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Biomedical subjects

M L Gomez-Lus

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

11 recordsLinked to original sources

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↗

Influence of the decrease in ciprofloxacin susceptibility and the presence of human serum on the in vitro susceptibility of Streptococcus pneumoniae to five new quinolones.

Sixty recent Streptococcus pneumoniae isolates with different susceptibilities to ciprofloxacin (14 with MIC 0.5 mg/L, 10 with MIC 1 mg/L, eight with MIC 2 mg/L, 11 with MIC 4 mg/L and 17 with MIC > or =8 mg/L) were tested against five new quinolones using Todd-Hewitt broth with and without 80% serum. The final inoculum was 5 x 10(5) cfu/mL. Gemifloxacin and clinafloxacin exhibited the lowest MIC90 values and resistance rates (percentage above and defined breakpoint) with and without serum for strains with a ciprofloxacin MIC of > or =4 mg/L. Other quinolones tested were less active against strains with reduced ciprofloxacin susceptibility. The presence of serum did not affect susceptibility to moxifloxacin, but increased the resistance rates to other new quinolones for strains with high ciprofloxacin MICs.

Anti-Infective Agents↗

Efficacy of trovafloxacin in an in vitro pharmacodynamic simulation of an intraabdominal infection.

An in vitro model simulating trovafloxacin concentrations in human serum after standard doses was used to investigate the activity of this drug with time against Bacteroides fragilis, Escherichia coli, Enterococcus faecalis and Staphylococcus aureus. Antibiotic concentrations used for each incubation period were: 4.24 mg/l (0-1 h), 3.69 mg/l (1-3 h), 3.25 mg/l (3-6 h), 2.38 mg/l (6-8 h), 1.35 mg/l (8-24 h). A 99.9% initial inoculum reduction (> 3 log10 cfu/ml) was defined as bactericidal activity. Bactericidal activity against these organisms was obtained with trovafloxacin after the first hour of incubation, and similar activity was obtained against B. fragilis, E. faecalis and S. aureus after 3 h, when they were tested individually. When the strains were tested as mixed culture, there was bactericidal activity against E. coli after 1 h incubation and after 3 h for S. aureus. This activity was observed against B. fragilis and E. faecalis after 6 h incubation in the mixed culture assays and after 3 h when organisms were tested individually. Regrowth was not observed over a 24 h period. These data show that trovafloxacin might be effective in intraabdominal infections caused by mixed aerobic and anaerobic microorganisms.

Abdominal Abscess↗

Postanitbiotic and sub-MIC effects of azithromycin and isepamicin against Staphylococcus aureus and Escherichia coli.

Investigations of pharmacodynamic parameters (postantibiotic effect [PAE], sub-MIC effects [SMEs], etc.) have been progressively employed for the design of dosing schedules of antimicrobial agents. However, there are fewer in vivo than in vitro data, probably because of the simplicity of the in vitro procedures. In this study, we have investigated the in vitro PAE, SME, and previously treated (postantibiotic [PA]) SME (1/2 MIC, 1/4 MIC and 1/8 MIC) of azithromycin and isepamicin against standard strains of Staphylococcus aureus and Escherichia coli by using centrifugation to remove the antibiotics. In addition, the in vivo PAE and SME have been studied with the thigh infection model in neutropenic mice. Finally, in vivo killing curves with two dosing schedules were determined to examine whether the PAE can cover the time that antimicrobial agents are below the MIC. The two antimicrobial agents induced moderate-to-high in vitro PAEs, SMEs, and PA SMEs against S. aureus (>8 h) and E. coli (3.38 to >7.64 h). The in vivo PAEs were also high (from 3.0 to 3.6 h), despite the fact that isepamicin had lower times above the MIC in serum. Only azithromycin showed a high in vivo SME against the two strains (1.22 and 1.75 h), which indicated that the in vivo PAEs were possibly overestimated. In the killing kinetics, no great differences (<0.5 log10) were observed between the schedule that took the PAE into account and the continuous administration of doses. These results are comparable with those of other authors and suggest that these antimicrobial agents could be administered at longer intervals without losing effectiveness.

Animals↗

In vivo and in vitro study of several pharmacodynamic effects of meropenem.

Several pharmacodynamic parameters are being studied and applied to the design of dosage regimens. The thigh infection model in neutropenic mice has been used in this study to investigate the in vivo postantibiotic effect (PAE) of meropenem against S. aureus, E. coli and P. aeruginosa. The sub-minimum inhibitory concentration (sub-MIC) postantibiotic effect (PA SME) of 1/2, 1/4 and 1/8 x MIC was also determined in vitro on S. aureus and E. coli after pre-exposure of these microorganisms to 10 x MIC of meropenem. The in vitro PAE was also determined. In vivo killing curves using 2 different short dosage regimens were also studied to relate the lethal effect to the time that serum levels were above the MIC. No significant in vivo and in vitro PAEs were observed. The PA SMEs were higher for S. aureus than for E. coli. The 2 short dosage regimens, in vivo, were equally effective in killing S. aureus, but not E. coli. These results suggest that the pharmacodynamics of meropenem on Gram-negative strains may need further study to elucidate the mechanisms and characteristics of these parameters. On the other hand, we need to standardize a reliable in vitro method to monitor regrowth with a good correlation with the in vivo conditions.

Animals↗

Comparative activity of cefotetan against plasmid-encoded aminoglycoside-resistant enterobacteria strains.

304 strains of R-plasmid harbouring enterobacteria resistant to aminoglycosides were studied for their susceptibilities to a range of antibiotics, including cefotetan. Cefotetan and latamoxef were the most active of the four cephamycins tested and all were stable to the beta-lactamases produced by these strains. No new beta-lactamases (SHV-2, CTX-1, TEM-4, CAZ-1) were found in these strains capable of hydrolysing third generation cephalosporins. The activity of cefotetan against these multi-resistant, beta-lactamase producing strains may be of clinical value.

Aminoglycosides↗

Stability of dactimicin to aminoglycoside-modifying enzymes.

Dactimicin was active against strains expressing the activities of aminoglycoside acetylating enzymes [AAC(3)-II, III, IV and V, AAC(2'), AAC(6')-I and II], aminoglycoside-nucleotidylating enzymes [ANT(2"), AAD(3")] and aminoglycoside-phosphorylating enzymes [APH(3')-I-II and III], with the exception of AAC(3)-I and one staphylococcal AAC(6')-IV. Apparently this is the first report of one 6'-N-acetylating enzyme which modifies and inactivates dactimicin. The authors' data suggest that the differences in the behaviour of dactimicin, gentamicin and amikacin against the aminoglycoside-resistant strains tested were mainly due to the production of aminoglycoside-modifying enzymes. If the results are summarized, it may be concluded that dactamicin is the most stable to the majority of aminoglycoside-modifying enzymes demonstrated [APH(3'), APH(2"), APH(3"), ANT(2"), AAD(3"), AAC(2') and AAC(6')], with the exception of AAC(3)-I and staphylococcal AAC(6')-IV.

Acetylation↗

Pharmacodynamic effects of ciprofloxacin, fleroxacin and lomefloxacin in vivo and in vitro.

The present study investigates the postantibiotic effect (PAE) in vivo, and the postantibiotic subinhibitory concentration effects (PA-SE) in vitro and SE in vivo of three 4-fluoroquinolones (ciprofloxacin, fleroxacin and lomefloxacin) against standard strains of Staphylococcus aureus and Escherichia coli. In vivo killing kinetics have also been performed using two different short administrations to study if the PAE duration could cover the time that the antibiotic was below the minimal inhibitory concentration (MIC) in serum. The results show that the three antimicrobial agents induced long PAEs (1.9-3.1 h) against the two microorganisms. Moderate but significant in vitro PA-SEs were also produced (1-->9 h). The in vivo SEs were not significant except when the effect of lomefloxacin on E. coli was assayed (0.54 h). Finally, the in vivo killing kinetics showed that the administrations that included the PAE duration were as effective as the schedule that maintained the antibiotic levels in serum above the MIC. Only when fleroxacin and S. aureus were assayed, this last administration was more effective (+0.9 log10 colony-forming units/thigh).

Animals↗