Analysis of the Effectiveness of Biling Weitong Granules Combined with Trimethoprim and Vonoprazan in The Treatment of Reflux Esophagitis

Objective:To analyze the effectiveness of Biling Weitong Granules(BLWTG)combined with trimethoprim and vonoprazan in treating reflux esophagitis.Methods:Sixty patients with reflux esophagitis admitted to our hospital from March 2020 to March 2023 were selected as study subjects and randomly divided into a control group and an experimental group,with 30 cases in each group.The control group received only the combination treatment of trimethoprim and vonoprazan,while the experimental group was treated with BLWTG based on the control group.The acid reflux and heartburn symptom scores,quality-of-life scores,clinical efficacy,Chinese medicine symptom incidences,and the occurrence of adverse reactions before and after treatment in the two groups were compared.Results:After treatment,the acid reflux and heartburn symptom scores of patients in the experimental group were lower than those of the treatment control group,and the quality-of-life scores were higher than those of the treatment control group(P<0.05).The total clinical efficacy of the experimental group was 96.66%,which was significantly higher than that of the control group(73.33%,P<0.05).After treatment,the incidence of Chinese medicine symptoms,such as nausea and vomiting,abdominal distension and abdominal pain,and loss of appetite of the patients in the experimental group were significantly lower than those of the control group(P<0.05).During the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups,which indicated that the safety of the two treatments was comparable(P>0.05).Conclusion:BLWTG combined with trimethoprim and vonoprazan was safe and reliable in treating reflux esophagitis,effectively relieving the symptoms and improving its clinical efficacy.This treatment is worthy of popularization.

Preparation of Monoclonal Antibodies to Trimethoprim and ELISA Kit for Rapid Detection

[Objective] This study was conducted to find out an approach for determining trimethoprim residues in water. [Method] Trimethoprim antigen was prepared through a series of reactions from trimethoprim hapten which was generated through the reaction between trimethoprim and maleic anhydride. And trimethoprim monoclonal antibodies were prepared by animal immune, and used to prepare ELISA kit to detect trimethoprim residues in water. Finally, the limit of detection （LED） of the ELISA kit was determined. [Result] The standard curve covered a concentration range of 0-80 μg/L. The LeD of trimethoprim in water using the ELISA kit was 2.34 μg/kg; the IC50 （half maximal inhibitory concentration） was 4.8 μg/L; the recovery rate of added trimethoprim standard ranged from 60.5% to 79.7%; within-and among-batches RSD was less than 10%. The trimethoprim monoclonal antibody was specific, as the cross-reactivity rate of trimethoprim antibody and diaveridine was less than 1%. The stability tests revealed that the ELISA kit was stable after being stored at 4 ℃ for 12 months. [Conclusion] The results will provide references for controlling the abuse of trimethoprim.

Simultaneous kinetic spectrophotometric determination of cephalexin and trimethoprim in pharmaceutical preparation and human urine with the aid of chemometrics

A procedure for the simultaneous kinetic spectrophotometric determination of cephalexin and trimethoprim was described. It was based on the different reaction rate of oxidation of these compounds with yellow ammonium cerous （Ⅳ） sulfate in acidic medium and colorless cerous （Ⅲ） sulfate was produced. The overlapped kinetic data was quantitatively resolved by the use of chemometric methods, partial least squares （PLS）, principal component regression （PCR） and radial basis function-artificial neural network （RBF-ANN）. The proposed method was also applied to the simultaneous determination of cephalexin and trimethoprim in pharmaceutical preparation and human urine with satisfied results, which compared well with those obtained by HPLC.

Enhancing chloramphenicol and trimethoprim in vitro activity by Ocimum sanctum Linn.(Lamiaceae) leaf extract against Salmonella enterica serovar Typhi

Objective:To evaluate the antibacterial activity of Ocimum sanctum(O.sanctum) leaf extract, alone,and in combination with chloramphenicol(C) and trimethoprim(Tm) against Salmonella enterica serovar Typhi(S.typhi).Methods:The antibacterial activity of ethanolic extract of tulsi, 0.sanctum,leaf(TLE:500μg) for 23 S.typhi isolates was determined following agar diffusion. The C(30μg) and Tm(5μg) activity alone and in combination with TLE(250μg) was determined by disk diffusion.The zone diameter of inhibition(ZDI) for the agents was recorded, and growth inhibitory indices(Glls) were calculated.Results:The S.typhi isolates(n=23),which were resistant to both C(ZDI 6 mm) and Tm(ZDI 6 mm),had TLE(500μg) ZDIs 16-24 mm.The ZDIs of C and Tm were increased up to 15-21 mm and 17-23 mm,respectively,when TLE(250μg) was added to the C and Tm discs.The Glls ranged 0.789-1.235 and 0.894-1.352,due to combined activity against S.typhi isolates,of C and TLE and Tm and TLE.respeclivelv.Conclusions:The data suggest that TLE,in combination with C and Tm,had synergistic activity for S.typhi isolates, and hence O.sanclum is potential in combating S.typhi drug resistance,as well promising in the development of non-antibiotic drug for S.typhi infection.

Biofilm formation in trimethoprim/sulfamethoxazole-susceptible and trimethoprim/sulfamethoxazoleresistant uropathogenic Escherichia coli

Objective: To compare bioi lm formation in trimethoprim/sulfamethoxazole(SXT)-susceptible Escherichia coli(E. coli)(SSEC) and SXT-resistant E. coli(SREC) isolated from patients with urinary tract infections, and study the motile ability and physical characteristics of the isolates.Methods: A total of 74 E. coli isolates were tested for antimicrobial susceptibility with the disc diffusion assay. Based on the SXT-susceptibility test, the E. coli isolates were divided into SSEC(N = 30) and SREC(N = 44) groups. All E. coli isolates were examined for motile ability by using a motility test medium, and for checking bioi lm formation a scanning electron microscope was used. Bacterial colony size was measured with a vernier caliper and bacterial cell length was measured under a light microscope. The bacterial growth rate was studied by plotting the cell growth(absorbance) versus the incubation time. Results: The frequencies of non-motility and biofilm formation in the SREC group were signii cantly higher than that in the SSEC group(P < 0.01). The SREC bacterial cell length was shorter than that in the SSEC group [(1.35 ± 0.05) vs.(1.53 ± 0.05) μm, P < 0.05)], whereas the bacterial colony size and mid-log phase of the growth curve were not signii cantly dif erent. Conclusions: The present study indicated that bioi lm formation and phenotypic change of uropathogenic E. coli can be attributed to the mechanism of E. coli SXT resistance.

Antimicrobial therapy using sulfamethoxazole trimethoprim for Kawasaki disease patients unresponsive to intravenous immunoglobulin

Our previous study suggested that the production of superantigens and heat-shock protein 60 by small intestinal bacteria might play a role in Kawasaki disease (KD). We demonstrated that they were all resistant to commonly used antibiotics, except for sulamethoxazole trimethoprim (SMX-TMP). We used SMX-TMP for 7 cases of KD that were unresponsive to intravenous immunoglobulin (IVIG) and studied the antipyretic potency of this treatment. In 6 out of the 7 cases, we demonstrated that antipyretic potency was observed without side effects within 2 days of the initial administration. Antimicrobial therapy using SMX-TMP might represent a novel strategy for cases of KD that are unresponsive to IVIG.

Successful Conservative Management of Trimethoprim Induced Life-Threatening Hyperkalaemia in a Patient with <i>Pneumocystis jirovecii</i>Pneumonia

Co-trimoxazole is a combination antibiotic made up of trimethoprim and sulphamethoxazole that is first line treatment for Pneumocystis jirovecii pneumonia (PJP). Hyperkalaemia is a relatively common side effect of the trimethoprim component of co-trimoxazole but it is not well recognised by clinicians. The mechanism of action causing hyperkalaemia due to trimethoprim is similar to the potassium sparing diuretic effect of amiloride. It has been suggested on this basis that the hyperkalaemia can be reversed by the administration of furosemide and 0.9% saline to promote kaliuresis. We present what we believe to be the first published case of successfully managing trimethoprim induced hyperkalaemia with furosemide and 0.9% saline allowing the continued use of co-trimoxazole to treat severe PJP.

A Patient with Acute Liver Injury after Sulfamethoxazole/Trimethoprim Treatment for Pyelonephritis

Background: Sulfamethoxazole/Trimethoprim is a commonly used drug in a variety of clinically indicated scenarios, but it is not without side effect. Case-reports have stated that adverse reactions secondary to Sulfamethoxazole/Trimethoprim can present very early in the course of treatment, especially in patients who have a higher predisposition. Thus, the burden is placed on the clinician to be wary of these side effects and be able to recognize them in the correct clinic scenario. Objective: To discuss the risk of developing cholestatic hepatic dysfunction secondary to treatment with sulfamethoxazole/trimethoprim. Methods: We present the history, physical findings, laboratory investigations, and clinical course of a 47-year-old African-American female who developed cholestatic hepatic dysfunction after treatment with sulfamethoxazole/trimethoprim for pyelonephritis. Results: Drug-induced liver injury is a rare complication of sulfamethoxazole/trimethoprim therapy and only 20% of cases are secondary to cholestatic hepatic dysfunction. Our patient, who had been on sulfamethoxazole/trimethoprim for 7 days for pyelonephritis, presented to our hospital with a clinical picture consistent with hepatic injury;her laboratory investigations were noteworthy for an elevated white blood cell count, platelet count, and elevated transaminases, along with alkaline phosphatase levels greater than 2 times the upper limit of normal. Promptly following the discontinuation of sulfamethoxazole/trimethoprim, our patient improved clinically and her liver enzymes down-trended during the course of her hospital stay. She returned to normal at her 4 month follow up, thus confirming the diagnosis of cholestatic hepatic dysfunction secondary to sulfamethoxazole/trimethoprim. Conclusion: Cholestatic hepatic dysfunction is a form of drug-induced liver injury and a rare complication of sulfamethoxazole/trimethoprim treatment. The majority of cases resolve following discontinuation of the offending medication. However, a small percentage of patients may progress to liver failure and ultimately require liver transplantation. Clinicians should be aware of these risks to avoid delaying the discontinuation of sulfamethoxazole/trimethoprim.

Comparative Study of the Mutant Prevention Concentrations of Sulfamethoxazole-Trimethoprim Alone and in Combination with Levofloxacin against <i>Stenotrophomonas maltophilia</i>

Objectives: To determine the mutant prevention concentration (MPC) of sulfamethoxazole-trimethoprim (SXT) alone and in combination with levofloxacin (LVX) against Stenotrophomonas maltophilia (S. maltophilia) and to determine if the combination may decrease the emergence of resistant mutants. Methods: The MPC with 20 S. maltophilia strains which were both susceptible to SXT and LVX were determined by inhibiting visible growth among 1010 CFU on four agar plates after 72 hours incubation at 37°C. Results: All except two strains (18/20) showed a mutant prevention concentration ≥ 152/8 μg/mL for SXT and the range of the mutant prevention concentration for the SXT in combination with LVX is 9.5/0.5~608/32 μg/mL, which demonstrates at least 2 fold reduction except one strain. There was a significant difference (P < 0.01) between SXT alone and in combination with LVX on the mutant prevention concentration and mutant prevention concentration/minimum inhibitory concentration values. Conclusions: The MPC/MIC values were narrowed for SXT by combining with LVX against the S maltophilia. The combination may decrease the enrichment of mutant bacterial populations. Much study is needed to verify whether the using of drug combinations may restrict or even block the selection of S. maltophilia mutants.

Trimethoprim-Sulfamethoxazole-Induced Hepatitis in Mixed Connective Tissue Disease

Trimethoprim-Sulfamethoxazole (TMP-SMZ) is associated with severe hepatic toxicity or liver failure. We present a case of severe hepatic toxicity for whom TMP-SMZ was prescribed as part of treatment for mixed connective tissue disease (MCTD). TMP-SMZ was used to prevent complications from steroid therapy, but fever and hepatic toxicity developed with repeated TMP-SMZ medication. While the drug lymphocyte stimulation test (DLST) for TMP-SMZ showed negative, the genotype for N-acetyltransferase 2 (NAT2) showed type *6/*7, which is the slow acetylating type for NAT2 activity. This finding for NAT2 genotype and the patient’s clinical history lead us to speculate that her fever and hepatic toxicity were caused by TMP-SMZ.

Sulfamethoxazole-Trimethoprim-Induced Rhabdomyolysis in an Immunocompetent Patient: A Case Report

Sulfamethoxazole-trimethoprim (TMP-SMX)-induced rhabdomyolysis is a rare complication of a commonly used antibiotic. This is a case report of a 43-year old immunocompetent African American woman with a history of depression and chronic alcohol consumption who presented to the emergency department (ED) with worsening bilateral leg pain. Before presentation, the patient was prescribed a twice daily dose of TMP-SMX for a urinary tract infection. The patient reported the development of intensifying leg pain after taking five doses of TMP-SMX. On presentation to the ED she was hemodynamically stable, afebrile, and leg pain intensity 10 out of 10. The patient admitted to daily alcohol consumption and taking vortioxetine 10 mg per day for treatment of depression. Initial labs drawn in the ED showed an elevated creatine kinase (CK) of 26,231 U/L and a normal serum creatinine (SCr) of 1 mg/dL. Through patient history and laboratory tests, common causes of rhabdomyolysis were ruled out. Treatment was initiated with IV fluids plus thiamine and folic acid supplementation, TMP-SMX was discontinued, and vortioxetine 10 mg per day was continued until hospital day five. The patient began to show improvement in lower extremity pain and tenderness and was discharged on hospital day eight with minimal residual leg pain and a CK of 2809 U/L. This case report presents only the third incidence of an immunocompetent patient developing TMP-SMX-induced rhabdomyolysis. This case highlights an opportunity for a pharmacist’s intervention and the need for future research to determine risk factors of TMP-SMX-induced rhabdomyolysis in immunocompetent patients.

Green batch prepared a novel C/P co-doping urchin-like TiO_(2)for enhanced photocatalytic degradation and mineralization of trimethoprim

In advancing the practical application of photocatalytic degradation for pollutant removal,batch preparation of environmentally friendly photocatalysts plays a crucial role.Herein,we prepared C/P co-doped urchin-like TiO_(2)(C/PeTiO_(2))through a straightforward room temperature impregnation and atmospheric annealing process.Phytic acid served as the dopant precursor for introducing C and P onto the TiO_(2)surface.This doping process was verified through energy dispersive X-ray spectroscopy(EDX),electron spin resonance(ESR),and X-ray photoelectron spectroscopy(XPS)analysis.The C/PeTiO_(2)photocatalyst exhibited exceptional efficiency in degrading the target compound trimethoprim(TMP),achieving a degradation of 98%TMP within 60 min and a mineralization of 40%TMP within 120 min,which were respectively 2.4 and 1.6 times higher than that of pristine TiO_(2).The intermediate products of TMP were detected,and a plausible degradation pathway was proposed.Photoelectric characterization results also confirmed that C/P co-doping could effectively enhance the carrier separation efficiency of C/PeTiO_(2).The catalysts prepared using the scaled-up impregnation system and reusing the phytic acid solution consistently demonstrated stable catalytic performance,which confirmed the viability of the method for green and batch preparation of C/P co-doped TiO_(2).Notably,the obtained catalyst consistently exhibited high degradation efficacy in various real water bodies,highlighting its substantial potential for practical application.The green and batch preparation method of C/PeTiO_(2)introduces a novel approach to the practical application of photocatalysis technology in treatment of water contaminants.

1例类鼻疽脓毒症患者的全程个体化药学监护

目的为类鼻疽脓毒症(MS)抗菌药物治疗方案的调整、不良反应的识别和个体化药学监护提供参考。方法临床药师利用血药浓度和基因检测全程参与1例MS患者强化期和根除期治疗过程。通过测定β-内酰胺类和复方磺胺甲噁唑(TMP/SMZ)血药浓度并计算其药代动力学与药效学(PK/PD)参数,结合文献对MS抗菌药物治疗方案进行调整;同时通过高通量测序检测药物相关基因多态性,对药物不良反应的发生原因进行分析并进行处理。结果临床药师利用血药浓度和基因检测手段,提出了亚胺培南西司他丁钠(IMP)给药剂量调整建议,分析了多种药物不良反应的发生原因;通过测定β-内酰胺类药物和TMP/SMZ血药浓度计算PK/PD靶标,通过查询指南和文献为临床医生解释类鼻疽患者脓毒症期和非脓毒症期状态下的达标情况;利用血药浓度和基因检测分析MS患者神经毒性与IMP cmin的相关性,并发现肾毒性与TMP/SMZ的cmax无关,而与患者饮水量相关。经全程抗菌药物治疗后,患者病情好转出院,不良反应得到有效处理。结论临床药师基于抗菌药物血药浓度和基因检测结果解读情况协助临床医生制定MS治疗方案,并为患者提供全程用药监护,提高了临床药物治疗的安全性和有效性。

复方磺胺甲噁唑人体药动学与生物等效性研究

目的研究单次空腹口服复方磺胺甲噁唑片在健康受试者体内的人体药代动力学特征和生物等效性。方法试验采用单中心、随机、开放、单剂量、两制剂、两周期、两序列交叉设计,24例受试者分别空腹口服复方磺胺甲噁唑受试制剂T或参比制剂R。采用超高效液相色谱-串联质谱(UPLC-MS/MS)检测血浆中的磺胺甲噁唑和甲氧苄啶的血药浓度,用Phoenix WinNonlin 8.2软件计算药动学参数,评价两制剂生物等效性。结果空腹试验受试制剂T和参比制剂R的磺胺甲噁唑C max、AUC 0-t、AUC 0-∞分别为(27.340±3.400)和(28.042±3.527)μg/mL、(375.2±38.7)和(371.5±35.4)h·μg/mL、(390.0±42.9)和(386.7±41.0)h·μg/mL;甲氧苄啶C max、AUC 0-t、AUC 0-∞分别为(0.845±0.198)和(0.838±0.144)μg/mL、(8.7±1.3)和(8.2±1.5)h·μg/mL、(8.9±1.3)和(8.4±1.5)h·μg/mL,药动学参数最小二乘几何均值比的90%置信区间均落在80.00%~125.00%判定范围内(P均>0.05)。结论复方磺胺甲噁唑片受试制剂与参比制剂在健康受试者中具有生物等效性。

中国肾脏移植术后耶氏肺孢子菌肺炎临床诊疗指南

肾脏移植术后受者因使用免疫抑制药长期处于免疫抑制状态,是耶氏肺孢子菌肺炎(PJP)感染的高危人群。肾脏移植术后6个月内和强化抗排斥反应治疗后是PJP发生的高危期,发热、干咳、进行性呼吸困难和低氧血症是肾脏移植术后PJP常见的临床表现。甲氧苄啶-磺胺甲噁唑(TMP-SMX)可有效预防和治疗PJP,显著降低PJP的发生率和患者病死率。为规范肾脏移植术后PJP的诊断、治疗和预防,中华医学会器官移植学分会组织国内相关专家,从临床关注问题出发,制订《中国肾脏移植术后耶氏肺孢子菌肺炎临床诊疗指南》,指导肾脏移植术后PJP的预防和临床综合治疗。

畜禽组织中甲氧苄啶和氟苯尼考的同时免疫层析检测方法研究

针对动物源性食品中甲氧苄啶(TMP)和氟苯尼考(FF)复配使用残留的问题,以乳胶微球作为示踪信号探针,建立了同时检测鸡肉和猪肉样品中甲氧苄啶和氟苯尼考的乳胶微球侧流免疫层析方法(LMs-LFIA)。基于特异性单克隆抗体7E6和SF15,通过逐步优化策略考察了探针制备条件、试纸条工作缓冲液以及样品垫处理液缓冲体系等对LMs-LFIA性能的影响。结果表明:在优化条件下,所建立的LMs-LFIA对鸡肉和猪肉样品中甲氧苄啶和氟苯尼考的可视化检出限分别为8 ng/g和12 ng/g,检测时间为8 min,且与甲氧苄啶和氟苯尼考的结构及功能类似物无明显交叉反应,方法特异性良好。所建方法对鸡、猪肉盲样的检测结果与超高效液相色谱-串联质谱(UPLC-MS/MS)仪器确证方法一致,适用于畜禽组织样本中甲氧苄啶和氟苯尼考残留的同时检测。

铜绿假单胞菌 prtN 突变引起甲氧苄啶耐药

耐药铜绿假单胞菌(PAO1)在临床感染过程中造成非常棘手的问题,研究其耐药机制有助于临床的治疗。研究结果表明,相对于野生型,ΔprtN表现出明显的甲氧苄啶(Tmp)抗性。为了了解其抗性出现的机理,测定了Tmp作用靶点folA的表达情况。相比于PAO1,folA在ΔprtN中的表达并未升高,反而有所下降。进一步研究发现,PrtN调控的S型绿脓杆菌素基因和prtN的双突变体对Tmp的抗性稍有降低,而脂多糖缺陷菌株ΔwbpL对Tmp的抗性略有升高。在ΔprtN中活性氧(ROS)相关基因(oxyR,katA,ahpC)的表达水平、生物被膜及外排泵相关抗生素抗性检测结果都显示与野生型无显著性差异。综上,prtN基因突变引起的Tmp抗性可能是通过PrtN调控S型绿脓杆菌素及脂多糖相关靶标作用的结果。

碳包覆中空磁性微球活化过硫酸盐降解水中甲氧苄啶

采用溶剂热合成法制备碳包覆铁酸锰中空磁性微球(CHM-MnFe_(2)O_(4)),通过SEM、TEM、XRD、VSM、FTIR、BET/BJH、XPS方法对其表观形貌进行分析,并将其应用于活化过硫酸盐(PMS)降解水中的甲氧苄啶(TMP),以高效液相色谱法对TMP的降解效率进行评估.经条件优化得出,在pH=7.0、PMS浓度为1.0 mmol·L^(−1)的条件下,投加0.10 g·L^(−1)的CHM-MnFe_(2)O_(4)纳米材料可在60 min内完全降解10.0 mg·L^(−1)的TMP.考察了无机阴离子和腐殖酸对TMP降解过程的影响:Cl−对TMP的降解具有双重作用,低浓度抑制高浓度促进;HCO_(3)−、HPO_(4)^(2−)和腐殖酸(HA)均具有一定抑制作用.通过自由基猝灭实验发现降解体系受到自由基·OH、SO_(4)^(−)·和非自由基1O_(2)的影响.循环实验和金属溶出实验证明CHM-MnFe_(2)O_(4)纳米材料具有良好的循环利用性能.

抗生素甲氧苄氨嘧啶对剩余污泥与白酒废水共发酵产酸的影响

为了研究甲氧苄氨嘧啶(TMP)对剩余污泥与白酒废水共发酵系统的影响,考察不同浓度TMP在短期内(14 d)对剩余污泥和白酒废水共发酵系统的影响,并阐述了TMP对共发酵系统的作用机理。结果表明,TMP在低质量浓度范围内(0~5 mg/L)投加量与挥发性脂肪酸(VFAs)积累量呈正相关,超过该剂量后,积累量略有回落。关键酶活性的分析表明,TMP可促进共发酵系统的溶解、水解和酸化过程,抑制了产甲烷过程。结果对于实现剩余污泥、白酒废水和抗生素无害化及资源化具有一定的指导意义。

复方磺胺甲噁唑联合伏立康唑致高钾并低钠血症3例报告及分析

目的 探讨复方磺胺甲噁唑(SMZ co)联合伏立康唑致高钾并低钠血症的原因及其处置措施。方法 收集2023年1-2月因重症肺炎入住陕西省人民医院,联合使用了SMZ co与伏立康唑导致高钾并低钠血症的3例病人的临床资料并分析。结果SMZ co联合伏立康唑可增加高钾并低钠血症风险,3例病人血钾最高分别上升至8.1、6.1、5.6 mmol/L,血钠最低分别下降至128、134、122 mmol/L,经口服环硅酸锆钠及补钠治疗后,3例病人血钾分别恢复至4.9、5.1、4.5 mmol/L,血钠恢复至136、135、137 mmol/L。结论 联合使用SMZ co与伏立康唑可导致高钾血症及低钠血症风险增加,原因可能为SMZ co的甲氧苄啶(TMP)成分竞争性抑制远端肾小管和集合管上皮细胞的阿米洛利样敏感钠通道,阻断钠离子(Na+)-氢离子(H+)和Na+-钾离子(K+)交换,抑制钠的吸收,并减少钾的排泄,从而导致低钠及高钾血症;联合用药可能导致血清伏立康唑水平异常升高而增加高钾血症风险。发生药源性高钾血症时及时停药并口服环硅酸锆钠可有效降钾,低钠血症通过口服及静脉补充高渗盐即可纠正。