Validity of using imipenem as a representative carbapenems and levofloxacin as a representative fluoroquinolones in antibiotics susceptibility test for enterobacteriaceae

In antimicrobial susceptibility test for enterobacteriaceae, the efficacies of carpapenems are predicted by the minimum inhibitory concentration (MIC) of imipenem, and that of fluoroquinolones are predicted by the MIC of levofloxacin. To assess its judgement, we compared the MICs of imipenem, meropenem, panipenem, and doripenem for carbapenems, and ciprofloxacin, levofloxacin, tosufloxacin and pazufloxacin for fluoroquinolones of clinically isolated enterobacteria, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Enterobacter cloacae and Citrobacterfreundii, those resistant to the third generation cephalosporin. MIC distributions in low concentration range are estranged in some strains, conspicuously S. marcescens, E. cloacae and C. freundii: meropenem and doripenem displayed low MIC value than imipenem and panipenem. Since the estrangements are appeared MIC value of less than 8 microg/ml, the interpretive results (susceptible, intermediate, resistant) are not affected. In fluoroquinolones, all 4 agents showed almost identical MIC distributions, thus the MIC of levofloxacin is accepted to use the reference for other fluoroquinolones. The existence of the strains harboring carbapenem-resistant gene displaying low MIC value of carbapenems was reported. For the sensitive detection of the candidate of carbapenem-resistant strains, cut-off value of each carbapenem should be reconsidered, and also other phonotype analysis should be applied. Genomic analysis also would be required to detect the carbapenem-resistant gene.     

以消化道出血为首发表现的特发性门脉高压1例

特发性门脉高压在临床上少见,虽作为排他性诊断,但目前我国尚无统一的诊断及治疗指南,易误诊或漏诊,本文旨通过总结2021年8月6日入暨南大学附属第一医院急诊治疗的1例特发性门脉高压诊治经验并结合文献,探讨该病的诊断流程及治疗方法。     

Synthesis and antibacterial activities of 4-pyrrolidinylthio carbapenems: containing heteroaromatics as a side chain

The synthesis of a new series of 2-alkyl-4-pyrrolidinylthio-b-methylcarbapenems containing the substituted heteroaromatic moieties is described. Their in vitro antibacterial activities against both gram-positive and gram-negative bacteria were tested. The effect of substituents on the nitrogen atoms at heteroaromatic rings was investigated. Particular compounds (14 b, 14 c) containing 3-methyl- and 3, 5-dimethylpyrazolethio substituted moiety showed the most potent antibacterial activity.     

Review article: the prothrombin time test as a measure of bleeding risk and prognosis in liver disease

BACKGROUND: Prothrombin time (PT)-derived international normalized ratio (INR) is used to assess bleeding risk and prognosis in cirrhosis, and to guide management of associated coagulation disturbances. Recent studies cast doubt on the validity of the assumptions that form the basis for these applications. AIMS: To review and critique the use of the PT-INR in cirrhosis. METHODS: Search of the literature. RESULTS: In cirrhosis, there is a decrease in both pro- and anti-coagulants. The PT-INR measures only the activity of procoagulants and fails to capture changes in anticoagulants. It is therefore not surprising that the PT does not predict the bleeding risk. The PT-INR provides a robust measure of liver function but recent data showed INR inter-laboratory variability in this setting. This is not surprising as the INR was validated to normalize results for patients on vitamin-K antagonists, not for cirrhosis. This limitation was not appreciated, but the INR is used to construct the model for end-stage liver disease score to prioritize patients for liver transplantation. Reports showed that model for end-stage liver disease is modified by the thromboplastin used for testing. CONCLUSIONS: Alternate tests to predict bleeding risk should be developed. The potential for misuse of the PT-INR should drive the development of alternate algorithms for organ allocation.     

肝硬化并发食管及胃底静脉曲张出血的药物治疗进展

食管胃底静脉曲张破裂出血(Esophagogastric variceal bleeding，EGVB)是肝硬化最常见的并发症之一。据文献报道。EGVB约占所有上消化道出血的10％-30％，大约25％-35％的肝硬化患者会发生曲张静脉出血，而这些患者出血的原因中。有80％-90％是由静脉曲张破裂所引起的。肝硬化后首次食管胃底静脉曲张出血的早期死亡率约为30％-50％，而幸存者中再出血的发生率高达70％。另这些患者出血后一年的生存率也较低(32％-80％)。     

Studies on beta-lactam antibiotics. XIX. Structure-activity relationships of cephalosporins having a thiadiazolylthiomethyl group at the C-3 side chain

The synthesis and antibacterial activity of 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-(hydroxy or alkoxy)iminoacetamido]cephalosporins with various thiadiazolylthiomethyl moieties at the 3-position are discussed. Of the compounds (1a-1e, 7a-7d), 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-hydroxyiminoacetamido]-3-[(1,2 ,4- thiadiazol-5-yl)thiomethyl]cephalosporin (1d: FK312) exhibited the highest activity against Gram-positive and Gram-negative bacteria, especially, against methicillin-resistant Staphylococcus aureus. Furthermore, the pharmacokinetic profiles of the compound 1d showed longer serum levels than that of ceftriaxone in rats.     

Myelodysplastic syndrome associated with clopidogrel: a case report

More than 3 million patients around the world have received clopidogrel, an inhibitor of platelet aggregation, which has largely replaced ticlopidine in clinical practice as it was believed to be devoid of the side effects caused by ticlopidine. We herein report the case of a woman who developed myelodysplastic syndrome (MDS) after 1 year of treatment with clopidogrel. The absence of other plausible causes suggests that her MDS was induced by clopidogrel. Although this is a very rare case, clinicians should be alert to the possibility of MDS associated with clopidogrel use.     

Hepatotoxicity upon using niacin to pass a drug test: A case report

Objectives

To report a case of hepatotoxicity when niacin was used by a patient with HIV to pass a drug test.

A new series of the SMTP plasminogen modulators with a phenylamine-based side chain

SMTPs are a family of small-molecule plasminogen modulators that enhance plasminogen activation. SMTP-7, one of the most potent congeners, is effective in treating thrombotic cerebral infarction. The SMTP molecule consists of a tricyclic γ-lactam moiety, a geranylmethyl group, and an N-linked side chain. The presence of both an aromatic group and a negatively ionizable group in the N-linked side chain is crucial for activity. Investigations of the congeners with a phenylglycine-based side chain suggest that a phenolic hydroxy group affects potency. In this study, we isolate and characterize a series of novel SMTP congeners with a phenylamine-based N-linked side chain. Of the 11 congeners isolated, SMTP-19 (with a 4-phenylcarboxylic acid moiety), SMTP-22 (with a 3-hydroxyphenyl-4-carboxylic acid moiety) and SMTP-25 (with a 2-hydroxyphenyl-3-carboxylic acid moiety) are as potent as SMTP-7 in plasminogen-modulating activity. Their isomers with a carboxylic acid group and/or a phenolic hydroxy group at different positions have <40% of the activity of these congeners. Both SMTP-22 and SMTP-25 have >1.7 times more oxygen radical absorbance capacity as compared with SMTP-7.