Method for Improving the Determination of Dibromoacetic Acid in Cefathiamidine

[Objectives]To establish an LC-MS method for the determination of dibromoacetic acid in Cefathiamidine and Cefathiamidine for Injection.[Methods]Shiseido PC HILIC column(2.0 mm ×100 mm,3μ.m)was used.The mobile phase was 0.005 Mammonium formate and the mobile phase was acetonitrile with gradient elution.The flow rate was 0.3-0.8mL/min.[Results]The limit of detection was 0.2500 ng/mL and the limit of quantification was 0.500 ng/mL,which were 2.5%and 5.0%of the impurity limits,respectively.The recov-ery rate was 103.85%.[Conclusions]This method improved the detection of dibromoacetic acid impurities in Cefathiamidine,and has that advantage of good specificity,low limit of detection and limit of quantification,high sensitivity,high accuracy,interference resistance,can meet the detection requirements of Cefathiamidine,and is suitable for the quality control of Cefathiamidine.

Historical Cohort Study of the Efficacy and Safety of Piperacillin/Tazobactam Versus Fourth-Generation Cephalosporins for Empirical Treatment of Febrile Neutropenia in Patients with Hematological Malignancies

We retrospectively evaluated the efficacy and safety of the combination drug piperacillin/tazobactam (PIPC/TAZ) in comparison with those of fourth-generation cephalosporins (4th Cephs) as initial empirical treatment in hematological malignancies patients with febrile neutropenia (FN). Among 200 patients assessed in this study, 49 had received PIPC/TAZ and 151 4th Cephs. Patient background characteristics were comparable between the two treatment groups. The overall efficacy rate in those receiving 4th Cephs and PIPC/TAZ was 57.0% (86/151 patients) and 59.2% (29/49 patients), respectively, with no significant difference detected between the two treatment regimens (P = 0.78). Treat-ment did not need to be discontinued or interrupted due to development of adverse drug reactions in any of the patients. Therefore in this study the efficacy and safety of PIPC/TAZ as initial antimicrobial treatment for FN in patients with hematological malignancies were not inferior to those of 4th Cephs. Based on the preliminary data obtained in this study, we propose to conduct a multicenter, prospective, controlled study to compare PIPC/TAZ versus CFPM given as empirical antimicrobial treatment against FN in patients with hematological malignancies.

Spectophotometric method for determination of certain cephalosporins using 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl)

A simple, accurate and precise spectrophotometric method has been proposed for the determination of eleven cephalosporins, namely;cefaclor monohydrate, cefadroxil monohydrate, cefalexin anhydrous, cefradine anhydrous, cefotaxime sodium, cefoperazone sodium, ceftriaxone sodium, ceftazidime penthydrate, cefazolin sodium, cefixime and cefpodoxime pro- xetil in bulk drug and in pharmaceutical formulations. The method depends on hydrolysis of the studied drugs using 0.5M NaOH at 100°C and subsequent reaction of the formed sulfide ions with NBD-Cl (4-chloro-7-nitrobenzo-2-oxa-1, 3-diazole) to form a yellow-colored chromogen measured at 390 nm. Different variables affecting the reaction (e.g. NaOH concentration, hydrolysis time, NBD-Cl concentration and diluting solvent) were studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9990- 0.9999) were found in the range of 5-160 μg mL-1 for all studied drugs. The limits of assay detection and quantitiation ranged from 0.289 to 5.867 and from 0.878 to 17.778 μg mL-1;respectively. The accuracy and precision of the proposed method were satisfactory. The method was successfully applied for analysis of the studied drugs in their pharmaceutical formulations and the recovery percentages ranged from 96.6 to 103.5%.

Kinetic spectrophotometric determination of certain cephalosporins using iodate/iodide mixture

A simple, precise and accurate kinetic spectro-photometric method for determination of ce-fradine anhydrous, cefaclor monohydrate, ce-fadroxil monohydrate, cefalexin anhydrous and cefixime in bulk and in pharmaceutical formula-tions has been developed. The method based on a kinetic investigation of the reaction of the free carboxylic acid group of the drug with a mixture of potassium iodate and potassium iodide at room temperature to form yellow coloured triiodide ions. The reaction was followed up spectrophotometrically by measuring the increase in absorbance at 352 nm as a function of time. The initial rate, fixed time, variable time and rate-constant methods were adopted for constructing the calibration curves but fixed time method has been found to be more applicable. The analytical performance of the method, in terms of accuracy and precision, was statistically validated;the results were satisfactory. The method has been successfully applied to the determination of the studied drugs in commercial pharmaceutical formulations. Statistical comparison of the results with a well established reported method showed excellent ag- reement and proved that there is no significant difference in the accuracy and precision.

Variable selection in near infrared spectroscopy for quantitative models of homologous analogs of cephalosporins

Two universal spectral ranges(4550-4100 cm^(-1) and 6190-5510 cm^(-1))for construction of quantitative models of homologous analogs of cephalosporins were proposed by evaluating theperformance of five spectral ranges and their combinations,using three data sets of cephalos-porins for injection,ie.,cefuroxime sodium,cetriaxone sodium and cefoperazone sodium.Subsequently,the proposed ranges were validated by using eight calibration sets of otherhomologous analogs of cephalosporins for injection,namely cefmenoxime hydrochloride,ceftezole sodium,cefmetazole,cefoxitin sodium,cefotaxime sodium,cefradine,cephazolin sodium and ceftizoxime sodium.All the constructed quantitative models for the eight kinds of cephalosporinsusing these universal ranges could fulill the requirements for quick quantification.After that,competitive adaptive reweighted sampling(CARS)algorithm and infrared(IR)-near infrared(NIR)two-dimensional(2D)correlation spectral analysis were used to determine the scientific basis of these two spectral ranges as the universal regions for the construction of quantitativemodels of cephalosporins.The CAR.S algorithm demonstrated that the ranges of 4550-4100 cm^(-1) and 6190-5510 cm^(-1) included some key wavenumbers which could be attributed to content changes of cephalosporins.The IR-NIR 2D spectral analysis showed that certain wavenumbersin these two regions have strong correlations to the structures of those cephalosporins that wereeasy to degrade.

Studies on Semisynthesis and Anibacterial Activity of 7 β-(5-Methyl-1-Aryl-1H-1,2,3-Triazoly-4-Carboxamido) Cephalosporins

Nine new derivatives of 7 β - (5- methyl- 1- aryl- 1H-1, 2, 3- triazoly- 4- carboxamido) cephalosporins were synthesized by acylction of 7 β -amino group of 7-ACA, 7-ADCA and 7-ACT with 5 -methsyl- 1 -aryl- 1 H- 1,2,3-triazoly-4-formyl chloride. The structure of the compounds were confirmed by elementray analysis IR, HNMR and FAB-MS. Some of them showed significant antibacterial activity

Computational Calculations of Molecular Properties and Molecular Docking of New and Reference Cephalosporins on Penicillin Binding Proteins and Various β-Lactamases

An approach of using molinspiration calculations and molecular docking on PBPs （penicillin-binding proteins） and certain β-lactamases is employed to predict the molecular properties, bioactivity and resistance of newer and reference cephalosporins. The previously synthesized cephalosporins 1-8 and reference cephalosporins were subjected to extensive evaluations by calculating the molecular properties, drug-likeness scores on the bases of Lipinski＇s rule and bioactivity prediction using the method of molinspiration web-based software. The TPSA （topological polar surface area）, OH-NH interactions, n-violation and the molinspiration Log partition coefficient （miLogP） values were also calculated. The investigated cephalosporins were subjected to molecular docking study on PBPs （lpyy） and on β-lactamases produced by S. aureus, K. pneumonia, E. coil and P. auroginosa using 1-click-docking website. Molecular properties of 1-8 recorded higher ＂FPSA than cephalexin and were lower than the reference cephalosporins and do not fulfill the requirements for Lipinski＇s rule. Bioactivities of 1-8 were predicted to be less and their docking scores on PBPs were comparable to those of the reference cephalosporins, particularly ceftobiprole. The references recorded various docking scores on the above β-lactamases and as expected, cefiobiprole recorded the lowest scores on all β-lactarnases. Cephalosporins 1-8 recorded various docking scores on β-lactamases. Molecular docking studies on PBPs and β-lactamases are considered as very useful, reliable and practical approach for predicting the bioactivity scores and to afford some information about the stability and selectivity of the newly proposed cephalosporins against β-lactamases of certain pathogenic microbes, such as P. auroginosa and MRSA, by recording the relative docking scores in comparison with those of reference cephalosporins.

Theoretical Analysis of Structural Characteristics of Morin Rearrangement for Cephalosporins Prepared from Penicillin Sulfoxide

The structure of penicillin sulfoxide is rearranged to cephalosporins by the Morin rearrangement. It is a unit reaction for the preparation of various types of cephalosporins. In order to make better use of the reaction and in view of the shortage of the reaction theory, this study used m062x/6-311++G(d, p) to explore the possible ring-opening reaction of the penicillin sulfoxide. It is found that the isomer of(S)-sulfoxide is a necessary structure. At the same time, the intramolecular hydrogen bonding effect between the side-chain amide proton(-CONH-) and the sulfinyl oxygen(-SO) is the decisive structure factor for the formation of alkenyl in ring-opening reaction, and the best reaction path is S0-> TS2-> IN1 channel. The main effect of acid catalysis is to catalyze the dehydration reaction of sulfenic acid to form sulfur cations for subsequently ring closing reaction.

Dissimilarity of different cephalosporins on volatile fatty acids production and antibiotic resistance genes fates during sludge fermentation and underlying mechanisms

The distinct influences of cephalosporins(CEPs, i.e., cefamandole nafate and cefpirome sulfate) affiliated to different generations on the volatile fatty acids(VFAs) production and antibiotic resistance genes(ARGs) fates during waste activated sludge(WAS) fermentation were unveiled. The presence of CEPs mainly exhibited negative effects on the total VFAs production(5%–15% reduction), especially the cefamandole nafate, which is quite different to previous understanding. Further investigation revealed that the CEPs contributed to the solubilization and hydrolysis but inhibited the acidification process by affecting the functional microbial populations(i.e., Tissierella) and general microbial metabolic activities(i.e., pyruvate metabolism and VFAs biosynthesis). In addition, CEPs(especially the cefpirome sulfate)caused the propagation of ARGs(i.e., bla TEM, tet X and mex F) during WAS fermentation. CEPs enhanced the cell membrane permeability to promote the antibiotics mechanism of efflux pump and the horizontal transfer of ARGs. Also, the CEPs altered the regulatory systems(i.e., two component system) and microbial populations associated with ARGs, resulting in the proliferation of specific ARGs. Overall, the dissimilarity of different CEPs impacts on the WAS fermentation for VFAs production and ARGs variations enlightened the diverse environmental behaviors of anthropogenic pollutants and evoked the caution of ecological risks.

Investigation of the pharmacokinetics and determination of certain cephalosporins in rabbit plasma by a kinetic spectrophotometric method with the aid of chemometrics

This paper describes a kinetic spectrophotometric method for simultaneous determination of three cephalosporin antibiotics,cephradine,cefaclor and cefixime,with the aid of chemometrics. The method relies on their oxidation with KMnO4 to produce green manganate with different kinetic rates in alkaline medium. The proposed method was successfully applied to a pharmacokinetic study of three cephalosporin antibiotics in rabbit plasma via intravenous injections. The results indicated that the amount of cephradine,cefaclor and cefixime were reduced rapidly in rabbit blood,showing clear dose-dependency and the half-life of cefixime (160 min) was longer than those of cephradine (60 min) and cefaclor (60 min).

Decreasing susceptibility of bacteria to ampicillin/sulbactam and third generation cephalosporins in urinary tract infections

Background:Urinary tract infections(UTIs)are among the most common bacterial infections worldwide and have become more difficult to treat over the years.Inappropriate antibiotic use has led to increased antibiotic resistance.Materials and methods:We examined 1921 urine culture samples from a single hospital and analyzed them for bacterial spectrum and antibiotic susceptibility.We further analyzed changes in the rates of detected bacteria and of the sensitivity of these uropathogens to antibiotics over the years.Results:In our hospital-based analysis,cystitis was the most frequently diagnosed UTI in women(76%)and men(79%).Escherichia coli(48%)was the most commonly identified uropathogen.Samples demonstrated an increase in the proportion of E.coli(p<0.001)and a decrease in Enterococcus faecalis(p<0.001)over the study time period.Antimicrobial susceptibility analysis showed an increase over time in the number of isolates with resistance to ampicillin/sulbactam(p<0.001)and to third-generation cephalosporins cefotaxime(p=0.043)and ceftazidime(p<0.001).Conclusions:Ampicillin/sulbactam and third-generation cephalosporins are antibiotics frequently used in the treatment of UTIs.When selecting an optimal antimicrobial treatment regimen for patients with UTIs,it is imperative to understand regional and timedependent differences in the prevalence of various uropathogens and antimicrobial resistance patterns.Therefore,continuous surveillance of local pathogen and antimicrobial susceptibility patterns for frequently used antibiotics should be prioritized.

第三代头孢菌素治疗社区获得性自发性细菌性腹膜炎效果预测模型的临床价值

目的探讨第三代头孢菌素(3^(rd)GC)治疗社区获得性自发性细菌性腹膜炎(CASBP)效果预测模型的临床应用价值。方法前瞻性选取2021年1月—2022年6月南昌市第九医院新入院的肝硬化伴CASBP患者50例,随机分为优化治疗组(n=25)与传统治疗组(n=25),前者基于效果预测模型采用头孢他啶或亚胺培南初治,后者均采用头孢他啶初治,此后依据初治效果调整抗生素,比较两组的初治有效率、第5天治愈率及30天病死率。计量资料两组间比较采用成组t检验或MannWhitney U检验。计数资料两组间比较采用χ^(2)检验或Fisher精确概率法。结果所有患者均完成研究。优化治疗组初治有效率明显高于传统治疗组(88.0%vs 60.0%,χ^(2)=5.094,P=0.024),两组第5天治愈率相当(80.0%vs 56.6%,χ^(2)=3.309,P=0.069)。均使用头孢他定初治的患者中,优化治疗组初治有效率亦明显高于传统治疗组(88.9%vs 60.0%,χ^(2)=4.341,P=0.037),两组第5天治愈率相当(83.3%vs 56.0%,χ^(2)=2.425,P=0.119)。两组患者的30天病死率分别为8.0%和20.0%,差异无统计学意义(χ^(2)=0.664,P=0.415)。所有入组患者初治有效与第5天治愈关联明显(OR=9.643,95%CI:2.292~40.564),第5天治愈与患者30天死亡关联明显(OR=0.138,95%CI:0.023~0.813)。结论该疗效预测模型有助于临床医生筛选3rdGC治疗的优势患者,提高3rdGC经验性治疗CASBP的初治疗效。

静脉注射头孢菌素类药物患者过敏反应发生率及其影响因素的多中心临床研究

目的:分析头孢菌素类药物过敏反应的发生率及其影响因素。方法:横断面调研2021年4月1日至6月30日浙江省29家医疗机构所有接受静脉注射头孢菌素类药物的患者,统计头孢菌素类药物过敏反应的发生率,采用泊松回归模型分析头孢菌素类药物诱导过敏反应发生的相关影响因素。结果:研究共纳入56155例患者,头孢菌素类药物过敏反应总发生率为1.67‰,过敏反应发生率最高的是头孢唑肟(4.27‰),其次是头孢曲松(3.49‰)和头孢噻肟(2.40‰)。与皮试阴性组比较,非皮试组患者过敏反应发生率无明显增加(分别为1.75‰与1.63‰,RR=1.07,95%CI:0.70~1.63,P>0.05)。泊松回归分析结果显示,体重指数低于18.5 kg/m^(2)(RR=2.43,95%CI:1.23~4.82,P<0.05)、其他β-内酰胺类药物过敏史(RR=33.88,95%CI:1.47~781.12,P<0.05)会增加头孢菌素类药物过敏反应的发生率,且与头孢呋辛比较,头孢曲松(RR=3.08,95%CI:1.70~5.59,P<0.01)、头孢他啶(RR=1.89,95%CI:1.03~3.47,P<0.05)和头孢唑肟(RR=3.74,95%CI:1.64~8.50,P<0.01)过敏反应发生的风险增加。结论:头孢菌素类药物过敏反应与低体重指数和β-内酰胺类药物过敏史有关,头孢菌素类药物的常规皮试筛查并不能减少过敏反应发生。

头孢类抗生素致敏红细胞检测与溶血性贫血的关系

【目的】探讨头孢类抗生素致敏红细胞检测与溶血性贫血的关系。【方法】收集在本院住院的996例患者(选择做血型检测及准备输血)的血液标本,使用抗球蛋白卡式法检测药物致敏的红细胞直接抗球蛋白试验(DAT)阳性情况,统计临床DAT检测结果及患者在临床中的科室分布。采用抗球蛋白卡式法对DAT阳性血液标本进行抗体分型,DAT阳性强度分布及分类、头孢类抗生素致敏红细胞检测,了解DAT阳性使用抗生素种类。观察患者是否发生溶血性贫血,分析头孢类抗生素致敏红细胞检测与溶血性贫血的关系。【结果】DAT阳性检出率为7.83%(78/996),其中内科患者DAT阳性率高于外科(P<0.05)。78例DAT阳性患者血液标本在抗球蛋白卡中的反应强度为1+、2+、3+、4+的占比分别为28.21%、24.36%、25.64%、21.79%,反应强度分布比较,差异无统计学意义(P>0.05)。DAT阳性分类中抗IgG、抗C3d、抗IgG+C3d占比分别为39.74%、33.33%、26.92%,DAT阳性分类构成比较,差异无统计学意义(P>0.05)。78例DAT阳性患者血液标本中,共检测出4种抗生素致敏红细胞9例,其中头孢克洛致敏红细胞占比均高于头孢哌酮舒巴坦钠、头孢吡肟、头孢他啶(P<0.05),其余抗生素种类间比较,差异均无统计学意义(P>0.05)。DAT阳性患者血液标本中,使用抗生素患者临床溶血性贫血发生率高于未使用抗生素者(P<0.05),使用抗生素致敏红细胞者溶血性贫血发生率高于抗生素未致敏者(P<0.05)。使用抗生素未致敏患者溶血性贫血发生率与未使用抗生素者比较,差异无统计学意义(P>0.05)。【结论】头孢类抗生素致敏红细胞检测与溶血性贫血存在一定的相关性。

我国医务人员头孢菌素类药物皮试知信行的调查研究

目的分析我国医疗机构医务人员对头孢菌素类药物皮试的知信行现状及其影响因素,为规范皮试相关医疗行为提供参考。方法采用自行设计的头孢菌素类药物皮试知信行问卷对我国医务人员进行调查。通过微信向全国医疗机构发放问卷二维码,被调查者采用匿名方式自愿参加。统计不同文化程度,工作岗位、职称医务人员的知识、态度、行为得分,应用Wilcoxon秩和检验、多元线性回归分析等方法分析其影响因素。结果30个省份205家医疗机构的873名医务人员参与调查。对头孢菌素类药物皮试知识(总分16分)、态度(总分20分)、行为(总分20分)得分分别为10(8,12)分,13(12,15)分和12(9,15)分。多元线性回归结果显示,文化程度、工作岗位和职称与知识、态度得分相关(P<0.05)。研究生比专科医务人员知识掌握情况好、态度积极;药师比医生、护士知识掌握情况好、态度积极;中级、高级比初级及以下职称医务人员知识掌握情况好、态度积极。知识水平与态度正相关(P<0.05)。性别、工作岗位和职称与行为得分相关(P<0.05)。女性比男性医务人员行为消极,护士比药师行为积极;高级比初级及以下职称医务人员行为积极。知识水平、态度与行为正相关(P<0.05),态度在知识对行为影响中的中介效应差异无统计学意义(P=0.085)。结论我国医疗机构医务人员头孢菌素类药物皮试知信行有待加强,应结合不同岗位、职称等方面的知信行差异,对医务人员开展培训,以提升知识水平、树立积极态度、规范皮试相关医疗行为。

高效凝胶色谱联用质谱法快速鉴定盐酸头孢吡肟中的聚合物

目的:采用高效凝胶色谱法联用质谱法推断注射用盐酸头孢吡肟中聚合物的结构。方法:采用TSK gel G2000SWxl高效分子排阻色谱柱,以5 mM甲酸铵溶液-乙腈(95∶5)为流动相,流速为0.8 mL·min^(-1),检测波长为254 nm,柱温为25℃。在正离子模式下获取各聚合物杂质的质谱数据,结合头孢类抗生素聚合物的质谱裂解规律、降解反应原理,解析相关聚合物的结构。结果:推断出4种聚合物的化学结构,其中2个是头孢吡肟二聚体杂质,另外2个是三聚体杂质,其中三聚体杂质为首次报道。结论:采用高效凝胶色谱法联用质谱技术,可快速推断出注射用盐酸头孢吡肟中的聚合物的化学结构,可为其他头孢菌素聚合物的分离、鉴定及产品质量提高提供参考。

皮肤试验预测头孢菌素过敏反应的研究进展

头孢菌素是以7-氨基头孢烷酸(7-amino-cephalosporanic acid)为母核,通过连接不同侧链而形成的一类β-内酰胺类抗菌药物。通过不断迭代研发,头孢菌素在抗菌谱、抗菌作用和药物安全性等方面得到不断优化。然而,在临床使用过程中,头孢菌素仍会出现过敏反应等药物不良反应,国内一直以来都是通过皮肤试验进行预测,但相关研究对皮肤试验的预测和应用价值是存在质疑的。为此,笔者从β-内酰胺类药物致过敏反应的分子机制和影响因素、皮肤试验的经济学价值、国内外头孢菌素的皮肤试验开展现状等方面对相关研究进行了综述,为临床评估皮肤试验对头孢菌素过敏反应的预测价值和应用前景提供参考。

阿莫西林克拉维酸钾联合第三代头孢类抗菌药治疗新生儿肺炎的临床效果及其对肠道菌群的影响

目的分析阿莫西林克拉维酸钾与第三代头孢类抗菌药联合应用于新生儿肺炎患儿的应用效果及其对患儿肠道菌群的影响。方法选择在2021年2月—2022年11月期间于我院新生儿科接受相关治疗的100例新生儿肺炎患儿,依照简单随机化法将患儿分为研究组(n=50)及参照组(n=50)。给予参照组常规新生儿肺炎治疗,在此基础上给予研究组患者阿莫西林克拉维酸钾与第三代头孢类抗菌药的联合治疗。治疗结束后对比两组患儿的血清因子水平、肠道菌落情况、临床疗效以及不良反应发生情况。结果治疗前,两组患儿的血清因子水平、肠道内菌群数量比较差异无统计学意义(P>0.05),治疗后两组患儿的降钙素原(procalcitonin,PCT)、C-反应蛋白(C-reactive protein,CRP)、白细胞计数(white blood cell count,WBC)、肠球菌、肠杆菌、双歧杆菌以及乳酸杆菌水平均有改善(P<0.05),其中研究组的PCT、CRP、WBC、肠球菌、双歧杆菌以及乳酸杆菌数量低于参照组,而研究组的肠杆菌数量高于参照组;同时研究组的临床有效率(94.00%)与参照组的临床有效率(86.00%)比较差异无统计学意义(P>0.05);两组患儿的不良反应发生率比较差异无统计学意义(P>0.05),但其中研究组腹泻的发生率高于参照组(P<0.05)。结论在对新生儿肺炎患儿进行治疗时采取阿莫西林克拉维酸钾单纯治疗与阿莫西林克拉维酸钾+第三代头孢类抗菌药(头孢他啶)的临床疗效相当,联合用药虽能更为显著地减少患儿机体的细菌数量,改善血清因子水平,但更易发生腹泻的并发症,且为了减少耐药性,应适当采用单独用药。

头孢菌素菌渣有机肥对玉米土壤中耐药菌及相关抗性基因的影响

【目的】研究头孢菌素菌渣有机肥施用后对玉米农田土壤中耐药菌及相关抗性基因丰度的影响,为头孢菌素菌渣有机肥施用生物安全性评价提供科学依据。【方法】设置不施菌渣有机肥(CK)、施用菌渣有机肥500 kg/667m^(2)(B_(1))、1000 kg/667m^(2)(B_(2))3个处理,分别采用可培养方法和实时荧光定量检测,分析各处理下玉米农田中耐药菌及相关抗性基因丰度变化。【结果】施用头孢菌素菌渣有机肥能显著提高玉米苗期和结果期土壤中细菌总数及苗期时头孢拉定耐药菌菌数。获得了主要抗生素耐药菌株41株,其中,头孢拉定耐药菌8株,分属于6个属。【结论】施用头孢菌素菌渣有机肥能显著提高玉米苗期土壤中各ARGs基因的相对丰度,但在结果期各处理间β-内酰胺类ARGs基因bla TEM相对丰度无显著影响,并对其它耐药基因无明显规律性影响。