Search

The in vitro activity of four new quinolones against 355 obligate anaerobes was investigated. MICs were determined using the reference method of Sutter et al. [14]. The four fluorinated quinolones tested differ from nalidixic acid which is inactive on most anaerobes except for some Clostridium perfringens strains. All strains tested were inhibited by 64 and 16 mg/l pefloxacin and ofloxacin respectively. Except for Bacteroides, all strains were inhibited by 64 mg/l norfloxacin or enoxacin. Clostridium strains other than C. perfringens exhibited heterogeneity; C. difficile and C. ramosum had the highest MICs. Bacteroides fragilis proved less susceptible to fluorinated quinolones than the other obligate anaerobes. Ofloxacin showed the greatest activity, with 4 mg/l inhibiting 100% of C. perfringens and 83% of all anaerobes investigated.

The dynamics of transition from wakefulness to drowsiness can be modified by psycho-active compounds. These two states of vigilance have different electroencephalographic characteristics, which can be also modified by the administration of substances. This paper describes a method intended to discriminate between these two aspects of drug action, using a mini-computer. Investigation of sleep-wakefulness cycles with continuous EEG and EMG recording necessitates an efficient method of data reduction. On-line computation of Hjorth parameters with a micro-computer, and further processing witha mini-computer has been used. A pharmacological approach to the study of sleep-wakefulness cycles is proposed; this avoids a strict distinction of sleep phases, and concentrates on the coninuum of vigilance states. Differents ways of showing drug-induced modifications on that continuum are presented with examples.

The structure-activity relationships of nine products of the acrylophenone family have been studied. In a previous report 2-(4-methyl-1-piperazinylmethyl)acrylophenone was shown to be an antimicrotubular drug. The effects of these drugs on the bovine brain tubulin polymerization were determined by a turbidimetric assay. The median inhibitory concentrations (ID50) ranged from 1.5 X 10(-5) to 5 X 10(-5) mol/l. Their action on the inhibition of 3H-colchicine binding to tubulin was determined by DEAE (diethylaminoethyl)cellulose filter assay. These compounds are weak inhibitors of colchicine binding. Pharmacological studies of these drugs revealed a strong inhibition of the human ADP-induced platelet aggregation. Moreover, they markedly decreased the serum cholesterol, triglycerides and phospholipids levels of rats after injection of Triton WR 1339 (4-(1,1,3,3-tetramethylbutyl)phenol polymer with formaldehyde and oxirane). They inhibited Candida albicans, Penicillium notatum and Aspergillus versicolor growth. Thus, these nine compounds possess interesting pharmacological properties which are very likely to be related to the acrylic moiety of the molecules.

The in vitro activity of imipenem, a new penem antibiotic, was determined against 210 clinical Gram-positive anaerobic isolates and compared with the activities of metronidazole, clindamycin, cefoxitin, moxalactam, ceftizoxime, ceftriaxone and cefotiam. All investigated strains were inhibited by a 4-mg/l concentration of imipenem. Cefoxitin demonstrated good activity against most strains with exception of some Clostridium difficile and Clostridium ramosum strains. Cephalosporins were classed in decreasing activity order as follows: cefoxitin moxalactam ceftriaxone ceftizoxime cefotiam. Metronidazole had better activity against Clostridium spp. than against non-sporulated bacilli. Clindamycin resistance rates were superior to 10% for most groups, with the exception of Clostridium perfringens. Actinomyces and Bifidobacterium. Imipenem was the most potent inhibitor, as 81% and 95% of tested strains were inhibited at concentrations of 0.25 and 0.5 mg/l respectively.

The minimal inhibitory concentrations of three antimicrobial agents were determined by two fold dilution in Wilkins Chalgren agar for over 569 anaerobes isolated and collected from 20 French hospitals. Metronidazole, cefoxitin and clindamycin inhibited respectively 95, 97 and 91% of tested strains. No metronidazole resistant strains could be found among Bacteroides fragilis group, Fusobacterium and Clostridium other than C. perfringens. Cefoxitin was the most active against C. perfringens, Gram positive cocci and non sporulated bacilli. Clindamycin resistance was observed mainly with B. fragilis and Clostridium other than C perfringens. This phenomenon occurred in most hospitals where strains were isolated.

Minimal inhibitory concentrations of 105 anaerobic Gram negative bacilli were determined by two-fold dilution in Wilkins - Chalgren agar following the reference method proposed by Sutter et al. No resistance was observed with thienamycin, which is especially active against the Bacteroides fragilis group (MIC 50 = 0.125 mg/l). Among the beta-lactams investigated, cefoxitin and moxalactam proved more active than ceftizoxime and ceftriaxone, while cefotiam exhibited poor activity. While most Fusobacteria were susceptible to studied beta-lactams, some Fusobacterium varium demonstrated resistance to cephalosporins and cephamycins .