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Background The application of a uniform definition for acute kidney injury (AKI) is vital to advance understanding and management of AKI. International Classification of Diseases (Tenth Revision) (ICD-10) coding is frequently used to define AKI, but its accuracy is unclear. The aim of this study was to determine whether ICD-10 coding is a reliable method of monitoring rates and outcomes of AKI in inpatients compared with biochemically defined AKI, and whether electronic alerts (e-alerts) for AKI affect ICD-10 AKI coding. Methods An observational cohort study of all 505 662 adult admissions to acute hospitals in two Scottish Health Boards [National Health Service (NHS) Tayside and NHS Fife] from January 2013 to April 2017 was performed. AKI e-alerts were implemented in NHS Tayside in April 2015. Sensitivity, specificity, positive and negative predictive values of ICD-10 coding for AKI compared with biochemically defined AKI using the Kidney Disease: Improving Global Outcomes definition and relative risk of 30-day mortality in people with ICD-10 and biochemically defined AKI before and after AKI e-alert implementation were performed. Results Sensitivity of ICD-10 coding for identifying biochemically defined AKI was very poor in both health boards for all AKI (Tayside 25.7% and Fife 35.8%) and for Stages 2 and 3 AKI (Tayside 43.8% and Fife 53.8%). Positive predictive value was poor both for all AKI (Tayside 76.1% and Fife 45.5%) and for Stages 2 and 3 AKI (Tayside 45.5% and Fife 36.8%). Measured mortality fell following implementation of AKI e-alerts in the ICD-10-coded population but not in the biochemically defined AKI population, reflecting an increase in the proportion of Stage 1 AKI in ICD-10-coded AKI. There was no evidence that the introduction of AKI e-alerts in Tayside improved ICD-10 coding of AKI. Conclusion ICD-10 coding should not be used for monitoring of rates and outcomes of AKI for either research or improvement programmes. [ABSTRACT FROM AUTHOR]

Background: Reducing unnecessary antibiotic exposure is a key strategy in reducing the development and selection of antibiotic-resistant bacteria. Hospital antimicrobial stewardship (AMS) interventions are inherently complex, often requiring multiple healthcare professionals to change multiple behaviours at multiple timepoints along the care pathway. Inaction can arise when roles and responsibilities are unclear. A behavioural perspective can offer insights to maximize the chances of successful implementation.Objectives: To apply a behavioural framework [the Target Action Context Timing Actors (TACTA) framework] to existing evidence about hospital AMS interventions to specify which key behavioural aspects of interventions are detailed.Methods: Randomized controlled trials (RCTs) and interrupted time series (ITS) studies with a focus on reducing unnecessary exposure to antibiotics were identified from the most recent Cochrane review of interventions to improve hospital AMS. The TACTA framework was applied to published intervention reports to assess the extent to which key details were reported about what behaviour should be performed, who is responsible for doing it and when, where, how often and with whom it should be performed.Results: The included studies (n = 45; 31 RCTs and 14 ITS studies with 49 outcome measures) reported what should be done, where and to whom. However, key details were missing about who should act (45%) and when (22%). Specification of who should act was missing in 79% of 15 interventions to reduce duration of treatment in continuing-care wards.Conclusions: The lack of precise specification within AMS interventions limits the generalizability and reproducibility of evidence, hampering efforts to implement AMS interventions in practice. [ABSTRACT FROM AUTHOR]

Background Development of acute kidney injury (AKI) following the use of antibiotics such as sulphonamides, trimethoprim and aminoglycosides is a frequently described phenomenon. More recently, an association between fluoroquinolone use and AKI has been suggested. The aim of this study was to evaluate the risk of AKI as an unintended consequence of commonly prescribed antibiotics in a large community cohort using a method that fully adjusts for underlying patient characteristics, including potential unmeasured confounders. Methods A self-controlled case study was conducted and included all individuals aged 18 years and over in the Tayside region of Scotland who had a serum creatinine measured between 1 January 2004 and 31 December 2012. AKI episodes were defined using the Kidney Disease: Improving Global Outcomes definition. Data on oral community-prescribed antibiotics (penicillins, cephalosporins, fluoroquinolones, sulphonamides and trimethoprim, macrolides and nitrofurantoin) were collected for all individuals. Incidence rate ratios (IRRs) for AKI associated with antibiotic exposure versus time periods without antibiotic exposure were calculated. Results Combined use of sulphonamides, trimethoprim and nitrofurantoin rose by 47% and incidence of community-acquired AKI rose by 16% between 2008 and 2012. During the study period 12 777 individuals developed 14 900 episodes of AKI in the community, of which 68% was AKI Stage 1, 16% Stage 2 and 16% Stage 3. The IRR of AKI during any antibiotic use was 1.16 [95% confidence interval (CI) 1.10—1.23], and this was highest during sulphonamides or trimethoprim use; IRR 3.07 (95% CI 2.81–3.35). Fluoroquinolone and nitrofurantoin use was not associated with a significantly increased rate of AKI; IRR 1.13 (95% CI 0.94–1.35) and 1.16 (95% CI 0.91–1.50), respectively. Conclusions Incidence of AKI rose by 16% between 2008 and 2012. In the same period the use of sulphonamides, trimethoprim and nitrofurantoin increased by 47%. A significant increased risk of AKI was seen with the use of sulphonamides and trimethoprim, but not with fluoroquinolones or nitrofurantoin. [ABSTRACT FROM AUTHOR]

Addressing the growing threat of antimicrobial resistance is, in part, reliant on the complex challenge of changing human behaviour-in terms of reducing inappropriate antibiotic use and preventing infection. Whilst there is no 'one size fits all' recommended behavioural solution for improving antimicrobial stewardship, the behavioural and social sciences offer a range of theories, frameworks, methods and evidence-based principles that can help inform the design of behaviour change interventions that are context-specific and thus more likely to be effective. However, the state-of-the-art in antimicrobial stewardship research and practice suggests that behavioural and social influences are often not given due consideration in the design and evaluation of interventions to improve antimicrobial prescribing. In this paper, we discuss four potential areas where the behavioural and social sciences can help drive more effective and sustained behaviour change in antimicrobial stewardship: (i) defining the problem in behavioural terms and understanding current behaviour in context; (ii) adopting a theory-driven, systematic approach to intervention design; (iii) investigating implementation and sustainability of interventions in practice; and (iv) maximizing learning through evidence synthesis and detailed intervention reporting. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial exposure is associated with increased risk of Clostridium difficile infection (CDI), but the impact of prescribing interventions on CDI and other outcomes is less clear.Objectives: To evaluate the effect of an antimicrobial stewardship intervention targeting high-risk antimicrobials (HRA), implemented in October 2008, and to compare the findings with similar studies from a systematic review.Methods: All patients admitted to Medicine and Surgery in Ninewells Hospital from October 2006 to September 2010 were included. Intervention effects on HRA use (dispensed DDD), CDI cases and mortality rates, per 1000 admissions per month, were analysed separately in Medicine and Surgery using segmented regression of interrupted time series (ITS) data. Data from comparable published studies were reanalysed using the same method.Results: Six months post-intervention, there were relative reductions in HRA use of 33% (95% CI 11-56) in Medicine and 32% (95% CI 19-46) in Surgery. At 12 months, there was an estimated reduction in CDI of 7.0 cases/1000 admissions [relative change -24% (95% CI - 55 to 6)] in Medicine, but no change in Surgery {estimated 0.1 fewer cases/1000 admissions [-2% (95% CI - 116 to 112)]}. Mortality reduced throughout the study period, unaffected by the intervention. In all six comparable studies, HRA use reduced significantly, but reductions in CDI rates were only statistically significant in two and none measured mortality. Pre-intervention CDI rates and trends influenced the intervention effect.Conclusions: Despite large reductions in HRA prescribing and reductions in CDI, demonstrating real-world impact of stewardship interventions remains challenging. [ABSTRACT FROM AUTHOR]

Drawing on a Cochrane systematic review, this paper examines the relatively limited range of outcomes measured in published evaluations of antimicrobial stewardship interventions (ASIs) in hospitals. We describe a structured framework for considering the range of consequences that ASIs can have, in terms of their desirability and the extent to which they were expected when planning an ASI: expected, desirable consequences (intervention goals); expected, undesirable consequences (intervention trade-offs); unexpected, undesirable consequences (unpleasant surprises); and unexpected, desirable consequences (pleasant surprises). Of 49 randomized controlled trials identified by the Cochrane review, 28 (57%) pre-specified increased length of stay and/or mortality as potential trade-offs of ASI, with measurement intended to provide reassurance about safety. In actuality, some studies found unexpected decreases in length of stay (a pleasant surprise). In contrast, only 11 (10%) of 110 interrupted time series studies included any information about unintended consequences, with 10 examining unexpected, undesirable outcomes (unpleasant surprises) using case-control, qualitative or cohort designs. Overall, a large proportion of the ASIs reported in the literature only assess impact on their targeted process goals-antimicrobial prescribing-with limited examination of other potential outcomes, including microbial and clinical outcomes. Achieving a balanced accounting of the impact of an ASI requires careful consideration of expected undesirable effects (potential trade-offs) from the outset, and more consideration of unexpected effects after implementation (both pleasant and unpleasant surprises, although the latter will often be more important). The proposed framework supports the systematic consideration of all types of consequences of improvement before and after implementation. [ABSTRACT FROM AUTHOR]

Seagrasses are unique angiosperms that carry out growth and reproduction submerged in seawater. They occur in at least three families of the Alismatales. All have chloroplasts mainly in the cells of the epidermis. Living in seawater, the supply of inorganic carbon (Ci) to the chloroplasts is diffusion limited, especially under unstirred conditions. Therefore, the supply of CO2 and bicarbonate across the diffusive boundary layer on the outer side of the epidermis is often a limiting factor. Here we discuss the evidence for mechanisms that enhance the uptake of Ci into the epidermal cells. Since bicarbonate is plentiful in seawater, a bicarbonate pump might be expected; however, the evidence for such a pump is not strongly supported. There is evidence for a carbonic anhydrase outside the outer plasmalemma. This, together with evidence for an outward proton pump, suggests the possibility that local acidification leads to enhanced concentrations of CO2 adjacent to the outer tangential epidermal walls, which enhances the uptake of CO2, and this could be followed by a carbon-concentrating mechanism (CCM) in the cytoplasm and/or chloroplasts. The lines of evidence for such an epidermal CCM are discussed, including evidence for special 'transfer cells' in some but not all seagrass leaves in the tangential inner walls of the epidermal cells. It is concluded that seagrasses have a CCM but that the case for concentration of CO2 at the site of Rubisco carboxylation is not proven. [ABSTRACT FROM AUTHOR]

Background: Community-associated Clostridium difficile infection (CA-CDI; defined as cases without prior hospitalization in the previous 12 weeks who were either tested outside of hospital or tested within 2 days of admission to hospital) is a major public health problem. This study estimates the magnitude of the association between temporal and cumulative prescribing of antimicrobials in primary care and CA-CDI.Methods: Three national patient-level datasets, covering CDI cases, community prescriptions and hospitalizations, were linked by the NHS Scotland unique patient identifier, the Community Health Index (CHI). All validated cases of CDI from August 2010 to July 2013 were extracted and up to six population-based controls were matched to each case from the CHI register for Scotland. Statistical analysis used conditional logistic regression.Results: The 1446 unique cases of CA-CDI were linked with 7964 age-, sex- and location-matched controls. Cumulative exposure to any antimicrobial in the previous 6 months has a monotonic dose-response association with CA-CDI. Individuals with more than 28 DDDs to any antimicrobial (19.9% of cases) had an OR of 4.4 (95% CI 3.4-5.6) compared with those unexposed. Individuals exposed to 29+ DDDs of high-risk antimicrobials (cephalosporins, clindamycin, co-amoxiclav or fluoroquinolones) had an OR of 17.9 (95% CI 7.6-42.2). Elevated CA-CDI risk following high-risk antimicrobial exposure was greatest in the first month (OR = 12.5, 95% CI 8.9-17.4), but was still present 4-6 months later (OR = 2.6, 95% CI 1.7-3.9). Cases exposed to 29+ DDDs had prescription patterns more consistent with repeated therapeutic courses, using different antimicrobials, than long-term prophylactic use.Conclusions: This analysis demonstrated temporal and dose-response associations between CA-CDI risk and antimicrobials, with an impact of exposure to high-risk antimicrobials remaining 4-6 months later. [ABSTRACT FROM AUTHOR]

Objectives: Evidence has shown that a prophylactic antibiotic regimen of flucloxacillin and gentamicin for orthopaedic surgery was associated with increased rates of post-operative acute kidney injury (AKI). This resulted in changes in the national antibiotic policy recommendation for orthopaedic surgical prophylaxis. This study aimed to assess whether this change from flucloxacillin and gentamicin to co-amoxiclav was associated with changes in the rates of AKI and Clostridium difficile infection (CDI).Methods: An observational study and interrupted time series analyses were used to assess rates of post-operative AKI separately in patients undergoing neck of femur (NOF) repair and other orthopaedic operations that required antibiotic prophylaxis. Incidence rate ratios were used to evaluate changes in CDI rates.Results: Following the change in policy, from flucloxacillin and gentamicin to co-amoxiclav, there was a relative change in rates of post-operative AKI of -63% (95% CI -77% to -49%) at 18 months in the other orthopaedic operations group. In the NOF repair group, there was no change in the rate of post-operative AKI [-10% (95% CI -35%-15%)] at 18 months. The incident rate ratio for CDI in the other orthopaedic operations group was 0.29 (95% CI 0.09-0.96) and in the NOF repair group was 0.76 (95% CI 0.28-2.08).Conclusions: The use of co-amoxiclav for antibiotic prophylaxis in orthopaedic surgery was associated with a decreased rate of post-operative AKI compared with flucloxacillin and gentamicin and was not associated with increased rates of CDI. [ABSTRACT FROM AUTHOR]

The pressing need to measure and improve antibiotic use was recognized >40 years ago, so why have we failed to achieve sustained improvement at scale? In his 2014 Reith Lectures about the future of medicine, the US surgeon Atul Gawande said that failure in medicine is largely due to ineptitude (failure to use existing knowledge) rather than ignorance (lack of knowledge). Consequently, it is notable that most interventions to improve antimicrobial prescribing are either designed to educate individual practitioners or patients about policies or to restrict prescribing to make practitioners follow policies. Interventions that enable practitioners to apply existing knowledge through decision support, feedback and action planning are relatively uncommon. There is an urgent need to improve the design and reporting of interventions to change behaviour. However, achieving sustained improvement at scale will also require a more profound understanding of the role of context. What makes contexts receptive to change and which elements of context, under what circumstances, are important for human performance? Answering these questions will require interdisciplinary work with social scientists to integrate complementary approaches from human factors and ergonomics, improvement science and educational research. We need to rethink professional education to embrace complexity and enable teams to learn in practice. Workplace-based learning of improvement science will enable students and early-career professionals to become change agents and transform training from a burden on clinical teams into a driver for improvement. This will make better use of existing resources, which is the key to sustainability at scale. [ABSTRACT FROM AUTHOR]

Objectives Concern about Clostridium difficile infection (CDI) and resistance has driven interventions internationally to reduce broad-spectrum antimicrobial use. An intervention combining guidelines, education and feedback was implemented in Tayside, Scotland in 2009 aiming to reduce primary care prescribing of co-amoxiclav, cephalosporins, fluoroquinolones and clindamycin ('4C antimicrobials'). Our aim was to assess the impact of this real-world intervention on antimicrobial prescribing rates. Methods We used interrupted time series with segmented regression analysis to examine associations between the intervention and changes in antimicrobial prescribing (quarterly rates of patients exposed to 4C antimicrobials, non-4C antimicrobials and any antimicrobial in 2005-12). Results The intervention was associated with a highly significant and sustained decrease in 4C antimicrobial prescribing, by 33.5% (95% CI -26.1 to -40.9), 42.2% (95% CI -34.2 to -50.2) and 55.5% (95% CI -45.9 to -65.1) at 6, 12 and 24 months after intervention, respectively. The effect was seen across all age groups, with the largest reductions in people aged 65 years and over (58.4% reduction at 24 months, 95% CI -46.7 to -70.1) and care home residents (65.6% reduction at 24 months, 95% CI -51.8 to -79.4). There were balancing increases in doxycycline, nitrofurantoin and trimethoprim prescribing as well as a reduction in macrolide prescribing. Total antimicrobial exposure did not change. Conclusions A real-world intervention to reduce primary care prescribing of antimicrobials associated with CDI led to large, sustained reductions in the targeted prescribing, largely due to substitution with guideline-recommended antimicrobials rather than by avoiding antimicrobial use altogether. Further research is needed to examine the impact on antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the impact of ‘Resident Antimicrobial Management Plan’ (RAMP), a novel antimicrobial stewardship tool on systemic antibiotic use for treatment of infection in nursing homes (NHs). Methods A pilot cluster randomized control study was conducted in 30 NHs in London. Pre-intervention, we collected point prevalence data on antimicrobial use on three occasions and total antimicrobial consumption for a 12 week period. Post-intervention data were collected in the same manner and included assessment of compliance with RAMP in the intervention group (IG). Results The number of residents included was 1628 pre-intervention [825 IG/803 control group (CG)] and 1610 post-intervention (838 IG/772 CG). The corresponding pre- and post-intervention point prevalence of systemic antibiotic prescribing for treatment of infection was 6.46% and 6.52% in the IG [estimated prevalence ratio: 1.01 (95% CI: 0.81–1.25), P = 0.94] compared with 5.27% and 5.83%, respectively, in the CG [estimated prevalence ratio: 1.11 (95% CI: 0.87–1.41), P = 0.4]. Total antibiotic consumption was 69.78 defined daily doses/1000 residents/day (DRD) pre-intervention and 66.53 DRD post-intervention in the IG compared with 49.68 and 51.92 DRD, respectively, in the CG. There was a significant decrease of 4.9% (3.25 DRD) in the IG (95% CI: 1.0%–8.6%) (P = 0.02) compared with a significant increase of 5.1% (2.24 DRD) in the CG (95% CI: 0.2%–10.2%) (P = 0.04). Main indications for antibiotics were lower respiratory tract infections (34.1%), urinary tract infections (28.5%) and skin/soft tissue infections (25.1%). Conclusions This pilot study demonstrated that use of RAMP was associated with a statistically significant decrease in total antibiotic consumption and has the potential to be an important antimicrobial stewardship tool for NHs. [ABSTRACT FROM PUBLISHER]

Objectives To estimate the risks of community-associated Clostridium difficile infection (CA-CDI) among the population aged ≥65 years associated with antibiotic exposure and care home residence. Population and methods We linked cases from a prospective study in Tayside, Scotland from 1 November 2008 to 31 October 2009 to population datasets to conduct a cohort study and a nested, matched (1 : 10 by age and gender) case–control study. Results There were 79 039 eligible residents. CA-CDI incidence was 20.3/10 000 person years. In the cohort study, after adjustment, we found a significantly increasing risk of CA-CDI with increasing age and comorbidity, prior hospital admission, care home residence [hazard ratio (HR) 1.96, 95% CI 1.14–3.34] and baseline antibiotic exposure (1.94, 1.35–2.77). In separate adjusted models, ‘4C’ antibiotics (clindamycin, co-amoxiclav, cephalosporins, ciprofloxacin; 2.75, 1.78–4.26) and fluoroquinolones (3.33, 1.95–5.67) had higher associated risks. We matched 62 CA-CDI cases without recent (prior 3 months) hospital admission to 620 controls. In adjusted logistic regression models, exposure to any antibiotics increased the risk of CA-CDI (OR 6.04, 95% CI 3.19–11.43). Exposure to 4C antibiotics or fluoroquinolones had higher associated risks: adjusted OR 11.60 (95% CI 5.57–24.15) and 13.04 (4.91–34.64), respectively. Risk of CA-CDI increased with cumulative antibiotic exposure. Subgroup analysis of 42 cases with C. difficile cultured and 420 controls amplified all associations between antibiotic exposure and CA-CDI. Care home residence independently increased the risk of CA-CDI in all models. Conclusions Our results have two important implications. First, they validate the classification of 4C antibiotics and fluoroquinolones in primary care as high risk for CA-CDI. Second, they demonstrate the importance of prior antibiotic exposure and place of residence for risk assessment by primary care prescribers. [ABSTRACT FROM PUBLISHER]

Background Several severity scoring systems have been proposed for skin and soft tissue infections (SSTIs), but none has been tested prospectively. Methods We prospectively enrolled adult, acute medical admissions with SSTI between April 2009 and June 2010. Severity was assessed using two proposed SSTI scoring systems, one based on a generic sepsis definition. Antimicrobial prescribing was compared with guideline recommendations. Results We enrolled 79 patients. One of the scoring systems classified 47% into class I (no sepsis or comorbidity), 5% into class II (no sepsis, but comorbidity), 34% into class III [sepsis, but standardized early warning system (SEWS) <4], and 14% into class IV (sepsis with SEWS ≥4). The other system classified 39% as mild and 61% as moderate/severe. There were significant discrepancies between the two scoring systems. Using the worst clinical observations in the first 24 h, 19% of patients had more severe disease than was apparent on admission. Under-treatment of patients with sepsis occurred in 13% of patients according to admission observations, increasing to 22% according to the worst observations. Seventy-nine percent of patients with sepsis received antibiotics within 4 h of admission. This was associated with fewer adverse outcomes (P = 0.05). Conclusions There is significant room for improvement in the management of SSTIs presenting to acute medical units. The added value of specific SSTI severity scores over generic sepsis assessment requires validation in a larger prospective study. We have changed our antibiotics policy for SSTI to use generic sepsis scores, and we emphasize the need to reassess patients on the day of admission. [ABSTRACT FROM PUBLISHER]

Background Skin and soft tissue infections (SSTIs) are caused by bacterial invasion of the skin and underlying soft tissues and can present with a wide spectrum of signs, symptoms and illness severity. They are a common indication for antimicrobial therapy. However, there are few data on treatment outcomes or the validity of clinical severity scores. Methods Two hundred and five adult patients admitted to Ninewells Hospital, Scotland in 2005, and treated with antibiotics for SSTI, were identified. They were stratified into four classes of severity (class IV = most severe) based on sepsis, co-morbidity and their standardized early warning score (SEWS). Empirical antimicrobial therapy by severity class was compared with the recommendations of a UK guideline. Results Thirty-five different empirical antimicrobial regimens were prescribed. Overall, 43% of patients were over-treated, this being particularly common in the lowest severity class I (65% patients). Thirty-day mortality was 9% (18/205) and 17 patients (8%) died during their index admission. Mortality (30 day) and inadequate therapy increased with severity class: I, no sepsis or co-morbidity (45% patients, 1% mortality, 14% therapy inadequate); II, significant co-morbidity but no sepsis (32% patients, 11% mortality, 39% therapy inadequate); III, sepsis but SEWS <4 (17% of patients, 17% mortality, 39% therapy inadequate); and IV, sepsis plus SEWS ≥4 (6% of patients, 33% mortality, 92% therapy inadequate). Conclusions SSTI in hospital is associated with significant mortality. Choice of empirical therapy is not evidence based, with significant under-treatment of severely ill patients. [ABSTRACT FROM PUBLISHER]

Objectives The main objective was to study the impact of in-hospital bacteraemia caused by Staphylococcus aureus on mortality within 90 days after admission. We compared methicillin-resistant S. aureus (MRSA) with methicillin-susceptible S. aureus (MSSA). Patients and methods The study population consisted of adult residents of Tayside, Scotland, UK, from 1 January 2005 to 30 September 2006 who had a new admission to Ninewells Hospital between 1 July 2005 and 30 June 2006. All patients (n = 3132) in the same wards as the patients infected with S. aureus were included. We addressed key weaknesses in previous studies by using a cohort design and applying a multistate model, which addressed the temporal dynamics. Critically, the model recognized that death and discharge from the hospital are competing events and that delay in discharge independently increases the risk of death. Results The cohort included 3132 patients, of whom 494 died within 90 days after admission, 34 developed MRSA bacteraemia and 26 MSSA bacteraemia in the hospital. In comparison with patients without S. aureus bacteraemia, the death hazard was 5.6 times greater with MRSA [95% confidence interval (CI) 3.36–9.41] and 2.7 times greater with MSSA bacteraemia (95% CI 1.33–5.39). After adjustment for co-morbidity, hospitalization, age and sex, the death hazard was 2.9 times greater with MRSA (95% CI 1.70–4.88) and 1.7 times greater with MSSA bacteraemia (95% CI 0.84–3.47). Conclusions Time-dependent models such as the proposed multistate model are necessary to address the temporal dynamics of admission, infection, discharge and death. The impact of S. aureus bacteraemia on mortality should be considered on two levels: the burden of disease, i.e. nosocomial infection with S. aureus bacteraemia, and the burden of resistance to methicillin. [ABSTRACT FROM PUBLISHER]

Objectives Since electronic prescribing is limited to few hospitals, point prevalence surveys, such as the standardized European Surveillance of Antimicrobial Consumption point prevalence survey (ESAC PPS), are an alternative tool for monitoring prescribing and helping to identify performance indicators and prescribing trends. The main objective of this study was to identify and assess targets for quality improvement. Methods Each hospital had to carry out the survey within 2 weeks. Each department had to be surveyed in 1day. Data collected, for all inpatients, included age and gender. For patients on systemic antimicrobial treatment, the antimicrobial/s, infection/prophylaxis site, reason in medical notes and guideline compliance were also collected. A central database using a web-based tool (WebPPS) developed in-house was used for data entry. Results Combination of two or more antimicrobials accounted for 30% of use. Surgical prophylaxis was prolonged (>1 day) in 53% of cases. ‘Intensive care’ had higher proportions of treated patients (53% versus 29%), combination therapy (49% versus 31%), hospital-acquired infections (49% versus 31%) and parenteral administration (91% versus 61%). ‘Reason in notes’ was documented in 76%, and ‘guideline compliance’ occurred in 62% of patients. Conclusions The ESAC PPS provided useful information on the quality of prescribing, which identified a number of targets for quality improvement. These could apply to specific departments or whole hospitals. Intensive care, which has different characteristics, should not be compared with general wards with respect to combination therapy, hospital-acquired infections or parenteral proportion. The study confirmed that the ESAC PPS methodology can be used on a large number of hospitals at regional, national, continental or global level. [ABSTRACT FROM PUBLISHER]

Background: Antimicrobials are the most common medicines prescribed to children, but very little is known about patterns of hospital paediatric antimicrobial prescribing. This study aimed at describing paediatric antimicrobial prescribing in European hospitals to identify targets for quality improvement. [ABSTRACT FROM PUBLISHER]

Objectives: To determine the effect of the 2008 English public antibiotic campaigns. [ABSTRACT FROM PUBLISHER]

Background. Point-prevalence surveys have been used to document antimicrobial use in hospitals for 120 years. However, published surveys are inconsistent with respect to population, indication, and the details of therapy that were included. We aimed to standardize a method for surveillance of antibacterial use in hospitals from different health care systems and to identify targets for quality improvement. Methods. We adapted a Web-based reporting system from STRAMA, the Swedish Strategic Programme against antibiotic resistance. One hospital from each of 20 countries took part in the survey, which was completed during 2 calendar weeks during 1 April 2006 through 31 May 2006. The survey included all inpatient beds for adults and children and identified all patients who were receiving systemic antibacterial treatments on the day of survey and all patients who had received antibacterial prophylaxis for surgery on the previous day. Results. On the day of survey there were 11,571 inpatients in the 20 participating hospitals, of whom 30.1% were receiving antibacterial treatment (range, 19%-59%). The most common anatomic sites of infection for which antibacterials were prescribed were respiratory tract (24%); skin, bone, and joint (18%); intra-abdominal organs (16%); and urinary tract (11%). The following 3 quality indicators were identified: indication documented in case notes (64%), prophylaxis for surgery not continued for >24 h (60%), and therapy for community-acquired pneumonia not including third-generation cephalosporins or quinolones (78.5%). Conclusion. A Web-based method for a point-prevalence survey was successfully piloted in 20 hospitals across Europe and offers a standardized instrument that can identify targets for quality improvement. [ABSTRACT FROM AUTHOR]

Antibiotics are overused across the world by prescription, self-medication or over the counter (OTC) availability. In the UK, the agenda to increase patient choice has stimulated a move towards greater availability of OTC antibiotics. This trend needs to be urgently reviewed and controlled. The Medicines and Healthcare products Regulatory Agency is currently reviewing applications for reclassification of trimethoprim and nitrofurantoin from prescription-only medicines to pharmacy availability or OTC. It is important that anti-infectives do not become more freely available. With the quantity of antibiotic use linked to antibiotic resistance, Society should seek to preserve the use of this irreplaceable resource by education and regulation. [ABSTRACT FROM PUBLISHER]

Objectives: To compare the effectiveness of cranberry extract with low-dose trimethoprim in the prevention of recurrent urinary tract infections (UTIs) in older women.Patients and Methods: One hundred and thirty-seven women with two or more antibiotic-treated UTIs in the previous 12 months were randomized to receive either 500 mg of cranberry extract or 100 mg of trimethoprim for 6 months.Results: Thirty-nine of 137 participants (28%) had an antibiotic-treated UTI (25 in the cranberry group and 14 in the trimethoprim group); difference in proportions relative risk 1.616 (95% CI: 0.93, 2.79) P = 0.084. The time to first recurrence of UTI was not significantly different between the groups (P = 0.100). The median time to recurrence of UTI was 84.5 days for the cranberry group and 91 days for the trimethoprim group (U = 166, P = 0.479). There were 17/137 (12%) withdrawals from the study, 6/69 (9%) from the cranberry group and 11/68 (16%) from the trimethoprim group (P = 0.205), with a relative risk of withdrawal from the cranberry group of 0.54 (95% CI: 0.19, 1.37).Conclusions: Trimethoprim had a very limited advantage over cranberry extract in the prevention of recurrent UTIs in older women and had more adverse effects. Our findings will allow older women with recurrent UTIs to weigh up with their clinicians the inherent attractions of a cheap, natural product like cranberry extract whose use does not carry the risk of antimicrobial resistance or super-infection with Clostridium difficile or fungi. [ABSTRACT FROM AUTHOR]

Bone and joint infections are significant causes of morbidity, mortality and healthcare costs. The cost of treatment for such infections is driven primarily by the length of hospital stay. Many of these infections will require treatment with prolonged periods of parenteral antibiotic therapy. Clinicians and healthcare managers are being attracted increasingly by administering treatment in the ambulatory setting as this offers clinical, economic and quality of life advantages from both the hospital's and patient's perspective. Our retrospective audit of managing 55 treatment episodes of bone and joint infections with teicoplanin delivered in the outpatient or home setting revealed that the mean cost of care per episode of infection was less with treatment in the ambulatory setting ( pound 1749.15) compared with the in-patient setting ( pound 11 400) or compared with the hypothetical situation of treatment with oral linezolid in the home setting ( pound 2546). Teicoplanin therapeutic drug monitoring appears to be valuable in establishing optimal serum levels, which appear to correlate with good clinical outcomes. The potential for alternative day or thrice weekly dosing with teicoplanin may offer further cost advantages whilst maintaining equivalent clinical effectiveness. [ABSTRACT FROM AUTHOR]

The study objectives were to measure time from birth to first exposure to antibacterials in children and compare the characteristics of children who submit urine samples with the general population. Antibacterials were dispensed to 63% of children within 1 year of birth, increasing to 75% within 2 years after birth. Boys had earlier exposure to antibacterials than girls. Children submitting urine samples were more likely to be socio-economically deprived, have prior exposure to antibacterials and have prior hospital admission. In conclusion, urine samples are unsuitable for a prospective cohort study of the relationship between antibacterial exposure and resistance in children. [ABSTRACT FROM AUTHOR]

Quality-assessment indicators for community-acquired pneumonia (CAP) founded on health care structure, process, and outcome have been recommended as a potential audit tool to evaluate the delivery of care. We prospectively audited the treatment of 205 patients admitted with CAP to 2 hospitals in Dundee against some of these key standards. Patients with severe CAP were more likely to die (mortality rate, 42% versus 7%) and to receive antibiotics by the intravenous route (relative risk [RR], 1.81; 95% confidence interval [CI], 1.38--2.37) and within 4 hours of admission to the hospital (RR, 1.22; 95% CI, 0.92--1.62). There was a lack of uniformity regarding the amount of oxygen prescribed, with evidence of poor case record and drug prescription chart documentation related to oxygen therapy. Adherence to the recommended antibiotic policy was associated with reduced risk of death or readmission to the hospital (RR, 0.58; 95% CI, 0.34--1.00). However, in a multivariate analysis, severity of pneumonia was the strongest predictor of death or readmission ( ), P p .004 and adherence to the antibiotic policy was not statistically significant ( ). Our study has confirmed P p .154 the value of quality indicators in evaluating our CAP management and has stimulated the development and implementation of a local hospital--based integrated care pathway. [ABSTRACT FROM AUTHOR]

The reported association between antibiotic prescribing and resistance may be subject to bias or confounding. Bias describes any effect at any stage of investigation or inference tending to produce results that depart systematically from the true value. A confounding variable is one that is associated independently with both exposure and outcome. Confounding variables may create an apparent association or mask a real association. Pharmacoepidemiology is the study of the use and the effects of drugs in large numbers of people. We have used standard pharmacoepidemiological methods to investigate sources of bias and confounding in the association between prescribing and resistance. We conclude that the association is statistically valid and that the consistency of evidence supports a cause-effect relationship. Nonetheless, several important sources of bias and confounding must be taken into account in future studies that analyze the impact of prescribing policies on resistance. [ABSTRACT FROM AUTHOR]

Trimethoprim resistance is increasingly prevalent in community-acquired urinary infections. The objective of this study was to evaluate the association between exposure to community-prescribed trimethoprim and other risk factors in subjects and subsequent trimethoprim-resistant urinary tract infection. The design was a nested case–control study using a record-linkage database. Study subjects submitted a urine sample to the Ninewells Hospital Laboratory between July 1993 and December 1995. Antibiotic exposure in subjects with trimethoprim-resistant isolates (cases) was compared with antibiotic exposure in subjects with trimethoprim-susceptible isolates (controls). Study subjects were drawn from the catchment area of a large teaching hospital in Tayside, Scotland. There were 13765 males and females aged 1–106 years who submitted their first urine sample for culture during the study period. After adjustment for significant risk factors and confounding variables, logistic regression analysis showed exposure to trimethoprim [odds ratio (OR) 4.35] or any antibiotic other than trimethoprim (OR 1.32) to be predictive of resistance. The growth of Proteus spp. (OR 115.14) and bacterial growth other than Escherichia coli and Proteus spp. (OR 2.83) were also predictor variables. Hospitalization in the previous 6 months was not independently associated with trimethoprim resistance. In conclusion, trimethoprim resistance was independently associated with exposure to trimethoprim and to antibiotics other than trimethoprim. Reduction in trimethoprim prescribing alone may not reduce the prevalence of trimethoprim resistance. [ABSTRACT FROM PUBLISHER]

Focuses on the role of guidelines for community-acquired pneumonia (CAP) in improving the cost-effectiveness of hospital care. Changes brought by CAP to medical care practices; Assessment of the cost-effectiveness of CAP implementation; Need for the inclusion of cost-effectiveness information.

People are more vulnerable to infection at the extremes of age for a variety of reasons, the most important being that they are more likely to be in hospital in a crowded ward environment and to be at risk from hospital acquired infection. Recognition of this increased vulnerability to infection should be accompanied by equal emphasis on their increased susceptibility to nosocomial disease arising from the diagnosis or treatment of infection. An economic evaluation of infection at the extremes of age should include an assessment of need made in terms of the capacity of patients to benefit from investigation or treatment. Benefits should not be confused with treatment effects such as reduction in pyrexia or correction of other physiological abnormalities. Ideally benefits should be quantified in a manner which allows comparison with the cost-effectiveness of other uses of health care resources. In order to achieve this aim clinicians must understand the economic terms opportunity cost and marginal cost-effectiveness. These terms are defined in general terms and then applied to examples of investigation, prevention and treatment of infection at the extremes of age. [ABSTRACT FROM PUBLISHER]

The fluoroquinolones have been extensively used in the neutropenic patient. When fluoroquinolone monotherapy was used as prophylaxis, frequently for extended periods, the rate of adverse effect of ciprofloxacin (6.9%) ofloxacin (11.6%) and norfloxacin (5.5%) were significantly lower than those of the comparator agents—co-trimoxazole, vancomycin and polymycin. Rash and gastrointestinal upset were the commonest adverse effects associated with the fluoroquinolones. When used as monotherapy for bacterial infections, often intravenously and in high dosages, the cumulative rate of adverse effects caused by the fluoroquinolones (12.6%) was similar to that caused by the comparator agents(10.3%), but significantly higher than reported for non-neutropenic patients (6.4%) and for prophylactic use. The main adverse events were also rashes (15.4%) and gastrointestinal upset (6.1%). When fluoroquinolones were used as therapy of bacterial infections in combination with other agents, the incidence of adverse events was 14.9%, which was similar to the comparator agents (13.5%). Adverse events were also similar except that nephrotoxicity was commonest with comparator combinations (4.0%). The data suggest that fluoroquinolone prophylaxis in neutropenic patients, even for prolonged periods, is safer than the comparator agents, but is associated with more frequent adverse events than in non-neutropenic patients. Fluoroquinolone therapy, frequently with high dosages, is associated with similar rate of adverse events as the comparator agents. When used in combination with the other antibiotics, fluoroquinolones are as safe as the comparator agents. [ABSTRACT FROM PUBLISHER]

Safety of teicoplanin has been assessed in 3377 patients treated in Europe up to the end of June 1990. One or more adverse events were experienced by 10% of patients. Age and teicoplanin dose had no significant effect on the incidence or type of adverse event. In comparative trials the incidence and profile of adverse events to teicoplanin have been similar to those seen with β-lactam therapy. Impaired renal function occurred consistently more frequently with vancomycin therapy than with teicoplanin therapy, particularly when these drugs were co-administered with aminoglyco-sides. Severe skin reactions have not been reported with teicoplanin, which, unlike vancomycin, does not cause infusion rate-related release of histamine. These data provide further evidence that teicoplanin is safer than vancomycin and does not have dose-related adverse effects in the dose range 3–10mg/kg. [ABSTRACT FROM PUBLISHER]

In the rat croton oil pouch model, treatment with ciprofloxacin, gentamicin or imipenem caused a sharp reduction in the numbers of Pseudomonas aeruginosa when applied 24 h after infection but treatment had little or no effect when delayed until 48 h after infection. Surviving bacteria from treated animals were fully susceptible on subculture in vitro. Between 24 h and 48 h after infection there was an increase in the concentration of magnesium and a decrease in the concentration of oxygen but no significant change in the pH of the pouch fluid. In-vitro, the MBC of gentamicin was increased four-fold by the addition of magnesium ions and eight-fold under anaerobic conditions whereas these variables had no significant effect upon the MBC of ciprofloxacin and imipenem. However, cells of P. aeruginosa incubated in batch culture for 4, 24 and 48 h became progressively more tolerant to killing by all three drugs. We conclude that the tolerance of P. aeruginosa in vivo was only partly explained by biochemical changes at the site of infection. The stationary growth phase was associated with progressive tolerance to killing by ciprofloxacin, gentamicin and imipenem both in vivo and in vitro. [ABSTRACT FROM AUTHOR]

The in-vitro MICs and MBCs of ciprofloxacin, cefoperazone, ceftazidime, ceftriaxone, gentamicin and imipenem were measured for five strains each of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa with standard and high inocula. The MBC was raised more than the MIC at the higher inoculum for all the drugs except ciprofloxacin. However, the MBC of imipenem against P. aeruginosa was increased relatively little at the higher inoculum in contrast to the findings with other beta-lactam drugs. In a rabbit model of endophthalmitis both cefoperazone and imipenem were markedly more bactericidal against a high inoculum of K. pneumoniae than would have been predicted from the results of in-vitro time kill curve studies. We conclude that the therapeutic relevance of the inoculum effect remains to be proved. [ABSTRACT FROM AUTHOR]

Data were collected prospectively from 59 patients receiving vancomycin and 20 patients receiving teicoplanin. The mean daily drug cost was 52.40 pounds for teicoplanin and 31.13 pounds for vancomycin; the 95% Confidence Intervals (CI) for the difference in mean drug costs varied between 14.40 pounds and 28.10 pounds in favour of vancomycin. Use of a loading dose of teicoplanin significantly increased mean daily drug costs if the duration of treatment was less than 10 days. Costs of preparation, administration and monitoring were consistently higher for vancomycin than for teicoplanin and inclusion of these costs reduced the difference in mean daily costs to 13.01 pounds (95% CI 6.10 to 19.90 pounds). In Dundee 11 of 20 patients who received teicoplanin had received some of their treatment after discharge from the hospital and a survey of UK hospitals confirmed that teicoplanin treatment after discharge is being used in a wide range of conditions. The median proportion of teicoplanin treatment in Dundee given after discharge was 28.4% for each patient who received the drug: the median proportion of non-inpatient therapy was 50% per patient of those who received any teicoplanin treatment after discharge. Assuming that teicoplanin costs 20 pounds per day more than vancomycin, use of teicoplanin implies an investment of 70.42 pounds to gain one hospital day through earlier discharge of patients receiving teicoplanin. [ABSTRACT FROM AUTHOR]

Single intravitreal doses of ciprofloxacin, gentamicin, or imipenem were administered to rabbits with pseudomonas endophthalmitis for determination of the maximally effective dose. Treatment was given 24 hr (“early”) or 48 hr (“late”) after infection. With early treatment the dose-response relationship between the drug concentration and the diminution in bacterial counts in the vitreous humor was linear with all three drugs. By contrast, with late treatment the same vitreal concentrations had no significant effect on bacterial counts. The failure of late treatment was not due to an increased rate of clearance of drugs from the eyes and could not be reproduced with a similar bacterial inoculum in vitro. Bacteria cultured from treated eyes were fully sensitive when plated directly onto drug-containing agar. The poor bactericidal effect of late treatment may in part be related to transient phenotypic alterations in the bacteria in response to changes in the environment of infection such as hypoxia, low pH, and exhaustion of critical bacterial nutrients. [ABSTRACT FROM PUBLISHER]

Antibiotic guidelines for community-acquired pneumonia (CAP) often recommend broad-spectrum agents for severe pneumonia. While these may be entirely appropriate in terms of their spectrum of activity and efficacy, there is a risk that such recommendations could result in over-prescribing of broad-spectrum agents with consequent ‘collateral damage’, meaning superinfection by resistant pathogens, or selection of antibiotic resistance. Narrow-spectrum agents are often as effective and result in less collateral damage. National and local antibiotic guidance should promote choices of agents for narrow-spectrum prescribing even for severe CAP where appropriate. [ABSTRACT FROM PUBLISHER]

The article discusses the role of cranberries in the treatment of urinary tract infection (UTI) among older people. It mentions that the fruit contains tannins called proanthocyanidins, which exhibits potent in vitro anti-adhesion activity against P-fimbriated Escherichia coli. It relates that a study revealed that cranberries can reduce the number of symptomatic UTIs on younger women.

The authors analyze whether the prevalence of quinolone resistance can be decreased by a reduction in community prescribing of quinolones. They say that selection pressure from antibiotic use in hospitals, primary care facilities, etc., give rise to resistance in bacteria that cause community-acquired infections. There are only few studies that provided evidence about the effect that interventions to reduce community antibiotic prescribing have on resistance.

Prudent antibiotic prescribing is a cornerstone of efforts to control the emergence and spread of antimicrobial resistance and to reduce the occurrence of Clostridium difficile associated diarrhoea, and is also currently the subject of a joint Working Party of the British Society for Antimicrobial Chemotherapy and the Hospital Infection Society. An article in this issue of the Journal describes a cluster randomized trial of an intervention to improve antibiotic prescribing using TREAT, a computerized decision support system. The results from this trial provide a significant contribution to the development of evidence-based prescribing of antibiotics. [ABSTRACT FROM PUBLISHER]

Objectives We tested a previously published model for the analysis of the temporal relationship between antibiotic use and the incidence of Clostridium difficile infection in a hospital with stable incidence of infection at >1 case per 1000 admissions per month. Methods The study period was from April 2004 to June 2008 and used data from Infection Control and Hospital Pharmacy. We first described the monthly variation in C. difficile infection and then constructed a multivariate transfer function model that included lag time (cases of C. difficile infection in previous months and delays between changes in antibiotic use and changes in C. difficile infection). Results The average incidence of C. difficile infection was 1.5 cases per 1000 patients per month with no significant increase over 3 years. The number of cases of C. difficile infection in 1 month was dependent on the average number of cases of C. difficile infection in the previous 2 months. The models with data from the whole hospital showed a statistically significant relationship between the number of both hospital-acquired C. difficile infections and total C. difficile infections and consumption of piperacillin/tazobactam, ciprofloxacin and cefuroxime. The association between C. difficile infection and consumption of co-amoxiclav was only significant for hospital-acquired C. difficile infection. The model for hospital-acquired C. difficile infections explained 61% of the variance in C. difficile infections. Conclusions These results provide support for antibiotic policies that minimize the use of broad-spectrum penicillins (co-amoxiclav and piperacillin/tazobactam), cephalosporins and fluoroquinolones. [ABSTRACT FROM AUTHOR]