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E J Perea

Publications and source records attributed to E J Perea.

At least 55 records · Page 3Linked to original sources

Comparative in-vitro activity of sparfloxacin against genital pathogens.

The in-vitro activity of sparfloxacin against four pathogens commonly implicated in genital infections was compared with that of a number of other commonly administered antimicrobials. Sparfloxacin demonstrated excellent activity against Neisseria gonorrhoeae (MIC range of < or = 0.0002-5 mg/L for beta-lactamase producing strains, and < or = 0.0002-0.03 mg/L for non-beta-lactamase producing strains). This activity was similar to that of lomefloxacin and ciprofloxacin and was greater than that of ofloxacin. Sparfloxacin was more active against Ureaplasma urealyticum (MIC90 1 mg/L) than the other three quinolones (MIC90 4 mg/L). Sparfloxacin was much more active against Mycoplasma hominis (MIC90 0.06 mg/L) than the other quinolones (MIC90 1 mg/L). Sparfloxacin showed the most potent inhibitory and bactericidal activity of the quinolones against Chlamydia trachomatis with MIC and MBC of 0.06 mg/L (ofloxacin MIC and MBC 1 mg/L; ciprofloxacin and lomefloxacin MIC and MBC 2 mg/L). The results of this study and others performed by workers using different methods are consistently similar. Since sparfloxacin has broad activity against pathogens implicated in genital infections it may be a good therapeutic alternative for these syndromes.

Anti-Infective Agents↗

Effect of paclitaxel alone or in combination on the intracellular penetration and activity of quinolones in human neutrophils.

We evaluated the effect of paclitaxel alone or in combination with cisplatin or doxorubicin, on the intracellular penetration and activity of ciprofloxacin, ofloxacin, levofloxacin and sparfloxacin in human polymorphonuclear leukocytes (PMN). In general, paclitaxel either alone or in combination did not affect the intracellular concentrations of the quinolones evaluated (intracellular to extracellular concentration ratio (C/E > 4). However, at high concentrations (20 mg/L) paclitaxel decreased the penetration of ofloxacin and levofloxacin although the C/E ratios remained higher than 3. Paclitaxel alone or in combination affected neither the production of oxygen radicals by PMN nor the intracellular activity of the quinolones against Staphylococcus aureus.

Anti-Infective Agents↗

Comparison of broth microdilution and E-test for susceptibility testing of Neisseria meningitidis.

The susceptibilities of 54 clinical isolates of Neisseria meningitidis to penicillin, cefotaxime, ceftriaxone, cefepime, imipenem, ciprofloxacin, chloramphenicol, and rifampin were determined by the microdilution method in both cation-adjusted Mueller-Hinton broth (CAMHB) and Haemophilus test medium (HTM). Poor growth was observed in 16.6 and 9% of the strains in CAMHB and HTM, respectively. As a result, the growth of the 54 N. meningitidis strains was evaluated in three other commercially available batches of CAMHB and in one in-house batch of HTM. Poor growth was observed for 9.3 to 16.6% of the strains in all four batches. More important, three of the CAMHB batches failed to support growth for 3.7 to 33.3% of the strains; 3.7% of the strains did not grow in the in-house-prepared HTM. Ten (18.7%) strains were relatively resistant to penicillin (RRP; MIC, > 0.125 mu g/ml) in CAMHB and 13 (24%) strains were RRP in HTM. The percentages of agreement obtained by using CAMHB as the reference ranged from 78% for cefepime to 100% for ceftriaxone. Seven minor errors were observed for penicillin; five of them were for strains susceptible to penicillin in CAMHB and RRP in HTM. All strains were susceptible to the other antimicrobial agents evaluated. The growth of N. meningitidis was also evaluated in four batches of Mueller-Hinton agar (MHA). In two of them, 3.7 and 44.4% of the strains did not grow, and considering all four batches, 5.5 to 11.1% grew poorly. All strains grew adequately in MHA supplemented with blood (MHA-b). The activities of penicillin and cefotaxime were also evaluated by the E-test in MHA and MHA-b. The proportion of RRP strains were 24% in MHA and 59% in MHA-b. For penicillin, the percentages of agreement of the E-test with the microdilution method in CAMHB (reference) were 64.8 and 70.3% in MHA and MHA-b, respectively. For cefotaxime, the agreement was 98.1%. Minor errors for the penicillin MIC were detected for 38% of the strains tested. Further studies are needed to define adequate culture media for reference methods to evaluate the susceptibility of N. meningitidis to antimicrobial agents.

Humans↗

[Intracellular penetration of 5 quinolones into non-phagocytic cells].

BACKGROUND: The intracellular penetration and activity of antimicrobial agents can be an important factor in the treatment of infections caused by intracellular pathogens. The new quinolones are able to penetrate into phagocytes, but only a few studies have evaluated other types of cells. The purpose of this study is to evaluate the intracellular penetration of ofloxacin, levofloxacin, lomefloxacin, sparfloxacin and BAY Y 3118 into human polymorphonuclear leukocytes and tissue cultured epithelial cells. METHODS: Intracellular penetration was evaluated by a fluorometric assay for all the quinolones evaluated except for sparfloxacin, which was evaluated by a radiometric assay. RESULTS: All the quinolones evaluated reached intracellular concentrations higher than extracellular ones. The penetration of sparfloxacin and BAY Y 3118 into the epithelial cells was similar to those observed for PMNs (cellular to extracellular concentration ratio; C/E > or = 4). The C/E values of ofloxacin, levofloxacin and lomefloxacin for epithelial cells were lower than those observed in PMN, but still yielding C/E values > or = 2.

Cells, Cultured↗

[Uptake of 5 fluoroquinolones into human polymorphonuclear cells].

BACKGROUND: A comparative evaluation of the intracellular penetration of norfloxacin, ofloxacin, levofloxacin, fleroxacin and lomefloxacin was carried out in human polymorphonuclear leucocytes (PMNs). METHODS: The fluorometric method was used based on the natural fluorescence of some fluoroquinolones. RESULTS: All the fluoroquinolones accumulated within the human polymorphonuclear leucocytes achieving a quotient of between 4 to 6 in intracellular and extracellular concentration (I/C) with no significant differences being observed between the two. Penetration was rapid and was not saturable within the intervals of extracellular concentrations tested. The intracellular penetration of these fluoroquinolones was dependent on temperature and cell viability was altered in only levofloxacin and norfloxacin. The I/E values obtained significantly decreased when the cells were incubated at 4 degrees C. These values showed an important increase to pH 5 and decreased to pH 9, with this pH being statistically significant only in ofloxacin. CONCLUSIONS: All the fluoroquinolones evaluated penetrated rapidly into the phagocytic cells achieving intracellular concentrations which were several fold higher than the extracellular concentrations, with no notable differences being observed being the two, thus providing an additional advantage for their use in infections produced by microorganisms capable of surviving intracellularly.

Anti-Infective Agents↗

[Effect of five fluoroquinolones on the bactericidal activity of human polymorphonuclear leukocytes against Staphylococcus aureus].

It has been evaluated the effect of norfloxacin, ofloxacin, levofloxacin, fleroxacin and lomefloxacin of the respiratory burst of human polymorphonuclear leukocytes and their intracellular activity against Staphylococcus aureus. None of these agents significantly affected the superoxide and hydrogen peroxide radicals production by the polymorphonuclear leukocytes. All the quinolones except norfloxacin showed significant intracellular activity against S. aureus.

Anti-Infective Agents↗

Factors affecting the intracellular accumulation and activity of azithromycin.

Azithromycin is a new macrolide which accumulates in high concentrations in human phagocytes. The cellular to extracellular ratio (C/E) of azithromycin concentrations (fixed extracellular concentration 1 mg/L) in human polymorphonuclear leucocytes (PMN) were significantly affected by small increases in the environmental temperature (C/E 20.3 +/- 2 and 59.4 +/- 6 at 37 degrees C and 40 degrees C, respectively). PMN-associated azithromycin was not affected by the presence of different concentrations of human serum. The intracellular accumulation of azithromycin decreased slightly (C/E approximately 5) when cells were activated with PMA or opsonized with zymosan. The phagocytosis of opsonized Staphylococcus aureus or Haemophilus influenzae, however, slightly increased the intracellular concentrations of azithromycin. At different extracellular concentrations, azithromycin did not affect the production of hydrogen peroxide and superoxide radicals by PMN. The intracellular survival of H. influenzae in human PMN was abolished in the presence of concentrations higher than 0.125 mg/L of azithromycin. Under the same experimental conditions, however, azithromycin did not show any intracellular activity against S. aureus.

Azithromycin↗

Activity of sparfloxacin on Staphylococcus epidermidis attached to plastic catheters.

The activity of sparfloxacin on Staphylococcus epidermidis biofilms on different plastic catheters was evaluated. Sparfloxacin showed high bactericidal activity against S. epidermidis biofilms on Vialon and polyvinylchloride catheters. The combination of sparfloxacin with amikacin or rifampicin significantly increased its activity against bacterial biofilms on polyurethane and Teflon catheters.

Amikacin↗

[Antimicrobial activity in Staphylococcus epidermidis biofilms on polyvinyl chloride catheters].

OBJECTIVES: We have evaluated the effect of polyvinylchloride (PVC) catheters on the activity of eight antimicrobials. Secondly the activity of these antimicrobials against Staphylococcus epidermidis biofilms on PVC catheters was also studied. METHOD: The MIC and MBC values of amikacine, clindamycine, cloxacilline, ciprofloxacine, vancomycine, teicoplanine, daptomycine and rifampicine was evaluated by a microdilution assay in the presence of 0.5 cm length segments of PVC catheters. Catheter segments with bacteria attached for different periods of time were used as inocula for the studies of antimicrobial activity against bacterial biofilms. Both slime producing and non-producing strains were evaluated. RESULTS: The presence of PVC did not affect the activity of the antimicrobials evaluated against S. epidermidis. For the non-slime producing strains MBC values against sessile bacteria were significantly higher than those against planktonic bacteria. For the slime-producing strain MBCs of ciprofloxacine, amikacine and teicoplanine against both bacterial populations were similar. At high concentrations (16 x MBC), clindamycine was the only antimicrobial that sterilized non-slime producing S. epidermidis biofilms on PVC. Against the slime producing strains ciprofloxacine yielded the highest reduction on bacterial viability (99.9%). CONCLUSIONS: S. epidermidis biofilms on PVC were more resistant to antimicrobials than planktonic bacteria. Slime production is not the only factor involved in this phenomenon.

Anti-Bacterial Agents↗

Activity of glycopeptides in combination with amikacin or rifampin against Staphylococcus epidermidis biofilms on plastic catheters.

The in vitro activity of vancomycin and teicoplanin (fourfold the MBC), alone and in combination with amikacin (16 mg/l) or rifampin (1 mg/l), against Staphylococcus epidermidis (slime-producing and non slime-producing strains) biofilms on different plastic catheters was evaluated. The addition of amikacin or rifampin significantly increased the activity of glycopeptides against sessile bacteria. With the slime-producing strain, these combinations were able to sterilize the surface of Vialon and polyvinylchloride catheters. It is concluded that the in vitro activity of glycopeptides against Staphylococcus epidermidis biofilms on plastic catheters can be increased by the addition of amikacin or rifampin.

Amikacin↗

Activity of eight antibacterial agents on Staphylococcus epidermidis attached to Teflon catheters.

The presence of a Teflon catheter had no effect on the in-vitro activity of a range of antibacterial agents against slime producing and non-producing Staphylococcus epidermidis strains as determined by a microdilution assay. The susceptibility of S. epidermidis attached to Teflon catheters for 6, 24 and 48 h was also evaluated. MICs for planktonic and attached bacteria were similar. When bacteria attached to Teflon for 6 h were used as inocula, MBC values increased 32-8192-fold for the antibacterial agents tested. Similar results were observed when bacteria attached for 24 and 48 h were used as inocula. The activity of a high concentration (16 x MBC) of these antimicrobial agents against S. epidermidis biofilms in Teflon catheters was evaluated; for five slime non-producing strains, the highest reduction (around 99%) in bacterial viability was produced by cloxacillin and teicoplanin; for the slime producers, the highest effect (99.5% reduction) was shown by amikacin, clindamycin cloxacillin and ciprofloxacin but all cases still showed bacterial counts higher than 10(3) cfu/catheter segment. It is concluded that adherence of S. epidermidis to Teflon catheters decreases the bactericidal activity of the antibacterial agents tested in vitro.

Anti-Bacterial Agents↗

Intracellular penetration and activity of BAY Y 3118 in human polymorphonuclear leukocytes.

The penetration of a new quinolone (BAY Y 3118) into human polymorphonuclear leukocytes (PMNs) was evaluated by a fluorometric assay. The cellular concentration-to-extracellular concentration (C/E) ratio was higher than 6.3 at extracellular concentrations ranging from 2 to 100 mg/liter. The uptake of BAY Y 3118 was rapid, reversible and nonsaturable. The intracellular penetration of BAY Y 3118 was significantly affected by environmental temperature (C/E ratio at 4 degrees C, 5.4 +/- 0.5; control, 7.5 +/- 0.9; P < 0.05) and cell viability (C/E ratio in dead PMNs, 5.5 +/- 0.8; control 7.5 +/- 0.9; P < 0.05), but it was not affected by metabolic inhibitors. The ingestion of opsonized zymosan or opsonized Staphylococcus aureus significantly decreased the levels of PMN-associated BAY Y 3118. Cell stimulation by a membrane activator, however, significantly increased the intracellular concentration of this quinolone. At therapeutic extracellular concentrations (0.5, 2, and 5 mg/liter), BAY Y 3118 showed intracellular activity greater than that of ciprofloxacin against S. aureus in human PMNs. It was concluded that BAY Y 3118 reaches high intracellular concentrations within human PMNs and remains active intracellularly.

Anti-Infective Agents↗