Activities of imipenem-relebactam combination against carbapenem-nonsusceptible Enterobacteriaceae in Taiwan.

BACKGROUND: Imipenem-relebactam is a new ß-lactam and ß-lactamase inhibitor combination to treat carbapenem-resistant gram-negative bacteria infections. However, difference in carbapenem resistant mechanisms existed with geographic variations. OBJECTIVE: To evaluate the susceptibility of imipenem-relebactam to 660 carbapenem-nonsusceptible Enterobacteriaceae isolates in Taiwan and to identify the in vivo efficacy with a Caenorhabditis elegans model. METHODS: 188 carbapenem-nonsusceptible Escherichia coli isolates and 472 carbapenem-nonsusceptible Klebsiella pneumoniae isolates were collected from a national surveillance study in Taiwan. The antimicrobial susceptibility profiles and carbapenemase distributions were determined. An agar dilution method was performed to evaluate the in vitro activities of imipenem monotherapy and imipenem-relebactam combination. Contributions of metallo-carbapenemase to imipenem-relebactam susceptibility was investigated via EDTA treatment. A C. elegans model was used to evaluate the in vivo efficacy of imipenem-relebactam combination. RESULTS: 87.8% and 82.2% susceptibility to imipenem-relebactam was observed for 188 carbapenem-nonsusceptible E. coli and 472 carbapenem-nonsusceptible K. pneumoniae, respectively. However, poor activities of imipenem-relebactam was observed against 23 metallo-carbapenemase producers tested in this study. In the in vivo C. elegans model, imipenem-relebactam significantly rescued nematodes from the infection of a blaKPC-producing K. pneumoniae isolate. CONCLUSION: Our study supports that imipenem-relebactam is a potential therapy against carbapenem-nonsusceptible Enterobacteriaceae, and to our knowledge, this is the first report of evaluation for imipenem-relebactam efficacy against carbapenem-nonsusceptible Enterobacteriaceae in Taiwan.

[Analysis of related factors and evaluation of quality of life of osteonecrosis of femoral head after internal fixation of femoral neck fracture].

OBJECTIVE: To explore the risk factors of osteonecrosis of femoral head after internal fixation of femoral neck fracture in young patients, to describe the quality of life of patients with surviving femoral head, and to quantify the predictive factors. METHODS: From January 2013 to December 2016, 172 patients (174 hips) with femoral neck fracture treated by closed reduction and cannulated screw internal fixation were selected for retrospective analysis. The general data of the patients were summarized, including age, gender, body mass index, trauma mechanism, trauma operation interval, trauma season and whether the internal fixation was removed. The imaging data included the Garden classification and Pauwel classification of fractures, femoral head retroversion angle, postoperative fracture reduction, screw distribution. Single factor analysis and multi-factor Logistic regression analysis were carried out to explore the risk factors of femoral head necrosis and internal fixation failure. The patients who survived the internal fixation were followed up. The quality of life of the patients was evaluated by the health survey of SF-36. The Harris score of hip joint function was used to evaluate the hip joint function. The predictors of the quality of life of the patients after the operation of femoral neck fracture were analyzed by multiple linear regression analysis. RESULTS: Total 172 patients(174 hips) were included in the study, 29 patients(16.67%) had necrosis of the femoral head. In multivariate Logistic regression analysis, the significant differences were reduction quality (OR=0.126, P=0.027) and posterior inclination angle (OR=4.380, P=0.010). One hundred and thirty six patients (137 hips) who survived the femoral head were included in the quality of life survey. Harris score was 90.14±7.92, including excellent 96 hips (70.07%), good 28 hips (20.44%), medium 13 hips (9.49%) and poor 0 hip. In SF-36 score, physical health summary (PCS) was 46.12±9.12, mental health summary(MCS) was 50.21±3.97, there was no linear correlation between them (P>0.05). In multiple linear regression analysis, the variables with significant difference in PCS were reduction quality and retroversion angle, and the variables with significant difference in MCS were fracture displacement and trauma mechanism. CONCLUSION: Poor reduction quality and posterior inclination angle>15° are the risk factors of femoral head necrosis. The function of hip joint and MCS of patients with femoral neck fracture recovered well, but PCS could not recover to the average level of normal people. The reduction quality and retroversion angle could be used as the predictors of PCS, and the displacement and trauma mechanism of fracture could be used as the predictors of MCS.

In Vitro and In Vivo Evaluations of ß-Lactam/ß-Lactamase Mono- and Combined Therapies against Carbapenem-Nonsusceptible Enterobacteriaceae in Taiwan.

Increasing carbapenem resistance rates worldwide underscored the urgent need of novel antimicrobials. Ceftazidime-avibactam and aztreonam-avibactam combinations are developed to combat carbapenem resistance, but biological and geographic variations must be considered for antibiotic susceptibility patterns varied. Thus, we sought to assess the susceptibilities of ceftazidime-avibactam and aztreonam-avibactam against 660 carbapenem-nonsusceptible Enterobacteriaceae isolates (472 Klebsiella pneumoniae and 188 Escherichia coli) collected during an earlier Taiwan surveillance study. Agar dilution method was used to determine ceftazidime-avibactam and aztreonam-avibactam susceptibility. Metallo-carbapenemase's contribution to resistance were investigated with EDTA addition. The in vivo efficacies were evaluated using a Caenorhabditis elegans model. High susceptibility rates were observed for ceftazidime-avibactam and aztreonam-avibactam against the 472 carbapenem-nonsusceptible K. pneumoniae (CnsKP) (85.2% and 95.3%, respectively) and 188 carbapenem-nonsusceptible E. coli (CnsEC) isolates (91.5% and 94.1%, respectively). For non-metallo-carbapenemase producers, the susceptibility rates for ceftazidime-avibactam were 93.6% for CnsKP and 97.7% for CnsEC, whereas only 7.1% CnsKP and 11.1% CnsEC in metallo-carbapenemase producers were susceptible to ceftazidime-avibactam. Of all isolates, 95.3% CnsKP and 94.1% CnsEC were susceptible to aztreonam-avibactam. In C. elegans model, ceftazidime-avibactam and aztreonam-avibactam revealed effective against a blaKPC-producing K. pneumoniae isolate in vivo. Our results propose a positive therapeutic approach for both combinations against carbapenem-nonsusceptible Enterobacteriaceae in Taiwan.

[Clinical observation of Yishen Huoxue decoction(YSHXD) for the treatment of non-traumatic osteonecrosis of femoral head at early and middle stage].

OBJECTIVE: To observe clinical efficacy of Yishen Huoxue decoction(YSHXD) for the treatment of non-traumatic osteonecrosis of femoral head at early and middle stage. METHODS: From January to June 2016, 69 patients (72 hips) with non-traumatic osteonecrosis of femoral head at early and middle stage were divided into treatment group and control group according to therapeutic methods. In treatment group, there were 35 patients 43 hips, including 15 males and 20 females, aged from 28 to 62 years old with an average of(41.80±11.03) years old, 6 hips were at the stage I, 27 hips were at the stageII, 10 hips were at the stage IIIa according to ARCO classification; and treated by using YSHXD, one dose a day for 12 months. In control group, there were 34 patients 39 hips, including 16 males and 18 females, aged from 31 to 61 years old with an average of (43.35±13.52) years old, 5 hips were at the stage I, 26 hips were at the stageII, 8 hips were at the stage IIIa according to ARCO classification; and treated by using alendronate sodium tablets 70 mg every week for 12 months. Preoperative and postoperative HSS score at 2 weeks were observed and compared, EQ-5D index was used to compare clinical effects. ARCO classification was applied to imaging evaluation, the stage of ARCO over IIIa was considered as end point of observation. The final following-up time and ARCO classification were recorded and performed Kaplan-Meier survival analysis. RESULTS: All patients were followed-up from 26 to 76 months with an average of(43.50±13.26) months. Postoperative Harris score at 2 years in treatment group (84.92±7.56) was higher than that of before treatment (73.58±10.02) (P<0.05), and higher than that of control group(79.61±10.92)(P<0.05), especially the scores of joint function and activity were higher than those of control group(P<0.05). EQ-5D index in treatment group 0.66±0.12 was higher than that of control group 0.59±0.12(P<0.05). Nine hips were collapsed in treatment group at final follow-up, and 10 hips were collapsed in control group, and had no statistical difference between two groups (P>0.05). There was no statistical difference in kaplan-meier survival analysis curves between two groups (P>0.05). There were statistical difference in survival rate between the early, middle ARCO stage and different Harris evaluation. CONCLUSIONS: YSHXD for the treatment of non-traumatic osteonecrosis of femoral head at early and middle stage has obviously clinical effects, could improve hip joint function, and quality of life, and delay the process of femoral head necrosis collapse.