Lysophosphatidylcholine acyltransferase level predicts the severity and prognosis of patients with community-acquired pneumonia: a prospective multicenter study.

Background: Identifying the diagnosis as well as prognosis for patients presented with community-acquired pneumonia (CAP) remains challenging. We aimed to identify the role of lysophosphatidylcholine acyl-transferase (LPCAT) for CAP along with assessing this protein's effectiveness as a biomarker for severity of disease and mortality. Methods: Prospective multicenter research study was carried out among hospitalized patients. A total of 299 CAP patients (including 97 severe CAP patients [SCAP]) and 20 healthy controls (HC) were included. A quantitative enzyme-linked immunosorbent test kit was employed for detecting the LPCAT level in plasma. We developed a deep-learning-based binary classification (SCAP or non-severe CAP [NSCAP]) model to process LPCAT levels and other laboratory test results. Results: The level of LPCAT in patients with SCAP and death outcome was significantly higher than that in other patients. LPCAT showed the highest predictive value for SCAP. LPCAT was able to predict 30-day mortality among CAP patients, combining LPCAT values with PSI scores or CURB-65 further enhance mortality prediction accuracy. Conclusion: The on admission level of LPCAT found significantly raised among SCAP patients and strongly predicted SCAP patients but with no correlation to etiology. Combining the LPCAT value with CURB-65 or PSI improved the 30-day mortality forecast significantly. Trial registration: NCT03093220 Registered on March 28th, 2017.

Proteomics Study of the Synergistic Killing of Tigecycline in Combination With Aminoglycosides Against Carbapenem-Resistant Klebsiella pneumoniae.

Co-administration of antibiotics with synergistic effects is one method to combat carbapenem-resistant organisms. Although the synergistic effects of tigecycline combined with aminoglycosides against carbapenem-resistant Klebsiella pneumoniae (CRKP) have been demonstrated in vitro and in animal models, the underlying mechanism remains elusive. Here we used proteomics analysis to assess the short-term bacterial responses to tigecycline and aminoglycosides alone or in combination. Emergence of tigecycline resistance during treatment and the susceptibility of tigecycline-resistant strains to aminoglycosides was further evaluated. The proteomic responses to tigecycline and aminoglycosides were divergent in monotherapy, with proteomic alterations to combination therapy dominated by tigecycline. Adaptive responses to tigecycline were associated with the upregulation of oxidative phosphorylation and translation-related proteins. These responses might confer CRKP hypersensitivity towards aminoglycosides by increasing the drug uptake and binding targets. Meanwhile, tigecycline might perturb adaptive responses to aminoglycosides through inhibition of heat shock response. Tigecycline-resistant strains could be isolated within 24 h exposure even in strains without heteroresistance, and the sensitivity to aminoglycosides significantly increased in resistant strains. Overall, these findings demonstrated that adaption to tigecycline in CRKP was a double-edged sword associated with the synergistic killing in tigecycline-aminoglycoside combination. Evolutionary hypersensitivity can provide novel insight into the mechanisms of antibiotic synergistic effects.

Effective Method of Estimating the Daily Evapotranspiration of Greenhouse Grapes in the Cold Area of Northeast China.

Evapotranspiration (ET) is an important basis and key link for guiding irrigation. One of the key problems to be solved is how to predict the dynamic change in the daily ET and estimate the total amount of ET in greenhouse through limited instantaneous data. In this paper, it is estimated that the daily scale of evapotranspiration by using four methods, including the evaporative fraction method (EF method), the reference evaporative fraction method (EF' method), the sine method, and the canopy resistance method (r c method), is based on the measured ET data of grapes in a solar greenhouse in Northeast China. The relative root-mean-square pair error (RRMSE) and the efficiency coefficient (ε) are also used to study their applicability in terms of leaf area index, radiation degree, and scale-up time point. In the results, under the condition of different LAI, the simulation accuracies of ET scaled by the four methods ranked as follows (from highest to lowest): the reference evaporative fraction method, the evaporative fraction method, the sine method, and the canopy resistance method. The average RRMSE and ε of the evaporative fraction method with the best simulation accuracy were 7.19-16.46% and 0.61-0.75, respectively. Under different radiation conditions, the simulation accuracies of the four methods ranked as follows (from highest to lowest): the evaporative fraction method, the reference evaporative fraction method, the sine method, and the canopy resistance method. Under different radiation conditions, the RRSME of the four methods ranged from 11.55 to 46.62%, and the maximum of ε was 0.75. The evaporative fraction and reference evaporative fraction methods had the highest simulation accuracy, whereas the reference evaporative fraction method required fewer parameters. We concluded that the reference evaporative fraction method was the best for estimating the daily ET of greenhouse grapes in the cold area of Northeast China.

Heteroresistance Is Associated With in vitro Regrowth During Colistin Treatment in Carbapenem-Resistant Klebsiella pneumoniae.

Polymyxins including polymyxin B and colistin (polymyxin E) are considered the last resort for treating infections caused by carbapenem-resistant gram-negative bacteria. However, in vitro regrowth with the emergence of resistance during treatment is common. Polymyxin heteroresistance, particularly in Acinetobacter baumannii and Klebsiella pneumoniae, has been widely reported. This study was primarily performed to evaluate the prevalence of colistin heteroresistance in carbapenem-resistant K. pneumoniae (CR-KP) and the association between in vitro regrowth and heteroresistance. The mechanisms of colistin resistance and the ability of combination therapies to suppress resistance selection were further investigated. A population analysis profile (PAP) analysis showed that 69 (71.9%) of 96 CR-KP strains had colistin heteroresistance. Time-kill assays revealed that the colistin monotherapy could quickly eliminate the bacterial cells in strains without heteroresistance within the first 6 h. Conversely, it could initially reduce the number of cells in heteroresistant strains, but then regrowth occurred rapidly. Resistance screening at 12 and 24 h in the time-kill assays indicated that susceptible populations were killed, and regrowth was the exact result of the continued growth of resistant subpopulations. Colistin resistance in the regrowth subpopulations was mainly due to the overexpression of phoPQ and pmrD. Colistin combined with tetracyclines (tigecycline or minocycline) or aminoglycosides (amikacin or gentamicin) could effectively suppress the resistance selection and significantly elicit in vitro synergistic effects. These findings suggested that the combination therapy can be used to treat infections caused by CR-KP with colistin heteroresistance. Nevertheless, further in vivo studies considering drugs pharmacokinetics/pharmacodynamics are needed to confirm these findings.