Antibacterial activity of various antibiotics against oral streptococci isolated in the oral cavity.

A total of 550 oral streptococci: 270 Streptococcus mitis, 110 Streptococcus sanguis, 90 Streptococcus anginosus, 50 Streptococcus mutans, 30 Streptococcus salivarius, were isolated from dental plaque and gengival crevices of patients and tested for their susceptibility to 12 ß-lactam antibiotics and to 5 non-ß-lactam antibiotics, using the microdiluition method. Overall, a reduced susceptibility to penicillin was recorded in 13.4% of cases. The percentage of strains resistant to penicillin appeared significantly higher in S. mitis (24%) than in S. sanguis (19%), in S. mutans (14%) and in S. salivarius (10%). No levels of penicillin resistance were shown by 90 strains of S. anginosus. In susceptibility test to antibiotics, imipenem was the most active molecule tested, confirming its general good activity against oral streptococci. Also third generation cephalosporins such as ceftriaxone and fourth generation cephalosporins such as cefepime, showed good activity. Chinolones, glycopeptides and rifampicin confirmed a good activity against oral streptococci.

In vitro activity of cefditoren versus other antibiotics against S. pneumoniae clinical strains isolated in Italy.

Over the last twenty years there has been an alarming increase in isolation of Streptococcus pneumoniae strains with a reduced susceptibility not only to penicillin, but also to other betalactams and macrolides. This phenomenon justifies the great interest in new antibiotics. Cefditoren, a new aminothiazolyl oral cephalosporin, recently commercialized in Italy, is characterized by an extended activity against penicillin-resistant S. pneumoniae. The aim of this study is to evaluate the incidence of the resistance/susceptibility to various antibiotics in 1000 strains of S. pneumoniae (678 SPSS, 219 SPPI and 103 SPPR), clinically isolated during 2009. The data obtained by our in vitro study show that cefditoren is the most active agent against S. pneumoniae. In fact, the MIC90 values of 0.5 micrograms/ml obtained could be particularly significant in therms of therapeutic predictivity.

Antibacterial activity and anti-biofilm effect of chitosan against strains of Streptococcus mutans isolated in dental plaque.

Streptococcus mutans is the major cause of dental plaque and is often associated with biofilm formation. The aim of this study is to evaluate the activity of a hydrosoluble derivative of chitosan against S. mutans biofilms in vitro and in vivo. Strains of S. mutans were isolated from the dental plaque of 84 patients enrolled in the study. The antibacterial activity of chitosan was determined by broth microdilutions. The effect of chitosan at different concentrations and exposure times on S. mutans biofilms at different phases of development was assessed by a clinical study using the classical "4-day plaque regrowth" experiment in adult volunteers. The MIC values of chitosan were between 0.5 and 2 g/L. Compared to distilled water, the chitosan solution significantly decreased the vitality of plaque microflora (p

Distribution of mef(A)-containing genetic elements in erythromycin-resistant isolates of Streptococcus pyogenes from Italy.

In total, 124 Streptococcus pyogenes isolates were obtained from throat cultures of different symptomatic patients. All isolates showed M-phenotype macrolide resistance and contained the macrolide efflux gene mef(A). The isolates were screened for the presence and insertion site of mef(A)-containing genetic elements. In 25.8% of the isolates, mef(A) was found to be carried by elements belonging to the Tn1207.3/Phi10394.4 family inserted in the comEC gene, while 74.2% contained chimeric elements with a different genetic structure and chromosomal location, probably associated with the recently described 60-kb tet(O)-mef(A) element.

Serum lysozyme increased by fructose-1, 6-diphosphate in men, rabbits, and mice.

Fructose-1, 6-diphosphate hydrated sodium salt (FDP), intravenously injected, remarkably stimulates the production of serum lysozyme in man, rabbit, and mouse with a different kinetics in each of them: Man and rabbit show, in the first hour, a concentration peak followed by a slow decrease, whereas in mouse the concentration is less variable with time.

In vitro selection of resistance to clarithromycin in Streptococcus pneumoniae clinical isolates.

In this study the effects of exposure to serum, lung and breakpoint concentrations on Streptococcus pneumoniae susceptibility to clarithromycin, azithromycin, amoxicillin/clavulanate, levofloxacin and moxifloxacin were evaluated. Development of resistance was determined by multi-step and single-step methodologies. In the first experimental set, minimum inhibitory concentrations (MICs) were determined after 10 passages on antibiotic-gradient plates and 10 passages on antibiotic-free plates. Acquisition of resistance was defined as an increase of > or = 4-fold from the starting MIC. In single-step studies, the rate of spontaneous mutations was calculated after a passage on antibiotic-containing agar plates. Azithromycin and levofloxacin gave the highest number of strains with MIC increased of at least 4 times the starting value, followed by moxifloxacin and by clarithromycin which only at the lowest concentration tested selected for resistance in 5 strains. Amoxicillin/clavulanate never displayed > or = 4-fold MIC increase. Frequencies of mutation were lower for clarithromycin and moxifloxacin than for the comparators. At lung concentrations clarithromycin had limited potential to select for resistance.

SmaI macrorestriction analysis of Italian isolates of erythromycin-resistant Streptococcus pyogenes and correlations with macrolide-resistance phenotypes.

High rates of erythromycin resistance among Streptococcus pyogenes strains have been reported in Italy in the last few years. In this study, 370 erythromycin-resistant (MIC, > or = 1 microg/mL) Italian isolates of this species obtained in 1997-1998 from throat swabs from symptomatic patients were typed by analyzing SmaI macrorestriction fragment patterns by pulsed-field gel electrophoresis (PFGE). Among the typable isolates (n = 341; the genomic DNA of the remaining 29 isolates was not restricted by SmaI), 48 distinct PFGE types were recognized, of which 31 were recorded in only one isolate (one-strain types). Fifty-two percent of typable isolates fell into three type clusters and 75% into six, suggesting that erythromycin-resistant group A streptococci circulating in Italy are polyclonal, but the majority of them probably derives from the spread of a limited number of clones. In parallel experiments, the 370 test strains were characterized for the macrolide resistance phenotype: 80 were assigned to phenotype cMLS, 89 to phenotype iMLS-A, 33 to phenotype iMLS-B, 11 to phenotype iMLS-C, and 157 to phenotype M. There was a close correlation between these phenotypic data and the genotypic results of PFGE analysis, the vast majority of the isolates assigned to individual PFGE classes belonging usually to a single phenotype of macrolide resistance. All of the 29 untypable isolates belonged to the M phenotype. Further correlations were observed with tetracycline resistance.

Antianginal and antiischemic efficacy of monotherapy extended-release nisoldipine (Coat Core) in chronic stable angina.

A double-blind, randomized, placebo-controlled study was conducted to test the peak and trough antianginal and antiischemic monotherapy efficacy and safety of a new extended-release formulation of nisoldipine (nisoldipine Coat Core [Bayer Corporation], 20 mg, 40 mg, and 60 mg once daily compared to placebo). Study patients had a history of chronic, stable angina pectoris, exercise-induced angina in association with ST segment depression, and exercise test reproducibility. Of the 483 patients enrolled in the study, results were valid for safety analysis for 312 and for efficacy analysis for 284. There was a statistically significant improvement in total exercise time at both peak and trough for patients taking 20 mg and 60 mg of nisoldipine compared with patients taking placebo, but the group taking 60 mg was not better than the group taking 20 mg (33.9 and 33.7 seconds, respectively, at trough). The results were similar for the secondary endpoints (time to onset of angina and time to 1 mm ST segment depression). No correlation was evident between plasma nisoldipine levels and total exercise duration. Headache and peripheral edema were the most frequently reported adverse events and were dose related. There were no discontinuations due to adverse events in patients randomized to the 20-mg nisoldipine group. No deaths occurred while patients were receiving active nisoldipine therapy. Therapy with this extended-release formulation of nisoldipine is an effective once-daily treatment for chronic stable angina pectoris. It represents one of the few dihydropyridine calcium channel antagonists that has shown efficacy when administered as monotherapy to patients with angina.

Plasmid curing effect of trovafloxacin.

The effect of sub-inhibitory concentrations of trovafloxacin, a recently developed fluoroquinolone molecule, on the capability of Escherichia coli cells to maintain three different types of plasmids has been investigated by a number of approaches, including the quantification of the loss of plasmid-borne functions and of plasmid DNA by quantitative PCR. The results obtained demonstrate that at concentrations ranging from the MIC to 1/8 of the MIC, trovafloxacin induces a clear, albeit incomplete, 'episome-curing' effect which was observed with plasmids differing in copy number, size and nature of the replication origin of the episome. This effect was most likely not due to an alteration of DNA supercoiling.

The efficacy and safety of once-daily nifedipine administered without food: the coat-core formulation compared with the gastrointestinal therapeutic system formulation in patients with mild-to-moderate hypertension. Nifedipine Study Group.

A parallel-group, randomized, double-blind, forced-titration, multicenter study was done to compare the efficacy and safety of once-daily nifedipine coat-core (NIF CC) and once-daily nifedipine gastrointestinal therapeutic system (NIF GITS) dosed in the fasting state in patients with mild-to-moderate essential hypertension. Both formulations have been shown to effectively and safely lower blood pressure in placebo-controlled trials. After a 4-week placebo run-in period, 228 patients were randomized to 4 weeks of treatment with either NIF CC 30 mg daily or NIF GITS 30 mg daily. This period was followed by a forced-titration period to nifedipine 60 mg daily for an additional 4 weeks of double-blind therapy. After the 30-mg treatment period (the primary time point), there were no statistically significant differences between treatment groups in mean change from baseline in trough supine diastolic blood pressure, the primary efficacy variable (NIF CC patients, -7.0 mm Hg; NIF GITS patients, -8.4 mm Hg; P = 0.139). Also, because the upper bound of the treatment difference confidence interval was < 3.0 mm Hg, equivalence--as defined in the protocol--was established. After the 60-mg treatment period, the change from baseline in trough supine diastolic blood pressure was significantly greater for patients treated with NIF GITS than for patients treated with NIF CC (NIF GITS patients, -12.0 mm Hg; NIF CC patients, -8.4 mm Hg; P < 0.001). Because the upper bound of the confidence interval was > 3 mm Hg, equivalence cannot be claimed. No statistically significant differences were noted for the comparison of mean 24-hour ambulatory blood pressure monitoring changes. Both formulations were well tolerated.

Quantitative assessment of mechanical prosthetic valve area by 3-dimensional transesophageal echocardiography.

OBJECTIVE: The goal of this study was to assess the geometric orifice area of mechanical valve prostheses by transesophageal 3-dimensional echocardiographic planimetry. METHODS AND RESULTS: Currently used Doppler methods for prosthetic assessment (orifice area-Doppler) were compared with 3D planimetry for orifice area (orifice area-3D) and with manufacturer's values (orifice area-manufacturer) for the corresponding prosthesis types and sizes and with historical controls provided by Doppler literature (orifice area-literature). Twenty-four mechanical valve prostheses (in 22 patients) were studied: 13 in mitral position and 11 in aortic position. Orifice area-manufacturer, orifice area-Doppler, orifice area-literature, and orifice area-3D were 3.6 +/- 1.1 cm(2), 2.3 +/- 0.9 cm(2), 2.4 +/- 0.9 cm(2), and 2.6 +/- 0.7 cm(2), respectively. Orifice area-manufacturer values were significantly larger. Correlation coefficients between orifice area-3D and orifice area-manufacturer, and between orifice area-3D and orifice area-Doppler and orifice area-literature were 0.83, 0.90, and 0.73, respectively (all P < .0001). CONCLUSION: Three-dimensional transesophageal echocardiography is feasible and has good correlation with orifice area-Doppler (in aortic position) and good correlation with orifice area-manufacturer (in aortic and mitral positions) methods.

Long-term efficacy and safety of cerivastatin 0.8 mg in patients with primary hypercholesterolemia.

BACKGROUND: Statins are the agents of choice in reducing elevated plasma low-density lipoprotein cholesterol (LDL-C). HYPOTHESIS: Cerivastatin 0.8 mg has greater long-term efficacy in reducing LDL-C than pravastatin 40 mg in primary hypercholesterolemia. METHODS: In this double-blind, parallel-group, 52-week study, patients (n = 1,170) were randomized (4:1:1) to cerivastatin 0.8 mg, cerivastatin 0.4 mg, or placebo daily. After 8 weeks, placebo was switched to pravastatin 40 mg. Patients with insufficient LDL-C lowering after 24 weeks were allowed open-labeled resin therapy. RESULTS: Cerivastatin 0.8 mg reduced LDL-C versus cerivastatin 0.4 mg (40.8 vs. 33.6%, p <0.0001) or pravastatin 40 mg (31.5%, p<0.0001), and brought 81.8% of all patients, and 54.1% of patients with atherosclerotic disease, to National Cholesterol Education Program (NCEP) goals. Cerivastatin 0.8 mg improved mean total C (-29.0%), triglycerides (-18.3%), and high-density lipoprotein cholesterol (HDL-C) (+9.7%) (all p < or = 0.013 vs. pravastatin 40 mg). Higher baseline triglycerides were associated with greater reductions in triglycerides and elevations in HDL-C with cerivastatin. Cerivastatin was well tolerated; the most commonly reported adverse events were arthralgia, headache, pharyngitis, and rhinitis. Symptomatic creatine kinase > 10x the upper limit of normal (ULN) occurred in 1, 1.5, and 0% of patients receiving cerivastatin 0.8 mg, cerivastatin 0.4 mg, and pravastatin 40 mg, respectively. Repeat hepatic transaminases >3 x ULN occurred in 0.3-0.5, 0.5, and 0% of patients, respectively. CONCLUSION: In long-term use, cerivastatin 0.8 mg effectively and safely brings the majority of patients to NCEP goal.

In vitro antibacterial activity of rifaximin against Clostridium difficile, Campylobacter jejunii and Yersinia spp.

Fifty-four isolates of Campylobacter jejunii, 91 isolates of Yersinia spp. and 56 isolates of Clostridium difficile, recovered from stools of patients with diarrhoea or other intestinal disturbances and from stools of asymptomatic patients receiving antibiotic therapy, were tested in vitro for susceptibility to rifaximin, rifampicin and neomycin. The in vitro antibacterial activities were found to be comparable against the aerobic bacterium; on the contrary, against microaerophilic and anaerobic bacteria rifaximin and rifampicin were much more effective than neomycin.

Determination of cefatrizine levels in blood, tonsils, paranasal sinuses and middle ear.

Levels of cefatrizine, a new oral cephalosporin, were determined in blood and in tonsils, paranasal sinus secretions and middle ear exudates from 18 patients with acute infections at these sites. Three and six hours after administration of 500 mg cefatrizine satisfactory levels of the antibiotic were found at all the sites examined. Levels in the tonsils and middle ear were higher than those in blood, while lower levels were recorded in nasal secretions.

Human intravenous and intramuscular pharmacokinetics of amoxicillin.

Amoxicillin was administered at doses of 500 mg and 1000 mg, intravenously and intramuscularly to normal volunteers in a parallel study. Intramuscular amoxicillin was 100% bioavailable at both dose levels. Mean peak serum levels observed for the 500 mg and 1000 mg doses, respectively, were: i.v. (5 min after dosing) 46 and 74 micrograms/ml; i.m. (30 min after dosing) 14 and 21 micrograms/ml. Six hour trough levels ranged between 0.5 and 0.9 micrograms/ml. Between 50% and 60% of the doses were excreted in urine as intact amoxicillin in the 24 h after dosing. Almost 90% of this excretion occurred in the first 3 h after dosing. There was a statistically significant increase in mean clearance, after i.v. dosing, from the 500 mg level (14.8 l/h) to the 1000 mg level (20.7 l/h) implying that amoxicillin pharmacokinetics are non-linear over this range. Since there was very little difference between mean renal clearances at these dose levels (9.2 and 11.7 l/h, respectively) this clearance change might be due to enhancement of non-renal clearance. It would not be expected that this non-linearity would have any therapeutic influence.

Pharmacokinetics of cefatrizine after oral administration in human volunteers.

The oral bioavailability of cefatrizine was studied in four groups, each of ten healthy young male volunteers. Capsules and suspension formulations were each administered at doses of 250 and 500 mg. Both the capsules and suspensions had mean peak plasma levels at 1.6 h at both dose levels. Mean peak plasma levels were 4.1 and 4.3 micrograms/ml for the 250 mg capsule and suspension doses respectively and 7.1 and 7.5 micrograms/ml for the 500 mg capsules and suspension doses respectively. The overall mean half-life was 1.7 h. For both types of formulations and at both dose levels 63-65% of the doses were excreted in the urine as intact cefatrizine, 85% of this amount within 8 h. The overall mean renal clearance was 157 ml/min. The cefatrizine capsule and suspension formulations were completely bioequivalent in regard to both rate and extent of bioavailability. Plasma concentrations and urinary recoveries of cefatrizine were higher than those previously reported, due to precautions taken in sample collection and storage.

Pharmacokinetics of cefoperazone after single and multiple doses.

The pharmacokinetics of cefoperazone was determined following single and multiple intravenous and intramuscular administrations in man. Ten subjects at each dose level were given eleven successive doses, at 12 h intervals of 500 and 1000 mg i.m. and i.v.. Serum concentrations and urinary excretion were determined in all subjects after the first, fifth and eleventh doses. The first i.m. doses yielded mean peak serum levels of 37 micrograms/ml and 76 micrograms/ml at 1.0 h after injection. The first i.v. doses yielded mean serum levels of 93 and 180 micrograms/ml at 5 min after the injection. No tendency toward drug accumulation was observed on multiple dosage. The pharmacokinetics could be described by a linear, open, two-compartment model of drug distribution. The terminal serum half-life (2.1-2.4 h after i.v. doses and 2.6-2.8 h after i.m. doses) remained essentially constant over the period of the study by dose levels. The no-significant differences of areas under the curve between the two routes, at two doses, show the absolute bioavailability of cefoperazone was about 95% following i.m. administration. The high binding to serum proteins (90%) influences favourably the pharmacokinetic parameters of cefoperazone. It yielded high and prolonged serum concentrations and has very useful distribution properties. These favourable properties, together with its good antibacterial activity, suggest that cefoperazone will be effective in treating bacterial infections in human beings.

Efficacy and safety of cerivastatin 0.8 mg in patients with hypercholesterolaemia: the pivotal placebo-controlled clinical trial. Cerivastatin Study Group.

This pivotal, multicentre, double-blind, parallel-group study evaluated the efficacy and safety of cerivastatin 0.8 mg. Patients with primary hypercholesterolaemia were randomized, after 10 weeks' dietary stabilization on an American Heart Association (AHA) Step I diet, to treatment with cerivastatin 0.8 mg (n = 776), cerivastatin 0.4 mg (n = 195) or placebo (n = 199) once daily for 8 weeks. Cerivastatin 0.8 mg reduced mean low density lipoprotein-cholesterol (LDL-C) by 41.8% compared with cerivastatin 0.4 mg (-35.6%, P < 0.0001) or placebo. In 90% of patients receiving cerivastatin 0.8 mg LDL-C was reduced by 23.9 -58.4% (6th - 95th percentile). Overall attainment of the National Cholesterol Education Program (NCEP) goal was achieved by 84% of patients receiving cerivastatin 0.8 mg and by 59% of those with coronary heart disease (CHD). In the sub-population meeting the NCEP criteria for pharmacological therapy for LDL-C reduction, 74.6% of patients, including the 59% with CHD, reached the goal with cerivastatin 0.8 mg. Cerivastatin 0.8 mg also reduced mean total cholesterol by 29.9%, apolipoprotein B by 33.2% and median triglycerides by 22.9% (all P < 0.0001). Mean high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 were elevated 8.7% (P < 0.0001) and 4.5% (P < 0.0001), respectively, by cerivastatin 0.8 mg. Reductions of triglyceride and elevation in HDL-C were dependent upon triglyceride baseline levels; in patients having baseline triglyceride levels 250 - 400 mg/dl, cerivastatin 0.8 mg reduced median triglycerides by 29.5% and elevated HDL-C by 13.2%. Cerivastatin 0.8 mg was well tolerated. The most commonly reported adverse events included headache, pharyngitis and rhinitis (4 - 6%). Symptomatic creatine kinase elevations > 10 times upper limit of normal occurred in 0%, 1% and 0.9% of patients receiving placebo, cerivastatin 0.4 mg or cerivastatin 0.8 mg, respectively. Cerivastatin 0.8 mg is an effective and safe treatment for patients with primary hypercholesterolaemia who need aggressive LDL-C lowering in order to achieve NCEP-recommended levels.

Zinc and the elderly.

It is frequent in the elderly a zinc deficit, for many causes, which frequently occur in old age. Mineral deficit cause humoral and cellular immunity depression, with large increase of susceptibility to infections and increase of morbidity and mortality; besides it increases the proteinic malnutrition so frequent in old people. This condition is particularly presented in surgical patients and in patients undergoing total parenteral nutrition, when not specifically zinc supplemented. The evaluation of plasmatic zinc for diagnostic aims is scarcely significant, because hypoproteinemia (above all, hypoalbuminemia) is constantly present in old people: more useful and important is the leucocytic mineral evaluation, particularly in polymorphonuclear neutrophils. The average of recommended daily allowance of zinc is 15 mg for elderly people.

Zinc and immune function.

Zinc and immune function relationship has been extensively studied. Both in experimentally induced mineral deficit and in genetically determined deficit observable in acrodermatitis enteropathica and in enteropathy of Danish A-46 cattle, a B and T dependent antibody response decrease, a T dependent cytolytic response decrease and a natural killer cytotoxic activity decrease are present noteviously. Serious reduction of the immune function is present, in proportion to the value of low zinc plasmatic level, in elderly patients, in malnourished and seriously zinc deficient children, in patients subjected to total parenteral supply, in HIV infections and especially in evident AIDS: in this condition the plasmatic zinc level can be considered, together with the CD4+ lymphocytes amount and the B2-microglobulin value, a disease progression marker. Zinc immunostimulating action mechanisms are complex, although thymic hormone (of which zinc is essential cofactor) stimulation seems to be most important. Zinc supplementation, also parenterally, can be useful in immunodeficiency (in the elderly, in the post-surgical patients, in genetically determined or alimentary induced deficit, in AIDS.