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The pharmacokinetic/pharmacodynamic (PK/PD) parameter for evaluating the efficacy of vancomycin is now recommended to target an AUC/MIC (area under the curve, AUC; minimum inhibitory concentration, MIC) ratio of 400 to 600, and trough concentration should not be used as a substitute. We report a case of intracranial infection caused by methicillin-resistant Staphylococcus epidermidis (MRSE), which was sensitive to vancomycin (MIC=2µg/mL) and linezolid (MIC=4µg/mL). The trough concentration of vancomycin in serum was 18.3 µg/mL, and the vancomycin concentration in CSF was 5.0 µg/mL, all within normal range. However, the AUC/MIC ratio was calculated to be 125 mg·h·L−1, unable to reach target AUC/MIC. Vancomycin was replaced with linezolid after 36 days of treatment due to poor outcome, and the patient was eventually cured. Further, 23 cases of intracranial methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant coagulase-negative Staphylococcus (MRCoNS) infections were reported, of which 1 case with MRSA had a vancomycin MIC of 1 µg/mL, while the remaining 22 cases had vancomycin MICs >1 µg/mL. The linezolid-containing regimen was used after drug susceptibility results or if the initial treatment failed, leading to recovery in 19 patients, microbial clearance in 3 patients, and treatment failure in 1 case. In conclusion, vancomycin dosing should be based on AUC-guided dosing and monitoring. When the vancomycin MIC of MRSA/MRCoNS is >1 µg/mL, the target AUC/MIC may not be achieved. In such cases, linezolid can effectively be considered as a good alternative to vancomycin.

Epithelial growth factor receptor (EGFR), as a malignancy marker, is overly expressed in multiple solid tumors including colorectal neoplasms, one of the most prevalent malignancies worldwide. The main objective of this study is to enhance the efficacy of anti-tumor therapy targeting EGFR by constructing a novel EGFR-specific immunotoxin (C-CUS245C) based on Cetuximab and recombinant Cucurmosin (CUS245C). E. coli BL21 (DE3) PlysS (E. coli) was used to express CUS245C with a cysteine residue inserting to the C-terminus of Cucurmosin. Then immobilized metal ion affinity chromatography (IMAC) was used to purify CUS245C. The chemical conjugation method was used for the preparation of C-CUS245C. Then dialysis and IMAC were used to purify C-CUS245C. Western blot as well as SDS-PAGE was carried out to characterize the formation of C-CUS245C. At last the anti-colorectal cancer activity of C-CUS245C was investigated in vitro and in vivo. CUS245C with high purity could be obtained from the prokaryotic system. C-CUS245C was successfully constructed and highly purified. The cytotoxicity assays in vitro showed a significant proliferation inhibition of C-CUS245C on EGFR-positive cells for 120 h with IC50 values less than 0.1 pM. Besides, the anti-tumor efficacy of C-CUS245C was remarkably more potent than that of Cetuximab, CUS245C, and C + CUS245C (P

Background The safety and efficacy of Voriconazole in Acquired Immune Deficiency Syndrome (AIDS) patients is difficult to guarantee. In this study, Therapeutic Drug Monitoring (TDM) of Voriconazole in AIDS patients was investigated with the aim to further verify the significance of voriconazole TDM in AIDS patients and to explore more strategies to improve individualized medication. Methods The data of AIDS patients who underwent voriconazole TDM in our hospital from May 2018 to August 2021 were collected. The basic information of patients, the results of voriconazole TDM, the individualized intervention, the affecting factors of voriconazole concentration were analyzed, as well as the relationship between voriconazole trough concentration and safety. Results A total of 46 tests of voriconazole TDM were performed in 28 AIDS patients. Only 57.14% patients reached the therapeutic range at first TDM, and 87.50% patients reached the therapeutic range after intervention based on first TDM. 21.43% patients develop voriconazole-related Adverse Drug Reactions (ADRs), and ADRs were mostly occurred when voriconazole concentration is above 5.0 µg/mL. Spearman correlation coefficient rs was calculated to be 0.729 for voriconazole trough concentration and the incidence of ADRs, exhibiting a significant, positive linear correlation (P=0. 017). 50% patients had polypharmacy and drug interactions are common. For example, rifampicin can significantly reduce the plasma concentration of voriconazole. Multiple linear regression analysis showed Hypoproteinemia was a significant factor affecting voriconazole trough concentration(P=0.006). Conclusion AIDS patients usually have a low attainment rate of voriconazole trough concentration after initiation of standard dosing regimen. The affecting factors seem multifactorial and complex, of which hypoproteinemia is of great significance. Meanwhile, we need to be alert to the effects of drug interactions. The incidence of voriconazole related ADRs is high, mostly occurring when voriconazole concentration is above 5.0 µg/mL. Therefore, TDM can provide meaningful guidance for dosage optimization of voriconazole, and the dosage adjustment method in Chinese Guideline is applicable for the population of AIDS patients.

Epithelial growth factor receptor (EGFR), as a malignancy marker, is overly expressed in multiple solid tumors including colorectal neoplasms, one of the most prevalent malignancies worldwide. The main objective of this study is to enhance the efficacy of anti-tumor therapy targeting EGFR by constructing a novel EGFR-specific immunotoxin (C-CUSE. coli BL21 (DE3) PlysS (E. coli) was used to express CUSCUSC-CUS

Background: To investigate the efficacy of linezolid in the treatment of intracranial infection caused by methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant coagulase-negative Staphylococcus (MRCoNS).Case presentation: The patient at our hospital was diagnosed with methicillin-resistant Staphylococcus epidermidis (MRSE) intracranial infection, which was resistant to oxacillin and sensitive to vancomycin (MIC = 2 µg/mL) and linezolid (MIC = 4 µg/mL). Vancomycin was replaced with linezolid after 36 days of treatment due to poor outcome, and the patient was eventually cured. Further, a total of 23 cases of intracranial MRSA/MRCoNS infections were reported, of which 1 case with MRSA had a vancomycin MIC = 1 µg/mL, while the remaining 22 cases had vancomycin MICs greater than 1 µg/mL, with MIC = 1.5 µg/mL in 1 case, MIC = 2 µg/mL in 19 cases and MIC = 4 µg/mL in 2 cases. The linezolid-containing regimen was used after drug susceptibility results or if the initial treatment failed, leading to recovery in 19 patients, microbial clearance in 3 patients (of which 2 patients died of comorbidities and 1 patient died of Pseudomonas aeruginosa infection), and treatment failure in 1 case.Conclusion: The PK/PD parameter for evaluating the efficacy of vancomycin is AUC/MIC ≥ 400 (assuming a vancomycin MICBMD of 1 µg/mL), and trough concentration should not be used as a substitute for AUC/MIC. For optimal management, vancomycin dosing should be based on AUC-guided dosing and monitoring. When the vancomycin MIC of MRSA/MRCoNS is > 1 µg/mL, the target AUC/MIC cannot be achieved. In such cases, linezolid can be used with good therapeutic effects.

// Cuimin Deng 1, * , Jiani Xiong 2, * , Xiaofan Gu 1 , Xiaoying Chen 3 , Shuifa Wu 4 , Zhe Wang 1 , Duanduan Wang 5 , Jinjin Tu 1 , Jieming Xie 1 1 Department of Pharmacology, Fujian Medical University, Fuzhou, Fujian, China 2 Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China 3 Department of Experimental Teaching Center of Basic Medical Science, Fujian Medical University, Fuzhou, Fujian, China 4 Department of Pharmacology, The 180th Hospital of PLA, Quanzhou, Fujian, China 5 Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China * These authors contributed equally to this work Correspondence to: Jieming Xie, email: jmxie@mail.fjmu.edu.cn Keywords: immunotoxins, nanobody, EGFR, cucurmosin Received: November 16, 2016 Accepted: March 24, 2017 Published: April 07, 2017 ABSTRACT Epidermal growth factor receptor (EGFR) overexpression is related to the increased aggressiveness, metastases, and poor prognosis in various cancers. In this study, we successfully constructed a new EGFR nanobody-based immunotoxin rE/CUS containing cucurmosin (CUS), The immunotoxin was expressed by prokaryotic system and we obtained a yield of 5 mg protein per liter expression medium. The percentage of it’s binding ability totumor cell lines A549, HepG2, SW116, which highly expressed EGFR was 55.6%, 79.6% and 97.1%, respectively, but SW620 was only 4.45%. rE/CUS has the ability to bind A549, HepG2, SW116 cells specifically, and the antigen binding capability was not affected because of extra part of CUS component. The rE/CUS significantly inhibited the cell viability against EGFR over expression tumor cell lines in a dose-and time-dependent manner. Moreover, rE/CUS also induced apoptosis of HepG2 and A549 mightily. Our results demonstrate that rE/CUS is a potential therapeutic strategy for treating EGFR-positive solid tumors.

Trastuzumab is a humanized monoclonal antibody against HER2 approved by FDA for breast and gastric cancer therapy. However, only a quarter of patients have the potential to benefit from it, and most of them develop resistance within therapy. The main purpose of this study is to broaden trastuzumab's therapeutic window by conjugating trastuzumab with recombinant cucurmosin to form an immunotoxin called T-CUS245C. T-CUS245C was chemically conjugated and the purification of T-CUS245C was evaluated by SDS-PAGE. SRB tests showed a remarkable cytotoxicity of T-CUS245C with IC50 values in picomolar range on HER2 positive cancer cells without significantly proliferation inhibition on HER2 negative cells (P