Intracellular activity of antibiotics against Coxiella burnetii in a model of activated human THP-1 cells

We evaluated antibiotic activity against the intracellular bacterium Coxiella burnetii using an activated THP-1 cell model of infection. At clinically-relevant concentrations, the intracellular bacterial load was reduced 300-fold by levofloxacin and finafloxacin, 40-fold by doxycycline, 4-fold by ciprofloxacin, and was unaffected by azithromycin. Acidification of the culture media reduced antibiotic activity with the exceptions of doxycycline (no change) and finafloxacin (slight improvement). This model may be used to select antibiotics to be evaluated in-vivo .

The effect of dietary supplementation with silkworm pupae meal on gastrointestinal function, nitrogen retention and blood biochemical parameters in rabbits

Background The aim of this study was to determine the effect of dietary inclusion of silkworm pupae meal (SPM) on nutrient digestibility, nitrogen utilization, gastrointestinal physiology and blood biochemical parameters in rabbits. Thirty Termond White rabbits were divided into three groups: SBM – fed a diet containing 10% soybean meal (SBM), SPM5 – fed a diet containing 5% SBM and 5% SPM, and SPM10 – fed a diet containing 10% SPM. Results Nutrient digestibility and nitrogen retention decreased with increasing SPM inclusion levels in rabbit diets. The dietary inclusion of SPM caused a significant increase in the stomach pH. Group SPM10 rabbits were characterized by the highest cecal tissue and digesta weights. The lowest cecal pH was noted in group SPM5. The relative weights of colonic tissue and digesta tended to increase with increasing levels of SPM. The total and intracellular activity of bacterial α-galactosidase decreased significantly in both SPM groups. The replacement of SBM with SPM led to a decrease in the activity of bacterial β-glucuronidase in the cecal digesta. The intracellular activity of bacterial α-arabinofuranosidase increased, and its release rate decreased in the cecum of rabbits in SPM groups. The extracellular activity of bacterial β-xylosidase in the cecal digesta tended to decrease in group SPM10. The highest extracellular and intracellular activity of bacterial β-cellobiosidase in the cecal digesta was noted in the SPM5 treatment. The lowest and the highest activity of bacterial N-acetyl-β-D-glucosaminidase (NAGase) was observed in groups SBM and SPM10. The SPM10 treatment contributed to a decrease in the cecal concentrations of butyric, iso-valeric and valeric acids. The lowest total concentration of putrefactive short-chain fatty acids (PSCFAs) was observed in group SPM10. The cecal concentration of propionic acid tended to increase in group SPM5, whereas the cecal concentration of iso-butyric acid tended to decrease in group SPM10. The colonic concentration of iso-valeric acid was lowest in group SPM5. SPM treatments resulted in a significant increase in plasma albumin concentration. Plasma urea concentration was significantly higher in group SPM10 than in SBM and SPM5. Conclusions The results of this study suggest that rabbit diets can be supplemented with SPM at up to 5%.

Rifampin, Rifapentine, and Rifabutin are Active Against Intracellular Periprosthetic Joint Infection-Associated Staphylococcus epidermidis

Staphylococcus epidermidis is a major cause of periprosthetic joint infection (PJI); its intracellular persistence within osteoblasts may compromise therapy if that therapy is not intracellularly active. The intracellular activity of rifampin, rifapentine, and rifabutin was assessed against five rifampin-susceptible and two rifampin-resistant S. epidermidis isolates. Compared to no treatment, treatment resulted in a ≥2-fold log10 reduction of intracellular rifampin-susceptible, but not rifampin-resistant S. epidermidis. These findings show activity of rifampin, rifapentine, and rifabutin against intra-osteoblast PJI-associated S. epidermidis.

Intracellular activity of pharyngeal motoneurons during breathing, swallowing, and coughing

We have provided the first demonstration of the multifunctional activity of the pharyngeal motoneurons at the level of membrane potential during respiration, swallowing, and coughing.

Inhaled tigecycline is effective against Mycobacterium abscessus in vitro and in vivo

Background Mycobacterium abscessus causes chronic pulmonary infections. Owing to its resistance to most classes of antibiotics, treatment is complex and cure rates are only 45%. Tigecycline is active against M. abscessus, but severe toxicity and the need for IV administration limit its use. Objectives To assess the potential of inhaled tigecycline as a treatment for M. abscessus pulmonary disease, by measuring its efficacy in a mouse model of chronic M. abscessus pulmonary disease, establishing the intracellular activity of tigecycline against M. abscessus in human macrophages and measuring the activity of tigecycline in the sputum of cystic fibrosis patients. Methods We infected GM-CSF knockout mice with M. abscessus by intrapulmonary aerosol. Infected mice were treated with tigecycline in 0.25, 1.25 and 2.5 mg doses, by inhalation, or untreated, for 28 days. Tigecycline was added to human peripheral blood-derived macrophages infected with M. abscessus to assess its intracellular activity. We performed a time–kill kinetics experiment of tigecycline against M. abscessus with and without sputum of cystic fibrosis patients. Results Inhaled tigecycline proved highly effective against M. abscessus in GM-CSF knockout mice. The effect was dose dependent. Tigecycline showed potent activity against M. abscessus in macrophages and retained most of its activity in the presence of sputum of cystic fibrosis patients. Conclusions Inhaled tigecycline may represent a viable treatment option for M. abscessus pulmonary disease, where treatment outcomes are currently very poor. A stable and safe formulation is required to proceed to further pharmacodynamic studies and ultimately clinical trials.

Bis-(imidazole/benzimidazole)-pyridine derivatives: synthesis, structure and antimycobacterial activity

Aim: Over the last decades, few significant achievements have been made in tuberculosis (TB) therapy. As a result, there is an urgent need for new anti-TB drugs. Results: Two new classes of bis-(imidazole/benzimidazole)-pyridine derivatives were designed, synthesized and evaluated for their antimycobacterial activity. Conclusion: The synthesis is efficient and straightforward, involving only two successive N-alkylations. The anti-TB assay reveal that our compounds have an excellent anti-TB activity against both replicating and nonreplicating Mtb, are not cytotoxic, exhibited a very good intracellular activity and are active against drug-resistant Mtb strains, some compounds have a bactericidal mechanism. The absorption, distribution, metabolism, excretion and toxicity studies performed for one compound are promising, indicating that it is a good candidate for a future drug.