Biomedical subjects

M D Kitzis

Publications and source records attributed to M D Kitzis.

At least 73 records · Page 4Linked to original sources

PubMed1988

Dissemination of the novel plasmid-mediated beta-lactamase CTX-1, which confers resistance to broad-spectrum cephalosporins, and its inhibition by beta-lactamase inhibitors.

The novel beta-lactamase CTX-1 (pI 6.3) encoded on a transferable 84-kilobase plasmid was found in six different bacterial species. It was responsible for a significant decrease in susceptibility towards most penicillins and cephalosporins, except imipenem, temocillin, and cephalosporins which have a 7-alpha-methoxy substituent. Synergy between either ampicillin, piperacillin, cefotaxime, ceftazidime, or aztreonam and three beta-lactamase inhibitors (clavulanic acid, sulbactam, and YTR 830) was generally found for different strains harboring CTX-1. This enzyme may be related to or derived from the TEM enzyme, since an intragenic probe of the TEM-1 gene hybridized with a fragment of the plasmid carrying CTX-1.

Cephalosporins↗

PubMed1988

Beta-lactamases in clinical isolates. Spectrum implications of sulbactam/ampicillin.

Combining ampicillin with an irreversible beta-lactamase inhibitor such as sulbactam is a promising technique for controlling infections due to resistant organisms. The combination not only restores the effectiveness of ampicillin against species that have acquired resistance to it, but it can extend the antimicrobial spectrum to species that have never exhibited susceptibility to ampicillin. However, the inhibition of beta-lactamases and the evaluation of inhibitors are still complicated by numerous factors known collectively as 'the epidemiology of beta-lactamases'. This refers to the distribution of enzymes in different bacterial species and in different geographical locations, the numerous types of enzymes, the variable number and amount of beta-lactamases that may exist in the same cell, and, of course, the potential for transfer of beta-lactamase resistance from one species to another.

Ampicillin↗

PubMed1988

[In vitro activity of roxithromycin against hospital bacteria and the concordance curve].

This study was set up to establish the regression curve for roxithromycin inhibition zone diameters (disks 15 micrograms) and MIC to create a strain distribution plot, in order to allow accurate interpretation of the disk diffusion method for testing susceptibility to roxithromycin. 373 bacterial strains were studied in three university hospital. Roxithromycin was active against erythromycin sensitive Staphylococcus aureus and coagulase negative Staphylococci at concentrations of 0.06 to 4 micrograms/ml (mode 0.5). Erythromycin resistant strains were also resistant to roxithromycin. Enterococci could be divided into two populations, one resistant (MIC greater than 128 micrograms/ml) and the other with MIC of 0.5 to 32 (mode 1-2). This was also the case for Streptococci and Pneumococci with MIC lower for susceptible strains (mode 0.06-0.12). Roxithromycin was active on Haemophilus at concentrations of 0.12 to 32 micrograms/ml; MIC for beta-lactamase producing strains were comparable to those of strains not producing. MIC for Gonococci were low (less than 0.008 to 0.12), except for three strains. They were higher for Meningococci (0.03 to 32) with a majority of strains inhibited by 0.5 to 4 micrograms/ml. MIC were 4 for Clostridium perfringens; Bacteroides fragilis strains were inhibited by 0.5 to 2 micrograms/ml. The correlation coefficient for regression curve was 0.79; for critical concentrations less than or equal to 1 and greater than 4 micrograms/ml, critical diameters are greater than or equal to 22 and less than 17 mm.

Anti-Bacterial Agents↗

PubMed1987

Bactericidal activity against Haemophilus influenzae of cerebrospinal fluid of patients given amoxicillin-clavulanic acid.

Patients with purulent meningitis received amoxicillin-clavulanic acid (200/20 mg/kg [body weight] per day). Clavulanic acid levels in cerebrospinal fluid were less than or equal to 0.05 micrograms/ml in 5 of 18 samples and ranged from 0.1 to 0.8 micrograms/ml in the others. Of 12 cerebrospinal fluid samples tested, 10 lacked bactericidal activity in vitro against a beta-lactamase-producing strain of Haemophilus influenzae.

Adolescent↗

PubMed1986

Synergism and antagonism in double beta-lactam antibiotic combinations.

Combinations of two beta-lactam antibiotics may be advantageous in certain clinical situations, providing a synergistic activity against specific organisms or a broad spectrum of antibiotic coverage. Depending on the combination and the bacteria, synergism, indifference, or antagonism can be observed. Synergism may occur when two beta-lactam antibiotics, acting on different penicillin-binding proteins, are combined or when a penicillinase-susceptible beta-lactam antibiotic is protected by another beta-lactam antibiotic acting as a beta-lactamase inhibitor in strains producing a penicillinase (chromosomal or plasmidic). With different species, such as Enterobacter, Citrobacter, indole-positive Proteus, Serratia, Aeromonas, and Pseudomonas, which produce an inducible chromosome-encoded cephalosporinase, antagonism will appear if one of the two combined antibiotics causes induction of the beta-lactamase and the other becomes inactivated by the increased amount of the enzyme. Although most combinations of new beta-lactam antibiotics (ureido-penicillins, third-generation cephalosporins, monobactams) appear to be indifferent, antagonism and possible selection of resistant mutants are the drawbacks of such combinations. Nevertheless, highly active compounds, if used at doses above the minimal inhibitory concentrations, especially in the case of potential cephalosporinase-inducers, may be safe in vivo as far as avoiding antagonism is concerned, but not necessarily with respect to the selection of resistant mutants.

Anti-Bacterial Agents↗

PubMed1986

Comparative evaluation of a new beta-lactamase inhibitor, YTR 830, combined with different beta-lactam antibiotics against bacteria harboring known beta-lactamases.

YTR 830, a new beta-lactamase inhibitor, combined with amoxicillin or carbenicillin, showed a synergistic effect similar to that observed with clavulanic acid, and generally better than that with sulbactam, against strains harboring chromosome-encoded penicillinases and broad-spectrum beta-lactamases or plasmid-determined beta-lactamases. With ampicillin, YTR 830 showed the best synergistic activity of the inhibitors against Proteus morganii, Citrobacter freundii, and Enterobacter cloacae and their mutants with a derepressed chromosome-encoded cephalosporinase.

Anti-Bacterial Agents↗

PubMed1986

[Multicenter study of ofloxacin activity on bacteria isolated from a hospital environment].

Minimal inhibitory concentrations (MICs) of ofloxacin were evaluated by agar dilution for 1508 bacterial strains isolated in five hospitals. For Enterobacteriaceae sensitive to nalidixic acid, MICs ranged from 0.008 to 1 microgram/ml (mode MIC: 0.12); the different species of Enterobacteriaceae exhibited similar mode MICs (0.12) with the exception of E. coli (0.06-0.12), P. mirabilis (0.5) and Providencia (0.25). Among strains intermediate and resistant to nalidixic acid, most of which were Serratia, Providencia and Citrobacter, 41% had a MIC within the susceptibility range, while the others had a MIC of 2 to 8 micrograms/ml, or even 64 micrograms/ml in a few instances. Ofloxacin also exhibited satisfactory activity against P. aeruginosa, with MICs ranging from 0.25 to 16 micrograms/ml (mode MIC: 2) for 87% of strains, and A. calcoaceticus, with MICs from 0.25 to 2 micrograms/ml (mode MIC: 1). Haemophilus sp. (MIC: 0.008 to 0.06 microgram/ml; mode MIC: 0.03), Gonococci (mode MIC: 0.008), and Meningococci (mode MIC: 0.016) were very sensitive to ofloxacin. The spectrum of ofloxacin included Gram positive cocci: MICs of Staphylococci were 0.06 to 2 micrograms/ml (mode MIC: 0.5); Enterococci, other Streptococci and Pneumococci were less sensitive, with MICs of 2 to 4 micrograms/ml for the majority of strains. As for anaerobic bacteria, ofloxacin proved more active against Clostridium (0.5 to 2 micrograms/ml) than Bacteroides (0.5 to 16 micrograms/ml).

Bacteria↗

PubMed1985

Cross-resistance to nalidixic acid, trimethoprim, and chloramphenicol associated with alterations in outer membrane proteins of Klebsiella, Enterobacter, and Serratia.

We studied in vitro mutants of Klebsiella, Enterobacter, and Serratia cross-resistant to nalidixic acid, trimethoprim, and chloramphenicol that were similar to mutants found in vivo. The sole mechanism for this type of resistance appeared to be a reduction in permeability of the cell envelope. The mutants had significantly lower rates of uptake of glucose and chloramphenicol, but binding of chloramphenicol to ribosomes was normal. In addition, the amounts of dihydrofolate reductase were similar in both wild-type and cross-resistant mutants of Klebsiella. Examination of the bacterial outer membrane revealed that the amount of at least one major protein, with a molecular size of approximately 40 kilodaltons, was decreased in the mutants. Therefore the resistance seemed likely to be due to the reduction in quantity of these outer membrane proteins, possibly porins, in the mutant bacteria.

Anti-Bacterial Agents↗

PubMed1985

In-vitro susceptibility of Nocardia asteroides to 21 beta-lactam antibiotics, in combination with three beta-lactamase inhibitors, and its relationship to the beta-lactamase content.

Twelve strains of Nocardia asteroides were studied for their susceptibility to 21 beta-lactam antibiotics, alone or in combination with clavulanic acid, sulbactam, or BLP 2013, and for their content of beta-lactamase. Eleven strains were shown to have beta-lactamase activities, which gave three different patterns after analytical isoelectric focusing. The only strain with no detectable beta-lactamase was the most susceptible to the antibiotics tested. The other strains containing beta-lactamases showed almost the same susceptibility profile. Clavulanic acid was the only beta-lactamase inhibitor to show a significant synergistic effect when combined with penicillins.

Anti-Bacterial Agents↗

PubMed1985

Sch 34343 activity against streptococci and beta-lactam-resistant Enterobacteriaceae.

The in-vitro activity of Sch 34343 was compared with that of cefotaxime, ceftazidime, latamoxef (moxalactam), aztreonam and ampicillin. Against pneumococci, Sch 34343 was as active as ampicillin, whereas against the other streptococci it was less active than ampicillin but significantly better than the other antibiotics against enterococci. With clinical isolates of Enterobacteriaceae resistant to cefotaxime, Sch 34343 had MICs generally less than 2 mg/l. After introduction of plasmid-mediated beta-lactamases into Escherichia coli Cla. there were no significant changes in the MICs of Sch 34343. Mutants of Enterobacter cloacae, Citrobacter freundii and Morganella morganii with derepressed cephalosporinases had susceptibilities equal to or less than 1 mg/l, which were generally lower than those of the other compounds tested. Comparison of parental strains and permeability mutants of E. coli, Ent. cloacae, and Serratia marcescens showed that the increase in MICs of Sch 34343 were lower than those found for the other antibiotics.

Anti-Bacterial Agents↗

PubMed1985

[In vitro activity of ceftriaxone on hospital bacteria. Results of a multicenter study].

Minimal inhibitory concentrations (MICs) of ceftriaxone were determined by agar dilution for 2 099 strains isolated in six teaching hospitals. MICs were less than 1 microgram/ml for the great majority of Enterobacteriaceae, with mode MICs varying across groups from less than 0.008 micrograms/ml for Proteus (mirabilis and indole-positive) to 0.25 for Enterobacter. Only a few resistant strains were found, mainly among Enterobacter and Citrobacter. Ceftriaxone proved noticeably less active against P. aeruginosa and Acinetobacter (mode MICs: 16 micrograms/ml). Haemophilus sp. and Gonococci, regardless of beta-lactamase production status, as well as Neisseria meningitidis, were highly susceptible (MIC less than 0.008-0.032). Ceftriaxone was moderately active against methicillin-susceptible staphylococci (MIC: 2 to 8 micrograms/ml) and failed to inhibit methicillin resistant strains. Enterococci were slightly susceptible or resistant, whereas the other Streptococci and Pneumococci had low MICs (0.03-0.25). A fairly wide range of MICs was found for anaerobes (Clostridium: 0.06-2, Bacteroides: 0.5-32). Our data show that its particularly strong activity against Proteus, Haemophilus and Neisseria sets ceftriaxone apart from the other third-generation cephalosporins.

Acinetobacter↗

PubMed1985

Single- and multiple-dose pharmacokinetics of lenampicillin (KBT-1585) in healthy human subjects: comparative studies with amoxicillin.

Lenampicillin (LAPC) is a novel prodrug of ampicillin (ABPC) which is under development by KANEBO Ltd. and TORII Pharmaceutical Co. The single- and multiple-dose pharmacokinetic studies were performed on six healthy male volunteers. Amoxicillin (AMPC) was used as control drug. The oral single-dose studies of LAPC (equivalent to 250 mg ANPC) and of AMPC (500 mg) demonstrated that the mean peak serum concentrations of ABPC and AMPC were 11.4 +/- 0.8 micrograms/ml at 40 min and 8.5 +/- 0.7 micrograms/ml at 50-90 min, respectively. The half-lives and the areas under the concentration-time curves were the same for both antibiotics on an equimolar basis. The oral multiple-dose studies of LAPC and AMPC (twice a day for 8 days with the same single dose as above) showed that no measurable accumulation and no remarkable variations between the single- and multiple-dose pharmacokinetics were observed. No adverse effects were recorded for any subject. LAPC proved to have unique pharmacokinetic properties as compared with AMPC and high safety, and its further development to clinical trials appears warranted.

Administration, Oral↗

PubMed1984

Recovery period after exposure of Staphylococcus aureus to sub-inhibitory and bactericidal concentrations of rifampicin: clinical implications.

The effects of rifampicin, at subinhibitory and bactericidal concentrations, were examined in the presence of and after the removal of the drug. After exposure to subinhibitory concentrations as low as one-tenth of the MIC an extended recovery period was observed. Incubation of exponential or stationary phase cultures for 30 min or 4 h with a bactericidal concentration also caused a significantly prolonged recovery period.

Colony-Forming Units Assay↗

PubMed1984

An evaluation of the bacteriolytic and biochemical properties of ceftiolene (42980RP).

Ceftiolene (42980RP) is a new cephalosporin with a broad antibacterial spectrum similar to cefotaxime or ceftriaxone. The characteristics of ceftiolene have been tested in a variety of assays involving various biochemical aspects of the mode of action of beta-lactam antibiotics. The affinities of ceftiolene for penicillin-binding proteins were very comparable with those of ceftriaxone and cefotaxime for Escherichia coli, and generally greater than those of latamoxef (moxalactam) for the higher molecular weight PBPs of E. coli. Enterobacter cloacae. Proteus mirabilis and Pseudomonas aeruginosa. The affinity of ceftiolene for PBP1 of Staphylococcus aureus was greater than those of cefotaxime or latamoxef, but comparable with these antibiotics for PBP3. The bacteriolytic activity of ceftiolene at defined concentrations against Gram-negative organisms was similar to that of ceftriaxone, and significantly better than that of the other third-generation cephalosporins tested. Introduction of plasmid-encoded beta-lactamases into E. coli reduced the wide variation in bacteriolytic effect of the different cephalosporins, and a significant inoculum effect was observed for the bacteriolysis. Chloramphenicol was less antagonistic against ceftiolene- or ceftriaxone-induced lysis than was observed for cefotaxime or latamoxef. Growth of Staph. aureus at low concentrations of ceftiolene caused the bacteria to become more sensitive to lysis by lysostaphin than organisms grown with cefotaxime or latamoxef under the same conditions. These observations confirm the necessity to use techniques other than routine MIC determinations to distinguish between antibiotics which would otherwise appear very similar.

Anti-Bacterial Agents↗

PubMed1984

[Bacteriostatic activity of apalcillin on Gram-negative bacilli and strict anaerobic bacteria. Multicenter study].

This work reports a multicenter study of the bacteriostatic activity of apalcillin, a new N-acyl-penicillin, against 1 827 clinical isolates of Gram-negative bacilli and obligate anaerobes. The modal minimal inhibitory concentrations (MICs) for susceptible strains are (mg/l) : Salmonella-Shigella : 1 ; E. coli : 0.5-2 ; Klebsiella : 4 ; Citrobacter : 1-2 ; Enterobacter : 2 ; Serratia : 8 ; Proteus-Providencia : 1 ; Acinetobacter : 1-4 ; P. aeruginosa : 2 ; H. influenzae : 0.06 ; C. perfringens : 0.03-01 ; Peptococcus : 0.2 ; B. fragilis : 16. Against Enterobacteriaceae and Acinetobacter, apalcillin is as active as mezlocillin and piperacillin, and much more than carbenicillin. Against P. aeruginosa, apalcillin is the most active penicillin : 2 to 16 fold more active than azlocillin and piperacillin, and 2 to 128 fold more active than ticarcillin. Against H. influenzae, C. perfringens and Peptococcus, apalcillin has MICs similar to those of other N-acyl penicillins, and inferior to those of carboxypenicillins . Apalcillin, as other penicillins, is poorly active against B. fragilis.

Ampicillin↗

PubMed1984

[Multicenter study of the antibacterial activity of a new cephalosporin: CM 40874].

Minimal inhibitory concentrations (MIC) of CM were evaluated on 2 548 bacterial strains isolated in 8 hospitals. CM demonstrated high activity on Enterobacteriaceae, the MIC being less than or equal to 0.125 micrograms/ml for 71% of the 1 362 strains tested, less than or equal to 1 for 99.6%, and less than or equal to 4 for 99.9%. Mode MIC varies little among the different groups of Enterobacteriaceae (from 0.06 to 0.12 micrograms/ml), with the exception of Serratia sp. (mode MIC : 0.25) and Klebsiella oxytoca (mode MIC : 0.03). Most of Enterobacter, Serratia, and Citrobacter sp. strains not inhibited by cefotaxime are readily inhibited by CM at the same concentrations than susceptible strains. CM has less activity on P. aeruginosa (MIC 2-32 micrograms/ml) and Acinetobacter sp. (MIC 8-128). Staphylococci (MIC 32) and Enterococci are not susceptible. Variable activity is found against other Streptococci. CM inhibits Haemophilus sp. at MICs of 0.12 to 0.5 micrograms/ml and Gonococci at MICs of 0.03 to 0.5 (whether the strains produce beta-lactamase or not). Meningococci have a mode MIC of 0.03 micrograms/ml (range 0.008 to 0.25). Thus, CM 40874 is a new third generation cephalosporin with high activity on Enterobacteriaceae, including those strains not susceptible to cefotaxime and good activity on Haemophilus sp. and Neisseria sp. This additional activity is probably supported by enhanced resistance to enzymatic inactivation by beta-lactamases.

Bacteria↗

PubMed1984

[Meningitis in otologic surgery of acoustic neurinoma].

Bacterial meningitis following operation for ablation of acoustic neurinoma is a rare but always possible complication. Of 350 cases of neurinoma operated upon between 1965 and 1982, this postoperative lesion was reported in eleven patients (3.4 p. 100). Recovery occurred in all cases without sequelae. Mode of onset, symptoms and signs, curative therapy and preventive factors are discussed.

Adult↗

PubMed1983

Pharmacokinetics of single intravenous and intramuscular doses of cefotetan in normal human volunteers.

The pharmacokinetic parameters of cefotetan were determined in six healthy adults after intramuscular (im) and intravenous (iv) administration of a single dose. After an iv bolus injection of 1 g cefotetan the mean peak serum level was 179.6 mg/l (S.E.M. +/- 14.2 mg/l) at 2 min. The apparent volume of distribution was 10.29 l (S.E.M. +/- 0.66 l). After im injections of 500 mg and 1 g of cefotetan the mean peak levels were 35 mg/l (S.E.M. +/- 1.6 mg/l) and 74 mg/l (S.E.M. +/- 3.6 mg/l) at 82 and 97 min respectively; the level at 12 h was 4.5 mg/l after 500 mg and 10.4 mg/l after 1 g. Cefotetan was slowly eliminated. The serum half-life was about 3.1 h after 1 g iv injection and varied from 3.4 to 3.7 h after the 500 mg and 1 g im injections. About 75% of the dose was excreted in the urine during the first 24 h after 1 g iv bolus injection; after 500 mg and 1 g im injection 60 to 65% of the dose was recovered in the urine during the same time period.

Adult↗