scholarly journals PK/PD Analysis by Nonlinear Mixed-Effects Modeling of a Marbofloxacin Dose Regimen for Treatment of Goat Mastitis Produced by Coagulase-Negative Staphylococci

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3098
Author(s):  
Augusto Matías Lorenzutti ◽  
Juan Pablo Vico ◽  
Juan Manuel Serrano-Rodríguez ◽  
Martín Alejandro Himelfarb ◽  
Manuel Ignacio San Andrés-Larrea ◽  
...  
Keyword(s):  
Dose Regimen ◽  
Goat Milk ◽  
Pharmacodynamic Modeling ◽  
Coagulase Negative Staphylococci ◽  
Context Sensitive ◽  
Mixed Effects Modeling ◽  
Cutoff Values ◽  
Mueller Hinton ◽  
Relationship Of ◽  
Mueller Hinton Broth

Coagulase-negative staphylococci are main pathogens that produce goat mastitis. Marbofloxacin is a third-generation fluoroquinolone approved for treat mastitis in animals. The objectives of this study were: (i) to determine the pharmacokinetics of marbofloxacin (10 mg/kg/24 h) in serum and milk administered intramuscularly for five days in goats with mastitis induced by coagulase-negative staphylococci; (ii) to characterize the concentration–effect relationship of marbofloxacin against coagulase-negative staphylococci in Mueller Hinton broth and goat milk; (iii) to determine AUC/MIC cutoff values of marbofloxacin, and (iv) to perform a PK/PD analysis to evaluate the efficacy of the dose regimen for the treatment of goat mastitis produced by coagulase-negative staphylococci. Marbofloxacin presented context-sensitive pharmacokinetics, influenced by the evolution of the disease, which decreased marbofloxacin disposition in serum and milk. Marbofloxacin showed a median (95%CI) fAUC/MIC values for MIC of 0.4 and 0.8 µg/mL of 26.66 (22.26–36.64) and 32.28 (26.57–48.35) related with −2 log10CFU/mL reduction; and 32.26 (24.81–81.50) and 41.39 (29.38–128.01) for −3 log10CFU/mL reduction in Mueller Hinton broth. For milk, −2 log10CFU/mL reduction was achieved with 41.48 (35.29–58.73) and 51.91 (39.09–131.63), and −3 log10CFU/mL reduction with 51.04 (41.6–82.1) and 65.65 (46.68–210.16). The proposed dose regimen was adequate for the treatment of goat mastitis produced by coagulase-negative staphylococci, resulting in microbiological and clinical cure of all animals. The animal model used in this study provided important pharmacokinetic information about the effect of the infection on the pharmacokinetics of marbofloxacin. Pharmacodynamic modeling showed that fAUC/MIC cutoff values were higher in goat milk compared with Mueller Hinton broth.

scholarly journals Pharmacokinetic-Pharmacodynamic Modeling of Propofol in Children

2010 ◽  
Vol 113 (2) ◽  
pp. 343-352 ◽  
Author(s):  
Agnes Rigouzzo ◽  
Frederique Servin ◽  
Isabelle Constant
Keyword(s):  
Peak Effect ◽  
Concentration Effect ◽  
Pharmacodynamic Modeling ◽  
Maximal Effect ◽  
Time To Peak ◽  
Effect Site ◽  
Mixed Effects Modeling ◽  
Effect Site Concentration ◽  
Relationship Of ◽  
The Relationship

Background The aim of this study was to identify the best model to describe pharmacokinetics and pharmacodynamics in prepubertal children and therefore to calculate the corresponding pharmacodynamic parameters. In addition, and to confirm our method, a group of postpubertal subjects was also studied. Methods Sixteen children (9.5 yr, range 6-12) and 13 adults (22 yr, range 13-35) were included. Induction was performed by plasma target-controlled infusion of propofol (6 microg/ml) based on the Kataria model in children and on the Schnider model in adults. The relationship of bispectral index to predicted concentrations was studied during induction using the Kataria, pediatric Marsh, Schüttler, and Schnider models in children. Because the best performance was obtained, strangely enough, with the Schnider model, the two groups were pooled to investigate influence of puberty on pharmacodynamic parameters (kE0 [plasma effect-site equilibration rate constant] and Ce50 [effect-site concentration corresponding with 50% of the maximal effect]). The time-to-peak effect was calculated, and the kE0 was determined for the Kataria model (nonlinear mixed-effects modeling; pkpdtools). Results In children, the predicted concentration/effect relationship was best described using the Schnider model. When the whole population was considered, a significant improvement in this model was obtained using puberty as a covariate for kE0 and Ce50. The time to peak effect, Tpeak (median, 0.71 [range, 0.37-1.64] and 1.73 [1.4-2.68] min), and the Ce50 (3.71 [1.88-4.4] and 3.07 [2.95-5.21] microg/ml) were shorter and higher, respectively, in children than in adults. The kE0 linked to the Kataria model was 4.6 [1.4-11] min. Conclusions In children, the predicted concentration/effect relationships were best described using the Schnider model described for adults compared with classic pediatric models. The study suggests that the Schnider model might be useful for propofol target-control infusion in children.

scholarly journals Plasticity of Coagulase-Negative Staphylococcal Membrane Fatty Acid Composition and Implications for Responses to Antimicrobial Agents

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 214
Author(s):  
Kiran B. Tiwari ◽  
Craig Gatto ◽  
Brian J. Wilkinson
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Antimicrobial Agents ◽  
Straight Chain ◽  
Coagulase Negative Staphylococci ◽  
Branched Chain Fatty Acids ◽  
Mueller Hinton ◽  
Branched Chain ◽  
Mueller Hinton Broth ◽  
Chain Fatty Acids

Staphylococcus aureus demonstrates considerable membrane lipid plasticity in response to different growth environments, which is of potential relevance to response and resistance to various antimicrobial agents. This information is not available for various species of coagulase-negative staphylococci, which are common skin inhabitants, can be significant human pathogens, and are resistant to multiple antibiotics. We determined the total fatty acid compositions of Staphylococcus auricularis, Staphylococcus capitis, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, and Staphylococcus aureus for comparison purposes. Different proportions of branched-chain and straight-chain fatty acids were observed amongst the different species. However, growth in cation-supplemented Mueller–Hinton broth significantly increased the proportion of branched-chain fatty acids, and membrane fluidities as measured by fluorescence anisotropy. Cation-supplemented Mueller–Hinton broth is used for routine determination of antimicrobial susceptibilities. Growth in serum led to significant increases in straight-chain unsaturated fatty acids in the total fatty acid profiles, and decreases in branched-chain fatty acids. This indicates preformed fatty acids can replace biosynthesized fatty acids in the glycerolipids of coagulase-negative staphylococci, and indicates that bacterial fatty acid biosynthesis system II may not be a good target for antimicrobial agents in these organisms. Even though the different species are expected to be exposed to skin antimicrobial fatty acids, they were susceptible to the major skin antimicrobial fatty acid sapienic acid (C16:1Δ6). Certain species were not susceptible to linoleic acid (C18:2Δ9,12), but no obvious relationship to fatty acid composition could be discerned.

scholarly journals Recording the Presence of Peanibacillus larvae larvae Colonies on MYPGP Substrates Using a Multi-Sensor Array Based on Solid-State Gas Sensors

Sensors ◽  
2021 ◽  
Vol 21 (14) ◽  
pp. 4917
Author(s):  
Beata Bąk ◽  
Jakub Wilk ◽  
Piotr Artiemjew ◽  
Jerzy Wilde
Keyword(s):  
Gas Sensors ◽  
Culture Media ◽  
Laboratory Diagnosis ◽  
Baseline Correction ◽  
American Foulbrood ◽  
Sensor Signal ◽  
Sodium Pyruvate ◽  
Mueller Hinton ◽  
Regeneration Phase ◽  
Mueller Hinton Broth

American foulbrood is a dangerous disease of bee broods found worldwide, caused by the Paenibacillus larvae larvae L. bacterium. In an experiment, the possibility of detecting colonies of this bacterium on MYPGP substrates (which contains yeast extract, Mueller-Hinton broth, glucose, K2HPO4, sodium pyruvate, and agar) was tested using a prototype of a multi-sensor recorder of the MCA-8 sensor signal with a matrix of six semiconductors: TGS 823, TGS 826, TGS 832, TGS 2600, TGS 2602, and TGS 2603 from Figaro. Two twin prototypes of the MCA-8 measurement device, M1 and M2, were used in the study. Each prototype was attached to two laboratory test chambers: a wooden one and a polystyrene one. For the experiment, the strain used was P. l. larvae ATCC 9545, ERIC I. On MYPGP medium, often used for laboratory diagnosis of American foulbrood, this bacterium produces small, transparent, smooth, and shiny colonies. Gas samples from over culture media of one- and two-day-old foulbrood P. l. larvae (with no colonies visible to the naked eye) and from over culture media older than 2 days (with visible bacterial colonies) were examined. In addition, the air from empty chambers was tested. The measurement time was 20 min, including a 10-min testing exposure phase and a 10-min sensor regeneration phase. The results were analyzed in two variants: without baseline correction and with baseline correction. We tested 14 classifiers and found that a prototype of a multi-sensor recorder of the MCA-8 sensor signal was capable of detecting colonies of P. l. larvae on MYPGP substrate with a 97% efficiency and could distinguish between MYPGP substrates with 1–2 days of culture, and substrates with older cultures. The efficacy of copies of the prototypes M1 and M2 was shown to differ slightly. The weighted method with Canberra metrics (Canberra.811) and kNN with Canberra and Manhattan metrics (Canberra. 1nn and manhattan.1nn) proved to be the most effective classifiers.

scholarly journals In Vitro Activities of Daptomycin against 2,789 Clinical Isolates from 11 North American Medical Centers

2001 ◽  
Vol 45 (6) ◽  
pp. 1919-1922 ◽  
Author(s):  
Arthur L. Barry ◽  
Peter C. Fuchs ◽  
Steven D. Brown
Keyword(s):  
Clinical Isolates ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Medical Centers ◽  
Mueller Hinton ◽  
Calcium Cations ◽  
Important Exception ◽  
Mueller Hinton Broth

ABSTRACT The in vitro activity of daptomycin is affected by the concentration of calcium cations in the test medium. Mueller-Hinton broth is currently adjusted to contain 10 to 12.5 mg of magnesium per liter and 20 to 25 mg of calcium per liter, but for testing of daptomycin, greater concentrations of calcium (50 mg/liter) are recommended to better resemble the normal concentration of ionized calcium in human serum. Two levels of calcium were used for broth microdilution tests of 2,789 recent clinical isolates of gram-positive bacterial pathogens. MICs of daptomycin were two- to fourfold lower when the broth contained additional calcium. For most species, however, the percentages of strains that were inhibited by 2.0 μg of daptomycin per ml were essentially identical with the two broth media. Enterococci were the important exception; i.e., 92% were inhibited when tested in calcium-supplemented broth but only 35% were inhibited by 2.0 μg/ml without the additional calcium. This type of information should be considered when selecting criteria for defining in vitro susceptibility to daptomycin.

Effect of Ethanol/Trisodium Citrate Lock on Microorganisms Causing Hemodialysis Catheter-Related Infections

2007 ◽  
Vol 8 (4) ◽  
pp. 262-267 ◽  
Author(s):  
T.A. Takla ◽  
S.A. Zelenitsky ◽  
L.M. Vercaigne
Keyword(s):  
In Vitro Study ◽  
Trisodium Citrate ◽  
Methicillin Resistant ◽  
Hemodialysis Catheter ◽  
E Coli ◽  
Lock Solution ◽  
Mueller Hinton ◽  
Mueller Hinton Broth ◽  
Made In

Purpose This in vitro study tested the effectiveness of a novel 30% ethanol/4% trisodium citrate (TSC) lock solution against the most common pathogens causing hemodialysis catheter-related infections. Methods Clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) (n=4), methicillin-sensitive S. aureus (MSSA) (n=8), methicillin-resistant Staphylococcus epidermidis (MRSE) (n=8), Pseudomonas aeruginosa (n=4) and Escherichia coli (n=4) were tested in duplicate. Bacterial suspensions of each isolate were made in a control solution of normal saline and Mueller-Hinton broth (MHB), and in a lock solution of ethanol 30%, TSC 4% and MHB. Suspensions were incubated at 37 °C for 48 h. Colony counts were determined from samples collected at t=0 h (before exposure to the ethanol/TSC lock), t=1 h (one hour after exposure to the ethanol/TSC lock), t=24 h and t=48 h. To confirm the absence of viable organisms in the lock solution, the remaining volume at 48 h was filtered through a 0.45 μm filter. The filter was rinsed with 15 mL sterile water and plated on tryptic soy agar (TSA). Results All controls demonstrated significant growth over 48 h. In the lock solutions, initial inocula were reduced to 0 viable colonies by t=1 h (6-log kill), and there was no growth at t=24 and 48 h. Filtering of lock solutions also showed no growth. These results were consistent among duplicates of all isolates. Conclusions The 30% ethanol/4% TSC lock solution consistently eradicated MRSA, MSSA, MRSE, P. aeruginosa and E. coli within 1 h of exposure. Experiments are currently underway to test this novel lock solution on preventing biofilm production by these pathogens.

scholarly journals An Overview of Specific Pathogens in Goat Mastitis

2019 ◽  
Vol 76 (2) ◽  
pp. 118
Author(s):  
Cristiana Ștefania NOVAC ◽  
Sanda ANDREI ◽  
Nicodim Iosif FIȚ
Keyword(s):  
Somatic Cell Count ◽  
Goat Milk ◽  
Subclinical Mastitis ◽  
Clinical Mastitis ◽  
Economic Consequences ◽  
The Other ◽  
Aetiological Agent ◽  
Dairy Goats ◽  
Coagulase Negative Staphylococci ◽  
Intramammary Infections

Goat milk ranks fourth in terms of global milk production and lately it has become increasingly popular among consumers. Unfortunately, mastitis is one of the most common diseases that affects dairy goats, with serious economic consequences and food safety matters. The prevalence of clinical mastitis is lower than 5% and the main aetiological agent is S. aureus. On the other hand, the prevalence of subclinical mastitis is between 5-30%, with coagulase negative staphylococci (CNS) representing the most often isolated microorganisms.The aim of this paper is to highlight the main aspects regarding the aetiology of goat mastitis, as well as the importance of the milk somatic cell count (MSCC) in the diagnosis process. Although the inflammation of the mammary gland in goats is not as frequently diagnosed compared to cow mastitis, there are several aspects worth discussing in order to fully understand the pathogenesis of intramammary infections.

scholarly journals Antimicrobial susceptibility pattern of Corynebacterium striatum.

1996 ◽  
Vol 40 (11) ◽  
pp. 2671-2672 ◽  
Author(s):  
L Martínez-Martínez ◽  
A Pascual ◽  
K Bernard ◽  
A I Suárez
Keyword(s):  
Antimicrobial Susceptibility ◽  
Antimicrobial Agents ◽  
Susceptibility Pattern ◽  
Beta Lactams ◽  
Antimicrobial Susceptibility Pattern ◽  
Mueller Hinton ◽  
Corynebacterium Striatum ◽  
Mueller Hinton Broth

The in vitro activities of 16 antimicrobial agents against 86 strains of Corynebacterium striatum were evaluated by microdilution using cation-adjusted Mueller-Hinton broth. MICs at which 90% of strains were inhibited were 0.06 microgram/ml for teicoplanin, 1 microgram/ml for vancomycin, 0.03 to 8 micrograms/ml for beta-lactams, 8 micrograms/ml for sparfloxacin, 16 micrograms/ml for ciprofloxacin, 16/304 micrograms/ml for co-trimoxazole (trimethoprim-sulfamethoxazole), 64 micrograms/ml for tetracycline, 128 micrograms/ml for gentamicin, and > 128 micrograms/ml for amikacin, erythromycin, and rifampin.

scholarly journals 1588. Delafloxacin Activity Against Staphylococcus aureus with Reduced Susceptibility or Resistance to Methicillin, Vancomycin, Daptomycin, or Linezolid

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S579-S580
Author(s):  
Louis D Saravolatz ◽  
Joan Pawlak
Keyword(s):  
Antimicrobial Agents ◽  
Minimal Bactericidal Concentration ◽  
Limited Data ◽  
Methicillin Resistant ◽  
Mueller Hinton ◽  
Spectrum Activity ◽  
Resistant Strains ◽  
Gram Negative Organisms ◽  
Mueller Hinton Broth ◽  
Broad Spectrum Activity

Abstract Background Delafloxacin is a recently approved anionic fluoroquinolone antibiotic with broad-spectrum activity against Gram-positive and Gram-negative organisms. The drug has been approved for patients with acute bacterial skin and skin structure infections including those caused by methicillin-resistant S. aureus. There is limited data available against methicillin-resistant S. aureus blood isolates (MRSABI), vancomycin intermediate strains (VISA), vancomycin-resistant strains (VRSA), daptomycin non-susceptible strains (DNSSA) and linezolid-resistant S. aureus (LRSA). Methods Antimicrobial activity of delafloxacin, levofloxacin, vancomycin, daptomycin, ceftaroline, and linezolid was determined against recent (2016–2018) MRSABI (110), VRSA (15), VISA (35), DNSSA (40), and LRSA (6). Broth microdilution testing using Mueller–Hinton broth was used to determine minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) according to CLSI guidelines. FDA breakpoints were used to determine delafloxacin susceptibility, and CLSI breakpoints were used for all other antibiotics. Results Antimicrobial MIC90 expressed in mg/L and (% susceptible) None of the LRSA were susceptible to delafloxacin or levofloxacin. All strains that were susceptible to the antimicrobial agents above had an MBC that was the same as the MIC or one dilution greater except for linezolid which demonstrated an MBC that was more than eight-fold greater than the MIC. For MRSABI isolates with a levofloxacin MIC ≥ 8 mg/L (55/110) suggesting multiple mutations in the quinolone-resistant determining region, the delafloxacin MIC90 was 1 mg/L with a 36.4% susceptibility rate. Conclusion Delafloxacin demonstrates superior activity to levofloxacin against recent MRSA blood isolates, VISA, VRSA, and DNSSA. Disclosures All authors: No reported disclosures.

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