Respiratory tract infections (RTIs) in primary care: narrative review of C reactive protein (CRP) point-of-care testing (POCT) and antibacterial use in patients who present with symptoms of RTI.

Antimicrobial resistance (AMR) continues to be a global problem and continues to be addressed through national strategies to improve diagnostics, develop new antimicrobials and promote antimicrobial stewardship. Patients who attend general (ambulatory) practice with symptoms of respiratory tract infections (RTIs) are invariably assessed by some sort of clinical decision rule (CDR). However, CDRs rely on a cluster of non-specific clinical observations. A narrative review of the literature was undertaken to ascertain the value of C reactive protein (CRP) point-of-care testing (POCT) to guide antibacterial prescribing in adult patients presenting to general practitioner (GP) practices with symptoms of RTI. Studies that were included were Cochrane reviews, systematic reviews, randomised controlled trials, cluster randomised trials, controlled before and after studies, cohort studies and economic evaluations. An overwhelming number of studies demonstrated that the use of CRP tests in patients presenting with RTI symptoms reduces index antibacterial prescribing. GPs and patients report a good acceptability for a CRP POCT and economic evaluations show cost-effectiveness of CRP POCT over existing RTI management in primary care. POCTs increase diagnostic precision for GPs in the better management of patients with RTI. With the rapid development of artificial intelligence, patients will expect greater precision in diagnosing and managing their illnesses. Adopting systems that markedly reduce antibiotic consumption is a no-brainer for governments that are struggling to address the rise in AMR.

Exploratory randomised controlled clinical study to evaluate the comparative efficacy of two occluding toothpastes - a 5% calcium sodium phosphosilicate toothpaste and an 8% arginine/calcium carbonate toothpaste - for the longer-term relief of dentine hypersensitivity.

OBJECTIVE: To compare the longer-term clinical efficacy of two occlusion-technology toothpastes - a 5% calcium sodium phosphosilicate (CSPS) toothpaste and a commercially available 8% arginine/calcium carbonate toothpaste - in relieving dentine hypersensitivity (DH). Efficacy was also compared with that of a regular fluoride toothpaste control. METHODS: This was an exploratory, randomised, examiner-blind, parallel-group, 11-week, controlled study in healthy adults with self-reported and clinically diagnosed DH. After an acclimatisation period, subjects were randomised to one of three study treatments with which they brushed their teeth twice daily. Sensitivity was assessed at baseline and after 1, 2, 4, 6 and 11 weeks treatment in response to evaporative (air) and tactile stimuli (measured by the Schiff Sensitivity Scale/visual analogue scale and tactile threshold, respectively). RESULTS: A total of 135 subjects were randomised to treatment. The two occlusion-technology toothpastes performed similarly over the 11-week treatment period. All study treatments showed statistically significant reductions from baseline in DH at all timepoints for all measures (p<0.05). Statistically significant and clinically relevant sensitivity relief was observed for both occluding formulations compared with the regular fluoride toothpaste: for evaporative (air) sensitivity within 1 week and for tactile sensitivity at Week 11. No significant differences were detected between the two occluding formulations at any timepoint, for any endpoint. Study treatments were generally well tolerated. CONCLUSIONS: In this exploratory study, a 5% CSPS occluding toothpaste was effective in relieving DH compared with a regular fluoride toothpaste; an 8% arginine/calcium carbonate anti-sensitivity toothpaste provided similar benefits. Improvements in DH continued throughout the 11-week study. CLINICAL SIGNIFICANCE: Dentine hypersensitivity (DH) is a common and painful condition. Twice-daily use of a 5% calcium sodium phosphosilicate toothpaste reduces DH within 1-2 weeks of initiating use. Ongoing, twice daily use of the sensitivity toothpastes evaluated in this study was associated with continued, clinically significant improvements in DH.

Reactive oxygen: A novel antimicrobial mechanism for targeting biofilm-associated infection.

Reactive oxygen species (ROS) is a novel therapeutic strategy for topical or local application to wounds, mucosa or internal structures where there may be heavy bacterial bioburden with biofilm and chronic inflammation. Bacterial biofilms are a significant problem in clinical settings owing to their increased tolerance towards conventionally prescribed antibiotics and their propensity for selection of further antibacterial resistance. There is therefore a pressing need for the development of alternative therapeutic strategies that can improve antibiotic efficacy towards biofilms. ROS has been successful in treating chronic wounds and in clearing multidrug-resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA), and carbapenemase-producing isolates from wounds and vascular line sites. There is significant antifungal activity of ROS against planktonic and biofilm forms. Nebulised ROS has been evaluated in limited subjects to assess reductions in bioburden in chronically colonised respiratory tracts. The antibiofilm activity of ROS could have great implications for the treatment of a variety of persistent respiratory conditions. Use of ROS on internal prosthetic devices shows promise. A variety of novel delivery mechanisms are being developed to apply ROS activity to different anatomical sites.

Hot topics in reactive oxygen therapy: Antimicrobial and immunological mechanisms, safety and clinical applications.

Reactive oxygen species (ROS), when combined with various delivery mechanisms, has the potential to become a powerful novel therapeutic agent against difficult-to-treat infections, especially those involving biofilm. It is important in the context of the global antibiotic resistance crisis. ROS is rapidly active in vitro against all Gram-positive and Gram-negative bacteria tested. ROS also has antifungal and antiviral properties. ROS prevents the formation of biofilms caused by a range of bacterial species in wounds and respiratory epithelium. ROS has been successfully used in infection prevention, eradication of multiresistant organisms, prevention of surgical site infection, and intravascular line care. This antimicrobial mechanism has great potential for the control of bioburden and biofilm at many sites, thus providing an alternative to systemic antibiotics on epithelial/mucosal surfaces, for wound and cavity infection, chronic respiratory infections and possibly recurrent urinary infections as well as local delivery to deeper structures and prosthetic devices. Its simplicity and stability lend itself to use in developing economies as well.

Rasch analysis of the Antimicrobial Self-Assessment Toolkit for National Health Service (NHS) Trusts (ASAT v17).

OBJECTIVES: The Antimicrobial Self-Assessment Toolkit for National Health Service (NHS) Trusts (ASAT) was developed to evaluate hospital-based antimicrobial stewardship programmes. Iterative validity investigations of the ASAT were used to produce a 91-item ASAT v17 utilizing qualitative methodology. Rasch analysis was used to generate question (item) behaviour estimates and to investigate the validity of ASAT v17. METHODS: In 2012, the partial credit model (PCM) was used to analyse ASAT responses from 33 NHS Trusts within England. WINSTEPS® outputs such as fit statistics and respondent/item maps were examined to determine unidimensionality, item discrimination and item hierarchy. Ordinary least squares regression modelling was used to determine the predictive validity using NHS Trust ability estimates generated from the PCM and corresponding Clostridium difficile rates. RESULTS: Each domain contained items that were misfitting the PCM (with INFIT MNSQ <0.7 or >1.3), except Domain 3. Subsequent iterative item removal had a negligible effect on the fit indices within most ASAT domains. Scale analysis demonstrated that most items were productive for measurement (n = 81). Respondent/item maps showed ceiling effects (n = 3) and floor effects (n = 1) within ASAT domains. Ordinary least squares regression modelling identified that there was limited predictive validity due to the small positive correlation between the predictor and outcome variables for participating hospitals (ρ = 0.146; P = 0.418). CONCLUSIONS: Rasch analysis was an effective measurement technique for evaluating the validity of ASAT v17 by providing evidence that each sub-scale and the overall scale demonstrated unidimensionality (construct validity). Improved item targeting may be required to improve item discrimination within the toolkit.

Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process.

Reactive oxygen species (ROS) play a pivotal role in the orchestration of the normal wound-healing response. They act as secondary messengers to many immunocytes and non-lymphoid cells, which are involved in the repair process, and appear to be important in coordinating the recruitment of lymphoid cells to the wound site and effective tissue repair. ROS also possess the ability to regulate the formation of blood vessels (angiogenesis) at the wound site and the optimal perfusion of blood into the wound-healing area. ROS act in the host's defence through phagocytes that induce an ROS burst onto the pathogens present in wounds, leading to their destruction, and during this period, excess ROS leakage into the surrounding environment has further bacteriostatic effects. In light of these important roles of ROS in wound healing and the continued quest for therapeutic strategies to treat wounds in general and chronic wounds, such as diabetic foot ulcers, venous and arterial leg ulcers and pressure ulcers in particular, the manipulation of ROS represents a promising avenue for improving wound-healing responses when they are stalled. This article presents a review of the evidence supporting the critical role of ROS in wound healing and infection control at the wound site, and some of the new emerging concepts associated with ROS modulation and its potential in improving wound healing are discussed.

Perspectives of clinical microbiologists on antimicrobial stewardship programmes within NHS trusts in England.

BACKGROUND: The Antimicrobial Self-Assessment Toolkit for NHS Trusts (ASAT) was developed in England by a National Pharmacist Reference Group of an Advisory Non-Departmental Public Body on Antimicrobial Resistance and Healthcare Associated Infections (ARHAI), in conjunction with the Department of Health. It is intended to identify and evaluate interventions for the promotion and implementation hospital-based antimicrobial stewardship programmes (ASPs). ASAT v16 was produced by iterative validity testing with end-users utilising a sequential exploratory strategy. It was highlighted that there was a need for the inclusion of the domain which targeted the role of clinical microbiologists due to their substantial roles in hospital-based ASP development and implementation. METHODS: This study aimed to investigate the content validity of ASAT v16 and a proposed draft domain for clinical microbiologists and hence produce ASAT v17. From June to September 2011, semi-structured interviews were conducted with ten consultant clinical microbiologists from secondary and tertiary care National Health Service (NHS) Trusts within England. Interviews were conducted until no novel themes were identified i.e., data saturation was achieved. Each interview was digitally recorded and transcribed verbatim and then analysed using a thematic framework that facilitated the identification of emergent themes and sub-themes. RESULTS: Nine emergent themes were identified which included common enablers and challenges associated with the implementation of effective and sustainable hospital-based ASPs. Key themes included formal governmental mandates, IT infrastructure and also prescribers' knowledge base of antimicrobial chemotherapy and infectious diseases. Most respondents agreed with the content of ASATv16 and the proposed draft section however they suggested that minor modifications were required to improve question sensitivity and hence reduce measurement error. CONCLUSIONS: Although, the ASAT been through multiple iterations and content validity testing, further modifications were required to produce the next iteration, ASAT v17. Question merging and other minor modifications were conducted as indicated by study findings. This study reinforces the need for stakeholder engagement during the development and implementation of tools that evaluate hospital-based implementation strategies.

Narrative review of primary care point-of-care testing (POCT) and antibacterial use in respiratory tract infection (RTI).

Antimicrobial resistance is a global problem and is being addressed through national strategies to improve diagnostics, develop new antimicrobials and promote antimicrobial stewardship. A narrative review of the literature was undertaken to ascertain the value of C reactive protein (CRP) and procalcitonin, measurements to guide antibacterial prescribing in adult patients presenting to GP practices with symptoms of respiratory tract infection (RTI). Studies that were included were randomised controlled trials, controlled before and after studies, cohort studies and economic evaluations. Many studies demonstrated that the use of CRP tests in patients presenting with RTI symptoms reduces antibiotic prescribing by 23.3% to 36.16%. Procalcitonin is not currently available as a point-of-care testing (POCT), but has shown value for patients with RTI admitted to hospital. GPs and patients report a good acceptability for a CRP POCT and economic evaluations show cost-effectiveness of CRP POCT over existing RTI management in primary care. POCTs increase diagnostic precision for GPs in the better management of patients with RTI. CRP POCT can better target antibacterial prescribing by GPs and contribute to national antimicrobial resistance strategies. Health services need to develop ways to ensure funding is transferred in order for POCT to be implemented.

Understanding the causes of intravenous medication administration errors in hospitals: a qualitative critical incident study.

OBJECTIVES: To investigate the underlying causes of intravenous medication administration errors (MAEs) in National Health Service (NHS) hospitals. SETTING: Two NHS teaching hospitals in the North West of England. PARTICIPANTS: Twenty nurses working in a range of inpatient clinical environments were identified and recruited using purposive sampling at each study site. PRIMARY OUTCOME MEASURES: Semistructured interviews were conducted with nurse participants using the critical incident technique, where they were asked to discuss perceived causes of intravenous MAEs that they had been directly involved with. Transcribed interviews were analysed using the Framework approach and emerging themes were categorised according to Reason's model of accident causation. RESULTS: In total, 21 intravenous MAEs were discussed containing 23 individual active failures which included slips and lapses (n=11), mistakes (n=8) and deliberate violations of policy (n=4). Each active failure was associated with a range of error and violation provoking conditions. The working environment was implicated when nurses lacked healthcare team support and/or were exposed to a perceived increased workload during ward rounds, shift changes or emergencies. Nurses frequently reported that the quality of intravenous dose-checking activities was compromised due to high perceived workload and working relationships. Nurses described using approaches such as subconscious functioning and prioritising to manage their duties, which at times contributed to errors. CONCLUSIONS: Complex interactions between active and latent failures can lead to intravenous MAEs in hospitals. Future interventions may need to be multimodal in design in order to mitigate these risks and reduce the burden of intravenous MAEs.

The antimicrobial activity of prototype modified honeys that generate reactive oxygen species (ROS) hydrogen peroxide.

BACKGROUND: Antimicrobial resistance continues to be a global issue in healthcare organisations. Honey has long been shown to possess wound healing and antimicrobial properties that are dependent on a number of physical and chemical properties of the honey. We tested the antimicrobial activity of a medicinal honey, Surgihoney® (SH) and two prototype modified honeys made by Apis mellifera (honeybee) against Staphylococcus aureus (NCIMB 9518). We also examined the modified honey prototypes for the ability to generate reactive oxygen species (ROS) by changing the level of production of hydrogen peroxide from the samples. METHODS: Surgihoney® (SH) was compared with two modified honeys, Prototype 1 (PT1) and Prototype 2 (PT2) using a bioassay method against a standard strain of Staphylococcus aureus. Further work studied the rate of generation of ROS hydrogen peroxide from these preparations. RESULTS: Surgihoney® antimicrobial activity was shown to be largely due to ROS hydrogen peroxide production. By modification of Surgihoney®, two more potent honey prototypes were shown to generate between a two- and three-fold greater antibacterial activity and up to ten times greater ROS peroxide activity. CONCLUSIONS: Surgihoney® is a clinically available wound antiseptic dressing that shows good antimicrobial activity. Two further honey prototypes have been shown to have antimicrobial activity that is possible to be enhanced due to demonstrated increases in ROS peroxide activity.

Longitudinal trends and cross-sectional analysis of English national hospital antibacterial use over 5 years (2008-13): working towards hospital prescribing quality measures.

OBJECTIVES: There is global concern that antimicrobial resistance is a major threat to healthcare. Antimicrobial use is a primary driver of resistance but little information exists about the variation in antimicrobial use in individual hospitals in England over time or comparative use between hospitals. The objective of this study was to collate, analyse and report issue data from pharmacy records of 158 National Health Service (NHS) acute hospitals. METHODS: This was a cohort study of inpatient antibacterial use in acute hospitals in England analysed over 5 years through a data warehouse from IMS Health, a leading provider of information, services and technology for the healthcare industry. Around 98% of NHS hospitals were included in a country with a population of 50 million residents. RESULTS: There was a dramatic change in the usage of different groups of antibacterials between 2009 and 2013 with a marked reduction in the use of first-generation cephalosporins by 24.7% and second-generation cephalosporins by 41%, but little change in the use of third-generation cephalosporins (+5.7%) and fluoroquinolones (+1.6%). In contrast, use of co-amoxiclav, carbapenems and piperacillin/tazobactam increased by 60.1%, 61.4% and 94.8%, respectively. There was wide variation in the total and relative amounts of antibacterials used between individual hospitals. CONCLUSIONS: Longitudinal analysis of antibacterial use demonstrated remarkable changes in NHS hospitals, probably reflecting governmental and professional guidance to mitigate the risk of Clostridium difficile infection. The wide variation in usage between individual hospitals suggests potential for quality improvement and benchmarking. Quality measures of optimal hospital antimicrobial prescribing need urgent development and validation to support antimicrobial stewardship initiatives.

Association between Clostridium difficile infection and antimicrobial usage in a large group of English hospitals.

AIMS: This study aimed to determine the association between the reduction in the number of Clostridium difficile infection (CDI) cases reported by the English National Health Service (NHS) hospitals and concurrent antimicrobial use. METHODS: A retrospective ecological study for January 2005 to December 2008 was conducted using data from 26 of the 29 NHS trusts (i.e. a trust manages one or more hospitals) located in the North West Strategic Health Authority of England. Antimicrobial use data, for patients of all ages, were provided by IMS Health, and CDI case data for patients aged ≥65 years were provided by the Health Protection Agency. Antimicrobial use was converted into defined daily doses (DDDs). The overall association between antimicrobial use and CDI for the trusts was investigated using multilevel models. RESULTS: Our study shows a positive significant association between the CDI cases and the use of the following antimicrobials: 'third-generation cephalosporins' [11.62 CDI cases per 1000 DDDs; 95% confidence interval (CI), 5.92­17.31]; 'fluoroquinolones' (4.79 CDI cases per 1000 DDDs; 95% CI, 2.83­6.74); and 'second-generation cephalosporins' (4.25 CDI cases per 1000 DDDs; 95% CI, 1.66­6.83). The strength of this association was not significantly different (95% CI) among the antimicrobial groups. CONCLUSIONS: This study shows that the reduction in the number of CDI cases reported by the English NHS hospitals is associated with concurrent reductions in antimicrobial use. This means that the number of CDI cases over time decreased in a similar fashion to the usage of various antimicrobials.

Impact of interventions designed to reduce medication administration errors in hospitals: a systematic review.

BACKGROUND: There is a need to identify effective interventions to minimize the threat posed by medication administration errors (MAEs). OBJECTIVE: Our objective was to review and critically appraise interventions designed to reduce MAEs in the hospital setting. DATA SOURCES: Ten electronic databases were searched between 1985 and November 2013. METHODS: Randomized controlled trials (RCTs) and controlled trials (CTs) reporting rates of MAEs or related adverse drug events between an intervention group and a comparator group were included. Data from each study were independently extracted and assessed for potential risk of bias by two authors. Risk ratios (RRs, with 95 % confidence intervals [CIs]) were used to examine the effect of an intervention. RESULTS: Six RCTs and seven CTs were included. Types of interventions clustered around four main themes: medication use technology (n = 4); nurse education and training (n = 3); changing practice in anesthesia (n = 2); and ward system changes (n = 4). Reductions in MAE rates were reported by five studies; these included automated drug dispensing (RR 0.72, 95 % CI 0.53-1.00), computerized physician order entry (RR 0.51, 95 % 0.40-0.66), barcode-assisted medication administration with electronic administration records (RR 0.71, 95 % CI 0.53-0.95), nursing education/training using simulation (RR 0.17, 95 % CI 0.08-0.38), and clinical pharmacist-led training (RR 0.76, 95 % CI 0.67-0.87). Increased or equivocal outcome rates were found for the remaining studies. Weaknesses in the internal or external validity were apparent for most included studies. LIMITATIONS: Theses and conference proceedings were excluded and data produced outside commercial publishing were not searched. CONCLUSIONS: There is emerging evidence of the impact of specific interventions to reduce MAEs in hospitals, which warrant further investigation using rigorous and standardized study designs. Theory-driven efforts to understand the underlying causes of MAEs may lead to more effective interventions in the future.

When antibiotics can be avoided in skin inflammation and bacterial colonization: a review of topical treatments.

PURPOSE OF REVIEW: This review looks at the recent evidence on the safety, toxicity, microbiology and the prevention and management of acute and chronic wound infections with regard to antiseptics and antiseptic wound dressings. It is timely and relevant because of the global concerns of antimicrobial resistance and the need to address the inappropriate use of antimicrobials in the healthcare setting. RECENT FINDINGS: There have been a number of recent Cochrane reviews that have concluded that there is little evidence to delineate clinical outcomes between antiseptics and antiseptic dressings. Published in-vitro evidence offers some new techniques and evaluates some new dressings and antiseptics. There are no economic evaluations of antiseptics and antiseptic dressings. SUMMARY: Better clinical trials on the effectiveness and cost-effectiveness of wound dressings are needed to ensure evidence-based guidance is developed for optimizing the treatment of patients. It is surprising that with the paucity of evidence of clinical effectiveness, healthcare organizations continue to spend considerable resources on poorly evaluated topical wound products.

Engineered honey: In vitro antimicrobial activity of a novel topical wound care treatment.

Surgihoney is a novel engineered organic honey product for wound care. Its antimicrobial activity can be controlled and adjusted by the engineering process, allowing preparation of three different potencies, labelled Surgihoney 1-3. Susceptibility testing of a range of wound and ulcer bacterial isolates to Surgihoney by the disc diffusion method, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) determination, and time-kill measurements by time suspension tests were performed. Surgihoney demonstrated highly potent inhibitory and cidal activity against a wide range of Gram-positive and Gram-negative bacteria and fungi. MICs/MBCs were significantly lower than concentrations likely to be achieved in topical clinical use. The topical concentration of Surgihoney in wounds was estimated at ca. 500g/L. MICs/MBCs for Staphylococcus aureus were 32/125g/L for Surgihoney 1 and 0.12/0.25g/L for Surgihoney 3. Cidal speed depended on potency, being 48h for Surgihoney 1 and 30min for Surgihoney 3. Maintenance of the Surgihoney inoculum preparation for up to a week demonstrated complete cidal activity and no bacterial persistence. Surgihoney has wide potential as a highly active topical treatment combining the effects of the healing properties of honey with the potent antimicrobial activity of the engineered product for skin lesions, wounds, ulcers and cavities. It is highly active against multidrug-resistant bacteria. It is more active than other honeys tested and is comparable with chemical antiseptics in antimicrobial activity.

Causes of medication administration errors in hospitals: a systematic review of quantitative and qualitative evidence.

BACKGROUND: Underlying systems factors have been seen to be crucial contributors to the occurrence of medication errors. By understanding the causes of these errors, the most appropriate interventions can be designed and implemented to minimise their occurrence. OBJECTIVE: This study aimed to systematically review and appraise empirical evidence relating to the causes of medication administration errors (MAEs) in hospital settings. DATA SOURCES: Nine electronic databases (MEDLINE, EMBASE, International Pharmaceutical Abstracts, ASSIA, PsycINFO, British Nursing Index, CINAHL, Health Management Information Consortium and Social Science Citations Index) were searched between 1985 and May 2013. STUDY SELECTION: Inclusion and exclusion criteria were applied to identify eligible publications through title analysis followed by abstract and then full text examination. English language publications reporting empirical data on causes of MAEs were included. Reference lists of included articles and relevant review papers were hand searched for additional studies. Studies were excluded if they did not report data on specific MAEs, used accounts from individuals not directly involved in the MAE concerned or were presented as conference abstracts with insufficient detail. DATA APPRAISAL AND SYNTHESIS METHODS: A total of 54 unique studies were included. Causes of MAEs were categorised according to Reason's model of accident causation. Studies were assessed to determine relevance to the research question and how likely the results were to reflect the potential underlying causes of MAEs based on the method(s) used. RESULTS: Slips and lapses were the most commonly reported unsafe acts, followed by knowledge-based mistakes and deliberate violations. Error-provoking conditions influencing administration errors included inadequate written communication (prescriptions, documentation, transcription), problems with medicines supply and storage (pharmacy dispensing errors and ward stock management), high perceived workload, problems with ward-based equipment (access, functionality), patient factors (availability, acuity), staff health status (fatigue, stress) and interruptions/distractions during drug administration. Few studies sought to determine the causes of intravenous MAEs. A number of latent pathway conditions were less well explored, including local working culture and high-level managerial decisions. Causes were often described superficially; this may be related to the use of quantitative surveys and observation methods in many studies, limited use of established error causation frameworks to analyse data and a predominant focus on issues other than the causes of MAEs among studies. LIMITATIONS: As only English language publications were included, some relevant studies may have been missed. CONCLUSIONS: Limited evidence from studies included in this systematic review suggests that MAEs are influenced by multiple systems factors, but if and how these arise and interconnect to lead to errors remains to be fully determined. Further research with a theoretical focus is needed to investigate the MAE causation pathway, with an emphasis on ensuring interventions designed to minimise MAEs target recognised underlying causes of errors to maximise their impact.

Prevalence and nature of medication administration errors in health care settings: a systematic review of direct observational evidence.

OBJECTIVE: To systematically review empirical evidence on the prevalence and nature of medication administration errors (MAEs) in health care settings. DATA SOURCES: Ten electronic databases (MEDLINE, EMBASE, International Pharmaceutical Abstracts, Scopus, Applied Social Sciences Index and Abstracts, PsycINFO, Cochrane Reviews and Trials, British Nursing Index, Cumulative Index to Nursing and Allied Health Literature, and Health Management Information Consortium) were searched (1985-May 2012). STUDY SELECTION AND DATA EXTRACTION: English-language publications reporting MAE data using the direct observation method were included, providing an error rate could be determined. Reference lists of all included articles were screened for additional studies. DATA SYNTHESIS: In all, 91 unique studies were included. The median error rate (interquartile range) was 19.6% (8.6-28.3%) of total opportunities for error including wrong-time errors and 8.0% (5.1-10.9%) without timing errors, when each dose could be considered only correct or incorrect. The median rate of error when more than 1 error could be counted per dose was 25.6% (20.8-41.7%) and 20.7% (9.7-30.3%), excluding wrong-time errors. A higher median MAE rate was observed for the intravenous route (53.3% excluding timing errors (IQR 26.6-57.9%)) compared to when all administration routes were studied (20.1%; 9.0-24.6%), where each dose could accumulate more than one error. Studies consistently reported wrong time, omission, and wrong dosage among the 3 most common MAE subtypes. Common medication groups associated with MAEs were those affecting nutrition and blood, gastrointestinal system, cardiovascular system, central nervous system, and antiinfectives. Medication administration error rates varied greatly as a product of differing medication error definitions, data collection methods, and settings of included studies. Although MAEs remained a common occurrence in health care settings throughout the time covered by this review, potential targets for intervention to minimize MAEs were identified. CONCLUSIONS: Future research should attend to the wide methodological inconsistencies between studies to gain a greater measure of comparability to help guide any forthcoming interventions.