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

Analysis of different genetic traits and their association with biofilm formation in Staphylococcus epidermidis isolates from central venous catheter infections.

The aim of the present study was to characterize clinical isolates of Staphylococcus epidermidis, one of the bacterial species most often implicated in foreign-body-associated infections, for their ability to form biofilms and for the presence of mecA and IS256 element. Sixty-seven Staphylococcus epidermidis clinical isolates, obtained from implantable medical devices, were investigated. Overall, 70% of the strains were positive for ica operon genes, 85% possessed atlE, and 46% contained aap. In 89% of the population, the Congo red agar test confirmed the correlation between the presence of ica genes and slime expression. Almost all of the strains could be classified as biofilm producers by both the crystal violet assay and microscopy. The bacterial population studied showed a very high frequency of strains positive for mecA as well as for the IS256 element. Although well-structured biofilms have been previously observed only in those strains possessing genes belonging to the ica operon, this study demonstrates that strains lacking specific biofilm-formation determinants can be isolated from catheters and can form a biofilm in vitro. Hence, different and yet-to-be identified factors may work together in the formation and organization of complex staphylococcal microbial communities and sustain infections associated with implanted medical devices.

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.

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.

Assessment of the left atrial appendage mechanical function by three-dimensional echocardiography.

AIMS: We evaluated the feasibility of three-dimensional echocardiography, in the assessment of left atrial appendage (LAA) function. METHODS AND RESULTS: Forty-five patients underwent multiplane transoesophageal echocardiography. In addition to Doppler and two-dimensional echocardiography, data for three-dimensional echocardiography reconstruction were obtained during transoesophageal echocardiography. Left atrial appendage ejection fraction based on three-dimensional echocardiography volume measurements (EFv) and two-dimensional echocardiography area measurements (EFa), coupled with other echocardiographic data, were related to left atrial appendage late peak emptying velocity, a frequently used indicator of left atrial appendage function. Multiple regression analysis has revealed a significant association of peak emptying velocity with EFv (P<0.0001), spontaneous echocardiographic contrast (P=0.001), tricuspid regurgitation (P=0.03) and left ventricular hypertrophy (P=0.05). No significant relation was observed between peak emptying velocity and EFa, presence or absence of atrial fibrillation, left ventricular dysfunction, mitral stenosis and insufficiency, left atrial dilatation, pulmonary venous peak systolic, diastolic and peak reverse flow velocity at atrial contraction as well as left atrial appendage volumes derived from two-dimensional echocardiography and three-dimensional echocardiography. In a simple linear correlation, the degree of association between peak emptying velocity and EFv was higher as between peak emptying velocity and EFa (r=0.7 vs 0.4, both P<0.001). Observer variabilities for calculating EFv were considerably lower than for two-dimensional echocardiography derived EFa. Ejection fractions determined by two-dimensional echocardiography area measurements at 45 degrees, 90 degrees and 135 degrees cutplane angulations were related to EFv only at 135 degrees. CONCLUSIONS: Left atrial appendage ejection fraction calculation by three-dimensional echocardiography is feasible, more accurate than by two-dimensional echocardiography and has lower observer variability. Furthermore, an optimal cutplane angulation of the left atrial appendage view at 135 degrees has been demonstrated.

[Severe mitral insufficiency caused by the rupture of the chordae tendinae in acromegaly. Report of a case]. / Insufficienza mitralica severa da rottura di corda tendinea in acromegalia. Descrizione di un caso.

Cardiovascular disease is a common finding in patients with acromegaly. In such patients, heart failure frequently leads to death. Cardiovascular manifestations of acromegaly include cardiomegaly and very often hypertension, coronary atherosclerosis, and diabetes. Primary valvular disease is less commonly observed. Because it is not clear whether acromegaly-related cardiomyopathy is a specific entity and since there are not many necropsy reports regarding mitral valve prolapse in acromegalic patients, we report the case of severe mitral regurgitation due to rupture of the chordae tendinae in a patient with mitral valve prolapse and acromegaly.

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.

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.

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.

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.

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.

Nationwide survey in Italy of treatment of Streptococcus pyogenes pharyngitis in children: influence of macrolide resistance on clinical and microbiological outcomes. Artemis-Italy Study Group.

Throat swab specimens were obtained from 3,227 children with symptoms of acute pharyngotonsillitis. After 14 to 21 days, a second throat swab specimen was obtained at a follow-up visit. Over 42% of the 934 strains of Streptococcus pyogenes isolated in the primary study were resistant to erythromycin, azithromycin, and clarithromycin. Eradication rates among the 668 patients who entered the follow-up study were as follows: 84.1%, penicillin recipients; 82.7%, cephalosporin recipients; and 71.7%, macrolide recipients. Among patients treated with macrolides, the eradication rate was approximately 80% when the infecting organisms were erythromycin-susceptible and approximately 60% when they were erythromycin-resistant. These results indicate substantial in vitro macrolide resistance among Italian isolates of S. pyogenes. However, at least for a minor self-limiting condition such as acute S. pyogenes pharyngitis, our findings point to a limited overall correlation between in vitro susceptibility (to penicillins, cephalosporins, or macrolides) and eradication in patients treated with these drugs and an even weaker correlation between in vitro resistance (to macrolides) and noneradication in patients receiving macrolide therapy.

In vitro antibacterial activity of trovafloxacin and five other fluoroquinolones.

The in vitro inhibitory and bactericidal activities of the investigational fluoroquinolone trovafloxacin were studied and compared with those of five other fluoroquinolones (ciprofloxacin, ofloxacin, pefloxacin, rufloxacin and sparfloxacin) against a wide range of clinical isolates from Italian hospitals. Against gram-positive bacteria, trovafloxacin was overall more active than the other antibiotics tested, including sparfloxacin, another gram-positive-oriented fluoroquinolone, and was active against all ciprofloxacin-resistant streptococci, enterococci, and listeriae, all ciprofloxacin-resistant Staphylococcus aureus isolates and most ciprofloxacin-resistant coagulase-negative staphylococci. Its antistaphylococcal activity was not affected by oxacillin resistance or susceptibility of the isolates, nor was its antipneumococcal activity affected by whether isolates were susceptible or resistant to penicillin. Against gram-negative bacteria, trovafloxacin retained a high potency mostly comparable with that of ciprofloxacin. Rufloxacin and pefloxacin were less active than the other fluoroquinolones against most test strains of both gram-positive and gram-negative organisms. Trovafloxacin minimal bactericidal concentrations usually equalled or exceeded by 2-4 times the minimal inhibitory concentration values, indicating that the compound is overall highly bactericidal.

Are failured cardiomyopathies a zinc-deficit related disease? A study on Zn and Cu in patients with chronic failured dilated and hypertrophic cardiomyopathies.

BACKGROUND: Muscle zinc deficit may be important in cardiac failure pathogenesis. We studied whether Zn deficit is present in dilated (DCM) and hypertrophic (HCM) cardiomyopathies with chronic cardiac failure. The aim was to find out whether it might be a diagnostic and prognostic marker. METHODS: Zn and Cu values were measured in plasma, urine and red blood cells by flame atomic absorption spectrophotometer in normal subjects, in 15 patients with DCM and in 11 patients with HCM in chronic cardiac failure. RESULTS: There is a statistically important increase of zincuria as well as low plasmatic and erythrocytic zinc in DCM; low plasmatic and erythrocytic zinc was found in HCM. CONCLUSIONS: It is likely that chronic cardiac failure, by atrial natriuretic peptide activation, increases zincuria and involves a secondary loss of plasmatic and erythrocytic zinc. Primitive or secondary zinc deficit causes marked structural and functional myocardial cell impairment. Hypozinchemia from increased zincuria seems to represent an important diagnostic and prognostic marker in chronic failured cardiomyopathies. Dilated cardiomyopathy, particularly in elder subjects, may be considered as a primitive or a secondary Zn-deficit myocardial disease. In the essay, the possible pathogenetic mechanisms underlying hypozinchemia and determining functional and structural myocardial cell changes are discussed. The main consequence of present results is pharmacological Zn administration as a new pathogenetic therapy in chronic failured cardiomyopathies.

Purpuromycin: an antibiotic inhibiting tRNA aminoacylation.

Purpuromycin, an antibiotic produced by Actinoplanes ianthinogenes, had been reported previously to inhibit protein synthesis. In the present report, we demonstrate that the mechanism of action of this antibiotic is quite novel in that it binds with fairly high affinity to all tRNAs, inhibiting their acceptor capacity. Although more than one molecule of purpuromycin is bound to each tRNA molecule, the inhibitory activity of this antibiotic was found to be selective for the tRNA acceptor function; in fact, after the aminoacylation step, purpuromycin was found to affect none of the other tested functions of tRNA (interaction with the ribosomal P- and A-sites and interaction with translation factors). Accordingly, purpuromycin was found to inhibit protein synthesis only when translation depended on the aminoacylation of tRNA and not when the system was supplemented with pre-formed aminoacyl-tRNAs. Because purpuromycin did not interfere with the ATP-PPi exchange reaction of the synthetase or with the initial interaction of the enzyme with its tRNA substrate, the basis for the inhibition of aminoacylation is presumably the formation of a nonproductive synthetase-tRNA complex in the presence of purpuromycin in which the tRNA is unable to be charged with the corresponding amino acid.