Time for a change? Yes, but not to ciprofloxacin.
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Biomedical subjects
Publications and source records attributed to Keryn Christiansen.
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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.
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Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a notable cause of hospital-acquired infections. A statewide screening and control policy was implemented in Western Australia (WA) after an outbreak of epidemic MRSA in a Perth hospital in 1982. We report on statutory notifications from 1998 to 2002 and review the 20-year period from 1983 to 2002. The rate of reporting of community-associated Western Australia MRSA (WAMRSA) escalated from 1998 to 2002 but may have peaked in 2001. Several outbreaks were halted, but they resulted in an increase in reports as a result of screening. A notable increase in ciprofloxacin resistance during the study period was observed as a result of more United Kingdom epidemic MRSA (EMRSA) -15 and -16. WA has seen a persistently low incidence of multidrug-resistant MRSA because of the screening and decolonization program. Non-multidrug-resistant, community-associated WAMRSA strains have not established in WA hospitals.
Three distinct Enterococcus faecalis VanE-type isolates-BM4574, BM4575, and BM4576-obtained in Australia were studied. Expression of the resistance genes was constitutive in BM4575, probably due to a 2-bp deletion into the vanSE gene, and inducible in BM4574 and BM4576. Transcription analysis of the vanE operons suggested that the five genes were cotranscribed from an initiation site located 25 bp upstream from the ATG start codon of vanE.
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There are multiple interventions available that may help to control the development and spread of resistance to antimicrobial agents in bacteria implicated in community-acquired respiratory tract infections. Unfortunately, very few studies have assessed the effectiveness of these interventions using objective end-points, such as reduction in resistance rates and improvement in clinical outcomes. Most interventions are centered on reducing inappropriate or unnecessary use of antibiotics; others focus on reducing disease burden and bacterial colonization. With regard to antibiotic use, efforts should be concentrated at both the prescriber and consumer levels. Interventions that target prescribers include: provision of educational materials; strategies and tools to improve diagnosis; implementation of practice guidelines; personalized interactive sessions with feedback on the practice profile; and use of delayed prescription and alternative prescribing strategies. Optimal results are usually obtained when these interventions are combined with consumer education. Regulatory interventions (e.g. licensing regulations and controlled access to drugs), restrictions in the use of agents for growth promotion in animals, and use of nonantimicrobial therapies (e.g. probiotics) may help further to reduce inappropriate antibiotic use and thereby decrease the selective pressure for development of resistance. Infection-control strategies, public health measures, vaccination programs, and new antibiotics all have a role in minimizing the spread of resistant organisms. Ideally, resistance-control programs should include predefined criteria for success and integral audit processes based on objective end-points (antibiotic use, resistance trends, and health outcomes). Standardization of data collection is imperative so that the relative merits of various interventions can be compared. Effective implementation and audit of interventions is often difficult in developing countries owing to poor health-care infrastructures, lack of resources, poor education/training, and minimal regulatory controls on the supply and quality of antimicrobials. Substantial support from governments and health-care organizations across the globe is required to initiate and sustain effective intervention programs to control antimicrobial resistance.
An incidence of between 2 and 44 per 1000 population has been reported for community-acquired pneumonia. Epidemiologic studies describe a wide range of causative organisms, including Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella spp., Moraxella catarrhalis, Chlamydia pneumoniae and viruses such as influenza A and B. However, the frequency with which they are reported varies widely. On analysis of these studies, the variation can be explained by a number of factors. The results depend on the definition of pneumonia and the criteria for assigning a causative role to any particular organism. Older studies have not included diagnostic methods for newly described organisms such as C. pneumoniae and Legionella spp. The improved diagnostic methods for these organisms and for Mycoplasma pneumoniae are reflected in more recent studies. Further variation depends on the population studied. As many patients with mild pneumonia are successfully treated in the community, those studies that are hospital-based include patients with more severe pneumonia often in the elderly or in patients with underlying diseases such as chronic obstructive pulmonary disease. The prior use of antibiotics not only contributes to the high percentage of cases for which no etiologic agent is found, but also ensures that treatment failures are selected for hospitalization. This further changes the result, depending on the antibiotic agents used most commonly in the community. The inclusion of nursing home patients or groups where alcoholism is more common will also favor particular organisms. Finally, the timing of the study may be such that an epidemic is included. This has relevance mostly for Mycoplasma pneumoniae, C. pneumoniae, Legionella spp. and influenza. In the assessment of the patient with community-acquired pneumonia, any one of the above organisms can be considered to be responsible. As initial treatment is empirical, other information can be used to ensure that an antibiotic with an adequate spectrum is chosen. Factors of importance are age, underlying illness, severity of disease and any locally recognized epidemics or endemic organisms. Differences in clinical presentation are not sufficiently distinct to allow for accurate prediction of the causative agent. Similarly, chest radiograph changes are not sufficiently specific to discriminate reliably between diverse organisms such as S. pneumoniae, Mycoplasma pneumoniae and Legionella spp. Current recommendations for choice of an empirical antibiotic agent are therefore based, not on the assumption of a single etiologic agent indicated by clinical presentation or radiographic appearances, but on age of the patient, severity of illness, the presence of underlying conditions and the range of possible organisms in that patient group.
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