Expert Consensus on Polymyxin Antimicrobial Susceptibility Testing and Clinical Interpretation.

The polymyxins are important antimicrobial agents against antibiotic-resistant gram-negative bacilli. In 2020, the Clinical and Laboratory Standards Institute modified the clinical breakpoints for polymyxin susceptibility test by eliminating the "susceptible" interpretive category, only reporting intermediate (≤2 mg/L) and resistant (≥4 mg/L). However, the European Committee on Antimicrobial Susceptibility Testing recommended the use of clinical breakpoints of ≤2 mg/L as susceptible and >2 mg/L as resistant. The first-line laboratorians and clinicians in China have been perplexed by the inconsistence of international polymyxin clinical breakpoints and discouraged by the difficulty of conducting polymyxin susceptibility testing. Therefore, it is urgently needed to make it clear for the laboratorians in China to know how to accurately carry out polymyxin susceptibility testing and standardize the interpretation of susceptibility testing results. To this end, the experts from relevant fields were convened to formulate this consensus statement on the testing and clinical interpretation of polymyxin susceptibility. Relevant recommendations are proposed accordingly for laboratorians and clinicians to streamline their daily work.

Therapeutic drug monitoring of vancomycin: a guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

BACKGROUND: Guideline development should be based on the quality of evidence, balance of benefits and harms, economic evaluation and patients' views and preferences. Therefore, these factors were considered in the development of a new guideline for therapeutic drug monitoring (TDM) of vancomycin. OBJECTIVES: To develop an evidence-based guideline for vancomycin TDM and to promote standardized vancomycin TDM in clinical practice in China. METHODS: We referred to the WHO Handbook for Guideline Development and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to rate the quality of evidence and grade the strength of recommendations, according to economic evaluation and patients' views and preferences. We used the GRADE Grid method to formulate the recommendations. RESULTS: The guideline presents recommendations about who should receive vancomycin TDM, how to monitor vancomycin efficacy and renal safety, therapeutic trough concentrations, time to start initial vancomycin TDM, loading dose and how to administer and adjust the vancomycin dose. CONCLUSIONS: We developed an evidence-based guideline for vancomycin TDM, which provides recommendations for clinicians and pharmacists to conduct vancomycin TDM in China.

The accuracy of presepsin (sCD14-ST) for the diagnosis of sepsis in adults: a meta-analysis.

INTRODUCTION: The early diagnosis of sepsis remains a challenge. Recently, soluble cluster of differentiation 14 subtype (sCD14-ST), also known as presepsin, has been identified as a potential biomarker of sepsis. We performed a meta-analysis to assess the diagnostic accuracy of presepsin for sepsis in patients with systemic inflammation. METHODS: We systematically searched the PubMed, Embase, Web of Knowledge and Cochrane databases. Studies were included if they assessed the diagnostic accuracy of presepsin for sepsis in adult patients with systemic inflammatory response syndrome (SIRS). Furthermore, a 2 × 2 contingency table was constructed based on these results. Two authors independently judged the studies and extracted the data. The diagnostic accuracy of presepsin in sepsis was calculated using a bivariate meta-analysis model. The Q-test and I (2) index were used to test the heterogeneity. RESULTS: Eight studies involving a total of 1,815 patients were included in the present study. The pooled sensitivity, specificity, diagnostic odds ratio, positive likelihood ratio and negative likelihood ratio were 0.86 (95% CI: 0.79-0.91), 0.78 (95% CI: 0.68-0.85), 22 (95% CI: 10-48), 3.8 (95% CI: 2.6-5.7), and 0.18 (95% CI: 0.11-0.28), respectively. The area under the summary receiver operator characteristic curve was 0.89 (95% CI: 0.86-0.92). Meta-regression analysis revealed that consecutive patient selection, sample size and setting significantly accounted for the heterogeneity of sensitivity. CONCLUSIONS: Our findings suggest that presepsin exhibits very good diagnostic accuracy (AUC=0.89) for the diagnosis for sepsis. Nevertheless, an overall assessment of all the clinical indexes for sepsis diagnosis and continual re-evaluation of presepsin during the course of the disease are needed.

Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related miRNAs.

The goal of the present study was to identify novel protein biomarkers from the target genes of six serum miRNAs that we identified previously in patients with sepsis. The target genes were predicted by bioinformatics analysis; the levels of the respective proteins in the sera of patients with sepsis were detected by ELISA. ACVR2A (activin A receptor, type IIA), FOXO1 (forkhead box O1), IHH (Indian hedgehog), STK4 (serine/threonine kinase 4) and DUSP3 (dual specificity phosphatase 3) were predicted to be the targets of the six miRNAs, and their encoded proteins were used for biomarker identification. Levels of ACVR2A (P<0.01) and FOXO1 (P<0.01) were significantly different among normal controls, patients with sepsis, patients with severe sepsis and patients with septic shock. Furthermore, levels of ACVR2A (P=0.025), FOXO1 (P<0.001), IHH (P=0.001) and STK4 (P=0.001) were differentially expressed in survivors and non-survivors. DUSP3 levels were not significantly different between any groups. Conjoin analysis of the four differentially expressed proteins showed that the area under the curve of the predictive probabilities was 0.875 [95% CI (confidence interval): 0.785-0.965], which was higher than the SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores. When the value of predictive probabilities was 0.449, the four proteins yielded a sensitivity of 68% and a specificity of 91%. Dynamic changes in ACVR2A, FOXO1 and IHH levels showed differential expression between survivors and non-survivors at all time points. On the basis of a combined analysis of the four identified proteins, their predictive value of 28-day mortality of patients with sepsis was better than the SOFA or APACHE II scores.

Serum miR-122 levels are related to coagulation disorders in sepsis patients.

BACKGROUND: Coagulation abnormalities may have a major impact on the outcome of sepsis in patients. This study aimed to explore the relationship between miRNA levels and coagulation disorders during sepsis. METHODS: Blood samples from 123 sepsis patients were collected on the day of admission and another 45 sepsis patients on days 1, 3, 5, 7, 10, and 14 following admission to the intensive care unit. miR-223, miR-15a, miR-16, miR-122, miR-193b*, and miR-483-5p levels were evaluated by quantitative reverse transcription polymerase chain reaction. Based on the International Society on Thrombosis and Haemostasis (ISTH) Disseminated Intravascular Coagulation (DIC) score, sepsis patients were divided into coagulation abnormal (CA) group and coagulation normal (CN) group. RESULTS: Only the levels of miR-122 were significantly higher in CA patients than in CN patients (p<0.001). Serum levels of miR-122 were correlated to the serum activated partial thromboplastin time (APTT) ratios (R=0.426, p=0.008) and the fibrinogen (FIB; R=0.398, p=0.008) and antithrombin III (R=0.913, p<0.001) levels. In addition, Pearson's correlation coefficients for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) with miR-122 were 0.663 (p<0.001) and 0.445 (p=0.001), respectively. In the 45 patients, the miR-122 levels were significantly higher on day 1, 3, 7, and 10 in the CA group than in the CN group, and no difference in the ISTH-DIC scores was evident. CONCLUSIONS: Serum levels of miR-122 were correlated to the coagulation disorder in sepsis patients.

[Survey of macrolide resistance in Mycoplasma pneumoniae in adult patients with community-acquired pneumonia in Beijing, China].

OBJECTIVE: To explore the tendency of macrolide resistance in Mycoplasma pneumoniae infection in community-acquired pneumonia (CAP) patients in Beijing. METHODS: Adult CAP patients of ≥ 18 yrs were enrolled in 3 medical centers in Beijing , China. Throat swab samples were taken from all the patients to perform the culture of M. pneumoniae . All the isolated M. pneumoniae strains were subjected to susceptibility evaluation for 6 agents, including macrolides such as erythromycin and azithromycin. In strains showing macrolide resistance, the 23S rRNA gene was analyzed. RESULTS: A total 53 strains of M. pneumoniae were isolated from 321 enrolled patients. Thirty-eight of the isolated strains (71.7%) were resistant to erythromycin and 32 of them (60.4%) were resistant to azithromycin. Six strains with moderate or low level of erythromycin-resistance were still susceptible to azithromycin. No fluoroquinolone-resistant or tetracycline-resistant strains were observed in our study. Point transition of A2063G in the 23S ribosomal RNA gene was the main reason for the high prevalence of macrolide resistance. CONCLUSIONS: The prevalence of macrolide resistance in M. pneumoniae is very high in adult CAP patients in Beijing. Studies are needed to clarify the clinical meaning of prevalence of macrolide-resistant M. pneumoniae in adults CAP patients.

Efficacy and safety of Lianhua Qingwen capsules combined with standard of care in the treatment of adult patients with mild to moderate COVID-19 (FLOSAN): protocol for a randomized, double-blind, international multicenter clinical trial.

Background: Effective anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs are not only the next defense after vaccines but also the key part of establishing a multi-tiered coronavirus disease 2019 (COVID-19) prevention and control system. Previous studies had indicated that Lianhua Qingwen (LHQW) capsules could be an efficacious Chinese patent drug for treating mild to moderate COVID-19. However, pharmacoeconomic evaluations are lacking, and few trials have been conducted in other countries or regions to evaluate the efficacy and safety of LHQW treatment. So, this study aims to explore the clinical efficacy, safety, and economy of LHQW for treating adult patients with mild to moderate COVID-19. Methods: This is a randomized, double-blind, placebo-controlled, international multicenter clinical trial protocol. A total of 860 eligible subjects are randomized at a 1:1 ratio into the LHQW or placebo group to receive two-week treatment and follow-up visits on days 0, 3, 7, 10, and 14. Clinical symptoms, patient compliance, adverse effects, cost scale, and other indicators are recorded. The primary outcomes will be the measured median time to sustained improvement or resolution of the nine major symptoms during the 14-day observation period. Secondary outcomes regarding clinical efficacy will be evaluated in detail on the basis of clinical symptoms (especially body temperature, gastrointestinal symptoms, smell loss, and taste loss), viral nucleic acid, imaging (CT/chest X-ray), the incidence of severe/critical illness, mortality, and inflammatory factors. Moreover, we will assess health care cost, health utility, and incremental cost-effectiveness ratio (ICER) for economic evaluation. Discussion: This is the first international multicenter randomized controlled trial (RCT) of Chinese patent medicine for the treatment of early COVID-19 in accordance with WHO guidelines on COVID-19 management. This study will help clarify the potential efficacy and cost-effectiveness of LHQW in the treatment of mild to moderate COVID-19, facilitating decision-making by healthcare workers. Registration: This study is registered at the Chinese Clinical Trial Registry, with registration number: ChiCTR2200056727 (date of first registration: 11/02/2022).

Caspofungin for prophylaxis and treatment of fungal infections in adolescents and adults: a meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Caspofungin, a novel echinocandin compound, has been approved for the treatment of esophageal and suspected invasive candidiasis and as salvage therapy for invasive aspergillosis. The aim of this study was to assess the efficacy and safety of caspofungin for the prophylaxis and treatment of fungal infections, compared with other medications. METHODS: PubMed, Embase, and the Cochrane Library were searched to identify relevant randomized controlled trials (RCTs) of caspofungin. Nine RCTs were included in this meta-analysis, performed using Review Manager Version 5.0. Analyses of favorable response, microbiological response, mortality rate, survival rate, relapse rate, and adverse events were performed to evaluate caspofungin. RESULTS: Caspofungin produced similar effects in favorable response rate [relative risk (RR) = 1.07, 95% confidence interval (CI) 0.98-1.17], microbiological response rate (RR = 1.02, 95%CI 0.90-1.15), mortality rate (RR = 0.98, 95%CI 0.78-1.24), survival rate after 7-day follow-up (RR = 1.00, 95% CI 0.91-1.10), and relapse rate (RR =1.18, 95% CI 0.81-1.73) compared with other antifungal agents in the prophylaxis and treatment of patients with fungal infections, particularly those caused by Candida. There were significant differences in clinical and laboratory adverse events between caspofungin and other antifungal agents in favor of caspofungin (RR = 0.66, 95% CI 0.49-0.89) (RR = 0.66, 95% CI 0.57-0.75). CONCLUSION: This meta-analysis shows that caspofungin can be used as effectively as other antifungal agents for prophylaxis and treatment of fungal infections, mainly for Candida, and that it is associated with fewer adverse effects than comparable agents.

[Adult hospital acquired pneumonia: a multicenter study on microbiology and clinical characteristics of patients from 9 Chinese cities].

OBJECTIVE: To investigate the etiology and clinical characteristics of hospital-acquired pneumonia (HAP) in China and to provide evidence for appropriate therapy. METHODS: We performed a prospective multicenter study in 13 Chinese urban tertiary hospitals. All HAP cases diagnosed at respiratory general ward and respiratory intensive care unit (RICU) from August 2008 to December 2010 were studied. Epidemiological data, etiology and clinical characteristics of enrolled patients were collected. Sputum or tracheal aspirate and blood cultures, Legionella antibodies and Streptococcus pneumoniae urinary antigen tests were performed. Bacteria to antimicrobial susceptibility test was performed. RESULTS: A total of 610 cases of HAP were diagnosed during the study, with an overall incidence of 1.4% among 42 877 hospitalized patients, while the incidence was 0.9% (362/41 261) in respiratory general ward and 15.4% (248/1616) in RICU. 93.9% (573 cases) of patients had at least one underlying disease, and 91.0% (555 cases) had exposure to at least one antimicrobial agent within 90 days prior to HAP diagnosis. Pathogens were identified in 487 patients, with Acinetobacter baumannii [30.0% (183/610)], Pseudomonas aeruginosa [22.0% (134/610)], Staphylococcus aureus [13.4% (82/610)] and Klebsiella pneumonia [9.7% (59/610)] being the most common pathogens. Eighteen patients (3.0%) had infection with fastidious bacteria. A. baumannii and S. aureus were the more frequent pathogens in the ventilator-associated pneumonia (VAP) cases [50.5% (97/192) and 21.4% (41/192)] as compared to non-VAP cases [20.6% (86/418) and 9.8% (41/418), P < 0.01]. A. baumannii and S. aureus were also frequent pathogens in cases with a score of more than 20 by the acute physiology and chronic health evaluation II (APACHEII) scoring [45.7% (69/151) and 20.5% (31/151)], as compared to cases with a score of less than 20 of APACHE II [24.8% (114/459) and 11.1% (51/459), P < 0.01]. A. baumannii showed high resistance rates to carbapenems [more than 70% (109/142)], and the susceptibility to cefoperazone/sulbactam, polymyxin B and tigecycline were 40.8% (58/142), 99.3% (141/142) and 95.8% (136/142) respectively. Resistance rates of P. aeruginosa to meropenem and imipenem were 48.8% (40/82) and 70.7% (58/82) respectively. Methicillin-resistant S. aureus (MRSA) accounted for 87.8% (43/49) in all strains of S. aureus. Mortality rate of VAP cases was 34.5% (61/177), significantly more than that of HAP patients [22.3% (135/605), P < 0.05]. The average hospital stay of patients with HAP was (23.8 ± 20.5) days, significantly more than that of the average for inpatients [(13.2 ± 13.6) days, P < 0.01] during the study period. Mean costs of HAP were (108 950 ± 116 608) yuan, significantly higher than the average hospital costs of respiratory inpatients (17 999 ± 33 364) yuan. CONCLUSIONS: Among Chinese patients hospitalized in urban tertiary medical centers, HAP incidence and mortality rate were high, which increased the patients' hospital stay and the medical costs. Common pathogens were A. baumannii, P. aeruginosa, S. aureus and K. pneumonia. The common bacteria of HAP in China showed high resistance rates to antibiotics.

[A multicentre retrospective study of pulmonary mycosis clinically proven from 1998 to 2007].

OBJECTIVE: To investigate the pathogens, clinical manifestations, prognosis of and the risk factors for pulmonary mycosis in China. METHODS: All cases of pulmonary mycosis from 16 centers in 10 cities from Jan. 1998 to Dec. 2007 that met the diagnostic criteria were included for clinical, microbiological and radiological analysis. RESULTS: Totally 474 cases of pulmonary mycosis were retrieved. The top 5 pulmonary mycosis was pulmonary aspergillosis (180 cases, 37.9%), pulmonary candidiasis (162 cases, 34.2%), pulmonary cryptococcosis (74 cases, 15.6%), pneumocystis carinii pneumonia (23 cases, 4.8%) and pulmonary mucormycosis (10 cases, 2.1%). The constituent ratio in the last 3 years was similar to that in the former 7 years. The main pathogens of pulmonary candidiasis were Candida albicans (308/474, 65.0%) and Candida tropicalis (57/474, 12.0%), which were sensitive to common azoles. Compared with bacterial pneumonia, pulmonary mycosis showed more symptoms of hemoptysis (147/474, 31.0%) and pleural effusion (95/474, 20.0%), and less radiological specificity. Classical halo sign (4/474, 0.8%) and crescentic sign (17/474, 3.6%) were only shown in several cases of pulmonary mycosis. The most common underlying diseases were tumor (including solid tumor and malignant hematological diseases) (94/474, 19.8%), chronic obstructive pulmonary disease (52/474, 11.0%), pulmonary tuberculosis (50/474, 10.5%) and diabetes (48/474, 10.1%). Compared with the other common pulmonary mycosis, pulmonary cryptococcosis affected younger patients, and more cases were community-acquired, but fewer cases with underlining diseases or compromised immune function, and had a better prognosis. CONCLUSION: The ahead five species of pulmonary mycosis in China were orderly pulmonary aspergillosis, pulmonary candidosis, pulmonary cryptococcosis, pneumocystis carinii pneumonia and pulmonary mucormycosis. The main pathogens of pulmonary candidosis were Candida albicans and Candida tropicalis, which were sensitive to common azoles. Compared with the other common pulmonary mycosis, pulmonary cryptococcosis catch younger patients, had more community-acquired cases, and had better prognosis.

Experimental pulmonary infection and colonization of Haemophilus influenzae in emphysematous hamsters.

BACKGROUND: Bacterial infection has been considered the main cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). However, experimental model of COPD exacerbation induced by Haemophilus influenzae infection was not available up to now. Furthermore, only a few studies on evaluation of antibiotics using an H. influenzae infection model in mice have been reported. The aim of this work was to evaluate the activity of moxifloxacin on experimental pulmonary infection and colonization of H. influenzae in emphysematous hamsters. METHODS: Pulmonary emphysema was developed by intratracheal instillation of porcine pancreatic elastase in golden hamsters, which were infected by agar-beads enclosing H. influenzae to establish animal models of AECOPD. Alterations of lung histopathology, inflammatory factor levels in plasma and bronchoalveolar lavage fluids (BALFs), viable cell counting of lung tissue were determined on different days after challenge and moxifloxacin administration. RESULTS: Lung bacterial counts of BALFs and homogenates were significantly higher in emphysematous hamsters than those in normal non-emphysematous animals from 1 to 3 weeks after intratracheal inoculation of bacterial agar-beads suspensions. Moreover, H. influenzae colonized and survived for a longer period of time in emphysematous lungs than in normal non-emphysematous lungs after challenge. Efficacy of 3-day intragastric administration of moxifloxacin was proved by reduction in pulmonary H. influenzae burden and alleviation of inflammatory responses on days 4, 8 and 21 post-inoculation. No planktonic bacteria were isolated from BALFs in the first week after moxifloxacin treatment, and bacterial load in lung tissue homogenates declined significantly. Nevertheless, after 3 weeks, bacterial load in BALFs and homogenates of emphysematous lungs recovered to a large quantity. Inflammation in lung tissue, including lung consolidation, hemorrhage, and neutrophils infiltration, was conspicuously improved after administration of moxifloxacin. Levels of inflammatory factors in plasma were significantly decreased on days 8 and 21 after treatment compared with that without drug therapy. Inflammatory factors in BALF were also reduced, among which IL-8 dropped down markedly in early stage. CONCLUSION: Our results suggest that chronic bacterial infection and colonization is highly correlated with lung emphysematous lesions, which would be one of the important mechanisms for repeated attacks of acute exacerbations of chronic pulmonary diseases and uncertain efficacies of antibiotics.

[The effect of spontaneous breathing trial on weaning from ventilators].

OBJECTIVE: To investigate whether spontaneous breathing trial is an essential process during weaning from ventilator in critically cared patients without chronic obstructive pulmonary disease (COPD). METHODS: The study was performed with a prospective, randomized, double-blinded method. A total of 67 adult patients, mechanically ventilated for at least 48 h in SICU of a teaching hospital, were enrolled. As soon as the patients were ready for weaning from ventilators, they were randomly assigned to 2 groups with target extubation without spontaneous breathing trial (SBT) (non-SBT group) and with SBT (SBT group). In the SBT group, the patient who tolerated the spontaneous breathing trial underwent immediate extubation. In the non-SBT group, as soon as a patient met weaning readiness criteria, he or she underwent extubation without SBT process. The primary outcome measure was successful extubation, defined as the ability to maintain spontaneous breathing for 48 hrs after extubation. Results were expressed as mean +/- SD. Mean values between the 2 groups were compared by student's t tests. The differences in proportions between the 2 groups were determined using chi(2)-test. RESULTS: There were no significant differences in demographic, respiratory, and hemodynamic characteristics between the 2 groups at the end of assessing weaning readiness criteria. Three (9.7%) patients in the SBT group and 3 (9.4%) patients in the non-SBT group needed reintubation (chi(2) = 0.013, P = 0.908). Five patients in the non-SBT group and 4 in the SBT group required noninvasive ventilation following extubation (chi(2) = 0.253, P = 0.727). There were no significant differences in in-hospital mortality between the 2 groups (chi(2) = 0.276, P = 0.600). CONCLUSION: The result suggests that spontaneous breathing trial may be not a necessary procedure preceding extubation in a general intensive care population.

[Enterococcus faecium lung abscess: one case report and literature review].

OBJECTIVE: to study the diagnosis and treatment of enterococcus faecium lung abscess. METHODS: a retrospective analysis of one case of Enterococcus faecium lung abscess and literature review was conducted. RESULTS: this patient suffered from cough and sputum over 6 months and complicated with hemoptysis over 3 months. Pulmonary embolism and lung cancer were suspected initially. After 2 times of CT-guided percutaneous transthoracic needle aspiration biopsy the diagnosis of pneumonia was made in other hospitals. However, the consolidation in the lung progressed and cavity appeared although antibiotic therapy was conducted. After admission to our hospital, CT-guided percutaneous transthoracic needle aspiration biopsy was made and the lung tissue was sent for bacterial culture. Enterococcus faecium was cultured and it was susceptible to vancomycin, teicoplanin and linezolid. The disease improved significantly after treatment with these 3 antibiotics in turn. In addition, 13 cases of enterococcus pneumonia or lung abscess were reviewed, including 3 cases of enterococcus faecium lung abscess. CONCLUSIONS: enterococcus faecium is rarely a pathogen for lung abscess. The diagnosis of enterococcus faecium lung abscess could be confirmed by lung biopsy and bacterial culture of lung tissue which could also provide the susceptibility of antibiotics and guide the antibiotic therapy.

[Effects of vaporized perfluorocarbon therapy on seawater respiratory distress syndrome in rabbit models].

OBJECTIVE: To investigate the effects of vaporized perfluorocarbon therapy on pulmonary gas exchange and lung compliance in seawater respiratory distress syndrome rabbit models. METHODS: After induction of seawater respiratory distress syndrome by means of intratracheal injection of seawater, 24 female New Zealand rabbits were randomly divided into 3 groups: (1) CMV group (n = 8): Animals were ventilated with equal tidal volumes of 8 ml/kg during gas ventilation for 6 h. (2) PFC group (n = 8): For the first 2 h, animals received vaporized PFC with volumes of 6 - 7 mlxkg(-1)xh(-1), followed by gas ventilation for 4 h. (3) control group (n = 8): No ventilation was administered. Physiological and blood gas data were compared among the 3 groups by analysis of variance. The right lung of each animal was cut into 2 or 3 slides which were fixed with 10% buffered formalin for pathological evaluation. RESULTS: After lung injury, the measurements of lung compliance and oxygenation became significantly worse. After vaporized PFC for 30 min, lung compliance and oxygenation improved significantly as compared to the CMV group [(2 +/- 1) mm Hg/cm H2O vs (1 +/- 0) mm Hg/cm H2O (1 mm Hg = 0.133 kPa, 1 cm H2O = 0.098 kPa), F = 20, P < 0.05; (158 +/- 65) mm Hg vs (74 +/- 12) mm Hg, F = 26, P < 0.05]. After PFC inhalation, the improvement of oxygenation in PFC group lasted for 4 h [(253 +/- 96) mm Hg vs (78 +/- 19) mm Hg, F = 15, P < 0.05]. The lung injury score was also decreased in the PFC group compared to the CMV group (6.9 +/- 1.6 vs 9.8 +/- 1.3, chi(2) = 22, P < 0.05). All animals in the control group died in 15 min without ventilation. CONCLUSION: Vaporized PFC improved oxygenation and lung compliance and attenuated lung injury in a rat model of seawater induced respiratory distress syndrome.

[Effects of positive end expiratory pressure ventilation upon respiratory function and hydrophobic surfactants proteins in rabbit with seawater respiratory distress syndrome].

OBJECTIVE: To investigate the effects of positive end-expiratory pressure (PEEP) ventilation upon respiratory function and lung surfactant protein B (SP-B)/SP-C in seawater respiratory distress syndrome (SW-RDS) rabbit. METHODS: Twenty-four female New Zealand rabbits were randomly equally divided into three groups:conventional mechanical ventilation (CMV) group, PEEP group, and control group. After anesthesia and tracheal intubation followed by 20 minutes of CMV, SW-RDS model was established by lung perfusion of artificial seawater through tracheal intubation. Then the CMV group ventilated for 6 hours (each parameter unchanged); PEEP group ventilated with PEEP of 8 cm H2O for 2 hours based on prior parameters and subsequently with CMV for 4 hours; control group without ventilation after modeling. Oxygenation indices and lung compliance were continuously monitored during ventilation. After ventilation, the rabbits in study groups were sacrificed while those dying a natural death in the control group selected. Bronchoalveolar lavage fluid of the left lung was collected to determine the alveolar surface tension and the right lung was harvested to measure the mRNA expression of SP-B/SP-C by real-time PCR as well as SP-B protein by Western blotting. RESULTS: After modeling, the data of lung compliance and oxygenation indices became significantly worse in every group but without statistical difference in three groups. All rabbits in control group died within 15 minutes of ventilator withdrawal. After receiving PEEP ventilation for 30 minutes, these indices significantly improved compared with CMV group in which there was no significant change of the indices (P < 0.05). Minimal alveolar surface tension in CMV group (mN/m, 30.8 +/- 6.3) was greater than in PEEP group (21.1 +/- 4.4, P < 0.05) and control group (23.6 +/- 4.6, P < 0.05); SP-B/SP-C mRNA relative expression (0.37 +/- 0.15/0.60 +/- 0.19) and SP-B relative protein abundance (0.38 +/- 0.17) in CMV group were obviously lower than in PEEP group (0.73 +/- 0.15/0.92 +/- 0.40, 0.52 +/- 0.22, P < 0.05). CONCLUSIONS: PEEP ventilation can improve the oxygenation indices and lung compliance in SW-RDS animals. And such an effect is correlated with both the mRNA expressions of SP-B/SP-C and mechanical distension.

[The establishment of a rat model of chronic pulmonary infection due to Pseudomonas aeruginosa].

OBJECTIVE: To establish a rat model of chronic pulmonary infection by inoculating two different Pseudomonas aeruginosa embedded in minute seaweed alginate beads made by an ejection set with an acuminata hole to Sprague-Dawley rats. To evaluate the animal model with bacteriology and pathology values. METHOD: (1) 300 healthy, clean Sprague-Dawley rats were divided into 3 groups randomly: the wide-type Pseudomonas aeruginosa group (PAO(1) group), the mutant type Pseudomonas aeruginosa group (PAO-JP2 group) and the control group. (2) Two different Pseudomonas aeruginosa were embedded in minute seaweed alginate beads by an ejection set with an acuminata hole. Then the beads were inoculated into the rats' lung through tracheal intubation. The bacteria numbers in lung and pathology scores were measured 3, 7, 14, 28 days after infection. RESULTS: (1) The bacteriology values: No bacterium were detected in the control group. PAO(1) and PAO-JP2 were detected from rats of PAO1 and PAO-JP2 infected groups respectively. Bacterial number was higher than 10(5) CFU/g 3, 7 days after infection (LgCFU/g): 3 d: PAO1 group: 19 +/- 6, PAO-JP2 group: 17 +/- 7; 7 d: PAO1 group: 13 +/- 4, PAO-JP2 group: 12 +/- 4) and higher than 10(3) CFU/g 14, 28 days after infection (LgCFU/g: 14 d: PAO1 group: 11.3 +/- 2.8, PAO-JP2 group: 9.6 +/- 3.3; 28 d: PAO1 group: 9.1 +/- 1.5, PAO-JP2 group: 4.2 +/- 3.0). (2) The pathological changes showed: 3, 7 days after infection, lung abscess, edema, consolidation, haemorrhage can be seen from lungs of both groups. And at optical microscopic, alginate-Pseudomonas aeruginosa caused a pronounced inflammatory reaction with polymorphonuclear cells surrounding a bead. Small microcolonies formed at the periphery of the bead were also seen. 14, 28 days after infection, the consolidation reduced gradually and lung atelectasis, fibrinous adhesions and granulomas became the major pathological changes, which is more significant in the PAO(1) group. CONCLUSION: The animal model of chronic pulmonary infection can be established by inoculating Pseudomonas aeruginosa embedded in minute seaweed alginate beads made by an ejection set with an acuminata hole to Sprague-Dawley rats.

[The preventive effects of intraperitoneal injection of perfluorocarbon on acute lung injury in rat].

OBJECTIVE: To evaluate the preventive effects of intraperitoneal injection of perfluorocarbon (PFC) on acute lung injury (ALI) in rat. METHODS: Sixty-three male Wistar rats were randomly divided into normal control (NC) group, lipopolysaccharide (LPS) group and C8F18 group. Rats in NC group were sacrificed 2 hours after anesthesia, and in LPS group and C8F18 group rats were either treated with normal saline or C8F18 15 ml/kg intraperitoneally 48 hours before LPS challenge. ALI was reproduced by intravenous injection of 7 ml/kg LPS, and the extent of lung injury was assessed by arterial partial pressure of oxygen (PaO(2)) level, histological examination, right lung wet weight/body weight (W/D) ratio, tumor necrosis factor-alpha (TNF-alpha) level in serum and broncho alveolar lavage fluid (BALF) at 2, 4, 6 hours after injury. RESULTS: PaO(2) in LPS group and C8F18 group was significant lower than that in NC group (both P<0.05). There were no difference in PaO(2) between LPS group and C8F18 group at 2, 4, 6 hours after injury (all P>0.05). Compared with NC group, TNF-alpha level in blood and BALF increased obviously in LPS group and C8F18 group (both P<0.05). There was no significant change in content of TNF-alpha in C8F18 group BALF at 6 hours was significantly lower than that in LPS group (P<0.05). CONCLUSION: Intraperitoneal administration of C8F18 (15 ml/kg) can not attenuate pathological changes or improve PaO(2) in rats with ALI induced by LPS in a short time.

Diagnosis and treatment of community-acquired pneumonia in adults: 2016 clinical practice guidelines by the Chinese Thoracic Society, Chinese Medical Association.

Community-acquired pneumonia (CAP) in adults is an infectious disease with high morbidity in China and the rest of the world. With the changing pattern in the etiological profile of CAP and advances in medical techniques in diagnosis and treatment over time, Chinese Thoracic Society of Chinese Medical Association updated its CAP guideline in 2016 to address the standard management of CAP in Chinese adults. Extensive and comprehensive literature search was made to collect the data and evidence for experts to review and evaluate the level of evidence. Corresponding recommendations are provided appropriately based on the level of evidence. This updated guideline covers comprehensive topics on CAP, including aetiology, antimicrobial resistance profile, diagnosis, empirical and targeted treatments, adjunctive and supportive therapies, as well as prophylaxis. The recommendations may help clinicians manage CAP patients more effectively and efficiently. CAP in pediatric patients and immunocompromised adults is beyond the scope of this guideline. This guideline is only applicable for the immunocompetent CAP patients aged 18 years and older. The recommendations on selection of antimicrobial agents and the dosing regimens are not mandatory. The clinicians are recommended to prescribe and adjust antimicrobial therapies primarily based on their local etiological profile and results of susceptibility testing, with reference to this guideline.

[Effect of vaporized perfluorocarbon inspiration on cell apoptosis of intestine mucosa: experiment with pigs with acute lung injury].

OBJECTIVE: To investigate the effect of vaporized perfluorocarbon (PFC) inspiration on cell apoptosis of intestine mucosa. METHODS: 18 piglets are randomly assigned to 3 groups, VMV group (n=8), undergoing intra-bronchial infusion of dioctyl sodium sulfosuccinate so as to cause acute lung injury (ALI), then routine mechanical ventilation (MV) for 8 h during which vaporized PFC inspiration was given for 2 h, and then killed to have the small intestine taken out, CMV group (n=8), undergoing routine MV for 8 h after the establishment of ALI model as MV control group, and sham operation group (n=2), undergoing only laparotomy to take out the small intestine. Apoptosis index of intestine mucosa was examined by TUNEL. Immunohistochemistry was used to detect the protein expression of BAX and bcl-2. RT-PCR was used to detect the mRNA expression of BAX and bcl-2. RESULTS: The apoptotic cells were mainly distributed in the intestinal villi of the VMV and CMV groups, and only a few apoptotic cells could be seen in the sham operation group. The apoptosis rate of the VMV group was (22.9+/-2.3)%, significantly lower than that of the CMV group [(70.6+/-3.4)%, P<0.05]. The protein expression of BAX of the VMV group was significantly lower than that of the CMV group (P<0.05), and the protein expressing of bcl-2 of the VMV group was significantly higher than that of the CMV group (P<0.05). The mRNA expression of BAX of the VMV group was 7.10+/-0.32, significantly lower than that of the CMV group (9.29+/-1.06, P<0.05), and the MRNA expression of bcl-2 of the VMV group was 10.29+/-2.51, significantly higher than that of the CMV group (5.18+/-1.08, P<0.05). The mRNA expression and protein expression of BAX and bcl-2 were all at very low levels in the sham operating group. CONCLUSION: PFC vaporized inspiration may reduce mucosa apoptosis of small intestine, with the possible mechanism of inhibiting the expression of the BAX gene and raising the expression of the bcl-2 gene.