Monotherapy vs combination therapy in patients with Klebsiella pneumoniae bloodstream infection: A systematic review and meta-analysis.

OBJECTIVE: To determine whether mortality is lower in patients with Klebsiella pneumoniae bloodstream infection (BSI) who receive combination antimicrobial therapy than in those who receive monotherapy. METHODS: Two authors independently searched for relevant articles in the PubMed, Embase, Web of Science, and Cochrane Library databases through to August 10, 2023. Risk of bias was evaluated using the ROBINS-I tool. Possible sources of heterogeneity were evaluated by meta-regression using a mixed-effects model. RESULTS: Among 8044 articles screened, there were 23 studies (3443 patients) that were eligible for meta-analysis. Meta-regression analysis identified the proportion of patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) BSI to be a potential source of heterogeneity. Subgroup analysis showed that mortality on monotherapy was significantly higher when the proportion of patients with CRKP BSI was ≥50% (OR 1.75, 95% CI 1.33-2.30) and significantly lower when this proportion was <50% (OR 0.55, 95% CI 0.24-1.24). Overall mortality was significantly higher on tigecycline monotherapy (OR 2.86, 95% CI 1.46-5.59) than on combination therapy containing both these agents. There was a trend in favor of colistin/polymyxin B-containing combination therapy (OR 1.37, 95% CI 0.83-2.28). CONCLUSIONS: Combination antimicrobial therapy can lower mortality in patients with CRKP but may not show a survival advantage over monotherapy when the proportion of patients with CRKP BSI is <50%. High-quality prospective observational studies are needed because of the high risk of bias and limited data in the studies performed to date.

Bacterial distinctions in practical rural sewage collection systems caused by the location, season, and system type.

Bacteria in rural sewage collection systems have the important influences on operation and maintenance risks, such as sedimentation blockage and harmful gas accumulation, and pollutant pre-treatment ability. It is necessary to analyze and interpret the influence on bacterial communities caused by the location (sewage, biofilms, and deposits), season (winter and spring, summer and autumn), and system type (sewers and ditches) to better understand the bacterial characteristics in rural sewage collection systems. To achieve the above purpose, 96 samples obtained from practical rural sewage collection systems in eight villages were analyzed by 16S rRNA whole region sequencing methods. The results indicate that locations and seasons caused significant influences on the overall bacterial communities, which were mainly affected by temperature, sewage quality and bacterial survival preference, and 13 genera of sulfate-reducing bacteria (SRB), 2 genera of ammonia-oxidizing bacteria (AOB), 2 genera of nitrite-oxidizing bacteria (NOB), and 9 genera of water-related pathogenic bacteria (WPB) were detected in rural sewage collection systems. SRB, AOB, NOB, and WPB tended to inhabit in biofilms or deposits rather than in sewage. The total relative abundance of SRB in summer and autumn (∼2.19%) was higher than in winter and spring (∼0.41%), and the WPB distribution in different seasons showed significant distinction. Additionally, some of SRB, AOB, NOB, and WPB also showed significant differences in sewers and ditches. Overall, this study provided a deeper understanding of bacteria in rural sewage collection systems and could further provide the basic parameter for the operation and maintenance risk control.

Blapsimidazolium A: A new imidazolium carboxylate derivative with anti-inflammatory activity from medicinal insect Blaps rynchopetera.

Blaps rynchopetera Fairmaire is a medicinal insect of Yi-nationality medicine used for a long time in Yunnan, China. In the present study, a new blapsimidazolium A (1), together with twelve known N-containing compounds (2-13), were isolated from this insect. The structures were elucidated by extensive spectroscopic analyses (1D and 2D NMR, HR-MS) and comparisons with the reported literature. Blapsimidazolium A was identified as racemic mixture by optical rotation and chiral analysis. Blapsimidazolium A (1) has a unique architecture containing an imidazolium carboxylate moiety. The results of molecular docking showed that blapsimidazolium A bound well to IL-1ß, IL-6 and iNOS. The racemates of (±)-blapsimidazolium A (1) exerted anti-inflammatory activity in LPS-stimulated THP-1 cells by significantly decreasing the production of the proinflammatory cytokines IL-1ß, IL-6 and iNOS. This is the first report describing the anti-inflammatory activity of this type imidazolium carboxylate derivative.

Advances in Bone Turnover Markers (PINP and CTX) in Optimizing Anti-resorptive and Anabolic Therapies Against Osteoporosis.

Osteoporosis has been a major health problem for many elderly people and postmenopausal women with poor prognosis. Bone turnover markers (BTMs) reflecting bone metabolisms are applied to evaluating clinical results and monitoring of compliance in anti-resorptive and anabolic therapy for osteoporosis. The numerical changes and clinical significance of BTMs in two therapies are summarized and the practical application and potential value of PINP and CTX as therapeutic target, threshold of follow-up therapy, and evaluation of fracture risk in different regimes such as bisphosphonates, denosumab, raloxifene, teriparatide, abaloparatide, and romosozumab are reviewed in this paper. The application of BTMs is expected to improve the efficacy of the treatments and reduce the rate of osteoporotic fracture in clinical practice.

Cytotoxicity of the Defensive Secretion from the Medicinal Insect Blaps rynchopetera.

Blaps rynchopetera Fairmaire has long been used as a folk medicine by the Yi and Bai ethnic groups in China to treat fever, cough, gastritis, boils, and tumors. In the present study, the cytotoxicity of the defensive secretion (TDS) of B. rynchopetera against AGS Caco-2, HepG2 U251 and Bel-7402 was tested, and the results revealed that TDS had potent cytotoxicity against testing cells with IC50 values of 45.8, 17.4, 53.6, 98.4 and 23.4 µg/mL, respectively. Gas chromatography-mass spectrometry (GC-MS) analysis was employed to clarify the cytotoxic constituents in TDS of B. rynchopetera and five volatile compounds, including 2-ethyl-2,5-cyclohexadiene-1,4-dione (3, 31.00%), 1-tridecene (5, 28.02%), 2-methyl-2,5-cyclohexadiene-1,4-dione (2, 22.86%), hydroquinone (4, 1.33%), and p-benzoquinone (1, 1.01%), were identified. Chemical constituent investigation on TDS further supported the presence of 5 above compounds. A cytotoxic assay indicated that compounds 1, 2, 3 and 4 exhibited significant cytotoxicity against the testing cell lines, implying that benzoquinones and hydroquinone played important roles in the cytotoxicity of TDS of B. rynchopetera. TDS is a cytotoxic natural material and further studies investigating mechanisms and inhibitory activities on other cell lines is warranted.

Five New Phenolic Compounds with Antioxidant Activities from the Medicinal Insect Blaps rynchopetera.

Five new phenolic compounds rynchopeterines A-E (1-5), in addition to thirteen known phenolics, were isolated from Blaps rynchopetera Fairmaire, a kind of medicinal insect utilized by the Yi Nationality in Yunnan Province of China. Their structures were established on the basis of extensive spectroscopic analyses (1D and 2D NMR, HR-MS, IR) along with calculated electronic circular dichroism method. Rynchopeterines A-E (1-4) exhibited significant antioxidant activities with IC50 values of 7.67-12.3 µg/mL measured by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Besides, rynchopeterines B (2) and C (3) showed mild cytotoxicity against tumor cell Caco-2 and A549.

[Two New Abietane Type Diterpenes from Pinecones of Pinus griffithii].

Objective: To study the chemical constituents from the pinecones of Pinus griffithii. Methods: The constituents were separated and purified with chromatographic methods,and spectroscopic analysis were employed for structural elucidation. Results: Two new abietane type diterpenes and seven known compounds were isolated from the pinecones of Pinus griffithii,and were identified as 15-hydroxy-7α-methoxy-abiet-8,11,13-trien-18-oic acid( 1),7α,13-dihydroxy-podocarpane-8,11,13-trien-18-oic acid( 2),7,12,13,15-tetrahydroxy-abiet-8( 14)-en-18-oic acid( 3),7ß,15-dihydroxy-abiet-8,11,13-trien-18-oic acid( 4),18-norabiet-8,11,13-trien-4,7,15-triol( 5),15-hydroxy-abiet-8,11,13-trien-18-oic acid( 6),7α-hydroxy-15-methoxy-abiet-8,11,13-trien-18-oic acid( 7),7α-hydroxypodocarpen-8( 14)-en-13-one-18-oic acid( 8), oleanolic acid( 9). Conclusion: Compounds 1,2 are the new abietane type diterpene,and all compounds are isolated from this plant for first time.