Exploring therapeutic options for mild diabetic-related foot infections: a comparative in vitro study of cefditoren versus amoxicillin/clavulanic acid.

Skin and soft tissue infections (SSTIs), and particularly diabetic-related foot infections (DFI), present diagnostic and therapeutic complexities, often leading to severe complications. This study aims to evaluate the in vitro efficacy of cefditoren and amoxicillin/clavulanic acid against typical DFI pathogens. Clinical samples from 40 patients with mild SSTIs were analyzed, revealing a predominance of Staphylococcus spp. and Streptococcus spp. species. Cefditoren exhibited activity against 90% of isolates, with superior potency over amoxicillin/clavulanic acid. These findings underscore the utility of cefditoren in empirical treatment of DFI, although a larger sample size would be desirable for further validation.

Beta-amyloidolysis and glutathione in Alzheimer's disease.

In this review, we hypothesized the importance of the interaction between the brain glutathione (GSH) system, the proteolytic tissue plasminogen activator (t-PA)/plasminogen/ plasmin system, regulated by plasminogen activator inhibitor (PAI-1), and neuroserpin in the pathogenesis of Alzheimer's disease. The histopathological characteristic hallmark that gives personality to the diagnosis of Alzheimer's disease is the accumulation of neurofibroid tangles located intracellularly in the brain, such as the protein tau and extracellular senile plaques made primarily of amyloidal substance. These formations of complex etiology are intimately related to GSH, brain protective antioxidants, and the proteolytic system, in which t-PA plays a key role. There is scientific evidence that suggests a relationship between aging, a number of neurodegenerative disorders, and the excessive production of reactive oxygen species and accompanying decreased brain proteolysis. The plasminogen system in the brain is an essential proteolytic mechanism that effectively degrades amyloid peptides ("beta-amyloidolysis") through action of the plasmin, and this physiologic process may be considered to be a means of prevention of neurodegenerative disorders. In parallel to the decrease in GSH levels seen in aging, there is also a decrease in plasmin brain activity and a progressive decrease of t-PA activity, caused by a decrease in the expression of the t-PA together with an increase of the PAI-1 levels, which rise to an increment in the production of amyloid peptides and a lesser clearance of them. Better knowledge of the GSH mechanism and cerebral proteolysis will allow us to hypothesize about therapeutic practices.

A 40-month multicentre, randomised placebo-controlled study to assess the efficacy and carry-over effect of repeated intra-articular injections of hyaluronic acid in knee osteoarthritis: the AMELIA project.

OBJECTIVE: AMELIA (OsteoArthritis Modifying Effects of Long-term Intra-articular Adant) was designed to compare against placebo the efficacy and safety of repeated injections of hyaluronic acid (HA) and its effect on disease progression over 40 months. METHODS: A multicentre, randomised, patient and evaluator-blinded, controlled study in 306 patients fulfilling American College of Rheumatology criteria for knee osteoarthritis, radiological grades II-III (Kellgren-Lawrence) and joint space width ≥ 2 mm. Patients received four cycles of five intra-articular HA or placebo injections with a follow-up of 6 months after the first and second cycles, and 1 year after the third and fourth cycles. Osteoarthritis Research Society International (OARSI) 2004 responder criteria were used to assess efficacy. The consumption of rescue medication was a secondary outcome. Adverse events were recorded for safety purposes. RESULTS: At the 40-month visit significantly more patients responded to HA compared with placebo (OARSI 2004, p=0.004). The number of responders to HA increased through the study, whereas those to placebo did not change. Significant differences were also found in favour of HA for each individual component of the OARSI 2004. No safety problems were recorded. CONCLUSIONS: The results of AMELIA offer pioneer evidence that repeated cycles of intra-articular injections of HA not only improve knee osteoarthritis symptoms during the in-between cycle period but also exert a marked carry-over effect for at least 1 year after the last cycle. In this respect, it is not possible to establish if this carry-over effect reflects true osteoarthritis remission or just a modification of the disease's natural course. ClinicalTrials.gov number, NCT00669032.

Cefditoren versus ceftazidime in inducer-substrate combinations for the evaluation of AmpC production in a disc approximation test.

OBJECTIVE: To evaluate cefditoren in inducer-substrate combinations to screen for AmpC induction. METHODS: 100 clinical isolates (25 P. aeruginosa, 25 E. cloacae, 14 M. morganii, 13 S. marcescens, 12 C. freundii, 7 P. rettgeri, and 4 E. aerogenes) were tested by the Kirby-Bauer disc approximation method using cefditoren and ceftazidime discs as substrates, and cefditoren and imipenem discs as inducers. RESULTS: None of the strains showed induction of AmpC with cefditoren-ceftazidime as inducer-substrate combination. Imipenem-cefditoren as inducer-substrate combination was not useful for evaluating strains of P. aeruginosa since no inhibition zones surrounding the cefditoren disc were found. Among evaluable enterobacteria (those showing substrate inhibition zone), inducible Amp C was detected in 48 out of 63 (76.2%) with cefditoren, and in 33 out of 68 (48.5%) isolates with ceftazidime as substrate. Significantly (p=0.013) higher number of AmpC producers were detected with cefditoren versus ceftazidime (76.2% vs. 48.5%), due to the differences found for E. cloacae (72.8% vs. 21.7%; p=0.0009) and S. marcescens (100% vs. 54.5%; p=0.03). Higher mean reductions of diameters around substrate discs were found for cefditoren (4.17 mm) vs. ceftazidime (3.79 mm), reaching statistical significance (p<0.05) for indol-positive proteae: M. morganii (5.32 mm vs. 3.92 mm) and P. rettgeri (3.47 mm vs. 2.64 mm). CONCLUSION: Cefditoren showed no induction capability, and when used as substrate (with imipenem as inducer) it offered detection rates of AmpC inducible enterobacteria higher than the imipenem-ceftazidime combination, mainly for Enterobacter spp. and Serratia spp., with higher diameter reductions for indol-positive proteae.

Use of sulodexide in patients with peripheral vascular disease.

Sulodexide is a highly purified glycosaminoglycan containing a combination of heparan sulfate with affinity for antithrombin III and dermatan sulfate with affinity for heparin cofactor II. This antithrombotic and antithrombin activity is of great pharmacologic interest and makes sulodexide a suitable drug for the prophylaxis and treatment of arterial and venous peripheral diseases. In arterial pathology, changes in the Winsor Index, improvement in peripheral blood flow, and reduction in pain-free walking distance confirm that treatment with oral sulodexide is effective. Lipid components linked to the genesis of peripheral vascular processes, including triglycerides, total cholesterol, and low-density lipoprotein fractions, as well as plasma and blood viscosity, are reduced by the administration of sulodexide, whereas the high-density lipoprotein fraction increases. Sulodexide inhibits aggregation and adhesion of platelets at the level of the vascular wall, reduces plasma fibrinogen concentrations, reduces plasminogen activator inhibitor-1, and increases tissue plasminogen activator, as well as systemic fibrinolytic and thrombolytic activity, thereby demonstrating efficacy in the treatment of thromboembolic disease. There is no interaction between sulodexide and other drugs used as long-term treatment for peripheral vascular disease. It is well tolerated, and the adverse reactions described after oral administration are related mainly to transient gastrointestinal intolerance, ie, nausea, dyspepsia, and minor bowel symptoms. Sulodexide may become the treatment of choice when dealing with vascular diseases and their complications, as well as for the prevention of venous thromboembolic disease, being particularly indicated in elderly patients, due to its good tolerability and ease of management.

In vitro interference of beta-lactams with biofilm development by prevalent community respiratory tract isolates.

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.

Safety profile of cefditoren. A pooled analysis of data from clinical trials in community-acquired respiratory tract infections.

INTRODUCTION: A high number of individuals in the population are exposed to antibiotics for the treatment of respiratory tract infections. It is important to review the adverse events profile related to antibiotic exposure during the clinical development of drugs that are or have been recently included in the therapeutic armamentarium. MATERIAL AND METHODS: Safety data from all 13 clinical trials of cefditoren on community acquired respiratory infections were reviewed. Safety population was defined as all randomized patients with at least one dose intake. Adverse events considered by investigators as related during antibiotic exposure were considered. RESULTS: The overall safety population consisted in 4,592 patients for cefditoren and 2,784 for comparators. Overall reported diarrhoea related to cefditoren administration was significantly higher (p < or = 0.001) than comparators (9.9% vs 6.9%) due to the significant difference in the pooled pharyngotonsillitis studies (8.3% vs 3.2%), while no significant differences in others pathologies were found, with 9.4% (with cefditoren) vs 10.3% (with comparators) in the case of community-acquired pneumonia (CAP). Dyspepsia and abdominal pain were reported as adverse events in < 2.7% patients regardless the treated disease. In females population lower related vaginosis rate was found in cefditoren vs comparators, mainly due to differences among patients treated for sinusitis (4.5% vs 8.1%) and CAP (2.3% vs 5.5%) although differences were not significant (p = 0.017 and p = 0.008, respectively). CONCLUSION: This study analysing reported adverse events from clinical trials showed an adverse events profile of cefditoren similar to those of standard antibiotics used in the treatment of respiratory tract infections.

Safety profile of cefditoren. A pooled analysis of data from clinical trials in community-acquired respiratory tract infections / Perfil de seguridad de cefditoren. Análisis combinado de los datos de ensayos clínicos en el tratamiento de infecciones respiratorias comunitarias

Introducción. Gran número de sujetos en la población se expone a antibióticos como tratamiento de infecciones respiratorias. Por ello es importante la revisión del perfil de acontecimientos adversos relacionados con la exposición a los antibióticos durante el desarrollo clínico de aquellos que han sido o van a ser incluidos en el arsenal terapéutico. Material y métodos. Se revisaron los datos de seguridad de 13 ensayos clínicos de cefditoren en el tratamiento de infecciones respiratorias comunitarias. La población para análisis de seguridad se definió con todos los pacientes randomizados que recibieron al menos una dosis de la medicación del estudio. Se analizaron los acontecimientos adversos considerados por los investigadores como relacionados a la exposición al antibiótico. Resultados. La población para análisis de seguridad consistió en 4.592 pacientes tratados con cefditoren y 2.784 con los comparadores. La tasa global de diarrea comunicada con cefditoren fue significativamente mayor (p ≤ 0,001) que la de los comparadores, debido a la diferencia significativa en el análisis de los estudios de faringoamigdalitis (8,3 % frente a 3,2 %). No hubo diferencias significativas en las otras patologías estudiadas, con unas tasas de diarrea relacionada de 9,4% para cefditoren y 10,3% para los comparadores en el caso de la neumonía adquirida en la comunidad (NAC). Se comunicó dispesia y dolor abdominal en menos del 2,7% de los pacientes con independencia de la infección tratada o tratamiento. En mujeres, la tasa de vaginosis fue menor con cefditoren frente a comparadores, fundamentalmente debido a las diferencias en sinusitis (4,5% frente a 8,1%) y NAC (2,3% frente a 5,5%), aunque éstas no alcanzaron significación estadística (p = 0,017 y p = 0,008, respectivamente). Conclusión. Cefditoren presenta un perfil de acontecimientos adversos similar al de los antibióticos comúnmente utilizados en el tratamiento de la infección respiratoria comunitaria (AU)

Introduction. A high number of individuals in the population are exposed to antibiotics for the treatment of respiratory tract infections. It is important to review the adverse events profile related to antibiotic exposure during the clinical development of drugs that are or have been recently included in the therapeutic armamentarium. Material and methods. Safety data from all 13 clinical trials of cefditoren on community acquired respiratory infections were reviewed. Safety population was defined as all randomized patients with at least one dose intake. Adverse events considered by investigators as related during antibiotic exposure were considered. Results. The overall safety population consisted in 4,592 patients for cefditoren and 2,784 for comparators. Overall reported diarrhoea related to cefditoren administration was significantly higher (p ≤ 0.001) than comparators (9.9% vs 6.9%) due to the significant difference in the pooled pharyngotonsillitis studies (8.3% vs 3.2%), while no significant differences in others pathologies were found, with 9.4% (with cefditoren) vs 10.3% (with comparators) in the case of community-acquired pneumonia (CAP). Dyspepsia and abdominal pain were reported as adverse events in < 2.7% patients regardless the treated disease. In females population lower related vaginosis rate was found in cefditoren vs comparators, mainly due to differences among patients treated for sinusitis (4.5% vs 8.1%) and CAP (2.3% vs 5.5%) although differences were not significant (p = 0.017 and p = 0.008, respectively). Conclusion. This study analysing reported adverse events from clinical trials showed an adverse events profile of cefditoren similar to those of standard antibiotics used in the treatment of respiratory tract infections (AU)

beta-lactam susceptibility of Escherichia coli isolates from urinary tract infections exhibiting different resistance phenotypes.

Susceptibility to beta-lactams was determined in 203 recent Spanish E. coli isolates from urinary tract infections exhibiting different resistance phenotypes: a) susceptible (n = 60); b) quinolone-resistant (n = 45); c) penicillinase (n=64); d) hyperproduction of penicillinase (n=8); e) inhibitor resistant TEM (IRT) (n=18), and f) extended spectrum betalactamase (ESBL) (n=8).Minimum inhibitory concentration (MIC) determination by agar dilution and susceptibility tests for ESBL detection by macrodilution were performed following CLSI recommendations. All the beta-lactams tested showed high activity against susceptible and penicillinase phenotypes, with close to 100 % susceptibility. Hyperproduction of penicillinase increased MIC90 values for all antibiotics except for meropenem, with 100% resistance to cefuroxime and amoxicillin/clavulanic acid, and 100% susceptibility to cefotaxime, piperacillin/tazobactam and meropenem. All the antibiotics, except for amoxicillin/clavulanic acid, exhibited high activity against IRT. Meropenem, cefminox and piperacillin/tazobactam exhibited the highest activity against ESBL, followed by amoxicillin/clavulanic acid. The most active compound among the parenteral antibiotics was meropenem, regardless of the resistance phenotype. Among the oral antibiotics, the most active compound was cefditoren with the exception of ESBL where amoxicillin/clavulanic acid where the MIC90 value was one dilution lower.

â - lactam susceptibility of Escherichia coli isolates from urinary tract infections exhibiting different resistance phenotypes

Susceptibility to â-lactams was determined in 203 recentSpanish E. coli isolates from urinary tract infectionsexhibiting different resistance phenotypes: a) susceptible(n = 60); b) quinolone-resistant (n = 45); c) penicillinase(n=64); d) hyperproduction of penicillinase (n=8); e) inhibitorresistant TEM (IRT) (n=18), and f) extended spectrumbetalactamase (ESBL) (n=8). Minimum inhibitory concentration(MIC) determination by agar dilution and susceptibilitytests for ESBL detection by macrodilution were performedfollowing CLSI recommendations. All the â-lactamstested showed high activity against susceptible and penicillinasephenotypes, with close to 100 % susceptibility.Hyperproduction of penicillinase increased MIC90 values forall antibiotics except for meropenem, with 100% resistanceto cefuroxime and amoxicillin/clavulanic acid, and 100%susceptibility to cefotaxime, piperacillin/tazobactam andmeropenem. All the antibiotics, except for amoxicillin/clavulanicacid, exhibited high activity against IRT. Meropenem,cefminox and piperacillin/tazobactam exhibited thehighest activity against ESBL, followed by amoxicillin/clavulanicacid. The most active compound among the parenteralantibiotics was meropenem, regardless of the resistancephenotype. Among the oral antibiotics, the most activecompound was cefditoren with the exception of ESBL whereamoxicillin/clavulanic acid where the MIC90 value wasone dilution lower (AU)

Se determinó la susceptibilidad a betalactámicos de203 aislados recientes de E. coli procedentes de infeccionesdel tracto urinario en España y que presentaban distintosfenotipos de resistencia: a) susceptible (n = 60);b) resistente a quinolonas (n=45); c) productor de penicilinasa(n=64); d) hiperproductor de penicilinasa (n=8);e) resistente a inhibidores de TEM (IRT) (n=18), y f) productorde betalactamasas de espectro extendido (BLEE)(n=8). La determinación de la concentración mínima inhibitoria(CMI) por dilución en agar y los tests de susceptibilidadpara la detección de BLEE se realizaron siguiendolas recomendaciones del Clinical and Laboratory StandardsInstitute (CLSI). Frente a los fenotipos susceptible yproductor de penicilinasa, todos los betalactámicos ensayadosexhibieron gran actividad, con una sensibilidadcercana al 100% de los aislados. La hiperproducción depenicilinasa incrementó los valores de CMI90 de todos losantibióticos, excepto de meropenem, con un 100% de resistenciaa cefuroxima y amoxicilina/clavulánico y un 100% desensibilidad a cefotaxime, piperacilina/tazobactam y meropenem.Todos los antibióticos, excepto amoxicilina/clavulánico,presentaron gran actividad frente a las cepas IRT.Meropenem, cefminox y piperacilina/tazobactam presentaronla mayor actividad frente a BLEE, seguidas de amoxicilina/clavulánico. Entre los antibióticos parenterales, elcompuesto más activo fue meropenem, con independenciadel fenotipo de resistencia. Entre los antibióticos oralesel compuesto más activo fue cefditoren, excepto frentea las cepas BLEE, donde amoxicilina/clavulánico presentóen un valor de CMI90 una dilución menor (AU)

In vitro activity of oral cephalosporins against pediatric isolates of Streptococcus pneumoniae non-susceptible to penicillin, amoxicillin or erythromycin.

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 with <10% 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 from >90% 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.

Efficacy of cefditoren in the treatment of upper respiratory tract infections: a pooled analysis of six clinical trials.

OBJECTIVE: A pooled analysis of all upper respiratory tract infection studies performed with cefditoren (CDN) was performed. METHODS: Studies were prospective, comparative, multicentre and randomised. Comparators were penicillin V (pharyngitis) and cefuroxime or amoxicillin/clavulanate (sinusitis). A total of 1,322 patients were randomized, 1,241 included in intention-to-treat (ITT) and 1,010 in per-protocol populations (PP) in pharyngotonsillitis studies, and 1,819 randomized, 1,726 included in ITT and 1,589 in PP in acute sinusitis studies. RESULTS: No significant differences in pharyngitis clinical response were found (success rates: 89.4 % to 95.3 %). S. pyogenes eradication was higher with cefditoren at end of therapy (EOT) (90.4% vs. 82.7%; p=0.002) and follow-up (84.7% vs. 76.7%; p=0.008), although no statistically significant (p<0.001). In both groups, clinical failures were significantly higher (p<0.001) in patients showing S. pyogenes persistence than in those showing eradication (> or =98.5% vs. 51.4 %). No differences in sinusitis clinical response were found between CDN and comparators both at EOT (80.2% vs. 84.8%) and at end of follow-up (71.2% vs. 77.4%). CONCLUSION: Cefditoren had similar point estimates of clinical efficacy to comparators in pharyngotonsillitis and sinusitis, and a tendency to higher S. pyogenes eradication in pharyngotonsillitis.

Beta-lactam activity against penicillin-resistant Streptococcus pneumoniae strains exhibiting higher amoxicillin versus penicillin minimum inhibitory concentration values: an in vitro pharmacodynamic simulation.

BACKGROUND: Activity of simulated serum concentrations after oral therapy with 400 mg cefditoren pivoxil b.i.d., 500 mg cefuroxime axetil b.i.d. and 875/125 mg amoxicillin/clavulanic acid b.i.d. and t.i.d. regimens was explored over 24 h against Streptococcus pneumoniae. METHODS: Computerized pharmacodynamic simulations were performed against strains with penicillin/amoxicillin/cefuroxime/cefditoren minimum inhibitory concentrations (MICs, microg/ml) and serotypes: strain 1 (0.25/0.12/1/0.12; serotype 6A), strain 2 (2/4/ 2/0.25; serotype 6B), strain 3 (4/16/4/0.5; serotype 14), and strain 4 (4/16/8/1; serotype 14). RESULTS: Bactericidal activity (> or =3 log(10) reduction) at 12 and 24 h was obtained against all strains with cefditoren, against strains 1 and 2 with cefuroxime and amoxicillin/clavulanic acid t.i.d., but only against strain 1 with amoxicillin/clavulanic acid b.i.d.. Bactericidal activity at 24 h was related to T > MIC of >30% dosing interval, 1.7-2.0 log(10) reductions with T > MIC of 20-30%, and <1 log(10) reduction or regrowth with T > MIC of 0%. CONCLUSIONS: It is difficult to achieve pharmacodynamic coverage and bactericidal activity by physiological concentrations of oral beta-lactams against penicillin-resistant pneumococcal strains exhibiting higher amoxicillin versus penicillin MICs. Cefditoren may offer alternatives.

Feasibility of utilizing bioindicators for testing microbial inactivation in sweetpotato purees processed with a continuous-flow microwave system.

Continuous-flow microwave heating has potential in aseptic processing of various food products, including purees from sweetpotatoes and other vegetables. Establishing the feasibility of a new processing technology for achieving commercial sterility requires evaluating microbial inactivation. This study aimed to assess the feasibility of using commercially available plastic pouches of bioindicators containing spores of Geobacillius stearothermophilus ATCC 7953 and Bacillus subtilis ATCC 35021 for evaluating the degree of microbial inactivation achieved in vegetable purees processed in a continuous-flow microwave heating unit. Sweetpotato puree seeded with the bioindicators was subjected to 3 levels of processing based on the fastest particles: undertarget process (F(0) approximately 0.65), target process (F(0) approximately 2.8), and overtarget process (F(0) approximately 10.10). After initial experiments, we found it was necessary to engineer a setup with 2 removable tubes connected to the continuous-flow microwave system to facilitate the injection of indicators into the unit without interrupting the puree flow. Using this approach, 60% of the indicators injected into the system could be recovered postprocess. Spore survival after processing, as evaluated by use of growth indicator dyes and standard plating methods, verified inactivation of the spores in sweetpotato puree. The log reduction results for B. subtilis were equivalent to the predesigned degrees of sterilization (F(0)). This study presents the first report suggesting that bioindicators such as the flexible, food-grade plastic pouches can be used for microbial validation of commercial sterilization in aseptic processing of foods using a continuous-flow microwave system.

Measurement of dielectric properties of pumpable food materials under static and continuous flow conditions.

Continuous flow microwave sterilization is an emerging technology that has the potential to replace the conventional heating processes for viscous and pumpable food products. Dielectric properties of pumpable food products were measured by a new approach (under continuous flow conditions) at a temperature range of 20 to 130 degrees C and compared with those measured by the conventional approach (under static conditions). The food products chosen for this study were skim milk, green pea puree, carrot puree, and salsa con queso. Second-order polynomial correlations for the dependence of dielectric properties at 915 MHz of the food products on temperature were developed. Dielectric properties measured under static and continuous flow conditions were similar for homogeneous food products such as skim milk and vegetable puree, but they were significantly different for salsa con queso, which is a multiphase food product. The results from this study suggest that, for a multiphase product, dielectric properties measured under continuous flow conditions should be used for designing a continuous flow microwave heating system.

Feasibility of aseptic processing of a low-acid multiphase food product (salsa con queso) using a continuous flow microwave system.

Aseptic processing of a low-acid multiphase food product using a continuous flow microwave heating system can combine the advantages of an aseptic process along with those of microwave heating. Dielectric properties of 2 different brands of 1 such product (salsa con queso) were measured under continuous flow conditions at a temperature range of 20 to 130 degrees C. At 915 MHz, the dielectric constant ranged from 58.7 at 20 degrees C to 41.3 at 130 degrees C with dielectric loss factor ranging from 41.0 at 20 degrees C to 145.5 at 130 degrees C. The loss tangent at 915 MHz ranged from 0.61 at 20 degrees C to 3.52 at 130 degrees C. The temperature profiles at the outlet during processing of salsa con queso in a 5-kW microwave unit showed a narrow temperature distribution between the center and the wall of the tube. The study showed the feasibility of aseptic processing of salsa con queso using a continuous flow microwave system.

influence of TEM-1 beta-lactamase on the pharmacodynamic activity of simulated total versus free-drug serum concentrations of cefditoren (400 milligrams) versus amoxicillin-clavulanic acid (2,000/125 milligrams) against Haemophilus influenzae strains exhibiting an N526K mutation in the ftsI gene.

The aim of this study was to explore bactericidal activity of total and free serum simulated concentrations after the oral administration of cefditoren (400 mg, twice daily [bid]) versus the oral administration of amoxicillin-clavulanic acid extended release formulation (2,000/125 mg bid) against Haemophilus influenzae. A computerized pharmacodynamic simulation was performed, and colony counts and beta-lactamase activity were determined over 48 h. Three strains were used: ampicillin-susceptible, beta-lactamase-negative ampicillin-resistant (BLNAR) (also resistant to amoxicillin-clavulanic acid) and beta-lactamase-positive amoxicillin-clavulanic acid-resistant (BLPACR) strains, with cefditoren MICs of < or =0.12 microg/ml and amoxicillin-clavulanic acid MICs of 2, 8, and 8 microg/ml, respectively. Against the ampicillin-susceptible and BLNAR strains, bactericidal activity (> or =3 log(10) reduction) was obtained from 6 h on with either total and free cefditoren or amoxicillin-clavulanic acid. Against the BLPACR strain, free cefditoren showed bactericidal activity from 8 h on. In amoxicillin-clavulanic acid simulations the increase in colony counts from 4 h on occurred in parallel with the increase in beta-lactamase activity for the BLPACR strain. Since both BLNAR and BLPACR strains exhibited the same MIC, this was due to the significantly lower (P < or = 0.012) amoxicillin concentrations from 4 h on in simulations with beta-lactamase positive versus negative strains, thus decreasing the time above MIC (T>MIC). From a pharmacodynamic point of view, the theoretical amoxicillin T>MIC against strains with elevated ampicillin/amoxicillin-clavulanic acid MICs should be considered with caution since the presence of beta-lactamase inactivates the antibiotic, thus rendering inaccurate theoretical calculations. The experimental bactericidal activity of cefditoren is maintained over the dosing interval regardless of the presence of a mutation in the ftsI gene or beta-lactamase production.

Antimicrobial susceptibilities of amoxycillin-non-susceptible and susceptible isolates among penicillin-non-susceptible Streptococcus pneumoniae.

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.