scholarly journals Influence of Flunixin on the Disposition Kinetic of Cefepime in Goats

2014 ◽  
Vol 2014 ◽  
pp. 1-5
Author(s):  
Mohamed El-Hewaity
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Intramuscular Injection ◽  
Test Organism ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Maximum Serum ◽  
Maximum Serum Concentration ◽  
The Mean

The pharmacokinetic profile of cefepime (10 mg/kg b.w.) was studied following intravenous and intramuscular administration of cefepime alone and coadministered with flunixin (2.2 mg/kg b.w.) in goats. Cefepime concentrations in serum were determined by microbiological assay technique usingEscherichia coli(MTCC 443) as test organism. Following intravenous injection of cefepime alone and in combination with flunixin, there are no significant changes in the pharmacokinetic parameters. Following intramuscular injection of cefepime alone and in combination with flunixin, the maximum serum concentration was significantly increased in flunixin coadministered group compared with cefepime alone. However, no significant changes were reported in other pharmacokinetic parameters. The result ofin vitroprotein binding study indicated that 15.62% of cefepime was bound to goat’s serum protein. The mean bioavailability was 92.66% and 95.27% in cefepime alone and coadministered with flunixin, respectively. The results generated from the present study suggest that cefepime may be coadministered with flunixin without change in dose regimen. Cefepime may be given intramuscularly at 12 h intervals to combat susceptible bacterial infections.

scholarly journals Effect of three anticoccidials on pharmacokinetics of tilmicosin in broiler chickens

2016 ◽  
Vol 4 (2) ◽  
pp. 150
Author(s):  
Mohamed El-Hewaity
Keyword(s):  
Oral Administration ◽  
Broiler Chickens ◽  
Broiler Chicken ◽  
Test Organism ◽  
Pharmacokinetic Profile ◽  
Maximum Serum ◽  
Elimination Half ◽  
Bacillus Subtilis Atcc ◽  
Maximum Serum Concentration ◽  
Compartment Open Model

The disposition kinetic of tilmicosin (25mg/kg) was studied following oral administration alone, pretreated with amprolium (240 ppm), pretreated with diclazuril (2.5 ppm) and pretreated with toltrazuril (25 ppm) in broiler chickens. The serum tilmicosin concentrations were determined by microbiological assay technique using Bacillus subtilis (ATCC 6633) as the test organism. Following oral administration of tilmicosin, the disposition curve was best described by two-compartment open model. The maximum serum concentration (Cmax) was 1.90 ± 0.11, 1.27 ± 0.13, 1.50 ± 0.14 and 1.41 ± 0.11µg/ml for tilmicosin alone and in the presence of amprolium, diclazuril and toltrazuril, respectively. The elimination half-life (T0.5 (el)) was significantly decreased (5.28 ± 0.30, 5.88 ± 0.33, 6.03 ± 0.25 h, respectively) in amprolium, diclazuril and toltrazuril pretreated broiler chicken compared to tilmicosin alone (7.30 ± 0.41 h). The outcomes illustrated a significant decrease in the interval between doses in amprolium, diclazuril and toltrazuril pretreated broiler chicken compared to tilmicosin alone. Amprolium diclazuril and toltrazuril, resulted in a significance decrease in AUC (12.02 ± 1.14, 15.50 ± 1.26 and 14.56 ± 1.46 µg.h.ml-1, respectively) compared to tilmicosin alone (21.98±1.83 µg.h.ml-1). It is concluded that the administration of amprolium, diclazuril and toltrazuril before tilmicosin would altered its pharmacokinetic profile in broiler chicken.

Comparative Bioavailability of Praziquantel Tablets

DICP ◽  
1989 ◽  
Vol 23 (1) ◽  
pp. 29-32 ◽  
Author(s):  
Sming Kaojarern ◽  
Surapol Nathakarnkikool ◽  
Uthai Suvanakoot
Keyword(s):  
High Performance ◽  
Area Under The Curve ◽  
Pharmacokinetic Parameters ◽  
Disintegration Time ◽  
Maximum Serum ◽  
British Pharmacopoeia ◽  
Elimination Half ◽  
Comparative Bioavailability ◽  
Maximum Serum Concentration

Six different brands of 600 mg praziquantel tablets were evaluated. In vitro studies demonstrated that all but one of the products met the British Pharmacopoeia 1980 disintegration time specifications. The comparative bioavailability of four of the internationally available brands of praziquantel tablets were then studied in eight healthy volunteers using a crossover design. Serum praziquantel levels were determined by high-performance liquid chromatography. Individual serum profiles were analyzed for pharmacokinetic parameters such as maximum serum concentration, time to reach maximum, and area under the curve. Following administration of praziquantel 40 mg/kg po, the mean peak serum concentrations and the time to reach the peak ranged from 1.007 to 1.625 μg/ml and from 1.72 to 2.81 hours, respectively. The elimination half-life of praziquantel was 1.15 (0.94–1.25) hours. Differences greater than 20 percent (p < 0.05) were noted for these parameters between the original brand and the generic formulations. The relative bioavailabilities of the generic praziquantel formulations, with respect to the original brand, were 91.25, 80.95, and 69.86 percent. This is due to the failure of disintegration and subsequently poor dissolution. The effect of 30 percent reduction of bioavailability may lead to unacceptably high rates of treatment failure.

scholarly journals Comparative Pharmacokinetics of Cefquinome (Cobactan 2.5%) following Repeated Intramuscular Administrations in Sheep and Goats

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Mohamed El-Hewaity ◽  
Amera Abd El Latif ◽  
Ahmed Soliman ◽  
Mohamed Aboubakr
Keyword(s):  
Intramuscular Injection ◽  
Micrococcus Luteus ◽  
Test Organism ◽  
Cumulative Effect ◽  
Serum Levels ◽  
Pharmacokinetic Profile ◽  
Sheep And Goats ◽  
Intramuscular Dose ◽  
Intramuscular Injections

The comparative pharmacokinetic profile of cefquinome was studied in sheep and goats following repeated intramuscular (IM) administrations of 2 mg/kg body weight. Cefquinome concentrations in serum were determined by microbiological assay technique using Micrococcus luteus (ATCC 9341) as test organism. Following intramuscular injection of cefquinome in sheep and goats, the disposition curves were best described by two-compartment open model in both sheep and goats. The pharmacokinetics of cefquinome did not differ significantly between sheep and goats; similar intramuscular dose rate of cefquinome should therefore be applicable to both species. On comparing the data of serum levels of repeated intramuscular injections with first intramuscular injection, it was revealed that repeated intramuscular injections of cefquinome have cumulative effect in both species sheep and goats. The in vitro serum protein-binding tendency was 15.65% in sheep and 14.42% in goats. The serum concentrations of cefquinome along 24 h after injection in this study were exceeding the MICs of different susceptible microorganisms responsible for serious disease problems. These findings indicate successful use of cefquinome in sheep and goats.

scholarly journals Bacterial Strain-to-Strain Variation in Pharmacodynamic Index Magnitude, a Hitherto Unconsidered Factor in Establishing Antibiotic Clinical Breakpoints

2009 ◽  
Vol 53 (12) ◽  
pp. 5181-5184 ◽  
Author(s):  
Alasdair P. MacGowan ◽  
Rosy Reynolds ◽  
Alan R. Noel ◽  
Karen E. Bowker
Keyword(s):  
Serum Concentration ◽  
Bacterial Pathogen ◽  
Pharmacodynamic Modeling ◽  
Human Pharmacokinetics ◽  
Maximum Serum ◽  
Clinical Breakpoints ◽  
Dose Ranging ◽  
Maximum Serum Concentration ◽  
The Relationship

ABSTRACT Antibiotic pharmacodynamic modeling allows variations in pathogen susceptibility and human pharmacokinetics to be accounted for when considering antibiotic doses, potential bacterial pathogen targets for therapy, and clinical susceptibility breakpoints. Variation in the pharmacodynamic index (area-under-the-concentration curve to 24 h [AUC24]/MIC; maximum serum concentration of drug in the serum/MIC; time the serum concentration remains higher than the MIC [T > MIC]) is not usually considered. In an in vitro pharmacokinetic model of infection using a dose-ranging design, we established the relationship between AUC24/MIC and the antibacterial effect for moxifloxacin against 10 strains of Staphylococcus aureus. The distributions of AUC24/MIC targets for 24-h bacteriostatic effect and 1-log, 2-log, and 3-log drops in bacterial counts were used to calculate potential clinical breakpoint values, and these were compared with those obtained by the more conventional approach of taking a single AUC24/MIC target. Consideration of the AUC24/MIC as a distribution rather than a single value resulted in a lower clinical breakpoint.

scholarly journals An In Vitro Chicken Gut Model Demonstrates Transfer of a Multidrug Resistance Plasmid from Salmonella to Commensal Escherichia coli

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Roderick M. Card ◽  
Shaun A. Cawthraw ◽  
Javier Nunez-Garcia ◽  
Richard J. Ellis ◽  
Gemma Kay ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Gastrointestinal Tract ◽  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Animal Health ◽  
Plasmid Transfer ◽  
High Rate ◽  
Antibiotic Administration

ABSTRACT The chicken gastrointestinal tract is richly populated by commensal bacteria that fulfill various beneficial roles for the host, including helping to resist colonization by pathogens. It can also facilitate the conjugative transfer of multidrug resistance (MDR) plasmids between commensal and pathogenic bacteria which is a significant public and animal health concern as it may affect our ability to treat bacterial infections. We used an in vitro chemostat system to approximate the chicken cecal microbiota, simulate colonization by an MDR Salmonella pathogen, and examine the dynamics of transfer of its MDR plasmid harboring several genes, including the extended-spectrum beta-lactamase bla CTX-M1. We also evaluated the impact of cefotaxime administration on plasmid transfer and microbial diversity. Bacterial community profiles obtained by culture-independent methods showed that Salmonella inoculation resulted in no significant changes to bacterial community alpha diversity and beta diversity, whereas administration of cefotaxime caused significant alterations to both measures of diversity, which largely recovered. MDR plasmid transfer from Salmonella to commensal Escherichia coli was demonstrated by PCR and whole-genome sequencing of isolates purified from agar plates containing cefotaxime. Transfer occurred to seven E. coli sequence types at high rates, even in the absence of cefotaxime, with resistant strains isolated within 3 days. Our chemostat system provides a good representation of bacterial interactions, including antibiotic resistance transfer in vivo. It can be used as an ethical and relatively inexpensive approach to model dissemination of antibiotic resistance within the gut of any animal or human and refine interventions that mitigate its spread before employing in vivo studies. IMPORTANCE The spread of antimicrobial resistance presents a grave threat to public health and animal health and is affecting our ability to respond to bacterial infections. Transfer of antimicrobial resistance via plasmid exchange is of particular concern as it enables unrelated bacteria to acquire resistance. The gastrointestinal tract is replete with bacteria and provides an environment for plasmid transfer between commensals and pathogens. Here we use the chicken gut microbiota as an exemplar to model the effects of bacterial infection, antibiotic administration, and plasmid transfer. We show that transfer of a multidrug-resistant plasmid from the zoonotic pathogen Salmonella to commensal Escherichia coli occurs at a high rate, even in the absence of antibiotic administration. Our work demonstrates that the in vitro gut model provides a powerful screening tool that can be used to assess and refine interventions that mitigate the spread of antibiotic resistance in the gut before undertaking animal studies. IMPORTANCE The spread of antimicrobial resistance presents a grave threat to public health and animal health and is affecting our ability to respond to bacterial infections. Transfer of antimicrobial resistance via plasmid exchange is of particular concern as it enables unrelated bacteria to acquire resistance. The gastrointestinal tract is replete with bacteria and provides an environment for plasmid transfer between commensals and pathogens. Here we use the chicken gut microbiota as an exemplar to model the effects of bacterial infection, antibiotic administration, and plasmid transfer. We show that transfer of a multidrug-resistant plasmid from the zoonotic pathogen Salmonella to commensal Escherichia coli occurs at a high rate, even in the absence of antibiotic administration. Our work demonstrates that the in vitro gut model provides a powerful screening tool that can be used to assess and refine interventions that mitigate the spread of antibiotic resistance in the gut before undertaking animal studies.

scholarly journals Enhanced Expression of miR-34a Enhances Escherichia coli Lipopolysaccharide-Mediated Endometritis by Targeting LGR4 to Activate the NF-κB Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Xiaofei Ma ◽  
Baoyi Yin ◽  
Shuai Guo ◽  
Talha Umar ◽  
Junfeng Liu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Luciferase Reporter ◽  
Blue Staining ◽  
Histopathological Analysis ◽  
Dependent Manner ◽  
Luciferase Reporter Gene ◽  
Gram Staining

Background. Persistent endometritis caused by bacterial infections has lethal effects on the reproductive performance of dairy cattle, which compromises animal welfare and delays or prevents pregnancy. The microRNA (miRNA) miR-34 family plays a pivotal role in the inflammatory process; however, the precise mechanism of miR-34a in endometritis has not been thoroughly elucidated to date. Methods. In this study, the endometrium of cows diagnosed with endometritis was harvested for bacterial culture and Gram staining to evaluate bacterial contamination of the uterus. Based on this, a bovine endometrial epithelial cell (BEND) inflammation model and a mouse model stimulated with lipopolysaccharide (LPS) in vitro and in vivo were constructed. Cell viability was assessed by CCK-8, trypan blue staining, and flow cytometry. H&E was applied to histopathological analysis. Immunohistochemical, immunofluorescence, qRT-PCR, and western blot assays were performed to measure the mRNA and protein expression of relevant genes. Online databases, plasmid construction, and dual-luciferase reporter gene assays were used to predict and validate the interaction between miR-34a and its target gene LGR4. Finally, mice were injected vaginally with a local antagomir to validate the role of miR-34a in murine uterine inflammation. Results. In this study, we observed that Gram-negative bacteria, represented by Escherichia coli, are the predominant pathogenic agents responsible for the recurrent occurrence of endometritis in dairy cows. Further, miR-34a was found to repress the expression of LGR4 by targeting the 3 ′ untranslated region (3 ′ UTR) of LGR4. miR-34a was upregulated in bovine uterine tissues and bovine endometrial epithelial cells stimulated with LPS. miR-34a induced the release of the proinflammatory cytokines IL-1β, IL-6, and TNF-α by activating the phosphorylation of NF-κB p65. Furthermore, IL-1β upregulated miR-34a transcription and downregulated LGR4 expression in an IL-1β-dependent manner. Conclusions. Taken together, our study confirmed that miR-34a is regulated by IL-1β and suppresses the level of the LGR4 3 ′ UTR, which in turn exacerbates the inflammatory response. Thus, the knockdown of miR-34a might be a new direction for the treatment of endometritis.

scholarly journals STUDY ON BOVINE SUB-CLINICAL MASTITIS ON FARM CONDITION WITH SPECIAL EMPHASIS ON ANTIBIOGRAM OF THE CAUSATIVE BACTERIA

2017 ◽  
Vol 14 (2) ◽  
pp. 161-166 ◽  
Author(s):  
M. T. Hasan ◽  
M. R. Islam ◽  
N. S. Runa ◽  
M, N. Hasan ◽  
A. H. M. M. Uddin ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infection ◽  
Bacterial Infections ◽  
Clinical Mastitis ◽  
Economic Effects ◽  
Single Infection ◽  
Bacterial Isolates ◽  
E Coli ◽  
Staphylococcus Spp

The study was conducted to find out the prevalence of sub-clinical mastitis (SCM) and antibiogram of the causative bacteria in dairy cows at the Sylhet govt. Dairy Farm (SGDF) and Local Farms of Sylhet (LFS) during the period of July2014 to June2015. These farms were selected to assess the predominant types of bacteria involved in causing sub-clinical mastitis and to know the in vitro antibiotic sensitivity spectrum of these bacterial isolates against the commonly used antibiotics and to study the economic effects due to SCM. Use of California Mastitis Test (CMT) for the detection of sub-clinical mastitis showed 42out of 100 samples were test positive, among which +(Trace) 22.0%, ++(Distinct) 12.0%, +++(Strong) 3.0%, ±(Doubtful) 5.0%.  Bacteriological examination of milk samples of 100 milch cows (400 quarters) revealed that 42 cows (42.0%) had suffering from SCM with different bacterial infection with 95% confidence limit was 32.1574-51.8426. Among 42 positive samples31 (31.0%) cows had mono-bacterial infection and 11 (11.0%) cows had mixed bacterial infections. Statistical analysis of the result of single and mixed bacterial infections in the milk of apparently healthy milch cows revealed that the single infection was significantly (P < 0.05) higher than mixed bacterial infection. Of the 31 mono-bacterial isolates, of which 23 (23.0%) isolates were Staphylococci, 3 (3.0%) isolates were Escherichia coli, 5 (5.0%) isolated Streptococcus spp. The 11 cows had mixed infection, of which 5 had Staphylococcus spp. + Streptococcus spp., 3 had E. coli + Staphylococcus spp., and 3 had Streptococcus spp. + E. coli. Of 42 positive cases of SCM Staphylococcus spp. isolated from 23 samples. Among these 23 positive samples 13 obtained from SGDF (37.14%) and 10 obtained from LFS (15.38%). Escherichia coli isolated from 3 samples. Among these 3 positive samples 3 obtained from LFS (4.62%). Streptococcus spp. isolated from 5 samples. Among these 5 positive samples 1 obtained from SGDF (2.86%) and 4 obtained from LFS (6.15%). Ceftriaxone, ciprofloxacin and gentamicin were the best drug for treating sub-clinical mastitis.

scholarly journals Nano-sized Droplets of Self-Emulsifying System for Enhancing Oral Bioavailability of Chemotherapeutic Agent VP-16 in Rats: A Nano Lipid Carrier for BCS Class IV Drugs

2018 ◽  
Vol 21 ◽  
pp. 398-408 ◽  
Author(s):  
Nayab Khalid ◽  
Muhammad Sarfraz ◽  
Mosab Arafat ◽  
Muhammad Akhtar ◽  
Raimar Löbenberg ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Chemotherapeutic Agent ◽  
Ternary Phase Diagram ◽  
In Vitro Dissolution ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
The Mean ◽  
Class Iv

PURPOSE: The purpose of this study was to investigate the ability of a self-nano-emulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of a BCS class IV drug, etoposide (VP-16). METHOD: A series of SNEDDS formulations with VP-16 were prepared consisting of medium chain triglycerides, polysorbate 80, diethylene glycol monoethyl ether and propylene glycol monolaurate type-1.  Based on an obtained ternary phase diagram, an optimum formulation was selected and characterized in terms of size, zeta potential, loading, morphology and in vitro drug release. The pharmacokinetic parameters and oral bioavailability of VP-16 suspension and VP-16 in SNEDDS was assessed using 30 Male Sprague–Dawley rats and compared with the commercial product (VePesid®). RESULTS: Pharmacokinetic data showed that the mean values for AUC0-t of VP-16 in SNEDDS was 6.4 fold higher compared to a drug suspension and 2.4-folds higher than VePesid®. Similarly, the mean value for Cmax of VP-16 in SNEDDS (1.13± 0.07 µg/ml µg.h/mL) was higher than VePesid® (0.62± 0.09 µg/mL) and drug suspension (0.13± 0.07 µg/mL). CONCLUSION: The SNEDDS formulation was able to enhance the oral bioavailability of the BCS Class IV chemotherapeutic agent VP-16 by increasing the dissolution and absorption of the drug. A good in vitro in vivo correlation was found between the in vitro dissolution and in vivo absorption data of VP-16 SNEDDS preparation. Therefore, SNEDDS formulations might be a very promising approach for BCS Class IV drugs.

scholarly journals An OMV-Based Nanovaccine Confers Safety and Protection against Pathogenic Escherichia coli via Both Humoral and Predominantly Th1 Immune Responses in Poultry

Nanomaterials ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2293
Author(s):  
Rujiu Hu ◽  
Haojing Liu ◽  
Mimi Wang ◽  
Jing Li ◽  
Hua Lin ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Immune Responses ◽  
Specific Antibody ◽  
Bacterial Infections ◽  
Outer Membrane Vesicles ◽  
Economic Losses ◽  
Broiler Chicks ◽  
Immunological Mechanism ◽  
Pathogenic Escherichia Coli

Avian pathogenic Escherichia coli (APEC) infection in poultry causes enormous economic losses and public health risks. Bacterial outer membrane vesicles (OMVs) and nano-sized proteolipids enriched with various immunogenic molecules have gained extensive interest as novel nanovaccines against bacterial infections. In this study, after the preparation of APEC O2-derived OMVs (APEC_OMVs) using the ultracentrifugation method and characterization of them using electron microscopy and nanoparticle tracking analyses, we examined the safety and vaccination effect of APEC_OMVs in broiler chicks and investigated the underlying immunological mechanism of protection. The results showed that APEC_OMVs had membrane-enclosed structures with an average diameter of 89 nm. Vaccination with 50 μg of APEC_OMVs had no side effects and efficiently protected chicks against homologous infection. APEC_OMVs could be effectively taken up by chicken macrophages and activated innate immune responses in macrophages in vitro. APEC_OMV vaccination significantly improved activities of serum non-specific immune factors, enhanced the specific antibody response and promoted the proliferation of splenic and peripheral blood lymphocytes in response to mitogen. Furthermore, APEC_OMVs also elicited a predominantly IFN-γ-mediated Th1 response in splenic lymphocytes. Our data revealed the involvement of both non-specific immune responses and specific antibody and cytokine responses in the APEC_OMV-mediated protection, providing broader knowledge for the development of multivalent APEC_OMV-based nanovaccine with high safety and efficacy in the future.

scholarly journals Synthetic Porcine Hepcidin Exhibits Different Roles in Escherichia coli and Salmonella Infections

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Dan Liu ◽  
Zhen-Shun Gan ◽  
Wan Ma ◽  
Hai-Tao Xiong ◽  
Yun-Qing Li ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Iron Status ◽  
Iron Chelator ◽  
Intracellular Iron ◽  
Content Type ◽  
Defense Strategies ◽  
Salmonella Infections

ABSTRACT Hepcidin, an antimicrobial peptide, was discovered to integrate diverse signals from iron status and an infection threat and orchestrate a series of host-protective responses. Several studies have investigated the antimicrobial role of hepcidin, but the results have been controversial. Here, we aimed to examine the role of hepcidin in bacterial adherence and invasion in vitro. We found that porcine hepcidin could decrease the amount of the extracellular pathogen enterotoxigenic Escherichia coli (ETEC) K88 that adhered to cells because it caused the aggregation of the bacteria. However, addition of hepcidin to macrophages infected with the intracellular pathogen Salmonella enterica serovar Typhimurium enhanced the intracellular growth of the pathogen through the degradation of ferroportin, an iron export protein, and then the sequestration of intracellular iron. Intracellular iron was unavailable by use of the iron chelator deferiprone (DFO), which reduced intracellular bacterial growth. These results demonstrate that hepcidin exhibits different functions in extracellular and intracellular bacterial infections, which suggests that different defense strategies should be taken to prevent bacterial infection.

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