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.

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.

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

为 cephalexin 和 trimethoprim 的同时的运动 spectrophotometric 决心的一个过程被描述。它与黄铵 cerous (IV ) 基于这些混合物的氧化的不同反应率在酸的中等、无色的 cerous (III ) 的硫酸盐硫酸盐被生产。重叠运动数据是 chemometric 方法的使用解决的份量上，部分最少的广场(请) ，主要部件回归(PCR ) 和光线的基础功能人工的神经网络(RBF-ANN ) 。建议方法也与满足的结果在药品的准备和人的尿被用于 cephalexin 和 trimethoprim 的同时的决心，它与那些由 HPLC 获得了作比较很好。

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。

Removal of trimethoprim and sulfamethoxazole in artificial composite soil treatment systems and diversity of microbial communities

Four artificial composite soil treatment systems(ACSTs)fed with reclaimed water containing trimethoprim(TMP)and sulfamethoxazole(SMX)were constructed to investigate SMX and TMP biodegradation efficiency,ammonia and nitrite removal conditions and the microbial community within ACST layers.Results showed SMX and TMP removal rates could reach 80% and 95%,respectively,and removal rates of ammonia and nitrite could reach 80% and 90%,respectively,in ACSTs.The MiSeq sequencing results showed that microbial community structures of the ACSTs were similar.The dominant microbial community in the adsorption and biodegradation layers of the ACSTs contained Proteobacteria,Chloroflexi,Acidobacteria,Firmicutes,Actinobacteria and Nitrospirae.Firmicutes and Proteobacteria were considerably dominant in the ACST biodegradation layers.The entire experimental results indicated that Nitrosomonadaceae_uncultured,Nitrospira and Bacillus were associated with nitrification processes,while Bacillus and Lactococcus were associated with SMX and TMP removal processes.The findings suggest that ACSTs are appropriate for engineering applications.

Removal of sulfamethoxazole and trimethoprim from reclaimed water and the biodegradation mechanism

Sulfamethoxazole (SMX)and trimethoprim (TMP)are two critical sulfonamide antibiotics with enhanced persistency that are commonly found in wastewater treatment plants.Recently,more scholars have showed interests in how SMX and TMP antibiotics are biodegraded,which is seldom reported previously.Novel artificial composite soil treatment systems were designed to allow biodegradafion to effectively remove adsorbed SMX and TMP from the surface of clay ceramsites.A synergy between sorption and biodegradation improves the removal of SMX and TMP.One highly efficient SMX and TMP degrading bacteria strain,Bacillus subtilis,was isolated from column reactors.In the removal process,this bacteria decade SMX and TMP to NH4^+,and then further convert NH4^+to NO3^- in a continuous process.Microbial adaptation time was longer for SMX degradation than for TMP,and SMX was also able to be degraded in aerobic conditions.Importantly,the artificial composite soil treatment system is suitable for application in practical engineering.

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。

UPLC-MS/MS快速检测蛋及再制蛋中13种磺胺及甲氧苄啶

建立UPLC-MS/MS法快速检测鲜蛋及再制蛋中13种磺胺类药物和甲氧苄啶残留的方法。样品经乙腈提取后,无水硫酸钠净化,氮气吹干复溶,正己烷除脂后得供试品。13种磺胺类药物和甲氧苄啶在0.5~50 ng/mL范围内相关系数r均高于0.9960,线性关系良好。方法检出限为0.2μg/kg,在添加水平2、5、10μg/kg时,回收率在76.6%~112.7%之间,相对标准偏差(n=6)均在7%以内。使用该方法检测100批鲜蛋和25批再制蛋,其中7批鲜蛋检出磺胺间甲氧嘧啶、甲氧苄啶、磺胺甲唑、磺胺喹啉,2批再制蛋检出磺胺间甲氧嘧啶和甲氧苄啶,含量范围为2.0~688.8μg/kg。该方法简便快速、准确可靠、灵敏度高、抗干扰力强,适用于鲜蛋和再制蛋中磺胺类药物和甲氧苄啶的快速检测。

复方磺胺甲噁唑片降解杂质分析

通过考察复方磺胺甲噁唑片的降解途径以及降解产物,有效地进行药物杂质分析,提高药品质量控制水平。取复方磺胺甲噁唑片、空白辅料、空白辅料加甲氧苄啶和空白辅料加磺胺甲噁唑四种组分的样品分别进行破坏试验,考察各样品在光、热、酸、碱、氧化条件下的降解情况。主要降解杂质有在氧化破坏条件下产生磺胺甲噁唑氧化杂质1和2、甲氧苄啶杂质F,光照破坏条件下产生较大的磺胺甲噁唑杂质C、D。通过降解杂质的研究,可以有效规避制剂处方工艺和储存等环节产生降解杂质的风险,还可以采用实验中液相色谱条件同时监测复方磺胺甲噁唑片中各降解杂质,提升质量标准。

Anaerobic biodegradation of trimethoprim with sulfate as an electron acceptor

Trimethoprim(TMP)is an antibiotic frequently detected in various environments.Microorganisms are the main drivers of emerging antibiotic contaminant degradation in the environment.However,the feasibility and stability of the anaerobic biodegradation of TMP with sulfate as an electron acceptor remain poorly understood.Here,TMP-degrading microbial consortia were successfully enriched from municipal activated sludge(AS)and river sediment(RS)as the initial inoculums.The acclimated consortia were capable of transforming TMP through demethylation,and the hydroxyl-substituted demethylated product(4-desmethyl-TMP)was further degraded.The biodegradation ofTMP followed a 3-parameter sigmoid kinetic model.The potential degraders(Acetobacterium,Desulfovibrio,Desulfbbulbus,and unidentified Peptococcaceae)and fermenters(Lentimicrobium and Petrimonas)were significantly enriched in the acclimated consortia.The AS-and RS-acclimated TMP-degrading consortia had similar core microbiomes.The anaerobic biodegradation ofTMP could be coupled with sulfate respiration,which gives new insights into the antibiotic fate in real environments and provides a new route for the bioremediation of antibiotic-contaminated environments.

LC-MS/MS法测定动物源性食品中三甲氧芐氨嘧啶残留量的不确定度评估

采用液相色谱-串联质谱法(LC-MS/MS)对猪肉中的三甲氧芐氨嘧啶残留量进行分析。按照SN/T 2538—2010《进出口动物源性食品中二甲氧苄氨嘧啶、三甲氧苄氨嘧啶和二甲氧甲基苄氨嘧啶残留量的检测方法液相色谱-质谱/质谱法》测定猪肉中三甲氧芐氨嘧啶残留量的含量,以CNAS-GL006—2019《化学分析中不确定度的评估指南》和JJF 1059.1—2012《测量不确定度评定与表示》的要求和方法为参照,对整个实验过程中的不确定度因素进行系统分析,计算不确定度分量和扩展不确定度。所测猪肉中三甲氧苄氨嘧啶残留量的含量为14.29μg/kg,置信概率为95%时,测定结果中合成不确定度为0.74μg/kg,扩展不确定度为1.48μg/kg(k=2)。结果表明,液相色谱串联质谱仪的校准和标准溶液是猪肉中三甲氧苄氨嘧啶残留量测量不确定度的主要来源。

HPLC法同时测定复方磺胺间甲氧嘧啶注射液中磺胺间甲氧嘧啶钠和甲氧苄啶含量

利用高效液相色谱法(HPLC)同时测定复方磺胺间甲氧嘧啶钠注射液中磺胺间甲氧嘧啶钠和甲氧苄啶的含量。采用C18柱(5μm,4.6 mm×250.0 mm),以乙腈∶0.1%磷酸溶液(20∶80,V/V)为流动相,检测波长230 nm,柱温30℃,流速1.0 mL/min。结果表明,磺胺间甲氧嘧啶在5.00~200.00μg/mL浓度范围内与峰面积线性关系良好(R2=0.9996),平均回收率为99.49%,RSD为0.18%;甲氧苄啶在1.00~50.00μg/mL浓度范围内与峰面积线性关系良好(R2=0.9997),平均回收率为99.02%,RSD为0.60%。本方法简单快捷,精密度好,可用于控制复方磺胺间甲氧嘧啶钠注射液中磺胺间甲氧嘧啶钠和甲氧苄啶的含量。