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.

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。

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。

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。

复方新诺明致高血钾不良反应的药学管理

目的为复方新诺明(Sulfamethoxazole/trimethoprim,SMZ-TMP)致高血钾不良反应(Adverse drug reaction,ADR)的药学管理提供参考。方法回顾性分析临床药师参与的1例重症肺孢子菌肺炎(Pneumocystis jiroveci pneumonia,PJP)患者使用SMZ-TMP后出现高钾血症的诊疗过程,对该ADR进行了相关性分析和SMZ-TMP致高血钾ADR风险因素和管理措施探讨。结果该患者在使用SMZ-TMP后血钾呈上升趋势,第6天达峰值5.78 mmol/L,经钙剂、胰岛素、降钾树脂以及连续肾脏替代治疗后,高钾血症得到有效缓解,Naranjo’s评分5分,二者很可能相关。高剂量SMZ-TMP以及合并使用损害肾钾排泄的药物使高钾血症风险增加。结论SMZ-TMP在使用过程中可能发生高血钾,合并使用泼尼松的患者,需提高警惕;在治疗过程中(前2~4 d)应及时监测血钾,确定易感患者,避免发生严重ADR;若患者不能耐受SMZ-TMP时,建议可选择伯氨喹+克林霉素或喷他脒或阿托伐醌替代治疗。

1例复方磺胺甲唑片联合用药致高钾血症及危险因素分析

目的:探讨复方磺胺甲噁唑片(TMP-SMZ)联合用药引起高钾血症的机制。方法:分析1例使用TMP-SMZ联合螺内酯片、贝那普利片治疗致狼疮性肾炎患儿发生高钾血症的诊疗经过,并结合文献分析探讨该患儿血钾水平升高的机制。结果:患儿联合使用TMP-SMZ、螺内酯片及贝那普利片治疗1 d后出现血钾水平升高,立即予停服上述药物及常规降钾处理,其血钾水平仍居高不下,予血液透析治疗后患儿血钾水平逐渐降至正常。结论:高钾血症事件的发生与TMP-SMZ密切相关,而患儿联用相关药物(贝那普利片、螺内酯片)、存在基础肾脏疾病(狼疮性肾炎、肾功能不全)、代谢性酸中毒是促使高钾血症发生的危险因素。对于存在基础肾脏疾病的患者,即使是低剂量TMP-SMZ,在与螺内酯片、血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体拮抗剂类药物联合应用时,仍需警惕高钾血症的发生。

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。

高效液相色谱法测定复方磺胺嘧啶粉(水产用)中磺胺嘧啶和甲氧苄啶含量

建立同时测定复方磺胺嘧啶粉(水产用)中磺胺嘧啶和甲氧苄啶含量的HPLC方法。采用C18色谱柱进行分离,以水-乙腈-三乙胺(799∶200∶1)(pH 5.9)为流动相,检测波长为240 nm,进样量为10μL。结果显示,磺胺嘧啶和甲氧苄啶分别在25~400μg/mL和5~80μg/mL浓度范围内线性关系良好(R^(2)=1),回收率在97.83%~101.95%范围内,RSD在0.3%~1.2%范围内,精密度、稳定性和耐用性RSD均小于2.0%。结果表明,该方法快速、准确、环保,可用于测定该制剂中2种主药的含量,并能有效提升该制剂的质量标准和控制水平。

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。

甲氧苄啶增溶技术研究

本文首先测定了甲氧苄啶在水中的溶解度,然后采用表面活性剂增溶、β环糊精包合、固体分散体等药剂学常用增溶技术对甲氧苄啶开展了溶解度提升研究。实验结果显示,甲氧苄啶在水中的溶解性为0.31 mg/mL,使用表面活性剂增溶、β环糊精包合、固体分散体三种增溶技术后,甲氧苄啶在水中的最高溶解度分别为0.37 mg/mL、7.06μg/mL和3.3 mg/mL。通过三种药物制剂技术的对比说明,固体分散体制备的最优方法为溶剂法,最优载体为聚维酮K30,最优冷冻时间为2小时,制得甲氧苄啶固体分散体溶液甲氧苄啶的浓度可以达到3.3 mg/mL,与自身溶解度0.31 mg/mL相比,浓度达到甲氧苄啶普通水溶液的10.64倍,有效提高了甲氧苄啶在水中的溶解性。

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。

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.

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.

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.

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.

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.