Staphylococcus aureus small-colony variants: Formation, infection, and treatment.

Background Florfenicol might be ineffective for treating Staphylococcus aureus small colony variants (SCVs) mastitis. Objectives In this study, florfenicol-loaded chitosan (CS)-sodium tripolyphosphate (TPP) composite nanogels were prepared to allow targeted delivery to SCV infected sites. Methods The formulation screening, the characteristics, in vitro release, antibacterial activity, therapeutic efficacy, and biosafety of the florfenicol composite nanogels were studied. Results The optimized formulation was obtained when the CS and TPP were 10 and 5 mg/mL, respectively. The encapsulation efficiency, loading capacity, size, polydispersity index, and zeta potential of the optimized florfenicol composite nanogels were 87.3% ± 2.7%, 5.8% ± 1.4%, 280.3 ± 1.5 nm, 0.15 ± 0.03, and 36.3 ± 1.4 mv, respectively. Optical and scanning electron microscopy showed that spherical particles with a relatively uniform distribution and drugs might be incorporated in cross-linked polymeric networks. The in vitro release study showed that the florfenicol composite nanogels exhibited a biphasic pattern with the sustained release of 72.2% ± 1.8% at 48 h in pH 5.5 phosphate-buffered saline. The minimal inhibitory concentrations of commercial florfenicol solution and florfenicol composite nanogels against SCVs were 1 and 0.25 µg/mL, respectively. The time-killing curves and live–dead bacterial staining showed that the florfenicol composite nanogels were concentration-dependent. Furthermore, the florfenicol composite nanogels displayed good therapeutic efficacy against SCVs mastitis. Biological safety studies showed that the florfenicol composite nanogels might be a biocompatible preparation because of their non-toxic effects on the renal tissue and liver. Conclusions Florfenicol composite nanogels might improve the treatment of SCV infections.

Antibacterial activity of florfenicol composite nanogels against Staphylococcus aureus small colony variants

: Inappropriate application of antimicrobial agents can result in resistance by bacteria to drugs and changes in bacterial ecology. In particular, the emergence of multi-drug resistant bacteria seriously aff ects the antibacterial eﬃ cacy of drugs, which threatens the health and lives of humans and animals. Pharmacokinetic/Pharmacodynamic (PK/PD) models can be used to analyze the relationship between PK and PD data and the antibacterial eff ect. PK/PD models provide valuable guidance for optimization of dosage regimens, development of new drugs, setting of susceptibility breakpoints, and analyses of resistant mutants. Th e main models of PK/PD integration are in vitro PK/PD, ex vivo PK/PD, and in vivo PK/PD. Each of these models has its own advantages and disadvantages. Hence, knowing how to choose the appropriate PK/PD model has a huge infl uence on obtaining accurate PK/PD data. In this review, we describe the commonly used PK/PD methods. In this way, we provide a reference for optimizing drug regimens and preventing and controlling drug-resistant bacterial infections. drugs, PK/PD integration model, Multi-drug resistance, Dosage regimen optimization, In vivo PK/PD model

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Antibakteriyel İlaçların Farmakokinetik/Farmakodinamik Entegrasyonu Üzerine Metodolojik Bir İnceleme

Introduction Biofilm formation is the major pathogenicity of Staphylococcus epidermidis (S. epidermidis), which enhances bacterial resistance to antibiotics. Isookanin has potential inhibitory activity on biofilm. Method The inhibiting mechanisms of isookanin against biofilm formation through surface hydrophobicity assay, exopolysaccharides, eDNA, gene expression analysis, microscopic visualization, and molecular docking were explored. Additionally, the combination of isookanin and β-lactam antibiotics were evaluated by the broth micro-checkerboard assay. Results The results showed that isookanin could decrease the biofilm formation of S. epidermidis by ≥85% at 250 μg/mL. The exopolysaccharides, eDNA and surface hydrophobicity were reduced after treatment with isookanin. Microscopic visualization analysis showed that there were fewer bacteria on the surface of the microscopic coverslip and the bacterial cell membrane was damaged after treatment with isookanin. The down-regulation of icaB and up-regulation of icaR were observed after treatment with isookanin. Additionally, the RNAIII gene was significantly up-regulated (p < 0.0001) at the mRNA level. Molecular docking showed that isookanin could bind to biofilm-related proteins. This indicated that isookanin can affect biofilm formation at the initial attachment phase and the aggregation phase. The FICI index showed that the combination of isookanin and β-lactam antibiotics were synergistic and could reduce doses of antibiotics by inhibiting biofilm formation. Discussion This study improved the antibiotic susceptibility of S. epidermidis through inhibition of the biofilm formation, and provided a guidance for the treatment of antibiotic resistance caused by biofilm

/pdf/down-regulation-of-b-lactam-antibiotics-resistance-and-1lmxsgen.pdf

Down-regulation of β-lactam antibiotics resistance and biofilm formation by Staphylococcus epidermidis is associated with isookanin

/pdf/enhanced-antibacterial-activity-of-tilmicosin-against-15zl97098d.pdf

Enhanced antibacterial activity of tilmicosin against Staphylococcus aureus small colony variants by chitosan oligosaccharide-sodium carboxymethyl cellulose composite nanogels

BACKGROUND Our previously prepared ceftiofur (CEF) hydrochloride oily suspension shows potential wide applications for controlling swine Streptococcus suis infections, while the irrational dose has not been formulated OBJECTIVES The rational dose regimens of CEF oily suspension against S suis were systematically studied using a pharmacokinetic-pharmacodynamic model method METHODS The healthy and infected pigs were intramuscularly administered CEF hydrochloride oily suspension at a single dose of 5 mg/kg, and then the plasma and pulmonary epithelial lining fluid (PELF) were collected at different times The minimum inhibitory concentration (MIC), minimal bactericidal concentration, mutant prevention concentration (MPC), post-antibiotic effect (PAE), and time-killing curves were determined Subsequently, the area under the curve by the MIC (AUC0-24h/MIC) values of desfuroylceftiofur (DFC) in the PELF was obtained by integrating in vivo pharmacokinetic data of the infected pigs and ex vivo pharmacodynamic data using the sigmoid Emax (Hill) equation The dose was calculated based on the AUC0-24h/MIC values for bacteriostatic action, bactericidal action, and bacterial elimination RESULTS The peak concentration, the area under the concentration-time curve, and the time to peak for PELF's DFC were 2476 ± 092 µg/mL, 81199 ± 5470 μg·h/mL, and 800 h in healthy pigs, and 3304 ± 099 µg/mL, 73585 ± 2620 μg·h/mL, and 800 h in infected pigs, respectively The MIC of PELF's DFC against S suis strain was 025 µg/mL There was strong concentration-dependent activity as determined by MPC, PAE, and the time-killing curves The AUC0-24h/MIC values of PELF's DFC for bacteriostatic activity, bactericidal activity, and virtual eradication of bacteria were 654 h, 969 h, and 1149 h, respectively Thus, a dosage regimen of 194 mg/kg every 72 h could be sufficient to reach bactericidal activity CONCLUSIONS A rational dosage regimen was recommended, and it could assist in increasing the treatment effectiveness of CEF hydrochloride oily suspension against S Suis infections

https://vetsci.org/pdf/10.4142/jvs.2021.22.e41

Formulation of a rational dosage regimen of ceftiofur hydrochloride oily suspension by pharmacokinetic-pharmacodynamic (PK-PD) model for treatment of swine Streptococcus suis infection.

Wanhe Luo

Papers

Enhanced antibacterial activity of tilmicosin against Staphylococcus aureus small colony variants by chitosan oligosaccharide-sodium carboxymethyl cellulose composite nanogels

Formulation of a rational dosage regimen of ceftiofur hydrochloride oily suspension by pharmacokinetic-pharmacodynamic (PK-PD) model for treatment of swine Streptococcus suis infection.