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The aim of this study was to evaluate the effects of human serum albumin (HSA), ibuprofen sodium (IBU) and N-acetyl-L-cysteine (NAC) against biofilm formation by seven biofilm-producing strains of Escherichia coli. Biofilm formation was studied using polystyrene microtitre plates in static conditions. The impact of the three compounds on bacterial growth and biofilm formation was tested by applying each compound in solution and as pre-treatment (coating) of polystyrene wells. When studied in solution, the minimum biofilm inhibitory concentrations of HSA, IBU and NAC were 8 mg/L (all strains), 2-125 mg/L (five strains) and 30-125 mg/L (five strains), respectively. Pre-treatment of polystyrene plates with HSA at 8 and 32,000 mg/L significantly reduced biofilm formation by all strains, whereas coating with 125 mg/L IBU and 1000 mg/L NAC did not. When HSA at 8 and 32,000 mg/L was combined with either 125 mg/L IBU or 1000 mg/L NAC in pre-treatment assays, more potent inhibition of biofilm was observed for some strains. Our results suggest that biofilm formation by E. coli may be prevented by coating medical devices with HSA alone or in combination with IBU or NAC. In addition, IBU and NAC could be useful in the treatment of urinary tract infections caused by E. coli due to their inhibitory effect on both bacterial growth and biofilm formation.

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The in vitro and in vivo activity of miltefosine against penicillin-sensitive and penicillin-resistant pneumococcal strains was studied. The minimum inhibitory concentrations (MICs) of miltefosine were determined in cation-adjusted Mueller Hinton plus 2% lysed horse blood (CAMHB) and in Todd-Hewitt (TH) broth. The respective MICs were higher using CAMHB (128 and 64 mg/L) than using TH broth (4 and 8 mg/L). The in vivo activity was studied in a murine peritonitis-sepsis model. Miltefosine was orally administered at doses of 15 and 30 mg/kg/day after, at the time of, and before bacterial challenge for 3-5 days. All control and 16 out of the 17 (94.1%) miltefosine-treated animals that were inoculated with the penicillin-sensitive strain died. No survival was observed among control and miltefosine-treated animals inoculated with the penicillin-resistant pneumococcal strain. The in vivo unresponsiveness of miltefosine in this sepsis model could be attributed to some inhibitory effect of blood, inadequate pharmacokinetics and/or the extracellular localization of the pneumococcus.

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AIMS: In this study, we have evaluated the impact of methodological approaches in the determination of biofilm formation by four clinical isolates of Escherichia coli in static assays. METHODS AND RESULTS: The assays were performed in microtitre plates with two minimal and two enriched broths, with one- or two-steps protocol, and using three different mathematical formulas to quantify adherent bacteria. Different biofilm formation patterns were found depending on the E. coli strain, culture medium and reading optical density on one- and two-steps protocol. Strong or moderate biofilm formation occurred mostly in minimal media. The mathematical formulas used to quantify biofilm formation also gave different results and bacterial growth rate should be taken into account to quantify biofilm. CONCLUSIONS: Escherichia coli forms biofilms on static assays in a method-dependent fashion, depending on strain, and it is strongly modulated by culture conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: As verified in the studied E. coli strains, biofilm formation by any organism should be cautiously interpreted, considering all variables in the experimental settings.

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The oropharynx is both the reservoir where antibiotic-resistant Streptococcus pneumoniae strains are selected and the focus for further spread of these organisms. In order to select antibiotic-resistant organisms, the antibiotic must be able to eradicate the susceptible population. How an antibiotic acts on oropharyngeal flora is not fully understood, although data on salivary antibiotic concentrations could be useful for establishing some correlation. Many beta-lactam antibiotics are very active against S. pneumoniae, and although their saliva concentrations are very low, there may be enough to eradicate the majority of beta-lactam-sensitive strains. Other antibiotics achieve salivary concentrations in the range 10-30% of serum concentrations (erythromycin, clindamycin, doxycycline and rifampicin), and are also able to eradicate the antibiotic-susceptible population. Antibiotics achieving higher salivary concentrations (>/=40% of the serum levels) are not very active against S. pneumoniae (ciprofloxacin) or are able to eradicate antibiotic-sensitive and -intermediate strains (clarithromycin, azithromycin and telithromycin). Only antibiotics for which there are no highly resistant pneumococcal strains, for instance some beta-lactams administered at very high dose and for a short course, are associated with a lower risk of antibiotic resistance selection. To diminish the risk, the antibiotics should be dosed in order to obtain inhibitory quotients (maximal serum concentration/MIC ratios) >/= 4, which depends not only on the antibiotic concentration achieved but also on the lack of highly resistant organisms.

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Moxifloxacin, an 8-methoxyquinolone with broad-spectrum activity in vitro, was studied in the rabbit model of Escherichia coli meningitis. The purposes of this study were to evaluate the bactericidal effectiveness and the pharmacodynamic profile of moxifloxacin in cerebrospinal fluid (CSF) and to compare the bactericidal activity with that of ceftriaxone and meropenem therapy. After induction of meningitis, animals were given single doses of 10, 20, and 40 mg/kg or divided-dose regimens of 5, 10, and 20 mg/kg twice, separated by 6 h. After single doses, the penetration of moxifloxacin into purulent CSF, measured as percentage of the area under the concentration-time curve (AUC) in CSF relative to the AUC in plasma, was approximately 50%. After single doses of 10, 20, and 40 mg/kg, the maximum CSF concentration (C(max)) values were 1.8, 4.2, and 4.9 microg/ml, respectively; the AUC values (total drug) were 13.4, 25.4, and 27.1 microg/ml x h, respectively, and the half-life values (t(1/2)) were 6.7, 6.6, and 4.7 h, respectively. The bacterial killing in CSF for moxifloxacin, calculated as the Deltalog(10) CFU per milliliter per hour, at 3, 6, and 12 h after single doses of 10, 20, and 40 mg/kg were -5.70, -6.62, and -7.02; -7.37, -7.37, and -6.87; and -6.62, -6.62, and -6.62, respectively, whereas those of ceftriaxone and meropenem were -4.18, -5.24, and -4.43, and -3.64, -3.59, and -4.12, respectively. The CSF pharmacodynamic indices of AUC/MBC and C(max)/MBC were interrelated (r = 0.81); there was less correlation with T > MBC (r = 0.74). In this model, therapy with moxifloxacin appears to be at least as effective as ceftriaxone and more effective than meropenem therapy in eradicating E. coli from CSF.

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BMS-284756 is a novel des-fluoro(6) quinolone with a broad antimicrobial activity, including Streptococcus pneumoniae. The purpose of this study was to evaluate the pharmacodynamic profile and effectiveness of BMS-284756 for therapy of experimental meningitis caused by penicillin- and cephalosporin-resistant S. pneumoniae (CRSP). Meningitis was induced in rabbits by intracisternal inoculation of CRSP. BMS-284756 was given intravenously 16 h after intracisternal inoculation in single doses of 2.5 (n = 5 animals), 5 (n = 6), 10 (n = 6), 20 (n = 8), and 30 mg/kg (n = 6), in two doses of 10 mg/kg each separated by 5 h (n = 4), and as a 20-mg/kg dose followed 5 h later by 10 mg/kg (n = 5). The MICs and MBCs of BMS-284756, ceftriaxone, and vancomycin were 0.06 and 0.06, 4 and 4, and 0.25 and 0.25 microg/ml, respectively. After single doses of 10, 20, and 30 mg/kg, the maximum concentrations in cerebrospinal fluid (CSF) (mean +/- standard deviation) were 0.32 +/- 0.12, 0.81 +/- 0.38, and 1.08 +/- 0.43 microg/ml, respectively; the elimination half-life in CSF was 4.5 to 6.3 h. The CSF bacterial killing rates (BKR) at 5 h of the single-dose regimens of 10, 20 and 30 mg/kg were -0.84 +/- 0.48, -1.09 +/- 0.32, and -1.35 +/- 0.05 Deltalog(10) CFU/ml/h. The BKR(0-5) of the divided regimens (10 mg/kg twice and 20 mg/kg followed by 10 mg/kg) was -0.82 +/- 0.52 and -1.24 +/- 0.34 Deltalog(10) CFU/ml/h, respectively. The BKR(0-5) of the combined therapy with vancomycin and ceftriaxone was -1.09 +/- 0.39 Deltalog(10) CFU/ml/h. The penetration of BMS-284756 into purulent CSF relative to plasma was 14 to 25%. The bactericidal effect of BMS-284756 in CSF was concentration dependent. BMS-284756 at 30 mg/kg as a single or divided dose was as effective as standard therapy with vancomycin and ceftriaxone.

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