Oxazolidinones are a potent class of synthetic antimicrobial agents with activity mainly against Gram-positive strains.In this review,we summarize the mechanism of action and resistance,as well as the safety from clinical experience of oxazolidinones.The structural modifications and structure-activity relationships of oxazolidinones derivatives will also be presented.

Objective To evaluate the optimal administration regimen of flomoxef for the bacterial infection based on pharmacokinetic/pharmacodynamic (PK/PD) models.Methods A literature search was conducted in PubMed to capture the pharmacokinetic data of flomoxef.Minimum inhibitory concentrations (MICs) were determined using two-fold agar dilution method.The percent time that drug concentration exceeds the minimum inhibitory concentration (％fT＞MIC) was used as the PK/PD indicator correlated with efficacy.Monte Carlo simulation was employed to determine the appropriate regimens of flomoxef based on the probability of target attainment (PTA) against the clinical isolates of strains.Results The regimens of 1 g q6 h,1 g q8 h and 1 g q12 h with 1 hour infusion at 70％ of ％ fT＞MIC achieved 93.1％,89.1％ and 66.8％ of PTA against Escherichia coli (ESBL +),respectively.For the Klebsiella pneumoniae (ESBL+),these regimens achieved 81.8％,78.7％ and 62.3％ of PTA at ％fT＞MIC =70％.The regimen of 2 g q12 h achieved the similar PTA as 1g q6 h and 1 g q8 h at 50％ and 70％ of ％fT＞MIC,but not at higher ％ fT＞MIC.Furthermore,flomoxef also showed potent bactericidal activity against Escherichia coli (ESBL-),Klebsiella pneumoniae (ESBL-),methicillin-susceptible S.aureus (MSSA),methicillin-susceptible S.Epidermidis (MSSE) and Moraxella catarrhalis,etc.with all dosing regimens according to the PK/PD analysis.Conclusion As a time-dependent antibiotic,the clinical outcome of flomoxef can be improved by shortening dosing interval,extending infusion time and/or increasing dose.The first two strategies played more significant roles.

Objective To evaluate the pharmacokinetics of multiple dose of antofloxacin hydroehloride tablet under fast and food state in Chinese healthy subjects.Methods A randomized,open and multiple dose study was conducted.Three dose groups with 16 subjects per group were given the dose of 200,400 and 600 mg antofloxacin hydrochloride tablet,once daily for 7 days respectively.8 subjects (4 male and 4 female) were administrated under fast state and 8 subjects (4 male and 4 female) under food state in each dose.The concentrations of antofloxacin in plasma and urine were determined by HPLC method.Results The main pharmacokinetics parameters of three dose (200,400 and 600 mg) under fast at first day were as follows:Cmax were (2.23 ±0.38),(4.59 ± 1.40),(5.03 ±0.77)mg · L-1,t1/2βwere(11.99 ±3.31),(10.97 ±5.33),(14.39 ± 1.63)h,tmax were (1.37 ±0.78),(2.04 ± 1.42),(2.90 ±2.02)h,AUC0-t were (27.61 ±6.14),(51.77 ±22.09),(73.62 ±10.14)mg · L-1 · h,AUC0-∞ were (38.28 ± 13.49),(72.28 ± 42.80),(108.91 ± 13.26) mg · L-1 · h,V/F were (92.84 ± 12.98),(91.90±14.55),(116.28±22.62)L,CL/F were (5.73 ±1.71),(7.67 ±4.65),(5.58 ±0.66)L· h-1,respectively;under food state at first day,Cmax were (2.36 ± 0.43),(4.11 ± 1.53),(5.60 ± 1.00) mg · L-1,t1/2β were (14.37 ±4.34),(11.25 ±5.39),(15.53 ±2.94) h,tmax were (2.69 ± 1.62),(2.40 ± 1.50),(2.65 ±1.29)h,AUC0-t were (33.69 ±4.00),(48.07 ±22.19),(78.01 ±17.18)mg · L-1 · h,AUC0-∞ were (50.71 ± 8.86),(67.37 ± 41.98),(121.31.66 ± 33.54) mg · L-1 · h,V/F were (81.04 ± 16.35),(106.32 ±34.33),(114.08±20.00)L,CL/Fwere (4.07 ±0.82),(8.28 ±5.29),(5.23 ±1.18)L · h-1,respectively.After 7 days,the main pharmacokinetics parameters of three dose (200,400 and 600 mg) under fast were as follows:Cmax were (3.69 ± 1.39),(7.54 ± 2.95),(8.50 ± 0.93) mg · L-1,t1/2β were (25.22 ± 3.34),(19.56 ±12.47),(15.95 ±2.85)h,tmax were (1.64±1.29),(1.31 ±0.79),(1.60±1.07)h;AUC0-twere (72.29 ± 24.00),(142.96 ± 67.20),(180.81 ± 35.33) mg · L-1 · h,AUC0-∞ were (75.90 ± 25.46),(148.26 ±69.86),(183.30±35.11)mg · L-1 · h,V/F were (184.77 ±52.51),(119.22 ±53.92),(118.91 ±30.13) L,CL/F were (5.06 ± 1.18),(4.75 ± 1.72),(5.15 ±0.72)L · h-1;under food state,Cmax were (3.53 ± 1.06),(6.54 ±1.43),(8.52 ±1.80)mg · L-1,t1/2βwere (24.08 ±6.12),(20.64 ±9.16),(18.69 ±6.49)h,tmax were (2.94 ± 1.02),(1.96 ± 1.05),(2.69 ±0.96)h,AUC0-t were (94.71 ±31.03),(142.17 ±52.46),(211.34.01 ±52.99)mg · L-1 · h,AUC0-∞were (99.32 ±33.93),(149.77 ±55.19),(213.76 ±53.00)mg· L-1 · h,V/F were (139.40±37.39),(140.24±71.11),(130.20 ±71.09)L;CL/F were (4.11 ±1.13),(4.81 ± 1.17),(4.69 ± 0.88)L · h-1.Urinary recovery rates after 7 days doses from zero to 120 h were (67.24±13.56)％,(68.62±14.45)％ and (74.31 ±12.99)％,respectively.Conclusion Food had no obvious influence on pharmacokinetics parameters after multiple oral dose of 200,400 and 600 mg antofloxacin hydrochloride tablet under fast and food state,except that tmax increased.There was no accumulation in human body.It can be considered that food had no effect in the clinical use of antofloxacin hydrochloride tablet.

Objective To compare the results of sample size and power calculated with different methods.Methods Several methods used for the determination of sample size and power in the assessing the bioequivalence of average bioavailability were provided,their principles were introduced,and examples were demonstrated.Results Different estimation methods gave similar results.Conclusion Methods by looking up tables and abbreviated calculation are easy and quick to use,and can satisfy majority of the task requirements.Exact calculation of sample size and power can only be accomplished by using the programs provided.Detailed tables with sample size and power at different situations are provided for reference.

The individual pathological and physiological characteristics of different patient population can significantly affect the pharmacokinetic (PK) behavior.Although the PK study results from healthy subjects play an important role in guiding clinical rational medication,they may not be necessarily applicable to the population of elderly,children and gravida,and may not be suitable for all morbid states.Therefore,this article will review the PK clinical studies of various special population.

Objective To investigate the antibacterial resistance in nationwide's tietiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 18 hospitals and the minimal inhibitory concentrations (MICs) were tested using agar dilution method recommended by Clinical and Laboratory Standards Institute (CLSI) in central laboratory.The susceptibilities of isolates to antimicrobial agents were determined by using CLSI or European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2017 guideline.Results A total of 4333 pathogenic isolates from 18 tertiary hospitals in 18 cities nationwide over the period from July 2015 to June 2016 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase (ESBLs) phenotype rates of 59.4％ and 27.5％,respectively;decreased by 7 to 10 percentage points comparing the last time.Carbapenems,amikacin,moxalactam,β-lactam/β-lactamase inhibitor combinations,tigecycline,and fosfomycin displayed desirable antibacterial activity against Enterbacteriaceae,but a significant increasing of carbapenems resistance Klebsiella pneumoniae were noted.For non-fermenting Gram-negative isolates,resistance rate of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipennnem were 29.5％ and 69.8％ and multidrug-resistant (MDR) detection rate were 35.6％ and 78.3％,extensively drug-resistant (XDR) were 10.2％ and 72.5％,respectively.Klebsiella pneumoniae isolated from children were more resistant to β-lactam than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion Though the decline of ESBLs detection rate,carbapenem non-susceptible Klebsiella pneumoniae rates continued to increase,which should be paid more attention.

Objective To investigate the gram-positive coccus resistance in nationwide's tietiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 18 hospitals and the minimal inhibitory concentrations (MICs) were tested using agar/broth dilution method recommended by Clinical and Laboratory Standards Institute (CLSI) in central laboratory.The susceptibilities of isolates to antimicrobial agents were determined by using CLSI or European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2017 guideline.Results A total of 2301 Gram-positive cocci isolated from 18 hospitals in 18 cities nationwide were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus (MRSA) and methicillin resistant Stapylococcus epidermidis (MRSE) were 39.9％ and 86.6％ respectively.No vancomycin insensitive Staphylococcus was detected.Staphylococcus aureus were 100％ susceptibile to linezolid and teicoplanin,but resistant or insensitive for drugs other than vancomycin were observed among Coagulase Negative Staphylococci (CoNS).Antibiotic resistance rate of Enterococcus faecalis and Enterococcusfaecium to ampicillin were 4.5％ and 85.1％.The detectation rate of vancomycin resistant Enterococcus(VRE) was 2.1％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 7.8％,showing slight increase than last time.The prevalence of penicillin nonsusceptible Streptococcus pneumoniae (PNSSP) was 6.6％ based on non-meningitis and parenteral administration criterion;while for cases of oral penicillin,the rate was 70.0％,was as flat as last time.There were no significant differenees of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis Enterococcus faecalis and Enterococcus faecium among various groups such as different department,age,or specimen source.Conclusion Compared with past surveillance result,VRE detection ratio was steady,while MRSA detection ratio decreased.The emergence of resistance and non-susceptible strains to new antibiotics such as linezolid,tigecycline and daptomycin should be payed more attention.

Objective To investigate the involvement of heme oxygenase (HO-1) in PM2.5 induced toxic responses in human umbilical vein endothelial cells (HUVECs).Methods The experiment groups are as follows:(1) control group; (2) PM2.5 groups:the cells were cultured with various concentrations of PM2.5 (200,400,800 μg/ml) for 24 h and 400 μg/ml was chosen for the main study; (3) PM2.5 + Trion group:the cells were pre-treated by 10 μmol/L Trion [a scavenger of reactive oxygen species(ROS)] for 1 h before PM2.5 (400 μg/ml) treatment for 24 h; (4) PM2.5 +ZnPP group:the cells were pretreated by HO-1 inhibitor ZnPP (10 μmol/L) for 1 h before treatment with PM2.5 (400 μg/ml) for 24 h.MTT assay was used to detect cell viability.Reverse transcription polymerase chain reaction (RT-PCR) and indirect immunofluorescence assay were used to determine the mRNA and protein expressions of HO-1.Fluorescence labeling probe method was used to measure intracellular ROS level and flow cytometry was used for cell apoptosis.Colorimetric assay was used to detect intracellular caspase-3 activity.Results Compared with control,PM2.5 significantly decreased cell viability,increased intracellular ROS,cell apoptosis and caspase-3 activity (all P ＜ 0.05),these effects were significantly attenuated in PM2.5 + Tiron group while enhanced in PM2.5 + ZnPP group (all P ＜ 0.05 vs.PM2.5 group).PM2.5 upregulated HO-1 mRNA and protein expressions in HUVECs which was downregulated in both PM2.5 + Tiron group and PM2.5 + ZnPP group.Conclusion PM2.5 could induce oxidative injury through increasing ROS production via modulating HO-1 mRNA and protein expressions,the injury could be aggravated with inhibition of the activity of HO-1 suggesting a potential protective role of HO-1 against PM2.5 induced oxidative stress in HUVECs.

Objective To explore the mechanism of fine particulate matter (PM2.5) induced endothelial injury and the efficacy and mechanism of ginsenoside Rg1 on the inhibition of endothelium injuries in human endothelial cells exposured to PM2.5.Methods Human umbilical vein endothelial cells (HUVECs) were stimulated with various concentrations PM2.5 (0.1,0.2,0.4,0.8 mg/ml) and PM2.5 at concentration 0.8 mg/ml induced significant endothelial injury and was chosen for the main study in the presence or absence of Rg1 (0.04 mg/ml).After 24 h treatment,cell growth A value was detected through MTT,intracellular reactive oxygen species (ROS) level through fluorescence labeling probe method and HO-1,Nrf2 mRNA expression was detected by RT-PCR.Results The cell A value was significantly lower while the ROS fluorescence gray value and the average optical density ratio of HO-1 were significantly higher in PM2.5 group than in the control group (all P ＜ 0.05).The average optical density ratio of Nrf2 was similar between PM2.5 group and control group (P ＞ 0.05).The A value and the average optical density ratio of HO-1 were significantly higher while the ROS fluorescence gray value was significantly lower in co-treated PM2.5 (0.8mg/ml) + Rgl (0.04 mg/ml) group than in the PM2.5 (0.8 mg/ml) group (all P ＜ 0.05).Conclusion PM2.5 could induce human endothelial cells injury by increasing oxidative stress which could be attenuated by ginsenoside Rg1.

Objective To evaluate the effect of combination of autologous fascia and fat injection into vocal fold for the treatment of patients with unilateral vocal fold paralysis and to observe the long-term effectiveness of this procedure. Methods A total of 26 unilateral vocal fold paralysis patients underwent vocal fold injection under general anesthesia, meanwhile, the mucosa of the injected point was sutured through laryngoscope under direct vision. There were 6 patients underwent autologous fat injection into vocal fold ( group A), and 20 patients underwent autologous anterior rectus sheath fascia and fat injection ( group B). Therapeutic efficacy were evaluated by videostroboscopy, voice-related parameters analysis and voice evaluation before and after treatment. Clinical analysis of this procedure was retrospectively performed in this serial of patients. Results All patients were followed up for 24 months. On the third day after operation,there was an acute inflammatory reaction induced by the graft. This reaction disappeared three months later.In all 20 eases, videolaryngostroboscopy showed significant improvement of the glottic closure, the improvement in acoustical parameters was statistically significant ( P ＜ 0. 01 ). Perceptual evaluation of GRBAS scale showed significant improvement of phonatory function on G, B, A scale. The results remained stable 6 -24 months after operation and were not changed by the length of follow-up. And in the 6 cases,videolaryngostroboscopy showed significant improvement of the glottic closure at 3 months compared with preoperative observation, a little spindle-shaped disclosure. The improvement in acoustical parameters was significant statistically at 3, 6 and 24 months (P ＜ 0. 05 or ＜ 0. 01 ), the voice quality decreased significantly at 6 and 24 months compared with 3 months (P ＜0. 05 or ＜0. 0l ). The significant differences were not observed between 6 and 24 months (P ＞ 0. 05 ). No complications were observed in all patients perioperatively or during the follow-up period. Voice-related parameters jitter, normalized noise energy and maximum phonation time showed significant differences between Group A and Group B on 24 months ( P ＜0. 05 or ＜ 0. 01 ). Conclusion The combination of autologous fascia and fat vocal fold injection is an effective procedure for the treatment of unilateral vocal fold paralysis, and the stable results can be achieved during the follow-up period for 24 months.