Fever clinic construction and management targeted to prevention and control of healthcare-associated respiratory viral infections in Jiangsu, China: A cross-sectional observational study.

To analyze the post-COVID-19 construction and management of fever clinics targeted to prevention and control of healthcare-associated respiratory viral infections in medical institutions at all levels in China, and to provide a basis for promoting their standardized construction, we conducted this survey on the construction of fever clinics in 429 medical institutions of Jiangsu Province from July to December 2020. Contents of the questionnaire included the general situation of medical institutions, the construction status and future construction plans of fever clinics. We find the construction rate of fever clinic in medical institutions of Jiangsu province was 75.3%. All construction indicators, quality management systems and processes fail to fully meet the requirements of documents and standards. Jiangsu province actively promotes the construction of fever clinic layout, but there is still a gap with the construction standard. As a result, it is necessary to further promote standardized construction of fever clinic, and necessary financial input should be increased to expand all constructions of fever clinic in primary medical institutions.

Safety and immunogenicity of a modified COVID-19 mRNA vaccine, SW-BIC-213, as a heterologous booster in healthy adults: an open-labeled, two-centered and multi-arm randomised, phase 1 trial.

BACKGROUND: We assessed the safety and immunogenicity of a core-shell structured lipopolyplex (LPP) based COVID-19 mRNA vaccine, SW-BIC-213, as a heterologous booster in healthy adults. METHODS: We conducted an open-labeled, two-centered, and three-arm randomised phase 1 trial. Healthy adults, who had completed a two-dose of inactivated COVID-19 vaccine for more than six months, were enrolled and randomized to receive a booster dose of COVILO (inactivated vaccine) (n = 20) or SW-BIC-213-25µg (n = 20), or SW-BIC-213-45µg (n = 20). The primary study endpoint was adverse events within 30 days post-boosting. The secondary endpoint was the titers of binding antibodies and neutralizing antibodies against the wild-type (WT) of SARS-CoV-2 as well as variants of concern in serum. The exploratory endpoint was the cellular immune responses. This trial was registered with http://www.chictr.org.cn (ChiCTR2200060355). FINDINGS: Between Jun 6 and Jun 22, 2022, 60 participants were enrolled and randomized to receive a booster dose of SW-BIC-213 (25 µg, n = 20, or 45 µg, n = 20) or COVILO (n = 20). The baseline demographic characteristics of the participants at enrollment were similar among the treatment groups. For the primary outcome, injection site pain and fever were more common in the SW-BIC-213 groups (25 µg and 45 µg). Grade 3 fever was reported in 25% (5/20) of participants in the SW-BIC-213-45µg group but was resolved within 48 h after onset. No fatal events or adverse events leading to study discontinuation were observed. For secondary and exploratory outcomes, SW-BIC-213 elicited higher and longer humoral and cellular immune responses than that in the COVILO group. INTERPRETATION: SW-BIC-213, a core-shell structured lipopolyplex (LPP) based mRNA vaccine, was safe, tolerable, and immunogenic as a heterologous booster in healthy Chinese adults. FUNDING: Shanghai Municipal Government, the Science and Technology and Economic Commission of Shanghai Pudong New Area, and mRNA Innovation and Translation Center of Shanghai.

Diagnostic accuracy of metagenomic next-generation sequencing for cryptococcosis in immunocompetent and immunocompromised patients.

Objective: To compare the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) for cryptococcosis in patients with different immune statuses with that of conventional detection. Methods: A total of 1442 specimens including 71 specimens from patients with cryptococcosis were analyzed in the study. The chi square test was used to screen the sensitivity and specificity of different detection methods for different specimen types. One-way ANOVA was used to compare the mNGS results with age, CD4, lymphocytes, IFN, IL-6, IL-2 and serum antigen assay. Results: The sensitivity of mNGS was 44.29% in Cryptococcus infection cases. The positive rate of mNGS results for bronchoalveolar lavage fluid (BALF, 87.50%) from immunocompromised patients was higher than that of BALF from immunocompetent patients (40.00%, p=0.04). The sensitivity of the serum Cryptococcus capsular antigen assay was 80.00% in immunocompetent patients and 96.42% in immunocompromised patients (p = 0.049). A positive rate of detection of Cryptococcus from mNGS was higher when cryptococcal antigen ≥1:160 (p=0.022) in immunocompromised patients. A positive rate of detection of Cryptococcus from mNGS was higher when lymphocyte counts were lower in both immunocompetent patients(p=0.017) and in immunocompromised patients(p=0.029). Conclusions: The sensitivity of mNGS is lower than that of serum cryptococcal antigen assay and histopathology in immunocompetent patients. However, BALF detection is recommend for immunocompromised patients compared with tissue and CSF. The positive mNGS result was correlated with lower lymphocyte counts, higher IL-2 and higher serum antigen assay in immunocompromised patients.

Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients.

BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS: In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.

Evaluation of manual and electronic healthcare-associated infections surveillance: a multi-center study with 21 tertiary general hospitals in China.

BACKGROUND: Healthcare-associated infections (HAIs) are still a major health threats worldwide. Traditional surveillance methods involving manual surveillance by infection control practitioners (ICPs) for data collection processes are laborious, inefficient, and generate data of variable quality. In this study, we sought to evaluate the impact of surveillance and interaction platform system (SIPS) for HAIs surveillance compared to manual survey in tertiary general hospitals. METHODS: A large multi-center study including 21 tertiary general hospitals and 63 wards were performed to evaluate the impact of electronic SIPS for HAIs. RESULTS: We collected 4,098 consecutive patients and found that the hospitals installed with SIPS significantly increased work efficiency of ICPs achieving satisfactory diagnostic performance of HAIs with 0.73 for sensitivity, 0.81 for specificity and 0.81 area under the curve (AUC). However, there were significant heterogeneity own to regions, time of SIPS installation, departments and sample size. CONCLUSIONS: SIPS significantly improved ICPs efficiency and HAIs monitoring effectiveness, but there were shortcomings such as untimely maintenance and high cost.

Gastropulmonary Route of Infection and the Prevalence of Microaspiration in the Elderly Patients with Ventilator-Associated Pneumonia Verified by Molecular Microbiology-GM-PFGE.

Gastropulmonary route of infection was considered to be an important mechanism of ventilator-associated pneumonia (VAP). However there is little evidence to support this assumption. Moreover, the prevalence of microaspiration in elderly ventilated patients was not well understood. To confirm gastropulmonary infection route and investigate the prevalence of microaspiration in elderly ventilated patients using genome macrorestriction-pulsed field gel electrophoresis (GM-PFGE). Patients over 60 years old, expected to receive mechanical ventilation longer than 48 h, were prospectively enrolled from October 2009 to January 2012. Clinical data were collected and recorded until they died, developed pneumonia, or were extubated. Samples from gastric fluid, subglottic secretion and lower respiratory tract (LRT) were collected during the follow-up for microbiological examination. To evaluate the homogeneity, GM-PFGE was performed on strains responsible for VAP that had the same biochemical phenotype as those isolated from gastric juice and subglottic secretions sequentially. Among 44 VAP patients, 76 strains were isolated from LRT and considered responsible for VAP. Twenty-two isolates had the same biochemical phenotype with the corresponding gastric isolates. The homology was further confirmed using GM-PFGE in 12 episodes of VAP. Nearly 30% of VAPs were caused by microaspiration based on the analysis of bacterial phenotype or GM-PFGE. In addition, 58.3% patients with gastric colonization developed VAP, especially late-onset VAP (LOP). Gastropulmonary infection route exists in VAP especially LOP in elderly ventilated patients. It is one of the important mechanisms in the development of VAP.

[Analysis of resistance tendency of bloodstream-infecting pathogens in China].

OBJECTIVE: To investigate the resistance profiles and the trend of bloodstream-infecting pathogens isolated from hospitalized patients during 2004-2010. METHODS: The bloodstream isolates were collected from 18 hospitals in 17 cities. Minimum inhibition concentrations (MIC) were determined using the agar dilution method recommended by CLSI (Clinical and Laboratory Standards Institute), and susceptibility results were analyzed according to the 2011 CLSI guideline. RESULTS: Among the 2004-2005, 2007-2008 and 2009-2010 periods, the proportions of clinical isolates were similar; 43.1% (149 isolates), 34.0% (151 isolates) and 47.5% (776 isolates) for Gram positive strains, 56.9% (197 isolates), 66.0% (293 isolates) and 52.5% (858 isolates) for Gram negative strains, respectively. The isolating rate of MRSA was 54.1% (20/37) in 2007-2008, which was the highest among the 3 periods during 2004 to 2010, while it decreased in 2009-2010 (36.5%, 62/170). The MRCNS proportions were similar across the 3 periods. One (1.8%) vancomycin-resistant Enterococcus faecium and 1 linezolid-resistant Enterococcus faecalis were found. Although the isolating rates of penicillin non-sensitive strains (oral) were similar between 2009-2010 and 2007-2008 [54.5% (6/11) and 53.9% (7/13), respectively], the resistant rates increased from 0% in 2007-2008 to 30.8% (4/13) in 2009-2010. The results were similar according to the non-meningitis criterion (IV), and the susceptibility rates decreased from 100.0% (11 isolates) in 2007-2008 to 84.6% (11/13) in 2009-2010. ESBL-harboring strains in E. coli were similar among the 3 periods during 2004 to 2010 [66.7% (30/45), 73.2% (71/97) and 67.9% (233/343), respectively]. ESBL-producing strains in Klebsilla pnuemoniae decreased year after year, 72.4% (21/29), 50.0% (18/36) and 41.1% (65/158) in 2004-2005, 2007-2008 and 2009-2010, respectively. Except that the sensitive rate of Enterobacter cloacae to ertapenem was 80% (32/40), the sensitive rates of other strains to carbapenems were still above 90% and the resistance rates were less than 5%. Acinetobacter baumannii had the highest multi-drug resistance rate (81.8%, 81/99). One strain (1.0%, 1/99) of Acinetobacter baumannii isolated in 2009-2010 was reported to be pan-resistant. CONCLUSIONS: We are facing a more serious situation of bacterial resistance. Acinetobacter baumannii resistance was most serious, usually with the characteristics of multiple drug resistance, and even pan-resistance. Carbapenems remain to be the most effective against enterobacteriaceae. Strains resistant to novel antibiotics (linezolid and tigecycline) have emerged.

[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.

[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.

Induction of rapid cell death by an environmental isolate of Legionella pneumophila in mouse macrophages.

Legionella pneumophila, the etiological agent for Legionnaires' disease, is ubiquitous in the aqueous environment, where it replicates as an intracellular parasite of free-living protozoa. Our understanding of L. pneumophila pathogenicity is obtained mostly from study of derivatives of several clinical isolates, which employ almost identical virulent determinants to exploit host functions. To determine whether environmental L. pneumophila isolates interact similarly with the model host systems, we analyzed intracellular replication of several recently isolated such strains and found that these strains cannot productively grow in bone marrow-derived macrophages of A/J mice, which are permissive for all examined laboratory strains. By focusing on one strain called LPE509, we found that its deficiency in intracellular replication in primary A/J macrophages is not caused by the lack of important pathogenic determinants because this strain replicates proficiently in two protozoan hosts and the human macrophage U937 cell. We also found that in the early phase of infection, the trafficking of this strain in A/J macrophages is similar to that of JR32, a derivative of strain Philadelphia 1. Furthermore, infection of these cells by LPE509 caused extensive cell death in a process that requires the Dot/Icm type IV secretion system. Finally, we showed that the cell death is caused neither by the activation of the NAIP5/NLRC4 inflammasome nor by the recently described caspase 11-dependent pathway. Our results revealed that some environmental L. pneumophila strains are unable to overcome the defense conferred by primary macrophages from mice known to be permissive for laboratory L. pneumophila strains. These results also suggest the existence of a host immune surveillance mechanism differing from those currently known in responding to L. pneumophila infection.

[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.

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.

[Antimicrobial susceptibility of community-acquired respiratory tract pathogens isolated from adults in China during 2009 and 2010].

OBJECTIVE: To investigate the drug-resistance rates of community-acquired respiratory tract pathogens isolated from adults in China during 2009 and 2010. METHODS: A total of 1793 strains (S. aureus 421, S. pneumoniae 420, K. pneumoniae 404, H. influenzae 313, other Streptococcus. spp 149, and M. catarrhalis 86) of non-duplicated community-acquired respiratory tract pathogens were isolated from 11 hospitals in 6 cities. The MIC values were determined by the broth microdilution method, and the production of ß-lactamase was tested using a nitrocefin-based test. RESULTS: All of the S.aureus isolates were methicillin-sensitive (MSSA). Of the MSSA isolates, less than 1% (4/421) was resistant to ß-lactamase inhibitor combinations, about 13.1% (55/421) and 9% (38/421) resistant to levofloxacin and moxifloxacin, and 57% (240/421), 53.2% (224/421), and 88.7% (373/421) resistant to azithromycin, clarithromycin, and penicillin, respectively. No S. aureus isolates resistant to vancomycin were detected in this study. Based on different criteria, the percentages of penicillin-sensitive S. pneumoniae (PSSP), penicillin-intermediate S. pneumoniae (PISP), and penicillin-resistant S. pneumoniae (PRSP) were 24.4% (102/420), 27.3% (115/420), 48.3% (203/420) (Oral) and 1.9% (8/420), 9% (38/420), 89.1% (374/420) (parenteral), respectively. The resistance rates of S. pneumonia to azithromycin, clarithromycin, cefaclor, cefuroxime, ceftriaxone and amoxicillin with clavulanic acid were 88.2% (370/420), 87.4% (367/420), 45.3% (190/420), 41.9% (176/420), 10.2% (43/420), and 5.2% (22/420), respectively. About 2.6% (11/420) and 0.2% (1/420) of S. pneumonia isolates were resistant to levofloxacin and moxifloxacin. More than 70% (104/149) of ß-hemolytic streptococci isolates were resistant to azithromycin and clarithromycin, and about 10.1% (15/149) of isolates were resistant to levofloxacin. The resistance rates of K.pneumonia to most antibiotics were > 20% (81/404), and that of ceftazidime was lower than cefuroxime, cefaclor, and ceftriaxone. The mean prevalence value of ESBL producing K. pneumonia was 38.8% (157/404), with significantly regional variations. More than 90% of H. influenza and M. catarrhalis were susceptible to most antibiotics, with resistance rate of < 5% (16/313, H. influenza; 4/86, M. catarrhalis). The mean productions of ß-lactamase in H. influenza and M. catarrhalis were 13.1% (41/313) and 91.7% (79/86), respectively. CONCLUSIONS: The percentage of PRSP increased significantly, and the resistance rates of community-acquired respiratory tract pathogens to common antibiotics such as macrolide and cephalosporins increased gradually. New fluoroquinolones such as moxifloxacin showed a high antimicrobial activity against most of the respiratory pathogens.

[Activity of macrolides and fluoroquinolones against intracellular Legionella pneumophila].

OBJECTIVE: To evaluate the activity of macrolides and fluoroquinolones against Legionella pneumophila by intracellular susceptibility testing. METHODS: Minimum inhibitory concentration (MIC) was determined by standard agar dilution test according to the CLSI. For intracellular assays, legionella pneumonia was used to infect human monocytic cell line THP-1. Erythromycin, azithromycin, levofloxacin and moxifloxacin at 1 × MIC, 4 × MIC, 8 × MIC were added following phagocytosis. Number of viable bacteria was enumerated at 24 h on BCYE (buffered charcoal yeast extract) agar in duplicates using standard plate count method. The result was expressed as percentage inhibition. Mann-Whitney U test was used to determine the significant differences in mean percentage inhibition between agents. RESULTS: Percentage inhibition at 24 h were as follows: Erythromycin 1 × MIC (50.18 ± 27.29)%, 4 × MIC (79.48 ± 20.08)%, 8 × MIC (91.46 ± 8.70)%; Azithromycin 1 × MIC (66.77 ± 26.18)%, 4 × MIC (91.73 ± 8.72)%, 8 × MIC (97.10 ± 3.37)%; Levofloxacin 1 × MIC (99.84 ± 0.25)%, 4 × MIC (99.99 ± 0.02)%, 8 × MIC (99.99 ± 0.01)%; Moxifloxacin 1 × MIC (99.90 ± 0.10)%, 4 × MIC (99.99 ± 0.03)%, 8 × MIC (99.99 ± 0.03)%. The fluoroquinolones showed greater inhibitory activity than macrolides against legionella pneumophila(u = 1.0, 2.0, 5.0, P < 0.05). Levofloxacin and moxifloxacin had the same intracellular activity against legionella pneumophila (u = 190, 183, 217, P > 0.05). Azithromycin was more effective than erythromycin in inhibiting intracellular legionella pneumophila (u = 132, 125, 128, P < 0.05). CONCLUSIONS: The fluoroquinolones were more active than macrolides against legionella pneumophila. The intracellular activity of levofloxacin against legionella pneumophila appeared to be similar to moxifloxacin. Azithromycin was demonstrated to have superior activity against legionella pneumophila compared with erythromycin.

[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.

[An antimicrobial resistance surveillance of gram-positive cocci isolated from 12 teaching hospitals in China in 2009].

OBJECTIVE: To investigate antimicrobial resistance among gram-positive cocci in China in 2009. METHODS: From June to December 2009, 1169 consecutive and non-repetitive gram-positive cocci were collected from 12 teaching hospitals at 9 cities. The minimal inhibitory concentration (MIC) of antibacterial agents was determined by agar dilution method. RESULTS: The prevalences of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococci (MRCoNS) were 45.3% (211/466) and 89.5% (214/239), respectively. The isolation rate of MRSA was 33.3% - 68.1% from different samples. All Staphylococci isolates were susceptible to vancomycin, teicoplanin and linezolid. Five point five percent (7/128) E.faecium strains were resistant to vancomycin. All E. faecalis strains were susceptible to vancomycin. About 99.1% (108/109) of E.faecalis and E.faecium were susceptible to linezolid. The prevalence of penicillin-intermediate Streptococcus pneumoniae (PISP) was 21.6% (48/222). Only 1 (0.5%, 1/222) Streptococcus pneumoniae strain was resistant to penicillin. Teicoplanin, vancomycin, linezolid and tigecycline were the most active agents against Streptococcus pneumoniae (susceptible rate 100%). CONCLUSIONS: The high prevalence of methicillin-resistance is among Staphylococcus strains. Different samples show a different MRSA prevalence. Teicoplanin, vancomycin and linezolid show very high activity to Staphylococci, E. faecalis, E. faecium and Streptococcus pneumoniae.

[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.

[The role of gastro-intestinal tract microorganisms in the development of ventilator-associated pneumonia: an experimental study].

OBJECTIVE: To study the role of microorganisms in the gastro-intestinal (GI) tract in the development of ventilator-associated pneumonia (VAP). METHODS: Forty-four healthy New Zealand white rabbits were randomly divided into a control group (n = 2), a mechanical ventilation (MV) group (n = 5), a mechanical ventilation with bacterial gastric inoculation (B) group (n = 11), a mechanical ventilation with bacterial gastric inoculation plus mosapride citrate (P) group (n = 13), and a mechanical ventilation with bacterial gastric inoculation plus loperamide (I) group (n = 13). 5% NaHCO3 was used to remain the pH value of gastric juices higher than 3.0. The flora in oropharynx, bronchi, and gastric juices were monitored during mechanical ventilation (MV). The pulmonary score and bacterial culture of the lung were performed at the end of mechanical ventilation. RESULTS: The incidence of lung infection caused by gastric bacterial inoculation was 10.8% (4/37). Taken together, mosapride citrate and loperamide didn't alter the incidence of VAP (chi2 = 0.83, P > 0.05), however, the occurrence of lung infection caused by inoculated bacteria in P group was lower than that in I group [(0.0%, 0/13) vs (23.1%, 3/13), chi2 = 4.55, P < 0.05]; the time of the emergence of the gastric inoculated bacteria in oropharynx in P group was later than that in I group; and the pulmonary score of B group was higher than that of MV group. CONCLUSIONS: Bacteria in the GI tract were not the main source of early-onset VAP, however, they may contribute to the development of late-onset VAP. Gastrointestinal dynamic promoting drugs, which enhance gastrointestinal motility, are useful to reduce the incidence of VAP caused by bacteria colonized in the digestive tract.

[A multicenter prospective cohort study on risk factors for hospital-acquired pneumonia in the elderly].

OBJECTIVE: To investigate the incidence and the risk factors for hospital-acquired pneumonia (HAP) in the elderly in Shanghai. METHODS: This was a multicenter prospective clinical cohort study. A total of 5299 patients more than 65 years old, admitted into 31 secondary or tertiary hospitals in Shanghai, were enrolled. Measurements of the demographic and potential risk factors reflecting illness severity, nutrition, drug exposure, surgery and ventilation were performed. Pneumonia was classified by the definition of Chinese Medical Association. Risk factors were analyzed by univariate Pearson Chi-squared test and multivariable logistic regression analysis with backward (Likelihood ratio). RESULTS: Of the enrolled patients, 2805 male and 2494 female, 255 (4.81%) developed hospital-acquired pneumonia. The incidence was 46.75/1000 hospitalizations. Among them 38 died; and the rough mortality was 14.90%. The incidence of HAP was higher in ICU (21.43%), hematology (12.17%), chest surgery (11.41%), and respiratory medicine (7.92%) departments. The mean of acute physiology and chronic health evaluation (APACHE II) score was 8.3 +/- 3.4 (5 - 31). Multivariable logistic regression analysis with backward (Wald) method found that admission into secondary hospitals, admission into ICU, history of chronic obstructive pulmonary disease > or = 10 years, immunosuppression, administration of antibiotics, insertion of nasogastric tube, mechanical ventilation, administration of H-2 antagonists or antacid and < or = 7 d, central nervous system diseases, depressed level of consciousness, supine position, albumin < 35 g/L were independent risk factors of HAP in the elderly. CONCLUSION: Hospital-acquired pneumonia in the elderly was the usual type of nosocomial infections. The risk factors identified from this study may prove useful to target future clinical interventions to prevent HAP in the elderly.