Over the last decade, methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged as serious pathogens. These strains are often multiresistant to several antibiotic classes and are a ...major cause of serious hospital- and now community-acquired infections and associated morbidity and mortality. As a result of increasing antimicrobial resistance, glycopeptides, such as vancomycin, are widely used as first-line therapy for serious MRSA infections. However, the emergence of glycopeptide tolerance and resistance has complicated treatment and there remains a clinical need for new antibiotics with suitable pharmacokinetic properties with activity against MRSA and other Gram-positive pathogens. Infections caused by MRSA and other bacteria usually respond as well to bacteriostatic agents as to bactericidal ones. Nevertheless, there is evidence that rapid bacterial killing has potential clinical advantages over bacteriostatic therapy in certain infections. Daptomycin, the first of the cyclic lipopeptides, shows rapid bactericidal activity against S. aureus, including strains tolerant or resistant to other agents. This review outlines the methods by which bactericidal and bacteriostatic properties are defined and tested, discusses the potential importance of bactericidal therapy in MRSA and other infections and examines the potential role of daptomycin in treatment.
Summary The emergence of antibiotic resistance in bacterial pathogens is an inevitable consequence of antibiotic use. Despite repeated warnings, negligent antibiotic use and poor infection-control ...practice have led to the continuing development of extensive resistance problems worldwide. Multidrug-resistant pathogens are now characterized by their heterogeneity, increasing virulence, resistance even to reserve agents and spread within and between hospitals and the community. Examples are glycopeptide-resistant meticillin-resistant Staphylococcus aureus (MRSA) and enterococci, extended-spectrum β-lactamase- and carbapenemase-producing coliforms, and toxin-hyperproducing Clostridium difficile. Effective national and international programmes of control to combat these problems are urgently needed. The potential for success of such coordinated efforts has been demonstrated by the recent dramatic reductions in MRSA and C. difficile infections in England.
Simulation studies using susceptible-infectious-recovered models were conducted to estimate individuals' risk of infection and time to infection in small-world and randomly mixing networks. Infection ...transmitted more rapidly but ultimately resulted in fewer infected individuals in the small-world, compared with the random, network. The ability of measures of network centrality to identify high-risk individuals was also assessed. “Centrality” describes an individual's position in a population; numerous parameters are available to assess this attribute. Here, the authors use the centrality measures degree (number of contacts), random-walk betweenness (a measure of the proportion of times an individual lies on the path between other individuals), shortest-path betweenness (the proportion of times an individual lies on the shortest path between other individuals), and farness (the sum of the number of steps between an individual and all other individuals). Each was associated with time to infection and risk of infection in the simulated outbreaks. In the networks examined, degree (which is the most readily measured) was at least as good as other network parameters in predicting risk of infection. Identification of more central individuals in populations may be used to inform surveillance and infection control strategies.
Provision of preoperative information can alleviate patients' anxiety. However, the ideal method of delivering this information is unknown. Video information has been shown to reduce patients' ...anxiety, although little is known regarding the effect of preoperative multimedia information on anxiety in patients undergoing regional anaesthesia.
We randomized 110 patients undergoing upper or lower limb surgery under regional anaesthesia into the study and control groups. The study group watched a short film (created by the authors) depicting the patient's in-hospital journey including either a spinal anaesthetic or a brachial plexus block. Patients' anxiety was assessed before and after the film and 1 h before and within 8 h after their operation, using the Spielberger state trait anxiety inventory and a visual analogue scale.
There was no difference in state and trait anxiety between the two groups at enrolment. Women had higher baseline state and trait anxiety than men (P=0.02). Patients in the control group experienced an increase in state anxiety immediately before surgery (P<0.001), and patients in the film group were less anxious before operation than those in the control group (P=0.04). After operation, there was a decrease in state anxiety from baseline in both groups, but patients in the film group were less anxious than the control group (P=0.005).
Preoperative multimedia information reduces the anxiety of patients undergoing surgery under regional anaesthesia. This type of information is easily delivered and can benefit many patients.
Increasing antimicrobial resistance and multiple resistance have resulted in increasing difficulties in the treatment of bacterial infections. Resistance leads to inappropriate empirical therapy, ...delay in starting effective treatment, and the use of less effective, more toxic, and more expensive drugs. Although studies are not always consistent, antimicrobial resistance in the infecting organisms is associated with treatment failure, prolonged or additional hospitalization, increased costs of care, and increased mortality. Additional costs and lost bed days are incurred by the need to control the spread of antimicrobial-resistant organisms within hospitals. All this has significant direct impact on patients and their families and also secondary effects on the cost effectiveness of healthcare delivery. There is an urgent need to control antimicrobial resistance by improved antibiotic usage and reduction of hospital cross-infection.
Summary Community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) was first noticed as a cause of infection in community-based individuals without healthcare contact. As the global ...epidemic of CA-MRSA has continued, CA-MRSA strain types have begun to emerge as a cause of healthcare-associated infections (HAIs) and hospital outbreaks have occurred worldwide. In areas where CA-MRSA clones have become established with high prevalence, for example USA300 (ST8-IV) in the USA, CA-MRSA are beginning to supplant or overtake traditional healthcare-associated MRSA strains as causes of HAI. The emergence of CA-MRSA as a cause of HAI puts a wider group of hospitalised patients, healthcare workers and their community contacts potentially at risk of MRSA infection. It also exposes CA-MRSA strains to the selective pressure of antibiotic use in hospitals, potentially resulting in increased antibiotic resistance, challenges traditional definitions of CA-MRSA and hampers control efforts due to the constant re-introduction of MRSA from an emerging community reservoir. There is thus an urgent need to clarify the definitions, prevalence and epidemiology of CA-MRSA and to develop systems for the identification and control of these organisms in the community, in hospitals and other healthcare facilities, and at the community–hospital interface.
To identify genetic determinants of classical swine fever virus (CSFV) virulence and host range, chimeras of the highly pathogenic Brescia strain and the attenuated vaccine strain CS were constructed ...and evaluated for viral virulence in swine. Upon initial screening, only chimeras 138.8v and 337.14v, the only chimeras containing the E2 glycoprotein of CS, were attenuated in swine despite exhibiting unaltered growth characteristics in primary porcine macrophage cell cultures. Additional viral chimeras were constructed to confirm the role of E2 in virulence. Chimeric virus 319.1v, which contained only the CS E2 glycoprotein in the Brescia background, was markedly attenuated in pigs, exhibiting significantly decreased virus replication in tonsils, a transient viremia, limited generalization of infection, and decreased virus shedding. Chimeras encoding all Brescia structural proteins in a CS genetic background remained attenuated, indicating that additional mutations outside the structural region are important for CS vaccine virus attenuation. These results demonstrate that CS E2 alone is sufficient for attenuating Brescia, indicating a significant role for the CSFV E2 glycoprotein in swine virulence.
Summary Background Surface contamination in hospitals is involved in the transmission of pathogens in a proportion of healthcare-associated infections. Admission to a room previously occupied by a ...patient colonized or infected with certain nosocomial pathogens increases the risk of acquisition by subsequent occupants; thus, there is a need to improve terminal disinfection of these patient rooms. Conventional disinfection methods may be limited by reliance on the operator to ensure appropriate selection, formulation, distribution and contact time of the agent. These problems can be reduced by the use of ‘no-touch’ automated room disinfection (NTD) systems. Aim To summarize published data related to NTD systems. Methods Pubmed searches for relevant articles. Findings A number of NTD systems have emerged, which remove or reduce reliance on the operator to ensure distribution, contact time and process repeatability, and aim to improve the level of disinfection and thus mitigate the increased risk from the prior room occupant. Available NTD systems include hydrogen peroxide (H2 O2 ) vapour systems, aerosolized hydrogen peroxide (aHP) and ultraviolet radiation. These systems have important differences in their active agent, delivery mechanism, efficacy, process time and ease of use. Typically, there is a trade-off between time and effectiveness among NTD systems. The choice of NTD system should be influenced by the intended application, the evidence base for effectiveness, practicalities of implementation and cost constraints. Conclusion NTD systems are gaining acceptance as a useful tool for infection prevention and control.
Summary Background New distinct strains of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) have emerged as a cause of infection in previously healthy individuals in ...community settings. It is important to identify CA-MRSA for clinical management, epidemiological analysis, infection prevention and control, and regulatory reporting, but definitions and nomenclature of these strains are confused. Aim To review attempts to define CA-MRSA and propose a new definition. Methods Non-systematic review. Findings Epidemiological definitions were useful for differentiating CA-MRSA and healthcare-associated (HA)-MRSA strain types in the past. However, although HA-MRSA strain types are rarely transmitted in the community, CA-MRSA strains have started to be transmitted in healthcare facilities, so epidemiological definitions are breaking down. CA-MRSA are community strains of S. aureus that have acquired the meticillin resistance gene, mecA. They are distinct from HA-MRSA and should be defined genetically. This may be done by combining genotypic typing by multi-locus sequence or spa with analysis of the staphylococcal cassette chromosome mec . Carriage of Panton-Valentine leukocidin or antimicrobial susceptibility profiles can be useful indicators of CA-MRSA but should not be used for their definition. Conclusion For full assessment of their epidemiology, MRSA infections should be characterized as: (1) caused by HA- or CA-MRSA strain types; (2) acquired in community or healthcare settings; and (3) onset in the community or healthcare facility.
Most pregnant women with epilepsy require antiepileptic drug (AED) therapy. Present guidelines recommend optimizing treatment prior to conception, choosing the most effective AED for seizure type and ...syndrome, using monotherapy and lowest effective dose, and supplementing with folate. The Epilepsy Therapy Project established the international Health Outcomes in Pregnancy and Epilepsy (HOPE) forum to learn more about the impact of AEDs on the developing fetus, particularly the role of pregnancy registries in studying AED teratogenicity. The primary outcome of interest in these registries is the occurrence of major congenital malformations, with some data collected on minor malformations. Cognitive and behavioral outcomes are often beyond the timeframe for follow-up of these registries and require independent study. The HOPE consensus report describes the current state of knowledge and the limitations to interpretations of information from the various sources. Data regarding specific risks for both older and newer AEDs need to be analyzed carefully, considering study designs and confounding factors. There is a critical need for investigations to delineate the underlying mechanisms and explain the variance seen in outcomes across AEDs and within a single AED.
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