A positive interaction between inhibitors of protein synthesis and cefepime in the fight against methicillin-resistant Staphylococcus aureus

Quinupristin-dalfopristin (Q-D) synergizes with cefepime for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Here, we studied whether the synergism was restricted to MRSA and if it extended to non-beta-lactam cell wall inhibitors or to other inhibitors of protein synthesis. Three MRSA and two methicillin-susceptible S. aureus (MSSA) strains were tested, including an isogenic pair of mecA −/mecA + S. aureus Newman. The drug interactions were determined by fractional inhibitory concentration (FIC) indices and population analysis profiles. The antibacterial drugs that we used included beta-lactam (cefepime) and non-beta-lactam cell wall inhibitors (D-cycloserine, fosfomycin, vancomycin, teicoplanin), inhibitors of protein synthesis (Q-D, erythromycin, chloramphenicol, tetracycline, linezolid, fusidic acid), and polynucleotide inhibitors (cotrimoxazole, ciprofloxacin). The addition of each protein inhibitor to cefepime was synergistic (FIC ≤ 0.5) or additive (FIC > 0.5 but < 1) against MRSA, but mostly indifferent against MSSA (FIC ≥ 1 but ≤ 4). This segregation was not observed after adding cotrimoxazole or ciprofloxacin to cefepime. Population analysis profiles were performed on plates in the presence of increasing concentrations of the cell wall inhibitors plus 0.25 × minimum inhibitory concentration (MIC) of Q-D. Cefepime combined with Q-D was synergistic against MRSA, but D-cycloserine and glycopeptides were not. Thus, the synergism was specific to beta-lactam antibiotics. Moreover, the synergism was not lost against fem mutants, indicating that it acted at another level. The restriction of the beneficial effect to MRSA suggests that the functionality of penicillin-binding protein 2A (PBP2A) was affected, either directly or indirectly. Further studies are necessary in order to provide a mechanism for this positive interactio

Genetic relationships among local Vitis vinifera cultivars from Campania (Italy)

A total of 114 accessions putatively corresponding to 69 local grape cultivars from Campania (Southern Italy) were analysed with 8 microsatellite markers (VVS2, VVMD5, VVMD7, VVMD25, VVMD27, VVMD31, VrZAG62 and VrZAG79) in order to evaluate their genetic diversity and relationships. According to their unique genotype at SSR loci finally 56 varieties were found. Interesting cases of synonymy, i.e. Greco di Tufo and Asprinio, Palummina and Piedirosso, and homonymy were disclosed. Pairwise genetic distances were calculated between all cultivars. Clustering of cultivars did not reflect their current distribution and this suggests that grape cultivars of Campania might have been introduced from various and distinct geographic areas

Therapeutic use exemption

Football players who have either physical symptoms or disease after injury may need to be treated with specific medicines that are on the list of prohibited substances. Therapeutic use exemption may be granted to such players, in accordance with strictly defined criteria—these are presented in this article. Procedures of how to request for an abbreviated or a standard therapeutic use exemption are explained, and data on therapeutic use exemptions (UEFA and FIFA, 2004 and 2005) are also presented

The parentage of 'Sangiovese', the most important Italian wine grape

A previous microsatellite study pointed out a possible parent-offspring relationship between 'Sangiovese', the most widespread red grape cultivar in Italy, and 'Ciliegiolo', an ancient Tuscan variety. Testing 'Sangiovese' as a parent of 'Ciliegiolo', we searched for the putative other parent in our extensive, private and standardized database, but we did not find any candidate. Testing 'Ciliegiolo' as a parent of 'Sangiovese', we found four candidate cultivars. After the analysis of 50 microsatellites, only one stood the paternity test and we established with a strong statistical support that 'Sangiovese' is a progeny of 'Ciliegiolo' and 'Calabrese di Montenuovo', an obscure grapevine from Campania, Italy. This cultivar does not have a registered name and is supposed to have been introduced from Calabria. Among 180 additional local grape cultivars from Calabria, Campania or Tuscany, we did not find any matching variety. As a consequence, we propose to adopt the name 'Calabrese di Montenuovo' for this grape cultivar. In addition, we found relatives of 'Sangiovese' and 'Calabrese di Montenuovo' in Calabria, thus strongly suggesting a Calabrian origin for 'Calabrese di Montenuovo' and indicating that 'Sangiovese' has ancestors and/or progenies in Tuscany and in Southern Italy.

A positive interaction between inhibitors of protein synthesis and cefepime in the fight against methicillin-resistant Staphylococcus aureus.

Quinupristin-dalfopristin (Q-D) synergizes with cefepime for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Here, we studied whether the synergism was restricted to MRSA and if it extended to non-beta-lactam cell wall inhibitors or to other inhibitors of protein synthesis. Three MRSA and two methicillin-susceptible S. aureus (MSSA) strains were tested, including an isogenic pair of mecA (-)/mecA (+) S. aureus Newman. The drug interactions were determined by fractional inhibitory concentration (FIC) indices and population analysis profiles. The antibacterial drugs that we used included beta-lactam (cefepime) and non-beta-lactam cell wall inhibitors (D-cycloserine, fosfomycin, vancomycin, teicoplanin), inhibitors of protein synthesis (Q-D, erythromycin, chloramphenicol, tetracycline, linezolid, fusidic acid), and polynucleotide inhibitors (cotrimoxazole, ciprofloxacin). The addition of each protein inhibitor to cefepime was synergistic (FIC ≤ 0.5) or additive (FIC &gt; 0.5 but &lt; 1) against MRSA, but mostly indifferent against MSSA (FIC ≥ 1 but ≤ 4). This segregation was not observed after adding cotrimoxazole or ciprofloxacin to cefepime. Population analysis profiles were performed on plates in the presence of increasing concentrations of the cell wall inhibitors plus 0.25 × minimum inhibitory concentration (MIC) of Q-D. Cefepime combined with Q-D was synergistic against MRSA, but D-cycloserine and glycopeptides were not. Thus, the synergism was specific to beta-lactam antibiotics. Moreover, the synergism was not lost against fem mutants, indicating that it acted at another level. The restriction of the beneficial effect to MRSA suggests that the functionality of penicillin-binding protein 2A (PBP2A) was affected, either directly or indirectly. Further studies are necessary in order to provide a mechanism for this positive interaction

Efficacy of daptomycin in the treatment of experimental endocarditis due to susceptible and multidrug-resistant enterococci.

OBJECTIVES: Daptomycin was tested in vitro and in rats with experimental endocarditis against the ampicillin-susceptible and vancomycin-susceptible Enterococcus faecalis JH2-2, the vancomycin-resistant (VanA type) mutant of strain JH2-2 (strain JH2-2/pIP819), and the ampicillin-resistant and vancomycin-resistant (VanB type) Enterococcus faecium D366. METHODS: Rats with catheter-induced aortic vegetations were treated with doses simulating intravenously kinetics in humans of daptomycin (6 mg/kg every 24 h), amoxicillin (2 g every 6 h), vancomycin (1 g every 12 h) or teicoplanin (12 mg/kg every 12 h). Treatment was started 16 h post-inoculation and continued for 2 days. RESULTS: MICs of daptomycin were 1, 1 and 2 mg/L, respectively, for strains JH2-2, JH2-2/pIP819 and D366. In time-kill studies, daptomycin showed rapid (within 2 h) bactericidal activity against all strains. Daptomycin was highly bound to rat serum proteins (89%). In the presence of 50% rat serum, simulating free concentrations, daptomycin killing was maintained but delayed (6-24 h). In vivo, daptomycin treatment resulted in 10 of 12 (83%), 9 of 11 (82%) and 11 of 12 (91%) culture-negative vegetations in rats infected with strains JH2-2, JH2-2/pIP819 and D366, respectively (P &lt; 0.001 compared to controls). Daptomycin efficacy was comparable to that of amoxicillin and vancomycin for susceptible isolates. Daptomycin, however, was significantly (P &lt; 0.05) more effective than teicoplanin against the glycopeptide-susceptible strain JH2-2 and superior to all comparators against resistant isolates. CONCLUSIONS: These results support the use of the newly proposed daptomycin dose of 6 mg/kg every 24 h for treatment of enterococcal infections in humans

Relationships between rainfall and groundwater recharge in seasonally humid Benin: a comparative analysis of long-term hydrographs in sedimentary and crystalline aquifers

Groundwater is a vital source of freshwater throughout the tropics enabling access to safe water for domestic, agricultural and industrial purposes close to the point of demand. The sustainability of groundwater withdrawals is controlled, in part, by groundwater recharge, yet the conversion of rainfall into recharge remains inadequately understood, particularly in the tropics. This study examines a rare set of 19–25-year records of observed groundwater levels and rainfall under humid conditions (mean rainfall is ~1,200 mm year⁻¹) in three common geological environments of Benin and other parts of West Africa: Quaternary sands, Mio-Pliocene sandstone, and crystalline rocks. Recharge is estimated from groundwater-level fluctuations and employs values of specific yield derived from magnetic resonance soundings. Recharge is observed to occur seasonally and linearly in response to rainfall exceeding an apparent threshold of between 140 and 250 mm year⁻¹. Inter-annual changes in groundwater storage correlate well to inter-annual rainfall variability. However, recharge varies substantially depending upon the geological environment: annual recharge to shallow aquifers of Quaternary sands amounts to as much as 40% of annual rainfall, whereas in deeper aquifers of Mio-Pliocene sandstone and weathered crystalline rocks, annual fractions of rainfall generating recharge are 13 and 4%, respectively. Differences are primarily attributed to the thickness of the unsaturated zone and to the lithological controls on the transmission and storage of rain-fed recharge

Prophylaxis of experimental endocarditis with antiplatelet and antithrombin agents : a role for long-term prevention of infective endocarditis in humans?

BACKGROUND: Infective endocarditis (IE) mostly occurs after spontaneous low-grade bacteremia. Thus, IE cannot be prevented by circumstantial antibiotic prophylaxis. Platelet activation following bacterial-fibrinogen interaction or thrombin-mediated fibrinogen-fibrin polymerization is a critical step in vegetation formation. We tested the efficacy of antiplatelet and antithrombin to prevent experimental IE. METHODS: A rat model of experimental IE following prolonged low-grade bacteremia mimicking smoldering bacteremia in humans was used. Prophylaxis with antiplatelets (aspirin, ticlopidine [alone or in combination], eptifibatide, or abciximab) or anticoagulants (antithrombin dabigatran etexilate or anti-vitamin K acenocoumarol) was started 2 days before inoculation with Streptococcus gordonii or Staphylococcus aureus. Valve infection was assessed 24 hours later. RESULTS: Aspirin plus ticlopidine, as well as abciximab, protected 45%-88% of animals against S. gordonii and S. aureus IE (P &lt; .05). Dabigatran etexilate protected 75% of rats against IE due to S. aureus (P &lt; .005) but failed to protect against S. gordonii (&lt;30% protection). Acenocoumarol was ineffective. CONCLUSIONS: Antiplatelet and direct antithrombin agents may be useful in the prophylaxis of IE in humans. In particular, the potential dual benefit of dabigatran etexilate might be reconsidered for patients with prosthetic valves, who require life-long anticoagulation and in whom S. aureus IE is associated with high mortality

Unraveling the genetic origin of 'Glera', 'Ribolla Gialla' and other autochthonous grapevine varieties from Friuli Venezia Giulia (northeastern Italy)

'Glera' and 'Ribolla Gialla' are the most economically relevant local grapevine cultivars of Friuli Venezia Giulia region (north-eastern Italy). 'Glera' is used to produce the world-renowned Prosecco wine. 'Ribolla Gialla' cultivation is constantly increasing due to the strong demand for sparkling wine and is the most important variety in Brda (Slovenia). Knowledge of local varieties history in terms of migration and pedigree relationships has scientific and marketing appeal. Following prospections, genotyping and ampelographic characterization of minor germplasm in Friuli Venezia Giulia, a further research was developed to understand the parentage relationships among the grapevine varieties grown in this region. An integrated strategy was followed combining the analysis of nuclear and chloroplast microsatellites with the Vitis 18k SNP chip. Two main recurrent parents were found, which can be regarded as "founders": 'Vulpea', an Austrian variety parent-offspring related with at least ten Friuli Venezia Giulia cultivars, among them 'Glera', and 'Refosco Nostrano', first degree related with other six Friuli Venezia Giulia varieties. 'Ribolla Gialla' was shown to be another member of the impressively long list of offspring derived from the prolific 'Heunisch Weiss'. Combining molecular markers and historical references was a high-performance strategy for retracing and adjusting the history of cultivars