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Biomedical subjects

M J Giménez

Publications and source records attributed to M J Giménez.

At least 19 recordsLinked to original sources

[Activity of cefpodoxime and other oral beta-lactams against Haemophilus influenzae and Streptococcus pneumoniae with different susceptibilities to penicillin].

This study explores the influence on the intrinsic activity of different oral beta-lactams of beta-lactamase production in Haemophilus influenzae and penicillin resistance in Streptococcus pneumoniae. Three substudies were performed: a) a general susceptibility study, analyzing 550 strains received by the Spanish Laboratorio de Referencia de Neumococos throughout February and March 2005; b) a study on the influence of penicillin resistance on the activity of beta-lactams, analyzing 251 penicillin-susceptible strains (MIC or=2 mg/l) randomly chosen among those received by the Spanish Laboratorio de Referencia de Neumococos throughout 2005; and c) an H. influenzae susceptibility study analyzing 150 strains received by Instituto Valenciano de Microbiologia throughout 2005. A total of 71% of S. pneumoniae strains were susceptible to penicillin, 21% exhibited intermediate resistance and 8% strains presented full resistance. H. influenzae beta-lactamase production rate was 18.6%. Of the non-beta-lactamase-producing strains, 3% were not susceptible to ampicillin. Cefpodoxime and cefixime exhibited the highest intrinsic activity against H. influenzae, while amoxicillin and cefpodoxime were the most active compounds against S. pneumoniae. All H. influenzae strains were susceptible to oral cephalosporins and amoxicillin/clavulanic acid. The increase in penicillin resistance in S. pneumoniae influenced cefixime, cefaclor and cefuroxime to a higher degree than amoxicillin and cefpodoxime.

Ceftizoxime↗

In vivo activity of gemifloxacin, moxifloxacin and levofloxacin against pneumococci with gyrA and parC point mutations in a sepsis mouse model measured with the all or nothing mortality end-point.

A dose-decreasing immunocompetent sepsis mouse model was used to evaluate the in vivo effect of levofloxacin, moxifloxacin and gemifloxacin, using a ciprofloxacin/levofloxacin susceptible serotype 6B strain (ciprofloxacin MIC: 1 mg/l) and two resistant serotype 14 and 19F strains with gyrA and parC point mutations (ciprofloxacin MICs of 32 and 64 mg/l, respectively). Significant higher in vivo activity was found for moxifloxacin and gemifloxacin than for levofloxacin against strains 1 and 2, and for gemifloxacin versus moxifloxacin or levofloxacin against strain 3. Gemifloxacin treatment resulted in 100% survival against strains 1 and 2(AUC0-24 h/MIC of 30 and 62) but against strain 3, survival was 60-80% (AUC0-24 h/MIC of 93). Similar AUC0-24 h/MIC values produced different therapeutic results suggesting that in vitro parameters other than the MIC could influence efficacy predictions based on in vitro susceptibility tests (MICs) or pharmacodynamic parameters (AUC0-24 h/MIC).

Animals↗

[From knowledge of bacterial etiology to the treatment and prevention of the most prevalent infections in the community: odontological infections].

The prevalence of community odontological infections and their relevance to public health were reviewed. Knowledge of bacterial etiology (and the transmittability of these microbial agents) was used to study the disease (individual susceptibility to etiological agents) in order to review the effect of treatment on odontological pathogens and human microbials. The synergy between the primary care physician and the dentist is fundamental to the control of this endemic disease.

Anti-Bacterial Agents↗

Effects of amoxicillin subinhibitory concentrations on the cross-protection developed by pneumococcal antibodies in mouse sepsis caused by an amoxicillin-resistant serotype 6B Streptococcus pneumoniae strain.

A model of mouse sepsis caused by a serotype 6B Streptococcus pneumoniae strain (amoxicillin MIC of 8 microg/ml) was developed to investigate the therapeutic effect of an amoxicillin dose (3.12 mg/kg of body weight three times daily for 48 h) producing, over the whole treatment period, subinhibitory concentrations in serum (peak concentration [C(max)]: 6.1 microg/ml) in animals that prior to infection had been passively immunized with a 6B or 23F hyperimmune serum (obtained by immunization with a whole-cell heat-inactivated inoculum and diluted to produce no protective effect by itself). Mortality in nonimmunized animals treated with antibiotic (3.12 mg/kg) was 90%, and mortality in animals immunized but not treated with the antibiotic was 100%. Antibiotic treatment in immunized animals produced mortality rates </=20% when the hyperimmune serum was used, thus showing cross-protection and synergism (defined as the situation in which there is no response to the single agents [no differences versus placebo] while the combination exhibits significant activity) with subinhibitory concentrations of the antibiotic. The presence of antipneumococcal antibodies allowed antibiotic efficacy with negligible values of pharmacodynamic parameters (C(max)/MIC ratio of <1 and thus a null value for the time that serum levels exceed the MIC). This in vivo synergism offers a potential therapeutic strategy against resistant strains.

Amoxicillin↗

Opsonophagocytosis versus complement bactericidal killing as effectors following Neisseria meningitidis group C vaccination.

BACKGROUND: Opsonophagocytosis and complement-mediated Neisseria meningitidis killing after vaccination were investigated. METHODS: Twelve seronegative healthy volunteers received one dose of polysaccharide A/C vaccine and were followed for 3 years. Ex vivo serum killing rates with polymorphonuclear cells (PMN) and/or complement were performed at 0, 1.5, 6, 12, 18, 24, 30 and 36 months. RESULTS: High mean total and median bactericidal antibodies were detected over time in all subjects. Considerable reduction of the initial inoculum was obtained only in the presence of complement, with or without PMN (with significant differences compared to curves without complement) a long time after vaccination. CONCLUSION: PMN did not increase post-vaccination bacterial killing, suggesting that antibody complement-mediated killing, and not opsonophagocytosis, is the main immune effector of the vaccine protection against N. meningitidis.

Blood Bactericidal Activity↗

Efficacy and pharmacodynamics of gemifloxacin versus levofloxacin in guinea pig pneumococcal pneumonia induced by strains with decreased ciprofloxacin susceptibility.

Quinolone in vivo bactericidal activity was investigated in a guinea pig pneumonia model using three Streptococcus pneumoniae strains with decreasing susceptibility to ciprofloxacin. Treatment regimens resulted in values of AUC(0-24 h) and C(30 min) similar to those of standard oral regimens in human serum. Efficacy was defined as a significant difference in number of viable bacteria in the lungs compared with the control. Ciprofloxacin, levofloxacin and gemifloxacin were effective against the levofloxacin-susceptible strain. Only gemifloxacin achieved a >/=99.9% reduction versus control against the levofloxacin intermediate-resistant strain. Gemifloxacin achieved a 99.69% reduction and was the only quinolone significantly different from the control (P<0.05) against the levofloxacin-resistant strain. Gemifloxacin offers in vivo activity against ciprofloxacin- to levofloxacin-resistant pneumococci.

Animals↗

Introgression of 1Dx5+1Dy10 into tritordeum.

The uses of hexaploid tritordeum as a crop for human consumption require improvement of its bread-making quality. For this purpose chromosome 1D of bread wheat with the Glu-D1 allele encoding for high-molecular-weight glutenin subunits Dx5+Dy10 was introgressed into tritordeum. Different primary tritordeums were crossed with wheats carrying subunits Dx5+Dy10. The hybrids were backcrossed to tritordeum and seeds for the next backcross (or selfing) were selected for the presence of chromosome 1D using SDS-PAGE. Forty two chromosome plants carrying subunits Dx5+Dy10 were obtained after two backcrosses and selfing. Chromosome characterization of these plants using fluorescence in situ hybridisation (FISH) proved that either chromosome substitution 1H(ch)/1D or 1A/1D had been obtained. A homozygous plant with a translocation of the entire 1DL arm to 1H(ch)S was also obtained. The complete chromosome substitution lines have better agronomic characteristics than the lines with translocations.

Alleles↗

Modification of bacteraemia by specific antibodies and relation with mortality in a pneumococcal mouse sepsis model.

The relationship between mortality and the bacteraemic profile was investigated in a pneumococcal (serotype 6B) sepsis BALB/c mouse model where animals received protection by specific hyperimmune serum. A single intraperitoneal dose of hyperimmune serum obtained from mice immunized with the heat-inactivated strain was administered (non-diluted or diluted to 1/4 or to 1/16) to 5-mice study groups 1 h prior to intraperitoneal inoculation with the infective inoculum (3.57 x 108 cfu/ml). Blood cultures were performed daily over 15 days, with 8 microl of blood being collected from the tail vein; the samples were resuspended in Todd-Hewitt broth containing 10% trisodium citrate and plated onto blood agar for colony counting. Animals included in the control group received placebo (PBS). Mortality was 100% in control animals within the first 48 h. Hyperimmune serum decreased and delayed mortality in a dose-related trend, producing 100%, 80%, 60% and 40% survival rates at 72, 96, 144 and 360 h, with non-diluted serum. Bacteraemic profiles with maximum colony counts > or =5 x 107 cfu/ml in blood during the follow-up period were related to > or =65% probability of death, regardless of the serum dilution administered.

Animals↗

Beta-lactam modification of the bacteraemic profile and its relationship with mortality in a pneumococcal mouse sepsis model.

A sepsis BALB/c mice model was used to investigate the relationship between mortality and the bacteraemic profile produced by a serotype 6B Streptococcus pneumoniae clinical isolate (MIC/MBC of amoxicillin 4/4 mg/L and of cefotaxime 2/4 mg/L). Animals were treated subcutaneously with doses of amoxicillin or cefotaxime ranging from 6.25 to 50 mg/kg tds for 48 h, starting 1 h after intraperitoneal inoculation (2 x 10(7) cfu/mouse). Blood cultures were carried out daily over 15 days. A survival rate of 100% was obtained with amoxicillin 25 mg/kg and of 60% with cefotaxime 50 mg/kg. A statistically significant (P = 0.012) relationship was found between the maximum cfu/mL in blood and mortality. A maximum log cfu/mL of 6.5 was associated with an 84% probability of death.

Animals↗