GRACE and the development of an education and training curriculum.

Antimicrobial resistance is a serious threat and compromises the management of infectious disease. This has particular significance in relation to infections of the respiratory tract, which are the lead cause of antibiotic prescribing. Education is fundamental to the correct use of antibiotics. A novel open access curriculum has been developed in the context of a European Union funded research project Genomics to combat Resistance against Antibiotics in Community-acquired lower respiratory tract infections in Europe (GRACE http://www.grace-lrti.org). The curriculum was developed in modular format and populated with clinical and scientific topics relevant to community-acquired lower respiratory tract infections. This curriculum informed the content of a series of postgraduate courses and workshops and permitted the creation of an open access e-Learning portal. A total of 153 presentations matching the topics within the curriculum together with slide material and handouts and 104 webcasts are available through the GRACE e-Learning portal, which is fully searchable using a 'mindmap' to navigate the contents. Metrics of access provided a means for assessing usage. The GRACE project has permitted the development of a unique on-line open access curriculum that comprehensively addresses the issues relevant to community-acquired lower respiratory tract infections and has provided a resource not only for personal learning, but also to support independent teaching activities such as lectures, workshops, seminars and course work.

Sporicides for Clostridium difficile: the devil is in the detail.

A taskforce has now been formed with representatives from the Department of Health's Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infection (ARHAI), the Hospital Infection Society (HIS), the Department of Health (England) and the Health Protection Agency. The aims of the ARHAI/HIS Taskforce on Sporicidal Disinfectants are: to develop an accepted standard for laboratory testing of disinfectants which claim to have activity against C. difficile spores; to develop a network of laboratories with capability to perform in vitro assays of sporicidal activity of disinfectants; and to explore the creation of a national quality assessment scheme for laboratories which perform in vitro assays of sporicidal activity of disinfectants.

Safety and efficacy of glycopeptide antibiotics.

It would be difficult to envision the practice of infectious diseases over the past 20 years without the availability of the glycopeptide antibiotics. The two agents currently in clinical use, vancomycin and teicoplanin, have proven remarkably versatile in many common applications. Several attributes of these agents account for this favourable profile: (i) their broad spectrum of activity against Gram-positive bacteria, including strains resistant to many other antimicrobials; (ii) their favourable pharmacokinetic properties that allow the once- or twice-daily dosing regimens that have made out-of-hospital therapy possible; and (iii) their generally good safety profiles which, along with their structural dissimilarity to beta-lactam and other antimicrobials, permits their use in many patients who are intolerant of other antibiotic regimens. It is not entirely surprising, therefore, that despite more than 40 years of clinical use and the interim appearance of bacterial strains resistant to this drug class, there remains continued interest in the development of newer members of the glycopeptide antibiotic class. This paper is intended to provide a global overview of the efficacy and safety of glycopeptide antibiotics currently in use, as background to understanding the need for and potential roles of new agents of this class.

Hepatitis C virus infection.

Hepatitis C virus (HCV) infection is a major public health problem. Up to 3% of the world's population is infected with HCV, and at least 200 000 adults in the UK carry the virus. Of those exposed to HCV, 80% become chronically infected, and at least 30% of carriers develop chronic liver disease, including cirrhosis and hepatocellular carcinoma. This review provides an overview of selected features of the molecular biology and pathogenesis of HCV infection, and thereafter discusses in detail the epidemiology of HCV, the hepatic and extra-hepatic diseases caused by the virus, and the current treatment options for both acute and chronic virus infection. The special cases of healthcare workers, prison inmates and individuals coinfected with human immunodeficiency virus and HCV are considered in detail.

Immunomodulating activity of rifampicin.

It has been shown that some antibiotics can modify cytokine production. We have examined the effect of rifampicin on secretion of interleukin-1beta (IL-1beta), IL-6, IL-10, and tumor necrosis factor alpha (TNF-alpha) by lipopolysaccharide (LPS)-stimulated or heat killed staphylococci (Pansorbin) stimulated monocytes. Secretion of IL-1beta and TNF-a were significantly inhibited (P<0.002) whereas secretion of IL-6 and IL-10 were significantly increased (P<0.003) by rifampicin treated mononuclear cells. Rifampicin had immunomodulatory effects through its capacity to alter the secretion of tested cytokines by human monocytes.

Introduction: standards of antibacterial performance.

The development and clinical use of antimicrobial agents continue to evolve in line with new science, understanding and needs. While antimicrobial resistance remains an important determinant for drug development and therapeutic choice, pharmacokinetic and pharmacodynamic parameters are having an ever-increasing importance in defining performance targets for new and established agents. Recently licensed new therapies are largely directed at serious hospital-associated Gram-positive infections, whereas in the community, therapeutic choice remains dependent on well-established agents from limited classes of antimicrobials. In order to maximise the benefits from such agents, it is appropriate that dosage regimens and antibacterial choices be reviewed in the light of new knowledge, particularly in the area of pharmacokinetics and pharmacodynamics. Antimicrobial resistance continues to evolve, notably within respiratory pathogens, therefore steps must be taken to maintain optimum therapeutic outcomes and also limit the development and spread of resistant strains. Whilst changes in patient and physician attitudes and behaviour towards better quality prescribing are important, new agents must also be developed to provide adequate coverage for resistant pathogens. Development times for novel agents and classes of antimicrobials are long, with uncertain safety profiles and chances of success. Thus, the development of new formulations of existing agents, designed to overcome current resistance patterns, constitutes a potentially important additional strategy towards appropriate prescribing.

Sales of over-the-counter remedies as an early warning system for winter bed crises.

OBJECTIVES: To evaluate the pattern of emergency adult medical admissions during the winter period and the usefulness of sales of over-the-counter cough/cold remedies as a predictor of these. METHODS: The databases of a single NHS trust acute unit and pharmacy outlets in its catchment area were analyzed retrospectively, comparing numbers of emergency admissions, ICD-10 discharge codes, local electronic point-of-sale (EPOS) and national sales data. RESULTS: Over nine consecutive winter periods from 1992/3, peak admissions always occurred within a defined ten-day period from 29th December to 9th January. Emergency admissions increased significantly during this period (P = 0.0002). Pharmaceutical/retail data were available for three consecutive winters 1998/99, 1999/2000 and 2000/2001, none of which coincided with increased influenza activity nationally. Acute respiratory illness as defined by International Classification of Diseases, 10th edition (ICD-10) discharge coding did not appear to contribute to the increase in admissions at the peak. However, National and Local EPOS sales were positively correlated with admissions and the rate of EPOS sales exceeded an empiric threshold of 1000 units per week two weeks prior to the admissions peak in each year. CONCLUSIONS: Emergency admissions over the winter period are increasing and can be expected within a period of only ten days each year. No firm relationship between acute respiratory illness and admissions could be defined but local EPOS data may give up to two weeks warning of the peak in admissions and merits further prospective evaluation.

Limitations of presently available glycopeptides in the treatment of Gram-positive infection.

The glycopeptide antibacterial drugs vancomycin and teicoplanin are widely used in hospitals for therapy of severe or multiresistant Gram-positive infections, notably staphylococcal, enterococcal and rarely pneumococcal. Vancomycin has also been used in the management of Clostridium difficile enteropathy. The incidence and potential for resistance differ between agents. The in vitro activity, pharmacokinetics and clinical use of glycopeptide, as well as epidemiology of glycopeptide resistance are discussed. There are limited comparative studies indicating the need for further investigation. Therapeutic drug monitoring has been widely used for vancomycin and less commonly for teicoplanin, but remains controversial. Advances in our understanding of their pharmacodynamics and clinical studies are helping clarify the situation. This paper reviews the current literature and highlights limitations of glycopeptides in treating Gram-positive infection.

A novel method for collecting and detecting amoxycillin in urine: a tool for testing antibiotic compliance in the community.

Assessing compliance to prescribed antibiotics in community studies of respiratory tract infections is difficult. We describe a simple method for collecting and detecting amoxycillin in urine using urine dip-sticks in conjunction with a bioassay. Urine was collected at timed intervals from eight healthy volunteers following oral amoxycillin administration. Dip-sticks inoculated with urine collected 1 and 8 h after antibiotic resulted in mean zones of inhibition of 1.75 and 1.37 cm, respectively. Amoxycillin activity remained demonstrable 14 days after inoculation of dip-sticks with urine. Dip-sticks inoculated with urine from control subjects who had not taken amoxycillin did not cause inhibition.

Ciprofloxacin: efficacy and indications.

Ciprofloxacin's strength is in 'below-the-diaphragm' indications. Information about the efficacy of the new fluoroquinolones in this indication is currently limited. Ciprofloxacin is effective in both uncomplicated and complicated urinary tract infections, but is probably best reserved for complicated, hospital-acquired or recurrent infections. Ciprofloxacin is effective in complicated and severe lower respiratory tract infections, including those in patients with infective exacerbations of chronic bronchitis and cystic fibrosis, and pseudomonal infections. Ciprofloxacin is effective in the treatment of serious, non-self-limiting intra-abdominal infections, peritonitis in CAPD, pelvic inflammatory disease, endometritis and gall-bladder infections. Ciprofloxacin is effective in the treatment of a range of serious, non-self-limiting gastrointestinal infections (e.g. Salmonella and typhoid fever). Ciprofloxacin is effective in the empirical treatment of febrile neutropenic episodes, and prophylaxis of gram-negative bacteraemia in neutropenia and bone marrow transplantation. Ciprofloxacin is also effective in a range of other indications (e.g. eye infections, skin and soft tissue infections, bone and joint infections, and gonorrhoea).

Self-medication of antibacterials without prescription (also called 'over-the-counter' use). A report of a Working Party of the British Society for Antimicrobial Chemotherapy.

The availability of antimicrobial agents for self-medication may increase and could include antibacterial agents for oral or topical use. Wholesale deregulation of antibacterials would be undesirable and likely to encourage misuse of classes of agents currently important in the management of serious infections. Changed regulation from Prescription-Only Medicine (POM) to Pharmacy (P) medicine of selected agents with indications for short-term use in specific minor infections and illness is likely to have advantages to the user. However, safeguards to their use would need to be included in the Patient Information Leaflet (PIL). Agents and indications for self-medication are discussed. Any alteration in licensed status from POM to P will require careful risk-benefit assessment, including the likely impact on bacterial resistance. Safety issues also include concerns relating to age of the user, pregnancy, underlying disease and the potential for drug interactions. The importance of appropriate information with the PIL is emphasized, as is the role of the pharmacist, while ways of improving adverse event notification and monitoring are discussed. The paucity of good denominator-controlled data on the prevalence of in-vitro resistance is highlighted, and recommendations for improving the situation are made. There are currently no levels of resistance accepted by regulatory bodies on which to base a licensing decision, be it for granting a product licence, renewal of a licence or a change in licensed status from POM to P. Due consideration should be given to: the validation of user-defined indications in comparison with those medically defined; the enhancement of pharmacy advice in the purchase of such agents; improved safety monitoring; the establishment of systematic surveillance of susceptibility data.

A review of worldwide experience with sparfloxacin in the treatment of community-acquired pneumonia and acute bacterial exacerbations of chronic bronchitis.

The worldwide occurrence of community-acquired pneumonia (CAP) shows an undiminished prevalence of this serious illness and hospitalisation is common in those patients with severe illness. The diversity of bacterial pathogens that can act as aetiologic agents presents a challenge to initial empiric antimicrobial management. In recent years, treatment has been further complicated by an increased incidence of antibiotic resistance in pathogens such as Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. The newly available fluoroquinolones including sparfloxacin offer an alternative approach to empiric management. Sparfloxacin is active against many typical and atypical pathogens, as well as strains resistant to conventional agents. In comparative studies, the in vitro potency of sparfloxacin and its pharmacokinetic profile have been confirmed. The clinical trial efficacy and safety data suggest it might be a useful empiric therapy for both CAP and acute bacterial exacerbation of chronic bronchitis.

Acute exacerbation of vasculitis during interferon-alpha therapy for hepatitis C-associated cryoglobulinaemia.

A significant, previously unreported, adverse reaction to interferon-alpha therapy is reported. Immediately after the commencement of low dose therapy a man with hepatitis-C associated cryoglobulinaemia developed a purpuric rash and a severe, reversible impairment of renal function. This observation may elucidate the immunopathogenesis of vasculitis.