Aciclovir desensitisation and rechallenge.

A 29-year-old patient with HIV developed a facial angioedema hypersensitivity reaction to aciclovir when treated for acute retinal necrosis secondary to a herpes virus infection. She developed a similar reaction to famciclovir. Successful rapid desensitisation with oral aciclovir was performed and she became tolerant to aciclovir. She successfully completed 28 months of continuous treatment with no further reactions. However, 28 months later she experienced blurred vision and resumed taking oral aciclovir without a preceding desensitisation regimen. No allergic reaction occurred.

Antimicrobial drug resistance, regulation, and research.

Innovative regulatory and legislative measures to stimulate and facilitate the development of new antimicrobial drugs are needed. We discuss research approaches that can aid regulatory decision making on the treatment of resistant infections and minimization of resistance selection. We also outline current and future measures that regulatory agencies may employ to help control resistance and promote drug development. Pharmacokinetic/pharmacodynamic research models offer promising approaches to define the determinants of resistance selection and drug doses that optimize efficacy and reduce resistance selection. Internationally, variations exist in how regulators use drug scheduling, subsidy restrictions, central directives, educational guidelines, amendments to prescribing information, and indication review. Recent consultations and collaborations between regulators, academics, and industry are welcome. Efforts to coordinate regulatory measures would benefit from greater levels of international dialogue.

Antibiotic resistance: a view from the prescriber.

Antibiotic resistance is increasingly affecting the management of infectious diseases. The prescribing clinician is not only important to the development of the problem but also central to its solution. This article addresses the current weaknesses in the information systems and the evidence base that support prescribing. Remedies necessary for improvements in prudent prescribing include better guidance in managing specific diseases where resistance is of prognostic significance and also increasing diagnostic precision.

Educational interventions to improve antibiotic use in the community: report from the International Forum on Antibiotic Resistance (IFAR) colloquium, 2002.

National and international strategies for the control of antibiotic resistance recommend education for health-care professionals and the public to promote prudent antibiotic use. This paper, based on discussions at the 2002 colloquium of the International Forum on Antibiotic Resistance (IFAR), provides an international discourse between theoretical approaches to behaviour change and practical experience gained in large-scale antibiotic use educational campaigns. Interventions are more likely to be effective if their aim is to change behaviour, rather than provide information. They should target all relevant groups, especially parents, children, day-care staff, and health-care professionals. They should use clear and consistent messages concerning bacterial versus viral infection, prudent antibiotic use, symptomatic treatment, and infection-control measures (eg, handwashing). Campaigns should use a range of communications using pilot-testing, strong branding, and sociocultural adaptation. Prime-time television is likely to be the most effective public medium, while academic detailing is especially useful for health-care professionals. Multifaceted interventions can improve antibiotic prescribing to some degree. However, there are few data on their effects on resistance patterns and patient outcomes, and on their cost-effectiveness. Current research aims include the application of behaviour-change models, the development and validation of prudent antibiotic prescribing standards, and the refinement of tools to assess educational interventions.

Rifampicin concentrations in bronchial mucosa, epithelial lining fluid, alveolar macrophages and serum following a single 600 mg oral dose in patients undergoing fibre-optic bronchoscopy.

The concentrations of rifampicin in epithelial lining fluid (ELF), human alveolar macrophages (AM), bronchial mucosal biopsies and serum were measured after a single oral dose of 600 mg rifampicin from 15 patients undergoing fibre-optic bronchoscopy. The samples of ELF, AM, the bronchial mucosal biopsies and serum were obtained approximately 2-5 h after dosing. The mean concentrations (mean +/- standard error) were 5.25 mg/L (+/-0.67) in ELF, 7.93 mg/kg (+/-1.61) in bronchial biopsies, 15.48 mg/L (+/-1.41) in serum and 251.8 mg/L (+/-65.92) in alveolar macrophages. These site concentrations exceeded the MIC90 for common respiratory pathogens including Mycobacterium tuberculosis and support the observed clinical efficacy of rifampicin in the treatment of a wide range of respiratory tract infections.

A critical assessment of published guidelines and other decision-support systems for the antibiotic treatment of community-acquired respiratory tract infections.

Guidelines are an important means by which professional associations and governments have sought to improve the quality and cost-effectiveness of disease management for infectious diseases. Prescribing of initial antibiotic therapy for community-acquired respiratory tract infections (RTIs) is primarily empiric and physicians may often have a limited appreciation of bacterial resistance. Recent guidelines for managing RTIs have adopted a more evidence-based approach. This process has highlighted important gaps in the existing knowledge base, e.g. concerning the impact of resistance on the effectiveness of oral antibiotics for outpatient community-acquired pneumonia and the level of resistance that should prompt a change in empiric prescribing. In upper RTIs, the challenge is to identify patients in whom antibiotic therapy is warranted. Concentrated, sustained efforts are needed to secure physicians' use of guidelines. The information should be distilled into a simple format available at the point of prescribing and supported by other behavioral change techniques (e.g. educational outreach visits). Advances in information technology offer the promise of more dynamic, computer-assisted forms of guidance. Thus, RTI prescribing guidelines and other prescribing support systems should help control bacterial resistance in the community. However, their effect on resistance patterns is largely unknown and there is an urgent need for collaborative research in this area. Rapid, cost-effective diagnostic techniques are also required and new antibiotics will continue to have a role in disease management.

Penicillin-resistant pneumococci-implications for management of community-acquired pneumonia and meningitis.

Penicillin-nonsusceptible Streptococcus pneumoniae isolates have become increasingly prevalent worldwide. They are well-known agents of community-acquired infections such as otitis media, pneumonia and bacterial meningitis. Therapy of pneumococcal infections is made difficult by the emergence and spread of bacterial resistance to penicillin and other beta-lactams, as well as other antimicrobials such as macrolides. This article reviews current concepts of epidemiology and the implications of penicillin-nonsusceptible pneumococci for management of community-acquired pneumonia and meningitis.