Evaluation of the Short-Term Effects of Antimicrobial Stewardship in the Intensive Care Unit at a Tertiary Hospital in China

<div><p>Antibiotic abuse can lead to antibiotic resistance, which is a severe problem in China. The purpose of this study is to evaluate the short-term effects of antimicrobial stewardship strategies, including formulary restriction, preauthorization, perioperative quinolone restriction, and control of total antibiotic consumption in the ICU at a tertiary hospital in China. After implementation of antimicrobial stewardship, the total antibiotic consumption in the ICU significantly decreased. The defined daily doses (DDDs) per 100 patient-days decreased from 197.65 to 143.41; however, the consumption of cephalosporins increased from 53.65 to 63.17 DDDs. Significant improvements in resistance to amikacin, gentamicin, ciprofloxacin, ofloxacin, ceftriaxone, ceftazidime, and piperacillin in Enterobacteriaceae and resistance to ceftazidime, imipenem, and meropenem in non-fermenting Gram-negative rods were observed. In addition, the initial use of no antibiotics or of a single antibiotic significantly increased (P<0.001) and the use of two antibiotics in combination significantly decreased (P<0.001). Our results demonstrate that implementation of antimicrobial stewardship in a short period in the ICU dramatically reduced antibiotic consumption and significantly improved antibiotic resistance, which leads to more reasonable antibiotic selections by ICU physicians.</p></div

Changes of percentage of bacterial isolates with antibiotic resistance (%) after antimicrobial stewardship.

<p>Changes of percentage of bacterial isolates with antibiotic resistance (%) after antimicrobial stewardship.</p

Self [3 + 4] Cycloadditions of Isatin <i>N</i>,<i>N</i>′‑Cyclic Azomethine Imine 1,3-Dipole with <i>N</i>‑(<i>o</i>‑Chloromethyl)aryl Amides

A [3 + 4] annulation of isatin <i>N</i>,<i>N</i>′-cyclic azomethine imine 1,3-dipole <b>1</b> with in situ-generated aza-oQMs has been established for the synthesis of spirooxindole seven-membered scaffolds. These highly functionalized scaffolds were assembled in moderate to good yields (up to 96% yield). The novel spirooxindole scaffolds displayed moderate antitumor activities, which represented promising lead compounds for antitumor drug discovery

Comparison of the ICU physicians' initial antibiotic selection before and after antimicrobial stewardship.

<p>Initial antibiotic combination therapy in ‘before’ and ‘after’ period: χ² = 217.924, P<0.001.</p>1<p>Before antimicrobial stewardship, χ² = 3.339, P = 0.297.</p>2<p>After antimicrobial stewardship, χ² = 8.487, P = 0.012.</p

Self [3 + 4] Cycloadditions of Isatin <i>N</i>,<i>N</i>′‑Cyclic Azomethine Imine 1,3-Dipole with <i>N</i>‑(<i>o</i>‑Chloromethyl)aryl Amides

A [3 + 4] annulation of isatin <i>N</i>,<i>N</i>′-cyclic azomethine imine 1,3-dipole <b>1</b> with in situ-generated aza-oQMs has been established for the synthesis of spirooxindole seven-membered scaffolds. These highly functionalized scaffolds were assembled in moderate to good yields (up to 96% yield). The novel spirooxindole scaffolds displayed moderate antitumor activities, which represented promising lead compounds for antitumor drug discovery

Flow chart of antimicrobial stewardship strategies applied in the ICU at a tertiary hospital in China.

<p>These strategies primarily included formulary restriction, preauthorization, perioperative quinolone restriction, and control of total antibiotic consumption.</p

Antihyperlipidaemic effect of triterpenic acid-enriched fraction from <i>Cyclocarya paliurus</i> leaves in hyperlipidaemic rats

<p><b>Context:</b><i>Cyclocarya paliurus</i> (Batal) Iljinskaja (Juglandaceae) is an edible and medicinal plant; the leaves are used in Chinese folkloric medicine to treat dyslipidaemia and diabetes.</p> <p><b>Objective:</b> This study evaluates the antihyperlipidaemic potential of the triterpenic acid-enriched fraction (TAE) from <i>C. paliurus</i> and the underlying mechanism.</p> <p><b>Materials and methods:</b> The hyperlipidaemic rats were induced by high fat diet for 6 weeks. After oral administration of TAE (200 and 400 mg/kg), the neutral fraction (150 and 300 mg/kg) and statin (4 mg/kg) to the hyperlipidaemic rats for 4 weeks, lipid profile and apolipoprotein (apoB48) level in plasma, and the expression levels of apoB48, microsomal triglyceride transfer protein (MTP), phosphorylation of mitogen-activated protein kinase (MAPK) and tumour necrosis factor α (TNF-α) in intestine were examined. The main constituents in the TAE were identified by HPLC-MS.</p> <p><b>Results:</b> TAE administration (400 mg/kg) decreased the levels of atherogenic lipids in serum and liver (<i>p</i> < 0.05) and increased serum high-density lipoprotein cholesterol by 19.7%. Furthermore, TAE treatment (200 and 400 mg/kg) decreased plasma apoB48 level by 15.3 and 19.5%, downregulated intestinal apoB48 and MTP expression levels (<i>p</i> < 0.05), and inhibited TNF-α expression by 36.2 and 56.2% and the phosphorylation level of MAPK by 8.8 and 13.2%, respectively. HPLC analysis revealed the presence of pentacyclic- and tetracyclic-triterpene acids in TAE.</p> <p><b>Conclusion and discussion:</b> These findings suggested that TAE possessed antihyperlipidaemic activity partially involved in the inhibitory effect on apoB48 overproduction, which may provide evidence about its potential role in ameliorating dyslipidaemia.</p

Radiolabeled Rhein as Small-Molecule Necrosis Avid Agents for Imaging of Necrotic Myocardium

A rapid and accurate identification of necrotic myocardium is of great importance for diagnosis, risk stratification, clinical decision-making, and prognosis evaluation of myocardial infarction. Here, we explored technetium-99m labeled rhein derivatives for rapid imaging of the necrotic myocardium. Three hydrazinonicotinic acid-linker-rhein (HYNIC-linker-rhein) derivatives were synthesized, and then, these synthetic compounds were labeled with technetium-99m using ethylenediaminediacetic acid (EDDA) and tricine as coligands [^99mTc­(EDDA)-HYNIC-linker-rhein]. The necrosis avidity of the three ^99mTc-labeled rhein derivatives was tested in a mouse model of ethanol-induced muscular necrosis by gamma counting, histochemical staining, and autoradiography. A lead tracer for visualization of necrotic myocardium was assessed by single photon emission computed tomography/computed tomography (SPECT/CT) imaging in a rat model with reperfused myocardial infarction. The necrosis avidity mechanism of the tracer was explored by DNA binding studies <i>in vitro</i> and blocking experiments <i>in vivo</i>. Results showed that the uptake in necrotic muscles of the three ^99mTc-compounds was higher than that in viable muscles (<i>P</i> < 0.001). Autoradiography and histochemical staining results were consistent with selective uptake of the radiotracer in the necrotic regions. Among the these tracers, ^99mTc­(EDDA)-HYNIC-ethylenediamine-rhein [^99mTc­(EDDA)-HYNIC-2C-rhein] displayed the best distribution profiles for imaging. The necrotic myocardium lesions were clearly visualized by SPECT/CT using ^99mTc­(EDDA)-HYNIC-2C-rhein at 1 h after injection. The necrotic-to-viable myocardium and necrotic myocardium-to-blood uptake ratios of ^99mTc­(EDDA)-HYNIC-2C-rhein were 4.79 and 3.02 at 1 h after injection. DNA binding studies suggested HYNIC-linker-rhein bound to DNA through intercalation. The uptake of ^99mTc­(EDDA)-HYNIC-2C-rhein in necrotic muscle was significantly blocked by excessive unlabeled rhein, with 77.61% decline at 1 h after coinjection. These findings suggested ^99mTc­(EDDA)-HYNIC-2C-rhein emerged as a “hot spot” imaging probe that has a potential for rapid imaging of necrotic myocardium. The necrosis avidity mechanism of ^99mTc­(EDDA)-HYNIC-linker-rhein may be due to its interaction with exposed DNA in necrotic tissues

Effects of skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones

<p>Necrosis avid agents (NAAs) can be used for diagnose of necrosis-related diseases, evaluation of therapeutic responses and targeted therapeutics of tumor. In order to probe into the effects of molecular skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones, four dianthrone compounds with the same substituents but different skeletal structures, namely Hypericin (Hyp), protohypericin (ProHyp), emodin dianthrone mesomer (ED-1) and emodin dianthrone raceme (ED-2) were synthesized and radioiodinated. Then radioiodinated dianthrones were evaluated <i>in vitro</i> for their necrosis avidity in A549 lung cancer cells untreated and treated with H₂O₂. Their biodistribution and pharmacokinetic properties were determined in rat models of induced necrosis. <i>In vitro</i> cell assay revealed that destruction of rigid skeleton structure dramatically reduced their necrosis targeting ability. Animal studies demonstrated that destruction of rigid skeleton structure dramatically reduced the necrotic tissue uptake and speed up the clearance from the most normal tissues for the studied compounds. Among these ¹³¹I-dianthrones, ¹³¹I-Hyp exhibited the highest uptake and persistent retention in necrotic tissues. Hepatic infarction could be clearly visualized by SPECT/CT using ¹³¹I-Hyp as an imaging probe. The results suggest that the skeleton structure of Hyp is the lead structure for further structure optimization of this class of NAAs.</p

Biodistribution and anti-tumor efficacy of intratumorally injected necrosis-avid theranostic agent radioiodinated hypericin in rodent tumor models

<div><p></p><p>Hypericin has an excellent necrosis-specific targeting capacity; thus, we explored small-molecular tumor necrosis therapy (SMTNT) for inhibiting tumor growth in rodent tumor models. H22 and S180 tumor-bearing Kunming (KM) mice were intratumorally injected with ¹³¹I-monoiodohypericin (¹³¹I-MIH) to investigate the biodistribution of ¹³¹I-MIH as a function of time. Single-photon emission computed tomography (SPECT), autoradiography, fluorescence microscopy and hematoxylin and eosin (H&E) staining were performed to determine the intra-tumoral distribution of ¹³¹I-MIH. A therapeutic evaluation study was also performed in the tumor-bearing KM mice using saline and a positive drug as controls. Gamma counting, SPECT images, autoradiography and fluorescence microscopy and H&E staining results revealed intense retention of ¹³¹I-MIH in the necrotic tumor over 168 h and good <i>in vivo</i> stability of the agent. Therapy with a single dose of intra-tumoral administration of ¹³¹I-MIH caused significant tumor growth delay. A histopathological analysis of the tumors and normal organs further validated the therapeutic efficacy and limited systemic toxicity of ¹³¹I-MIH. The prolonged tumor retention and effective therapy indicated that ¹³¹I-MIH may be a promising intratumorally injected SMTNT agent.</p></div