Synthesis and cloxacillin antimicrobial enhancement of 2-methylsulfonylimidazolyl-1,4-dihydropyridine derivatives

BACKGROUND AND THE PURPOSE OF THE STUDY: Hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) has been a major problem worldwide in chemotherapy of infection disease. This study was designed to assess the enhancing effects of a new group of dihydropyridine-3,5dicarboxamides, in combination with cloxacillin with distinctly different mechanisms of action against MRSAs. MATERIAL AND METHODS: Dihydropyridine-3,5-dicarboxamides with 2-methylsulfonylimidazole at 4 position 6a-k were synthesized by the reaction of corresponding aldehyde 5 with different N-aryl acetoacetamides 3 in the presence of ammonium hydroxide. Agar disc diffusion method was used to determine the antibacterial and potentiating activity of different synthetic compounds in the presence and absence of cloxacillin to evaluate their activity as modulators of multidrugresistant (MDR). RESULTS AND MAJOR CONCLUSION: The antibacterial effect of cloxacillin was enhanced by compounds 6g and 6h against cloxacillin-resistant strains (MRSA(1) and MRSA(2)). The potentiation was found 1 2 to be statistically significant (p<0.01). Compound 6g at concentration of 1000 μg/disc, caused a 329 percent potentiation of the activity of cloxacillin against MRSA(1).     

氟喹诺酮类药物治疗耐多药结核病临床疗效研究

目的:观察和评价氟喹诺酮类药物结合一、二线抗TB药物治疗耐多药结核病(MDR-TB)临床有效性及安全性。方法:将156例MDR-TB患者随机分为2组,其中观察组采用6MfxZPtoKmPAS/18MfxZPtoPAS(莫西沙星+吡嗪酰胺+丙硫异烟胺+卡那霉素+对氨基水杨酸)化疗方案;对照组采用6LfxZPtoKmPAS/18LfxZPtoPAS(左氧氟沙星+吡嗪酰胺+丙硫异烟胺+卡那霉素+对氨基水杨酸)化疗方案。疗程24个月。结果:2组疗程完成后,观察组79例患者显效62例,总有效率为96.20%,对照组77例患者显效49例,总有效率为84.42%,2组临床疗效比较差异有显著性(P<0.01),而观察组患者3个月、12个月痰菌阴转率分别为55.69%,73.42%,24个月疗程结束时累计有68例患者痰菌阴转,阴转率为86.08%,均高于对照组,且差异显著有统计学意义(P<0.05),观察组不良反应发生率为16.46%(13/79);对照组为15.58%(12/77),2组比较差异无统计学意义(P>0.05)。结论:氟喹诺酮类药物结合一、二线抗TB药物治疗耐多药结核病(MDR-TB)临床无交叉耐药性,疗效显著,且有较高安全性。     

PDCA循环法在多重耐药菌医院感染管理中的应用

目的加强多重耐药菌管理,预防和控制多重耐药菌传播,保障患者和医护人员安全,提高医疗质量。方法 2011年将PDCA循环法用于多重耐药菌医院感染管理,提高认识,加强医院感染意识,加强组织建设,建立多部门合作机制,更新制定多重耐药菌相关管理制度及措施。结果 2011—2013年未发生多重耐药菌医院内交叉感染,提高了多重耐药菌防控意识,达到了多重耐药菌医院感染管理持续改进,有效避免了医院感染流行。结论 PDCA循环法应用于多重耐药菌医院感染管理,可提升存在问题的整改执行力,有助于医疗质量的持续改进。     

Levofloxacin for the treatment of pneumonia caused by Streptococcus pneumoniae including multidrug-resistant strains: pooled analysis

ABSTRACT

Objective: To determine the clinical and microbiologic efficacy of levofloxacin for the treatment of subjects with pneumonia caused by multidrug-resistant (MDR) Streptococcus pneumoniae (MDRSP) and non-MDRSP strains.

Research design and methods: A pooled analysis was conducted using data from ten clinical studies in pneumonia: five comparative studies and five noncomparative studies conducted from 1992 to 2002. This analysis included data from levofloxacin-treated subjects with S.?pneumoniae isolated at study entry. Susceptibility of S.?pneumoniae isolated from subjects at study entry was determined against representative agents from five antimicrobial classes: tetracyclines, sulfonamides, second-generation cephalosporins, penicillins, and macrolides. Isolates were classified as MDRSP (based on resistance to two or more antimicrobial classes) or non-MDRSP (intermediate resistance or susceptible to all classes or resistant to 1 antimicrobial class). Clinical and microbiologic efficacy of levofloxacin (i.v., p.o., or i.v./p.o. for 5 to 14 days) in the microbiologically evaluable population was determined at post-therapy; a test for homogeneity of the odds ratio of the difference in clinical success for comparative versus noncomparative studies was performed.

Main outcome measures and results: The main outcome measures were clinical success rates and microbiologic eradication rates of 419 microbiologically evaluable levofloxacin-treated subjects with MDRSP or non-MDRSP. Clinical success rates were 96.3% (52/54) and 95.1% (347/365), respectively (difference ?1.2; 95% confidence interval [CI]: ?6.7, 4.3). Similarly, per pathogen microbiologic eradication rates for MDRSP and non-MDRSP were 96.3% (52/54) and 95.6% (350/366), respectively (difference ?0.7; 95%?CI: ?6.1, 4.8). Study limitations include the use of data from comparative and noncomparative studies. A test for homogeneity of the odds ratios for clinical success in comparative versus noncomparative studies showed no significant difference (p?=?0.27).

Conclusions: These data support the use of levofloxacin for patients with community-acquired pneumonia caused by S.?pneumoniae, including MDR strains.     

Infection Control Practices in Patients With Hematological Malignancies and Multidrug-Resistant Organisms: Special Considerations and Challenges

Infectious complications contribute greatly to morbidity and mortality in patients with hematological malignancies. As these patients undergo prolonged chemotherapy and are in frequent contact with health care settings, they are at high risk for nosocomial and health care-associated infections. This long-term relationship with the hospital setting represents a major opportunity for infection prevention. In this review, we describe several infection control strategies that are currently used to reduce the transmission of hospital-acquired infections in patients with hematological malignancies, particularly infections with multidrug-resistant organisms.     

三磷酸腺苷发光法在耐多药结核分枝杆菌诊断中的运用

目的通过与罗氏固体培养法比较,评估三磷酸腺苷发光法检测耐多药结核分枝杆菌的可行性。方法采用三磷酸腺苷发光法与罗氏固体培养法同时检测和分析149例临床分离的结核分枝杆菌。结果三磷酸腺苷发光法与罗氏固体培养法的一致率为92．6％（138／149）,差异无统计学意义（X^2=0．57,P=0．45）。三磷酸腺苷发光法检测时间为（6．6±2．1）d,明显快于传统罗氏固体培养法的28d（t=422．7,P〈0．001）。结论与常规检测方法比较,三磷酸腺苷发光法具有快速、简便、准确性高等优点,对耐多药结核患者的早期诊断和耐药结核分枝杆菌流行的控制有很大帮助,适合实验室开展。     

Diagnosis of ventilator-associated respiratory infections (VARI): microbiologic clues for tracheobronchitis (VAT) and pneumonia (VAP)

Intubated patients are at risk of bacterial colonization and ventilator-associated respiratory infection (VARI). VARI includes tracheobronchitis (VAT) or pneumonia (VAP). VAT and VAP caused by multidrug-resistant (MDR) pathogens are increasing in the United States and Europe. In patients with risk factors for MDR pathogens, empiric antibiotics are often initiated for 48 to 72 hours pending the availability of pathogen identification and antibiotic sensitivity data. Extensive data indicate that early, appropriate antibiotic therapy improves outcomes for patients with VAP. Recognizing and treating VARI may allow earlier appropriate therapy and improved patient outcomes.     

规范医院感染管理降低多药耐药菌传播

目的加强合理用药、标准预防和接触隔离预防的实施,降低多药耐药菌的感染与传播。方法根据规范要求制定医院感染管理相关制度、流程,运用选择式目标管理,要求多药耐药菌隔离率≥85.0%;手消毒剂使用合格率≥80.0%;手术预防用药时机达标率≥80.0%。结果经多药耐药菌隔离、手卫生、手术预防用药的目标管理,产超广谱β-内酰胺酶(ESBLs)肺炎克雷伯菌、ESBLs大肠埃希菌、耐甲氧西林金黄色葡萄球菌(MRSA)、耐甲氧西林凝固酶阴性葡萄球菌(MRSCN)的感染分别由2006年的55.4%、50.7%、81.6%和83.0%下降至2010年的26.5%、43.8%、65.9%和62.4%。结论合理使用抗菌药物,规范隔离预防措施的实施是降低多药耐药菌感染的有效手段。     

某综合医院多药耐药菌医院感染调查与分析

目的了解多药耐药菌(MDROs)医院感染的特点。方法对2008年7月1日-2010年6月30日所有金黄色葡萄球菌、肠球菌属、大肠埃希菌、肺炎克雷伯菌和鲍氏不动杆菌培养阳性的患者进行前瞻性调查,调查多药耐药菌医院感染情况。结果 2008年7月-2010年6月住院患者中发生金黄色葡萄球菌、肠球菌属、鲍氏不动杆菌、大肠埃希菌和肺炎克雷伯菌感染1646例次,MDROs感染比例为44.3%,医院感染中MDROs感染比例为52.2%,较MDROs总的感染比高,且差异有统计学意义(P<0.01);在各科室中,重症监护病房MDROs医院感染比例最高,占68.5%;在各医院感染部位中,以呼吸系统MDROs感染比例最高占68.1%。结论在多药耐药菌感染预防控制过程中,要特别关注重症监护病房以及呼吸系统多药耐药菌医院感染的预防控制。