[Antimicrobial susceptibility of community-acquired respiratory tract pathogens isolated from patients in primary hospitals in Shanghai from 2007 to 2010].

OBJECTIVE: To investigate the etiology of community-acquired respiratory tract infections (CARTI) and the antimicrobial resistance of the major pathogens in primary hospitals in Shanghai. METHODS: Patients with CARTI were prospectively recruited from 30 primary hospitals from December 2007 to July 2010. Those who had used antimicrobials within previous 2 weeks were excluded from the study. The clinical information such as temperature, white blood cell (WBC) count and percentage of neutrophils was recorded, and throat swab or deep cough sputum was collected to isolate pathogens. The specimens were collected and couriered to the Zhongshan Hospital microbiology laboratory within 2 h for bacterial culture. The minimal inhibition concentrations (MIC) of penicillin G, amoxicillin, cephradine, cephalexin, cefadroxil, sulfamethoxazole/trimethoprim and azithromycin were determined using the agar dilution test. RESULTS: Totally 806 qualified cases were enrolled in this study. Fever (T ≥ 38 °C) was present in 51.7% (n = 417) , and increased WBC count (>10×10(9)/L) was noted in 68.5% (n = 552 cases) of the patients. For bacterial culture, 184 strains were isolated from throat swabs of 688 patients with upper respiratory infection; the most frequently isolated bacteria were Haemophilus influenzae (44, 23.9%), Staphylococcus aureus (44, 23.9%) and Group G streptococcus (43, 23.0%). Thirty-three strains were isolated from 118 patients with lower respiratory infections, with Haemophilus influenza (21, 63.6%), Group G streptococcus (6,18.2%) and Streptococcus pneumoniae (3,9.1%) as the leading pathogens. All strains of Haemophilus influenzae were susceptible to azithromycin. The susceptibility rate of Streptococcus pneumoniae to penicillin was as high as 94.7%, while that to azithromycin was significantly decreased (21.1%). The MIC90 values of cephalexin, cefadroxil and ceftazidime for ß-hemolytic streptococcus spp were ≤ 2 mg/L. CONCLUSIONS: Upper respiratory infections were responsible for most cases of CARTI. The commonly used antimicrobials in primary hospitals kept a high susceptibility to the frequent pathogens for CARTI. However, Streptococcus pneumoniae showed a decreased susceptibility to macrolides, which should be used carefully as a single agent when treating CARTI.

[The incidence and risk factors for heterogeneous vancomycin intermediate Staphylococcus aureus].

OBJECTIVES: To investigate the prevalence of heterogeneous vancomycin intermediate Staphylococcus aureus (hVISA) and the sensitivity of hVISA to novel antibiotics, and to explore the risk factors and infection attributable mortality associated with hVISA infection. METHODS: A total of 456 methicillin resistant Staphylococcus aureus (MRSA) isolates were isolated in Zhongshan Hospital from January, 2008 to November, 2010. All MRSA isolates were investigated for hVISA by two agar screening methods BHIA5T (brain-heart infusion containing teicoplanin 5 mg/L) or BHIA6V (brain-heart infusion containing vancomycin 6 mg/L), as well as macroEtest method (MET). Possible hVISA isolates were tested by modified population analysis profile-area under the curve (PAP-AUC). The minimal inhibitory concentrations (MICs) of vancomycin, teicoplanin and linezolid were determined by microbroth dilution as recommended by Clinical Laboratory Standards Institute (CLSI). The contribution difference between hVISA and vancomycin susceptible Staphylococcus aureus (VSSA) in different MIC range was compared. A retrospective case-control study of the patients with hVISA infection or VSSA infection was carried out and statistical analysis was performed using t test, Mann-Whitney test, χ(2) test and Fisher exact test. RESULTS: A total of 105 isolates of hVISA were screened by BHIA5T and BHIA6V (23.0%) with other 23 isolates by MET (5.0%) and 21 by PAP-AUC (4.6%). All isolates were 100% sensitive to vancomycin, teicoplanin and linezolid. The vancomycin MIC [(1.76 ± 0.16) mg/L] in hVISA group was significantly higher than that in VSSA group [(1.09 ± 0.07) mg/L, P < 0.01], which was a potential risk factor for hVISA infection. The retrospective study showed chronic obstructive pulmonary disease (COPD) was also a risk factor for hVISA infection of the lower respiratory tract. No significant difference in infection attributable mortality was showed between the hVISA group and the VSSA group. CONCLUSIONS: The overall prevalence of hVISA in Zhongshan Hospital is estimated as 4.6%, while the prevalence of hVISA isolated from blood is as high as 12.5%. All isolates are 100% sensitive to vancomycin and linezolid. COPD is a risk factor for hVISA infection of the lower respiratory tract.

[An analysis of resistance of nosocomial infection pathogens isolated from 13 teaching hospitals in 2011].

OBJECTIVE: To investigate the pathogen profile of nosocomial infection in China, and to survey the susceptibility rates of these pathogens to the clinical common antibiotics. METHODS: The non-repetitive nosocomial pathogens isolated from bloodstream infection (BSI), hospital acquired pneumonia (HAP) and intra-abdominal infection (IAI) and the case data were collected from 13 teaching hospitals in different areas of China and sent to a central laboratory for re-identification and susceptibility testing. The levels of minimal inhibitory concentration (MIC) of the common antibiotics were determined by agar dilution method. The data were analyzed by WHONET 5.6 software. RESULTS: A total of 2103 clinical isolates were collected from January to December 2011, of which gram positive cocci and gram negative organisms accounted for 23.2% and 76.8% respectively. The top three pathogens of BSI were E. coli (31.0%, 243/784), K. pneumoniae (14.8%, 116/784) and S. aureus (10.6%, 83/784). The top three pathogens of HAP were A. baumannii (24.2%, 158/652), P. aeruginosa (23.0%, 150/652) and K. pneumoniae (16.4%, 107/652). The top three pathogens of IAI were E. coli (34.3%, 229/667), E. faecium (13.3%, 89/667) and K. pneumoniae (9.6%, 64/667). Methicillin-resistant S. aureus (MRSA) and coagulase negative Staphylococcus (MRCNS) accounted for 64.4% and 78.1% respectively. The susceptibility rates of Staphylococcus species to tigecycline, vancomycin, teicoplanin and linezolid were all 100%. The prevalence of MRSA in HAP was significantly higher than that in BSI or IAI. The susceptibility rates of Enterococcus species to tigecycline, teicoplanin and linezolid were all 100%. The prevalence of extended-spectrum ß-lactamases (ESBL) was 64.3% in E. coli and 38.3% in K. pneumonia. Against Enterobacteriaceae, the most active agents were as following in order: tigecycline (92.3% - 100%) [except P.mirabilis], meropenem (87.5% - 100%), imipenem (87.5% - 100%) [except M. morganii], amikacin (87.5% - 100%), polymyxin B (75% - 100%) [except S. marcescens, P. mirabilis and M morganii], cefepime (67.8% - 100%), cefoperazone-sulbactam (66.6% - 100%), piperacillin-tazobactam (61.5% - 100%). Carbapenem-resistance Enterobacteriaceae strains emerged. The susceptibility rates of P. aeruginosa to imipenem and meropenem were 66.2% and 72.2%, respectively. The susceptibility rates of A. baumannii to imipenem and meropenem were 27.7% and 25.9%, respectively. The most active agents against A. baumannii were polymyxin B (100%), followed by tigecycline (79.8%) and minocycline (50.4%). The susceptibility rates of P.aeruginosa to antibiotics in BSI were higher than those in HAP and IAI. Susceptibility rates of S. maltophilia to trimethoprim-sulfamethoxazole, minocycline and levofloxacin were about 90% or above. Susceptibility rates of B. cepacia to trimethoprim-sulfamethoxazole, ceftazidime and meropenem were all 100%. Several P.aeruginosa and A. baumannii strains were resistant to all tested antibiotics except polymyxin B. CONCLUSIONS: The pathogen profile is different in different types of infection. The prevalence of multi-drug resistant A. baumannii is high, which is still a key problem of nosocomial infection. Tigecycline remains relatively high activity against gram-positive cocci and gram-negative bacteria (except P. aeruginosa and P. mirabilis) in vitro.

[Analysis of clinical characteristics and risk factors associated with prognosis of patients with candidemia].

OBJECTIVE: To explore the microbiological and clinical characteristics of patients with candidemia and analyze their prognostic risk factors. METHODS: A retrospective analysis was conducted for hospitalized patients with candidemia from January 2008 to December 2012 at Affiliated Zhongshan Hospital, Fudan University. Pathogen spectrum, resistance pattern, underlying diseases, therapy received and patient prognosis were collected by chart review. The univariate and multivariate Logistic regression analyses were used to determine the prognostic risk factors of candidemia. RESULTS: A total of 138 inpatients were identified. There were 98 males and 40 females with a mean age of (61.3 ± 16.6) years. The morbidity rate of candidemia in annual discharged patients was 0.034%-0.051%. The most common pathogens were Candida albicans (n = 72, 52.2%), Candida parapsilosis (n = 29, 21.0%) and Candida tropicalis (n = 16, 11.6%). The antibiotic susceptible rate of azole for Candida was 90.9%-97.4% while 55.6%-83.3% for Candida tropicalis. The overall case fatality rate of candidemia was 39.1% (54/138) while the attributable case fatality rate 31.9% (44/138). Multivariate Logistic regression analysis indicated acute physiology and chronic health evaluation II(APACHE II) score ≥ 20 points (OR = 8.025, 95%CI: 2.032-31.696, P = 0.003), hypoproteinemia (OR = 6.213, 95%CI: 1.849-20.879, P = 0.003), concurrent bacteremia (OR = 5.541, 95%CI: 1.576-19.487, P = 0.008) and indwelling urethral catheter (OR = 13.776, 95%CI: 1.402-135.352, P = 0.024) were the independent risk factors of candidemia-related mortality, while removal or replacement of central venous catheter (OR = 0.231, 59%CI: 0.075-0.716, P = 0.011) and surgery within 30 days (OR = 0.206, 95%CI: 0.050-0.857, P = 0.030) were the protective factors. CONCLUSIONS: Candida albicans is the most common causative agent. The case fatality rate of candidemia has remained high. APACHE II score ≥ 20 points, hypoproteinemia, indwelling urethral catheter and concurrent bacteremia are independent risk factors attributing to candidemia-related mortality while removal or replacement of central venous catheter and surgery within 30 days are the protective ones.

[Intervention of chronic hepatitis B liver fibrosis patients in different stages by syndrome typing and different activating blood removing stasis methods: a clinical study].

OBJECTIVE: To observe the clinical efficacy of treating chronic hepatitis B liver fibrosis (CHBLF) in different stages by syndrome typing and different activating blood removing stasis methods (ABRSM). METHODS: Totally 100 CHBLF patients of vital qi deficiency blood stasis syndrome (VQDBSS) treated at the Department of Liver Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences from July 2008 to December 2011, were randomly assigned to the treatment group and the control group, 50 in each group. Those in the treatment group were treated by self-formulated decoctions for activating blood nourishing blood (ABNB), activating blood removing stasis (ABRS), and activating blood softening hard mass (ABSHM) according to their stages of disease conditions (mild, moderate, and severe). Those in the control group were treated with Compound Biejia Ruangan Tablet (CBRT). Integrals of Chinese medical syndromes, liver functions [mainly including alanine aminotransferase (ALT), albumin/globulin (A/ G)], ultrasonographic examinations of liver (mainly including echoes of liver, width of spleens, width of portal vein), four indicators of serum hepatic fibrosis [including serum hyaluronic acid (HA), laminin (LN), type IV collagen (IV-C), type III collagen peptide (P-III-P)] were statistically analyzed. The therapeutic course was 6 months for all. RESULTS: Compared with before treatment in the same group, the integrals of Chinese medical syndromes both decreased after treatment in the two groups (P < 0.05). The width of spleens decreased in the treatment group more obviously after treatment than before treatment (P < 0.05). Compared with the control group, the integrals of Chinese medical syndromes and the width of spleens were more obviously improved in the treatment group, showing statistical difference (P < 0.05). Compared with before treatment in the same group, levels of ALT, HA, and LN significantly decreased, and the level of A/G significantly increased after treatment in the two groups, showing statistical difference (P < 0.05). Compared with the control group, the A/G level, HA, and LN were more obviously improved in the treatment group, showing statistical difference (P < 0.05). The total effective rate was 76% in the treatment group and 46% in the control group, showing statistical difference (P < 0.05). CONCLUSIONS: Treating CH-BLF in different stages by ABRSM got better effect than using CBRT alone. It could favorably improve clinical symptoms of CHBLF patients and their serum biochemical indicators.

[The therapeutic effect of propranolol with 1064 nm Nd: YAG laser on proliferating hemangioma in body surface].

OBJECTIVE: To observe the therapeutic effect of propranolol with 1 064 nm Nd:YAG laser on proliferating hemangioma in body surface. METHODS: 97 patients with proliferating hemangiomas in body surface were randomly assigned to three groups: A group (32 patients were treated by propranolol with 1064 nm Nd:YAG laser), B group (35 patients were treated by 1064 nm Nd:YAG laser), C group (30 patients were treated by propranolol). Their visual analog scores, clinical outcomes and adverse events were compared respectively. RESULTS: 18 weeks later, A group had a mean visual analog score of 65.50 +/- 16.55, compared with 54.03 +/- 20.13 in B group, 28.08 +/- 30.34 in C group (P < 0.05); 24 weeks later, the mean visual analog scores of three groups were 76.88 +/- 19.05, 63.89 +/- 19.43 and 45.48 +/- 31.86 (P < 0.05). After 24 weeks' treatment, 9 cases (28.1%) in A group, 3 cases (8.6%) in B group, 1 cases (4.0%) in C group obtained complete healing (P < 0.05). To effect of adverse events in body surface, the mean score of B group was higher than the scores of A group and C group (P < 0.05). CONCLUSIONS: Propranolol with 1064 nm Nd:YAG laser is effective and safe in the treatment of proliferating hemangioma.

Etiology and antimicrobial resistance of community-acquired pneumonia in adult patients in China.

BACKGROUND: Appropriate antimicrobial therapy of community-acquired pneumonia (CAP) is mainly based on the distribution of etiology and antimicrobial resistance of major pathogens. We performed a prospective observational study of adult with CAP in 36 hospitals in China. METHODS: Etiological pathogens were isolated in each of the centers, and all of the isolated pathogens were sent to Zhongshan Hospital for antimicrobial susceptibility tests using agar dilution. RESULTS: A total of 593 patients were enrolled in this study, and 242 strains of bacteria were isolated from 225 patients. Streptococcus pneumoniae (79/242, 32.6%) was the most frequently isolated pathogen, followed by Haemophilus influenzae (55/242, 22.7%) and Klebsiella pneumoniae (25/242, 10.3%). Totally 527 patients underwent serological tests for atypical pathogens; Mycoplasma pneumoniae and Chlamydia pneumoniae infections were identified in 205 (38.9%) and 60 (11.4%) patients respectively. Legionella pneumophila infections were identified in 4.0% (13/324) of patients. The non-susceptibility rate of isolated Streptococcus pneumoniae to erythromycin and penicillin was 63.2% and 19.1% respectively. Six patients died from the disease, the 30-day mortality rate was 1.1% (6/533). CONCLUSIONS: The top three bacteria responsible for CAP in Chinese adults were Streptococcus pneumonia, Haemophilus influenza and Klebsiella pneumonia. There was also a high prevalence of atypical pathogens and mixed pathogens. The resistance rates of the major isolated pathogens were relatively low except for the high prevalence of macrolide resistance in Streptococcus pneumoniae.

[Anti-HIV-1 activity and structure-activity relationship of pyranocoumarin analogs].

The purpose of this study is to find out anti-HIV-1 reverse transcriptase (RT)/protease (PR) activity and inhibition of virus replication in cell cultures of novel coumarin analogs and determine their structure-activity relationship. Coumarin derivatives have been demonstrated to inhibit the activity of HIV-1 RT/PR in cell free system. It also shows inhibition effects to HIV-1 replication in cell culture. Based on the Chinese traditional pharmacological characteristics and protein three dimension computer aided design, analogs of tetracyclic dipyranocoumarin were synthesized from natural leading compounds. We studied the relationship of antiviral effects and chemical structures via HIV-1 PR/RT enzyme models and cell culture model system. Seven compounds were designed and tested. Several compounds showed anti-HIV-1 activity in varying degrees, especially V0201 showed much higher anti-HIV-1 activity with 3.56 and 0.78 micromol x L(-1) of IC50 against HIV-1 PR/RT and 0.036 micromol x L(-1) against HIV-1 replication in PBMC cultures. V0201 with a novel structure may be a new leading compound. These new compounds are valuable for development of new anti-HIV drugs in the future.

[Genetic diversity of Legionella pneumophila serogroup 1 in hospital water distribution systems in Shanghai].

OBJECTIVE: To classify Legionella pneumophila serogroup 1 (LP1) isolated from the water distribution systems in hospitals of Shanghai by using genotying methods, and therefore to explore the genetic relationship between different genotypes. METHODS: LP1 was isolated from 8 hospitals in Shanghai, and strains of LP1 were subtyped using pulse field gel electrophoresis (PFGE). Genotyping results of PFGE were classified as dendrogram, and cluster analysis was used to compare the genetic characteristics of different strains. RESULTS: Twenty-four strains of LP1 were isolated from 193 water specimens. LP1 belonged to 6 PFGE genotypes, of which 21 belonged to 3 predominant genotypes. Different hospitals shared the same genotype, while some strains isolated from the same hospital had different genotypes. CONCLUSION: The genetic characteristics are stable in environmental LP1. Molecular biology techniques should be added to epidemiological study for hospital acquired legionellosis due to the genetic diversity in one hospital.

[The characteristics of CT imaging and diagnosis of pulmonary cryptococcosis in 42 cases with non-acquired immune deficiency syndrome].

OBJECTIVE: To further elucidate the CT characteristics and diagnostic approaches to non-acquired immune deficiency syndrome patients with pulmonary cryptococcosis. METHODS: The histories of forty-two pulmonary cryptococcosis (PC) patients diagnosed in Zhongshan Hospital from 2003-2008 were collected and analyzed for demography data, underlying conditions, clinical symptoms, chest CT and diagnostic studies. RESULTS: None of the 42 PC patients had avian or its feces contacting history, and 71.4% (30/42) of them were immunocompetent. The most frequent CT lesions were multiple nodules (67.9%) with peripheral predominance (67.9%), and cavitations (50%) often presented within them. Masses/consolidation (31.4%) and patching lesions (2.9%) could exist occasionally. Positive detection rates of non-aggressive examinations including sputum, bronchoalveolar lavage fluid and bronchofibroscopy aspiration were 4.3%, 8.3% and 6.3% respectively, while those of aggressive approaches including transbronchial lung biopsy (TBLB), thin needle aspiration biopsy (TNAB) and pneumonectomy by surgery were 64.7%, 64.3% and 100% respectively. Non-aggressive serum cryptococcus antigen test was performed in 14 patients who had been diagnosed by histopathology or pathogen culture, and all of them were positive. CONCLUSION: Our study suggests that PC is common in immunocompetent population. Avian or its feces contacting is not so important as used opinion to PC differential diagnosis. CT characteristics of PC are diversiform and always change very slowly. Besides the most frequent multiple nodules with subpleural predominance, pulmonary lesions can present as masses, consolidation or patching. Aggressive techniques such as TBLB and TNAB are benefit to clinical diagnosis of PC, and non-aggressive serum cryptococcus antigen test may be promising for its early diagnosis as well as clinical course follow-up and therapeutic effect evaluation.

Improved synthesis and pharmacological evaluation of racemic 11 -demethylcalanolide A.

An improved and practical synthesis of racemic 11-demethylcalanolide A [(+/-)-1] was developed. This improved process involved Pechmann reaction on phloroglucinol with ethyl butyrylacetate to give 5,7,-dihydroxy4-n-propylcoumarin (3). Poly phosphoric acid (PPA) catalyzed acylation of compound (3) with crotonic acid, then intramolecular cyclization was achieved simultaneously in one step to afford the key intermediate chromanone (4). A microwave assisted synthetic method preparing chromene (6) using chromenynation of chromanone (4) with 1, 1-diethoxy-methyl-2-butene was conducted. Luche reduction of chromene (6) using NaBH4 with CeCl3 x 7H2O preferably gave (+/-)-1. The overall yield of this four step synthesis of (+/-)-1 was around 32% increasing one fold more than that of the previous method. An in vitro investigation showed that (+/-)-1 exhibited inhibitory activities against both wild-type and drug-resistant HIV-1 in HIV-1 RT and cell culture assay, and significant synergistic effects in combination with AZT, T-20, and indinavir. Its LD50 of acute toxicity in mice by intragastric administration and by intraperitoneal injection were 735.65 mg kg(-1) and 525.10 mg x kg(-1), respectively. The Cmax and AUC(0-infinity) were 0.54 microg x mL(-1) and 1.08 (microg x mL(-1) x h, respectively. The dynamics study of the inhibition of mice sera on HIV-1 RT showed that mice treated with 100 mg x kg(-1 (+/-)-1 once intraperitoneally were similar to that of 5 mg x kg(-1) of known clinical effective anti-HIV-1 drug neverapine. The results suggested that further investigation of the anti-HIV candidate (+/-)-1 was warranted.