Objective To analyze the current status of anti-bacterial activity of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli clinically isolated from hospitalized patients,detect their related resistance genes,and provide reference for the clinical treatment of carbapenem resistant Enterobacteria(CRE)infections and the rational use of antibiotics.Methods A total of 400 non-repetitive isolates of Klebsiella pneumoniae and Escherichia coli isolated from clinical specimens of Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine from January 2022 to December were collected.The minimum inhibitory concentrations of these strains against commonly used antibiotics were determined by the broth microdilution method.The carbapenemase and related resistance genes of CRE were detected by drug resistance phenotype testing and PCR.Results Among the 400 strains,51 strains were identified as CRE,accounting for 12.75%.Among these,49 strains produced carbapenemases,with 41 strains(80.39%)being CR Klebsiella pneumoniae and 10 strains(19.61%)being CR Escherichia coli.Among the CRE strains,34 strains(66.67%)carried blaKPC,13 strains(25.49%)carried blaNDM,and 2 strains(3.92%)carried blaOXA-48.Conclusion Compared with other commonly used antibiotics,colistin and tigecycline exhibited good in vitro antibacterial activity against carbapenemase-producing Klebsiella pneumoniae and Escherichia coli.In addition,there was good concordance between drug resistance phenotype testing and genotyping.Clinical microbiology laboratories could continuously monitor the drug resistance phenotype and genotype of CRE and develop appropriate treatment plans based on actual conditions.

Objective:To investigate the clinical features and influencing factors of long-term prognosis of tuberculous meningitis(TBM), and to provide a recommendation for treatment and early intervention of TBM.Methods:Clinical data of TBM patients were retrospectively collected at Peking Union Medical College Hospital from January 2014 to December 2021. Patients who were followed-up more than one year were divided into two groups according to modified Rankin Scale (mRS). Risk factors associated with long-term prognosis were analyze by conditional logistic stepwise regression.Results:A total of 60 subjects were enrolled including 33 (55%) males and 27 (45%) females with age 15-79 (44.5±19.8) years. There were 30 cases (50%) complicated with encephalitis, 21 cases (35%) with miliary tuberculosis. The diagnosis was microbiologically confirmed in 22 patients (36.7%), including 5 cases (22.7%, 5/22) by acid-fast staining, 8 cases (36.4%, 8/22) by Mycobacterium tuberculosis (MTB) culture, and 20 cases (90.9%, 20/22) by molecular biology. The median follow-up period was 52(43, 66 ) months in 55 cases surviving more than one year. Among them, 40 cases (72.7%) were in favorable group (mRS 0-2) and 15 cases (27.3%) were in unfavorable group (mRS 3-6) with poor prognosis. The mortality rate was 20% (11/55). Elderly ( OR=1.06, P=0.048 ) , hyponatremia( OR=0.81, P=0.020), high protein level in cerebrospinal fluid (CSF) ( OR=3.32, P=0.033), cerebral infarction( OR=10.50, P=0.040) and hydrocephalus( OR=8.51, P=0.049) were associated with poor prognosis in TBM patients. Conclusions:The mortality rate is high in patients with TBM. Molecular biology tests improves the sensitivity and shorten the diagnosis time of TBM. Elderly, hyponatremia, high protein level in CSF, cerebral infarction and hydrocephalus are independent risk factors of long-term survival in TBM patients.

Objective:To analyze the epidemiological characteristics of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infected patients in Beijing and investigate the associated factors.Methods:The clinical data of patients with HIV infection who were treated in HIV/AIDS designated hospitals (Peking Union Medical College Hospital, Beijing Ditan Hospital and Beijing Youan Hospital) were retrospectively analyzed.Results:A total of 11 572 patients were finally included in the study, among whom 532 patients (4.6%) were co-infected with HIV and HBV. Most of the co-infected patients were young male adults (28~48 years old), accounting for 85.9%. The main transmission route was homosexual behavior (74.8%). There were 87.4% co-infected patients treated with two anti-HBV drugs, including lamivudine (3TC) and tenofovir (TDF). From 2013 to 2018, the annual prevalence of HIV and HBV co-infection decreased gradually, with the rate of 6.37%, 4.55%, 3.92%, 4.68%, 4.24% and 2.74%, respectively. In our study, The main influencing factors of HIV and HBV co-infection were age older than 28 years old versus<28 years old ( OR=2.807, 95% CI 1.241-6.345) and marriage status (married versus unmarried, OR=1.259, 95% CI 1.004-1.579). Conclusions:The proportion of HBV infection in HIV-infected patients is 4.60% (532) in our cohort. From 2013 to 2018, the prevalence of HIV and HBV co-infection in Beijing shows a decreasing trend. The risk of co-infection is higher in married young adults (28~48 years old).

Talaromyces Marneffei infection is rarely reported in patients with chronic active Epstein-Barr virus (EBV) infection. We reported an old man with chronic fever, pleomorphic rash, cough, EBV viraemia, and secondary hemophagocytic syndrome. Repeated histological biopsy and culture of skin lesions revealed Talaromyces Marneffei. This patient was diagnosed as chronic active EBV infection, and Talaromyces Marneffei infection. After treated with glucocorticoid steroids and anti-fungal therapy, the patient finally recovered. EBV infection is usually seen in immune compromised patients, who are susceptible to opportunistic pathogens rarely as Talaromyces Marneffei in this case.

Patients with end-stage liver disease complicated by invasive fungal infection have poor tolerance, difficulties in pharmacotherapy, and high mortality. Invasive fungal infection in patients with end-stage liver disease should be taken seriously in clinical practice. Pathogen test should be performed as early as possible, and standard antifungal treatment should be started at the right time to improve prognosis.

Cryptococcal meningitis is a common and refractory central nervous system infection,with high rates of mortality and disability.The experts of the Society of Infectious Diseases of Chinese Medical Association have reached this consensus after a thorough discussion.Based on the current situation of cryptococcal meningitis in China,the management of cryptococcal meningitis includes 6 aspects:introduction,microorganism identification,clinical manifestations and diagnosis,principles of antifungal therapy,treatment of refractory and recurrent meningitis,treatment of intracranial hypertension.There is not a separate consensus on human immunodeficiency virus (HIV) infection in patients with cryptococcal meningitis.This article focuses on different antifungal regimens and reducing intracranial pressure by reference to Infectious Disease Society of America (IDSA) guidelines.The importance of early diagnosis,combined long-term antifungal therapy,control of intracranial hypertension are emphasized.

Objective To observe and evaluate the short-term therapeutic effect of intravitreal injection with topotecan for refractory vitreous seeding from retinoblastoma (RB).Methods Eleven patients (11 eyes) of RB with refractory vitreous seeding (received intravenous chemotherapy,intra-arterial chemotherapy,intravitreal melphalan,laser,cryotherapy and subsequently developed refractory viable vitreous seeds) were enrolled in this study.There were 6 males (6 eyes) and 5 females (5 eyes).The aged from 9 to 44 months,with the mean age of 26 months.According to International Intraocular Retinoblastoma Classification,11 eyes were initially classified as group E (3 eyes),D (6 eyes),B (1 eye) or A (1 eye).All patients were received intravitreal injection with topotecan.A total of 32 intravitreal topotecan injections were performed with a mean of 2.9 injections (median 3 injections;range 2-4 injections).The mean follow-up was 10 months.The safety and effectiveness of intravitreal injection with topotecan for refractory vitreous seeding from RB were observed.Results Complete regression of vitreous seeds was achieved in 11 of 11 eyes (100％),including complete disappearance in 9 eyes and fibrosis in 2 eyes.None of the patients needed enucleation and occured ocular or systemic complications in the follow-up period.Conclusion Intravitreal injection with topotecan for refractory vitreous seeds from RB is effective and safe.

Objective To evaluate the pharmacokinetic profiles of lopinavir(LPV) in Chinese HIV-infected patients.Methods A total of 16 patients were enrolled in the LPV pharmacokinetic study.Blood samples were collected before LPV intake and 0.5,1.0,1.5,2.0,2.5,3.0,4.0,6.0,8.0,10.0,12.0 h after administration.Serum level of LPV was determined by the developed high performance liquid chromatography (HPLC) method.The pharmacokinetic profiles were assessed by WinNonlin software.Results The non-compartment model pharmacokinetic (PK) parameters were as follows:the peak time of LPV (Tmax) (3.88 ± 0.23) h,maximum plasma concentration (Cmax) (10.36 ± 3.42) mg/L,minimum plasma concentration (Cmin) (2.18 ± 0.34) mg/L,the 24 h area under plasma-concentration-time curve (AUC0-24) (116.22 ± 15.68) mg · h · L-1,half life(T1/2) (4.5 ± 0.13) h,and clearance rate (CL/F) (3.44 ± 1.34) L/h respectively.Conclusions The pharmacokinetic profiles of LPV in Chinese HIV-1 infected patients demonstrate lower Cmin than those of reported studies,while other parameters are similar.Patients should be educated for compliance based on the narrow gap between Cmin and minimum effect concentration.

Objective To investigate the genetic homology in clinical isolates of extensively drug-resistant Acinetobacter baumannii (XDRAB),so as to provide evidence for better controlling hospital infections.Methods The genotypes of 28 clinical XDRAB isolates were determined by Enterobacterial Repetitive Intergenic Consensus PCR (ERIC-PCR).PCR was conducted to analyze 9 types of β-lactamase genes (blaKPC,blaIMP,blaVIM,blaNDM-1,blaOXA-23,blaOXA-24,blaOXA-48, blaOXA-51 and blaOXA-58),the outer membrane porin gene (CarO)and insertion sequence (IS)ISAba1.We also carried out linkage analysis for ISAba1-OXA23 and ISAba1-OXA58.Results Most of the above 28 XDRAB strains were isolated from respiratory tract specimens from intensive care patients.The result of ERIC-PCR showed that there was high homology between all the strains,suggesting that they might derive from the same clone.The genes blaOXA-23,blaOXA-51,CarO and the IS ISAba1 except Class Bβ-lactamase genes,blaOXA-24,blaOXA-48,blaOXA-58,ISAba1-OXA23 and ISAba1-OXA58 were detected in all the clinical strains by PCR.Conclusions All the XDRAB isolates belong to the same clone and carry the same drug-resistant genes,indicating that there was clone spread among XDRAB isolates.

Objective To study the expression of p35 and p25 in rat after focal cerebral contusion and to provide experimental data for estimating brain injury time. Methods Fifty adult male SD rats were randomly divided into 0 h, 6 h, 12 h, 24 h, 3 d, 5 d, 7 d, 10 d after focal cerebral contusion, control and sham-operated groups (5 rats each group). The focal cerebral contusion rat model was established. The expression of p35 and p25 protein of the damage peripheral zone in brain were detected by HEstain-ing, immunohistochemistry and western blotting at different injury time. Results Alarge number of p35 protein and a small amount of p25 protein were expressed in control group and sham-operated group. After focal cerebral contusion, p35 presented unimodal change with time and p25 presented bimodal changes with time. Conclusion Expression of p35 and p25 showed different regularity with good time correlation, which could help to estimate the brain injury time.