PubMed Health⌕ Search

Biomedical subjects

M D Kitzis

Publications and source records attributed to M D Kitzis.

At least 37 records · Page 2Linked to original sources
PubMed1995

SYN987, SYN1193, and SYN1253, new quinolones highly active against gram-positive cocci.

SYN987, 1193 and 1253 are new fluorinated quinolones with enhanced activity against Gram-positive bacteria. The MICs of SYN 987, 1193 or 1253 were studied by an agar dilution method against 88 streptococci (including penicillin resistant Streptococcus pneumoniae), 30 enterococci and 62 Staphylococcus aureus. SYN 987, 1193 and 1253 were 2 to 4 times more active than sparfloxacin and 16-64 times more active than older fluoroquinolones against all streptococci and ciprofloxacin-resistant S. aureus. This study demonstrates that SYN 987, 1193 and 1253 are extremely potent antibacterial agents which deserve further evaluation.

Anti-Infective Agents↗
PubMed1995

Nebulizer performance: AFLM study. Association Française de Lutte contre la Mucoviscidose.

This study was conducted by the AFLM order to determine the performance characteristics of 12 commercially available nebulizers (6 ultrasonic and 6 jet) used in the treatment of cystic fibrosis (CF). The nebulizers were connected to a circuit which simulated the ventilation of a CF child and CF adult, and were tested using three drug solutions: tobramycin (T), colistin (C), and amiloride (A). Nebulizer performance was evaluated according to the volume of drug solution delivered in 10 min during the simulated inspiratory phase (VI), drug granulometry (G%), drug concentration modification in the nebulizer reservoir (delta C), and percentage of efficiently aerosolized drug EA%). The ultrasonic devices delivered a significantly higher VI than the jet nebulizers (p < 0.0001) for all three study drug. Ventilation rate did not influence VI. Regarding granulometry, higher percentages of T and A were found to be contained in droplets ranging from 0.5 to 5.0 micron following ultrasonic nebulization. Drug concentration modifications were independent of the nebulizer used but were influenced by drug type; overconcentrations of T and A were observed (delta C = +10.5 +/- 18.6 and +13.4 +/- 8.9%, respectively). On average, the ultrasonic devices achieved a higher EA% than the jet nebulizers (17.3 +/- 6.7 and 9.7 +/- 9.6%, respectively). This study highlights the significant variability in performance of different nebulizer types and empahsizes the importance of accurately testing nebulizers prior to clinical use so that the most efficacious nebulizer/drug combinations may be prescribed.

Administration, Inhalation↗
PubMed1994

Mechanisms of failure to decontaminate the gut with polymixin E, gentamicin and amphotericin B in patients in intensive care.

The objective of the present work was to assess the possible mechanisms of the poor efficiency of selective decontamination of the digestive tract (SDD) in medical and surgical intensive care unit (ICU) patients. Sixty-four consecutive mechanically ventilated patients received gut decontamination with polymixin E, gentamicin and amphotericin B via a nasogastric tube and were assessed for oropharyngeal, gastric and fecal colonization and for the presence of each antibiotic in the stomach and feces. A decrease in fecal colonization with Escherichia coli was observed over 20 days but not with other gram-negative bacteria or gram-positive cocci. Fifteen and 26% of the fecal colonizing gram-negative bacteria were resistant to polymixin E and gentamicin, respectively, at admission. These proportions increased to up to 50% after 16 days of treatment. Although 50% of staphylococci were initially sensitive to gentamicin, all strains were resistant to this drug after four days of SDD. Both antibiotics were found in concentrations of less than 20 micrograms/g in 11 of 38 stools. Of these 38 stools, nine were not contaminated, 20 were colonized with resistant bacteria and 16 with strains sensitive to one antibiotic present in the stool. Therefore, the poor efficiency of gut decontamination observed was probably due to the great proportion of resistant strains on admission of the patients, to the selection of such resistant strains with SDD, to poor intestinal transit of the antibiotics, and to inactivation of the drugs by the feces. These results support stringent monitoring of fecal colonization in patients undergoing SDD in order to detect the fecal carriage of gram-positive and multiresistant gram-negative bacteria.

Adult↗
PubMed1994

Different ratios of the piperacillin-tazobactam combination for treatment of experimental meningitis due to Klebsiella pneumoniae producing the TEM-3 extended-spectrum beta-lactamase.

We evaluated the pharmacokinetics and therapeutic efficacies of piperacillin and tazobactam, a beta-lactamase inhibitor, given either alone or in different combinations (80:10, 200:10, and 80:25 mg/kg/h), in experimental meningitis due to a strain of Klebsiella pneumoniae producing the TEM-3 extended-spectrum beta-lactamase. Treatment was administered intravenously as a 7-h constant infusion preceded by a bolus of 20% of the total dose. The mean (+/- standard deviation) rates of penetration into the cerebrospinal fluid (CSF) of infected animals were 6.7 +/- 3.9% for piperacillin given alone and 36.3 +/- 21.9% for tazobactam given alone. Combination treatment significantly magnified the concentration of either drug in CSF. Concentrations of bacteria in CSF increased throughout therapy in animals given either drug alone, even at high dosages. In animals given the combination at dosages of 80:10 and 200/10 mg/kg/h, only a suboptimal reduction of CSF bacterial titers was obtained in vivo, i.e. -0.49 +/- 0.34 and -0.73 +/- 0.49 log CFU/ml/h, respectively. An increase in the tazobactam dosage within the combination (80:25 mg/kg/h) was required in order to obtain a significantly faster elimination of viable organisms from the CSF (-0.97 +/- 0.35 log CFU/ml/h). The study shows that tazobactam is able to provide effective protection against piperacillin hydrolysis by the TEM-3 enzyme within the CSF. Appropriate dosage regimens of various beta-lactam-tazobactam combinations may deserve comparative studies in experimental meningitis caused by organisms producing extended-spectrum beta-lactamases.

Animals↗
PubMed1994

Emergence of clinical isolates of Escherichia coli producing TEM-1 derivatives or an OXA-1 beta-lactamase conferring resistance to beta-lactamase inhibitors.

Sixteen Escherichia coli clinical isolates which were resistant to ampicillin and amoxicillin-clavulanate but susceptible to cephalothin were studied. Eight strains showed the presence of a beta-lactamase which comigrates with reference OXA-1 enzyme. The eight other strains produced different TEM-1 derivatives which had in common a higher Km for penicillins and a higher 50% inhibitory concentration for the beta-lactamase inhibitors. By oligotyping and sequencing of PCR products, it was shown that Ser (AGC) (TEM-30; also called TRI-1) in three strains and Cys (TGC) (TEM-31; also called TRI-2) in one strain were substituted for Arg-241 (CGC), that Leu (CTG) (TEM-33) and Val (GTG) (TEM-34) in one strain each were substituted for Met-67 (ATG), and that in other mutants the two latter substitutions occurred together with the substitution of Asp (GAT) (TEM-35 and TEM-36) for Asn-272 (AAT). Therefore, different sets of amino acid substitutions of TEM-1 can be found in clinical isolates and lead to resistance to beta-lactamase inhibitors.

Amoxicillin↗
PubMed1994

N,N-dimethylglycyl-amido derivative of minocycline and 6-demethyl-6-desoxytetracycline, two new glycylcyclines highly effective against tetracycline-resistant gram-positive cocci.

The in vitro activities of the N,N-dimethylglycyl-amino derivative of minocycline (DMG-MINO) and 6-dimethyl-6-dexoxytetracycline (DMG-DMDOT), members of a new generation of tetracyclines, were evaluated by an agar dilution method and were compared with those of tetracycline and minocycline against 224 tetracycline-resistant and 73 tetracycline-susceptible recent clinical isolates of gram-positive cocci, including multiple-antibiotic-resistant methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. The MICs of DMG-MINO and DMG-DMDOT were up to 500- to 2,000-fold lower than those of tetracycline against methicillin-resistant S. aureus and Streptococcus pneumoniae (MIC for 50% of strains tested [MIC50], < 0.06 microgram/ml). Against Streptococcus groups A, B, C, and G and Enterococcus faecalis, the MIC50 was 0.5 microgram/ml. MIC50s were greater only for coagulase-negative staphylococci (2 micrograms/ml). These data indicate that DMG-MINO and DMG-DMDOT are very potent drugs, and further in vitro and in vivo studies are warranted.

Coagulase↗
PubMed1994

[In vitro antibacterial activity of a new fluoroquinolone, fleroxacin, against hospital bacteria and regression curve].

Minimal inhibitory concentrations (MICs) of fleroxacin (FLE) were determined by agar dilution for 1261 bacterial strains isolated in 1992 in 4 university hospitals; in addition, antibiograms by agar diffusion were performed with 5 micrograms disks. Activity of FLE against nalidixic acid (NAL) susceptible (S) Enterobacteriaceae was close to that of other fluoroquinolones (FQ) (MIC 50 and 90: 0.12-0.25 micrograms/ml); like for other FQ, this activity was reduced against NAL intermediate and resistant (R) Enterobacteriaceae (4-32). MICs of FLE against P. aeruginosa were between 1 and 128 (8-128). FLE had also a good activity against NAL-S A. baumannii (0.12-0.5) but this activity is reduced against NAL-R Acinetobacter (64-128). FLE was highly active against Haemophilus (0.06-0.12), Gonococci (0.03-0.25), Meningococci (0.016-0.03) and B. catarrhalis (0.12-0.25). FLE showed activity close to the currently available FQ against methicillin susceptible Staphylococci (0.25-1); the resistant strains (32- > 128) are usually methicillin resistant. FLE is less effective against Enterococci (4-128), Streptococci (8-16) and Pneumococci (4-8). The coefficient correlation of the regression curve is 0.93; for MIC breakpoints of 1 and 4 micrograms/ml, zone diameter breakpoints should be 20 and 15 mm.

Dose-Response Relationship, Drug↗
PubMed1994

[Antibacterial activity of ciprofloxacin in the urine during four days after a single 500 mg and 750 mg oral dose].

Antibacterial activity of ciprofloxacin was studied in the urine after a single 500 mg and 750 mg oral dose in ten healthy female volunteers. Urine was collected, after each single oral dose, during seven time periods: 0-3 h, 3-6 h, 6-12 h, 12-24 h, 24-48 h, 48-72 h, 72-96 h. Ciprofloxacin concentrations were assayed by microbiological method. Urine antibacterial activity was determined for five bacterial strains isolated in urine: 2 E. coli strains, one sensitive and the other resistant to nalidixic acid (Nal-A), 1 Klebsiella pneumoniae resistant to nalidixic acid (Nal-B), 1 Staphylococcus saprophyticus and 1 Enterococcus faecalis. MICs of ciprofloxacin against these strains were respectively 0.003, 0.06, 0.25, 0.06 and 0.5 micrograms/ml. Ciprofloxacin mean concentrations in the seven urine samples were 292.5 +/- 55.8, 81.1 +/- 16.9, 43.7 +/- 11.6, 11.5 +/- 1.9, 1.3 +/- 0.2, 0.3 +/- 0.05 et 0.1 +/- 0.05 micrograms/ml after a single 500 mg oral dose and 215.1 +/- 68.1, 56.1 +/- 17.8, 43 +/- 8.8, 14.4 +/- 5.5, 1.4 +/- 0.2, 0.4 +/- 0.1 and 0.2 +/- 0.05 micrograms/ml after a single 750 mg oral dose. Urine bacteriostatic activity was not very different after a 500 mg dose and a 750 mg dose. Against enterobacteriacae, after a 500 mg dose it was > or = 16 the first day; it was > or = 512 for the Nal-S E. coli. It was > or = 64 the first day, and remained between 2 and 32 the second day for the Nal-R strains (E. coli and Klebsiella).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Activity of the beta-lactamase inhibitor BRL 42715 against cephalosporinases produced by Enterobacteriaceae.

BRL 42715, a novel beta-lactamase inhibitor, was evaluated for its capacity to inhibit cephalosporinases. BRL 42715 was effective in potentiating the activity of antibiotics against clinical isolates of Enterobacteriaceae that produced high levels of cephalosporinases. This correlated well with the very low 50% inhibition values (< 0.004 mg/L) of BRL 42715 for cephalosporinases extracted from different species. When compared in vitro to clavulanic acid, sulbactam, and tazobactam, BRL 42715 was the most efficient inhibitor of cephalosporinase.

Anti-Bacterial Agents↗
PubMed1993

Susceptibility survey of piperacillin alone and in the presence of tazobactam.

Among 325 fresh isolates of bacteria from 153 hospital patients with serious infections, 142 were susceptible to piperacillin, 129 were resistant and a further 54 exhibited a marked inoculum effect. Tazobactam restored the susceptibility of resistant isolates of Staphylococcus aureus and Staphylococcus epidermidis (except methicillin-resistant isolates), Haemophilus influenzae, Moraxella catarrhalis, Acinetobacter spp. and Bacteroides fragilis. Among 87 Enterobacteriaceae that were resistant to piperacillin, or showed an inoculum effect, 78 (89%) were restored to susceptibility by tazobactam. Pseudomonas spp. resistant to piperacillin were mostly resistant to the combination.

Bacteria↗
PubMed1992

Daptomycin or teicoplanin in combination with gentamicin for treatment of experimental endocarditis due to a highly glycopeptide-resistant isolate of Enterococcus faecium.

Using an experimental endocarditis model, we studied the activity of daptomycin used alone or in combination with gentamicin against an Enterococcus faecium strain that was highly resistant to glycopeptides and susceptible to gentamicin. In vitro, the MIC of daptomycin was 1 micrograms/ml. In vivo, daptomycin appeared to be effective only when it was used in a high-dose regimen, i.e., 12 mg/kg of body weight every 8 h (-2.5 log10 CFU/g versus controls; P < 0.05), particularly when it was combined with gentamicin (-5.0 log10 CFU/g versus controls; P < 0.01). Since the distribution of daptomycin into cardiac vegetations, as evaluated by autoradiography, appeared to be homogeneous, the poor in vivo activity of daptomycin was considered to be related to its high degree of protein binding, as suggested by killing curves studies. Since the MIC of teicoplanin for the vancomycin-resistant E. faecium strain used in the study was only 64 micrograms/ml and since an in vitro synergy between teicoplanin at high dose and gentamicin was observed, a high-dose regimen of teicoplanin, i.e., 40 mg/kg every 12 h, was also assessed in vivo. This treatment provided marginal activity only when it was combined with gentamicin (-2.3 log10 CFU/g versus controls; P < 0.05). These results suggest that the levels of daptomycin or teicoplanin in serum required to cure experimental endocarditis caused by a highly glycopeptide-resistant strain of E. faecium would not be achievable in humans.

Animals↗
PubMed1991

Association of two resistance mechanisms in a clinical isolate of Enterobacter cloacae with high-level resistance to imipenem.

Carbapenem resistance was studied in a clinical isolate of Enterobacter cloacae, strain 201 (MIC of imipenem and meropenem, 16 micrograms/ml). This strain was analyzed comparatively with the carbapenem-susceptible parent strain 200, an equally susceptible revertant, 201-Rev, and in vitro-selected mutants with different levels of carbapenem resistance. All strains produced similarly high amounts of the same cephalosporinase (pIapp = 8.8). Strain 201 apparently lacked two major outer membrane proteins of ca. 37 and 38 kDa, while 201-Rev produced only the 37-kDa protein. The permeability coefficient, determined with cephaloridine, was reduced up to ninefold in the resistant strains which also showed a substantial reduction in the uptake of [14C]meropenem. The introduction of the plasmid-borne ampD gene (whose product decreases the expression of ampC) resulted in almost complete cessation of cephalosporinase production in all strains and a substantial decrease in the MICs of the carbapenems which remained, however, 8- to 16-fold higher than those determined for the susceptible strains containing the ampD gene. This "residual" resistance was attributed to reduced outer membrane permeability. The contribution of cephalosporinase production was verified in a reverse experiment, in which the introduction of ampC into a low-level cephalosporinase producer resulted in a fourfold increase in the carbapenem MICs. From these results, we infer that reduced outer membrane permeability and high-level cephalosporinase production can operate in conjunction in clinical isolates of E. cloacae to confer imipenem resistance.

Bacterial Outer Membrane Proteins↗
PubMed1991

[In vitro antibacterial activity of piperacillin-tazobactam combination on hospital isolates and regression curve].

Minimal inhibitory concentrations (MICs) of piperacillin (P) in combination with 4 micrograms/ml of tazobactam (T) were evaluated by agar dilution for 1,245 strains isolated in 4 hospitals. In addition antibiograms by agar diffusion were performed with disks loaded of 75 micrograms of P + 10 micrograms of T. For naturally non beta-lactamase producing Enterobacteriaceae (E), MIC 50 and 90% of P + T were (microgram/ml): E. coli 1-2; P. mirabilis: 0.5-1; activity was practically identical on plasmid mediated penicillinase (Pase) producing strains. Strains of K. pneumoniae only resistant (R) to amino- and carboxypenicillins (C) had MICs less than or equal to 4 (mode MIC 2); MICs of strains R to cephalothin and/or cefotaxime were 2 to 16 (mode MIC 4). For chromosomal cephalosporinase (Case) producing species, MICs of P + T were less than or equal to 8, including for acquired Pase producing strains, but were greater than or equal to 16 for Case hyperproducing strains. Strains of P. aeruginosa susceptible (S) to C were inhibited by 1 to 16 (with MIC 4) and strains R to C by 8 to greater than 128. MICs were generally 2 to 32 for A. baumannii S to C at 0.12 to greater than 128 for strains R to C. Haemophilus, S or R to ampicillin, were inhibited by 0.008 to 2 (MIC 50 and 90: 0.016-0.12). S. aureus S to methicillin (M), Pase producing on not, were inhibited by 0.5 to 2 (mode MIC 1) and strains R to M by 8 to greater than 128. Activity of P + T for coagulase-Staphylococci was similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Acinetobacter↗
PubMed1991

[In vitro antibacterial activity of a new fluoroquinolone, temafloxacin, against hospital isolates. Results of a multicenter study].

Minimal inhibitory concentrations (MICs) of temafloxacin (TMF) was determined by agar dilution for 2,510 bacterial strains isolated in 1989 in 9 university hospitals. Activity of TMF against nalidixic acid (NAL) susceptible (S) Enterobacteriaceae was close to that of other fluoroquinolones (FQ) (mode MIC: 0.06 micrograms/l); like for other FQ, this activity was reduced against NAL intermediate (mode 1) and resistant (R) (mode 4) Enterobacteriaceae. MICs of TMF against P. aeruginosa were between 0.12 and 128 (mode 0.5-1). TMF had also a good activity against NAL S A. baumannii (mode MIC: 0.06-0.12) but this activity is reduced against NAL R Acinetobacter (mode MIC: 16). TMF was highly active against Haemophilus mode MIC: less than or equal to 0.008), Gonococci (mode MIC: 0.008-0.032), Meningococci (mode MIC: 0.08) and B. catarrhalis (mode MIC: 0.016). TMF showed better activity to other fluoroquinolones against methicillin susceptible Staphylococci (mode MIC: 0.06); the resistant strains (mode MIC: 8) are usually methicillin resistant. Comparatively to the currently available FQ, TMF is so more effective against Enterococci (mode MIC: 1), Streptococci (mode MIC: 0.5-1) and Pneumococci (mode MIC: 0.5). Finally, for the anaerobic bacteria, TMF is more active against C. perfringens (mode MIC: 0.5) than against B. fragilis (mode MIC: 2).

4-Quinolones↗