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

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 (AUC 0–24h /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 E max (Hill) equation. The dose was calculated based on the AUC 0–24h /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 24.76 ± 0.92 µg/mL, 811.99 ± 54.70 μg·h/mL, and 8.00 h in healthy pigs, and 33.04 ± 0.99 µg/mL, 735.85 ± 26.20 μg·h/mL, and 8.00 h in infected pigs, respectively. The MIC of PELF's DFC against S. suis strain was 0.25 µg/mL. There was strong concentration-dependent activity as determined by MPC, PAE, and the time-killing curves. The AUC 0–24h /MIC values of PELF's DFC for bacteriostatic activity, bactericidal activity, and virtual eradication of bacteria were 6.54 h, 9.69 h, and 11.49 h, respectively. Thus, a dosage regimen of 1.94 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.

Metabolic Disposition and Elimination of Cyadox in Pigs, Chickens, Carp, and Rats.

The metabolism, distribution, and elimination of cyadox (CYA) is investigated in pigs, chickens, carp, and rats to identify the marker residue and target tissue of CYA in food animals for food safety concerns. Following a single oral gavage of [(3)H]-CYA, the total radioactivity was rapidly excreted, with more than 95% of the dose excreted within 14 days in the four species. Fecal excretion of the total radioactivity was 66.2% and 51.6%, and urinary excretion of the total radioactivity was 28.35% and 44.3% in rats and pigs, respectively. Radioactivity was observed in nearly all of the tissues in the first 6 h after 7 days of consecutive oral dosing. The highest radioactivity and longest persistence were in the livers and kidneys, where the majority of the radioactivity was cleared within 7 days. A total of 15 metabolites were identified in rats, pigs, chickens, and carp, and eight new metabolites were identified for the first time in vivo. No parent drug could be detected in the tissues of rats and pigs. The major metabolites of CYA were Cy1, Cy3, and Cy6 in pigs, Cy1, Cy5, and Cy6 in chickens, Cy1, Cy2, and Cy4 in carp, and Cy1, Cy2, Cy4, and Cy5 in rats. Cy1 was suggested to be the marker residue, and the kidneys were identified as the target tissue of CYA in pigs and chickens. These results provide comprehensive information for the food safety evaluation of CYA in food animals and will improve the understanding of the pharmacology and toxicology of CYA in animals.

Nursing care of infantile acute necrotizing fasciitis treated with vacuum sealing drainage and continuous irrigation / 中国实用护理杂志

Objective To conclude the practical nursing experiences of the infantile actue necrotizing fasciitis treated with vacuum sealing drainage(VSD) and continuous irrigation.Methods 21 cases of the infantile actue necrotizing fasciitis treated with with VSD and continuous irrigation were reviewed from January 2009 to December 2014.The nursing experiences of observation for the state of the illness,the safety management of VSD,the management of medication,mental nursing and health education were summarized.Results 21 infants all recovered and were discharged.Postoperative follow up 6 months later were conducted.No obvious disabilities of the extremities were found.Among them,8 cases were treated with VSD and continuous irrigation for 2 weeks and then had routine wound dressing changing for 10 days,the wound almost healed when discharged.13 cases were treated with VSD and continuous irrigation for one week and then had routine dressing changing for 12 to 13 days.The wound healed when discharged.No skin necrotizing,no scar of the incision and no other complications were detected.Conclusions Using VSD and continuous irrigation to treat the actue necrotizing fasciitis in infants are of great significance for the nurses to reduce the postoperative complication and promote rehabilitation doing as follows:turning over with the postoperative nursing of VSD in a standard manner,observation and management of the incision area,maintenance of the irrigation and VSD;observation and assessment of the infant's condition,management of the medication,mental nursing and health education.

Study on Mycobacterium tuberculosis-specific cellular immunity in individuals co-infected with Mycobacterium tuberculosis and human immunodeficiency virus / 中华传染病杂志

Objective To evaluate Mycobacterium tuberculosis (M. tuberculosis)-specific cellular immunity in individuals with latent or active tuberculosis and human immunodeficiency virus (HIV) coinfection. Methods One hundred HIV-infected individuals in Yunnan Province were enrolled. The enzyme-linked immunospot (ELISPOT) assay using early secreted antigenic target (ESAT)-6 and culture filtrate protein (CFP)-10 was employed to detect M. tuberculosis-specific T cells in the peripheral blood. The absolute number of CD3+ CD4+and CD3+ CD8+ T cells in the peripheral blood from the enrolled subjects were determined by flow cytometry. Data were analyzed using nonparametric Mann-Whitney test. Results The prevalence of latent tuberculosis co-infection in HIV-infected individuals without any clinical evidence of active tuberculosis was 67.6%. The absolute numbers of CD3+ CD4+ (532 × 106/L) and CD3+ CD8+ (473 × 106×/L) T cell in HIV-infected individuals with latent tuberculosis co-infection were similar to those of only HIV-infeeted individuals (406 ×106×/L and 504 × 106/L). While those in HIV-infected individuals with active tuberculosis co-infection were 189 × 106/L and 293 × 106/L, respectively, which were both significantly lower than those in other two groups (U=168. 0,U=163. 0,U= 374. 0,U=147. 0, all P<0. 01). Furthermore, ESAT-6 (31/106 cells) and CFP-10 (82/106 cells) specific spot-forming cells in HIV-infected individuals with active tuberculosis co-infection were significantly less than those in HIV-infected individuals with latent tuberculosis co-infection (92 × 106 cells and 109 × 106 cells, U= 507. 0,U= 529. 5, both P<0. 01). Conclusions The prevalence of latent tuberculosis in HIV-positive individuals without any clinical evidence of active tuberculosis is high in China. Both overall cellular immunity and M. tuberculosis-specific immune response in HIV-positive individuals with active tuberculosis co-infection are severely impaired.