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In a field study comparing isolation rates pre- and post-installation of an electro-chemical activation system for Legionella pneumophila disinfection of potable hot water in a Spanish hospital, a total of 250 tap samples pre-installation and 113 post-installation were collected. Chlorine levels were higher ( p < 0.001) post-installation (0.55 ± 0.41 vs. 1.19 ± 0.44 ppm). Of 38.0% (138/363) samples positive for L. pneumophila, 111 (80.4%) were serogroups 2—14. Post-installation, the isolation rate was lower (46.8% vs. 18.6%; p < 0.001, odds ratio (OR) 0.26, 95% confidence interval (CI) 0.15—0.44) due to significant ( p < 0.001; OR 0.25, 95% CI 0.14—0.45) reduction in L. pneumophila serogroups 2—14 from 38.4% to 13.3%. Post-installation, isolation rates were lower in spring (44.4% vs. 0.0%; p < 0.001), summer (80.0% vs. 25.0%; p = 0.003) and autumn (72.0% vs. 28.9%; p = 0.018), but not in winter (18.5% vs. 11.8%; p = 0.688). The seasonal wave constructed with pre-installation data significantly decreased post-installation by decreasing isolation rates in summer and autumn to rates similar to those found in winter pre-installation.

Temporal trends of serotypes from invasive pneumococcal disease (IPD) in Spain from 1979 to September 2007 under antibiotic and vaccine pressure were analyzed. A significant trend in pneumococcal conjugate 7-valent vaccine (PCV7) serotypes (except serotype 4) was found, whereby the prevalence increased from the early 1980s and decreased in the 2000s for all but serotype 23F, which began decreasing in the late 1980s. Among the major non-PCV7 serotypes, a significant decrease was observed for serotypes 1, 5, and 7F in the 1980s. From the late 1990s, serotypes 1, 5, 6A, 7F, and 19A increased significantly, while serotypes 3 and 8 showed similar but nonsignificant trends over time. The incidence of IPD cases was 10.7/100,000 for the period 1996 to 2006, with reporting coverage ranging from 18% to 43%. A significant decrease in IPD incidence due to PCV7 serotypes was observed, while the incidence of non-PCV7 serotypes increased, with the consequence that there was no clear pattern in the overall incidence of IPD. Penicillin nonsusceptibility was correlated with the proportion of PCV7 serotypes. Erythromycin nonsusceptibility increased in association with long-half-life macrolide consumption and then decreased in 2004 to 2007. The increase in PCV7 serotypes and antibiotic nonsusceptibility related to antibiotic consumption in the 1980s and 1990s was reversed in the 2000s, probably as a result of PCV7 immunization. The decrease in IPD incidence due to PCV7 serotypes was mirrored by an increase in that of non-PCV7 serotypes. The impact of various preventive/therapeutic strategies on pneumococcal evolution is serotype dependent, and the dynamics remain unpredictable.

The monomer of 2-butanone peroxide is a novel peroxygen derivative with potential use as biocide in the hospital environment. The aim of this study was to test the biocidal activity of different concentrations of the compound against American Tissue Culture Collection strains from 11 different micro-organisms, including bacteria, mycobacteria, spores, fungi and virus, following the European Standard guidelines. Toxicity tests were also carried out following United States Environmental Protection Agency Standards. 2-Butanone peroxide exhibited biocidal activity at 0.12% against Legionella pneumophila, at 0.5% against Escherichia coli, Pseudomonas aeruginosa and Enterococcus hirae, and at 1% against Staphylococcus aureus after 5 min contact at room temperature. Mycobactericidal activity was obtained at 0.5% after 60 min contact at 20 degrees C, and sporicidal activity was obtained at 4% after 60 min at 40 degrees C. Good fungicidal (against yeasts and moulds) and virucidal (adenovirus and poliovirus) activities were obtained at 0.5% after 60 min contact. Toxicity assessment showed negative results in the acute dermal irritation test, acute eye irritation test and acute oral toxicity test. The skin sensitisation test was negative. The safety profile in the toxicity tests and the basic cidal activity against the strains tested suggest that 2-butanone peroxide in the control of hospital infections.

Biofilm production was assessed in 52 Staphylococcus epidermidis isolates from the catheters of 52 patients with catheter-related bloodstream infections (CR-BSI) and compared with 14 isolates from the skin of healthy volunteers by spectrophotometry. The isolates were classified as non- (G1), weak- (G2) or strong- (G3) slime producers based on optical density, and as producers and non-producers based on the results of the Congo red agar test. Differences (p = 0.012) in the proportion of G1, G2 and G3 among the isolates were found between catheter and healthy skin strains: there was a higher percentage of G1 types among the healthy skin strains (35.7 vs. 11.5%; p = 0.046) and a higher percentage of G3 types among the catheter isolates (44.2 vs. 0%; p = 0.001). No significant differences were found with the Congo red agar test. G3 is a phenotypic marker for CR-BSI.

Surveillance of Legionella spp. in hospital water systems was performed in forty-four inpatient healthcare facilities in Spain during 2005-2006. A total of 2,341 samples were collected: 470 from cooling systems (cooling towers) and 1,871 from potable water systems. The latter included 211 from cold-water tanks and 260 from hot-water tanks, totalling 471 from central water reservoirs 136 from showers, 1,172 from unfiltered taps and 92 from filtered taps, totalling 1,400 from peripheral points. Temperature, chlorine levels and the presence of Legionella spp. were determined. In all, 373 (15.9%) samples yielded Legionella spp. Significantly higher isolation rates were obtained from cooling towers (23.8%) versus cold- and hot-water tanks (approximately 4.7%), due to the significantly higher number of samples positive for serogroup 1 (19.4 vs 0.9-3.5%). In potable water systems, no differences were found between central water tanks and showers, but significant differences in isolation rates between central water tanks and unfiltered taps were observed (4.7 vs 19.6%) due to differences in non-serogroup 1 L. pneumophila. Filters significantly decreased isolation rates of these serotypes (11 vs 0%). Some seasonal differences were noted, with higher isolation rates in summer for legionella serogroup 1 in cooling systems and for L. pneumophila serogroups 2-14 in potable water systems. In regression models, higher temperatures were associated with colonisation in cooling systems, while lower chlorine levels were associated with colonisation in potable water systems.

Antimicrobial susceptibilities of 244 amoxycillin-non-susceptible and 81 amoxycillin-susceptible pneumococcal isolates from 15 Spanish hospitals were determined and clonal relationships were investigated by pulsed-field gel electrophoresis after SmaI restriction. Amoxycillin-non-susceptible isolates exhibited higher rates of resistance to cefuroxime, cefixime, cefpodoxime and clarithromycin, but not to levofloxacin and cefotaxime. Cefditoren exhibited MIC(90) values one dilution lower than those of cefotaxime. Higher numbers of the Spain(14)-5 and Spain(6B)-2 clones, but not the Spain(9V)-3 and Spain(23F)-1 clones, were found among amoxycillin-non-susceptible isolates. Spain(14)-5 was the most problematic clone in terms of antibiotic resistance.

To investigate the bactericidal activity, against Haemophilus influenzae strains exhibiting different resistance phenotypes, of simulated serum concentrations obtained in humans after administration of 400 mg of cefditoren twice daily, 500 mg of cefuroxime twice daily, 875/125 mg of co-amoxiclav twice daily or 875/125 mg of co-amoxiclav three times daily.An in vitro computerized pharmacodynamic simulation was carried out and colony counts determined over 24 h. Four H. influenzae strains were used, one ampicillin-susceptible strain (Strain 1) and three ampicillin-resistant strains following CLSI and BSAC breakpoints: one beta-lactamase-positive strain with an MIC of co-amoxiclav of 0.5 mg/L (Strain 2), one beta-lactamase-negative ampicillin-resistant strain (BLNAR; ampicillin MIC = 16 mg/L) (Strain 3) and one beta-lactamase-positive strain with an MIC of co-amoxiclav of 4 mg/L (Strain 4). All strains were susceptible to cefuroxime and co-amoxiclav according to current CLSI breakpoints, but Strains 3 and 4 were resistant according to BSAC breakpoints. All strains exhibited cefditoren MICor= 0.12 mg/L.Bacterial counts of Strains 1 and 2 wereor= 6 log(10) reduced with all antibiotics tested at 12 and 24 h. Against Strains 3 and 4, log(10) reductions at 12 and 24 h were significantly higher for cefditoren versus cefuroxime (P0.01) (although both exhibited bactericidal activity, i.e.or= 3 log(10) reduction) and versus the two co-amoxiclav regimens (P0.001) (that exhibited negligible initial inocula reductions).Cefditoren exhibited the highest bactericidal activity maintained over time against ampicillin-resistant H. influenzae, regardless of beta-lactamase production and/or BLNAR phenotype. From the pharmacodynamic perspective, BSAC breakpoints seem more adequate to define or detect BLNAR strains.

To explore reproducibility of high amoxicillin minimum inhibitory concentrations (MIC(AMX) ), isolates received during 2002 and 2003 in the National Reference Laboratory of Streptococcus pneumoniae with an amoxicillin MIC of 16 microg/ml (43 strains) and 8 g/ml (12 strains) when singly determined on a routine basis in this center by agar dilution, were retested 10 times by agar dilution and microdilution following NCCLS guidelines, not only using double dilutions but also dilution steps of 2 microg/ml (i.e, 2, 4, 6, 8, 10, 12, 14 and 16 microg/ml). A significant (p0.05) shift to a higher MIC(AMX )was obtained with microdilution vs. agar dilution. Routine MIC(AMX )of 16 microg/ml were confirmed in 0 strains by agar dilution and in 6 by microdilution, when retested. These 6 strains presented a modal MIC(AMX )value of 10 microg/ml (5 cases) and of 14 micro g/ml (1 case) when using 2 microg/ml microdilution steps. There is low reproducibility of the highest MIC(AMX )values.

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.

The 8-hour In Vitro activity of serum-simulated concentrations of amoxicillin (obtained after 875 mg oral dose) and cefotaxime (obtained after a 1 g i.v. dose), against 20 strains of the 5 Streptococcus pneumoniae serotypes most prevalent in Spain, was explored. Despite a greater initial inocula decrease observed with cefotaxime against the resistant strains at the first sampling time, a decrease ≥99.9% was obtained with both β-lactams from 6h onwards against the penicillin-susceptible strains; the same was observed for the penicillin-resistant strains with amoxicillin but not with cefotaxime.

Resistant clones/phenotypes are putting into question the activity of commonly used beta-lactams, thus prompting the need for alternative options. A 500 mg levofloxacin vs. azithromycin once daily pharmacodynamic simulation was performed against 10(8) cfu/ml of four Streptococcus pneumoniae strains (exhibiting higher amoxicillin than penicillin MIC) and four Haemophilus influenzae strains: beta-lactamase producing, BLNAR (beta-lactamase-negative ampicillin-resistant) and BLPACR (beta-lactamase-positive amoxicillin/clavulanate-resistant). High levofloxacin AUC/MIC values for H. influenzae, and values of 50-100 for S. pneumoniae produced a5 log(10) reduction at 24h for all strains. Azithromycin AUC/MIC values of approximately 10 were needed to obtain a 2-3 log(10) reduction of S. pneumoniae initial inocula, but lower AUC/MIC values (of approximately 6) obtainedor =3 log(10) reduction against all strains of H. influenzae. While in vitro simulated serum concentrations of levofloxacin were bactericidal at the end of the dosing interval against all S. pneumoniae strains and azithromycin against the susceptible ones, both antimicrobials achieved this endpoint against the BLNAR and BLPACR strains.

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.

The effects of polymorphonuclear neutrophils (PMNs) and/or clavulanic acid on the bactericidal activity of amoxicillin (at human serum achievable concentrations) against a serotype 3 penicillin-susceptible Streptococcus pneumoniae strain [minimal inhibitory concentration/minimal bactericidal concentration (MIC/MBC) values of penicillin, amoxicillin, and amoxicillin/clavulanic acid (2:1) = 0.01/0.01 microgram/ml] and a serotype 9 penicillin-resistant strain [MIC/MBC of penicillin, amoxicillin, and amoxicillin/clavulanic acid (2:1) = 1/2 microgram/ml] were studied. Against the penicillin-resistant strain, subinhibitory concentrations of amoxicillin reduced the growth rate; this effect was increased by the addition of clavulanic acid. A reduction of the penicillin-resistant initial inocula (3 x 10(6) cfu/ml) at subinhibitory concentrations was obtained only with amoxicillin plus clavulanic acid and PMNs. At suprainhibitory concentrations, both clavulanic acid and PMNs increased the bactericidal activity of amoxicillin, as evidenced by an increased reduction in the penicillin-resistant initial inocula. The combined effect of these antibiotics and immune defenses may help explain the maintenance of their clinical efficacy in respiratory tract infections, despite the increase in the incidence of penicillin-resistant pneumococci.

Poor outcomes of invasive candidiasis (IC) are associated with the difficulty in establishing the microbiological diagnosis at an early stage. New scores and laboratory tests have been developed in order to make an early therapeutic intervention in an attempt to reduce the high mortality associated with invasive fungal infections. Candida albicans IFA IgG has been recently commercialized for germ tube antibody detection (CAGTA). This test provides a rapid and simple diagnosis of IC (84.4% sensitivity and 94.7% specificity). The aim of this study is to identify the patients who could be benefited by the use of CAGTA test in critical care setting.

Trends in serotype incidence and susceptibility (1997 to 2008) of Spanish Streptococcus pneumoniae pleural isolates ( n = 831) were explored. Penicillin (oral) nonsusceptibility rates and the incidence of 7-valent pneumococcal conjugate vaccine (PCV-7) serotypes showed decreasing trends ( R 2 ≥ 0.600; P ≤ 0.002). The incidence of serotypes 1 and 19A showed increasing trends ( R 2 ≥ 0.759; P < 0.001), with no trends for serotype 3. Serotypes 19A, 1, and 3 represented 85% of pediatric isolates in 2008. In serotype 19A, the penicillin nonsusceptibility rate was 82.4% in 2008, associated with amoxicillin and cefotaxime nonsusceptibility in 21.4% of isolates. Inclusion of these serotypes in new vaccines offers the broadest coverage.

Interference of cefditoren (CDN) and amoxicillin/clavulanic acid (AMC) with biofilm production was studied using 11 Streptococcus pneumoniae isolates with minimum inhibitory concentrations (MICs) ranging from 0.015microg/mL to 0.5microg/mL for CDN and from 0.06microg/mL to 2microg/mL for AMC (except for one isolate with an AMC MIC of 8microg/mL) and 5 Haemophilus influenzae isolates with MICs of 0.03-0.06microg/mL for CDN and 0.5-16microg/mL for AMC. Slime production was assessed in antibiotic-free medium and with 0.03microg/mL CDN or 1/0.5microg/mL AMC by measuring the optical density at 450nm (OD(450)). Significantly lower mean OD(450) values were obtained for S. pneumoniae with antibiotics compared with controls (CDN, 0.088 vs. 0.118, P=0.003; and AMC, 0.095 vs. 0.112, P=0.003), with significant correlation between both antibiotics (r=0.752; P=0.008). Percent reduction in OD(450) values was higher for CDN compared with AMC (24.02% vs. 15.92%; P=0.008). For H. influenzae, significantly lower mean OD(450) values were obtained with CDN compared with controls (0.083 vs. 0.096; P=0.043) but not with AMC (0.086 vs. 0.095; P=0.08). Comparing percent reductions in S. pneumoniae versus H. influenzae for each antibiotic, no differences were found for AMC (15.92% vs. 9.40%; P=0.36), with a tendency for CDN (24.02% vs. 13.79%; P=0.069). Different beta-lactams may have different capabilities of interfering with S. pneumoniae biofilm development when tested under the same experimental conditions.

This study explored the influence of vancomycin tolerance and protein binding on the bactericidal activity of vancomycin versus daptomycin (protein binding 36.9% vs. 91.7%, respectively) against four vancomycin-tolerant methicillin-resistant Staphylococcus aureus (MRSA) [minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC)=0.5/16, 1/32, 2/32 and 1/32microg/mL for vancomycin and 1/1, 1/2, 2/2 and 2/4microg/mL for daptomycin]. Killing curves were performed with vancomycin/daptomycin concentrations equal to serum peak concentrations (C(max)) (65.70/98.60microg/mL) and trough concentrations (C(min)) (7.90/9.13microg/mL) in the presence and absence of a physiological human albumin concentration (4g/dL), controlled with curves with the theoretical free drug fraction of vancomycin/daptomycin C(max) (41.45/8.18microg/mL) and C(min) (4.98/0.76microg/mL). Vancomycin C(max) and C(min) concentrations, regardless of the media, showed a bacteriostatic profile not reaching a reduction of 99% or 99.9% of the initial inocula during the 24-h experimental time period. Daptomycin antibacterial profiles significantly differed when testing C(max) and C(min). C(max) was rapidly bactericidal (or =4h) with5 log(10) reduction in the initial inocula for all strains, regardless of the presence or not of albumin or the use of concentrations similar to free C(max). C(min) exhibited similar final colony counts at 0h and 24h in curves with albumin, but with3 log colony-forming units (CFU)/mL reduction ator =4h for strains with an MIC of 1microg/mL and ca. 2 logCFU/mL reduction ator =6h for strains with an MIC of 2microg/mL. This activity was significantly higher than the activity of the free C(min) fraction. The results of this study reinforce the idea that pharmacodynamics using concentrations calculated using reported protein binding are unreliable. Daptomycin exhibited rapid antibacterial activity against vancomycin-tolerant MRSA isolates even against those with high daptomycin MICs in the presence of physiological albumin concentrations.

Among 165 Spanish Haemophilus influenzae isolates with mutations in the ftsI gene (ftsI(+)) (2005 to 2007), 73% were beta-lactamase negative and 26.7% were positive. The proportion of beta-lactamase-negative isolates to beta-lactamase-positive isolates was 2:1 to 4:1 in general, versus 1:3 in pediatric hospitals. Among 44 beta-lactamase-positive strains, 8 strains produced ROB-1 (5 from the pediatric hospital). beta-Lactamase-positive ftsI(+) strains were phylogenetically closer than were beta-lactamase-negative strains.

OBJECTIVES The aim of the study was to analyse the evolution of antibiotic non-susceptibility in Spanish invasive Streptococcus pneumoniae after licensure of respiratory-quinolones for adults and 7-valent pneumococcal conjugate vaccine (PCV-7) for immunization of children. METHODS All invasive pneumococci received in the Reference Laboratory (January 2000-August 2007; n = 12 957 isolates) were serotyped, and susceptibility to penicillin/erythromycin/levofloxacin was determined. Antibiotic consumption and PCV-7 doses/year were provided by IMS and the manufacturer, respectively. RESULTS In 2000-07, PCV-7 distribution (doses/1000 inhabitants

To study the influence of penicillin/amoxicillin non-susceptibility on the activity of third-generation cephalosporins, 430 consecutive penicillin non-susceptible Streptococcus pneumoniae 2007 isolates received in the Spanish Reference Pneumococcal Laboratory were tested. For comparative purposes, 625 penicillin-susceptible 2007 isolates were also tested. Susceptibility was determined by agar dilution using Mueller-Hinton agar supplemented with 5% sheep blood. Penicillin-susceptible strains were susceptible to amoxicillin, cefotaxime and ceftriaxone, 99.8% to cefpodoxime and 99.5% to cefdinir, and were inhibited by 0.12 microg/ml of cefditoren and 4 microg/ml of cefixime. Penicillin-intermediate strains were susceptible to cefotaxime and ceftriaxone, with50% susceptibility to cefdinir and cefpodoxime. The MIC(50) and MIC(90) values of cefditoren were 0.25 microg/ml and 0.5 microg/ml, respectively, whereas cefixime exhibited only marginal activity (MIC(90)=16 microg/ml). Penicillin-resistant strains were resistant to cefdinir and cefpodoxime, with 74.8% and 94.1% susceptibility to cefotaxime and ceftriaxone, respectively. Cefditoren MIC(50)/MIC(90) (0.5/1 microg/ml) were lower than cefotaxime and ceftriaxone. Among amoxicillin non-susceptible strains, susceptibility to cefdinir and cefpodoxime was10%, and susceptibility to cefotaxime decreased from 87.9% in the intermediate category to 63.0% in the resistant group. Cefditoren MIC(50)/MIC(90) (0.5/1 microg/ml) were lower than cefotaxime. In conclusion, the activity of cefixime, cefdinir and cefpodoxime was highly affected by penicillin/amoxicillin non-susceptibility, while parenteral third-generation cephalosporins exhibited higher intrinsic activity (MIC(90)=1 microg/ml for penicillin-resistant and 2 microg/ml for amoxicillin-resistant strains). Cefditoren exhibited one-dilution lower MIC(90) values for these strains, even against those of the most troublesome serotypes.

Killing curves and a sepsis model were performed with Streptococcus pneumoniae strains (MICs of penicillin = 0.01, 1, 2 and 4 mg/L) to assess the in vivo effect of in vitro early bactericidal activity. Optimal bactericidal concentration (OBC) was defined as the minimal concentration needed to obtain the maximal bactericidal activity during the sampling time for colony counting in killing curves. Animals were treated with amoxycillin, cefuroxime or cefpodoxime every 8 h for 48 h, with doses ranging from 2.5 to 50 mg/kg. ED100 (minimal antibiotic dose obtaining a 100% survival) was used as efficacy endpoint. Cmax/MIC, AUC/MIC and deltaT >MIC did not accurately predict efficacy against the most resistant strains, deltaT >OBC being the most predictive efficacy parameter indicating the in vivo effect of early bactericidal activity. Lower deltaT >OBC values for amoxycilin vs oral cehalosporins were needed for efficacy. The higher early bactericidal activity of amoxycillin may explain its higher in vivo efficacy.

The in vitro activity of gemifloxacin versus those of 11 other antimicrobial agents against 400 strains of Neisseria gonorrhoeae was determined by microdilution with supplemented GC agar. A total of 37.5% of the strains were β-lactamase positive. A total of 70 and 6.4% of the β-lactamase-negative strains exhibited intermediate and high-level penicillin resistance, respectively. Ceftriaxone and gemifloxacin were the most active drugs (MICs at which 90% of isolates are inhibited, 0.01 versus 0.007 μg/ml, respectively), with 100% of strains inhibited by 0.12 μg/ml.

The MICs at which 90% of isolates are inhibited for gemifloxacin, trovafloxacin, and grepafloxacin were low (≤0.01 μg/ml) for 271 Legionella isolates when they were determined by the broth microdilution method but increased (≥6 dilutions) when they were determined by the agar dilution method. This was due to the charcoal in the agar dilution medium, as shown by the progressive decrease in the MICs when the charcoal concentrations decreased. As free drug is the active fraction, charcoal binding should be considered.

Serum bactericidal activity against a penicillin-susceptible strain and a penicillin-resistant strain of Streptococcus pneumoniae (amoxicillin and cefotaxime MICs, 0.001 and 1 microg/ml, respectively, and MBCs, 0.01 and 2 microg/ml, respectively) was measured in 12 healthy volunteers who each received an oral 875-mg dose of amoxicillin and an intramuscular 1-g dose of cefotaxime in a crossover fashion. The areas under the bactericidal activity-time curves for the two strains were found to be similar for both antibiotics despite the significantly higher (P < 0.002) AUC/MIC and peak level/MIC values for cefotaxime.

The prediction of urine antibacterial activity from pharmacological and microbiological parameters was assessed by using experimental urine levels and urine bactericidal titers determined up to 72 h after a 400-mg single dose of two quinolones in a phase I study. The area under the bactericidal curve (AUBC) was accurately predicted for norfloxacin but significantly (P < 0.001) underestimated for rufloxacin (actual value was four times higher than the predicted value against Escherichia coli and two times higher against Staphylococcus aureus). In vitro susceptibility differences between the two strains predicted the ex vivo AUBC differences for norfloxacin but not for rufloxacin, where ex vivo differences were greater than expected. Urine bactericidal titers for up to 72 h were accurately predicted for norfloxacin against E. coli and S. aureus and for rufloxacin against S. aureus, but experimental activity for up to 48 h was four times higher (P < 0.001) than the predicted activity for rufloxacin against E. coli. In the case of norfloxacin, the duration of adequate urine antibacterial activity against S. aureus was overestimated. Inaccurate estimations of ex vivo antibacterial activity of a suspected active metabolite (as with rufloxacin) when an adequate cutoff is not established may have dosing implications.

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.

The effects of concentrations that simulated those in human serum after a single intravenous dose of amoxicillin (2 g), amoxicillin-clavulanic acid (2,000 and 200 mg, respectively), or vancomycin (500 mg), on the viability and β-lactamase activity of two isogenic (β-lactamase and non-β-lactamase producer) heteroresistant Staphylococcus aureus strains were studied in an in vitro pharmacodynamic model. A reduction of ≥97% of the initial inoculum was obtained with vancomycin and amoxicillin-clavulanic acid against both strains, with respect to the total bacterial population and the oxacillin-resistant subpopulation. The same pattern was observed with amoxicillin and the β-lactamase-negative strain. β-Lactamase activity in the β-lactamase-positive strain changed over time parallel to viability, decreasing with amoxicillin-clavulanic acid or vancomycin and increasing in the amoxicillin and control groups. Clavulanic acid concentrations achievable in serum that changed over time allowed amoxicillin to act against the β-lactamase-producing methicillin-resistant S. aureus to a similar extent as vancomycin.

The in vitro susceptibility to trovafloxacin and gemifloxacin of Streptococcus pneumoniae strains exhibiting decreased susceptibility to ciprofloxacin (MICor =2 microg/ml; 30 strains with intermediate resistance [MIC 2 microg/ml] and 43 strains with complete resistance [MICor =4 microg/ml]) was determined. Seventy-three strains collected in a surveillance study carried out from May 1996 to April 1997 in Spain (prior to commercialisation of trovafloxacin and gemifloxacin) from patients with respiratory tract infections were tested. The antibacterial activity of gemifloxacin was affected to a lesser extent than that of trovafloxacin by the increase in the MIC of ciprofloxacin, with gemifloxacin showing significantly (Por =0.001) better antibacterial activity than trovafloxacin in all ciprofloxacin MIC categories (MIC50/MIC90 values of 0.015/0.03, 0.015/0.06, 0.03/0.06 and 0.12/0.25 microg/ml for gemifloxacin vs. 0.12/0.12, 0.12/1, 0.25/0.5 and 2/4 microg/ml for trovafloxacin in the 2, 4, 8 andor =16 microg/ml ciprofloxacin MIC categories, respectively). Nine (12.3%) of these 73 strains exhibited decreased susceptibility to trovafloxacin (or =2 microg/ml), whereas all strains were inhibited by 0.25 microg/ml of gemifloxacin.

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.

The aim of this study was to evaluate the effects of penicillin, amoxicillin or erythromycin resistance on the in vitro activity of oral cephalosporins against Streptococcus pneumoniae pediatric isolates. A total of 282 pediatric isolates received during 2005 in the Spanish Reference Pneumococcal Laboratory were tested by agar dilution: 104 strains were penicillin-susceptible, 72 intermediate, and 106 resistant. Serotypes 9 and 14 were the most troublesome with10% susceptibility to oral cephalosporins. Cefditoren exhibited the highest intrinsic activity against penicillin/amoxicillin-resistant pneumococci, with MIC(90s )of 0.5 microg/ml, followed by cefotaxime (2 microg/ml), cefpodoxime (4 microg/ml), cefuroxime (16 microg/ml), and cefaclor/cefixime (or= 32 microg/ml), with 0% susceptibility to cefaclor, cefuroxime and cefpodoxime. Cefditoren 0.5 microg/ml inhibited 95.3%, 95.5%, and 98.6% of penicillin-, amoxicillin-, and erythromycin-resistant isolates, respectively. Susceptibility to oral cephalosporins shifted from90% in penicillin-susceptible isolates to approximately 38% for cefuroxime/cefpodoxime and approximately 7% for cefaclor in penicillin-intermediate, and to 0% in resistant isolates. Despite the different in vitro activity of oral cephalosporins, full resistance to penicillin or amoxicillin implied lack of susceptibility to all oral cephalosporins with defined CLSI breakpoints, rendering them inadequate as empirical treatment in countries with a high prevalence of penicillin resistance.

Real, Ana et al., A strict gluten-free diet (GFD) is the only currently available therapeutic treatment for patients with celiac disease (CD). Traditionally, treatment with a GFD has excluded wheat, barley and rye, while the presence of oats is a subject of debate. The most-recent research indicates that some cultivars of oats can be a safe part of a GFD. In order to elucidate the toxicity of the prolamins from oat varieties with low, medium, and high CD toxicity, the avenin genes of these varieties were cloned and sequenced, and their expression quantified throughout the grain development. At the protein level, we have accomplished an exhaustive characterization and quantification of avenins by RP-HPLC and an analysis of immunogenicity of peptides present in prolamins of different oat cultivars. Avenin sequences were classified into three different groups, which have homology with S-rich prolamins of Triticeae. Avenin proteins presented a lower proline content than that of wheat gliadin; this may contribute to the low toxicity shown by oat avenins. The expression of avenin genes throughout the development stages has shown a pattern similar to that of prolamins of wheat and barley. RP-HPLC chromatograms showed protein peaks in the alcohol-soluble and reduced-soluble fractions. Therefore, oat grains had both monomeric and polymeric avenins, termed in this paper gliadin- and glutenin-like avenins. We found a direct correlation between the immunogenicity of the different oat varieties and the presence of the specific peptides with a higher/lower potential immunotoxicity. The specific peptides from the oat variety with the highest toxicity have shown a higher potential immunotoxicity. These results suggest that there is wide range of variation of potential immunotoxicity of oat cultivars that could be due to differences in the degree of immunogenicity in their sequences. © 2012 Real et al., This work was supported by the Spanish Ministerio de Economía y Competitividad (MINECO,Programa INNPACTO, IPT-2011-1321-010000) and the European Regional Development Fund (FEDER). FP is supported by a Ramón y Cajal research contract from the MINECO (RYC-2010-07345).