In-vitro activity of FCE 22101 and other beta-lactam antibiotics against Enterobacteriaceae resistant to third generation cephalosporins.

The in-vitro activity of FCE 22101 was compared with those of imipenem, aztreonam, cefotaxime, ceftriaxone and latamoxef against 225 Enterobacteriaceae (209 clinical isolates and 16 derivatives of Escherichia coli K12) chosen for their resistance (MIC greater than or equal to 8 mg/l) to third-generation cephalosporins. The beta-lactamases produced by the strains of Enterobacter cloacae, Klebsiella pneumoniae and Esch. coli were identified. The mean MICs of FCE 22101 were 2-8 mg/l for Ent. cloacae, Citrobacter freundii and Morganella morganii. For Ent. cloacae, the MICs were slightly higher for the cephalosporinase non overproducing (5.5-8 mg/l) than for the cephalosporinase overproducing (4.5 mg/l) strains. The mean MIC was 9 mg/l for Serratia spp. but for half of the strains the MICs were greater than or equal to 16 mg/l. The MICs of FCE 22101 were 0.5-1 mg/l for the resistant clinical isolates or isogenic derivatives of K. pneumoniae and Esch. coli producing extended broad-spectrum beta-lactamases (SHV-2, SHV-3 or CTX-1), whether measured in the presence of clavulanate or not, and against the sensitive controls. This showed that the compound was not affected by these new beta-lactamases. The MICs of imipenem, on the average four to five times lower than those of FCE 22101, were found to be very similar for resistant and sensitive strains. The MICs of aztreonam were high (32-128 mg/l) for C. freundii, K. oxytoca and cephalosporinase overproducing strains of Ent. cloacae. There was cross-resistance between the third-generation cephalosporins, but the MICs of latamoxef remained low (1 mg/l) against M. morganii, Klebsiella spp. and Esch. coli.

[Study of the minimal inhibitory concentration of rifabutine (Ansamycin LM 427) for Mycobacterium tuberculosis, Mycobacterium xenopi and Mycobacterium avium-intracellulare]. / Etude des concentrations minima inhibitrices de rifabutine (Ansamycine LM 427) pour Mycobacterium tuberculosis, Mycobacterium xenopi et Mycobacterium avium-intracellulare.

Ansamycin LM 427 (or rifabutine) is a spiropiperidyl-rifamycin which has been proposed as a treatment for tuberculosis and mycobacterial infections resistant to rifampicin. The minimal inhibitory concentration (MCI) of rifabutine and of rifampicin for 10 strains of M. tuberculosis sensitive to rifampicin, 15 strains of M. tuberculosis resistant to rifampicin, 10 strains of M. xenopi and 15 of M. avium-intracellulare have been measured in a comparative fashion on gel DIFCO 7H11 medium and also on a Loewenstein-Jensen medium. The MCI of rifampicin and of rifabutine inhibiting 90% of the strains (MCI 90) of M. tuberculosis sensitive to rifampicin have been 0.06 mg/l on 7H11 media and 1 mg/l on Loewenstein-Jensen media respectively. For strains of M. tuberculosis resistant to rifampicin they were respectively 256 and 8 mg/l on 7H11 and of 1024 and 128 Loewenstein-Jensen, for the strains of M. xenopi they were 8 and 0.5 on 7H11 and 64 and 4 mg/l on Loewenstein-Jensen respectively, and finally for strains of M. avium-intracellulare they were 64 and 2 mg on 7H11 and 256 and 16 on Loewenstein-Jensen media. With rare exceptions for proven mycobacterial infections there was a link of the order of 20:1 between the values for CMI of rifampicin and rifabutine measured on Loewenstein-Jensen medium and on 7H11; the MCIs were ten times more elevated on the first than on the second and the liaison between the MCI of rifampicin and the MCI of rifabutine tended to show that these two antibiotics have the same mode of action.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of pefloxacin and ciprofloxacin against Mycobacterium leprae in the mouse.

Because ciprofloxacin and pefloxacin are fluoroquinolones active against many mycobacterial species, both drugs were tested against Mycobacterium leprae in the mouse foot-pad system. Preliminary pharmacokinetic studies in the mouse showed that after a single oral dose of 150 mg/kg ciprofloxacin the peak serum concentration was 3.6 micrograms/ml, and after 50 mg/kg or 150 mg/kg pefloxacin peak serum concentrations were, respectively, 9.2 micrograms/ml and 16.9 micrograms/ml, the half-lives for serum elimination being about 2 hr for both drugs. The activity of daily 50 mg/kg and 150 mg/kg ciprofloxacin and pefloxacin against M. leprae was then tested in mice infected with 5 X 10(3) M. leprae. The growth of M. leprae was not prevented in mice treated continuously with either 50 mg/kg or 150 mg/kg ciprofloxacin, indicating that this drug had no or a limited bacteriostatic effect at the dosages used. In mice treated continuously with 50 mg/kg pefloxacin, growth of M. leprae was not prevented, but at monthly harvests the number of bacilli in the foot pads remained less than those of control mice (p less than 0.05). No growth of M. leprae occurred in mice treated continuously with 150 mg/kg pefloxacin. In mice treated for only 3 months with daily 150 mg/kg pefloxacin, the growth-delay that followed the stopping of the drug was 126 days, suggesting that approximately 99% of the M. leprae were killed. The pharmacokinetics of pefloxacin being more favorable in man than in the mouse, pefloxacin appears a possible drug for the chemotherapy of leprosy.

Electrophysiological studies of the sciatic nerves in Mycobacterium leprae foot pad-injected rats.

This study tested the possibility of developing an experimental model of neuropathy in female Wistar rats inoculated with Mycobacterium leprae in the foot pad and assessed by repeated electrophysiological methods. M. leprae multiplied in the rats but considerably less than in simultaneously inoculated mice. No acid-fast bacilli were found in nerves. Motor and sensory conduction velocities remained normal at the thigh level of the sciatic nerve. At the leg, they decreased significantly bilaterally for motor conduction and in the inoculated side for sensory conduction at 21 months after inoculation. These results suggest the possibility of developing an experimental model of leprosy neuropathy which might be useful for therapeutic research. Further histopathological studies are needed to assess this paucibacillary model.