Advances in research on virulence factors of Acinetobacter baumannii and their potential as novel therapeutic targets.

Acinetobacter baumannii is a strictly aerobic, nonmotile, nonfermenting, gram-negative bacillus. It is a highly infectious and invasive pathogen with high mortality and morbidity rates among immunodeficient patients. Due to increasing levels of drug resistance and the inefficiency of existing antimicrobial treatments, it is crucial to develop novel agents to control this pathogen. Several recent studies have investigated virulence factors that are associated with the pathogenesis of A. baumannii, and could thus serve as novel therapeutic targets. The present review comprehensively summarizes the current understanding of these virulence factors and their mechanisms in A. baumannii. We also highlight factors that could be potential therapeutic targets, as well as list candidate virulence factors for future researchers and clinical practitioners.

DeePMD-kit v2: A software package for deep potential models.

DeePMD-kit is a powerful open-source software package that facilitates molecular dynamics simulations using machine learning potentials known as Deep Potential (DP) models. This package, which was released in 2017, has been widely used in the fields of physics, chemistry, biology, and material science for studying atomistic systems. The current version of DeePMD-kit offers numerous advanced features, such as DeepPot-SE, attention-based and hybrid descriptors, the ability to fit tensile properties, type embedding, model deviation, DP-range correction, DP long range, graphics processing unit support for customized operators, model compression, non-von Neumann molecular dynamics, and improved usability, including documentation, compiled binary packages, graphical user interfaces, and application programming interfaces. This article presents an overview of the current major version of the DeePMD-kit package, highlighting its features and technical details. Additionally, this article presents a comprehensive procedure for conducting molecular dynamics as a representative application, benchmarks the accuracy and efficiency of different models, and discusses ongoing developments.

Microbial Contamination Characteristics on Touch Surfaces in Outpatient Self-Service Facilities.

BACKGROUND: With the development of science and technology, self-service facilities have been widely used in hospitals. This study aimed to assess the microbial contamination characteristics on touch surfaces in outpatient, self-service facilities from Monday to Friday. METHODS: Touch surfaces in outpatient facilities were swabbed and surveyed for total microbial growth before and after work every morning. Selected bacteria were identified to screen for pathogenic organisms. RESULTS: There were 360 samples collected, 87 samples (24.2%) were culture-positive. Staphylococcus species were the main microbial contamination. The three most common bacteria were S. hominis, S. epidermidis and S. hemolyticus. After work, more microbial contamination was found on Monday (p = 0.029). There was no difference in sample positive rates between self-service facilities and manual service area. Although, the antibiotic resistance patterns of different staphylococcus species were different, the overall drug resistance rate is low. Only one S. aureus was methicillin-Sensitive S. aureus. CONCLUSIONS: The self-service facilities' touch surfaces microbial contamination were similar to manual service area, but the more used, the more microbial contamination was found. Hospitals should enhance cleaning times of self-service facilities to keep them clean, especially on Mondays.

Pyruvate cycle increases aminoglycoside efficacy and provides respiratory energy in bacteria.

The emergence and ongoing spread of multidrug-resistant bacteria puts humans and other species at risk for potentially lethal infections. Thus, novel antibiotics or alternative approaches are needed to target drug-resistant bacteria, and metabolic modulation has been documented to improve antibiotic efficacy, but the relevant metabolic mechanisms require more studies. Here, we show that glutamate potentiates aminoglycoside antibiotics, resulting in improved elimination of antibiotic-resistant pathogens. When exploring the metabolic flux of glutamate, it was found that the enzymes that link the phosphoenolpyruvate (PEP)-pyruvate-AcCoA pathway to the TCA cycle were key players in this increased efficacy. Together, the PEP-pyruvate-AcCoA pathway and TCA cycle can be considered the pyruvate cycle (P cycle). Our results show that inhibition or gene depletion of the enzymes in the P cycle shut down the TCA cycle even in the presence of excess carbon sources, and that the P cycle operates routinely as a general mechanism for energy production and regulation in Escherichia coli and Edwardsiella tarda These findings address metabolic mechanisms of metabolite-induced potentiation and fundamental questions about bacterial biochemistry and energy metabolism.

Exploring the nexus between fatigue, body composition, and muscle strength in hemodialysis patients.

BACKGROUND: Fatigue is a relatively prevalent condition among hemodialysis patients, resulting in diminished health-related quality of life and decreased survival rates. The purpose of this study was to investigate the relationship between fatigue and body composition in hemodialysis patients. METHODS: This cross-sectional study included 92 patients in total. Fatigue was measured by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) (cut-off ≤ 34). Body composition was measured based on quantitative computed tomography (QCT), parameters including skeletal muscle index (SMI), intermuscular adipose tissue (IMAT), and bone mineral density (BMD). Handgrip strength was also collected. To explore the relationship between fatigue and body composition parameters, we conducted correlation analyses and binary logistic regression. RESULTS: The prevalence of fatigue was 37% (n = 34), abnormal bone density was 43.4% (n = 40). There was a positive correlation between handgrip strength and FACIT-F score (r = 0.448, p < 0.001). Age (r = - 0.411, p < 0.001), IMAT % (r = - 0.424, p < 0.001), negatively associated with FACIT-F score. Multivariate logistic regression analysis shows that older age, lower serum phosphorus, higher IMAT% are associated with a high risk of fatigue. CONCLUSION: The significantly increased incidence and degree of fatigue in hemodialysis patients is associated with more intermuscular adipose tissue in paraspinal muscle.

[Relation of serum Dickkopf-1 with bone destruction in patients with gouty arthritis].

OBJECTIVE: To explore the potential roles of serum Dickkopf-1 (DKK-1) and tartrate-resistant acid phosphatase 5b (TRAP5b) in gouty arthritis. METHODS: Blood serum DKK-1 and TRAP5b were assessed by ELISA method. The serum samples were collected from 150 patients with gouty arthritis, 100 with hyperuricemia and 100 healthy controls. Of the 150 gouty arthritis patients, 40 were diagnosed as acute gout (joint rash and pain), and the other 110 as chronic gout. At the time of serum sampling, various clinical and laboratory parameters were assessed. The correlations of DKK-1 or TRAP5b and clinical/laboratory parameters were analyzed. RESULTS: (1) The serum levels of DKK-1 were elevated in the patients with gouty arthritis [(2 574.8± 997.9) ng/L] and with hyperuricemia [(2 009.4±756.9) ng/L] compared with the healthy controls [(981.8±770.7) ng/L],F=49.59, P<0.001. (2) The serum levels of TRAP5b in the three groups were (3.2±1.4)U/L, (2.5±1.4)U/L and (0.2±0.2)U/L, respectively. F=103.039, P<0.001. (3) A significant difference of DKK-1 was observed between the patients with gouty arthritis and with hyperuricemia (t=3.998, P<0.001). Similarly, a significant difference of TRAP5b was observed between the patients with gouty arthritis and with hyperuricemia(t=3.391, P=0.004). (4) In the patients with gouty arthritis, there was a positive correlation between DKK-1 and TRAP5b(r=0.47, P<0.001), while the levels of DKK-1 were not related with age, disease duration, body mass index or serum uric acid(r=-0.153, -0.123, 0.158, 0.00,P=0.126, 0.509, 0.381, 0.926). (5) In the patients with gouty arthritis, the serum levels of TRAP5b were elevated in the patients with tophi compared with the patients without tophi[(8.4±6.4)U/L vs. (4.0±1.6)U/L,t=-2.938,P=0.007]. The level of TRAP5b was associated with the disease duration(r=0.455,P=0.01), while there was no correlation between TRAP5b and age, body mass index or serum uric acid (r=0.135, 0.278, 0.144,P=0.595, 0.117,0.132). CONCLUSION: In the patients with gouty arthritis, the levels of DKK-1 were remarkably elevated, and there was a positive correlation between DKK-1 and TRAP5b. Our results demonstrate that DKK-1 is involved in bone destruction in gouty arthritis.

[A multicenter study of coronary artery disease and its risk factors in rheumatoid arthritis in China].

OBJECTIVE: To learn about the prevalence and risk factors of coronary artery disease (CAD) in rheumatoid arthritis (RA). METHODS: Data were obtained from a 12-month retrospective investigation of the patients with RA, randomly selected from Departments of Rheumatology and Immunology in 21 big hospitals in China. The data were collected about their social conditions, clinical conditions, medications associated with RA, such as disease modifying anti-rheumatic drugs (DMARDs), non steroidal anti-inflammatory drugs (NSAIDs), glucocorticoid, biologic agents. A nonparameter test and multivariate logistic regression analysis were performed. RESULTS: In the study, 960 patients were enrolled. The prevalence of CAD was 3.5% in China, which was obviously higher than that of normal people. The prevalence of overweight and obesity, smoking, hypertension, diabetes mellitus, hypercholesterolemia and cerebrovascular disease were 35.1%, 12.3%, 17.0%, 7.7%, 0.4% and 3.0%, respectively. Compared with the control group, the CAD group had higher age [(64.7±9.3) years vs. (52.3±14.0) years,P<0.001], more rheumatoid nodules (14.7% vs. 3.1%,P=0.005), lower rate of hydroxychloroquine (HCQ) use (5.9% vs. 22.6%,P=0.021), higher prevalence rates of lung interstitial disease (17.5% vs. 7.0%,P<0.001), diabetes mellitus and hypertension (29.4% vs. 7.0%,P<0.001; 38.2% vs. 16.2%,P=0.001). There was no obvious correlation of CAD in RA with joint deformity, rheumatoid factor (RF) titer, glucocorticoid use, hypercholesterolemia and body mass index (BMI). Multivariate analysis showed higher age, diabetes mellitus and hypertension were independent predictors of CAD, and the use of HCQ was a protective factor of CAD. CONCLUSION: The prevalence of CAD is 3.5%. Higher age, diabetes mellitus and hypertension are independent predictors of CAD, and the use of HCQ is a protective factor of CAD.

[Survey of tumor necrosis factor inhibitors application in patients with rheumatoid arthritis in China].

OBJECTIVE: To investigate the current status of tumor necrosis factor (TNF) inhibitors application in rheumatoid arthritis (RA) patients in China and to analyze the related factors. METHODS: A retrospective survey was conducted in 21 hospitals from different parts of China. The patients with RA were randomly enrolled. Data of their social backgrounds, clinical conditions, usage and adverse effects of TNF inhibitors were collected. The costs of TNF inhibitors and the indirect costs of the disease were calculated. A multivariate Logistic regression analysis was performed to analyze the factors related to TNF inhibitors application. RESULTS: In the study, 1 095 RA patients from July 2009 to November 2010 were enrolled, of whom 112 had received TNF inhibitors, representing 10.2% of the total patients. The patients who received etanercept and infliximab were 7.4% (86/1 095) of the patients and 2.4% (26/1 095), respectively. There were 0.5% of the patients (5/1 095) who had received both of the TNF inhibitors. The patients who had accepted etanercept and treatment duration for less than 3 months and 3-6 months accounted for 38.5% and 25.0% respectively, while those treated with Infliximab were 38.1%. Their health assessment questionnaire (HAQ) scores were 1.1, 0.5 and 0.1, corresponding to treatment duration of infliximab for less than 3, 3-6 and 6-9 months and those were 1.3, 1.0, 0.3 corresponding to treatment duration of etanercept, respectively. Infliximab costs were RMB 24 525.0, 69 300.0 and 96 800.0 Yuan and etanercept costs were RMB 7 394.8, 9 158.6, 54 910.9 Yuan, respectively. Indirect costs for RA patients who accepted infliximab for less than 3, 3-6 and 6-9 months were RMB 365.6, 0 and 158.9 Yuan and those who accepted etanercept were RMB 2 158.4, 288.5 and 180.1 Yuan, respectively. Allergy and infection were the main side-effects of etanercept and both happened in 3.5% of all the patients. Liver damage happened in 2.3% of all the patients, while allergy and infection happened in 6.5% of all the patients who accepted infliximab. Logistic regression analysis showed that patients with higher education experience increased the odds of entering the TNF inhibitors group (OR: 1.292, 95%CI: 1.132-1.473, P=0.000). CONCLUSION: About one-tenth of RA patients in China have accepted TNF inhibitors. Higher education experience is the key factor for using TNF inhibitors.

[Sulphasalazine in patients with rheumatoid arthritis in China: a cross-sectional study].

OBJECTIVE: To investigate the medication status of rheumatoid arthritis (RA) patients and to analyze the clinical use of sulphasalazine (SSZ) and the adverse effect. METHODS: A total of 1 096 outpatients and inpatients diagnosed with RA were investigated in 21 hospitals all over China from July 2009 to December 2010, including gender, age of onset, clinical manifestations, as well as the clinical characteristics and medication status of 160 RA patients who received SSZ therapy. RESULTS: In the group of 160 patients who received SSZ, the male-to-female ratio was 1:7, The average age at onset was (46.1±15.0) years, while the average course was (9.9±7.8) years. The average dose of sulphasalazine was (1.87±0.52) g/d for a mean duration of (26.3± 14.6) months. Only 17% (27/160) of the patients received SSZ monotherapy. Methotrexate (63.1%), leflunomide (36.2%) and hydroxychloroquine (18.1%) were most commonly used combination drugs. And 36.2% (58/160) of the patients used the two-drug combination of methotrexate plus sulphasalazine .In this group, 41.9% (67/160) once used SSZ but withdrew for adverse events and other reasons, while 17.5% (28/160) withdrew for adverse events, of which the most common were gastrointestinal (8.8%), skin (3.8%) and liver toxicity (3.1%). CONCLUSION: Sulphaszlazine is not a common choice in the RA therapeutics in China, and the average dose of SSZ is lower than the standard dose of 2 to 3 g/d . The adverse events of SSZ are common; however, there are few severe adverse events or threat to life,SSZ is relatively safe in clinical practice.

[The effect of budesonide on thymic stromal lymphopoietin receptor and cytokine profile of dendritic cells in OVA-induced asthma in mice].

OBJECTIVE: To investigate the effect of budesonide (BUD) on thymic stromal lymphopoietin receptor (TSLPR) of dendritic cells (DCs) in OVA-induced mouse asthma models and to explore the mechanisms by studying the effect of BUD on function of DCs from the model. METHODS: Eighteen BALB/c female mice were randomly divided into a control group, an asthma group and a BUD intervention group, with 6 mice in each group. Mice were sensitized and challenged with ovalbumin (OVA) to establish the asthmatic model. The bronchoalveolar lavage fluid (BALF) and DCs of spleen from the 3 groups were harvested and the supernatants of BALF and DCs were analyzed for levels of TSLP and TSLPR, respectively, by commercially available ELISA kit. The percentage of eosinophils (EOS) in BALF was counted. The expression of CD40, CD80 and CD86 in DCs was detected by FACS. The DCs were then washed, and co-cultured in vitro with autologous T cells purified by a nylon cotton column. The supernatants of DC-T co-culture were collected after 72 h incubation, and analyzed for levels of interleukin-5 (IL-5) and interferon-γ (IFN-γ) by ELISA. RESULTS: The levels of TSLP in BALF and TSLPR in DCs from the asthma group were significantly increased compared with the control group [(44.0 ± 5.1) ng/L vs (14.2 ± 3.6) ng/L, P < 0.01 and (19.7 ± 2.2) ng/L vs (10.4 ± 1.2) ng/L, P < 0.05, respectively]. The expression of CD40, CD80 and CD86 of DCs and IL-5 in the culture supernatants of DC-T co-culture was significant up-regulated in the asthma group compared with the control group (P < 0.05). Furthermore, the addition of BUD reduced the expression of CD40, CD80, CD86, TSLPR in DCs, IL-5 in the culture supernatants of DC-T co-culture, TSLP and EOS in BALF. The level of INF-γ in the DC-T co-culture supernatants of the 3 groups did not achieve statistical significance (F = 0.82, P > 0.05). CONCLUSION: These results demonstrate that the therapeutic activity of BUD in asthmatic mice may be related to modulation of Th1 and Th2 cell functions and this effect is probably mediated through the TSLP-DC pathway.

Factors associated with the outcome of life-threatening necrotizing pneumonia due to community-acquired Staphylococcus aureus in adult and adolescent patients.

BACKGROUND: Although community-acquired Staphylococcus aureus pneumonia with highly virulent Panton-Valentine leukocidin (PVL)-positive strains, a severe disease with significant lethality, is rare, especially in adult and adolescent patients, recent reports highlight that these infections are on the rise. OBJECTIVES: To describe the demographic and clinical features of reported cases of life-threatening community-acquired S. aureus pneumonia with usually PVL-positive strains in adult and adolescent patients, to evaluate the variables related to death, and to select a more appropriate antimicrobial treatment for this potentially deadly disease. METHODS: We summarized all of the 92 reported cases and our case. The effect of 5 variables on mortality was measured using logistic regression. RESULTS: S. aureus community-acquired pneumonia (CAP) with usually PVL-positive strains is a severe disease with significant lethality, i.e. 42.9%; a short duration of the time from the onset of symptoms to death, i.e. 5.5 ± 10.1 days, and prolonged hospital admissions, i.e. 33.2 ± 29.5 days. Seventy-three cases have been tested for the gene for PVL, and 71 strains have been found to carry the PVL gene. Logistic regression analysis showed that leucopenia (p = 0.002), influenza-like symptoms or laboratory-confirmed influenza (p = 0.011), and hemoptysis (p = 0.024) were the factors associated with death. Antibiotic therapies inhibiting toxin production were associated with an improved outcome in these cases (p = 0.007). CONCLUSIONS: Physicians should pay special attention to those patients who acquired severe CAP during influenza season and have flu-like symptoms, hemoptysis, and leucopenia, and they should consider S. aureus more frequently among the possible pathogens of severe CAP. Empiric therapy for severe CAP with this distinct clinical picture should include coverage for S. aureus. Targeted treatment with antimicrobials inhibiting toxin production appears to be a more appropriate selection.

Linear Correlation between Water Adsorption Energies and Volta Potential Differences for Metal/water Interfaces.

Potential of zero charge (PZC) is an important reference for understanding the interface charge and structure at a given potential, and its difference from the work function of metal surface (ΦM) is defined as the Volta potential difference (ΔΦ). In this work, we model 11 metal/water interfaces with ab initio molecular dynamics. Interestingly, we find ΔΦ is linearly correlated with the adsorption energy of water (Eads) on the metal surface. It is revealed that the size of Eads directly determines the coverage of chemisorbed water on the metal surface and accordingly affects the interface potential change caused by electron redistribution (ΔΦel). Moreover, ΔΦ is dominated by the electronic component ΔΦel with little orientational dipole contributing, which explains the linear correlation between ΔΦ and Eads. Finally, it is expected that this correlation can be helpful for effectively estimating the ΔΦel and PZC of other metal surfaces in the future work.

Glutamine promotes antibiotic uptake to kill multidrug-resistant uropathogenic bacteria.

The prevalence of multidrug-resistant bacteria has been increasing rapidly worldwide, a trend that poses great risk to human and animal health and creates urgent need for pharmaceutical and nonpharmaceutical approaches to stop the spread of disease due to antimicrobial resistance. Here, we found that alanine, aspartate, and glutamate metabolism was inactivated, and glutamine was repressed in multidrug-resistant uropathogenic Escherichia coli using a comparative metabolomics approach. Exogenous glutamine promoted ß-lactam­, aminoglycoside-, quinolone-, and tetracycline-induced killing of uropathogenic E. coli and potentiated ampicillin to eliminate multidrug-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella peneumoniae, Edwardsiella tarda, Vibrio alginolyticus, and Vibrio parahaemolyticus. Glutamine-potentiated ampicillin-mediated killing was effective against biofilms of these bacteria in a mouse urinary tract infection model and against systemic infection caused by E. coli, P. aeruginosa, A. baumannii, or K. peneumoniae in a mouse model. Exogenous glutamine stimulated influx of ampicillin, leading to the accumulation of intracellular antibiotic concentrations that exceeded the amount tolerated by the multidrug-resistant bacteria. Furthermore, we demonstrated that exogenous glutamine promoted the biosynthesis of nucleosides including inosine, which in turn interacted with CpxA/CpxR and up-regulated OmpF. We validated the physiological relevance of the mechanism by showing that loss of purF, purH, cpxA, or ompF elevated antibiotic resistance in antibiotic-sensitive strains. In addition, glutamine retarded the development of ampicillin resistance. These results may facilitate future development of effective approaches for preventing or managing chronic, multidrug-resistant bacterial infections, bacterial persistence, and difficult-to-treat bacterial biofilms.

[Analysis of risk factors related to mortality of patients with community-acquired pneumonia due to methicillin-resistant Staphylococcus aureus].

OBJECTIVE: To describe the clinical features of reported cases of community-acquired pneumonia (CAP) due to methicillin-resistant Staphylococcus aureus (MRSA), and to evaluate the risk factors related to outcome. METHODS: A systematic search of databases from January 1995 to December 2009 was performed. Baseline characteristics of survivors and non-survivors in the hospital were compared with the chi2 test for categorical variables. Variables with P<0.2 were entered in Logistic regression. Survival analysis was estimated by the Kaplan-Meier method according to use of antimicrobials inhibiting toxin production. RESULTS: Fifty-two articles were identified reporting data on 74 patients, with 41.1% of total mortality, short duration of symptom onset to death [(6.1+/-11.0) days], and prolonged hospital admissions [(28.6+/-29.1) days]. Logistic regression analysis showed that influenza like symptoms (P=0.04), hemoptysis (P<0.01), leucopenia (P<0.01) were the risk factors associated with death, and using clindamycin or linezolid which could inhibit the Panton-Valentine leukocidin (PLV, P<0.01) was the factor associated with survival. Kaplan-Meier analysis indicated that the antibiotic therapies inhibiting toxin production were associated with improved outcome in these cases (chi2=21.59, P<0.01). CONCLUSION: CAP due to MRSA is a severe disease with significant lethality. Empiric therapy of severe CAP with flu-like symptoms, hemoptysis and leucopenia should include coverage for MRSA. Targeted treatment with antimicrobials inhibiting toxin production appear to be more appropriate selection.

[Pulmonary nocardiosis in immunocompromised host: report of 2 cases and review of the literature].

OBJECTIVE: To investigate the clinical, imaging and pathogenic features of pulmonary nocardiosis and the drug resistance of Nocardia. METHODS: The clinical and radiological data of 2 cases of pulmonary nocardiosis in this hospital were presented, and 32 cases reported in the Chinese literature since 1982 were reviewed. RESULTS: Among the 34 cases of Nocardia infections, there were 26 cases of pulmonary nocardiosis, and 4 of whom died. Multiple organ infection occurred in 11 patients, including 7 with pulmonary and skin infections, 3 with pulmonary, skin and intracranial infections, and 1 with pulmonary and intracranial infections. All patients with pulmonary nocardiosis had cough. Of the 34 cases, 27 had fever, including intermittent fever in 5, and sustained fever in 22 cases. Of the 11 cases of pulmonary nocardiosis complicated with skin or intracranial dissemination, 8 patients were immunocompromised and 3 were immunocompetent (chi(2) = 2.08, P > 0.05). Three cases died in the immunocompromised group and 1 died in the immunocompetent group. Nocardia asteroides was identified in 14 cases, Nocardia brasiliensis in 4 cases, and the other 8 were not classified. In the patients with complicated skin or intracranial infections, 8 were caused by Nocardia asteroids, and 2 were caused by Nocardia brasiliensis. Chest X-ray or CT imaging of the lungs showed pleural effusion in 8, masses in 7, infiltrates in 6, cavities in 6, and nodular lesions in 5 cases. Antimicrobial susceptibility testing showed that Nocardia was sensitive to sulfonamide, amikacin, cefotaxime, ceftriaxone, minocycline, fluoroquinolones, and linezolid. CONCLUSIONS: Immunosuppression is the most important predisposing factor for pulmonary nocardiosis. The most common pathogenic bacterium is Nocardia asteroids, which is frequently associated with disseminated lesions. The radiographic abnormalities of the lung show pleural effusion, masses, infiltration or cavity. With the increasing rate of resistance of Nocardia to the sulfonamide, the combination of antibiotic regimen according to susceptibility testing needs to be considered. Poor outcome is mostly found in immunocompromised hosts.

Differences in microbial etiology between hospital-acquired pneumonia and ventilator-associated pneumonia: a single-center retrospective study in Guang Zhou.

Purpose: Nosocomial pneumonia is a common nosocomial infection that includes hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia(VAP). It is an important cause of morbidity and mortality in hospitalized patients. This study aimed to evaluate the differences in microbial etiology and outcomes between HAP and VAP, particularly in related risk factors of multidrug-resistant organism (MDRO) causing HAP and VAP. Patients and methods: This single-center retrospective, observational study included patients with HAP/VAP. Clinical and epidemiological data of nosocomial pneumonia confirmed by microbial etiology that occurred in the Third Affiliated Hospital of Sun Yat-sen University, China, from January 2014 to December 2017 were obtained. Results: A total of 313 HAP cases and 106 VAP cases were included. The leading pathogens of HAP and VAP were similar, including Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Antimicrobial susceptibility of the pathogens was low, and P. aeruginosa in VAP was less susceptible. In the multivariate logistic regression analysis, the risk factors associated with MDRO-HAP were chronic obstructive pulmonary disease, antibiotic therapy in the preceding 90 days, and prior endotracheal tracheostomy. The risk factor of MDRO-VAP was ≥5 days of hospitalization. The 30-day mortality rates of HAP and VAP were 18.5% and 42.5%. Conclusion: The leading pathogens were similar in both HAP and VAP, and antimicrobial susceptibility of the pathogens was low. The risk factors associated with MDRO infection in HAP and VAP have significant variability; hence, attention should be paid to improve prognosis. VAP was associated with poorer outcomes compared with HAP.

Glycine, serine and threonine metabolism confounds efficacy of complement-mediated killing.

Serum resistance is a poorly understood but common trait of some difficult-to-treat pathogenic strains of bacteria. Here, we report that glycine, serine and threonine catabolic pathway is down-regulated in serum-resistant Escherichia coli, whereas exogenous glycine reverts the serum resistance and effectively potentiates serum to eliminate clinically-relevant bacterial pathogens in vitro and in vivo. We find that exogenous glycine increases the formation of membrane attack complex on bacterial membrane through two previously unrecognized regulations: 1) glycine negatively and positively regulates metabolic flux to purine biosynthesis and Krebs cycle, respectively. 2) α-Ketoglutarate inhibits adenosine triphosphate synthase, which in together promote the formation of cAMP/CRP regulon to increase the expression of complement-binding proteins HtrE, NfrA, and YhcD. The results could lead to effective strategies for managing the infection with serum-resistant bacteria, an especially valuable approach for treating individuals with weak acquired immunity but a normal complement system.

[Clinical analysis of community-acquired pneumonia in the elderly].

OBJECTIVES: To evaluate the clinical features, etiology, and outcome of patients over 65 years old hospitalized for community-acquired pneumonia (CAP). METHODS: A retrospective cohort analysis was performed for adult patients hospitalized with CAP in a 1000-bed teaching hospital between Jan 2002 and Jan 2006. Differences between < or = 65 yrs and > 65 yrs groups were calculated using chi(2) test. RESULTS: A total of 302 patients (166 males), with a mean age of (68 +/- 21) yrs, were enrolled. Of the 216 elderly patients, 67.1% had comorbid conditions, mostly cardiovascular diseases and chronic obstructive lung disease. For the risk stratification, 175 patients were classified as IV - V according to Fine's index. The mean hospital stay was 12 days and in-hospital mortality was 12.0%. The most frequent pathogen was Streptococcus pneumoniae in elderly patients. As compared to 86 younger patients (< or = 65yrs), altered mental status, dyspnea, tachypnea and tachycardia on hospital admission were more frequent in the elderly. The etiological distribution was also different between the two groups. CONCLUSIONS: CAP in elderly patients is a prevalent disease with high incidence of complications and mortality. More attention should be paid to the specific clinical manifestations of this patient population.

[The action of active efflux system on multi-drug resistance in methicillin resistant Staphylococcus aureus].

OBJECTIVE: To study the active efflux gene qacB, qacJ and smr in methicillin resistant Staphylococcus aureus (MRSA) and to investigate their effect on the multi-drug resistance (MDR) of MRSA. METHODS: The three pairs of ideal primers of active efflux gene qacB, qacJ and smr were designed by computer with Primer Premier 5.0 software. A total of 124 clinical isolates of MRSA were amplified respectively by polymerase chain reaction (PCR) with above mentioned primers. The PCR products were separated by electrophoresis on an 1.5% agarose gel with 0.5 microg/ml ethidium bromide. Reserpine inhibition test was used to observe the changes of the susceptibility to antibiotics of MRSA which had qacB, qacJ and smr genes separately. RESULTS: Of the 124 strains of MRSA, 86 strains had qacB, 45 strains had qacJ and 32 strains had smr gene. Reserpine inhibition test showed that the minimal inhibitory concentration (MIC) decreased 2 to 32 times for MRSA to levofloxacin and rifampin. CONCLUSION: MRSA have qacB, qacJ and smr active efflux systems, which play a very important role in multiple antibiotic resistance.

Exogenous l-Valine Promotes Phagocytosis to Kill Multidrug-Resistant Bacterial Pathogens.

The emergence of multidrug-resistant bacteria presents a severe threat to public health and causes extensive losses in livestock husbandry and aquaculture. Effective strategies to control such infections are in high demand. Enhancing host immunity is an ideal strategy with fewer side effects than antibiotics. To explore metabolite candidates, we applied a metabolomics approach to investigate the metabolic profiles of mice after Klebsiella pneumoniae infection. Compared with the mice that died from K. pneumoniae infection, mice that survived the infection displayed elevated levels of l-valine. Our analysis showed that l-valine increased macrophage phagocytosis, thereby reducing the load of pathogens; this effect was not only limited to K. pneumoniae but also included Escherichia coli clinical isolates in infected tissues. Two mechanisms are involved in this process: l-valine activating the PI3K/Akt1 pathway and promoting NO production through the inhibition of arginase activity. The NO precursor l-arginine is necessary for l-valine-stimulated macrophage phagocytosis. The valine-arginine combination therapy effectively killed K. pneumoniae and exerted similar effects in other Gram-negative (E. coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. Our study extends the role of metabolism in innate immunity and develops the possibility of employing the metabolic modulator-mediated innate immunity as a therapy for bacterial infections.