Tailoring Mesoporous Silica-Coated Silver Nanoparticles and Polyurethane-Doped Films for Enhanced Antimicrobial Applications.

The global increase in multidrug-resistant bacteria poses a challenge to public health and requires the development of new antibacterial materials. In this study, we examined the bactericidal properties of mesoporous silica-coated silver nanoparticles, varying the core sizes (ca. 28 nm and 51 nm). We also investigated gold nanoparticles (ca. 26 nm) coated with mesoporous silica as possible inert metal cores. To investigate the modification of antimicrobial activity after the surface charge change, we used silver nanoparticles with a silver core of 28 nm coated with a mesoporous shell (ca. 16 nm) and functionalized with a terminal amine group. Furthermore, we developed a facile method to create mesoporous silica-coated silver nanoparticles (Ag@mSiO2) doped films using polyurethane (IROGRAN®) as a polymer matrix via solution casting. The antibacterial effects of silver nanoparticles with different core sizes were analyzed against Gram-negative and Gram-positive bacteria relevant to the healthcare and food industry. The results demonstrated that gold nanoparticles were inert, while silver nanoparticles exhibited antibacterial effects against Gram-negative (Escherichia coli and Salmonella enterica subsp. enterica serovar Choleraesuis) and Gram-positive (Bacillus cereus) strains. In particular, the larger Ag@mSiO2 nanoparticles showed a minimum inhibitory concentration (MIC) and a minimum bactericidal concentration (MBC) of 18 µg/mL in the Salmonella strain. Furthermore, upon terminal amine functionalization, reversing the surface charge to positive values, there was a significant increase in the antibacterial activity of the NPs compared to their negative counterparts. Finally, the antimicrobial properties of the nanoparticle-doped polyurethane films revealed a substantial improvement in antibacterial efficacy. This study provides valuable information on the potential of mesoporous silica-coated silver nanoparticles and their applications in fighting multidrug-resistant bacteria, especially in the healthcare and food industries.

Dose selection for aztreonam-avibactam, including adjustments for renal impairment, for Phase IIa and Phase III evaluation.

PURPOSE: A series of iterative population pharmacokinetic (PK) modeling and probability of target attainment (PTA) analyses based on emerging data supported dose selection for aztreonam-avibactam, an investigational combination antibiotic for serious Gram-negative bacterial infections. METHODS: Two iterations of PK models built from avibactam data in infected patients and aztreonam data in healthy subjects with "patient-like" assumptions were used in joint PTA analyses (primary target: aztreonam 60% fT > 8 mg/L, avibactam 50% fT > 2.5 mg/L) exploring patient variability, infusion durations, and adjustments for moderate (estimated creatinine clearance [CrCL] > 30 to ≤ 50 mL/min) and severe renal impairment (> 15 to ≤ 30 mL/min). Achievement of > 90% joint PTA and the impact of differential renal clearance were considerations in dose selection. RESULTS: Iteration 1 simulations for Phase I/IIa dose selection/modification demonstrated that 3-h and continuous infusions provide comparable PTA; avibactam dose drives joint PTA within clinically relevant exposure targets; and loading doses support more rapid joint target attainment. An aztreonam/avibactam 500/137 mg 30-min loading dose and 1500/410 mg 3-h maintenance infusions q6h were selected for further evaluation. Iteration 2 simulations using expanded PK models supported an alteration to the regimen (500/167 mg loading; 1500/500 mg q6h maintenance 3-h infusions for CrCL > 50 mL/min) and selection of doses for renal impairment for Phase IIa/III clinical studies. CONCLUSION: A loading dose plus 3-h maintenance infusions of aztreonam-avibactam in a 3:1 fixed ratio q6h optimizes joint PTA. These analyses supported dose selection for the aztreonam-avibactam Phase III clinical program. CLINICAL TRIAL REGISTRATION: NCT01689207; NCT02655419; NCT03329092; NCT03580044.

The increasing importance of novel deep eutectic solvents as potential effective antimicrobials and other medicinal properties.

With the rise of antibiotic resistance globally, coupled with evolving and emerging infectious diseases, there is an urgent need for the development of novel antimicrobials. Deep eutectic solvents (DES) are a new generation of eutectic mixtures that depict promising attributes with several biological implications. DES exhibit unique properties such as low toxicity, biodegradability, and high thermal stability. Herein, the antimicrobial properties of DES and their mechanisms of action against a range of microorganisms, including bacteria, amoebae, fungi, viruses, and anti-cancer properties are reviewed. Overall, DES represent a promising class of novel antimicrobial agents as well as possessing other important biological attributes, however, future studies on DES are needed to investigate their underlying antimicrobial mechanism, as well as their in vivo effects, for use in the clinic and public at large.

[Evolution of the outpatient antibiotic prescription between 2012 and 2018. Characteristics of the ABPresclín platform created for the analysis of antibiotic prescription in the health service of the Balearic Islands.] / Evolución de la prescripción antibiótica ambulatoria entre 2012 y 2018. Características de la plataforma ABPresclín creada para el análisis de prescripción antibiótica en el Servicio de Salud de las Islas Baleares.

OBJECTIVE: One of the fist lines of action of the National Plan against Antibiotic Resistance (PRAN) is to monitor the use of antibiotics as a fundamental basis for the fight against resistance. In order to know the antibiotic prescription habits, we pretended to describe the outpatient prescription of systemic antibiotics in the Balearic Islands through exploitation of ABPresclín database. METHODS: It was an ecological descriptive study of the electronic outpatient prescriptions of systemic antibiotics of the Health Service of the Balearic Islands from 2012 to 2018. Combining the prescription with population information data by year and geographical area, prescription rates were obtained per 1,000 person, distributed by professional, health centres, geographical areas: distribution per patient characteristics, type of antibiotics and associated diagnoses. RESULTS: 3,517,101 prescriptions are analyzed with an average prescription period (TPp) per 1,000 person-years of 472.1. A quarter of the population received at least one prescription of antibiotics. TPp was higher in over 80 years (899.0) and in women (553.4). 68.9% of the prescription was made in primary care (AP) and 17.9% in out-of-hours settings. TPp in AP was 333.1, varying from 192.3 to 527.0, according to basic health areas. The TPp of the most commonly used antibiotics was: amoxicillin/clavulanic (143), amoxicillin (95.9), azithromycin (54.5), fosfomycin (41.5) and ciprofloxacin (29.7). The main associated diagnoses were: lower respiratory infections (16.5%), urinary infections (15%), non-infectious (15%), tonsillitis (14.3%) and upper respiratory infections (13%). CONCLUSIONS: Balearic Islands have a relatively low antibiotic prescription rate with a marked variability between prescribers. Amoxicillin/clavulanic was the most prescribed antibiotic, with an increase in azithromycin. Respiratory infections were the main reason for prescription. ABPresclín is useful to promote better use of antibiotics.

OBJETIVO: Una de las líneas de actuación del Plan Nacional frente a la Resistencia a los Antibióticos (PRAN) es la vigilancia del uso de los antibióticos como pilar fundamental en la lucha frente a la resistencia. Con la finalidad de conocer los hábitos de prescripción de antibióticos, este trabajo pretendió describir la prescripción ambulatoria de antibióticos sistémicos en Baleares mediante la explotación de la base de datos ABPresclín. METODOS: Se elaboró un diseño descriptivo ecológico de la prescripción ambulatoria de antibióticos sistémicos en el Servicio de Salud de las Islas Baleares, entre 2012 y 2018. Se realizó un análisis descriptivo de la prescripción antibiótica que, si se refería a un denominador poblacional por año o periodo, permitía obtener tasas de prescripciones por cada 1.000 personas, distribuidas por profesional, por cupo o por áreas geográficas (zonas básicas de salud y áreas), o bien según las características del paciente, el tipo de antibióticos y los diagnósticos asociados. RESULTADOS: Se analizaron 3.517.101 prescripciones, con una tasa de prescripción del período (TPp) por cada 1.000 personas-año de 472,1. Una cuarta parte de la población recibió al menos una prescripción de antibióticos. La TPp fue mayor en >80 años (899) y en mujeres (553,4). El 68,9% de la prescripción se realizó en consulta de atención primaria (AP) y el 17,9% en urgencias extrahospitalarias. La TPp en AP fue de 333,1, variando entre 192,3 y 527, según las zonas básicas de salud. La TPp de los antibióticos más utilizados fue: amoxicilina/clavulánico, 143; amoxicilina, 95,9; azitromicina, 54,5; fosfomicina, 41,5; y ciprofloxacino, 29,7. Se asociaron principalmente los diagnósticos de infecciones respiratorias de vías bajas (16,5%), infecciones urinarias (15%), no infecciosos (15%), amigdalitis (14,3%) e infecciones respiratorias de vías altas (13%). CONCLUSIONES: Baleares presenta una tasa de prescripción de antibióticos relativamente baja, con una marcada variabilidad. Amoxicilina/clavulánico es el antibiótico más prescrito, con incremento de la azitromicina. Las infecciones respiratorias son el principal motivo de prescripción. ABPresclín resulta útil para promover un mejor uso de antibióticos.

Chemical composition and antimicrobial activity of two extract of propolis against isolates of Staphylococcus spp. and multiresistant bacterials / Composição química e atividade antimicrobiana de dois extratos de própolis contra isolados de Staphylococcus spp. e bactérias multirresistentes

There is a growing need to discover and develop alternative therapies for the treatment of mastitis caused by Staphylococcus spp. and multidrug-resistant bacterial infections. This study examined the chemical composition and antimicrobial potential of two propolis extracts (EPA and EPB) against seventy-seven isolates of Staphylococcus spp. obtained from subclinical bovine mastitis; three clinical strains of MRSA and two from clinical strains of S. aureus ATCC, identified as S. aureus ATCC 6538 and S. aureus ATCC 25923. The total phenolic content was determined by the Folin-Ciocalteau method, the total flavonoid content by the Dowd method and the phenolic profile was quantified by HPLC-DAD. The MBC values of the extracts were evaluated by broth microdilution method. The amount of total phenolic and flavonoid compounds was higher in EPA than EPB. Both extracts revealed the presence of caffeic, coumaric, cinnamic, ferulic and 3,4-dihydroxybenzoic acids, with higher concentrations of coumaric and cinnamic acids. Staphylococcus spp. isolates were susceptible to EPA (90.9%), EPB (83.1%) and oxacillin (80.5%). The oxacillin susceptible isolates were also susceptible to EPA (70.1%) and EPB (80.6%), whereas those oxacillin-resistant strains were also susceptible to EPA (40.0%) and to EPB (26.7%). MBC ranged from 34.3 to 68.7µm/mL for EPA and from 68.7 to 137.5µg/mL for EPB. Both extracts inhibited significantly (100%) the clinical strains of MRSA, S. aureus ATCC 6538 and S. aureus ATCC 25923 at the concentration of 68.7µg/mL. It is concluded that both extracts of propolis, whose main constituents are coumaric and cinnamic acids, have high antimicrobial activity against the microorganisms studied, and EPA also against oxacillin-resistant strains. These findings reinforce its potential use for the treatment of bovine mastitis.(AU)

É cada vez mais oportuna a necessidade de descobrir e desenvolver terapias alternativas para tratamento da mastite causada por Staphylococcus spp. e de infecções bacterianas multirresistentes. Este estudo examinou a composição química e o potencial antimicrobiano de dois extratos etanólicos de própolis (EPA e EPB) contra setenta e sete isolados de Staphylococcus spp. obtidos a partir de mastite bovina subclínica; três estirpes clínicas de MRSA e duas de linhagens clínicas de S. aureus ATCC, identificadas como, S. aureus ATCC 6538 e S. aureus ATCC 25923, ambas metacilina resistentes. O teor total de fenólicos foi determinado pelo método de Folin-Ciocalteau, o teor de flavonoides totais pelo método Dowd e o perfil fenólico foi quantificado por HPLC-DAD. CBM dos extratos foi avaliada pelo método de microdiluição em caldo. A quantidade total de compostos fenólicos e flavonoides foi maior no EPA do que no EPB. Ambos os extratos revelaram a presença dos ácidos cafeico, cumárico, cinâmico, ferúlico e 3,4-di-hidroxibenzóico, com maiores concentrações de ácidos cumárico e cinâmico. Os isolados de Staphylococcus spp. foram sensíveis a EPA (90,9%), EPB (83,1%) e oxacilina (80,5%). Os isolados suscetíveis à oxacilina também foram suscetíveis ao EPA (70,1%) e ao EPB (80,6%), enquanto os do resistente à oxacilina foram suscetíveis ao EPA (40,0%) e ao EPB (26,7%). MBC variou de 34,3 a 68,7µm/mL para EPA e de 68,7 a 137,5µg/mL para EPB. Ambos os extratos inibiram significativamente (100%) as linhagens clínicas de MRSA, S. aureus ATCC 6538 e S. aureus ATCC 25923 na concentração de 68,7µg/mL. Conclui-se que os extratos etanólicos da própolis, cujos principais constituintes são os ácidos cumário e cinâmico, possuem atividade antimicrobiana contra os micro-organismos estudados, e o EPA também contra as cepas resistentes à oxacilina. Estes achados reforçam seu potencial uso para o tratamento da mastite bovina.(AU)

The Glucosinolates: A Sulphur Glucoside Family of Mustard Anti-Tumour and Antimicrobial Phytochemicals of Potential Therapeutic Application.

This study reviewed aspects of the biology of two members of the glucosinolate family, namely sinigrin and glucoraphanin and their anti-tumour and antimicrobial properties. Sinigrin and glucoraphanin are converted by the ß-sulphoglucosidase myrosinase or the gut microbiota into their bioactive forms, allyl isothiocyanate (AITC) and sulphoraphanin (SFN) which constitute part of a sophisticated defence system plants developed over several hundred million years of evolution to protect them from parasitic attack from aphids, ticks, bacteria or nematodes. Delivery of these components from consumption of cruciferous vegetables rich in the glucosinolates also delivers many other members of the glucosinolate family so the dietary AITCs and SFN do not act in isolation. In vitro experiments with purified AITC and SFN have demonstrated their therapeutic utility as antimicrobials against a range of clinically important bacteria and fungi. AITC and SFN are as potent as Vancomycin in the treatment of bacteria listed by the World Health Organisation as antibiotic-resistant "priority pathogens" and also act as anti-cancer agents through the induction of phase II antioxidant enzymes which inactivate potential carcinogens. Glucosinolates may be useful in the treatment of biofilms formed on medical implants and catheters by problematic pathogenic bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus and are potent antimicrobials against a range of clinically important bacteria and fungi. The glucosinolates have also been applied in the prevention of bacterial and fungal spoilage of food products in advanced atmospheric packaging technology which improves the shelf-life of these products.

Antibiotic treatment of women with uncomplicated cystitis before and after allowing pharmacist-supply of trimethoprim.

Background In 2012, New Zealand reclassified trimethoprim to allow specially trained pharmacists to supply it without a prescription to women with symptoms suggesting uncomplicated cystitis, under strict criteria for supply. Objective To assess how this policy change allowing pharmacist supply of trimethoprim affected overall antibiotic supply. Setting Randomly selected community pharmacies throughout New Zealand. Methods Data were collected in pharmacies before the implementation ('baseline') and 1 year later ('post-implementation'). Pharmacy staff recorded prescription and nonprescription supplies for treatment or prevention of suspected urinary tract infections. Women with a prescription for treatment or prevention of presumed urinary tract infection or purchasing a non-prescription medicine for this purpose were invited to self-complete a questionnaire. National prescribing data were extracted for trimethoprim, nitrofurantoin and norfloxacin. Main outcome measure Antibiotic use in women with UTIs from dispensed prescriptions (baseline and post-implementation) and pharmacist-supplied trimethoprim (post-implementation), particularly focusing on women aged 16-65 years with an antibiotic for presumed cystitis without complicating features. Results Baseline data were provided by 139 pharmacies, 120 of which provided post-implementation data. In women with presumed cystitis without complicating features, prescriptions before and after the implementation were primarily for trimethoprim. Overall antibiotic use, and use of second-line agents did not increase post-implementation. Pharmacist-supplies of trimethoprim were modest nearly 1 year after the service started. Conclusion Supply of trimethoprim by specially trained pharmacists working within strict criteria for supply appeared to have little overall effect on antibiotic use. Further research on patient outcomes, resistance and changes over time is recommended.

Invasive streptococcal disease: a review for clinicians.

INTRODUCTION: Streptococci are a genus of Gram-positive bacteria which cause diverse human diseases. Many of these species have the potential to cause invasive infection resulting from the presence of bacteria in a normally sterile site. SOURCES OF DATA: Original articles, reviews and guidelines. AREAS OF AGREEMENT: Invasive infection by a streptococcus species usually causes life-threatening illness. When measured in terms of deaths, disability and cost, these infections remain an important threat to health in the UK. Overall they are becoming more frequent among the elderly and those with underlying chronic illness. New observational evidence has become available to support the use of clindamycin and intravenous immunoglobulin in invasive Group A streptococcal disease. AREAS OF CONTROVERSY: Few interventions for the treatment and prevention of these infections have undergone rigorous evaluation in clinical trials. For example, the role of preventative strategies such as screening of pregnant women to prevent neonatal invasive Group B streptococcal disease needs to be clarified. FUTURE PROSPECTS: Studies of invasive streptococcal disease are challenging to undertake, not least because individual hospitals treat relatively few confirmed cases. Instead clinicians and scientists must work together to build national and international networks with the aim of developing a more complete evidence base for the treatment and prevention of these devastating infections.

Infective endocarditis:a review of 28 cases / 中华传染病杂志

Objective To investigate the clinical features,diagnostic examinations,treatment and clinical outcomes of patients with definite infective endocarditis (IE).Methods This retrospective study included 28 adults with IE who were admitted to Sir Run Run Shaw Hospital from January 1,2009 to June 30,2011.All the IE cases met the modified Duke criteria and the data were reviewed on clinical presentations,microbiological profiles,echocardiographic findings,in-hospital course and clinical outcomes.Results The mean age was (50.9± 17.4) years with a male preponderance.All patients had native valve IE.Mitral valve prolapse was the most common underlying heart disease.Fever was presented as the primary manifestation.Blood culture results were positive only in 36.4％ of the 11 cases.Streptococcus viridans represented the leading causative agent.Echocardiography was positive in 96.4％ of the cases.46.4％ of the cases underwent surgery for IE.Eighteen cases had at least one major complication.The in hospital mortality was 3.6％.Conclusions Typical clinical presentations of IE are rare.Comparing with previous studies,there are no changing trends in the microbiology.Advanced antibiotics are overused during the treatment,which is awaiting improvements.

Analysis of the usage of antibacterial drugs in 75 hernior-rhaphy inpatients during perioperative period / 中国现代普通外科进展

Objective: To evaluate the rationality of the use of antibiotic prophylaxis in the perioperative period of herniorrhaphy. Methods: Seventy-five cases of herniorrhaphy discharged in March, June and September of 2009 were collected. Parameters including indications, the types of antibacterial drugs, time of administration, solvent choice, usage and dosage, combination, etc, were assessed for the rationality according to the "the guiding principles of clinical use of antibacterial drugs"and other relevant documents. Results: The antibacterial drugs application rate was 100%, while the rationali-ty of the drug selection, the drug administration route, the single dose and the number of dosing, was 70.7%, 100% , 100% and 93.3% respectively. Sixty-two patients(82.7%)were treated with antibacterial drugs at 0.5～2 hours before surgery, and the average time course of the prophylactic use of antibiotics after surgery was 2.3 days. Conclusions: Some problems existed for the use of antibiotic prophylaxis in the perioperative period of herniorrhaphy. Surgeon should ensure the correct use of the antibacterial drugs to make the safety, efficiency, rationality, and economy for the patients.