Resistance to Beta Lactam Antibiotics of <i>Pseudomonas aeruginosa</i>Isolated in Community Infections within HIV Infected Persons in Lomé-Togo

Objective: Describe resistance to beta lactam antibiotics of Pseudomonas aeruginosa in community infection within HIV-1 infected persons. Methods: We have studied prospectively from June 15th to December 31st 2013 inthe Clinic Hotel-Dieu and NGO VISA of Lomé, adult HIV-1 infected patients under anti retroviral therapy combining tenofovir, lamivudine and efavirenz for at least one year. The technique of agar diffusion susceptibility using discs of Ticarcillin + clavulanic acid is used to study the β-lactamase production. The diagnosis of species was performed by the chloroform test and the test for sensitivity to kanamycin and colistin. Results: Thirty five strains of Pseudomonas aeruginosa were obtained. The T-lymphocytes CD4 mediane was 575 cells/mm3 of blood. Urine represented 15 cases, skin abscesses 11 cases, externa suppurate otitis 7 cases and vaginal swab for 2 cases. The phenotypes were: wild phenotypes 23 cases (65.7%), resistant phenotypes 12 cases. Among resistant phenotypes, 4 were complex phenotype;5 were ESBL phenotypes;2 were hyper productive cephalosporinases phenotypes and 1 was a specific phenotype with impermeability to imipenem. Conclusion: The acquisition of resistance of Pseudomonas aeruginosa to beta lactam antibiotics in community infections among HIV-1 infected person incentives controls and promotes the rational use of antibiotics.

Cancer Therapy Using Antibiotics

Anticancer antibiotics have made a successful impact in the field of chemotherapeutics. For most of them, DNA is the molecular target. Some act as DNA intercalators or some prevent DNA repair among other mechanisms of actions, they are seen to have. The major disadvantages of these drugs though are the constant side effects and toxicities. With more focus on discovery of new drugs with newer scaffolds, the urge to discover and modify anticancer antibiotics is being lost. Modifications or even the wider research can yield newer better drugs for clinical use. The review here discusses the current antibiotic therapeutics, newer discoveries in the field as well ideas for future research.

Simultaneous determination of 14β-lactam antibiotics in cosmetic products by liquid chromatography tandem mass spectrometry method

In this study,a simple and rapid high-performance liquid chromatography-tandem mass spectrometry（HPLC-MS/MS） method was established and validated to determine the 14β-lactam antibiotics in cosmetic products,including 1（ceftazidime）,2（cefaclor）, 3（cefdinir）,4（ampicillin）,5（cefalexin）,6（ceftezole）,7（cefotaxim）,8（cefradine）,9（cefuroxime）,10（cephazoline）,11 （cefathiamidine）,12（cefoperazone）,13（cafalotin）,14（piperacillin）.

Disarming superbugs by a combination of glycolipids with β-lactam antibiotics

With the generous support by the National Natural Science Foundation of China and the Ministry of Science and Technology of China,the research teams of China State Institute of Pharmaceutical Industry(Prof.Chen Daijie)and East China University of Science and Technology(Dr.He Xiaopeng)developed new glycolipid'weapons'to disarm superbugs(ACS Med Chem Lett,2015,6:793—7).This work has also been high-

Polymeric adsorbents with peptide pendants as artificial receptors for β-Mactam antibiotics by mimicking the binding sites of β-lactamases

A scries of polymeric adsorbents with peptide pendants were designed as the artificial receptors of β-laetarn antibiotics by mimicking the structures of binding site in β-lactamases.Crosslinked poly(N,N-dimethyl acry-lamide) gel as a carrier was prepared by suspension copolyrnerization of N,N-dimethyl acrylamide and N,N-bisacryl-diaminoethane and then functionalized with ethylenediamine after partial hydrolysis.Using solid-phase peptide synthesis with symmetrical anhydride of protected amino acid step by step,various peptide pendants were respectively anchored onto the functionalized carrier.The adsorption properties of these peptide-containing adsorbents for β-lactam antibiotics such as ampicillin and cefotaxime were then studied.The results showed that only those adsorbents in which peptide chains contained more than one lysine residues could obviously adsorb both β-lactams and that static interaction as well as hydrogen bond played an important role during the

Open tubular capillary electrochromatography with block co-polymer coating for separation of β-lactam antibiotics

A new open-tubular capillary electrochromatography (OT-CEC) method for analysis of β-lactam antibiotics has been developed with unique block co-polymer coating. To obtain the highly ordered block polymer chains, reversible addition fragmentation chain transfer radical polymerization method was used to synthesize poly (maleic anhydride-styrene-N-isopropylacrylamide). The prepared block copolymer coating was characterized with NMR, fourier transform infrared spectroscopy and scanning electron microscope. Several key separation factors of OT-CEC, which including polymer amount,stability of the coating, temperature, species of organic additives, buffer pH and concentration, were investigated in detail. Our results indicated that the separation efficiency was improved greatly with the coating capillary and the three test analytes could be baseline separated. Then, the separation mechanism was briefly explored. Moreover, the proposed OT-CEC method displayed promising quantitative analysis property of the three test analytes with good linearity (R2>0.99), repeatability (relative standard deviations <0.9%) and high recovery (95.4%-106.2%). Further, the assay was applied in monitoring the three test β-lactam antibiotics (cephradine, cephalexin and amoxicillin) in serum samples, providing a useful platform for construction of novel polymer coatings in OT-CEC system and for analysis of drugs in real bio-samples.

Rapid Detection of β-lactam Antibiotic Residue in Milk Using Biolayer Interferometry

[ Objective] This study aimed to establish a high-sensitivity method for rapid detection of^-lactam antibiotic residue in milk. [Method] Based on bio- layer interferometry technology, ampicillin-BSA conjugate was fixed on the bottom of APS fiber optic biosensor probe through hydrophobic interaction and bound to 40 mn colloidal gold-labeled/3-1actam antibiotic receptor, to detect β-lactam antibiotics in milk. [ Result] The sensitivity of colloidal gold-labeled BLI method was twice as high as that of immunechromatographic test strip in detection of β-1actam antibiotic residue in milk. Colloidal gold-labeled BLI method exhibited good speci- ficity and had no cross-reaction with 1 000 ng/ml aflatoxin M1, gentamicin, kanamycin, streptomycin, tylosin, chloromycetin and melamine. [Condusion] The colloidal gold-labeled BLI method is not suitable for quantitative detection in actual production due to its small quantitative range in detection of β-lactam antibiot- ics, but it is a simple and rapid qualitative detection method that can be used in rapid detection of β-1actam antibiotic residue in milk.

高效液相色谱法测定β-内酰胺抗生素中残留乙酸的含量

目的建立测定β-内酰胺类抗生素原料中乙酸残留量的HPLC方法。方法采用多因素组内设计方法,确定色谱流动相的组成、比例和pH值。参考ICH Q2,从专属性、检出限和定量限、线性、准确度、精密度和耐用性等6个方面对方法进行验证。用所建立的方法对19种β-内酰胺类抗生素原料进行了测定。结果采用C_(18)色谱柱,流动相:甲醇-0.02 mol/L磷酸二氢钾,梯度洗脱;柱温25℃;检测波长220 nm。供试品、溶剂和流动相对乙酸测定没有明显干扰;乙酸的最低检出限约为0.029μg,最低定量限约0.12μg;从定量限到限度2倍浓度范围内,方法的线性关系良好,拟合直线方程为y=388866.7186x-177.5720,r2=0.9999;低中高浓度加样回收率平均分别为93%,96%和99%;方法的重复性和中间精密度分别为2.37%和2.11%;在3根不同C_(18)色谱柱上的耐用性良好。19种β-内酰胺抗生素原料中有3种筛查出残留乙酸。结论所建方法可以实现对β-内酰胺类抗生素原料中残留乙酸的准确定量,为该类原料的生产过程控制和标准物质研制提供了依据。

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。

β内酰胺类抗菌药物皮肤试验最佳证据总结

目的 对β内酰胺类抗菌药物皮肤试验的相关证据进行最佳总结。方法 以“β内酰胺类抗菌药物”“青霉素”“头孢菌素”和“皮肤试验”为主题词检索了中国知网、万方数据库、Elsevier、PubMed、SpringerLink、Wiley InterScience和web of science等数据库,并对国际指南网、美国国家指南网、英国国家指南中心网、欧洲指南网、澳大利亚临床指南网和新西兰指南网等指南网站进行检索,检索时限为建库至2023年1月31日。结果 共纳入证据8篇,其中7篇指南,1篇专家共识。总结出β内酰胺类抗菌药物皮肤试验适应证、操作基本原则和结果判读、过敏史的甄别与过敏反应的救治4个方面的证据。结论 医护人员应该按照循证医学证据进行临床实践,有助于提升对β内酰胺类抗菌药物皮肤试验的认知和操作规范,保证医疗安全,提高护理质量。

β-内酰胺类抗菌药物皮试阴性患者出现过敏反应的临床特征及影响因素分析

目的探讨β-内酰胺类抗菌药物皮试阴性患者出现过敏反应的临床特征及影响因素分析。方法回顾性分析2021年10月~2023年2月β-内酰胺类抗菌药物皮试检测为阴性的230例患者的临床资料,根据患者过敏反应发生情况将其分为过敏反应组和非过敏反应组,记录过敏反应组患者的临床特征,并采用单因素以及多因素Logistic回归分析筛选β-内酰胺类抗菌药物皮试阴性患者出现过敏反应的相关危险因素。结果本研究过敏反应发生率为15.65%,以瘙痒、皮疹、风团为主;两组患者年龄、慢性呼吸系统疾病史、联合用药、低蛋白血症、慢性肾功能不全、恶性肿瘤等一般资料对比差异有统计学意义(P<0.05);多因素Logistic回归分析结果显示,年龄、慢性呼吸系统疾病史、联合用药、低蛋白血症、慢性肾功能不全、恶性肿瘤均是β-内酰胺类抗菌药物皮试阴性患者出现过敏反应的独立危险因素(P<0.05)。结论β-内酰胺类抗菌药物皮试阴性患者过敏反应受年龄、慢性呼吸系统疾病史、联合用药、低蛋白血症、慢性肾功能不全、恶性肿瘤等多种因素影响。

β-内酰胺类抗生素/β-内酰胺酶抑制剂复方制剂点评标准的建立及应用分析

目的建立β-内酰胺类抗生素/β-内酰胺酶抑制剂复方制剂的点评标准,结合临床应用情况,分析其应用效果,促进临床合理使用β-内酰胺类抗生素/β-内酰胺酶抑制剂复方制剂。方法参照相关指南及专家共识,制订β-内酰胺类抗生素/β-内酰胺酶抑制剂复方制剂的药物利用评价(DUE)标准。通过建立的DUE标准,采用回顾性研究方法,评价2019年7—12月南华大学附属第二医院使用头孢哌酮/舒巴坦和哌拉西林/他唑巴坦的894例病例的用药合理性。结果894例病例中,适应证合理率为93.62%,给药剂量合理率为90.49%,用药疗程合理率为89.37%,微生物送检合理率为75.84%。结论建立的头孢哌酮/舒巴坦和哌拉西林/他唑巴坦DUE标准能够作为临床合理用药的重要参考,该院头孢哌酮/舒巴坦和哌拉西林/他唑巴坦使用基本合理。

抗生素对接受免疫检查点抑制剂治疗的晚期食管癌患者预后的影响

目的探讨抗生素对应用免疫检查点抑制剂(ICIs)治疗晚期食管癌患者疗效的影响。方法回顾性分析2020年1月—2022年9月在徐州医科大学附属医院接受ICIs治疗的晚期食管癌患者的临床资料。根据抗生素使用情况,将入组患者分为抗生素组与非抗生素组,并对患者的生存情况进行随访。结果共纳入136例晚期食管癌患者,使用抗生素65例,未使用抗生素71例,2组临床特征如性别、年龄、临床分期等差异均无统计学意义(P>0.05);抗生素组患者中位总生存期(mOS)与中位无进展生存期(mPFS)均缩短(P<0.05);多因素分析显示治疗方案是影响患者预后的独立危险因素。亚组分析表明喹诺酮类和氨基糖苷类药物对使用抗生素患者mOS与mPFS无明显影响(P>0.05),而β-内酰胺类药物可缩短使用抗生素患者的mOS和mPFS(P<0.05)。结论抗生素影响ICIs的疗效,不同类型抗生素对临床结果的影响不同。正在接受或计划接受ICIs的晚期食管癌患者,应避免使用β-内酰胺类抗生素。

Pathogenicity and Antimicrobial Resistance in Coagulase-Negative Staphylococci

The coagulase-negative staphylococci (CoNS) group was considered saprophytic or rarely pathogenic for many years. Since the first case of septicemia caused by CoNS, there has been a progressive increase in the prevalence of healthcare-associated infections caused by CoNS. The CoNS group has emerged as one of the main causes of nosocomial infections related to vascular catheters and prostheses, especially among immunocompromised patients. This gradual increase in infections is due to the change in the relationship between patients and procedures since CoNS are closely related to devices implanted in the human body. CoNS are successful in colonizing the host because they have several virulence mechanisms, such as biofilm formation and production of enzymes and toxins, in addition to several mechanisms of resistance to antimicrobials. Despite their great clinical relevance, few studies have focused on CoNS’s pathogenicity and resistance to antimicrobials, which reveals the current need to better understand the factors by which this group became pathogenic to humans and other animals. This review aims to synthesize the aspects related to the pathogenicity and antimicrobial resistance in CoNS.

《2023SWAB指南:疑似抗生素过敏的处理方法》解读

谨慎处理报告的抗生素过敏是抗生素管理的一个重要方面。荷兰抗生素政策工作组(SWAB)于2023年4月发布了《SWAB指南:疑似抗生素过敏的处理方法》以下简称(指南),指南依据对疑似抗生素过敏人群的比较和结果问题研究,对每个问题进行系统的文献检索,并通过证据评价系统对现有最佳证据进行审查后制定。指南就疑似抗生素交叉过敏,速发型过敏和迟发型过敏等问题进行阐述,为报告抗生素过敏患者选用抗生素治疗的床旁决策提供基于现有研究的循证建议。本文对指南涉及12个关键问题进行解读,以期为疑似抗生素过敏患者临床治疗提供参考,使患者获益。

ANTIBIOTIC USE AND NOSOCOMIAL INFECTIONS IN THE USA

Gram-negative bacteriacontinue to be the most common cause ofnosocomial infection, often resulting inextended hospitalization and mortality.Ascompared with penicillins and aminogly-cosides, potent beta-lactam antibioticshave been recently introduced with fewertoxic side efTects and a broader spectrum ofantibacterial activity. The cephalosporinsare the most widely used antibiotics in theUnited States and account for almost$ 1. 6 billion in U. S. health-care dollarsin 1987, cephalosporins commanded 55%of the inpatient/parenteral market and40% of the outpatient/oral market.However, gram-negative organisms suchaspseudomonas aeruginosa and Serratiaspp. may be resistant to the older cepha-losporins, and Enterococcus, methicillin-resistant Staphylococcus spp.and Candidaalbicans are resistant to all cephalosporins.These troublesome pathogens now causean increasing numbers of nosocomialinfections and superinfections in patientswho have received prolonged antibiotictreatment Unfortunately, nosocomial infe-ctions often affect the growing number ofimmunocompromised patients. In the future,nosocomial infections will be more frequentlyassociated with the emergnce of more resistantbacterial strains. Oral monotherapy alternativesto parenteral cephalosporin therapy arebeing tested, and if proven useful mayhelp reduce the upward trend in antibioticcosts.

猪源链球菌对β-内酰胺类抗生素的耐药性研究进展

猪链球菌病是生猪养殖中比较常见且危害较大的动物疫病,该病的病原是球菌科链球菌属的多种链球菌,其中猪链球菌2型是重要的人畜共患病原菌。β-内酰胺类抗生素一直是治疗猪链球菌病的首选药物,但受长期选用的影响,猪源链球菌对β-内酰胺类抗生素的耐药性逐渐增强,给猪链球菌病的临床治疗带来威胁。文章对猪链球菌病的流行性及病原特点、猪源链球菌对β-内酰胺类抗生素的耐药机制和耐药现状进行概述,以期为指导临床用药和新药研发提供参考。

抗生素重要片段侧链酸的高效合成工艺

单环β-内酰胺类抗生素是抗生素新药研发的重要热点领域,在氨基噻唑的C5位引入甲基为重要技术方案之一。在原有合成路线基础上,通过反应机理深度分析,以3-氧戊酸乙酯为起始原料,经5步反应,高效合成了C5位引入甲基的氨基噻唑侧链酸,为候选药物目标化合物DPI-2016的临床前期研究奠定了基础。

Post-appendectomy pelvic abscess with extended-spectrum beta-lactamase producing Escherichia coli : A case report and review of literature

BACKGROUND Appendicitis, the inflammation of the appendix, is the most common abdominal surgical emergency requiring expedient surgical intervention. Extendedspectrum beta-lactamases(ESBLs) are bacterial enzymes that catalyse the degradation of the betalactam ring of penicillins and cephalosporins(but without carbapenemase activity), leading to resistance of these bacteria to beta-lactam antibiotics. Recent increases in incidence of ESBL-producing bacteria have caused alarm worldwide. Proportion estimates of ESBLEnterobacteriaceae hover around 46% in China, 42% in East Africa, 12% in Germany, and 8% in the United States.CASE SUMMARY The impact of ESBL-producing bacteria on appendiceal abscesses and consequent pelvic abscesses are yet to be examined in depth. A literature review using the search words "appendiceal abscesses" and "ESBL Escherichia coli(E. coli)" revealed very few cases involving ESBL E. coli in any capacity in the context of appendiceal abscesses. This report describes the clinical aspects of a patient with appendicitis whodeveloped a postoperative pelvic abscess infected with ESBL-producing E. coli. In this report, we discuss the risk factors for contracting ESBL E. coli infection in appendicitis and post-appendectomy pelvis abscesses. We also discuss our management approach for postappendectomy ESBL E. coli pelvic abscesses, including drainage, pathogen identification, and pathogen characterisation. When ESBL E. coli is confirmed, carbapenem antibiotics should be promptly administered, as was done efficaciously with this patient. Our report is the first one in a developed country involving ESBL E. coli related surgical complications in association with a routine laparoscopic appendectomy.CONCLUSION Our report is the first involving ESBL E. coli and appendiceal abscesses, and that too consequent to laparoscopic appendectomy.

Probabilistic Antibiotic Therapy in the Infectious Diseases Department of the Yalgado Ouédraogo University Hospital (CHU-YO) in Ouagadougou, Burkina Faso

Introduction: In Burkina Faso, as in most developing countries, limited access to biological tests forces practitioners to resort very often to probabilistic antibiotic therapy. The objective of this study is to determine the extent of this prescription. Patients and Methods: This was a cross-sectional study with retrospective data collection of patients hospitalized in the infectious diseases department in the period from January 1, 2005 to December 31, 2020. The records of patients who received probabilistic antibiotic therapy were included. Results: During the study period, 330 patients had received probabilistic antibiotic therapy. The majority of patients were male (53%), with a sex ratio of 1.12. The mean age of the patients was 33 years ± 14. The age range of 20 to 40 years was the most represented (42%). Fifteen percent (15%) of patients were living with HIV. The majority of patients were from urban areas (56.4%). Forty-nine percent (49%) of the patients worked in the informal sector. Clinically, the reasons for consultation were dominated by fever, alteration of general condition, neurological disorders, digestive disorders, respiratory signs, urinary signs and diffuse pain. The physical examination showed that 48.1% of the patients had meningeal irritation syndrome, 10% had convulsions and 10% had focal signs, trismus was present in 4% of the patients and facial paralysis in 3%. In the digestive system, hepatomegaly was present in 29% of patients and digestive candidiasis in 31%. Respiratory examination showed crepitus and fluid effusion syndrome in 26.83% and 20.62% of patients respectively. The presumptive diagnosis was dominated by bacterial meningitis, salmonellosis and bronchopneumonia with banal germs. In terms of treatment, the beta-lactam family of drugs was the most prescribed. They were followed by aminoglycosides and fluoroquinolones. The evolution was marked by the death of 50 patients (15%). Conclusion: The most prescribed molecules belong to the family of Beta-lactam. And this prescription improved the outcome of patients. Bacterial susceptibility studies will allow better orientation of probabilistic antibiotic therapy in order to limit the emergence of multi-resistant bacteria.