The antibacterial activities of aditoprim and its efficacy in the treatment of swine streptococcosis

Cheng, Guyue; Xu, Yamei; Zhu, Xudong; Xie, Shuyu; Wang, Liye; Huang, Lingli; Hao, Haihong; Liu, Zhenli; Pan, Yuanhu; Chen, Dongmei; Wang, Yulian; Zhang, Yuan

doi:10.1038/srep41370

Cited by 11 publications

(17 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bacterial isolates were tested for sensitivity determination for ADP and SMZ. T. Pyogenes was sensitive for ADP (MIC 0.25 µg/ml) but these MIC values were slightly higher than that found by Cheng et al, 2017. In our study, T. Pyogenes isolates were more susceptible to both drug combinations than single drug. Both drugs showed synergy by checkerboard (CB).…”

Section: Discussioncontrasting

confidence: 82%

Dose Optimization of Aditoprim-Sulfamethoxazole Combinations Against Trueperella pyogenes From Patients With Clinical Endometritis by Using Semi-mechanistic PK/PD Model

et al. 2021

Self Cite

View full text Add to dashboard Cite

Combinations of two and more drugs with different target sites are being used as a new treatment regimen for resistant clones of bacteria. Though, achieving the right combination of the drugs for optimal dosage regimen is challenging. In our study, we studied the antimicrobial effect of aditoprim, a novel dihydrofolate reductase inhibitor, and its synergistic effect with sulfamethoxazole. Synergy testing was performed by checkerboard micro dilution method and validation of different checkerboard ratios by static and dynamic time-kill analysis and in vitro pharmacokinetic/pharmacodynamics (PK/PD) model, and semi mechanistic PK/PD modeling was used to calculate and validate the synergistic effect of drug combination. Both checkerboard and static time-kill assays demonstrated the greater synergistic effect [fractional inhibitory concentration index (FICI) = 0.37] of the aditoprim [minimum inhibitory concentration (MIC) = 0.25 µg/ml]-sulfamethoxazole (MIC=>64 µg/ml) combination against all T. Pyogenes isolates. In the in vitro PK/PD model, the dosage proportion of sulfamethoxazole 4 mg/ml twice a day in combination with steady-state aditoprim 1 mg/ml efficiently repressed the growth of bacteria in 24 h with the ratio of 2-log10 decrease, related to the early inoculum against three T. Pyogenes isolates. The semi mechanistic PK/PD model projected that a combination of a high dose of aditoprim (2 mg/ml) with sulfamethoxazole (2 mg/day) was necessary to attain the killing of bacteria below the detection limit (limit of detection (LOD); i.e., 1 log10 CFU/ml) at 24 h with an MIC sulfamethoxazole (SMZ) of 64 µg/ml. However, it is anticipated that a combination of high dose of aditoprim with sulfamethoxazole is critical to attain the suppressed bacterial growth to < LOD. This study represents essential PK/PD modeling for optimization of combination of aditoprim and sulfamethoxazole to suppress growth of T. Pyogenens.

show abstract

Section: Discussioncontrasting

confidence: 82%

Dose Optimization of Aditoprim-Sulfamethoxazole Combinations Against Trueperella pyogenes From Patients With Clinical Endometritis by Using Semi-mechanistic PK/PD Model

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…For evaluating the therapeutic effect, plasma concentrations should be higher or equal to the MIC (Reeve-Johnson, 1998 ; Cheng et al, 2017 ). The plasma concentrations of ENR were higher than MICs of APP based on the calculated pharmacokinetic values (Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

“…When indicators were not alleviatived compared with the positive group, the drug would be assessed as ineffective. The presence of pathological changes in lungs after MS infection were scored as follows in order to make a daily clinical score: when diseased areas in lungs were 0, 1–25, 26–50, 51–75, and above 75%, they were scored as 0, 1, 2, 3, 4, respectively (Mutlu et al, 2012 ; Sibila et al, 2014 ; Cheng et al, 2017 ).…”

Section: Methodsmentioning

confidence: 99%

Clinical Efficacy and Residue Depletion of 10% Enrofloxacin Enteric-Coated Granules in Pigs

et al. 2017

View full text Add to dashboard Cite

A new, more palatable formulation of 10% enrofloxacin enteric-coated granules was investigated to evaluate the pharmacokinetic effect in plasma, the residue elimination in tissues and the clinical efficacy against Actinobacillus pleuropneumonia (APP) and Mycoplasam suis (MS) in pigs. In this study, the enrofloxacin concentrations in plasma and tissues were detected using high-performance liquid chromatography with phosphate buffer (pH = 3) and acetonitrile. The pharmacokinetics and elimination of enrofloxacin enteric-coated granules were performed after oral administration at a single dose of 10 mg/kg body weight (bw) and 5 mg/kg twice per day for 5 consecutive days, respectively. The in vivo antibacterial efficacy and clinical effectiveness of enrofloxacin enteric-coated granules against APP and MS were assayed at 2.5, 5, 10 mg/kg, compared with tiamulin (8 mg/kg) based on establishment of APP and MS infection models. 56 APP strains were selected and tested for in vitro antibacterial activity of enrofloxacin enteric-coated granules. The main parameters of elimination half-life (t1/2β), Tmax, and area under the curve (AUC) were 14.99 ± 4.19, 3.99 ± 0.10, and 38.93 ± 1.52 μg h/ml, respectively, revealing that the enrofloxacin concentration remained high and with a sustainable distribution in plasma. Moreover, the analysis on the evaluation of enrofloxacin and ciprofloxacin in muscle, fat, liver and kidney showed that the recovery were more than 84% recovery in accordance with the veterinary drug residue guidelines of United States pharmacopeia, and the withdrawal periods were 4.28, 3.81, 4.84, and 3.51 days, respectively, suggesting that the withdrawal period was 5 d after oral administration of 5 mg/kg twice per day. The optimal dosage of enrofloxacin enteric-coated granules against APP and MS was 5 mg/kg, with over 90% efficacy, which was significantly different (p < 0.05) to the 2.5 mg/kg group, but not to the 10 mg/kg group or the positive control group (tiamulin). In conclusion, 10% enrofloxacin enteric-coated granules had significant potential for treating APP and MS, and it provided an alternative enrofloxacin palatability formulation.

show abstract

“…It is assumed that for MBC/MIC ratio greater than 4, the agent is bacteriostatic, while for a ratio lower than 4, the agent is considered to be bactericidal. 48,49,53,54 To investigate the antimicrobial properties of green synthesized nanoparticles, the viability of each bacterial strain was also measured based on its OD 600 . Our findings not only further confirmed the MIC and MBC results but also showed that these nanoparticles can significantly decrease the microbial viability at concentrations lower than MIC (Figure 9).…”

Section: Cytotoxicitymentioning

confidence: 99%

Selective cytotoxicity of green synthesized silver nanoparticles against the MCF-7 tumor cell line and their enhanced antioxidant and antimicrobial properties

Khorrami¹,

Zarrabi²,

Khaleghi³

et al. 2018

IJN

437

226

View full text Add to dashboard Cite

IntroductionSilver nanoparticles (AgNPs) are of great interest due to their unique and controllable characteristics. Different synthesis methods have been proposed to produce these nanoparticles, which often require elevated temperatures/pressures or toxic solvents. Thus, green synthesis could be a replacement option as a simple, economically viable and environmentally friendly alternative approach for the synthesis of silver nanoparticles.MethodsHere, the potential of the walnut green husk was investigated in the production of silver nanoparticles. An aqueous solution extracted from walnut green husk was used as a reducing agent as well as a stabilizing agent. Then, the synthesized nanoparticles were characterized with respect of their anticancer, antioxidant, and antimicrobial properties.ResultsResults showed that the synthesized nanoparticles possessed an average size of 31.4 nm with a Zeta potential of −33.8 mV, indicating high stability. A significant improvement in the cytotoxicity and antioxidant characteristics of the green synthesized Ag nanoparticles against a cancerous cell line was observed in comparison with the walnut green husk extract and a commercial silver nanoparticle (CSN). This could be due to a synergistic effect of the synthesized silver nanoparticles and their biological coating. AgNPs and the extract exhibited 70% and 40% cytotoxicity against MCF-7 cancerous cells, respectively, while CSN caused 56% cell death (at the concentration of 60 µg/mL). It was observed that AgNPs were much less cytotoxic when tested against a noncancerous cell line (L-929) in comparison with the control material (CSN). The free radical scavenging analysis demonstrated profound anti-oxidant activity for the synthesized nanoparticles in comparison with the extract and CSN. It was also detected that the synthesized AgNPs possess antibacterial activity against nosocomial and standard strains of both Gram-positive and Gram-negative bacteria (minimum inhibitory concentration =5–30 µg/mL).ConclusionThese findings imply that the synthesized nanoparticles using green nanotechnology could be an ideal strategy to combat cancer and infectious diseases.

show abstract

The antibacterial activities of aditoprim and its efficacy in the treatment of swine streptococcosis

Cited by 11 publications

References 39 publications

Dose Optimization of Aditoprim-Sulfamethoxazole Combinations Against Trueperella pyogenes From Patients With Clinical Endometritis by Using Semi-mechanistic PK/PD Model

Dose Optimization of Aditoprim-Sulfamethoxazole Combinations Against Trueperella pyogenes From Patients With Clinical Endometritis by Using Semi-mechanistic PK/PD Model

Clinical Efficacy and Residue Depletion of 10% Enrofloxacin Enteric-Coated Granules in Pigs

Selective cytotoxicity of green synthesized silver nanoparticles against the MCF-7 tumor cell line and their enhanced antioxidant and antimicrobial properties

Contact Info

Product

Resources

About