Biliary tract excretion of ofloxacin in man.

This study examined the biliary tract excretion of ofloxacin in 6 post-cholecystectomy patients with a T-tube inserted into the common duct (group A) and 6 patients during cholecystectomy (group B). The patients were given 7 oral doses of ofloxacin 200mg with a 12-hour interval between each dose. Blood and common duct bile samples were collected in group A at various time intervals after the first and the seventh dose. Blood, gallbladder wall, and gallbladder and common duct bile were collected in group B during operation, 6 hours after the seventh dose. Assays were performed by use of high performance liquid chromatography (HPLC). In group A, mean serum Cmax and half-life were 2.6 mg/L and 7.6 hours after the first dose, and 5.3 mg/L and 8 hours after the seventh dose, respectively. Mean common duct bile Cmax and half-life were 6.5 mg/L and 7.5 hours after the first dose, and 12.0 mg/L and 14 hours after the seventh dose, respectively. In group B, mean concentrations (mg/L) were 2.6 in blood, 5.3 in gallbladder wall, 24.6 in gallbladder bile and 10.1 in common duct bile, 6 hours after the seventh dose. These data suggest that ofloxacin may be suitable for the treatment of biliary tract infections.

Differences between clavulanic acid and sulbactam in induction and inhibition of cephalosporinases in enterobacteria.

The ability of clavulanic acid and sulbactam to induce and inhibit cephalosporinases was evaluated in 16 clinical isolates of enterobacteria. Using the quantitative induction assay, the checkerboard method and the disc approximation test, clavulanic acid was shown to act as inducer for all species, whereas sulbactam only induced strains of Providencia stuartii. Antagonism was achieved using a combination of clavulanic acid and cefotaxime but a combination of sulbactam and cefotaxime was either synergistic or indifferent. This variation in effect was probably due to the fact that sulbactam, but not clavulanic acid could inhibit cephalosporinases. The data revealed a significant difference between sulbactam and clavulanic acid, which may have relevance to their relative usefulness in combination with beta-lactam antibiotics for the treatment of infections due to enterobacteria that produce inducible cephalosporinase.

[Lung disease due to Mycobacterium xenopi excluding AIDS. Apropos of 8 cases]. / Atteintes pulmonaires à Mycobacterium xenopi en dehors du SIDA. A propos de 8 cas.

Between 1994 and early 1999, Mycobacterium xenopi was isolated in 11 HIV-negative patients seen at the Respiratory Disease Department of the Dijon University Hospital. Eight of these patients met the criteria of lung infection. Clinical and radiological features simulated pulmonary tuberculosis which delayed diagnosis until the germ was identified. Treatment is considered to be mandatory though it is difficult to manage and often disappointing. In spite of long-term medical care, sometimes associated with surgery, outcome is currently determined by the underlying disease rather than by Mycobacterium xenopi infection.

[Fosfomycin-cefotaxime combination in severe staphylococcal infections in newborn infants]. / L'association fosfomycine-céfotaxime dans les infections sévères staphylococciques du nouveau-né.

Clinical and bacteriological effectiveness of the fosfomycin-cefotaxime combination is reported in four cases of serious staphylococcal infections in neonates (1 meningitis, 2 osteomyelitis, 1 superinfection of congenital varicella). Owing to the strong synergistic effect of this combination on methicillin-resistant staphylococcal strains, the authors suggest that the fosfomycin-cefotaxime combination should be considered for anti-staphylococcal therapy in neonates with deep tissue and/or methicillin-resistant infections.

[Treatment with a cefotaxime-fosfomycin combination of staphylococcal or enterobacterial meningitis in adults]. / Traitement par l'association céfotaxime-fosfomycine des méningites de l'adulte à staphylocoques ou à entérobactéries.

Thirty-two patients were included in this trial: 22 with staphylococcal meningitis (including 5 methicillin-resistant) and 10 with enterobacterial meningitis. Mean duration of treatment was 14.5 and 15.9 days respectively. The combination was synergistic in vitro against 10 of the 12 strains of Staphylococcus and 5 of the 6 strains of Enterobacteriaceae studied. Bacteriological sterilization occurred in all cases which could be evaluated, and clinical recovery was obtained in 95.2% of patients with staphylococcal meningitis (4 unrelated deaths) and 100% of patients with enterobacterial meningitis (2 deaths). Bactericidal power of the cerebro-spinal fluid, often less than 1/8, was not correlated with effectiveness against Staphylococci. Mean CSF concentrations of cefotaxime, desacetylcefotaxime and fosfomycin on the 2nd and 15th days of treatment were 4, 3.5 and 39.8 mg/l and 2.2, 2.1 and 28.0 mg/l, respectively. Clinical and biological acceptability was satisfactory. There were three cases of superinfection or colonization, by Pseudomonas and Enterobacter.

In vitro combinations of five intravenous antibiotics with dalfopristin-quinupristin against Staphylococcus aureus in a 3-dimensional model.

We compared the in vitro activity of dalfopristin and quinupristin combined with five intravenous antibiotics in a 3-dimensional model. We tested six strains of Staphylococcus aureus selected with different patterns of resistance to methicillin and erythromycin. Dalfopristin and quinupristin displayed a very synergistic activity against all the strains with a mean 16- or 32-fold decrease of inhibitory concentrations in combination. That synergy was even better against erythromycin-resistant strains. In combination with tigecycline or fosfomycin, the antibacterial activity could be consistently enhanced with the same decrease of inhibitory concentrations. A synergy was also observed, less regularly and at a lower level, with rifampin, gentamicin or vancomycin. Combinations of dalfopristin and quinupristin with tigecycline or fosfomycin could be very interesting in clinical practice because the inhibitory effect could be achieved with very low concentrations of each component, even when erythromycin-resistant strains are concerned.

Presumed pseudobacteremia outbreak resulting from contamination of proportional disinfectant dispenser.

Reported here are the microbiological and epidemiological details of a presumed outbreak of aerobic gram-negative bacilli infections affecting 19 hematological patients, which was traced to contaminated disinfectant. Over a 5-month period, the following organisms were isolated from the blood cultures of 19 neutropenic patients: Pseudomonas fluorescens (n = 13), Achromobacter xylosoxidans (n = 12), Comamonas testosteroni (n = 2) or Stenotrophomonas maltophilia (n = 1). The affected patients were all treated with an expensive regimen of broad-spectrum antibiotic therapy. The same bacteria were recovered from environmental samples as well as from the water pipes of an apparatus for dispensing disinfectant (didecyldimethylammonium chloride). Genotyping results indicated that many of the clinical strains were identical to strains isolated from the apparatus. It was eventually discovered that the night staff was in the habit of disinfecting the blood-culture bottles before use, thereby contaminating the bottles with bacteria contained in the disinfectant. Contamination of the apparatus resulted from faulty maintenance.

[Modulatory effect of antimicrobial agents or aminoacids on the oxidative burst of polymorphonuclear neutrophils triggered by formylmethionyl-leucyl-phenylalanine (fMLP)]. / Influence des antibiotiques et des acides aminés sur la réaction oxydative des polynucléaires neutrophiles déclenchée par la formylméthionyl-leucyl-phénylalanine (fMLP).

We have compared the interplay of several antimicrobial agents and aminoacids on the neutrophil respiratory burst in response to formylmethionyl-leucyl-phenylalanine (fMLP), a chemoattractant. Mainly, an inhibitory effect has been observed in the penicillin family of agents and an enhancing effect in the cephalosporin family of agents. The molecules in which the sulfur numbered 1 in the 6-APA or 7-ACA nucleus was replaced by a carbon or an oxygen, had a different effect as compared with the other members of the family. The modulatory effects of ampicillin and cephalothine were not significant at a concentration lower than 10 mg/l and the effect of cephalothine looked maximum at 20-40 mg/l. If studies in cell-free systems demonstrated that the inhibitory effect of some antimicrobials could be due to a direct oxidant-scavenger activity mainly of HOCl, only hypotheses are proposed to explain the enhancing activity of the others. It could be in relation with (i) a synergistic effect upon fMLP receptor leading to an increase in H(2)O(2)/HOCl production or (ii) the generation of new oxydant products originating in cephalosporin lysis under HOCl attack, which would be able to react with luminol. The interplay of antimicrobial agents with the respiratory burst measured outside the cells probably has no therapeutic consequences because the bactericidal activity of neutrophils is achieved inside phagosomes where few agents are known to come into and where chemical conditions are different. On the opposite, in clinical use, this interplay could be interesting to study for a prevention of side effects.

[Uptake of ofloxacin by Escherichia coli]. / Pénétration de l'ofloxacine chez Escherichia coli.

The uptake of ofloxacin by Escherichia coli NIHJ-JC2 was determined by a sensitive and convenient method using high-performance liquid chromatography (HPLC) with a fluorometric detection (sensitivity level: 1 ng/ml). Concentrations of ofloxacin were measured in bacteria after contact with 5 micrograms/ml of antibiotic for 1, 2, 3, 5, 10, 20 and 30 min. Ofloxacin uptake was rapid, 70% of broth concentration occurring within the first min and 96% after 5 min; then it reached a plateau which was 1.16 times as high as the broth concentration.

Imipenem resistance in clinical isolates of Proteus mirabilis associated with alterations in penicillin-binding proteins.

Two strains of Proteus mirabilis, IpR1 and IpR2, resistant to both imipenem and mecillinam, but susceptible to other beta-lactams were isolated from blood cultures of patients who had been treated with imipenem. Strain IpR1 was isolated in the same sample as a P. mirabilis IpS1 which was susceptible to imipenem and mecillinam. Strains IpR1 and IpR2 did not produce a beta-lactamase and their outer membrane protein profiles were similar to those of IpS1 and P. mirabilis ATCC 29906. Electrophoretic profiles of penicillin-binding proteins (PBPs) showed a decrease in PBP 1A of strains IpR1 and IpR2 compared with IpS1 and ATCC 29906. Competition experiments revealed a decrease in affinity of PBP 2 for imipenem from strain IpR1. These findings suggest that imipenem resistance in P. mirabilis might result from altered PBPs, as reported for Acinetobacter baumanii and Pseudomonas aeruginosa.

[In vitro antibacterial activity of piperacillin-tazobactam in combination with netilmicin or amikacin against Enterobacteriaceae resistant to amoxicillin]. / Activité antibactérienne in vitro de pipéracilline-tazobactam en association avec la nétilmicine ou l'amikacine sur des entérobactéries résistantes à l'amoxicilline.

The antibacterial in vitro activity of piperacillin and tazobactam (in a concentration ratio of 8/1) was studied in combination with netilmicin or amikacin by a microtiter checkerboard assay against 162 strains of Enterobacteriaceae. These strains were selected for their resistance pattern to beta-lactam antibiotics and their beta-lactamases were characterized by the mean of isoelectric focusing in comparison with reference strains. A comparison of the MICs of piperacillin, alone and in combination, assessed the efficacy of tazobactam as beta-lactamase inhibitor, particularly when a TEM-1 beta-lactamase was produced. When the strains were sensitive to the aminoglycosides (111 netilmicin-sensitive ones and 131 amikacin-sensitive ones), we observed 55% of synergistic effects and 45% of additions with the combinations piperacillin-tazobactam-netilmicin or amikacin. A synergistic effect was usually encountered with P. mirabilis, P. vulgaris, M. morganii and with the strains of E. coli, E. cloacae and S. marcescens which produced a cephalosporinase only. Among the 51 strains that were intermediate or resistant to netilmicin, 8 ones were inhibited by piperacillin-tazobactam-netilmicin at therapeutic levels (3 synergisms, 5 additions). Among the 31 strains that were intermediate or resistant to amikacin, 24 ones (18 synergisms, 6 additions) were inhibited by piperacillin-tazobactam-amikacin at therapeutic concentrations. In most of the cases, the combination of piperacillin-tazobactam with an aminoglycoside enhanced the antibacterial activity of these agents by decreasing the concentrations necessary to inhibit the strains.

In vitro bactericidal activity of sulbactam plus ampicillin against methicillin-resistant Staphylococcus aureus.

By a microtiter checkerboard method, the in vitro bactericidal activity of sulbactam/ampicillin was tested against three groups of Staphylococcus aureus strains: group PR (penicillin-resistant through the production of penicillinase; methicillin-susceptible both at 30 degrees C in medium containing 5% NaCl and at 35 degrees C in medium without NaCl; n = 10); group MR1 (methicillin-resistant under the former conditions but not under the latter; n = 15); and group MR2 (methicillin-resistant under both sets of conditions; n = 20). Sulbactam/ampicillin was synergistic against all strains (fractional bactericidal index, less than or equal to 0.10). Moreover, there was a linear relation in each group between the different concentrations of the two antibiotics required for bactericidal activity. Thus, an equation of bactericidal synergy could be formulated for the combination. The bactericidal activity of sulbactam/ampicillin was assessed against one strain of each group and against a reference strain (S. aureus ATCC 6538 P) in an in vitro model simulating the kinetics of both antibiotics in human blood after intravenous administration of 2 g of ampicillin and 1 g of sulbactam. The observed rate of killing was approximately 99% except with the MR2 strains, against which the combination was bacteriostatic.

[Inhibition of cephalosporinase of enterobacteria by ceftriaxone]. / Inhibition des céphalosporinases d'entérobactéries par la ceftriaxone.

Resistance of ceftriaxone, cefotaxime and cefmenoxime to inactivation by the chromosomal constitutive cephalosporinases of Enterobacter cloacae P99, Morganella morganii GN 1510 and Serratia liquefaciens 132 was determined using high performance liquid chromatography. The inhibitory properties of ceftriaxone against the same cephalosporinases were studied by determining the residual amount of cephalothin used as the substrate. With a 1:50 cephalosporinase-cephalosporin ratio, ceftriaxone was less resistant to hydrolysis than cefotaxime of cefmenoxime but showed stronger inhibitory properties.

[Comparative study of the antibacterial activity of cefpodoxime against enterobacteria producing beta lactamases]. / Etude comparative de l'activité antibactérienne du cefpodoxime sur les entérobactéries productrices de bêta lactamases.

Cefpodoxime proxetil (RU 51 807) is the oral prodrug of cefpodoxime (RU 51 763), a third generation cephalosporin. The antibacterial activity of cefpodoxime was compared with the activities of amoxicillin in combination with clavulanic acid (AUG), cefaclor (CCl), cefuroxime (CXM) and cefotaxime (CTX), against species of Enterobacteriaceae showing a resistance pattern against ampicillin (AMP), ticarcillin (TIC), cefalothin (CFT) and cefotaxime (CTX) respectively. For strains AMP and TIC R, CFT and CTX S, MICs 90% of cefpodoxime were 1 mg/l (E. coli), 0.5 (K. pneumoniae), 0.06 (P. mirabilis), 0.5 (Shigella sp.) and 1 (Salmonella sp.); they were 4 to 16 times as high for AUG -CCL -CXM and 4 to 16 times as low for CTX. For K. pneumoniae AMP and TIC R, CFT I/R and CTX S, similar résults were obsereved for the 5 beta-lactam antibiotics, but with an activity 10 times as low. Among the species AMP R, TIC S, CFT R and CTX S, cefpodoxime was active against P. rettgeri, P. stuartii, C. diversus, E. aerogenes and Y. enterocolitica (MICs 90% ranging from 2 to 4 mg/l; from 0.12 to 1 mg/l for CTX) and less active or inactive against P. vulgaris, E. cloacae, S. marcescens, M. morganii and E. coli (MICs 90% ranged from 16 to 32 mg/l; from 1 to 4 mg/l for CTX).(ABSTRACT TRUNCATED AT 250 WORDS)

Bactericidal activity of cefodizime on Enterobacteriaceae in an in-vitro model simulating plasma pharmacokinetics in humans.

An in-vitro dialysis model was employed to assess the feasibility of once-daily dosing of cefodizime in the treatment of infections caused by various Enterobacteriaceae: Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Serratia marcescens, Providencia stuartii and Enterobacter cloacae. This model simulated the concentrations of cefodizime detected in human blood after an intravenous (i.v.) bolus injection of 1 g or 2 g of the antibiotic. Validation of the model was undertaken to confirm its utility. Based on the data obtained with this model, once-daily dosing with 1 g cefodizime (i.v.) should be effective against infections due to the commonest Gram-negative bacteria (E. coli, K. pneumoniae, M. morganii). For infections caused by Enterobacteriaceae strains that produce large quantities of Class I beta-lactamases, twice-daily (P. stuartii or S. marcescens) or four times daily (E. cloacae) administration of 1 g cefodizime may be required.