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Background In recent years, interest in the consumption of ready-to-eat (RTE) food products has been increased in many countries. However, RTE products particularly those prepared by meat may be potential vehicles of antibiotic-resistance foodborne pathogens. Considering kebab and hamburger are the most popular RTE meat products in Iran, this study aimed to investigate the prevalence and antimicrobial resistance of common foodborne pathogens (Escherichia coli, Salmonella spp., Staphylococcus aureus, and Listeria monocytogenes) in raw kebab and hamburger samples collected from fast-food centers and restaurants. Therefore, total bacterial count (TBC), as well as the prevalence rates and antibiogram patterns of foodborne pathogens in the samples were investigated. Also, the presence of antibiotic-resistance genes (blaSHV, blaTEM,blaZ, and mecA) was studied in the isolates by PCR. Results The mean value of TBC in raw kebab and hamburger samples was 6.72 ± 0.68 log CFU/g and 6.64 ± 0.66 log CFU/g, respectively. E. coli had the highest prevalence rate among the investigated pathogenic bacteria in kebab (70%) and hamburger samples (48%). Salmonella spp., L. monocytogenes, and S. aureus were also recovered from 58, 50, and 36% of kebab samples, respectively. The contamination of hamburger samples was detected to S. aureus (22%), L. monocytogenes (22%), and Salmonella spp. (10%). In the antimicrobial susceptibility tests, all isolates exhibited high rates of antibiotic resistance, particularly against amoxicillin, penicillin, and cefalexin (79.66–100%). The blaTEM was the most common resistant gene in the isolates of E. coli (52.54%) and Salmonella spp. (44.11%). Fourteen isolates (23.72%) of E. coli and 10 isolates (29.41%) of Salmonella spp. were positive for blaSHV. Also, 16 isolates (55.17%) of S. aureus and 10 isolates (27.27%) of L. monocytogenes were positive for mecA gene. Conclusions The findings of this study showed that raw kebab and hamburger are potential carriers of antibiotic-resistance pathogenic bacteria, which can be a serious threat to public health.

Objectives The use of broad-spectrum cephalosporins is associated with induction of Clostridioides difficile infection (CDI). Recent knowledge on the importance of the healthy microbiota in preventing pathogen colonization/outgrowth highlights the caution needed when prescribing broad-spectrum antibiotics. The use of historical narrow-spectrum antibiotics, such as first-generation cephalosporins, is gaining increased attention once more as they have a reduced impact on the microbiota whilst treating infections. Here, the effects of two first-generation cephalosporins, compared with a third-generation cephalosporin, on the human microbiota were investigated and their propensity to induce simulated CDI. Methods Three in vitro chemostat models, which simulate the physiochemical conditions of the human colon, were seeded with a human faecal slurry and instilled with either narrow-spectrum cephalosporins, cefalexin and cefradine, or a broad-spectrum cephalosporin, ceftriaxone, at concentrations reflective of colonic levels. Results Instillation of cefalexin was associated with reduced recoveries of Bifidobacterium and Enterobacteriaceae; however, Clostridium spp. recoveries remained unaffected. Cefradine exposure was associated with decreased recoveries of Bifidobacterium spp., Bacteroides spp. and Enterobacteriaceae. These changes were not associated with induction of CDI, as we observed a lack of C. difficile spore germination/proliferation, thus no toxin was detected. This is in contrast to a model exposed to ceftriaxone, where CDI was observed. Conclusions These model data suggest that the minimal impact of first-generation cephalosporins, namely cefalexin and cefradine, on the intestinal microbiota results in a low propensity to induce CDI.

Objectives: We evaluated the effects of probenecid on the Pharmaco Kinetics (PK) and pharmacodynamics (PD) of oral cephalexin in healthy volunteers. Methods: Cephalexin 1000 mg was administered orally to 11 healthy volunteers following a standardized meal, with and without probenecid 500 mg orally, on two separate days one week apart. Total plasma concentrations of cephalexin and probenecid over a 12 h period were measured by liquid chromatography tandem mass spectrometry. Standard pharmacokinetic measures and contemporary PK/PD targets were compared. Results: Probenecid increased the mean (95% CI) cephalexin area under the concentration-time curve (AUC0-∞) 1.73-fold (1.61–1.85, p Conclusions: Probenecid prolonged and flattened the plasma concentration-time curve, enhancing the probability of attaining PK/PD targets. Co-administration of probenecid may expand the clinical benefits of oral cephalexin.

The zoonotic potential of Escherichia coli from chicken and beef food products is well documented. The uses of antibiotics on agriculture encourage the development of resistance bacteria capable of causing human disease and passing resistance to human pathogens. This study aimed to detect the antibiotic susceptibility and production of extended-spectrum beta-lactamase (ESBL) of E. coli strains isolated from meat. E. coli was isolated and identified according to standard techniques using traditional and chromogenic media and confirmed by biochemical reaction. Kirby-Bauer disk diffusion method was used to determine antimicrobial susceptibility towards twelve commonly used antibiotics. The resistance of the isolated E. coli towards the third generation of cephalosporins was detected using cefotaxime (30µg), ceftriaxone (30 µg) and ceftazidime (30 µg). ESBL producer E. coli was investigated using combination test. The results showed that 135 (75%) of the 180 meat samples revealed positive isolation of E. coli. 77.33% of the chicken meat samples showed positive isolation of E. coli, while 63.33% (19/30) of minced beef meat samples showed positive growth of E. coli. From these isolates, it was clear that most of them were highly resistant to tetracycline (10 µg), amoxiclav (30 µg) and cefalexin (30 µg). The lowest resistance was observed with ceftriaxone (30 µg) and ceftazidime (30 µg). The resistance of the isolated E. coli towards the third generation of cephalosporins was ranged between 5 to 33%. This study revealed that the isolated E. coli was ESBL producer as 85.71, 83.33, 70.83, 68.18 and 66.66% were detected in chickens leg, skin, wing, abdomen and chest respectively; while minced meat showed isolation of 15.78% of the ESBL producer E. coli. The study concluded that chicken and beef minced meat sold in Khartoum state have high hazardous risk for transmission of ESBLs producing E. coli; thus quality control application is highly needed. Policy actions should be implemented in order to prevent cross transmission of ESBLs producer E. coli to human. Key words: E. coli, ESBL producer E. coli, susceptibility pattern, meat quality.

The inhibition effect of Cefalexin on the corrosion of mild steel in sodium chloride has been examined with the use of weight loss and potentiodynamic polarization methods at ambient temperature. Cefalexin showed good protection ability by adsorbing on the mild steel surface. The mixed inhibition characteristics of Cefalexin were revealed by the Potentiodynamic polarization results. The inhibitor efficiency was found to be above 65% obeying the Langmuir and Freundlich isotherm law with correlation regression coefficients of R2 = 0.9984 and R2 = 0.9488, respectively. The closeness of these R2 values to unity established the reliability of Cefalexin as an inhibitor.

We report a survey (August 2017 to March 2018) and risk factor analysis of faecal carriage of antibacterial-resistant (ABR) Escherichia coli in 223 sixteen-week-old dogs in the United Kingdom. Raw feeding was associated with the presence of E. coli resistant to fluoroquinolones, tetracycline, amoxicillin, and streptomycin, but not to cefalexin or cefotaxime. Whole genome sequencing of 30 fluoroquinolone-resistant (FQ-R), 22 cefotaxime-resistant (CTX-R) and seven dual FQ-R/CTX-R E. coli isolates showed a wide range of sequence types (STs), an approximately 50:50 split of CTX-M:AmpC-mediated CTX-R, and almost exclusively mutational FQ-R dominated by ST744 and ST162. Comparisons between E. coli isolates from puppies known to be located within a 50 x 50 km region with those isolated from human urinary tract and bloodstream infections (isolated in parallel in the same region) identified a clone of ST963 E. coli carrying chromosomal blaCMY.2 in two puppies and causing two urinary tract infections and one bloodstream infection. Furthermore, an ST744 FQ-R clone was carried by one puppy and caused one urinary tract infection. Accordingly, we conclude that raw feeding is associated with carriage of ABR E. coli in dogs even at sixteen weeks of age and that bacteria carried by dogs are shared with humans.

Urinary tract infection (UTI) is one of the common infections in childhood. Prompt diagnosis and treatment reduces the risk of complications. The choice of antibiotic to treat UTI varies from region to region. Rational use and appropriately chosen antibiotic reduces the emergence of resistant uropathogens. We investigated the resistance pattern of uropathogens for commonly used antibiotics to treat UTI locally. Data was collected between 2009 and 2019 on all infants and children under 16 years of age with culture proven UTI. Results were compared with previously published figures between 2002 and 2008. A total of 1002 samples were analysed (91/year). Male to female ratio was 1:4.6. About 94% of the samples grew E. coli. As before, high resistance rates were recorded to Amoxicillin and Trimethoprim (Z = −0.325: P = 0.7452; not significant). Overall, average resistance has decreased for Nitrofurantoin from 10% between 2002 and 2008 to 5.84% between 2009 and 2019 (Z = 3.002: P = 0.0027). On the other hand, Cefalexin resistance has increased from 7.4 to 14.56% between the two study periods (Z = −4.2: P =

Diabetic foot infections (DFIs) are a significant health issue and a common complication among patients with diabetes. To develop antibiotic therapy for these high-risk patients, the current study evaluates the scope of DFIs and identifies the causing microbes. It also measures spectrum and antibiotic susceptibility of the pathogens isolated from adults with DFIs in Saudi Arabia. To achieve the study objectives, a cross-sectional study was implemented and the baseline characteristics for 44 patients with DFIs were defined. Optimal aerobic and anaerobic microbiological techniques were utilized to culture specimens isolated from infected foot ulcers. The standard microbiological methods were employed to identify the bacterial isolates and antibiotic susceptibility testing was conducted following the procedures of the Clinical and Laboratory Standards Institute (CLSI). Results showed that 12 microorganisms were isolated from the participants&rsquo, diabetic foot ulcers. Staphylococcus Aureus was ranked first because it appeared in 29 (65.9%) cases. Streptococcus Agalactiae was ranked second and multi-microbial infections were also found. Most of the organisms were susceptible to Vancomycin, Ciprofloxacin, and Cefalexin, but they were resistant to Methicillin, Gentamicin, and Ampicillin antibiotics. Staphylococcus Aureus was most sensitive to Ciprofloxacin, while it was resistant to Methicillin. About 10% of the isolates were multidrug-resistant. The study concludes that while Vancomycin should be used empirically for Gram-positive isolates, Ciprofloxacin can be taken into consideration for most of the Gram-negatives aerobes. Based on including various microorganisms and the advent of multidrug-resistant strains, proper culture and sensitivity testing are necessary prior to the empirical therapy.

Efficient mechanism-based design of antibiotics that are not susceptible to β-lactamases is hindered by the lack of comprehensive knowledge on the energetic landscapes for the hydrolysis of various β-lactams. Herein, we adopted efficient quantum mechanics/molecular mechanics simulations to explore the acylation reaction catalyzed by CTX-M-44 (Toho-1) β-lactamase. We show that the catalytic pathways for β-lactam hydrolysis are correlated to substrate scaffolds: using Glu166 as the only general base for acylation is viable for ampicillin but prohibitive for cefalexin. The present computational workflow provides quantitative insights to facilitate the optimization of future β-lactam antibiotics.

Comparative antimicrobial activities of the aqueous and ethanol leaf extracts of Alchornea cordifolia and some Cephalosporin antibiotics of different generations available in Uy, LGA of Akwa Ibom state of Nigeria were evaluated using macro dilution assay to determine the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of the plant aqueouse and ethanol leaf extracts and of the Cephalosporin antibiotics against some pathogenic Gram positive and Gram negative organisms. Results: The extraction yielded 59.9g for aqueouse leaf extract (ALE) and 74.10 g of the ethanol leaf extract. The MIC of the leaf extracts ranging from (1.953 mg/mL - 15.625 mg/ mL) and MBC ranging from (3.906 mg/mL – 62.50 mg/mL). The cephalosporin antibiotics; Ceftriaxone (Chupet®) MIC ranging from (0.0078-0.25 mg/mL), MBC (0.0312 mg/mL – 0.25 mg/mL), Cephalexin (Sporidex®) MIC ranging from (0.009766 mg/ mL - 0.625 mg/ mL), MBC (0.01953 mg/ mL -2.50 mg/ mL) and Cefuroxime with MIC ranging from (0.0078 mg/mL-0.25 mg/mL) and MBC (1.25 mg/mL - 2.5 mg/mL). Antimicrobial substances are considered as bactericidal agent when the ratio MBC/MIC ≤ 4 and bacteriostatic when the ratio MBC/MIC is > 4. The antimicrobial activities evaluated increased in the following order of potency; A. cordifolia leaf extracts > Ceftriaxone > Cefalexin > Cefuroxime considering the values of MBC/MIC. Keywords: Antimicrobial activities, bacteriostatic, bactericidal, cephalosporin, comparative.

This study was performed to determine the effects of dietary supplementation with β-glucan on the growth performance and skin-mucus microbiota of sea trout, Salmo trutta L. in Latvia. The investigations were performed during an eight-month period (September 2018 – April 2019). A total of 15,000 sea trout were divided into five groups. The experimental fish were fed formulated diets enriched with 1 g kg−1 β-glucan (D2), 3 g kg−1 β-glucan (D3), 6 g kg−1 biological product BGN-2 (BGN-2) (D4), and 14 g kg−1 BGN-2 (D5). The control diet (D1) was not supplemented. Our results showed that fish fed diets D4 and D5 achieved significantly (P < 0.05) higher growth parameters compared to those fed the other diets. Pseudomonas and Aeromonas were detected as the main component of fish skin and gill microbiota. Beta-glucan did not affect the skin-mucus microbiota of the sea trout. All isolates were resistant to amoxicillin, ampicillin, cefalexin, and erythromycin and susceptible to gentamicin. The multiple antibiotic resistance index for all isolates was higher than 0.2.

An indirect sensitive and selective spectrophotometric method has been developed for the determination of cephalexin monohydrate (CEM) ceftriaxone sodium (CFX) and cefotaxim sodium (CEF) in bulk and pharmaceutical formulation. The method is based on the oxidation of (CEM), (CFX) and (CEF) in hydrochloric acid medium with known excess on N-Bromosuccinimde and subsequent determination of unreacted oxidant by decolorization of Evans blue dye (EB) and measure the absorbance of residual dye at 608 nm. Calibration curves of evans blue dye in the presence of drugs were rectilinear over the ranges 1.0-9.0 , 1.0-8.0 and 1.0-9.0 µg/ml with molar absorptivity 2.75×104 , 9.28×104 and 7.81×104 l.mol-1.cm-1 and average recoveries 98.97, 102.08 and 100.08% for CEM, CFX and CEF respectively with RSD of less than 3.29%. The method was free from interference of many excipients and additives commonly found in pharmaceutical formulations. The developed method was successfully applied for determination of the studied drugs in their pharmaceutical formulation resulted in a good agreement with certified value and standard addition procedure.

Objective Antimicrobial peptides are widely present in nature, with many of the antimicrobial peptides having antimicrobial activity against Gram‐positive and Gram‐negative bacteria, fungi, parasites, and even coated viruses. Internal fixation of fractures is a reliable technique. However, the fracture is difficult to heal and internal fixation is not easy to maintain after infection. This study aims to verify the antibacterial effect of cationic peptide LL‐37 on Staphylococcus aureus, explore the anti‐biofilm effects of LL‐37, and compare the effects of the cationic peptide LL‐37 and Cefalexin in treatment of postoperative infection of femoral fracture in vivo. Methods The Staphylococcus aureus was clinically isolated from one patient with clinical infection after the fracture fixation at Wuxi 9th People's Hospital. The cationic peptide LL‐37 was synthesized by Shanghai Apeptide Co. Ltd. To compare the effects of the cationic peptide LL‐37 and Cefalexin in the treatment of postoperative infection of femoral fracture in vivo, 63 rabbits with internal fixation of femoral fractures were inoculated intravenously with clinically isolated pathogenic bacteria suspensions. Rabbits in the treatment groups were treated with peptide LL‐37 and Cefalexin after surgery. Rabbits in the control groups were treated with physiological saline after surgery. The biofilms on internal fixtures were harvested from euthanized rabbits 1 h, 12 h, 1 day, 2 days, and 7 days after injection of LL‐37, Cefalexin, or saline and calculated by colony count. The biofilms from treatment and control groups at 7 days were analyzed by fluorescence microscopy. Blood samples were collected at 1 h, 12 h, 1 day, 2 days, and 7 days following peptide LL‐37 and Cefalexin injection. Results The results were compared statistically using Student's t‐test or two‐way analysis of variance (ANOVA). Cationic peptide LL‐37 showed significant inhibitory effects on clinically isolated Staphylococcus aureus (P

To investigate international consumption patterns of child-appropriate oral formulations of antibiotics by formulation type, with a focus on dispersible tablets, using data from a global sales database.Antibiotic sales data for 2015 covering 74 countries and regional country groups were obtained from the MIDASGlobally, 17.7 billion standard units of child-appropriate oral antibiotic formulations were sold in 2015, representing 24% of total antibiotic sales of 74.4 billion units (both oral and parenteral) in the database. The top five child-appropriate Access antibiotics by sales volume were amoxicillin, amoxicillin with clavulanic acid, trimethoprim-sulfamethoxazole, cefalexin and ampicillin. The proportion of the top five sold for use as a syrup varied between 42% and 99%. Dispersible tablets represented only 22% of all child-appropriate oral formulation sales and made up only 15% of sales of 10 selected Access antibiotics on the model list for children.Globally most child-appropriate oral antibiotics were not sold as dispersible tablets in 2015, as recommended by WHO. There is a clear need for novel solid forms of antibiotics suitable for use in children.Étudier la consommation internationale d'antibiotiques à usage oral destinés aux enfants en fonction du type de formulation, en mettant l'accent sur les comprimés dispersibles. Et ce, en utilisant les données issues d'une base de données mondiale relative aux ventes.Les informations sur la vente d'antibiotiques en 2015 dans 74 pays et groupes régionaux de pays proviennent de la base de données de ventes pharmaceutiques MIDASÀ l'échelle mondiale, 17,7 milliards d'unités standard d'antibiotiques à usage oral destinés aux enfants ont été écoulées en 2015, ce qui équivaut à 24% du volume total de vente d'antibiotiques (74,4 milliards d'unités, tant par voie orale que parentérale) que contient la base de données. Les cinq principaux antibiotiques Access administrés aux enfants étaient l'amoxicilline, l'amoxicilline + acide clavulanique, le sulfaméthoxazole + triméthoprime, la céfalexine et l'ampicilline. Le pourcentage de vente pour ces cinq antibiotiques, commercialisés sous forme de sirop, était compris entre 42% et 99%. Les comprimés dispersibles ne représentaient que 22% de l'ensemble des formulations à usage pédiatrique, et seulement 15% des ventes pour les 10 antibiotiques Access sélectionnés dans la liste modèle.La plupart des antibiotiques administrés par voie orale aux enfants n'étaient pas vendus sous forme de comprimés dispersibles en 2015 dans le monde, contrairement aux recommandations de l'OMS. Il est donc nécessaire de développer de nouvelles formes solides d'antibiotiques, adaptées à un usage pédiatrique.Investigar los patrones de consumo internacional de las formulaciones pediátricas orales apropiadas de los antibióticos según el tipo de formulación, con énfasis en los comprimidos dispersables y mediante el uso de la información de una base de datos de ventas mundiales.Los datos sobre las ventas de antibióticos correspondientes a 2015, que abarcan 74 países y grupos regionales de países, se obtuvieron de la base de datos sobre las ventas de los productos farmacéuticos MIDASA nivel mundial, se vendieron 17 700 millones de unidades estándar de formulaciones pediátricas apropiadas de antibióticos orales en 2015, lo que representa el 24 % de las ventas totales de antibióticos de 74 400 millones de unidades (tanto por vía oral como parenteral) en la base de datos. Los cinco antibióticos principales del Grupo de acceso apropiados para niños según la cantidad que se vendió fueron la amoxicilina, la amoxicilina con ácido clavulánico, la trimetoprima-sulfametoxazol, la cefalexina y la ampicilina. El porcentaje de los cinco antibióticos más vendidos para su uso como jarabe varió entre el 42 % y el 99 %. Los comprimidos dispersables representaron solo el 22 % de todas las formulaciones pediátricas orales apropiadas que se vendieron y representaron solo el 15 % de las ventas de los 10 antibióticos del Grupo de acceso elegidos de la lista modelo pediátrica.La mayoría de los antibióticos orales apropiados para los niños no se vendieron en forma de comprimidos dispersables en 2015 a nivel mundial, como recomendó la OMS. Es evidente la necesidad de desarrollar nuevas formas sólidas de antibióticos adecuados para su uso pediátrico.الغرض استقصاء أنماط الاستهلاك الدولي للتركيبات المناسبة للمضادات الحيوية للأطفال عن طريق الفم، حسب نوع التركيب، مع التركيز على الأقراص القابلة للانتشار، وباستخدام البيانات من قاعدة بيانات المبيعات العالمية. الطريقة تم الحصول على بيانات مبيعات المضادات الحيوية لعام 2015، والتي تغطي 74 دولة ومجموعات دول إقليمية، من قاعدة بيانات المبيعات الصيدلانية ®MIDAS، والتي تشمل عينات من تجار الجملة وتجار التجزئة للصيدليات. كان التركيز على مبيعات التركيبات المناسبة عن طريق الفم للأطفال من المضادات الحيوية المتاحة في المتناول في القائمة النموذجية للأدوية الأساسية للأطفال التابعة لمنظمة الصحة العالمية (WHO) عام2017. يتم التعبير عن أحجام المبيعات باستخدام وحدة قياسية (أي قرص واحد، أو كبسولة واحدة، أو أمبول واحد، أو قنينة واحدة، أو 5 مل من السائل). وتم تحليل المبيعات تبعاً للمضاد الحيوي، ومنطقة منظمة الصحة العالمية، وتركيب المضاد الحيوي. النتائج على الصعيد العالمي، تم بيع 17.7 مليار وحدة قياسية من تركيبات المضادات الحيوية المناسبة للأطفال عن طريق الفم عام 2015، وهو ما يمثل 24٪ من إجمالي مبيعات المضادات الحيوية التي تبلغ 74.4 مليار وحدة (سواء عن طريق الفم أو بالحقن) في قاعدة البيانات. كانت المضادات الحيوية الخمسة الأولى، المتاحة في المتناول والمناسبة للأطفال، حسب حجم المبيعات هي: أموكسيسيلين، وأموكسيسيلين مع حمض كالفولانيك، وترايميثوبريم سلفاميثوكسازول، وسيفاليكسين، وأمبيسيلين. وتراوحت نسبة الخمسة الأكثر مبيعاً للاستخدام كشراب بين 42٪ و99٪. بينما كانت الأقراص القابلة للانتشار تمثل 22٪ فقط من جميع مبيعات التركيبات المناسبة للأطفال عن طريق الفم، وشكلت 15٪ فقط من مبيعات 10 من المضادات الحيوية المتاحة في المتناول، المختارة في القائمة النموذجية للأطفال. الاستنتاج لم يتم بيع معظم المضادات الحيوية المناسبة للأطفال عن طريق الفم على مستوى العالم كأقراص قابلة للانتشار في عام 2015، كما أوصت منظمة الصحة العالمية (WHO). هناك حاجة واضحة لأشكال صلبة جديدة من المضادات الحيوية المناسبة للاستخدام بواسطة الأطفال.旨在利用全球销售数据库的数据，按剂型调查儿童口服抗生素的国际消费模式，重点关注分散片。.选取 MIDAS® 医药销售数据库 2015 年涵盖的 74 个国家和地区国家组的抗生素销售数据，其中包括医药批发商和零售商的样本。重点关注 2017 年世界卫生组织（世卫组织）2015 年，全球共销售 177 亿个标准单位的儿童口服抗生素制剂，占数据库 744 亿个单位（口服和非口服）抗生素总销量的 24%。销售量最高的五种儿童口服抗生素制剂是阿莫西林、阿莫西林-克拉维酸、甲氧苄啶-磺胺甲恶唑、头孢氨苄和氨苄西林。在销售量最高的五种制剂中，用于制作糖浆的比例在 42%-99% 之间。分散片仅占所有儿童口服制剂销售量的 22%，在儿童清单选定的 10 种儿童抗生素销售量中仅占 15%。.2015 年全球大部分的儿童口服抗生素未按照世界卫生组织的建议作为分散片出售。显然，当前仍十分有必要研制出适合儿童使用的新型固体抗生素。.Исследование глобальных моделей потребления пероральных детских лекарственных форм антибиотиков с уделением особого внимания диспергируемым таблеткам с помощью сведений из глобальной базы данных о продажах.Данные о продажах антибиотиков в 74 странах мира и региональных группах стран за 2015 год были получены из базы данных продаж фармацевтической продукции MIDASВ 2015 году в мире было продано 17,7 млрд стандартных единиц пероральных лекарственных форм антибиотиков, приемлемых для детей, что составляет 24% от общего объема продаж антибиотиков (74,4 млрд единиц как пероральных, так и парентеральных лекарственных форм), зарегистрированного в базе данных. В пятерку лидеров по объемам продаж детских антибиотиков из группы массовой доступности вошли амоксициллин, амоксициллин + клавулановая кислота, триметоприм/сульфаметоксазол, цефалексин и ампициллин. Доля продаж пяти лидеров в виде сиропа варьировалась от 42 до 99%. Диспергируемые таблетки составляли лишь 22% от общего объема продаж пероральных детских лекарственных форм и всего 15% от общего объема продаж 10 выбранных антибиотиков из группы массовой доступности Примерного перечня основных лекарственных средств для детей.В 2015 году во всем мире большинство приемлемых для детей пероральных лекарственных форм антибиотиков не продавались в форме диспергируемых таблеток, как это было рекомендовано ВОЗ. Существует явная необходимость в выпуске новых твердых лекарственных форм антибиотиков, подходящих для применения у детей.

Objectives: This study determined the prevalence, antibiotic susceptibility and resistance genes among multidrug resistant Escherichia coli isolates from diarrheic patients in four hospitals within Minna, Nigeria.Methods: Stool samples from one hundred and seven (107) diarrheic patients were collected and analysed to check for E. coli using spread plate techniques. The resistance pattern of the E. coli isolates to ten (10) antibiotics using disc diffusion techniques was determined. Five isolates with multidrug resistant index ≥ 0.5 were screened for antibacterial resistant genes (Tn3bla, GyrA, ParC, aadA2 and Sul1) using polymerase chain reaction.Results: Seventy (70) samples representing 65.4% were E. coli positive while fifty-five (55) were resistant to at least one antibiotic. The highest level of resistance was against ampicillin (38.57%) while the least was against cefalexin (4.29%). Multidrug resistant isolates were 58.7% (41/70), while 28.6% (20/70) were resistant to three or more antibiotics. The result of the molecular characterization identified the five multidrug resistant isolates to be E. coli strain RAD34, E. coli strain CUSMBN2, E. coli strain CAU3471, and E. coli strain BYPFP. Tn3bla/GyrA/ParC resistant genes were detected in all the five isolates. E. coli isolate RAD34, E. coli strain CUSMBN2, E. coli strain CAU3471 and E. coli strain BYPFP possessed Sul1 gene. However, E. coli strain BYPFP, E. coli strain CAU3471 and E. coli strain CUSMBN2 had aadA2 gene.Conclusion: The result of this study established the active circulation of Tn3bla, GyrA, ParC, aadA2 and Sul1 resistant genes among E. coli in the study area.

AimsTo investigate whether on-farm antibacterial usage (ABU), environmental antibacterial resistant (ABR) Escherichia coli prevalence, and sampling and sample handling methodologies are associated with ABR E. coli positivity in individual faecal samples from dairy heifers.Methods and ResultsThree hundred and sixty-four heifers from 37 farms were sampled via rectal or faecal pat sampling. Samples were stored at -80°C for variable periods before microbiological analysis. Data analysis was through a multilevel, multivariable logistic regression approach.Individual rectal samples had increased odds of positivity for amoxicillin, cefalexin and tetracycline-resistant E. coli. Sample storage for 6-12 month was associated with decreased odds of finding amoxicillin and tetracycline-resistant E. coli. On-farm ABU had little influence, and environmental ABR E. coli prevalence had no significant influence on on the odds of sample-level positivity for ABR E. coli.ConclusionsSampling methodology and sample handling have a greater association than on-farm factors with the detection of ABR E. coli in individual faecal samples from dairy heifers.Significance and Impact of the StudySampling and storage methodologies should be considered carefully at the point of designing ABR surveillance studies in livestock and their environments and, where possible, standardised between and within future studies.

Cefalexin is a widely used first-generation cephalosporin, and resistance in Escherichia coli is caused by extended-spectrum (e.g., CTX-M) and AmpC β-lactamase production and therefore frequently coincides with third-generation cephalosporin resistance. However, we have recently identified large numbers of E. coli isolates from human infections, and from cattle, where cefalexin resistance is not β-lactamase mediated. Here, we show, by studying laboratory-selected mutants, clinical isolates, and isolates from cattle, that OmpF porin disruption or downregulation is a major cause of cefalexin resistance in E. coli. Importantly, we identify multiple regulatory mutations that cause OmpF downregulation. In addition to mutation of ompR, already known to downregulate OmpF and OmpC porin production, we find that rseA mutation, which strongly activates the sigma E regulon, greatly increases DegP production, which degrades OmpF, OmpC, and OmpA. Furthermore, we reveal that mutations affecting lipopolysaccharide structure, exemplified by the loss of GmhB, essential for lipopolysaccharide heptosylation, also modestly activate DegP production, resulting in OmpF degradation. Remarkably, given the critical importance attached to such systems for normal E. coli physiology, we find evidence for DegP-mediated OmpF downregulation and gmhB and rseA loss-of-function mutation in E. coli isolates derived from human infections. Finally, we show that these regulatory mutations enhance the ability of group 1 CTX-M β-lactamase to confer reduced carbapenem susceptibility, particularly those mutations that cause OmpC in addition to OmpF downregulation.

Objective An earlier three-way crossover study evaluating bioequivalence of 3 cefalexin formulations (capsule for reference, capsule and tablet for test) in healthy subjects in Malaysia showed that the intra-individual coefficients of variation were 9.25% for AUC0-t, 9.54% for AUC0-∞, and 13.90% for Cmax. It is preliminarily stated that cefalexin is not a high-variation product. The here-presented clinical study in China was carried out to analyze the pharmacokinetic properties of two preparations in fasting and postprandial condition to assess the bioequivalence of the test preparation and reference preparation when administered on a fasting and postprandial basis in healthy Chinese subjects and to observe the safety of the test preparation and reference preparation in healthy Chinese subjects. Materials and methods In this trial, a total of 56 eligible subjects were randomly assigned to the fasting group and the postprandial group. The two groups were given 250 mg of the test and reference preparation, respectively. Liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was applied to determine the plasma concentration of cefalexin. PhoenixWinNonlin software (V7.0) was used to calculate the pharmacokinetic parameters of cefalexin using the non-compartmental model (NCA), and the bioequivalence and safety results were calculated by SAS (V9.4) software. Results The main pharmacokinetic parameters of the test and reference preparations were as follows, the fasting group: Cmax 12.59 ± 2.65 μg/mL, 12.72 ± 2.28 μg/mL; AUC0-8h 20.43 ± 3.47 h×μg/mL, 20.66 ± 3.38 h×μg/mL; AUC0-∞ 20.77 ± 3.53 h×μg/mL, 21.02 ± 3.45 h×μg/mL; the postprandial group: Cmax 5.25 ± 0.94 μg/mL, 5.23 ± 0.80 μg/mL; AUC0-10h 16.92 ± 2.03 h×μg/mL, 17.09 ± 2.31 h×μg/mL; AUC0-∞ 17.33 ± 2.09 h×μg/mL, 17.67 ± 2.45 h×μg/mL. Conclusion The 90% confidence intervals of geometric mean ratios of test preparation and reference preparation were calculated, and the 90% confidence intervals of geometric mean ratios of max, AUC0-10h, and AUC0-∞ were within the 80.00% ~ 125.00% range in both groups. Both Cmax and AUC met the pre-determined criteria for assuming bioequivalence. The test and reference products were bioequivalent after administration under fasting as well as under fed conditions in healthy Chinese subjects. This study may suggest that successful generic versions of cefalexin not only guarantee the market supply of such drugs but can also improve the safety and effectiveness and quality controllability of cefalexin through a new process and a new drug composition ratio.

This research communication describes the lactating intramammary (IMM) antibiotic formulation most used by Irish dairy farmers at farm level through interviewing 202 dairy farmers. The IMM antibiotic usage data is not easily available to the researcher and farming community. This study determined that three commercial formulations (Synulox ™, Tetra Delta™ and Terrexine) made up 81% of the products used at farm level. The formulation Synulox™ was the most used at 34% first preference and 32% second preference and contains amoxicillin/clavulanic, a standard broad spectrum antibiotic, for which mastitis pathogen resistance remains low. The aminoglycosides were used in four of the IMM formulations analysed, including Tetra Delta™ and Terrexine. Of the 12 antibiotics identified in the IMM formulations studied, three including cefalexin, benzylpenicillin and penethamate are classified as highly important antibiotics (HIA) by the World Health Organisation (WHO) whilst the other 8 (dihydrostreptomycin, streptomycin, neomycin, framycetin, kanamycin, amoxicillin/clavulanic acid, and cefquinome), are considered critically important (CIA) for use in human health. This study has generated knowledge of the preferences of lactating IMM formulations used at farm level.

Considering the possibility that Escherichia coli carried by companion dogs could infect owners and human society, we investigated their pathogenicity and drug resistance. E. coli was isolated from stool samples of companion dogs (n = 90) to examine the O-serogroup, virulence genes, and drug susceptibility. The age of dogs ranged from 4 months to 16 years, and they were mainly treated with cefalexin, enrofloxacin, or amoxicillin. A total of 69 samples were positive for E. coli (76% of examined dogs), and the most common O-serogroup was O18 (n = 13). Nine diarrheagenic E. coli, including enteropathogenic E. coli (n = 3), enteroaggregative E. coli (n = 1), and astA-carrying E. coli (n = 5), were isolated. In addition, we isolated 28 E. coli strains resistant to at least one of six antimicrobials, including cephalothin (CET), ceftazidime (CAZ), cefotaxime (CTX), chloramphenicol (CP), fosfomycin (FOM), and norfloxacin (NLFX). The resistance pattern was as follows: CET, n = 16; NLFX, n = 3; CET/CP (resistance to both CET and CP), n = 1; CET/NLFX, n = 1; CET/CAZ/CTX, n = 3; CET/CTX/NLFX, n = 2; CET/CP/NLFX, n = 1; and CET/CAZ/CTX/NLFX, n = 1. Moreover, ten E. coli isolates were found to produce extended-spectrum β-lactamase (ESBL), including AmpC (n = 4; OUT, O18, O74, and O166), CTX-M-1 (n = 1; O25), CTX-M-9 (n = 4; OUT, O18, O18, and O125), and AmpC/CTX-M-9 (n = 1; OUT) groups. The AmpC-producing E. coli strains included enteropathogenic and astA-carrying E. coli. Our results showed that the human-infectious diarrheagenic E. coli was isolated from some dogs, and some strains exhibited ESBL. Therefore, future studies are needed to investigate the possibility of transmission of these E. coli strains to humans.

Introduction: Antibiotics analysis is performed by many methods such as spectrophotometry, fluorimetry, polarography, and high-performance liquid chromatography. This analysis doesn't require derivatization but requires expensive equipment and extensive preparation. When more than one antibiotic is present in a formulation, interactions may occur between the drugs that must be separated before measurement. Thin-layer chromatography is a useful technique for identifying antibiotics because of the low cost, high speed, and low servicing. Silica gel adsorbents have often been used as adsorbents in all thin-layer chromatography studies. In this study, zeolite was used as an adsorbent in thin- layer chromatography with high selectivity. Materials and Methods: The chromatographic behaviour of amoxicillin, ampicillin, cefazolin, cefixime, ceftriaxone, cefalexin, and penicillin was studied for the first time on a thin layer of zeolite with mobile, organic, and organic- organic phases. Discussion: The best separation of ceftriaxone from amoxicillin, ampicillin, cefazolin, cefixolin, cefalexin, and penicillin on a thin layer of zeolite using methanol as the mobile phase. The distance and rise time are 12 cm and 110 minutes, respectively. Conclusion: The results of the present study showed that using the current method, the selectivity of one antibiotic from other components as well as two-component andthree-component adsorption was obtained. Quantitative identification of antibiotics was also performed in multicomponent mixtures after selection of appropriate isolates.

Cefuroxime, cefuroxime axetil and cefalexin are broad-spectrum pluripotential cephalosporin antibiotics. Their determination in various objects suggests using expensive spectroscopic, chromatographic, electrochemical equipment and organic solvents. Potentiometric sensors can provide rapid detection of cephalosporin antibiotics in a small sample volume without a preliminary sample preparation. The study is aimed at the developing of modified solid-contact potentiometric sensors for determination of cefuroxime and cefalexin in aqueous, biological media, and pharmaceuticals. The electroanalytical characteristics of unmodified and modified polyaniline and copper oxide nanoparticle sensors are evaluated. Tetradecylammonium(TDA) with a silver (I) – cefuroxime complex are used as the active membrane components, whereas polyaniline and copper oxide nanoparticles are used as modifiers. The main electroanalytic and operational characteristics of the studied sensors in aqueous solutions of antibiotics and against the background of oral fluid (LRP) are determined. The results of comparative evaluation of the electroanalytical properties of unmodified and modified solid-contact sensors in aqueous media of some â-lactam antibiotics and against the background of oral fluid are presented. The sensors based on Ag (Cefur)2TDA are characterized by a short response time: for modified polyaniline (PAN) and copper oxide nanoparticles within 5 – 10 sec, for unmodified — 10 – 20 sec. The linear range of the electrode functions for unmodified and modified sensors is 1 × 10–4 – 1 × 10–1 M, the detection limit is 7.4 × 10–5 M for unmodified and 6.3 × 10–5 M for modified sensors, respectively. The potential drift is 6 – 12 and 4 – 6 mV/day, service life is 1.5 and 2 months for unmodified and modified sensors, respectively. The modifiers stabilize the electrode potential, perform the function of the electron transfer mediator thus enhancing the electroanalytical characteristics of the sensors. The effect of the redox agents on the sensor properties is revealed: 1 × 10–3 – 1 × 10–4 MK 2Cr2O7 and FeCl3 solutions reduce the linearity intervals of the electrode functions, KI and Mohr’s salt do not affect the characteristics of the sensors in cefuroxime and cephalexin solutions. The coefficients of potentiometric selectivity of cefuroxime-selective sensors (modified with CuO nanoparticles) with respect to cefazolin, cefotaxime, and cefalexin are close to unity; Kijpot with respect to inorganic anions being part of the oral fluid (, Cl Br,I,HCO3 ,H PO 24 ,HPO4 2) are n × 10–2 – n × 10–3. This indicates the possibility of using sensors for detecting individual cephalosporin antibiotics or their total content in the presence of 100 – 1000 fold excesses of inorganic ions in medicinal and biological environments, small sample volumes, which is important when studying the pharmacokinetics of antibiotics and in determination of the maximum therapeutic dose when adjusting the treatment process.

Mesocellular foams (MCF) silica nanometer mesoporous molecular sieve was successfully synthesized by hydrothermal route. This method used poly(ethylene glycol)-block-poly(propyl glycol)-block-poly(...

Anti-inflammatory and antipyretic analgesic western medicine chemicals such as aspirin and antibiotics have the potential to be illegally added into Guangdong herbal teas (GHT, Guangdong Liangcha) to enhance its efficacy. The present work reports firstly a ultrahigh performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method after HLB solid phase extraction (SPE) and purification for the simultaneous analysis of 8 chemical substances including aspirin, acetaminophen, chlortrimeton, diclofenac, cefradine, cefalexin, cefazolin and azithromycin illegally added into GHT. Supernatant was adjusted to pH 3–4 after high speed centrifugation of sample. It was subsequently extracted and purified in one step by HBL SPE. Eight target substances were separated on a C18 column by gradient elution with acetonitrile and 0.1% formic acid in water as mobile phase, scanned by dynamic switching of ESI positive ion mode and negative ion mode, detected with MS/MS in multiple reactions monitoring (MRM) mode and quantified by external standard method. The limit of detection, matrix effect, recovery and precision of the developed method were investigated. Results were linear in the concentration range of 1.0–200 μg/L for all analytes of interest, with R2 >0.999. Limits of detection (LOD) were in the range of 0.1–2.0 μg/kg. Matrix effects were in the range of 85–102%. Recoveries for negative samples at three spiked levels were between 80.2% and 103%, and the intra-day precision and inter-day precision were in the ranges of 3.1–9.0% and 4.7–11.8%, respectively. The method was successfully applied to analyze 8 western medicines chemicals in 36 GHT and 3 illegal chemical substances especially acetaminophen were detected in several Liangcha samples.

Amoxicillin, ampicillin, cefalexin and cefadroxil are the most extensively used beta-lactam antibiotics due to their broad spectrum of action and low cost. The quality of the pharmaceutical...

A highly sensitive, selective and precise HPTLC method coupled with fluorescence detection was developed and validated for the determination of α-aminocephalosporin antibiotics; namely cefalexin, cefadroxil and cefradine in their standard solutions. The applicability of the developed methodology was demonstrated via analysis of cefalexin in goat milk samples. Full optimization of the fluorescence derivatization reaction was carried out with regard to the standard solutions of the studied compounds or after extraction of milk samples. The separation of the studied compounds was performed on HPTLC precoated silica gel plates 60 F254 using acetonitrile: water in a ratio 85:15 (v/v) as a mobile phase. The retention behavior of the formed derivatives was discussed in detail. It was found that hydrophilic interaction mode is the main interaction mechanism governing the retention of the formed derivatives. In addition, an experimental design approach was conducted for optimization of the chromatographic conditions. Modified QuEChERS was applied as an efficient extraction technique of cefalexin from both spiked and real goat milk samples. Optimization of QuEChERS extraction technique to achieve the highest extraction recovery was performed and the results indicate that this method provides a good extraction recovery (83–116%) for cefalexin from goat milk samples. Limit of detection (LOD) of the developed method was found to be 0.023, 0.005, and 0.023 ng band−1 for cefalexin, cefadroxil and cefradine, respectively in their standard solutions and 0.165 ng band−1 for cefalexin in goat milk samples. According to the achieved LOD values, the method sensitivity was quasi-equivalent to other methods based on expensive techniques such as HPLC-UV and HPLC-MS and it is sufficient to determine cefalexin below its MRL in milk samples. Moreover, the method was successfully applied to a pharmacokinetic study of cefalexin in goat milk after single intramuscular injection of 10 mg of cefalexin kg−1 per body weight.

In the present study Delftia sp. Shakibaie, Forootanfar, and Ghazanfari (SFG), was applied for preparation of biogenic Bi nanoparticles (BiNPs) and antibacterial and anti-biofilm activities of the purified BiNPs were investigated by microdilution and disc diffusion methods. Transmission electron micrographs showed that the produced nanostructures were spherical with a size range of 40-120 nm. The measured minimum inhibitory concentration of both the Bi subnitrate and BiNPs against three biofilms producing bacterial pathogens of Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus mirabilis were found to be above 1280 µg/ml. Addition of BiNPs (1000 µg/disc) to antibiotic discs containing tobramycin, nalidixic acid, ceftriaxone, bacitracin, cefalexin, amoxicillin, and cefixime significantly increased the antibacterial effects against methicillin-resistant S. aureus (MRSA) in comparison with Bi subnitrate (p < 0.05). Furthermore, the biogenic BiNPs decreased the biofilm formation of S. aureus, P. aeruginosa, and P. mirabilis to 55, 85, and 15%, respectively. In comparison to Bi subnitrate, BiNPs indicated significant anti-biofilm activity against P. aeruginosa (p < 0.05) while the anti-biofilm activity of BiNPs against S. aureus and P. mirabilis was similar to that of Bi subnitrate. To sum up, the attained results showed that combination of biogenic BiNPs with commonly used antibiotics relatively enhanced their antibacterial effects against MRSA.

The results of microflora research of urinal canal of dogs with prostatitis and its sensitiveness to the antibiotics are shown . The aim of researches was to set the microflora of nephrogonoduct in clinically healthy dogs and microflora of urethral excretions at chronic prostatitis, and also its sensitiveness to the different groups of antibiotics. With the aim of research of biological properties of microflora of nephrogonoduct and urethral excretions at chronic prostatitis were selected 20 animals that were divided into 2 groups. The first group was laid down clinically by healthy animals, (n=10) and second -diseases with chronic prostatitis (n=10). Both patients and clinically healthy dogs was taken microbal material that was sown by a superficial and deep way on the agar nourishing environments of two types - МРА and environment of Еndo. Family belonging was found out on morphological and biological properties. The sensitiveness of microorganisms to the antibiotics was determined by the method of diffusion in an agar with the use of paper disks after the sizes of zones of oppression of height round a disk, on the methodology accepted in general lines. For research it was used 10 preparations: ceftriaxon, cefazolin, cefalexin, tylosin, gentamicin, tetracyclinum, enrofloxacinn, erythromysin, amoxycillin and penbex. The analysis of the obtained data asserted that the mixed urethral microflora distinguished from dogs with prostatitis showed an insignificant sensitiveness to the gentamicin and tetracyclinum, as a diameter of zone of detention of height of microorganisms of the mixed culture was very small or is quite absent, that is why expediency of their use is under a question, obviously, unjustified, taking into account considerable course duration of antibiotic therapy of chronic prostatitis. It is able to do a bactericidal and bacteriostatix action among antibiotics.

BACKGROUND Pharmacokinetic studies and therapeutic drug monitoring of antibiotics require a simple, rapid, and reliable analytical method for monitoring the concentrations in plasma, including unbound concentrations for highly protein-bound drugs. The aim of the current work was to develop and validate a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of total and unbound concentrations of 3 widely used β-lactam antibiotics (cefalexin, cefazolin, and flucloxacillin) and the often coadministered drug probenecid in human plasma, suitable for pharmacokinetic studies and for routine use in ordinary, busy hospital laboratories. METHODS Unbound drug was separated from bound drug by ultrafiltration. A simple 1-step protein precipitation was used for sample preparation. Cefalexin, cefazolin, flucloxacillin, probenecid, and their corresponding isotopically labeled internal standards were then resolved on a C18 (2) column. All the compounds were detected using electrospray ionization in the positive mode. RESULTS Standard curves were linear for all compounds over the concentration range of 0.2-100 mg/L (r > 0.99) for total drug in plasma and 0.01-10 mg/L (r > 0.99) for unbound drug in plasma ultrafiltrate. For both total and unbound drugs, bias was

The present work describes the occurrence of antibiotic residues in urban wastewaters discharged into southern Sfax wastewater treatment plant (WWTP). Thirteen out of the fifty-six antimicrobial compounds analyzed were detected in the wastewater samples with concentration ranging from 23.30 (for cefalexin) to 690.50 ng/L (for spiramycin) in WWTP influent and from 7.50 (for cefalexin) to 370.04 ng/L (for spiramycin) in WWTP effluent. The highest removal efficiency was observed for trimethoprim (88%), while the lowest one was observed for sulfapyridine (33%).The potential impact of the regenerated waters in the environment and pubic health is also discussed.