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Biomedical subjects

M L Gómez-Lus

Publications and source records attributed to M L Gómez-Lus.

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↗

Activity of oral antibiotics against respiratory tract pathogens in Spain.

The aim of this study was to carry out a nationwide survey to assess the susceptibility of clinical isolates of four respiratory pathogens against nine antibiotics. Eight Spanish centers participated in the study, collecting a total of 977 isolates of Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae and Moraxella catarrhalis. The susceptibility of S. pneumoniae to penicillin was 37.46% susceptible, 30.43% intermediate and 32.11% resistant. MIC(90) of all antibiotics against this microorganism were 48 mg/l, except cefaclor, cefixime and azithromycin. For S. pyogenes, all the strains were susceptible to penicillins and cephalosporins, and azithromycin was the least active with a rate of resistance of 11.43%. A total of 95 isolates of H. influenzae were betalactamase positive (26.32%). With regard to M. catarrhalis, only penicillin and amoxicillin showed MICs(90) >=8 mg/l.

Administration, Oral↗

Antimicrobial resistance: a class effect?

Antibiotic use has led to increased resistance to certain group markers: penicillin, erythromycin and ciprofloxacin for beta-lactams, macrolides and quinolones, respectively. The influence of resistance to markers in decreasing susceptibility to the drugs included (on the basis of chemical structure) in the corresponding antibiotic group can be defined as 'resistance class effect'. In the case of macrolides, this effect is dependent on the prevalent resistant phenotype among the isolates of the target bacteria: the class effect exists completely if the mechanism of resistance is constitutive MLS(B) (all macrolides are affected by resistance to erythromycin), and only partially if the mechanism is the efflux M phenotype (all but 16-membered macrolides are affected). In Spain, the first case is exemplified by Streptococcus pneumoniae and the second by Streptococcus pyogenes. For beta-lactams and quinolones, resistance to the group markers results in large decreases in the antimicrobial activity of the less potent members of the group, penicillin being a better driver of resistance for oral cephalosporins than for aminopenicillins, and ciprofloxacin being a better driver for older rather than for the newer quinolones, which have enhanced anti-pneumococcal activity. Empirical prescription guidelines based on the pharmacoepidemiology of resistance, recommending the use of potent drugs that are less influenced by resistance to the marker, may help to counter the spread of resistance in the community.

4-Quinolones↗

Evaluation of two in vitro pharmacodynamic simulation models: microfiltration versus centrifugation-filtration.

Pharmacodynamic in vitro models that simulate serum antimicrobial concentrations provide more information about the activity of an antibiotic than MICs or traditional time-kill methods. The aim of this study was to compare two pharmacodynamic simulation models using ATCC strains of five different species and five antibiotics. In the first model (Centriprep-10 system), a filtration-centrifugation process was used to eliminate the antibiotic; in the second model (microfiltration system) no centrifugation was necessary. The antibiotic concentrations tested were similar to those in serum after normal doses of cefuroxime, clarithromycin, ciprofloxacin, gentamicin and cefotaxime. No significant differences were observed in the killing rates between the models except in the case of Haemophilus influenzae and cefotaxime. The new microfiltration model had the following advantages: lack of the carry-over effect, the absence of centrifugation that could damage bacteria and the possibility of increasing the number of incubation periods to give a better fit of the kinetic profile of man.

Anti-Bacterial Agents↗

[Activity of new fluoroquinolones against clinical isolates of Acinetobacter baumannii].

Acinetobacter baumannii is an opportunistic pathogen associated with numerous nosocomial infections. In recent years it has shown extraordinary ease in developing resistance to most antimicrobial agents, which is a serious problem as it makes these infections difficult to treat. We determined the in vitro activity of eight quinolones, five betalactam agents and colistin in 160 clinical isolates of A. baumannii. In general, we observed a high rate of resistance to the quinolones (90%), excluding clinafloxacin (25%), and to ampicillin-sulbactam (61.25%) and imipenem (50%). Colistin is the agent with least resistance (13.125%), although its toxicity limits its therapeutic use. Clinafloxacin may be a good option to treat A. baumannii infections, especially in cases of therapeutic failure with other antimicrobial agents.

Acinetobacter↗

Ex vivo bactericidal activity against group C Neisseria meningitidis in seronegative subjects.

BACKGROUND: To determine the anti-meningococcal C immunological activity by adding functional tests (opsonophagocytosis) to the classical serology techniques. SUBJECTS AND METHODS: 42 adult volunteers were screened using serological methods (determination of total and bactericidal antibodies). Seronegative subjects were tested by opsonophagocytosis. RESULTS: 24 subjects (57%) showed serological evidence of previous contact with Neisseria meningitidis group C antigens: 19 subjects had both total and bactericidal antibodies, two subjects had only total antibodies and three subjects had only bactericidal antibodies. Of the 18 seronegative subjects, five showed ex vivo activity in killing curves with or without polymorphonuclear cells: two subjects exhibited only complement-mediated bactericidal activity, one subject only opsonophagocytosis, and two subjects exhibited both activities. CONCLUSION: The addition of functional tests to the classical serological determination increases the evidence of previous contact with N. meningitidis antigens by 12%.

Adult↗

In vitro activity of clarithromycin against penicillin-susceptible and penicillin-resistant strains of Streptococcus pneumoniae in a pharmacodynamic simulation model.

Clarithromycin has shown enhanced activity against Streptococcus pneumoniae, but increased resistance to macrolides has been observed in recent years. Our aim was to investigate its activity against strains of S. pneumoniae with variable susceptibility to this antibiotic and to penicillin. We determined killing curves using the Centriprep-10 pharmacodynamic simulation model, which permits using varying antibiotic concentrations to mimic a pharmacokinetic human profile in serum (corresponding to an oral dose of 500 mg). Four strains of S. pneumoniae were tested. In susceptible strains, clarithromycin showed bactericidal activity (reductions of up to 2.97 log10 cfu/ml of the initial inoculum). In resistant strains, clarithromycin showed a bacteriostatic effect (<1 log10 cfu/ml reduction). Penicillin-susceptible strains showed higher reductions than penicillin-resistant strains. This effect is important owing to the high minimum inhibitory concentration (MIC) of one of the resistant strains (32 microg/ml). More studies are needed to explain this bacteriostatic activity.

Anti-Bacterial Agents↗

[Pharmacodynamic basis for the use of amoxicillin-clavulanic acid in respiratory infections due to Streptococcus pneumoniae: In vitro studies in an experimental model].

Amoxicillin-clavulanic acid is a first choice treatment for respiratory tract infections caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. In a previous study we observed its high efficacy against penicillin-susceptible and intermediate-resistant strains of S. pneumoniae. We aimed to study the efficacy of this antibiotic against three strains of S. pneumoniae (susceptible, intermediate and resistant to penicillin) in a mouse model of pneumonia, and to determine the influence of the time of starting treatment and the in vitro postantibiotic effect. We also determined the serum levels of the antimicrobial agent in the mice, and correlated the pharmacodynamic parameters (Cmax/MIC, AUC/MIC and T>MIC) with the survival rate to establish the best predictor of efficacy. MICs with amoxicillin-clavulanic acid were 0. 03 mg/l, 0.25 mg/l and 2 mg/l for the penicillin-susceptible, -intermediate and -resistant strains, respectively. The ED90 were approximately 5 mg/kg for susceptible strains, 25 mg/kg for the intermediate and 50 mg/kg for the resistant strains. We observed a lower survival rate (approximately 55%) when the treatment began 31 h after infection than when it began 5 h (100%) and 19 h (approximately 90-100%) afterwards. Serum levels were dose dependent and the correlation with the pharmacodynamic parameters showed a significant association between survival and the T>MIC (r = 0.946). In vitro postantibiotic effects with 1, 4 and 10 times the MIC were 0.96 to 1.69 h for susceptible strains, 0.38 to 1.23 h for intermediate, and 1.52 to 2. 20 h for resistant strains. These results show the high efficacy of this antibiotic combination against strains with variable susceptibility to penicillin, with this activity being related mainly to the T>MIC of the microorganism. The postantibiotic effect would prolong the effect of the antibiotic in the dosing interval. These parameters and antimicrobial effects are important in terms of the clinical application of this antimicrobial agent.

Amoxicillin-Potassium Clavulanate Combination↗

Does the degree of penicillin susceptibility of Streptococcus pneumoniae affect the bactericidal activity of co-amoxiclav versus oral cephalosporins at physiological concentrations? An in vitro pharmacodynamic simulation.

An in vitro model simulating amoxicillin-clavulanic acid (co-amoxiclav) versus oral cephalosporin serum concentrations was used to explore activity over time against penicillin-susceptible and non-susceptible Streptococcus pneumoniae. Initial inoculum reduction > 4 log cfu/ml (>99.9%) was obtained with co-amoxiclav against both strains. Cefuroxime, cefpodoxime and cefaclor achieved a similar reduction against the susceptible strain, but no reduction against the non-susceptible strain.

Amoxicillin-Potassium Clavulanate Combination↗

In vitro bactericidal activity of peak serum concentrations of co-amoxiclav, amoxicillin and vancomycin against methicillin-resistant Staphylococcus aureus.

In order to explore the bactericidal activity of concentrations similar to the peak serum concentrations obtained after a single i.v. dose of 2,000/200 mg co-amoxiclav and 500 mg vancomycin, killing curves with co-amoxiclav (69/10 microg/ml), amoxicillin (69 microg/ml), clavulanic acid (10 microg/ml), and vancomycin (15 microg/ml) were performed against two isogenic (ss-lactamase positive and negative) methicillin-resistant Staphylococcus aureus strains in cation-supplemented Mueller-Hinton broth with 2% NaCl incubated at 35 degrees C. Colony counts were performed at 0, 1, 2, 3 and 4 hours in Mueller- Hinton plates supplemented with 4% NaCl and 25 microg/ml oxacillin to measure the resistant population. Similar initial inocula reductions were obtained for amoxicillin-clavulanic acid and vancomycin for both strains, and significant differences were found in comparison to the control. Clavulanic acid decreased the growth rate of the ss-lactamase negative strain when compared to control curves. The penicillin-binding protein 2a affinity of old ss-lactams in conjunction with clavulanic acid overcoming ss-lactamase resistance may explain these results.

Amoxicillin↗

[Effect of subinhibitory concentrations of various antimicrobials on insoluble glucan production, polystyrene adherence and bacterial surface hydrophobicity of Streptococcus sobrinus].

The effect of subinhibitory concentrations (1/2, 1/4, 1/8 of the MIC) of amoxicillin, teicoplanin, clindamycin and erythromycin on the factors influencing the adherence and pathogenicity of Streptococcus sobrinus was evaluated. These factors included insoluble glucan, polystyrene adherence and bacterial surface hydrophobicity. Insoluble glucan was detected using a spectrophotometric method; polystyrene adherence was assessed using microtiter plates; and surface hydrophobicity was determined using a biphasic system (water/p-xiline). Amoxicillin and teicoplanin induced a statistically significant decrease in adherence at subinhibitory concentrations, and they also decreased the hydrophobicity. However, clindamycin and erythromycin were unable to decrease these parameters. The adherence and hydrophobicity of S. sobrinus was also dependent on the concentration of sucrose in the culture medium.

Anti-Bacterial Agents↗

Effect of polymorphonuclear neutrophils on serum bactericidal activity against Streptococcus pneumoniae after amoxicillin administration.

The effect of phagocytic killing on serum bactericidal activity against Streptococcus pneumoniae was investigated 0, 1.5, 8 and 12 h after a single 875 mg oral dose of amoxicillin in healthy adults. Killing curves were determined with polymorphonuclear neutrophils (PMN), serum or PMN plus serum. Global killing (i. e. intracellular and extracellular killing) over 3 h of incubation was expressed as the area under the killing curve (AUKC; log cfu x h/ml). Amoxicillin did not affect the activity of PMN alone. For serum alone, the AUKC of post-administration samples (with supra-inhibitory amoxicillin concentrations) was significantly lower than in baseline samples. For serum plus PMN, significant bactericidal activity of serum was still found in samples after antibiotic concentrations had reached sub-inhibitory levels.

Adult↗