These evidence-based guidelines are an updated version of those issued in 2008. They have been produced following a review of the published literature (2007-18) pertaining to the treatment of infections caused by MRSA. The guidelines update, where appropriate, previous recommendations, taking into account changes in the UK epidemiology of MRSA, ongoing national surveillance data and the efficacy of novel anti-staphylococcal agents licensed for use in the UK. Emerging therapies that have not been licensed for use in the UK at the time of the review have also been assessed.

The UK guidelines for the treatment of infections caused by MRSA have been updated and are published in JAC-Antimicrobial Resistance. The update reviews new evidence published since the previous UK guidelines were published over 10 years ago. It includes evidence relating to antimicrobial agents that have been licensed since then for the treatment of Gram-positive bacterial infections including MRSA. It also considers the impact on treatment of the changing epidemiology of MRSA in the UK, especially relating to circulating community strains. A striking finding from the current literature review was the paucity of good quality evidence. The current guidelines therefore represent a hybrid of varying degrees of evidence and expert opinion. Where there was no new published evidence, we have retained some of the existing recommendations. We were unable to find strong evidence of the superior efficacy of newer agents compared with that of vancomycin.

BACKGROUND:Antibiotic resistance is a major public health problem. Infections caused by multidrug-resistant bacteria are associated with prolonged hospital stay and death compared with infections caused by susceptible bacteria. Appropriate antibiotic use in hospitals should ensure effective treatment of patients with infection and reduce unnecessary prescriptions. We updated this systematic review to evaluate the impact of interventions to improve antibiotic prescribing to hospital inpatients. OBJECTIVES:To estimate the effectiveness and safety of interventions to improve antibiotic prescribing to hospital inpatients and to investigate the effect of two intervention functions: restriction and enablement. SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library), MEDLINE, and Embase. We searched for additional studies using the bibliographies of included articles and personal files. The last search from which records were evaluated and any studies identified incorporated into the review was January 2015. SELECTION CRITERIA:We included randomised controlled trials (RCTs) and non-randomised studies (NRS). We included three non-randomised study designs to measure behavioural and clinical outcomes and analyse variation in the effects: non- randomised trials (NRT), controlled before-after (CBA) studies and interrupted time series (ITS) studies. For this update we also included three additional NRS designs (case control, cohort, and qualitative studies) to identify unintended consequences. Interventions included any professional or structural interventions as defined by the Cochrane Effective Practice and Organisation of Care Group. We defined restriction as 'using rules to reduce the opportunity to engage in the target behaviour (or increase the target behaviour by reducing the opportunity to engage in competing behaviours)'. We defined enablement as 'increasing means/reducing barriers to increase capability or opportunity'. The main comparison was between intervention and no intervention. DATA COLLECTION AND ANALYSIS:Two review authors extracted data and assessed study risk of bias. We performed meta-analysis and meta-regression of RCTs and meta-regression of ITS studies. We classified behaviour change functions for all interventions in the review, including those studies in the previously published versions. We analysed dichotomous data with a risk difference (RD). We assessed certainty of evidence with GRADE criteria. MAIN RESULTS:This review includes 221 studies (58 RCTs, and 163 NRS). Most studies were from North America (96) or Europe (87). The remaining studies were from Asia (19), South America (8), Australia (8), and the East Asia (3). Although 62% of RCTs were at a high risk of bias, the results for the main review outcomes were similar when we restricted the analysis to studies at low risk of bias.More hospital inpatients were treated according to antibiotic prescribing policy with the intervention compared with no intervention based on 29 RCTs of predominantly enablement interventions (RD 15%, 95% confidence interval (CI) 14% to 16%; 23,394 participants; high-certainty evidence). This represents an increase from 43% to 58% .There were high levels of heterogeneity of effect size but the direction consistently favoured intervention.The duration of antibiotic treatment decreased by 1.95 days (95% CI 2.22 to 1.67; 14 RCTs; 3318 participants; high-certainty evidence) from 11.0 days. Information from non-randomised studies showed interventions to be associated with improvement in prescribing according to antibiotic policy in routine clinical practice, with 70% of interventions being hospital-wide compared with 31% for RCTs. The risk of death was similar between intervention and control groups (11% in both arms), indicating that antibiotic use can likely be reduced without adversely affecting mortality (RD 0%, 95% CI -1% to 0%; 28 RCTs; 15,827 participants; moderate-certainty evidence). Antibiotic stewardship interventions probably reduce length of stay by 1.12 days (95% CI 0.7 to 1.54 days; 15 RCTs; 3834 participants; moderate-certainty evidence). One RCT and six NRS raised concerns that restrictive interventions may lead to delay in treatment and negative professional culture because of breakdown in communication and trust between infection specialists and clinical teams (low-certainty evidence).Both enablement and restriction were independently associated with increased compliance with antibiotic policies, and enablement enhanced the effect of restrictive interventions (high-certainty evidence). Enabling interventions that included feedback were probably more effective than those that did not (moderate-certainty evidence).There was very low-certainty evidence about the effect of the interventions on reducing Clostridium difficile infections (median -48.6%, interquartile range -80.7% to -19.2%; 7 studies). This was also the case for resistant gram-negative bacteria (median -12.9%, interquartile range -35.3% to 25.2%; 11 studies) and resistant gram-positive bacteria (median -19.3%, interquartile range -50.1% to +23.1%; 9 studies). There was too much variance in microbial outcomes to reliably assess the effect of change in antibiotic use. Heterogeneity of intervention effect on prescribing outcomesWe analysed effect modifiers in 29 RCTs and 91 ITS studies. Enablement and restriction were independently associated with a larger effect size (high-certainty evidence). Feedback was included in 4 (17%) of 23 RCTs and 20 (47%) of 43 ITS studies of enabling interventions and was associated with greater intervention effect. Enablement was included in 13 (45%) of 29 ITS studies with restrictive interventions and enhanced intervention effect. AUTHORS' CONCLUSIONS:We found high-certainty evidence that interventions are effective in increasing compliance with antibiotic policy and reducing duration of antibiotic treatment. Lower use of antibiotics probably does not increase mortality and likely reduces length of stay. Additional trials comparing antibiotic stewardship with no intervention are unlikely to change our conclusions. Enablement consistently increased the effect of interventions, including those with a restrictive component. Although feedback further increased intervention effect, it was used in only a minority of enabling interventions. Interventions were successful in safely reducing unnecessary antibiotic use in hospitals, despite the fact that the majority did not use the most effective behaviour change techniques. Consequently, effective dissemination of our findings could have considerable health service and policy impact. Future research should instead focus on targeting treatment and assessing other measures of patient safety, assess different stewardship interventions, and explore the barriers and facilitators to implementation. More research is required on unintended consequences of restrictive interventions.

The quality of research in hospital epidemiology (infection control) must be improved to be robust enough to influence policy and practice. In order to raise the standards of research and publication, a CONSORT equivalent for these largely quasi-experimental studies has been prepared by the authors of two relevant systematic reviews, following consultation with learned societies, editors of journals and researchers. It consists of a 22 item checklist, and a summary table. The emphasis is on transparency to improve the quality of reporting and on the use of appropriate statistical techniques. The statement has been endorsed by a number of professional special interest groups and societies. Like CONSORT, ORION should be considered a 'work in progress', which requires ongoing dialogue for successful promotion and dissemination. The statement is therefore offered for further public discussion. Journals and research councils are strongly recommended to incorporate it into their submission and reviewing processes. Feedback to the authors is encouraged and the statement will be revised in 2 years.

Accepted, November 21, 2005. OBJECTIVE: In patients with cerebrospinal fluid (CSF) shunt infection, removal of the shunt and antibiotic administration is the current standard of care. In 1986, we developed a protocol for the conservative management of patients with infected but functioning shunts. Treatment was based on the administration of a combination of intraventricular and systemic antibiotics. Intraventricular antibiotics were instilled via a separate access device. The purpose of this report is to describe our experience with this therapeutic intervention. METHODS: An observational study of all patients treated for CSF shunt infection between 1986 and 2003 was undertaken. Cure was defined by sterile CSF after completion of therapy and sterile shunt components at next revision or long-term freedom from recurrent infection (follow-up period, 6–88 mo). RESULTS: In total, 43 of 122 patients with CSF shunt infections were treated conservatively according to our protocol. Overall, 84% of these patients were cured, with a 92% success rate for patients with infections caused by bacteria other than Staphylococcus aureus. This included 30 coagulase-negative staphylococcal infections, of which two were treatment failures. We abandoned conservative treatment of patients with Staphylococcus aureus infections after early experience demonstrated that the success rate (four treatment failures in seven patients) was markedly lower than that for other pathogens. During the treatment and follow-up periods, there were three deaths, two of which were unrelated to shunt infection; treatment failure could not be completely excluded in the remaining patient. There was no toxicity related to intraventricular antibiotic administration. The incidence of shunt blockage among patients who were treated conservatively was not significantly different from that among a large cohort of patients with uninfected shunts. Ten patients received part of their courses of treatment as outpatients. CONCLUSION: The success rate of conservative management of patients with CSF shunt infections caused by coagulase-negative staphylococci is comparable with those in the published literature for patients treated conventionally. This form of management avoids surgical intervention, with its attendant risks, and is safe.

Of the interventions designed to reduce antibiotic resistance rates in hospitals, one that is currently attracting considerable interest, particularly in the intensive care unit setting, is antibiotic cycling or rotation. Cycling is the scheduled rotation of one class of antibiotics with one or more different classes exhibiting comparable spectra of activity; in order to fulfil the definition, the cycle must be repeated. Following a search of the literature we identified 11 articles in which the authors claimed to have evaluated the efficacy of this intervention. Only four were suitable for review, but, owing to multiple methodological flaws and a lack of standardization, the results of these studies do not permit reliable conclusions regarding the efficacy of cycling. Further studies are therefore required in order to resolve this question. However, before such studies can be undertaken, there are a great many issues relating to cycling which must be addressed. For the time being, we advise against the routine implementation of this measure as a means of reducing antibiotic resistance rates.

Laboratory services contribute to the management of patients with neurosurgical infections in a variety of ways and, in so doing, increase the likelihood of a favourable outcome. Microbiology laboratories and clinical microbiologists are able to confirm the diagnosis, identify the causative agents and facilitate optimal antimicrobial therapy. Other pathology specialties perform investigations which help neurosurgeons to differentiate between postoperative aseptic and bacterial meningitis, these disease processes being indistinguishable on clinical grounds. A broad range of variables have been evaluated to date, but only the lactate and interleukin-1β concentrations in cerebrospinal fluid have been shown to have sufficiently high sensitivities and specificities to be useful for this purpose. In preliminary studies measurement of the serum C-reactive protein concentration has been shown to be an effective criterion for monitoring the response to antibacterial therapy in patients with spinal extradural abscesses, postoperative discitis, brain abscesses and subdural empyemas, thereby enabling patients to be treated successfully with courses of these drugs that are markedly shorter than those currently recommended.

prospective audit of compliance with national guidelines for the empirical therapy of adult patients with bacterial meningitis in The Netherlands. The consensus-based guidelines were developed by a multidisciplinary group of experts in bacterial meningitis. Patients were assigned to one of four categories: age 16‐60 years, no risk factors; age � 60 years, no risk factors; age � 16 years with risk factors; age � 16 years, recent neurosurgery. An antibiotic regimen was recommended for patients in each of the categories. The guidelines were disseminated in booklet form and the audit was begun 1 year after they were issued. Overall, only 87 patients (33%) received treatment that was in accordance with the guidelines; the rates of compliance for patients in the four groups ranged from 16% to 49%. Reassuringly, although adoption of the guidelines was poor, 95% of patients were treated with antibiotics to which their pathogens were susceptible. In the case of the 87 patients whose treatment was in accordance with the guidelines, 98% of pathogens were susceptible. Why did so few clinicians in The Netherlands adopt national guidelines for the treatment of adult patients with bacterial meningitis? Unfortunately, van de Beek et al. 1 have provided only a few clues to the explanation and have themselves offered only speculation. Could it have been the method used to develop the guidelines? We are given very little information about the development process. Indeed, all we are told is that the guidelines were consensusbased. However, it is not clear whether or not they were also evidence-based and, therefore, scientifically valid. Consequently, individual practitioners may have simply disagreed with the recommendations. For example, 50 (39%) of the 127 patients in the largest group (those 16‐60 years of age with no risk factors), who were assigned to be given a penicillin as empirical therapy, actually received a regimen containing a third-generation cephalosporin. This may have been because their clinicians were concerned that they were infected with penicillin-resistant strains of either Streptococcus pneumoniae (even though the incidence of resistance to this antibiotic among pneumococci is only 1.8% in The Netherlands) or other less common bacterial pathogens. The observation that two of the 62 pathogens isolated from patients in this group whose clinicians were compliant with the guidelines were resistant to the recommended regimen, compared with none of the pathogens recovered from patients whose clinicians did not comply with the guidelines, might be seen as justification of these concerns. For this reason, as well as an innate mistrust of national guidelines, a large number of practitioners may have elected to follow their own locally developed antibiotic guidelines. Alternatively, the explanation may lie in the way the guidelines were disseminated. In the present study, they were distributed in booklet form—a poor means of ensuring that information is read by clinicians without the introduction of one or more other effective measures. Finally, the majority of practitioners may not have adopted the guidelines because of the failure to introduce any interventions to promote their implementation. Any one, or more likely all, of these explanations may have resulted in two out of three clinicians in The Netherlands ignoring national guidelines for the empirical therapy of patients with bacterial meningitis. This study should represent a salutary lesson to those who may be devising clinical guidelines for antibiotic usage (or, indeed, for any other purpose) that if the intended users of the guidelines fail to implement them, their efforts will have been wasted. In the light of the results of this study, and evidence that they are far from unique, as well as a greater trend toward producing guidelines for antibiotic usage, both nationally and locally, in response to increasing concerns about antibiotic resistance, it is timely to review the principles underlying the guideline process. Clinical guidelines are becoming increasingly popular as a means of influencing clinicians’ practice. This is particularly true of guidelines for antibiotic usage. In a survey of consultant microbiologists and hospital pharmacists conducted by a working party of the British Society for Antimicrobial Chemotherapy in 1990, 62% of respondents indicated that antibiotic guidelines were available in their hospitals. 2 More recently, a 1998 survey of hospitals in the USA participating in Project ICARE (Intensive Care Antimicrobial Resistance Epidemiology) showed that 70% of these institutions had introduced clinical guidelines for antibiotic usage. 3