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Minimum Inhibitory Concentration (minimum + inhibitory_concentration)
Selected AbstractsCorrelation of Minimum Inhibitory Concentrations Toward Oral Bacterial Growth Based on the Abraham ModelMOLECULAR INFORMATICS, Issue 10 2006Christina Mintz Abstract The Abraham solvation parameter model is used to construct mathematical correlations for describing the minimum inhibitory concentration of organic compounds for growth inhibition toward Porphyromonas gingivalis, Selenomonas artemidis, and Streptococcus sorbrinius. The derived mathematical correlations describe the observed published inhibitory data to within an overall average standard deviation of approximately 0.30 log units. A principal component analysis, shows that the derived equations for the three growth inhibitions are quite close to each other, are near to some, but not to all, equations for aqueous toxicity toward various organisms, and are quite far from most equations for water to solvent partition. A further analysis suggests that the three growth inhibition systems behave as though a solute is transferred from water to an environment that is still quite water-like. [source] Composition and antimicrobial activity of the volatile oil of Artemisia kopetdaghensis Krasch., M.Pop.FLAVOUR AND FRAGRANCE JOURNAL, Issue 6 2006& Linecz ex Poljak from Iran Abstract Artemisia kopetdaghensis Krasch., M.Pop. & Linecz ex Poljak (Asteraceae) is a common perennial herb growing wild in north-eastern parts of Iran. The essential oil of A. kopetdaghensis was isolated by hydrodistillation in 2.14% (v/w) yield. The chemical composition of the essential oil was examined by GC and GC,MS. Thirty-three compounds were identified, representing 86.8% of the total oil. The major constituents were methyleugenol (24.4%), geranial (13.6%), davanone (11.1%), camphor (9.8%) and neral (7.4%). Minimum inhibitory concentration was determined, using the agar dilution method, against eight bacteria and two fungal strains. The essential oil showed a moderate antimicrobial activity. Copyright © 2006 John Wiley & Sons, Ltd. [source] CHEMICAL CHARACTERIZATION AND ANTIFUNGAL ACTIVITY OF ORIGANUM ONITES L. ESSENTIAL OILS AND EXTRACTSJOURNAL OF FOOD SAFETY, Issue 1 2009MIHRIBAN KORUKLUOGLU ABSTRACT Essential oils (EOs) and extracts (methanol, acetone and diethyl ether) of fresh and dried oregano (Origanum onites L.) were used to determine the antifungal effect on Alternaria alternata, Aspergillus flavus (two strains), Aspergillus niger (two strains), Aspergillus parasiticus, Fusarium semitectum, Fusarium oxysporum, Mucor racemosus and Penicillium roqueforti by disk diffusion methods. Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of all samples were determined. The antifungal activity of the fresh herb was greater than that of the dried herb. MIC values for fresh and dried methanol extracts were 150,950 µg/mL and 750,950 µg/mL, respectively. MFC values for methanol extracts were determined between 300 and 1200 µg/mL for fresh oregano and between 750 and 1100 µg/mL for dried oregano. The EOs of fresh and dried oregano totally inhibited test fungi. EOs produced the lowest MIC and MFC values: 8.5 µg/mL and 9.0 µg/mL, respectively (P < 0.005). The highest extract activity was exhibited by fresh oregano against A. alternata (24 mm) followed by P. roqueforti (20 mm). The greatest total antifungal effect was observed from methanol extracts. The chemical composition of fresh oregano EO and extracts was examined using gas chromatography-mass spectrometry (GC-MS). Over 80 volatiles were detected, of which 42 were positively identified by matching both MS fragmentation patterns with standardized retention characteristics. p-Cymene, thymol and carvacrol were the most prominent, followed by ,-pinene, camphor and borneol. PRACTICAL APPLICATIONS In the past decade interest in natural antimicrobial plant extracts has been growing. Various plants have historically been used for the purposes of food preservation and flavor enhancement as well as medicinal purposes. An example is oregano, the leafy part of the plant belonging to the Labiatae family. It has been used to improve the flavor and the organoleptic properties of many foods from numerous cultures. It has also been used to prolong the storage life of foods probably because of antifungal properties. The preservative nature of fresh oregano has been employed in many food applications, including meat and fish products, as well as in pharmaceuticals, alternative medicines and natural therapies. [source] Different antibacterial actions of isoflavones isolated from Erythrina poeppigiana against methicillin-resistant Staphylococcus aureusLETTERS IN APPLIED MICROBIOLOGY, Issue 3 2006M. Sato Abstract Aims:, To screen six isoflavones isolated from Erythrina poeppigiana (Leguminosae) for their antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Methods and Results:, Stem bark of E. poeppigiana was macerated with acetone and the methylene chloride-soluble fraction of the residue was applied to repeated silica gel column chromatography and eluted. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by a broth dilution method. Inactive compounds that failed inhibiting bacterial growth at 25 ,g ml,1 were further investigated for their combination effects with methicillin and oxacillin. Of the isolated isoflavones, 5,7,4,-trihydroxy-8,3,-di(,,, -dimethylallyl)isoflavone (isolupalbigenin) exhibited the highest anti-MRSA activity (MICs: 1·56,3·13 ,g ml,1; MBCs: 6·25,12·5 ,g ml,1), followed by 5,7,4,-trihydroxy-6- ,,, -dimethylallylisoflavone (erythrinin B). Inactive compounds were combined with methicillin or oxacillin, 5,4,-dihydroxy-(3,,,4,,-dihydro-3,,-hydroxy)-2,,,2,,-dimethylpyrano[5,,,6,,:6,7]isoflavone (M-Wi-2) intensifying the susceptibility of MRSA strains to these antibiotics. In all but one strain, the MIC values of methicillin were reduced from ,100 to 6·25,12·5 ,g ml,1 in the presence of M-Wi-2 (25 ,g ml,1). Conclusions:, Isoflavones from E. poeppigiana showed two different antibacterial activities against MRSA: direct growth inhibition and intensification of methicillin sensitivity. Significance and Impact of the Study:, Isolupalbigenin and M-Wi-2 could lead to the development of compounds for new approaches against MRSA infection. [source] Vancomycin dosing assessment in intensive care unit patients based on a population pharmacokinetic/pharmacodynamic simulationBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2010Natalia Revilla WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Despite the frequent use of vancomycin in intensive care unit (ICU) patients, few studies aimed at characterizing vancomycin population pharmacokinetics have been performed in this critical population. , Population pharmacokinetics coupled with pharmacodynamic analysis, in order to optimize drug exposure and hence antibacterial effectiveness, has been little applied in these specific patients. WHAT THIS STUDY ADDS , Our population model characterized the pharmacokinetic profile of vancomycin in adult ICU patients, higher distribution volume values (V) being observed when the patient's serum creatinine (CrSe) was greater than 1 mg dl,1. , Age and creatinine clearance (CLcr) were identified as the main covariates explaining the pharmacokinetic variability in vancomycin CL. , Our pharmacokinetic/pharmacodynamic (PK/PD) simulation should aid clinicians to select initial vancomycin doses that will maximize the rate of response in the ICU setting, taking into account the patient's age and renal function as well as the susceptibility of Staphylococcus aureus. AIM To estimate the vancomycin pharmacokinetic profile in adult ICU patients and to assess vancomycin dosages for increasing the likelihood of optimal exposure. METHODS Five hundred and sixty-nine concentration,time data from 191 patients were analysed using a population pharmacokinetic approach (NONMENÔ). External model evaluation was made in 46 additional patients. The 24 h area under the concentration,time curve (AUC(0,24 h)) was derived from the final model. Minimum inhibitory concentration (MIC) values for S. aureus were obtained from the EUCAST database. AUC(0,24 h) : MIC , 400 was considered as PK/PD efficacy index. The probability of different dosages attaining the target considering different strains of S. aureus and patient subgroups was estimated with Monte Carlo simulation. RESULTS Vancomycin CL showed a significant dependence on patient age and renal function whereas CrSe > 1 mg dl,1 increased V more than twofold. For our representative ICU patient, 61 years, 73 kg, CrSe= 1.4 mg dl,1, measured CLCr= 74.7 ml min,1, the estimated values were CL = 1.06 ml min,1 kg,1 and V= 2.04 l kg,1. The cumulative fraction of response for a standard vancomycin dose (2 g day,1) was less than 25% for VISA strains, and 33% to 95% for susceptible S. aureus, depending on patient characteristics. CONCLUSIONS Simulations provide useful information regarding the initial assessment of vancomycin dosing, the conventional dosing regimen probably being suboptimal in adult ICU patients. A graphic approach provides the recommended dose for any selected probability of attaining the PK/PD efficacy target or to evaluate the cumulative fraction of response for any dosing regimen in this population. [source] Antimicrobial activity of endemic Crataegus tanacetifolia (Lam.) Pers and observation of the inhibition effect on bacterial cellsCELL BIOCHEMISTRY AND FUNCTION, Issue 8 2008Mehlika Benli Abstract Up to now an increasing number of antibiotic-resistant bacteria have been reported and thus new natural therapeutic agents are needed in order to eradicate these pathogens. Through the discovery of plants such as Crataegus tanacetifolia (Lam.) Pers that have antimicrobial activity, it will be possible to discover new natural drugs serving as chemotherapeutic agents for the treatment of nosocomial pathogens and take these antibiotic-resistant bacteria under control. The objective of the present study was to determine antimicrobial activity and the activity mechanism of C. tanacetifolia plant extract. The leaves of C. tanacetifolia, which is an endemic plant, were extracted using methanol and tested against 10 bacterial and 4 yeast strains by using a drop method. It was observed that the plant extract had antibacterial effects on Bacillus subtilis, Shigella, Staphylococcus aureus, and Listeria monocytogenes among the microorganisms that were tested. Minimum inhibitory concentration (MIC) results obtained at the end of an incubation of 24,h were found to be ,6.16,mg,ml,1 for B. subtilis, <394,mg,ml,1 for Shigella, and ,3.08,mg,ml,1 for L. monocytogenes and S. aureus and minimum bactericidal concentration (MBC) were found as ,24.63,mg,ml,1 for B. subtilis, ,394,mg,ml,1 for Shigella, ,6.16,mg,ml,1 for L. monocytogenes, and ,98.5,mg,ml,1 for S. aureus. According to the MBC results, it was found that the plant extract had bactericidal effects and in order to explain the activity mechanism and cell deformation of bacterial strains treated with plant extract, the scanning electron microscopy (SEM) was used. The results of SEM showed that the treated cells appeared shrunken and there was degradation of the cell walls. This study, in which the antibacterial effect of C. tanacetifolia was demonstrated, will be a base for further investigations on advanced purification and effect mechanism of action of its active compounds. Copyright © 2008 John Wiley & Sons, Ltd. [source] Ceragenin CSA-13 exhibits antimicrobial activity against cariogenic and periodontopathic bacteriaMOLECULAR ORAL MICROBIOLOGY, Issue 2 2009E. Isogai Introduction:, Ceragenin CSA-13 is a bile-acid-based mimic of endogenous antimicrobial peptides and shares a mechanism of action with many of these antimicrobial agents. Because CSA-13 is not peptide based, it is not a substrate for the proteases that are found in the oral cavity, which are capable of degrading antimicrobial peptides. Furthermore, the simplicity of the ceragenins makes them easier to prepare and purify than antimicrobial peptides. In this study, we examined the antimicrobial activities of CSA-13 against oral pathogens and found that this compound was bactericidal against all of the strains tested. Methods:, The strains used were isolates of Streptococcus mutans and Porphyromonas species. Minimum inhibitory concentrations (MIC) were determined using agar dilution methods. In susceptibility testing, viable counts were determined after incubation with CSA-13. Results:, CSA-13 was potent against all 23 strains tested with MICs of 1,8 ,g/ml for S. mutans and 1,16 ,g/ml for 24 strains of the genus Porphyromonas. The MIC50 was 2 and the MIC90 was 8 ,g/ml for S. mutans. MIC ranges for protease-positive P. gingivalis and P. cangingivaliswere 2,16 ,g/ml, and 1,2 ,g/ml for protease-negative P. circumdentaria. CSA-13 interacted with lipopolysaccharide-sensitized erythrocytes at a concentration of 5.0,20.0 ,g/ml. Conclusion:, CSA-13 displays broad-spectrum activity against cariogenic and periodontopathic bacteria. CSA-13 was effective against protease-positive Porphyromonas. It was shown to bind to erythrocytes coated with lipopolysaccharide and lipoteichoic acid from diverse bacterial strains. These results suggest that CSA-13 may be useful for the prevention and treatment of oral microbial diseases. [source] Antimicrobial activity of clove and rosemary essential oils alone and in combinationPHYTOTHERAPY RESEARCH, Issue 10 2007YuJie Fu Abstract In the present study, the antimicrobial activity of the essential oils from clove (Syzygium aromaticum (L.) Merr. et Perry) and rosemary (Rosmarinus officinalis L.) was tested alone and in combination. The compositions of the oils were analysed by GC/MS. Minimum inhibitory concentrations (MIC) against three Gram-positive bacteria, three Gram-negative bacteria and two fungi were determined for the essential oils and their mixtures. Furthermore, time-kill dynamic processes of clove and rosemary essential oils against Staphylococcus epidermidis, Escherichia coli and Candida albicans were tested. Both essential oils possessed significant antimicrobial effects against all microorganisms tested. The MICs of clove oil ranged from 0.062% to 0.500% (v/v), while the MICs of rosemary oil ranged from 0.125% to 1.000% (v/v). The antimicrobial activity of combinations of the two essential oils indicated their additive, synergistic or antagonistic effects against individual microorganism tests. The time-kill curves of clove and rosemary essential oils towards three strains showed clearly bactericidal and fungicidal processes of 1/2 × MIC, MIC, MBC and 2 × MIC. Copyright © 2007 John Wiley & Sons, Ltd. [source] Enhancement of Vancomycin Activity by Phenothiazines against Vancomycin-Resistant Enterococcus Faecium in vitroBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2010Mohammad Rahbar Minimum inhibitory concentrations (MIC) of the compounds were determined by agar dilution method, and synergy between phenothiazines and vancomycin was investigated using Checkerboard (microbroth dilution) technique. We found that all enterococci strains, regardless of their susceptibility to vancomycin, were inhibited by phenothiazines at concentrations varying from 8 to 256 ,g/ml, with thiethylperazine being the most potent inhibitory agent. Besides, all the phenothiazines showed partial synergy with vancomycin and could lessen MIC of vancomycin from 512 to 8 ,g/ml at their sub-inhibitory concentrations. The highest reduction in MIC was observed with chlorpromazine (32 times); however, thiethylperazine and promethazine stood next (24 times). Although resistance modification was observed at concentrations higher than those that phenothiazines reach in vivo, the potential offered by non-antibiotics justify further animal experiments as well as clinical trials to establish their clinical relevance. [source] The first case of cutaneous mucormycosis caused by Rhizopus azygosporusBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2005A. Fujimoto Summary A rapidly enlarging leg ulcer appeared in a 54-year-old woman with systemic lupus erythematosus receiving aggressive immunosuppressive therapy. Skin biopsy revealed proliferation of hyphae in the midst of a neutrophilic abscess. Culture yielded Rhizopus azygosporus. As no organ involvement was detected by thorough examination, the patient was diagnosed as having primary cutaneous mucormycosis. Although intravenous amphotericin B therapy seemed to be very effective, it had to be discontinued due to nephrotoxicity. She unfortunately died of subsequent disseminated fungal infection and cerebral infarction in which the primary cause could not be determined. Minimum inhibitory concentrations of several antifungal drugs to the isolate were examined and amphotericin B proved to be the only agent that may potentially reach the effective plasma concentration. This is the first case report of cutaneous mucormycosis caused by R. azygosporus. [source] Comparative serum pharmacokinetics of the fluoroquinolones enrofloxacin, difloxacin, marbofloxacin, and orbifloxacin in dogs after single oral administrationJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2002E. HEINEN The pharmacokinetics after oral application of the fluoroquinolones (FQs), enrofloxacin, difloxacin, marbofloxacin and orbifloxacin were compared in independent crossover studies in Beagle dogs. Commercially available tablet formulations were given at common dosage recommended by the manufacturers which were 2.0 mg/kg body weight (bw) for marbofloxacin, 2.5 mg/kg bw for orbifloxacin and 5.0 mg/kg bw for enrofloxacin and difloxacin. Analysis was performed by an agar diffusion assay. Pharmacokinetic parameters were calculated by noncompartmental methods. All FQs were rapidly absorbed and achieved average peak serum concentrations of 1.41, 1.11, 1.47 and 1.37 ,g/mL for enrofloxacin, difloxacin, marbofloxacin and orbifloxacin, respectively. Enrofloxacin was eliminated at a terminal half-life (t˝) of 4.1 h, difloxacin at 6.9 h, orbifloxacin at 7.1 h and marbofloxacin at 9.1 h. While the area under the serum concentration,time curve of the 24-h dosing interval (AUC0,24) for marbofloxacin and orbifloxacin were similar (approximately 13 ,g · h/mL), enrofloxacin attained an AUC0,24 of 8.7 and difloxacin of 9.3 ,g · h/mL. Because of its favourable pharmacokinetics combined with excellent in vitro activity, enrofloxacin exhibited superior pharmacodynamic predictors of in vivo antimicrobial activity as Cmax/MIC (maximum serum concentration/minimum inhibitory concentration) and AUC0,24/MIC (area under the 24-h serum concentration,time curve/minimum inhibitory concentration) compared with other FQs. [source] Ocular penetration of intravenously administered enrofloxacin in the horseEQUINE VETERINARY JOURNAL, Issue 2 2008T. J. DIVERS Summary Reason for performing study: Information on antibiotic concentrations in the equine eye following systemic therapy is limited. Reports that Leptospira spp. are frequently present in the eyes of horses with recurrent uveitis, emphasises a need for studies on ocular concentrations of specific antibiotics. Hypotheses: 1) Enrofloxacin, administered i.v. at 7.5 mg/kg bwt q. 24 h, results in aqueous humour concentrations greater than the reported minimum inhibitory concentration (MIC) for Leptospira pomona. 2) Aqueous humour paracentesis sufficiently disrupts the blood-aqueous humour barrier (BAB) to cause an increase in aqueous humour protein and enrofloxacin concentrations. Methods: Aqueous humour enrofloxacin and total protein concentrations were determined in 6 healthy, mature horses after i.v. administration of enrofloxacin. Paracentesis was performed on the left eye on Days 3 and 4, one hour following enrofloxacin administration, to determine enrofloxacin concentrations in healthy eyes and in eyes with mechanical disruption of the BAB. Paracentesis was also performed on the right eye 23 h after enrofloxacin administration. Blood samples were collected from the horses at identical times to determine enrofloxacin aqueous humour:plasma ratios. Results: Mean ± s.d. enrofloxacin concentration in the aqueous humour one hour post administration on Day 3 was 0.32 ± 0.10 mg/l (range 0.18-0.47); and aqueous humour enrofloxacin, total protein and aqueous humour:plasma enrofloxacin ratios were higher on Day 4 than Day 3. Conclusions and potential relevance: Following disruption of the BAB, enrofloxacin concentrations were above the reported MIC for Leptospira pomona. [source] Minimizing the release of proinflammatory and toxic bacterial products within the host: A promising approach to improve outcome in life-threatening infectionsFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2005Roland Nau Abstract Various bacterial components (e.g., endotoxin, teichoic and lipoteichoic acids, peptidoglycans, DNA) induce or enhance inflammation by stimulating the innate immune system and/or are directly toxic in eukariotic cells (e.g., hemolysins). When antibiotics which inhibit bacterial protein synthesis kill bacteria, smaller quantities of proinflammatory or toxic compounds are released in vitro and in vivo than during killing of bacteria by ,-lactams and other cell-wall active drugs. In general, high antibiotic concentrations liberate lower quantities of bacterial proinflammatory or toxic compounds than concentrations close to the minimum inhibitory concentration. In animal models of Escherichia coli Pseudomonas aeruginosa and Staphylococcus aureus peritonitis/sepsis and of Streptococcus pneumoniae meningitis, a lower release of proinflammatory bacterial compounds was associated with a reduced mortality or neuronal injury. Pre-treatment with a bacterial protein synthesis inhibitor reduced the strong release of bacterial products usually observed during treatment with a ,-lactam antibiotic. Data available strongly encourage clinical trials comparing antibiotic regimens with different release of proinflammatory/toxic bacterial products. The benefit of the approach to reduce the liberation of bacterial products should be greatest in patients with a high bacterial load. [source] Alaska Sentinel Surveillance for Antimicrobial Resistance in Helicobacter pylori Isolates from Alaska Native Persons, 1999,2003HELICOBACTER, Issue 6 2006Michael G. Bruce Abstract Background:, Previous studies in Alaska have demonstrated elevated proportions of antimicrobial resistance among Helicobacter pylori isolates. Materials and Methods:, We analyzed H. pylori data from the Centers for Disease Control and Prevention (CDC)'s sentinel surveillance in Alaska from July 1999 to June 2003 to determine the proportion of culture-positive biopsies from Alaska Native persons undergoing routine upper-endoscopy, and the susceptibility of H. pylori isolates to metronidazole [minimum inhibitory concentration (MIC) of > 8 g metronidazole/mL), clarithromycin (MIC , 1), tetracycline (MIC , 2) and amoxicillin (MIC , 1)] using agar dilution. Results:, Nine-hundred sixty-four biopsy specimens were obtained from 687 participants; 352 (51%) patients tested culture positive. Mean age of both culture-positive and culture-negative patients was 51 years. Metronidazole resistance was demonstrated in isolates from 155 (44%) persons, clarithromycin resistance from 108 (31%) persons, amoxicillin resistance from 8 (2%) persons, and 0 for tetracycline resistance. Metronidazole and clarithromycin resistance varied by geographic region. Female patients were more likely than male subjects to show metronidazole resistance (p < .01) and clarithromycin resistance (p = .05). Conclusions:, Resistance to metronidazole and clarithromycin is more common among H. pylori isolates from Alaska Native persons when compared with those from elsewhere in the USA. [source] Antimicrobial Susceptibility of Helicobacter pylori Strains in a Random Adult Swedish PopulationHELICOBACTER, Issue 4 2006Tom Storskrubb Abstract Background and Aim:, Antimicrobial resistance in Helicobacter pylori is a growing problem and has become an important factor leading to eradication failure. Information on antimicrobial susceptibility is important for selection of an optimum treatment regimen. The resistance rate in a random population has not been studied previously. Methods:, A random Swedish population sample (n = 3000, age 20,81 years) was surveyed using a mailed validated questionnaire assessing gastrointestinal symptoms (response rate of 74%). One-third of the responders was invited, in random order, and accepted an esophagogastroduodenoscopy with biopsies for H. pylori culture and histology. Subjects were not treated for their H. pylori infection but a minimum inhibitory concentration of metronidazole, clarithromycin, amoxicillin, and tetracycline for the H. pylori isolates (n = 333) was determined by agar dilution. Prescribed antibiotic in the area was recorded. Results:, Irrespective of symptomatology, 16.2% of the isolated H. pylori strains were resistant to metronidazole, 1.5% to clarithromycin, 0% to amoxicillin, and 0.3% to tetracycline. The antibiotic consumption was low from an international perspective. Conclusion:, The resistance to the antibiotics was lower than expected from patient sample studies, especially for clarithromycin, most probably due to a restrictive prescription policy in the area. Introduction of a test-and-treat strategy in Sweden would only marginally affect the usage of clarithromycin. [source] Enhancement of the efficacy of erythromycin in multiple antibiotic-resistant gram-negative bacterial pathogensJOURNAL OF APPLIED MICROBIOLOGY, Issue 3 2008S. Saha Abstract Aims:, To improve the efficacy of erythromycin, a hydrophobic antibiotic, against multiple antibiotic-resistant gram-negative bacterial pathogens by enhancing their outer membrane permeability. Methods and Results:, Fifty-one nonrepeat gram-negative bacterial pathogens of various genera, resistant to multiple antibiotics, including erythromycin, were selected by disc agar diffusion tests. The amphiphilic cationic steroid antibiotic, Ceragenin CSA-13, a potent permeabilizer of bacterial outer membranes, reduced the minimum inhibitory concentration of erythromycin in 92% of the bacterial pathogens selected for the test, when supplemented with erythromycin. A synergistic effect of Ceragenin CSA-13 and erythromycin in combination was also observed. Spectrofluorimetric study confirmed that Ceragenin CSA-13 acts by depolarizing the bacterial outer membrane. The toxicity of Ceragenin CSA-13 was evaluated to be insignificant by measuring ,median lethal dose' (LD50) on mouse model. Conclusions:, Ceragenin CSA-13 may be useful as an agent to make erythromycin effective against infections caused by multiple antibiotic resistant gram-negative bacteria. Significance and Impact of the Study:, The outcome of the study suggests erythromycin,Ceragenin combination as a new approach to overcome the problem associated with the rapid emergence of multi-drug-resistant pathogens. The insignificant toxicity of Ceragenin CSA-13, as found, supports the possibility of the application of this compound for human therapeutics. [source] Microencapsulation of doxycycline into poly(lactide- co -glycolide) by spray drying technique: Effect of polymer molecular weight on process parametersJOURNAL OF APPLIED POLYMER SCIENCE, Issue 6 2008Pradip Patel Abstract Poly(lactide- co -glycolide) (PLGA) polymers with three different molecular weights were prepared, and microparticles were produced by spray drying and water-in-oil-water (w/o/w) double emulsion techniques to encapsulate 86% of doxycycline (DXY), an antibiotic drug, for the use of periodontitis. Placebo and drug-loaded microspheres and pristine DXY were analyzed by Fourier transform infrared spectroscopy, which indicated no chemical interactions between DXY and PLGA. X-ray diffraction of drug-loaded microspheres confirmed the molecular level dispersion of DXY in PLGA. Scanning electron microscopy confirmed spherical nature and smooth surfaces of the microspheres. Mean particle size as measured by laser light scattering technique ranged between 10 and 25 ,m. In vitro release of DXY performed in 7.4 pH media continued up to 72 h and depended on molecular weight of PLGA and extent of DXY loading. Antimicrobial studies performed on one formulation and placebo microspheres suggested that drug concentrations during in vitro release are above the minimum inhibitory concentration (MIC) for Staphylococcus aureus growth. Overall, the release studies depended on the molecular weight of PLGA, extent of drug loading, and the method used to prepare microspheres. Statistical analyses of release data performed using the analysis of variance (ANOVA) method agreed well with experimental observations. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source] Effect of certain bioactive plant extracts on clinical isolates of ,-lactamase producing methicillin resistant Staphylococcus aureusJOURNAL OF BASIC MICROBIOLOGY, Issue 2 2005Farrukh Aqil Ethanolic extracts and some fractions from 10 Indian medicinal plants, known for antibacterial activity, were investigated for their ability to inhibit clinical isolates of ,-lactamase producing methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA). Synergistic interaction of plant extracts with certain antibiotics was also evaluated. The MRSA test strains were found to be multi-drug resistant and also exhibited high level of resistance to common ,-lactam antibiotics. These strains produced ,-lactamases, which hydrolyze one or other ,-lactam antibiotics, tested. The extract of the plants from Camellia sinensis (leaves), Delonix regia (flowers), Holarrhena antidysenterica (bark), Lawsonia inermis (leaves), Punica granatum (rind), Terminalia chebula (fruits) and Terminalia belerica (fruits) showed a broad-spectrum of antibacterial activity with an inhibition zone size of 11 mm to 27 mm, against all the test bacteria. The extracts from the leaves of Ocimum sanctum showed better activity against the three MRSA strains. On the other hand, extracts from Allium sativum (bulb) and Citrus sinensis (rind) exhibited little or no activity, against MRSA strains. The antibacterial potency of crude extracts was determined in terms of minimum inhibitory concentration (MIC) by the tube dilution method. MIC values, of the plant extracts, ranged from 1.3 to 8.2 mg/ml, against the test bacteria. Further, the extracts from Punica granatum and Delonix regia were fractionated in benzene, acetone and methanol. Antibacterial activity was observed in acetone as well as in the methanol fractions. In vitro synergistic interaction of crude extracts from Camellia sinensis, Lawsonia inermis, Punica granatum, Terminalia chebula and Terminalia belerica was detected with tetracycline. Moreover, the extract from Camellia sinensis also showed synergism with ampicillin. TLC of the above extracts revealed the presence of major phytocompounds, like alkaloids, glycosides, flavonoids, phenols and saponins. TLC-bioautography indicated phenols and flavonoids as major active compounds. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Intermittent watt-level ultrasonication facilitates vancomycin release from therapeutic acrylic bone cementJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2009Xun-Zi Cai Abstract Ultrasound holds promise for enhancing the vancomycin release from cement though the length of time when local drug level exceeded the minimum inhibitory concentration (T>MIC) was not prolonged by the previous protocol of milliwatt-level ultrasonication. Here vancomycin-loaded cements were subjected to continuous watt-level ultrasonication (CUG), intermittent watt-level ultrasonication (IUG) or no ultrasonication (NUG) for 14 d during immersion in 40-ml phosphate buffered saline (PBS) for 28 d. The T>MIC for IUG was more than three times that for NUG. In contrast, T>MIC for CUG was slightly shortened. The subtherapeutic release of vancomycin between 15 d and 28 d for IUG was one-ninth that for NUG. The fitting equations indicated a significant enhancement on the burst release and the slow release for IUG; however, the continuous ultrasonication hampered the slow release. SEM images exhibited denser craters and pores with larger diameters and less residual drug in specimens from IUG relative to those from both CUG and NUG. Intermittent watt-level ultrasonication improved the ultrasound-enhanced vancomycin release from cement in view of the prolonged T>MIC and the inhibited subtherapeutic release compared with continuous ultrasonication. The mechanisms may be associated with the distinctive effects of detaching forces and pushing forces by acoustic microstreams. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009 [source] Evaluation of extracts of Jatropha curcas and Moringa oleifera in culture media for selective inhibition of saprophytic fungal contaminantsJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2009Grace Mebi Ayanbimpe Abstract Most fungi occur in nature and utilize simple sources of carbohydrates and nitrogen for growth. Sabouraud's dextrose agar has been an ideal medium for primary isolation of fungi from clinical specimens, but for specimens from nonsterile sites or heavily contaminated ones, it has been necessary to include inhibitory substances such as antibiotics like chloramphenicol (antibacterial) and cycloheximide (antifungal). The problems we have in the our laboratory owing to frequent contamination of cultures and the delays in the procurement of cycloheximide have stimulated a search for alternatives in our local environment to enhance effective laboratory diagnoses of fungal infections. Purified extracts of the leaves and bark of Jatropha curcas and Moringa oleifera (common plants in our locality) were tested against clinical isolates of fungi at various concentrations to determine the minimum inhibitory concentration at which common fungal contaminants are inhibited, without affecting the growth of the pathogenic fungi sought for. At a concentration of 0.75,mg,ml,1 contaminants were totally inhibited by the leaf extracts. The bark extracts did not inhibit any fungus even at higher concentrations. From the results it was evident that the leaf extracts of both plants have potentials for use as inhibitory substances in culture media against contaminant fungi including Aspergillus spp., Penicillium spp., etc. J. curcas and M. oleifera are very common plants in our locality. They can be obtained at almost no cost and at any time needed. The benefits of these findings to mycology laboratories in a developing country are enormous. J. Clin. Lab. Anal. 23:161,164, 2009. © 2009 Wiley-Liss, Inc. [source] The garlic component, allicin, prevents disease caused by Aeromonas hydrophila in rainbow trout, Oncorhynchus mykiss (Walbaum)JOURNAL OF FISH DISEASES, Issue 4 2010E J Nya Abstract Allicin was fed at 0 (= control), 0.5 and 1.0 mL of Allimed® liquid 100 g,1 of feed for 14 days to rainbow trout, Oncorhynchus mykiss (Walbaum), fingerlings before infection with Aeromonas hydrophila with a resultant reduction in mortalities from 80% in the controls to 8% [relative percentage survival (RPS) = 90%] and 0% (RPS = 100%) among the treated fish. Allicin was strongly antibacterial compared to the control, with a minimum inhibitory concentration (MIC) of >400 ,L mL,1 of Allimed® liquid. Use of allicin led to a lower number of white blood cells (132.0 ± 0.4 × 103) compared to 175.0 ± 0.1 × 103 in the controls, but elicited increased phagocytic activity, i.e. a phagocytic value of 39.2% compared to 13.6% in the controls, and serum lysozyme activity, which showed significant (P > 0.05) differences compared to the control at 15 and 30 min after the first reading at 0 min of incubation. [source] Evaluation of diquat against an acute experimental infection of Flavobacterium columnare in channel catfish, Ictalurus punctatus (Rafinesque)JOURNAL OF FISH DISEASES, Issue 5 2009A M Darwish Abstract A trial was performed to evaluate the efficacy of diquat (6,7-dihydrodipyrido[1,2-a:2,,1,-c]pyrazinediium dibromide) against an acute experimental infection of Flavobacterium columnare in channel catfish, Ictalurus punctatus. Diquat is an Environmental Protection Agency-approved herbicide and has the potential to be legally and practically used against columnaris. Channel catfish were challenged, by cutaneous abrasion, and waterborne exposure to F. columnare and treated once at 22-h post-challenge with 2.5, 5.0, 10.0 and 15 mg L,1 of diquat active ingredient for 6 h. At the conclusion of the trial, 21-day post-challenge, diquat at 5.0, 10.0 and 15 mg L,1 significantly (P < 0.05) reduced the mortality of infected fish from 95% in the challenged non-treated fish to 68%, 59% and 49%, respectively. In vitro, the minimum inhibitory concentration (MIC) of 23 isolates of F. columnare was assayed. The majority of the isolates had an MIC value of 5 ,g mL,1 (15 of the 23 isolates). Infected fish exhibited acute clinical signs similar to a natural infection. The skin had severe ulcerative necrotizing dermatitis and the muscles had severe necrotizing myositis. The gills had severe multifocal necrotizing branchitis. The results demonstrate that diquat would reduce mortalities caused by an acute columnaris infection. [source] Bactericidal effect of dentin primer containing antibacterial monomer methacryloyloxydodecylpyridinium bromide (MDPB) against bacteria in human carious dentinJOURNAL OF ORAL REHABILITATION, Issue 4 2001S. Imazato The aim of this study was to investigate the bactericidal effect of a dentin primer incorporating the antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide (MDPB) against bacteria in human dentinal carious lesions. To evaluate the antibacterial activity of MDPB against anaerobes, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) against obligate anaerobes and facultative anaerobic strains of lactobacilli were determined. Bacteria were recovered from carious dentin samples obtained from the teeth of patients, and the bactericidal activities of the experimental primer containing 5% MDPB and three commercially available primers were compared by counting the number of viable cells after contact with diluted solutions of each primer for 30 s. MDPB showed strong antibacterial activity against anaerobes, the MIC and MBC values ranging from 3·9 to 31·3 ,g mL,1 and 15·6,125 ,g mL,1, respectively. Experimental primer containing MDPB was the most bactericidal among the materials tested (ANOVA, Fisher's PLSD test, P < 0·05) and was able to kill the bacteria completely even when diluted 40 times, while the three commercial products exhibited little activity at 40 times dilution. These results indicate that incorporation of MDPB into dentin primer could be beneficial for eliminating the residual bacteria in cavities. [source] Chitosan-coated antifungal formulations for nebulisationJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2010Yacoub Y. Albasarah Abstract Objectives, The aim of this study was to produce and characterise amphotericin B (AmB) containing chitosan-coated liposomes, and to determine their delivery from an air-jet nebuliser. Methods, Soya phosphatidylcholine : AmB (100 : 1) multilamellar vesicles were generated by dispersing ethanol-based proliposomes with 0.9% sodium chloride or different concentrations of chitosan chloride. These liposomes were compared with vesicles produced by the film hydration method and micelles. AmB loading, particle size, zeta potential and antifungal activity were determined for formulations, which were delivered into a two-stage impinger using a jet nebuliser. Key findings, AmB incorporation was highest for liposomes produced from proliposomes and was greatest (approximately 80% loading) in chitosan-coated formulations. Following nebulisation, approximately 60% of the AmB was deposited in the lower stage of the two-stage impinger for liposomal formulations, for which the mean liposome size was reduced. Although AmB loading in deoxycholate micellar formulations was high (99%), a smaller dose of AmB was delivered to the lower stage of the two-stage impinger compared to chitosan-coated liposomes generated from proliposomes. Chitosan-coated and uncoated liposomes loaded with AmB had antifungal activities against Candida albicans and C. tropicalis similar to AmB deoxycholate micelles, with a minimum inhibitory concentration of 0.5 µg/ml. Conclusions, This study has demonstrated that chitosan-coated liposomes, prepared by an ethanol-based proliposome method, are a promising carrier system for the delivery of AmB using an air-jet nebuliser, having a high drug-loading that is likely to be effectively delivered to the peripheral airways for the treatment of pulmonary fungal infections. [source] Thienyl analogues of acyclic monoterpene alcohols and their biological activityJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 12 2009Rados, aw Bonikowski Abstract BACKGROUND: Thienyl analogues of linalool, geraniol, nerol and citronellol were synthesised and their sensory and anti- microbial activities were investigated. RESULTS: The thienyl analogues of linalool, geraniol, nerol and citronellol, in which the isobutenyl moiety was replaced by a thiophene substituent, were synthesised from commercially available 2- and 3-methylthiophenes and 2- and 3-thiophenecarboxaldehydes. The olfactory properties of the new compounds were generally of the corresponding parent terpene type; however, their relative volatility determined by the headspace gas chromatography method was lower by a factor of 34,42 compared with the parent alcohols. Antimicrobial activity against Aspergillus niger and Penicillium expansum of some thienyl analogues of linalool was 1.5,3 times higher than that of linalool, with a minimum inhibitory concentration of 0.2,0.1 µL mL,1. CONCLUSION: Replacement of the isobutenyl moiety in acyclic monoterpene alcohols by a thienyl substituent results in the formation of new terpene analogues, some of which are interesting for perfumery and cosmetology because of their odour quality, tenacity and antimicrobial action. Copyright © 2009 Society of Chemical Industry [source] Disposition of oral telithromycin in foals and in vitro activity of the drug against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolatesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2010L. H. JAVSICAS Javsicas, LH., Gigučre, S., Womble, AY. Disposition of oral telithromycin in foals and in vitro activity of the drug against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolates. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2009.01151.x. The objectives of this study were to determine the serum and pulmonary disposition of telithromycin in foals and to determine the minimum inhibitory concentration (MIC) of telithromycin against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolates. A single dose of telithromycin (15 mg/kg of body weight) was administered to six healthy 6,10-week-old foals by the intragastric route. Activity of telithromycin was measured in serum, pulmonary epithelial lining fluid (PELF), and bronchoalveolar lavage (BAL) cells using a microbiological assay. The broth macrodilution method was used to determine the MIC of telithromycin, azithromycin, clarithromycin and erythromycin against R. equi. Following intragastric administration, mean ± SD time to peak serum telithromycin activity (Tmax) was 1.75 ± 0.76 h, maximum serum activity (Cmax) was 1.43 ± 0.37 ,g/mL, and terminal half-life (t˝) was 3.81 ± 0.40 h. Telithromycin activity, 4 h postadministration was significantly higher in BAL cells (50.9 ± 14.5 ,g/mL) than in PELF (5.07 ± 2.64 ,g/mL), and plasma (0.84 ± 0.25 ,g/mL). The MIC90 of telithromycin for macrolide-resistant R. equi isolates (8 ,g/mL) was significantly higher than that of macrolide-susceptible isolates (0.25 ,g/mL). The MIC of telithromycin for macrolide-resistant isolates (MIC50 = 4.0 ,g/mL) was significantly lower than that of clarithromycin (MIC50 = 24.0 ,g/mL), azithromycin (MIC50 =256 ,g/mL) and erythromycin (MIC50 = 24 ,g/mL). [source] Pharmacokinetics of intravenous ceftiofur sodium and concentration in body fluids of foalsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009S. MEYER The objectives of this study were to determine pharmacokinetics of intravenous (i.v.) ceftiofur in foals, to compare ultra-high performance liquid chromatography tandem mass spectometry (UPLC-MS/MS) and microbiologic assay for the measurement of ceftiofur concentrations, and to determine the minimum inhibitory concentration (MIC) of ceftiofur against common equine bacterial pathogens. In a cross-over design, ceftiofur sodium was administered i.v. to six foals (1,2 days-of-age and 4,5 weeks-of-age) at dosages of 5 and 10 mg/kg. Subsequently, five doses of ceftiofur were administered i.v. to six additional foals between 1 and 5 days of age at a dose of 5 mg/kg q 12 h. Concentrations of desfuroylceftiofur acetamide (DCA), the acetamide derivative of ceftiofur and desfuroylceftiofur-related metabolites were measured in plasma, synovial fluid, urine, and CSF by use of UPLC-MS/MS. A microbiologic assay was used to measure ceftiofur activity for a subset of plasma samples. Following i.v. administration of ceftiofur at a dose of 5 mg/kg to 1,2 day-old foals, DCA had a t˝ of 7.8 ± 0.1 h, a body clearance of 74.4 ± 8.4 mL/h/kg, and an apparent volume of distribution of 0.83 ± 0.09 L/kg. After multiple i.v. doses at 5 mg/kg, DCA concentrations in CSF were significantly lower than concurrent plasma concentrations. Ceftiofur activity using a microbiologic assay significantly underestimated plasma concentrations of DCA. The MIC of ceftiofur required to inhibit growth of 90% of isolates of Escherichia coli, Pasteurella spp, Klebsiella spp, and ,-hemolytic streptococci was <0.5 ,g/mL. Intravenous administration of ceftiofur sodium at the rate of 5 mg/kg every 12 h would provide sufficient coverage for the treatment of susceptible bacterial isolates. [source] Pharmacokinetics of sulfadimethoxine and ormetoprim in a 5:1 ratio following intraperitoneal and oral administration, in the hybrid striped bass (Morone chrysops × Morone saxitalis)JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2004R. S. Bakal Selected pharmacokinetic parameters for sulfadimethoxine and ormetoprim, administered in a 5:1 ratio, via the oral and intraperitoneal (i.p.) routes were determined in the hybrid striped bass (Morone chrysops × Morone saxitalis). Plasma concentrations of both drugs were determined by high-performance liquid chromatography. A first-order one-compartment model adequately described plasma drug disposition. The elimination half-lives for sulfadimethoxine following i.p. and oral administration were 26 and 10.5 h, respectively. The half-lives for ormetoprim administered via i.p. and oral routes were 7.5 and 3.9 h, respectively. Cmax for sulfadimethoxine via the i.p. and oral routes were calculated to be 27.7 (±9.0) ,g/mL at 3.6 h and 3.2 (±1.2) ,g/mL at 1.2 h, respectively. Cmax for ormetoprim via the i.p. route was calculated to be 1.2 (±0.5) ,g/mL at 9.1 h and 1.58 (±0.7) ,g/mL at 5.7 h for the oral route. The oral availability of sulfadimethoxine relative to the i.p. route was 4.6%, while the oral availability of ormetoprim relative to the i.p. route was 78.5%. Due to the nonconstant ratio of these drugs in the plasma of the animal, the actual drug ratio to use for determining minimum inhibitory concentration (MIC) is unclear. Using the ratio of the total amount of each drug that is absorbed as a surrogate for the mean actual ratio may be the best alternative to current methods. Using this ratio as determined in these studies, (2.14:1 sulfadimethoxine:ormetoprim) to determine the MICs the single 50 mg/kg oral dose of the 5:1 combination of sulfadimethoxine and ormetoprim appears to provide plasma concentrations high enough to inhibit the growth of Yersinia ruckeri, Edwardsiella tarda, and Escherichia coli. [source] Efficacy of trimethoprim-sulfadoxine against Escherichia coli in a tissue cage model in calvesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2002C. Greko Tissue cages implanted subcutaneously in calves were infected with Escherichia coli. Twenty-four hours later, the calves were treated either with single doses of 2.5 + 12.5 or 5 + 25 mg/kg trimethoprim (TMP) + sulfadoxine (SDX) or with five doses of 7.5 + 37.5 mg/kg TMP + SDX at 12-h intervals. In addition, one cage in each of three calves in the highest dose group was infected 3 h after initiation of treatment. Untreated calves were kept as controls. Concentrations of TMP and SDX in plasma and tissue cage fluid (TCF) and counts of viable bacteria in TCF were determined. In the highest dose group, concentrations of TMP in TCF remained above the minimum inhibitory concentration of the test strain for 94,101 h and peak to minimum inhibitory concentration (MIC) ratio was close to 10. In spite of this, an effect of treatment was noted only in cages infected after initiation of treatment. In vitro studies and analysis of thymidine content in serum and TCF from calves suggest that levels of thymidine in TCF are high enough to antagonize the antibacterial effect of TMP. The results indicate that soft tissue infections in secluded infection sites of calves are refractory to treatment with TMP + SDX. [source] Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudateJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2002F. SHOJAEE ALIABADI Aliabadi, F. S., Lees, P. Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudate. J. vet. Pharmacol. Therap.25, 161,174. Marbofloxacin is a fluoroquinolone antimicrobial drug used in cattle for the treatment of respiratory infections. In this investigation the pharmacokinetics (PK) of marbofloxacin were determined after intravenous and intramuscular dosing at a dosage of 2 mg/kg. In addition the ex vivo pharmacodynamics (PD) of the drug were determined in serum and three types of tissue cage fluid (transudate, inflammatory exudate generated by carrageenan and exudate generated by lipopolysaccharide). Marbofloxacin PK was characterized by a high volume of distribution after dosing by both routes (1.28 L/kg intravenous and 1.25 L/kg intramuscular). Corresponding area under the concentration,time curve (AUC) and elimination half-life (t˝el) values were 9.99 and 10.11 ,g h/mL and 4.23 and 4.33 h, respectively. Values of AUC for carrageenan-induced exudate, lipopolysaccharide-induced exudate and transudate were, respectively, 8.28, 7.83 and 7.75 ,g h/mL after intravenous and 8.84, 8.53 and 8.52 ,g h/mL after intramuscular dosing. Maximum concentration (Cmax) values were similar for the three tissue cage fluids after intravenous and intramuscular dosing. For in vivo PK data values of AUC: minimum inhibitory concentration (MIC) (AUIC) ratio for serum were 250 and 253, respectively, after intravenous and intramuscular dosing of marbofloxacin against a pathogenic strain of Mannheimia haemolytica (MIC=0.04 ,g/mL). For all tissue cage fluids AUIC values were >194 and >213 after intravenous and intramuscular dosing, and Cmax/MIC ratios were 9 or greater, indicating a likely high level of effectiveness in clinical infections caused by M. haemolytica of MIC 0.04 ,g/mL or less. This was confirmed by both in vitro (serum) and ex vivo (serum, exudate and transudate) measurements, which demonstrated a concentration-dependent killing profile for marbofloxacin against M. haemolytica. Ex vivo, after 24-h incubation, virtually all bacteria were killed (<10 cfu/mL) in all samples collected up to 9 h (serum), 24 h (carrageenan-induced exudate and transudate) and 36 h (lipopolysaccharide-induced exudate). Application of the sigmoid Emax equation to the ex vivo antibacterial data provided, for serum, AUIC24 h values of 37.1 for bacteriostasis, 46.3 for bactericidal activity and 119.6 for elimination of bacteria. These data may be used as a rational basis for setting dosing schedules which optimize clinical efficacy and minimize the opportunities for emergence of resistant organisms. [source] | |||||||||||||||||||||||||||||||||||||