M. Husson

Serum bactericidal activity of aztreonam, cefoperazone, and amikacin, alone or in combination, against Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa.

Serum samples from volunteers receiving (per kilogram) 20 mg of aztreonam, 20 mg of cefoperazone, 7.5 mg of amikacin, 20 mg of cefoperazone plus 20 mg of aztreonam, or 20 mg of aztreonam plus 7.5 mg of amikacin were evaluated for bactericidal activity against Escherichia coli, Klebsiella pneumonia, Serratia marcescens, and Pseudomonas aeruginosa. Serum bactericidal activities were similar for aztreonam alone or in combination but were lower for amikacin and cefoperazone alone, especially against S. marcescens and P. aeruginosa. Killing studies, performed with serum samples diluted 1:8, demonstrated a high killing rate for aztreonam plus amikacin, especially against P. aeruginosa.

Bactericidal activity of the combinations of gentamicin with clindamycin or chloramphenicol against species of Escherichia coli and Bacteroides fragilis

The bactericidal activity of clindamycin, chloramphenicol, and gentamicin alone and of gentamicin plus clindamycin and gentamicin plus chloramphenicol was studied on 8 strains of Escherichia coli and 10 strains of Bacteroides fragilis isolated from clinical material. Gentamicin did not interfere with the activity of clindamycin or chloramphenicol against B. fragilis. The activity of gentamicin against E. coli was not influenced by clindamycin, but chloramphenicol suppressed the rapid bactericidal activity of gentamicin in seven out of eight strains of E. coli examined.

Anaerobic Wound Infections in Cancer Patients: Comparative Trial of Clindamycin, Tinidazole, and Doxycycline

Clindamycin, tinidazole (a parent compound to metronidazole), and doxycycline were compared in vitro against 376 anaerobic bacteria isolated from clinical specimens. Bacteriostatic tests indicated that clindamycin was the most active drug, on a weight basis, against these strains except for Clostridium species. The three drugs were compared as therapies for anaerobic wound infections in cancer patients. In a randomized double-blind study, no statistically significant differences between clindamycin and tinidazole could be documented. Doxycycline was less active presumably because of the lack of clinical response in three out of four patients infected with doxycycline-resistant strains. No major untoward effects were observed. The bactericidal dilution of the serum was predictive of the clinical outcome.

Bactericidal activity and killing rate of serum from volunteers receiving pefloxacin alone or in combination with amikacin.

Serum bactericidal activities (SBAs) were studied after intravenous administration of pefloxacin (8 mg/kg) and amikacin (7.5 mg/kg) alone or in combination to 15 human volunteers. About 10 strains each of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus were tested. The serum levels of pefloxacin were measured microbiologically by using E. coli KP 1976-712 as the test organism at 0, 30, 60, 120, and 720 min after infusion; at 0, 30, 60, and 720 min these levels were 7 +/- 1.4, 5 +/- 0.8, 4.5 +/- 0.7, and 2.1 +/- 0.6 mg/liter (mean +/- standard deviation), respectively, with a terminal half-life of 10 h. The serum levels of pefloxacin in the presence of amikacin were measured similarly; 1% sodium polyanethol sulfonate was added to the agar to inactivate amikacin. Treatment with pefloxacin alone resulted in high SBAs against E. coli, K. pneumoniae strains susceptible to cephalothin, and Staphylococcus aureus at the peak concentration; 81 to 100% of the sera had SBAs of greater than or equal to 1:8. However, treatment with pefloxacin alone resulted in low SBAs against K. pneumoniae strains resistant to cephalothin and P. aeruginosa; only 34% of the sera had SBAs of greater than or equal to 1:8. At trough concentrations the percentages of sera with SBAs greater than or equal to 1:8 were 75 to 83% (E. coli), 9 to 27% (K. pneumoniae), 0% (P. aeruginosa), and 10% (S. aureus). The combination of pefloxacin plus amikacin was most often additive; the peak activity was due to amikacin, and the trough activity was due to pefloxacin. Occasionally antagonism occurred with P. aeruginosa, K. pneumoniae, and S. aureus strains. These observations were confirmed by the killing curves in pooled serum obtained at peak and trough levels. Regrowth was observed for seven strains of P. aeruginosa treated with pefloxacin alone; amikacin seemed to prevent this phenomenon.

Ex vivo pharmacodynamic study of piperacillin alone and in combination with tazobactam, compared with ticarcillin plus clavulanic acid.

Ten volunteers received piperacillin (4 g), piperacillin (4 g) plus tazobactam (0.5 g) (Tazocin), and ticarcillin (3 g) plus clavulanic acid (0.2 g) (Timentin) intravenously over 30 min in a cross-over blinded scheme. Blood samples were obtained 0.5 and 3 h after the end of infusion to measure by (high-pressure liquid chromatography) the concentration and bactericidal titers against 70 gram-negative bacilli. Serum time-kill curves were done against 35 strains to measure killing rates and area under the time-kill curve. Using the measure of serum bactericidal activity, ticarcillin-clavulanic acid and piperacillin-tazobactam were equally effective against Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, Serratia marcescens, and Bacteroides fragilis. Piperacillin-tazobactam was superior to ticarcillin-clavulanic acid against piperacillin-resistant Klebsiella pneumoniae (4 to 16 times) and S. marcescens (2 to 4 times). By using the area under the time-kill curve, piperacillin-tazobactam was equivalent to ticarcillin-clavulanic acid against piperacillin-susceptible strains; piperacillin-tazobactam was significantly more active than piperacillin against piperacillin-resistant strains and was more active than ticarcillin-clavulanic acid when the sample obtained 3 h after the end of infusion to volunteers was considered. Serum piperacillin concentrations (mean +/- standard error of the mean; in mg/liter) were 115 +/- 13 at 0.5 h and 7.4 +/- 1.4 at 3 h after the administration of piperacillin alone and 105.5 +/- 12.6 (0.5 h) and 7.7 +/- 1.6 after the administration of piperacillin-tazobactam. Serum tazobactam concentrations (in milligram per liter) were 13.1 +/- 1.4 at 0.5 h and 1.2 +/- 0.2 at 3 h. The piperacillin-tazobactam ratio was 8 +/- 0.3 at 0.5 h and 6.2 +/- 0.5 at 3 h. Piperacillin-tazobactam appears promising against beta-lactamase-producing gram-negative bacilli.

Serum bactericidal activity and killing rate for volunteers receiving imipenem, imipenem plus amikacin, and ceftazidime plus amikacin against Pseudomonas aeruginosa.

Serum bactericidal activity against 20 strains of Pseudomonas aeruginosa was studied in 10 volunteers after administration of imipenem (25 mg/kg), imipenem (25 mg/kg) plus amikacin (7.5 mg/kg), and ceftazidime (25 mg/kg) plus amikacin (7.5 mg/kg). Eight strains were susceptible and 12 were resistant to ticarcillin. Serum levels were measured microbiologically after 30 and 60 min and were, respectively, 97 and 46 micrograms/ml for imipenem given alone and 79 and 45 micrograms/ml for imipenem given with amikacin. Despite the very large dose of imipenem used, imipenem and imipenem plus amikacin appeared slightly less active than ceftazidime plus amikacin (P less than or equal to 0.1; Wilcoxon matched-pairs test), with respective median titers at 30 min of 1:128, 1:128, and 1:256 against ticarcillin-susceptible strains and 1:32, 1:32, and 1:64 against ticarcillin-resistant strains; however, more than 90% of the serum determinations, regardless of the regimen, had a serum bactericidal activity greater than or equal to 1:8. Amikacin significantly increased the rate of killing in serum of P. aeruginosa by imipenem. Imipenem plus amikacin appeared as effective as ceftazidime plus amikacin in reducing the viable counts of P. aeruginosa after 24 h of incubation.

Inaugural bilateral aspergillus endophthalmitis in a seriously immunocompromised patient

A. Georgala, B. Layeux, J. Kwan, I. Ahmad, J. Libert, F. Willermain, P. Koch, C. Heymans, M. Husson and M. Aoun Department of Internal Medicine – CHU Brugmann, Bruxelles, Belgium, Department of Clinical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Belgium, Department of Haematology, Institut Jules Bordet, Université Libre de Bruxelles, Belgium, Microbiology Laboratory ⁄ Section of Mycology, Institut Jules Bordet, Université Libre de Bruxelles, Belgium, Department of Ophthalmology, CHU-St Pierre, Bruxelles, Belgium and Department of Infectious Diseases, Institut Jules Bordet, Université Libre de Bruxelles, Belgium

Interaction Between the DNA-Gyrase Inhibitor Coumermycin and the Membrane of Human Neutrophils

We have previously shown that coumermycin, a DNA-gyrase inhibitor, was a potent inhibitor of superoxide generation stimulated by PMA (PMA = phorbol-12-myristate-13-acetate), Chemotaxis induced by fMLP (FMLP = n-formyl-methionyl-leucyl-phenylalanine), or opsonized zymosan, phagocytosis, and other membrane-related functions of human polymorphonuclear leukocytes (PMNs) [1–4]. In order better to characterize the interaction between coumermycin and the membrane of PMNs, we studied the inhibition of adenyl cyclase activity. In addition, the conformational analysis of the interaction was studied by computer model.

Influence of RO 236240 on Human Polymorphonuclear Leukocytes In Vitro

RO 236240 is a new trifluoroquinolone with very high in vitro activity against gram-negative and gram-positive bacteria particularly against methicillin-resistant Staphylococcus aureus. Since staphylococci may behave like intracellular pathogens [1, 2], we have studied the influence of RO 236240 on the functions of polymorphonuclear leukocytes (PMNLs) with a special interest for the intracellular killing.

Antibiotics and Phagocytic Cell Function: A Critical Review

Interest in the interaction between antibiotics and professional phagocytes has focused on several aspects [1, 2]: intracellular penetration and bioactivity, direct enhancing or depressing effects (toxicological approach), or indirect functional effects through specific action of the antimicrobial on the pathogen (enhancement below the minimum inhibitory concentration, MIC, or post antibiotic leukocyte enhancement).