Dosage regimen formulation and its therapeutic effect evaluation of cyadox nanosuspension against dairy cow mastitis caused by Staphylococcus aureus

2020 ◽  
Vol 18 ◽  
Author(s):  
Tingting Yue ◽  
Shuyu Xie ◽  
Kuiyu Meng ◽  
Shenhe Liu ◽  
Yuanhu Pan ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Dairy Cow ◽  
Dosage Regimen ◽  
Ex Vivo ◽  
Good Prospect ◽  
Effect Evaluation ◽  
Dosing Regimen ◽  
General Reference ◽  
Therapeutic Effect Evaluation ◽  
Clinical Experiment

Abstract:: In this study, the dosage regimen establishment of cyadox nanosuspension against dairy cow mastitis caused by Staphylococcus aureus (S. aureus) was used as example to provide a general reference for the other novel nanocrystal prepa-rations. The effect of cyadox against S. aureus isolates from dairy cows were firstly estimated and then the dosing regimen of nanosuspension after intramammary administration was optimized according to the model of ex vivo pharmacokinetic (PK) and pharmacodynamic (PD). The therapeutic efficacy of the predicted dosage regimen was evaluated. The results demonstrated that cyadox has a concentration-dependent effect on S. aureus. The smallest and highest values of minimum inhibitory concentration (MIC) against 80 isolates was 8 and 64 μg/mL, respectively. The corresponding MIC50 and MIC90 was 16 and 32 μg/mL, respectively. The MIC against the pathogenic S. aureus SAHZ156001 in broth and milk were 16 and 32 μg/mL, respectively. The AUC0-last and Cmax of cyadox in milk were 4442.877 μg*h/mL and 753.052 μg/mL, respective-ly. According to the inhibitory sigmoid Emax modeling and dosage equation, the daily doses were predicted 1.6, 6.6, and 12.2 mL/gland to achieve bacteriostatic, bactericidal, and elimination effects. The dosage internal was daily administration for continuous three days. The clinical experiment showed that the efficient rates were 100, 100, and 90.9%, and the curative rates were 100, 81.8, and 63.6% in 12.2, 6.6 and 1.6 ml/gland groups, respectively. These results showed that cyadox nano-suspension had a good prospect as intramammary infusion to cure dairy cow mastitis infected by S. aureus. This study will be helpful for providing reference for nanocrystal preparation dosage regimen formulation.

scholarly journals A Putative Cro-Like Repressor Contributes to Arylomycin Resistance in Staphylococcus aureus

2015 ◽  
Vol 59 (6) ◽  
pp. 3066-3074 ◽  
Author(s):  
Arryn Craney ◽  
Floyd E. Romesberg
Keyword(s):  
Staphylococcus Aureus ◽  
Ex Vivo ◽  
Transcriptional Regulator ◽  
Signal Peptidase ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Type I ◽  
Wall Teichoic Acid ◽  
Content Type ◽  
Wide Range

ABSTRACTAntibiotic-resistant bacteria are a significant public health concern and motivate efforts to develop new classes of antibiotics. One such class of antibiotics is the arylomycins, which target type I signal peptidase (SPase), the enzyme responsible for the release of secreted proteins from their N-terminal leader sequences. Despite the essentiality, conservation, and relative accessibility of SPase, the activity of the arylomycins is limited against some bacteria, including the important human pathogenStaphylococcus aureus. To understand the origins of the limited activity againstS. aureus, we characterized the susceptibility of a panel of strains to two arylomycin derivatives, arylomycin A-C16and its more potent analog arylomycin M131. We observed a wide range of susceptibilities to the two arylomycins and found that resistant strains were sensitized by cotreatment with tunicamycin, which inhibits the first step of wall teichoic acid synthesis. To further understand howS. aureusresponds to the arylomycins, we profiled the transcriptional response ofS. aureusNCTC 8325 to growth-inhibitory concentrations of arylomycin M131 and found that it upregulates the cell wall stress stimulon (CWSS) and an operon consisting of a putative transcriptional regulator and three hypothetical proteins. Interestingly, we found that mutations in the putative transcriptional regulator are correlated with resistance, and selection for resistanceex vivodemonstrated that mutations in this gene are sufficient for resistance. The results begin to elucidate howS. aureuscopes with secretion stress and how it evolves resistance to the inhibition of SPase.

scholarly journals Analysis of Staphylococcus aureus transcriptome in pediatric soft tissue abscesses and comparison to murine infections

2021 ◽  
Author(s):  
K Moffitt ◽  
E Cheung ◽  
T Yeung ◽  
C Stamoulis ◽  
R Malley
Keyword(s):  
Staphylococcus Aureus ◽  
Soft Tissue ◽  
Ex Vivo ◽  
Human Infection ◽  
Nucleic Acid Amplification ◽  
Clinical Strain ◽  
Nasal Colonization ◽  
Abscess Drainage ◽  
Mrna Transcripts

A comprehensive understanding of how Staphylococcus aureus adapts to cause infections in humans can inform development of diagnostic, therapeutic, and preventive approaches. Expression analysis of clinical strain libraries depicts in vitro conditions that differ from those in human infection, but low bacterial burden and the requirement for reverse transcription or nucleic acid amplification complicate such analyses of bacteria causing human infection. We developed methods to evaluate the mRNA transcript signature of S. aureus in pediatric skin and soft tissue (SSTI) infections directly ex vivo. Abscess drainage from 47 healthy pediatric patients undergoing drainage of a soft tissue infection was collected, and RNA was extracted from samples from patients with microbiologically confirmed S. aureus abscesses (42% due to methicillin-resistant S. aureus, MRSA). Using the Nanostring platform and primers targeting S. aureus mRNA transcripts encoding surface-expressed or secreted proteins, we measured direct counts of 188 S. aureus mRNA transcripts in abscess drainage. We further evaluated this mRNA signature in murine models of S. aureus SSTI and nasal colonization where the kinetics of the transcriptome could be determined. Heat maps of the S. aureus mRNA signatures from pediatric abscesses demonstrated consistent per target expression across patients. While there was significant overlap with the profiles from murine SSTI and nasal colonization, important differences were noted, which can inform efforts to develop therapeutic and vaccine approaches.

scholarly journals Genome Sequence of a Staphylococcus aureus Strain Isolated from a Dairy Cow That Was Nonresponsive to Antibiotic Treatment

2020 ◽  
Vol 9 (20) ◽  
Author(s):  
John D. Lippolis ◽  
Ellie J. Putz ◽  
Hao Ma ◽  
David P. Alt ◽  
Eduardo Casas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Dairy Cattle ◽  
Antibiotic Treatment ◽  
Genome Sequence ◽  
Dairy Cow ◽  
Aureus Strain ◽  
Chronic Case ◽  
Content Type

Staphylococcus aureus can cause mastitis in dairy cattle. We report the genome sequence of a Staphylococcus aureus strain isolated from a dairy cow with a chronic case of mastitis. The infection with this strain of Staphylococcus aureus was not cleared from the animal with antibiotic treatment.

scholarly journals Antimicrobial Activity against Intraosteoblastic Staphylococcus aureus

2015 ◽  
Vol 59 (4) ◽  
pp. 2029-2036 ◽  
Author(s):  
Florent Valour ◽  
Sophie Trouillet-Assant ◽  
Natacha Riffard ◽  
Jason Tasse ◽  
Sacha Flammier ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Ex Vivo ◽  
Joint Infection ◽  
Treatment Strategies ◽  
Bactericidal Effect ◽  
Infection Model ◽  
Content Type ◽  
Intracellular Activity ◽  
Mg63 Cells ◽  
Choice Of Treatment

ABSTRACTAlthoughStaphylococcus aureuspersistence in osteoblasts, partly as small-colony variants (SCVs), can contribute to bone and joint infection (BJI) relapses, the intracellular activity of antimicrobials is not currently considered in the choice of treatment strategies for BJI. Here, antistaphylococcal antimicrobials were evaluated for their intraosteoblastic activity and their impact on the intracellular emergence of SCVs in anex vivoosteoblast infection model. Osteoblastic MG63 cells were infected for 2 h with HG001S. aureus. After killing the remaining extracellular bacteria with lysostaphin, infected cells were incubated for 24 h with antimicrobials at the intraosseous concentrations reached with standard therapeutic doses. Intracellular bacteria and SCVs were then quantified by plating cell lysates. A bactericidal effect was observed with fosfomycin, linezolid, tigecycline, oxacillin, rifampin, ofloxacin, and clindamycin, with reductions in the intracellular inocula of −2.5, −3.1, −3.9, −4.2, −4.9, −4.9, and −5.2 log10CFU/100,000 cells, respectively (P< 10−4). Conversely, a bacteriostatic effect was observed with ceftaroline and teicoplanin, whereas vancomycin and daptomycin had no significant impact on intracellular bacterial growth. Ofloxacin, daptomycin, and vancomycin significantly limited intracellular SCV emergence. Overall, ofloxacin was the only molecule to combine an excellent intracellular activity while limiting the emergence of SCVs. These data provide a basis for refining the choice of antibiotics to prioritise in the management of BJI, justifying the combination of a fluoroquinolone for its intracellular activity with an anti-biofilm molecule, such as rifampin.

scholarly journals Pharmacokinetics and Pharmacodynamics of Levofloxacin against Streptococcus pneumoniae and Staphylococcus aureus in Human Skin Blister Fluid

2000 ◽  
Vol 44 (5) ◽  
pp. 1352-1355 ◽  
Author(s):  
Andrej Trampuz ◽  
Markus Wenk ◽  
Zarko Rajacic ◽  
Werner Zimmerli
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Oral Dose ◽  
Human Skin ◽  
Bactericidal Activity ◽  
Ex Vivo ◽  
Blister Fluid ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Skin Blister ◽  
And Staphylococcus Aureus

ABSTRACT The pharmacokinetics of levofloxacin in serum and in skin blister fluid (SBF) was determined for 20 volunteers after a single 500-mg oral dose of levofloxacin. In addition, ex vivo bactericidal activity of SBF against Streptococcus pneumoniae and Staphylococcus aureus was studied. SBF containing levofloxacin and granulocytes killed 5.2 log of Streptococcus pneumoniae bacteria and 2.0 log of Staphylococcus aureus bacteria during a 6-h incubation.

scholarly journals In Vitro and Ex Vivo Efficacy of Novel Trp-Arg Rich Analogue of α-MSH against Staphylococcus aureus

ACS Omega ◽  
2020 ◽  
Vol 5 (7) ◽  
pp. 3258-3270
Author(s):  
Jyotsna Singh ◽  
Sana Mumtaz ◽  
Seema Joshi ◽  
Kasturi Mukhopadhyay
Keyword(s):  
Staphylococcus Aureus ◽  
Ex Vivo

scholarly journals Interleukin (IL)-1β and IL-10 Host Responses in Patients With Staphylococcus aureus Bacteremia Determined by Antimicrobial Therapy

2019 ◽  
Vol 70 (12) ◽  
pp. 2634-2640 ◽  
Author(s):  
Cecilia F Volk ◽  
Sarah Burgdorf ◽  
Graham Edwardson ◽  
Victor Nizet ◽  
George Sakoulas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Therapy ◽  
Ex Vivo ◽  
Host Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Treatment Groups ◽  
Staphylococcus Aureus Bacteremia ◽  
Medical Centers ◽  
Persistent Bacteremia

Abstract Background Patient interleukin (IL)-1β and IL-10 responses early in Staphylococcus aureus bacteremia (SaB) are associated with bacteremia duration and mortality. We hypothesized that these responses vary depending on antimicrobial therapy, with particular interest in whether the superiority of β-lactams links to key cytokine pathways. Methods Three medical centers included 59 patients with SaB (47 methicillin-resistant S. aureus [MRSA], 12 methicillin-sensitive S. aureus [MSSA]) from 2015–2017. In the first 48 hours, patients were treated with either a β-lactam (n = 24), including oxacillin, cefazolin, or ceftaroline, or a glyco-/lipopeptide (n = 35), that is, vancomycin or daptomycin. Patient sera from days 1, 3, and 7 were assayed for IL-1β and IL-10 by enzyme-linked immunosorbent assay and compared using the Mann-Whitney U test. Results On presentation, IL-10 was elevated in mortality (P = .008) and persistent bacteremia (P = .034), while no difference occurred in IL-1β. Regarding treatment groups, IL-1β and IL-10 were similar prior to receiving antibiotic. Patients treated with β-lactam had higher IL-1β on days 3 (median +5.6 pg/mL; P = .007) and 7 (+10.9 pg/mL; P = .016). Ex vivo, addition of the IL-1 receptor antagonist anakinra to whole blood reduced staphylococcal killing, supporting an IL-1β functional significance in SaB clearance. β-lactam–treated patients had sharper declines in IL-10 than vancomycin or daptomycin –treated patients over 7 days. Conclusions These data underscore the importance of β-lactams for SaB, including consideration that the adjunctive role of β-lactams for MRSA in select patients helps elicit favorable host cytokine responses.

scholarly journals Rabbit model of Staphylococcus aureus implant-associated spinal infection

2020 ◽  
Vol 13 (7) ◽  
pp. dmm045385
Author(s):  
Oren Gordon ◽  
Robert J. Miller ◽  
John M. Thompson ◽  
Alvaro A. Ordonez ◽  
Mariah H. Klunk ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Remodeling ◽  
Ex Vivo ◽  
Rabbit Model ◽  
Pedicle Screws ◽  
Lumbar Vertebra ◽  
Wound Dehiscence ◽  
Spinal Infection ◽  
Positron Emission

ABSTRACTPost-surgical implant-associated spinal infection is a devastating complication commonly caused by Staphylococcus aureus. Biofilm formation is thought to reduce penetration of antibiotics and immune cells, contributing to chronic and difficult-to-treat infections. A rabbit model of a posterior-approach spinal surgery was created, in which bilateral titanium pedicle screws were interconnected by a plate at the level of lumbar vertebra L6 and inoculated with a methicillin-resistant S.aureus (MRSA) bioluminescent strain. In vivo whole-animal bioluminescence imaging (BLI) and ex vivo bacterial cultures demonstrated a peak in bacterial burden by day 14, when wound dehiscence occurred. Structures suggestive of biofilm, visualized by scanning electron microscopy, were evident up to 56 days following infection. Infection-induced inflammation and bone remodeling were also monitored using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and computed tomography (CT). PET imaging signals were noted in the soft tissue and bone surrounding the implanted materials. CT imaging demonstrated marked bone remodeling and a decrease in dense bone at the infection sites. This rabbit model of implant-associated spinal infection provides a valuable preclinical in vivo approach to investigate the pathogenesis of implant-associated spinal infections and to evaluate novel therapeutics.

scholarly journals Antimicrobial and Antibiofilm Activity against Staphylococcus aureus of Opuntia ficus-indica (L.) Mill. Cladode Polyphenolic Extracts

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 117 ◽  
Author(s):  
Federica Blando ◽  
Rossella Russo ◽  
Carmine Negro ◽  
Luigi De Bellis ◽  
Stefania Frassinetti
Keyword(s):  
Staphylococcus Aureus ◽  
Antioxidant Activity ◽  
Antioxidant Capacity ◽  
Biofilm Formation ◽  
Ex Vivo ◽  
Trolox Equivalent Antioxidant Capacity ◽  
Total Phenolic ◽  
Antibiofilm Activity ◽  
Opuntia Ficus Indica

Plant extracts are a rich source of natural compounds with antimicrobial properties, which are able to prevent, at some extent, the growth of foodborne pathogens. The aim of this study was to investigate the potential of polyphenolic extracts from cladodes of Opuntia ficus-indica (L.) Mill. to inhibit the growth of some enterobacteria and the biofilm formation by Staphylococcus aureus. Opuntia ficus-indica cladodes at two stages of development were analysed for total phenolic content and antioxidant activity by Oxygen Radical Absorbance Capacity (ORAC) and Trolox equivalent antioxidant capacity (TEAC) (in vitro assays) and by cellular antioxidant activity in red blood cells (CAA-RBC) (ex vivo assay). The Liquid Chromatography Time-of-Flight Mass Spectrometry (LC/MS–TOF) analysis of the polyphenolic extracts revealed high levels of piscidic acid, eucomic acid, isorhamnetin derivatives and rutin, particularly in the immature cladode extracts. Opuntia cladodes extracts showed a remarkable antioxidant activity (in vitro and ex vivo), a selective inhibition of the growth of Gram-positive bacteria, and an inhibition of Staphylococcus aureus biofilm formation. Our results suggest and confirm that Opuntia ficus-indica cladode extracts could be employed as functional food, due to the high polyphenolic content and antioxidant capacity, and used as natural additive for food process control and food safety.

Sign in / Sign up

Export Citation Format

Share Document