) and for AmS CbS CeR strains (Serratia, P. morganii). These combinations were frequently additive (FIC = 0.75 - 1.0) against the AmS CbS CeS or AmR CbR CeS strains. Thus, the synergistic activities of Ctx and Mox in combination with an aminoglycoside seem to be correlated with beta-lactamase type produced by the Enterobacteriaceae.

Aminoglycosides↗

[In vitro study of the bacteriostatic and bactericidal activity of temocillin (BRL 17421)].

Temocillin is a carboxypenicillin; a methoxy group in the 6-alpha position should confer to the molecule greater stability to beta-lactamases. 236 strains isolated from clinical specimens were tested. MICs were determined by agar dilution method. Enterobacteriaceae were very susceptible, MICs being generally less than or equal to 8 micrograms/ml and always less than 32 micrograms/ml. The activity of the drug was equal against the beta-lactamases producing strains. On the other hand temocillin was not active against aerobes (Pseudomonas aeruginosa and 90% of Acinetobacter), and against Gram positive bacteria. The bactericidal effect was strong: (formula; see text) A regression-line was proposed for Enterobacteriaceae and "break-points" were discussed.

Bacteria↗

[Effect of trimethoprim at a subinhibitory concentration on the appearance of mutants resistant to rifampicin].

Experiments have been performed to establish the effect of trimethoprim (Tmp) on the emergence of Staphylococcus aureus (S. aureus) mutants to rifampicin (Ramp). Four S. aureus strains were used: two strains with low MIC of Ramp (0,01 microgram/ml), two strains with enhanced MIC of Ramp (2 micrograms/ml). For each of them the frequency of mutants and the mutation rates to Ramp were determined when various concentrations of Tmp were added. Results showed that subinhibitory concentrations of Tmp reduced 10 to 100 folds the frequency of mutants and the rates of mutation to Ramp alone. The more the Tmp concentrations were near the MIC, the more this effect was important.

Drug Resistance, Microbial↗

[Diffusion of fosfomycin into bone tissue in man].

Fosfomycine diffusion into spongious and cortical bone was studied in 20 patients undergoing total replacement of the hip after an intravenous infusion of 4 g (1 g/h). The serum and bone samples were collected 1 h and 3 h after administration of the drug. Concentrations at 1 h were 105.0 +/- 12.4 micrograms/ml, 19.6 +/- 4.8 micrograms/g and 13.3 +/- 3.7 micrograms/g in serum, spongious bone and cortical bone respectively; at 3 h these concentrations had become respectively 67.8 +/- 15.9 micrograms/ml, 10.0 +/- 4.2 micrograms/g and 8.2 +/- 3.6 micrograms/g. Antibiotic levels in bone tissue decreased in direct ratio to corresponding serum values, the mean tissue/serum ratio remaining at 15 +/- 4%.

Adult↗

[Diffusion of rifampicin into spongy and compact bone tissue during total hip prosthesis operation].

Sixty eight patients received either an oral single dose of 300 mg (or 300 mg/12 h), or an oral single dose of 600 mg (or 600 mg/24 h) of rifampicin. In every case samples of serum and bone were collected 3 h, 12 h, and 24 h after the last oral dose. Rifampicin levels measured at 3 h and 12 h in cortical bone samples increased significantly with the dose of the drug. The only dose which determines activity in cortical bone at the 3rd hour was the dose of 600 mg. When the dose was increased from 300 mg/12 h to 600 mg/24 h the ratio spongious bone/serum increased from 0.19 to 0.41 at 3d h and from 0.24 to 0.29 at the 12th hour; the ratio cortical bone serum was 0.20 at the 3rd hour after a dose of 600 mg. In any case tissue levels varied in a parallel direction to serum levels and were superior in spongious bone to the MIC of S. aureus sensitive strains until 12 h after the 600 mg dose. According to these results, it appears that the best dose for treating S. aureus bone infection seems to be 600 mg/12 h.

Bone and Bones↗

[Rifampicin in the treatment of Staphylococcus arthritis].

Rifampicin is used for treating 20 Staphylococcus septic arthritis, in combination with another antibiotic. The former is chosen for its striking bone diffusion. The average duration of the whole antibiotic treatment is 3 months. Rifampicin is usually prescribed, in daily doses of 1 200 mg for 60 days, after one month of parenteral antibiotherapy. The bactericidal activity is controlled regularly by measuring serum inhibitory titre. For 2 patients, the administration of rifampicin is suspended after 12 and 25 days respectively, due to digestive disorders. Results are evaluated at the end of a period averaging 18 months. Articular infection has been cured in all patients. Taking these results into account, we are able to emphasize that the inclusion of rifampicin in the antibiotic scheme is of great value in treating bone and articular infections.

Adult↗

[Comparative bactericidal activity of beta-lactam-aminoglycoside combinations against Pseudomonas aeruginosa].

The effects of combining each of 10 beta-lactamins (carbenicillin, ticarcillin, piperacillin, azlocillin, cefotaxime, moxalactam, ceftriaxone, cefoperazone, ceftazidime, cefsulodin) with 6 aminoglycosides were studied in vitro against two strains of Pseudomonas aeruginosa. The bactericidal activity was tested by two methods: solid medium technique of "cellophane transfer" and "checkerboard" method (broth-dilution micromethod partly automatic). No single antagonism was observed. Concerning new penicillins, the percentage of synergy is increasing from carbenicillin, to ticarcillin, to azlocillin and finally to piperacillin. For recent cephalosporins, the most synergistic combinations are obtained with ceftriaxone, cefoperazone and ceftazidime. If aminoglycosides associations are considered, there is a good activity whichever antibiotic chosen, with a higher level for streptomycin and lower one for tobramycin. Dibekacin combinations, also tested by the checkerboard method, are particularly synergistic with azlocillin and piperacillin for new penicillins, and equally well with ceftriaxone for recent cephalosporins.

Aminoglycosides↗

[Statistical regression analysis for four new cephalosporins (author's transl)].

The MIC (agar dilution method) and the zone diameter (disk diffusion) were determined for two hundred and sixteen of the most frequently bacterial strains found in hospitals in order to establish the regression curves for four new cephalosporins : cefotaxime, cefoperazone, cefotiam, moxalactam. The dta (MIC, zone size) were represented by a series of points (Mi (Xi Yi) in semilogarithmic rectangular co-ordinates expressed as : Xi = log2 MIC + 7 ; Yi = zone diameter. Firstly, we tried to fit a regression polynomial to this series of points progressing from degree 1, simple equation (standard regression line) 2, 3, etc. in order to reduce if need be, the deviation between the model (polynomial) and the empirical data. For these four cephalosporins a regression polynomial was obtained. Secondly, the global series was divided into three series of points Mi corresponding to three ranges of MIC : MIC less than or equal to 4 microgram/ml ; 4 less than or equal to 16 micrograms/ml; MIC greater than or equal to 16 microgram/ml. A regression line was obtained for each series and compared with each other and each one with the global regression line (they do not coincide statistically). Concerning these antibiotics, it is better to use a regression polynomial rather than apply a standard regression line.

Bacteria↗

[Penetration of cloxacillin into human bone tissue after oral administration (author's transl)].

Cloxacillin diffusion into spongious and cortical bone was studied in 20 patients undergoing total replacement of the hip, after an oral single-dose of 1 g (10 patients) or an oral dose of 1 g every 8 hours (10 patients). Serum and bone samples were collected 2 and 3 hours after the last dose and assayed for antibiotic concentration by a microbiological method. Bone levels were similar in any group of patients, but significantly higher in spongious bone than in cortical bone. The bone/serum concentration ratios were 0.15 for spongious bone and 0.10 for cortical bone. Calculations from these data showed that adequate local levels inhibitory to Staphylococcus aureus, would be achieved by cloxacillin administration of 1 g dose every 4 hours orally.

Administration, Oral↗

[Antibacterial activity of netilmicin in combination with other antibiotics. Comparison with other aminoglycosides (author's transl)].

We studied in vitro bactericidal effects of netilmicin combined with other antibiotics, comparing with that obtained with other aminoglycosides combinations. We used strains of Streptococci and Gram negative rods tested versus 11 antibiotics : penicillin (P), ampicillin (Am), carbenicillin (Cb), cefalotin (Cth), cefazolin (Cfz), cefradin (Cfa), cefoxitin (Cxt), cefotaxime (CTX), erythromycin (E), pristinamycin (Pr), vancomycin (V). These were combined with streptomycin (Sm), tobramycin (To), amikacin (Ak), gentamicin (G) and netilmicin (Nl). First of all, we noted the high bactericidal power of Nl, whatever the strains tested. Against Streptococci, the activity of P + Nl and Am + Nl were equivalent or superior to that of P + G and Am + G. Among cephalosporins, we noted a synergistic effect of Ctx + Nl which did not exist with Ctx + G. In the same way, E + Nl showed synergism whereas E + G didn't. V + Nl combinations, as active upon Streptococci as V + G, are more active than V + G upon Enterococci. Against Gram negative bacilli, we observed good effects with Cb + Nl. Cephalosporins combinations were also interesting : Cfz + Nl were as active Cfz + G but Czt + Nl showed higher synergistic effect than Cxt + G. Ctx + Nl combinations were effective upon E. coli.

Aminoglycosides↗

[Osteoarticular infections due to Gram-negative bacilli].

An enquiry carried out on 20 French rheumatology units led us to find, out of a total of 1,202 cases of non-tuberculous osteo-arthritis of the adult, 137 gram negative bacillary infections. These were 64 cases of spondylodiscitis and 73 cases of septic arthritis, due mainly to Escherichia Coli, Pseudomonas and other enterobacteria. The frequency of gram-negative bacilli was 11.4% i.e. 9.2% in the case of arthritis and 15.6% in the case of spondylodiscitis. It is higher than in the middle of this century but does not seem to be progressing now. However, the seventy of this type of infection, which may cause important functional sequelae and numerous deaths (8 patients) justifies the routine search for these bacilli in appropriate culture media, in order to test their sensitivity to antibiotics.

Adult↗

[Role of the bacteriology laboratory in the diagnosis and treatment of osteoarthritis].

The etiological diagnosis of bone and joint infections, the choice of antibiotics adapted to the responsible bacteria and the supervision of their efficacy depend mainly on the bacteriology laboratory. A routine search for the causal bacteria in various samples, e.g. synovial fluid, blood cultures, synovial biopsy, inter-vertebral disc puncture, permit etiological diagnosis in about 80% of cases. The choice of antibiotics, limited to those whose synovial and bony diffusion is known, depends on the results of in vitro studies of sensitivity of the isolated bacteria (CMI and CMB) and of the bactericidal power of the associations. The measurement of the inhibitory power or concentrations of antibiotic in synovial fluid and serum give an indication of the efficacy of the treatment.

Adult↗

[The bactericidal power of antibiotic combinations. Application in the treatment of osteo-articular infections due to Staphylococcus aureus (author's transl)].

Study of the bactericidal power of antibiotic combinations against 18 strains of staphylococcus aureus causing osteoarthritis showed that the combinations most often synergistic or indifferent were: rifampicin + lincomycin or synergistine, rifampicin + fusidic acid, synergistine + fusidic acid or trimethoprim-sulphamethoxazole, cephalosporins + gentamycin, rifampicin or fusidic acid + gentamycin, trimethoprim-sulphamethoxazole + rifampicin or fusidic acid. Study of the antibiotic therapy used here was based upon the inhibitory power of serum and the measurement of antibiotic concentrations in healthy bone. Combinations which are synergistic or indifferent in vitro endow the serum with a high level of bactericidal activity. Certain antagonisms (cephalosporins or penicillin M + rifampicin) found in vitro may be reflected neither clinically nor in study of the inhibitory power of the serum.

Adolescent↗

[Osteo-articular infections: choice and monitoring of antibiotic therapy. Apropos of 26 observations with an identified organism].

Study of 26 cases of osteo-articular infections with an identified organism collected in a rheumatology department, has confirmed in the first place the increasing importance of gram negative organisms, compared with the staphylococcus which has always mainly predominated in this type of infection. In each case, the authors have made as complete a bacteriological study as possible, including antibiotic sensitivities, the measurement of the minimum inhibitory concentration of the antibiotics on the isolated strains, study of the bactericidal power in vitro of various combinations, and study of the inhibitory power of the serum on the organism. This study of the inhibitory power of the serum approximates most closely to testing the antibiotic activities in vivo, since one cannot make this assessment, in most cases, within the infective focus itself. Rifampicin, with the imperative condition that it is not used alone, is a major antibiotic in the osteo-articular infections, by reason of its very great activity against the staphylococcus, its excelent penetration into bone, and its ease of use. Other recognized anti-staphylococcal antibiotics behave in a more disappointing fashion. When the effectiveness of treatment is checked regularly by the inhibitory power of the serum, together with the other classical criteria of surveillance, cure of the infection as been achieved in every case.

Adolescent↗

[Comparative study of 7 cephalosporins on "Staphylococcus aureus" by the method of population analysis (author's transl)].

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.

Cefazolin↗