PubMed Health⌕ Search

Biomedical subjects

J C Pechère

Publications and source records attributed to J C Pechère.

At least 109 records · Page 6Linked to original sources
PubMed1986

Combination therapy: a way to limit emergence of resistance?

The ability of antibiotic combinations to limit the emergence of resistance during therapy was evaluated in a murine model. Peritonitis was produced by injecting a mixture containing 10(8) colony-forming units of bacteria and sterilized talcum into the peritoneum. Two hours later, a single antibiotic dose was administered subcutaneously. The next day, peritoneal bacterial populations were analyzed on Szybalski's gradients. Acquired resistance was recorded when there was at least a fourfold increase in minimum inhibitory concentrations compared with untreated animals. No resistance emerged after amikacin monotherapy (15 mg/kg); however, resistance was frequently observed after monotherapy with ceftriaxone (50 mg/kg) or pefloxacin (25 mg/kg). Resistance to ceftriaxone and pefloxacin emerged, respectively, in 15 percent and 83 percent of animals with Klebsiella pneumoniae, 71 percent and 54 percent with Enterobacter cloacae, 0 percent and 83 percent with Serratia marcescens, 25 percent and 100 percent with Pseudomonas aeruginosa, and 0 percent with both Escherichia coli and Staphylococcus aureus. In mice with K. pneumoniae or E. cloacae infections, any dual combination of amikacin, pefloxacin, and ceftriaxone produced less acquired resistance than did monotherapy. In these animals, the combination of ceftriaxone and pefloxacin abolished all resistance, whereas the combinations of amikacin plus ceftriaxone or amikacin plus pefloxacin reduced the frequency of resistance by more than half. In animals with P. aeruginosa or S. marcescens infections, resistance to pefloxacin diminished or disappeared after treatment with the combinations of pefloxacin plus ceftriaxone or pefloxacin plus amikacin. However, combinations with ceftriaxone resulted in more frequent resistance to ceftriaxone than did ceftriaxone alone. This was the case in P. aeruginosa infections treated with ceftriaxone plus amikacin (p less than 0.01), and in S. marcescens infections treated with ceftriaxone plus pefloxacin (p less than 0.05). Despite these certain notable exceptions, our data confirm that in most cases combination therapy does limit the emergence of resistance.

Amikacin↗
PubMed1986

Emergence of resistance after therapy with antibiotics used alone or combined in a murine model.

A murine model of peritonitis allowing detection and quantification of in-vivo acquired resistance during short term therapy has been used in order to evaluate the capacity of antimicrobial combinations to limit emergence of resistance, as compared to individual components of the regimens. Mice were challenged intraperitoneally with 10(8) cfu of bacteria. Two hours later, a single antibiotic dose was injected subcutaneously: amikacin (15 mg/kg), ceftriaxone (50 mg/kg), pefloxacin (25 mg/kg), amikacin + ceftriaxone, amikacin + pefloxacin or ceftriaxone + pefloxacin. Escherichia coli and Staphylococcus aureus never became resistant. Single drug therapy yielded resistant mutants in Enterobacter cloacae, Serratia marcescens, Klebsiella pneumoniae and Pseudomonas aeruginosa as follows: 74% of ceftriaxone-treated animals, 57% of pefloxacin treated animals and 27% of amikacin treated animals. All the tested combinations reduced the frequency of in-vivo acquired resistance produced by single drugs, and no combination selected resistance when the separate agents of the combination did not. Combining antimicrobial agents limits the risk of emergence of resistance during antibiotic therapy.

Amikacin↗
PubMed1986

In-vitro activity of newer quinolones against aerobic bacteria.

Nalidixic and five newer 4-quinolones, ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin were tested against 576 recent clinical aerobic bacterial isolates. The 4-quinolones were regularly active (MIC90 less than 4 mg/l) against the following bacteria: Staphylococcus aureus, S. epidermidis, S. saprophyticus, different Enterobacteriaceae, Haemophilus influenzae, Campylobacter jejuni, Pseudomonas aeruginosa, Agrobacter spp., Aeromonas spp., Plesiomonas spp., Neisseria meningitidis. Other bacteria were usually intermediately susceptible or resistant: different streptococci, Listeria monocytogenes, Nocardia asteroides, P. maltophilia, Achromobacter xylosoxydans and Alcaligenes denitrificans. Ciprofloxacin was the most potent compound, followed by ofloxacin and pefloxacin, norfloxacin and enoxacin being less active. All the 4-quinolones were much more active than nalidixic acid. The MBC/MIC ratios of the 4-quinolones were between 1 and 2 with a majority of strains, and between 2 and 3 with Streptococcus agalactiae, Str. faecalis and L. monocytogenes. A two- to eight-fold increase of MIC was observed by increasing the inoculum 10,000-fold with most of the strains tested. Susceptible bacterial population of Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens and P. aeruginosa contained more clones resistant to nalidixic acid (10(4) to 10(8) at four times the MIC) than to 4-quinolones (10(5) to 10(9) at four times the MIC). Supplementing the media with MgSO4 produced smaller inhibition zone diameters with a disc diffusion method than those obtained with non-supplemented agar, with all quinolone or strains. Less regular effect, or no effect was obtained after supplementation with ZnSO4 or Ca(NO3)2.

Anti-Bacterial Agents↗
PubMed1986

[Lincosamides].

The two main antibiotics that make up the group of lincosamides are lincomycin and its more recent derivative clindamycin; the latter, more active drug is gaining preference over the former. These antibiotics are active primarily against Gram positive cocci (i.e. staphylococci, pneumococci and group A and unclassifiable streptococci) and against most anaerobes (including Bacteroides fragilis). This action originates in binding to the 50S ribosomal fraction. Lincosamides may be given per os, intramuscularly or intravenously. After an oral dose of clindamycin, 90% of the drug is absorbed, and the peak serum level is reached within the first hour. Drug absorption is not modified by meals. Regardless of the route of administration, the serum half life of clindamycin is 2 to 3.8 hours in healthy individuals. Longer half lives are observed in patients with severe renal or hepatic failure, requiring that lower dosages be given by widening the intervals between doses. Diffusion of lincosamides into tissues is of clinical significance except for the central nervous system, especially the cerebrospinal fluid. On the whole, lincosamides are well tolerated. Pseudomembranous colitis is a potential hazard. The main indications of clindamycin are infections due to anaerobes, especially intestinal and vaginal infections. As clindamycin has virtually no effect against Gram negative aerobic pathogens, in most instances another antibiotic, usually an aminoglycoside, is given simultaneously. Other less common indications are some instances of aspiration pneumonia, septicemias due to B. fragilis, and actinomycoses. Because of the risk of pseudomembranous colitis, prophylactic use of clindamycin to prevent postoperative infections following colorectal surgery seems unadvisable.

Adult↗
PubMed1984

Does incubator noise increase risks of aminoglycoside ototoxicity?

One group of newborn rats were given 50 mg/kg gentamicin for 20 days, 8 days after birth and were housed during the treatment in a regular incubator. They were compared to a similar group housed in regular cages and to two groups of unintoxicated newborn rats, one being exposed to the incubator noise and one being unexposed. Incubator noise was found to have no influence on gentamicin ototoxicity and to induce only a temporary threshold shift.

Aminoglycosides↗
PubMed1983

Open study of ceftazidime in serious infections due to multiply-resistant bacteria.

We treated 37 infections in 32 patients who had one or more significant underlying diseases. Most of the responsible micro-organisms were multiresistant, but were initially sensitive to ceftazidime. They included 16 Pseudomonas spp., 10 Serratia spp., 6 Klebsiella spp., 7 other Enterobacteriaceae, 3 Staphylococcus spp., 3 strict anaerobes and 1 Acinetobacter anitratus. Indications for ceftazidime encompassed a broad spectrum of diseases: 10 complicated UTI, 13 skeletal and soft tissue infections, 4 bronchopulmonary infections, 6 intra-abdominal infections, 3 septicaemias, 1 brain abscess with meningitis. Ceftazidime was administered without other antimicrobials, except for metronidazole in two patients with intra-abdominal abscesses. Doses varied from 2 to 12 g/day (median: 3 g), given for 3-31 days (median: 12 days). Clinical cure was recorded in 26 patients (81%), 24 (75%) having also a bacteriological cure. In six patients, clinical findings subsided significantly but with incomplete resolution or relapse during follow-up. Four organisms developed resistance during therapy: 2 Pseudomonas, 1 Enterobacter cloacae and 1 Bacteroides vulgatus. Three patients developed mild superinfections (2 Candida, 1 Staph. epidermidis). Ceftazidime was well tolerated; adverse events were mild and reversible. Local thrombophlebitis was observed twice, two patients had a positive reaction to the direct Coombs' test, two had transitory elevation of transaminases and one suffered from drowsiness during intravenous injections. Ceftazidime appeared to be a valuable weapon for fighting severe infections in compromised patients, especially when Gram-negative bacilli were involved.

Abscess↗
PubMed1983

Comparative study of the beta-lactamase activity found in Achromobacter.

A survey of 21 clinical isolates of Achromobacter species demonstrated a high level of beta-lactamase activity in all strains tested. The beta-lactamases were characterized by isoelectric focusing, purification by affinity chromatography, determination of molecular weight, immunological identity, and genetic analysis. At least three distinct patterns of beta-lactamases were found in 19 strains. The kinetic values Km and Vmax measured by a microacidimetric method showed that all three types of enzymes are cephalosporinases and did not hydrolyse oxacillin, cloxacillin, and methicillin. Two of the three types of cephalosporinases studied, namely MULB 901 (isoelectric point (pI)7.4) and MULB 905(pI 9.3) are enzymes mediated by genes of chromosomal origin. The MULB 906 (pI 8.1) enzyme, however, which has been previously shown to be mediated by an 8.2 MDal nonconjugative plasmid, showed hydrolysis of cefoxitime, cefotaxin, and moxalactam by the bioassay. In all cases, beta-lactamase synthesis appeared constitutive. This study confirms that beta-lactamase activity is commonly found in Achromobacter and that these enzymes are different and of clinical interest when compared with those observed in other Gram-negative bacteria.

Alcaligenes↗
PubMed1983

Experimental colonization of vascular grafts with Staphylococcus aureus.

In an attempt to solve the problem of infection of arterial grafts, the authors designed an experimental model to reproduce, in vitro, hematogenous seeding of grafts with Staphylococcus aureus. The inoculum, containing an average of 10(7) viable bacterial cells per millilitre, was circulated through grafts of various types. Normal dog aortas were used as controls. They entrapped a mean of 8 bacteria/cm2. The prosthetic grafts, previously placed in dogs as femorofemoral arteriovenous bypasses for 2 hours, trapped many more cells: expanded polytetrafluoroethylene, 23 cells/cm2; bovine heterograft, 607 cells/cm2 and Dacron velour, 2801 cells/cm2. All cell counts were significantly (p less than 0.001) different from control values. Thoracoabdominal aortic bypass grafts implanted in dogs 2 months previously gave the following mean numbers of trapped bacteria: expanded polytetrafluoroethylene, 19 122 cells/cm2; bovine heterograft, 863 cells/cm2 and Dacron velour, 3500 cells/cm2. Polytetrafluoroethylene had significantly (p less than 0.001) higher numbers of trapped bacteria than any other type of prosthesis. The bacteria were located mainly on irregular fibrin strands and on surface defects of the grafts. The addition of cefazolin during the seeding process at concentrations 10 to 25 times the minimal inhibitory concentration did not decrease the numbers of bacteria in any graft. Bacterial colonization of prosthetic arterial grafts depends on the graft material and on the duration of implantation, but this study provided no answer to the controversial question of how to prevent arterial graft infections with antimicrobial agents in patients who undergo vascular procedures that expose them to bacteremia.

Animals↗
PubMed1982

A plasmid-mediated cephalosporinase from Achromobacter species.

An unusual cephalosporinase in Achromobacter species was characterized biochemically; the enzyme had a pI of 8.1 and a molecular mass of 36,200 daltons, and it was not inhibited by p-chloromercuribenzoate or cloxacillin. Specific antiserum neutralized enzymatic activity. Agarose gel electrophoresis of the DNA of two strains (MULB 906 and MULB 912) revealed at least three plasmid bands; cured strains demonstrated a simultaneous loss of beta-lactamase and plasmid DNA. Resistance to beta-lactam antibiotics was transferred by transformation of Escherichia coli strain HB101 with plasmid DNA. This plasmid-mediated beta-lactamase differed from the two types of chromosomal cephalosporinases (pI 7.4 and 9.3, respectively) found in a survey of clinical isolates of Achromobacter species. This enzyme also differed in its biochemical properties from all of the other known plasmid-mediated beta-lactamases.

Cephalosporinase↗