[Effects of four efflux pump inhibitors on the activities of clarithromycin against Mycobacterium abscessus].

Objective: To detect the effects of four efflux pump inhibitors on the minimum inhibitory concentration of clarithromycin (CLA) against Mycobacterium abscessus (M. abscessus) in vitro, and to explore the role of efflux pump in CLA resistance of M. abscessus. Methods: Four frequently-used efflux pump inhibitors (Carbonyl Cyanide 3-chlorophenylhydrazone, CCCP, N, N'-dicyclohexylcarbodiimide, DCC, Verapamil, VP, Reserpine, RSP) were evaluated in this study. The minimum inhibitory concentration (MIC) values of clarithromycin against M. abscessus reference strain and 60 clinical strains with or without efflux pump inhibitors were detected by Alamar Blue method. Sequence analysis of erm(41) and rrl genes known to be associated with CLA resistance in M. abscessus was performed to analyze the correlation between the effect of efflux pump inhibitors on MIC and mutation of resistance-related genes. Results: CCCP, DCC, VP and RSP could reduce the MIC of M. abscessus to CLA, and the effect of RSP was weaker than the other three efflux pump inhibitors. Among the sixty M. abscessus clinical strains, ten strains were resistant to clarithromycin, seven of which had rrl gene mutation. The CLA resistance rate of smooth phenotype isolates was higher than that of rough phenotype isolates. At 3 day of clarithromycin incubation, the MICs of resistant strains were all reduced by efflux pump inhibitors. Compared with the strains with rrl gene mutation, efflux pump inhibitors had a greater effect on the strains without rrl gene mutation. At 14 day of clarithromycin incubation, 83% of M. abscessus subsp. abscessus, were induced to be resistant, and all of them were T28 sequence type of erm(41). With the occurrence of induced drug resistance, the effect of efflux pump inhibitor on CLA MIC decreased. Efflux pump inhibitors had no statistically significant diffence in the effect of effcux pump inhibitors on CLA MIC levels in different phenotypes of isolates. Conclusions: Efflux pump is involved in the resistance process of M. abscessus to CLA. Efflux pump inhibitors reduce the drug resistance to clarithromycin against M. abscessus in different degrees. The use of efflux pump inhibitors may provide a new way to alleviate the drug resistance of M. abscessus.

[Analysis of resistance to clofazimine in tuberculosis patients].

Objective: To analyze the drug resistance of tuberculosis patients to clofazimine. Methods: Retrospective analysis was conducted on the case data of 1 770 tuberculosis patients in Department of tuberculosis, Beijing Chest Hospital affiliated to Capital Medical University from January 2015 to June 2018, including 1 225 males and 545 females, aged 8-92 (43.2±15.2) years old. Drug sensitivity tests using proportion method (hereinafter referred to as drug susceptibility test) for TB strains anti-tb drug resistance test. Using χ2 test or Fisher's exact test. Results: 1 770 cases of tuberculosis patients, 1 713 cases of patients with clofazimine sensitive, of 57 patients with drug resistance, and resistant rate was 3.2% (57/1 770), including patients with recurrent clofazimine, significantly higher than the initial percentages of patients [5.8% (38/656), 1.7% (19/1 114), χ²= 22.129, P = 0.000, P<0.01]; The drug resistance rates of poly-resistant, multi-drug resistant and extensively resistant patients to clofazimine were 1.0% (17/1 770), 1.2% (21/1 770) and 1.1% (19/1 770), respectively. Has a history of hospitalization of clofazimine resistance of multidrug-resistant and extensively drug-resistant patients resistant rate 2.4% (14/594), 2.7% (16/594), respectively, higher than 0.6% (7/1 176) with no history of hospitalized patients, 0.3% (3/1 176), the differences were statistically significant (χ²=10.447,22.099,P=0.001,<0.001). Conclusion: Clofazimine has a low resistance rate, which can improve the treatment success rate of patients with drug-resistant tuberculosis and has important value.

Therapeutic drug monitoring of cycloserine and linezolid during anti-tuberculosis treatment in Beijing, China.

SETTING: Plasma concentrations of cycloserine (CS) and linezolid (LZD) in tuberculosis (TB) patients are largely unknown. OBJECTIVE: To measure the plasma concentrations of CS and LZD after drug ingestion in drug-resistant TB patients. DESIGN: Patients who received CS and LZD as part of their treatment between 1 July 2012 and 1 July 2016 were studied retrospectively. CS and LZD plasma levels were determined using high-pressure liquid chromatography-tandem mass spectrometry. Plasma drug concentration, age, sex, liver disease, renal disease, administered doses and diabetes mellitus status were recorded. RESULTS: Based on 390 samples, CS plasma concentrations were below the lower limit of normal (54.87%, 214/390). There was a statistically significant difference between the low concentration group (14.0 ± 3.71 µg/ml) and the target concentration group (25.2 ± 3.73 µg/ml, P < 0.01). The mean plasma concentration of LZD was 15.6 ± 4.91 µg/ml, which was within the target concentration (12-26 µg/ml) in 65 patients. Variables that correlated with CS and LZD concentrations were not found in this retrospective study. CONCLUSION: Low plasma CS concentrations were common, while 83.1% (54/65) of plasma LZD concentrations were within the target range. Therapeutic drug monitoring is essential to maintain appropriate plasma drug concentrations in the era of precision medicine.

Sexual violence cases in a hospital setting in Hong Kong: victims' demographic, event characteristics, and management.

INTRODUCTION: Rainlily, the first one-stop crisis centre in Hong Kong, was set up in 2000 to protect female victims of sexual violence. This study aimed to analyse the characteristics of sexual assault cases and victims who presented to two hospitals in Hong Kong. The data are invaluable for health care professionals and policymakers to improve service provision to these victims. METHODS: This retrospective analysis of hospital records was conducted in two acute hospitals under the Hospital Authority in Hong Kong. Sexual assault victims who attended the two hospitals between May 2010 and April 2013 were included. Characteristics of the cases and the victims, the use of alcohol and drugs, involvement of violence, and the outcome of the victims were studied. RESULTS: During the study period, 154 sexual assault victims attended either one of the two hospitals. Their age ranged from 13 to 64 years. The time from assault to presentation ranged from 1 hour to more than 5 months. Approximately 50% of the assailants were strangers. Approximately 50% of victims presented with symptoms; the most common were pelvic and genitourinary symptoms. Those with symptoms (except pregnancy) presented earlier than those without. The use of alcohol and drugs was involved in 36.4% and 11.7% of cases, respectively. Approximately 10% of the screened victims were positive for Chlamydia trachomatis. There were 11 pregnancies with gestational age ranged from 6 weeks to 5 months at presentation. Less than half of the victims completed follow-up care. CONCLUSIONS: Involvement of alcohol and drugs is not uncommon in sexual assault cases. Efforts should be made to promote public education, enhance coordination between medical and social services, and improve the accessibility and availability of clinical care. Earlier management and better compliance with follow-up can minimise the health consequences and impact on victims.

[Frequency and clinical relevance of rapidly growing mycobacterium isolated from respiratory samples].

OBJECTIVE: To assess the frequency and clinical relevance of rapidly growing mycobacterium (RGM) isolates in a tuberculosis referral center in Beijing, China. METHODS: All isolates were identified by using targeted gene sequencing. RESULTS of species identification for 228 nontuberculous Mycobacterium (NTM) isolates from respiratory samples were analyzed, and available medical files of patients from whom NTM were isolated were reviewed retrospectively. Diagnostic criteria for RGM pulmonary disease issued by the American Thoracic Society (ATS) were used to determine clinical relevance. RESULTS: Isolates of Mycobacterium abscessus (M.abscessus) and Mycobacterium fortuitum (M.fortuitum) accounted for 28.9% (66 isolates) and 8.8% (20 isolates)of NTM isolates, respectively. Sixty-six M. abscessus isolates from 32 patients had evaluable medical files, including 28 cases diagnosed as definite M. abscessus lung disease, and 4 as probable M. abscessus lung disease. Eight M. fortuitum isolates from 8 cases had evaluable medical files, and all of them were diagnosed as unlikely lung disease. Mycobacteria Growth Indicator Tube (MGIT) was more effective to diagnose M. abscessus lung disease, as compared with Lowestein-Jensen medium (23/24 vs 18/28). CONCLUSIONS: RGM is a common NTM in our institute. M. abscessus is mostly associated with RGM lung disease, but M. fortuitum is not.

Role of bicyclol in preventing drug-induced liver injury in tuberculosis patients with liver disease.

SETTING: Four hospitals in China. OBJECTIVE: To evaluate the clinical efficacy and safety of using bicyclol in conjunction with glucurolactone in preventing drug-induced liver injury (DILI) in tuberculosis (TB) patients suffering from underlying liver disease. DESIGN: A total of 240 initially treated TB patients who were healthy hepatitis B carriers or had pure steatosis were randomised into two equal groups; both received an oral glucurolactone tablet 600 mg/day (200 mg three times daily) as basic liver protection. The test group also received 75 mg/day (25 mg three times daily) bicyclol tablets orally, while the control group received no other liver protection. The incidence of liver injury in the two groups, the adjustment or termination of anti-tuberculosis chemotherapy and any adverse reactions were assessed. RESULTS: The incidence rate and level of severity of liver injury and the termination rate of anti-tuberculosis treatment in the test group were lower than that of the control group (P < 0.05). The overall time of occurrence of liver injury was significantly different between the two groups (P < 0.05). CONCLUSION: Adding bicyclol to basic liver protectants may effectively and safely prevent the occurrence of anti-tuberculosis DILI in patients with underlying liver disease, and help simplify anti-tuberculosis treatment.

Subcortical somatosensory evoked potentials in patients with hepatic encephalopathy caused by severe acute hepatitis.

We studied the median nerve stimulated somatosensory evoked potentials (SEP) of 23 patients with hepatic encephalopathy (HE) resulting from severe acute hepatitis and 22 healthy volunteers. Ten patients who improved and survived more than 60 days were classified as Group 1 and the remaining 13 patients who died shortly after the SEP studies were classified as Group 2. The mean N9-N13 interpeak latencies (IPL) were not different among control and two patient groups. The mean N13-N20 IPL of Group 2 was significantly prolonged when compared with normal controls (P < 0.001) and Group 1 (P < 0.001). Five of the six patients with abnormal N13-N20 IPL died of hepatic failure within 24 h after SEP testing. The occurrence of abnormal subcortical conduction together with cortical dysfunction suggested that brain damage in terminal hepatic encephalopathy was diffuse. The presentation of abnormal prolongation of N13-N20 IPL of SEP during the course of severe acute hepatitis indicated a poor prognosis. Peripheral somatosensory conduction is unaffected even in terminal HE.

Improved tracheal allograft viability in immunosuppressed rats.

Airway ischemia has been a common cause of morbidity and mortality in clinical lung transplantation. The present study examined the effects of cyclosporin A (CsA) and methylprednisolone (MP) on the viability of the devascularized trachea after heterotopic transplantation and omentopexy. Thirty-six tracheal segments were harvested from 18 donor Lewis rats, wrapped in omentum, and heterotopically implanted into the abdomen of recipient rats. Tracheal segments were randomly allocated into one of six recipient groups (n = 6): Lewis syngeneic controls, and five groups of Brown Norway recipients, receiving either no treatment, CsA alone (5 mg.kg-1.day-1 or 15 mg.kg-1.day-1), or CsA in combination with MP (5 mg CsA + 1 mg MP per kg/day or 15 mg CsA + 2 mg MP per kg/day, respectively). After 14 days, the tracheal segments were histologically evaluated. Epithelial thickness and the degree of epithelial regeneration were significantly different (p < 0.05) between the syngeneic control group and the untreated Brown Norway group. Without immunosuppression there was virtually no epithelium, whereas low-dose immunosuppression yielded intermediate viability, and with high dose CsA and MP we observed improved tracheal viability. In this high-dose group, the epithelium was thicker than in even the syngeneic control group. These results indicate that, in heterotopic tracheal allografts, viability may be improved with an optimum combination of CsA and MP.