Prevalence of colonisation with third-generation cephalosporin-resistant Enterobacteriaceae in ICU patients of Heidelberg University Hospitals

The aim of this study was to assess colonisation and transmission of third-generation cephalosporin-resistant Enterobacteriaceae (CRE) from patients in 16 intensive care units. A prospective, repetitive point prevalence survey was performed over 6 months, involving samples from 1851 patients. CRE were isolated from 186 (10%) patients, with Enterobacter spp. being the most common. Mean point prevalence rates were significantly higher for paediatric wards (22.5%) compared to surgical (8.1%) and medical (5.5%) units. All CRE isolates were typed by pulsed-field gel electrophoresis. Non-outbreak nosocomial transmission rates of these pathogens were calculated as 12.8% for paediatric patients, compared to 6.8% for adult patients, which may reflect differences in sensitivity to overgrowth with resistant bacteria and contact with health care workers.     

Allergic reactions to betalactams: studies in a group of patients allergic to penicillin and evaluation of cross-reactivity with cephalosporin

A group of 34 penicillin-allergic patients was studied to determine skin test reactivity to the different penicillins involved in inducing the allergic reaction and the cross-reactivity with side-chain-related and side-chain-unrelated cephalosporins. All the subjects selected for the study had to be skin test positive to at least one of the following determinants: benzyl-penicilloyl-polylysine (BPO-PLL), minor-determinant mixture (MDM), amoxicillin (AX), or ampicillin (AMP), or to possess in vitro IgE to the following conjugates: benzyl-penicilloyl-human-serum albumin (BPO-HSA), ampicilloyl-human-serum albumin (AMP-HSA), and amoxicilloyl-human-serum albumin (AX-HSA). Cephalexin (CE) and ceftazidime (CEF) were used to assess cross-reactivity. If skin tests to any of these compounds were positive, the patient was considered to be allergic; if negative, a challenge test was performed. Sixteen patients (47%) were skin test positive to BPO and/or MDM, and nine (26%) exclusively to AX and/or AMP. In three cases (8%), the RAST was positive although the skin test was negative; one to BPO-HSA and two to AX-HSA and AMP-HSA. Six patients (17%) needed to be challenged with the penicillin involved to establish the diagnosis. In five patients (14%), the skin tests were positive to CE and in none to CEF. In all the others, the skin tests were negative to both cephalosporins, and the patients tolerated the drugs when challenged. These results indicate the relevance of side-chain-specific minor determinants in betalactams allergy and provide support for the role of this chemical structure in the evaluation of cross-reactivity between penicillins and cephalosporins.     

三代头孢菌素致尿毒症患者中枢神经系统不良反应的护理

目的总结三代头孢菌素引起尿毒症患者中枢神经系统不良反应的护理经验。方法对12例尿毒症患者使用三代头孢菌素后出现神经、精神症状,进行临床分析并采取相应的防护措施。结果 12例均及时停药,给予对症、支持治疗,其中4例维持性血液透析患者各增加1次透析、6例进行急诊血液透析,所有病例症状消失。结论尿毒症患者应用三代头孢菌素时需详细询问病史,严密观察用药反应,出现中枢神经系统不良反应后及时停药并积极采取相应的治疗护理措施,可避免严重并发症发生。     

Ceftaroline fosamil for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infection

Early diagnosis and therapy of the underlying insulin resistance of heritable polycystic ovary syndrome (PCOS), often manifested at menarche, facilitate the reduction and/or reversal of the reproductive and metabolic morbidity of PCOS, as well as reduce the risk factors for cardiovascular disease. PCOS is characterised by oligoamenorrhoea, clinical and biochemical hyperandrogenism, infertility, recurrent miscarriage, insulin resistance, hyperinsulinaemia, gestational diabetes, impaired glucose tolerance, Type 2 diabetes, morbid obesity, hypertension, hypofibrinolysis, hypertriglyceridaemia, low levels of high density lipoprotein-cholesterol and a sevenfold risk increase in cardiovascular disease. Insulin sensitising-lowering agents reduce insulin resistance and hyperinsulinaemia, reverse PCOS endocrinopathy and ameliorate the reproductive, metabolic and cardiovascular morbidity of the disorder. The largest literature on the subject discusses metformin. Improved pregnancy outcomes in women with PCOS receiving metformin may be attributed to its ability to reduce insulin resistance, hyperinsulinaemia and hypofibrinolytic plasminogen activator inhibitor activity by the enhancement of folliculogenesis and improvement of oocyte quality.     

Antibiotic treatment for acute haematogenous osteomyelitis of childhood: moving towards shorter courses and oral administration

Acute haematogenous osteomyelitis (AHOM) of childhood usually affects the long bones of the lower limbs. Although almost any agent may cause AHOM, Staphylococcus aureus is the most common bacterium, followed by Streptococcus pneumoniae and, in some countries, Salmonella spp. and Kingella kingae. Magnetic resonance imaging (MRI) has improved the diagnostic accuracy of traditional radiography and scintigraphy. Except for the pre-treatment diagnostic sample from bone before the institution of antibiotic therapy, no other surgery is usually required. Traditionally, non-neonatal AHOM has been treated with a 1-3-month course of antibiotics, including an intravenous (i.v.) phase for the first weeks, but recent prospective randomised studies challenge this approach. For most uncomplicated cases, a course of 20 days including an i.v. period of 2-4 days suffices, provided large enough doses of a well-absorbed agent (clindamycin or a first-generation cephalosporin, local resistance permitting) are used, administration is four times daily and most symptoms and signs subside within a few days. Serum C-reactive protein (CRP) is a good guide in monitoring the course of illness, and the antimicrobial can usually be discontinued if CRP has decreased to <20 mg/L. Newer and costly agents, such as linezolid, should be reserved for cases due to resistant S. aureus strains. AHOM in neonates and immunocompromised patients probably requires a different approach. Because sequelae may develop slowly, follow-up for at least 1 year post hospitalisation is recommended.     

药源性双硫仑样反应13例误诊分析

目的:探讨药物所致双硫仑样反应的临床特点及误诊原因。方法:回顾性分析初诊误诊的13例药源性双硫仑样反应患者的临床资料。结果:误诊为输液反应的3例,酒精中毒的3例,药物过敏的2例,急性冠脉综合征的1例,肺炎合并心力衰竭的1例,先兆流产的1例,感染性休克的1例,中暑的1例,误诊时间为1～12h,中位时间5h。对患者病史询问不详,对是否使用乙醇制品未予重视及医生对此病认识较少是主要的误诊原因。结论:提高对此病的认识,详细询问病史,是避免误诊的主要方法。     

Synthesis and relation between physicochemical properties and oral absorption of 7-O-acylmandelamido-3-methyl-3-cephem-4-carboxylic acids

O-Acylates (IV) of 7-d-mandelamido-3-methyl-3-cephem-4-carboxylic acid (I) were prepared and their physicochemical properties and oral absorption in mice were measured to search for an orally active cephalosporin having a 7-acyl group other than phenylglycine analogs. The pK_a and log P values of IB were 2.8 and 1.02–3.54, respectively, and IV were hydrolyzed to the parent drug (I) in a homogenate of mouse small intestine. The esters, IVb (propionate), IVc (n-butyrate), IVd (i-butyrate), and IVe (n-valerate) produced higher plasma levels of I and improved relative bioavailability (BA) than those observed after oral dosing with I. Among the esters, IVe showed the highest BA, 40.3%. Good correlations between log P and log BA and between log P and peak plasma level (log C_max) were observed. The esters resulting in good BA have log P values similar to those of orally active penicillins having an acyl group other than phenylglycine analogs, e.g. propicillin (PP-PC) and phenethicillin (PE-PC). The present study indicates that an ester prodrug of the parenteral cephalosporin having a 7-acyl group other than phenylglycine analog can be absorbed effectively through the gastrointestinal tract when log P and the pK_a values are in a selected range.     

7-氨基去乙酰氧基头孢烷酸的合成研究

7-氨基去乙酰氧基头孢烷酸（7-ADCA）是头孢菌素合成的重要中间体，一般以青霉素为原料，经氧化，扩环-重排，裂解三步反应制备。本文研究用ρ=20%过氧乙酸作氧化剂，反相HPLC监测扩环-重排反应，酰化酶反应裂解的方法。该工艺先进，反应温和，收率高，适合于工业化规模生产。