Modifiable healthcare factors affecting 28-day survival in bloodstream infection: a prospective cohort study.

BACKGROUND: Bloodstream infection is common in the UK and has significant mortality depending on the pathogen involved, site of infection and other patient factors. Healthcare staffing and ward activity may also impact on outcomes in a range of conditions, however there is little specific National Health Service (NHS) data on the impact for patients with bloodstream infection. Bloodstream Infections - Focus on Outcomes is a multicentre cohort study with the primary aim of identifying modifiable risk factors for 28-day mortality in patients with bloodstream infection due to one of six key pathogens. METHODS: Adults under the care of five NHS Trusts in England and Wales between November 2010 and May 2012 were included. Multivariable Cox regression was used to quantify the association between modifiable risk factors, including staffing levels and timing of appropriate therapy, and 28-day mortality, after adjusting for non-modifiable risk factors such as patient demographics and long-term comorbidities. RESULTS: A total of 1676 patients were included in the analysis population. Overall, 348/1676 (20.8%) died within 28 days. Modifiable factors associated with 28-day mortality were ward speciality, ward activity (admissions and discharges), movement within ward speciality, movement from critical care, and time to receipt of appropriate antimicrobial therapy in the first 7 days. For each additional admission or discharge per 10 beds, the hazard increased by 4% (95% CI 1 to 6%) in medical wards and 11% (95% CI 4 to 19%) in critical care. Patients who had moved wards within speciality or who had moved out of a critical care ward had a reduction in hazard of mortality. In the first 7 days, hazard of death increased with increasing time to receipt of appropriate antimicrobial therapy. CONCLUSION: This study underlines the importance of appropriate antimicrobials within the first 7 days, and the potential for ward activity and ward movements to impact on survival in bloodstream infection.

Risk Factors for Treatment Failure and Mortality Among Hospitalized Patients With Complicated Urinary Tract Infection: A Multicenter Retrospective Cohort Study (RESCUING Study Group).

Background: Complicated urinary tract infections (cUTIs) are responsible for a major share of all antibiotic consumption in hospitals. We aim to describe risk factors for treatment failure and mortality among patients with cUTIs. Methods: A multinational, multicentre retrospective cohort study, conducted in 20 countries in Europe and the Middle East. Data were collected from patients' files on hospitalised patients with a diagnosis of cUTI during 2013-2014. Primary outcome was treatment failure, secondary outcomes included 30 days all-cause mortality,among other outcomes. Multivariable analysis using a logistic model and the hospital as a random variable was performed to identify independent predictors for these outcomes. Results: A total of 981 patients with cUTI were included. Treatment failure was observed in 26.6% (261/981), all cause 30-day mortality rate was 8.7% (85/976), most of these in patients with catheter related UTI (CaUTI). Risk factors for treatment failure in multivariable analysis were ICU admission (OR 5.07, 95% CI 3.18-8.07), septic shock (OR 1.92, 95% CI 0.93-3.98), corticosteroid treatment (OR 1.92, 95% CI 1.12-3.54), bedridden (OR 2.11, 95%CI 1.4-3.18), older age (OR 1.02, 95% CI 1.0071.03-), metastatic cancer (OR 2.89, 95% CI 1.46-5.73) and CaUTI (OR 1.48, 95% CI 1.04-2.11). Management variables, such as inappropriate empirical antibiotic treatment or days to starting antibiotics were not associated with treatment failure or 30-day mortality. More patients with pyelonephritis were given appropriate empirical antibiotic therapy than other CaUTI [110/171; 64.3% vs. 116/270; 43%, p <0.005], nevertheless, this afforded no advantage in treatment failure rates nor mortality in these patients. Conclusions: In patients with cUTI we found no benefit of early appropriate empirical treatment on survival rates or other outcomes. Physicians might consider supportive treatment and watchful waiting in stable patients until the causative pathogen is defined.

Extent, quality and impact of patient and public involvement in antimicrobial drug development research: A systematic review.

BACKGROUND: Patient and public involvement (PPI) is increasingly recognized as bringing a range of benefits to clinical and health services research. Recent systematic reviews have identified and synthesized many benefits (eg higher recruitment rates) and some costs (eg extra time need). Much of the literature focuses on PPI in long-term conditions rather than more acute health care in which the majority of microbiological research is undertaken. OBJECTIVES: The aim was to identify the extent, quality and impact of PPI in antimicrobial drug development research. Objectives were to identify any relevant reporting of PPI in antimicrobial research; appraise the quality of reporting on PPI using recognized PPI reporting and critical appraisal tools; and extract and synthesize data on the impact of PPI. SEARCH STRATEGY: A systematic review was undertaken with a search strategy based on four word groups (PPI, patients, antimicrobial drug development and outcomes). Eight online databases were searched. INCLUSION CRITERIA: English language publication, publication between 1996 and 2016 and studies describing PPI in antimicrobial drug development research. MAIN RESULTS: No studies were found through online searching that met the search strategy and inclusion criteria. One relevant protocol paper with a brief mention of PPI was identified through expert recommendation. Commentary papers recommending PPI were identified through website searching and expert opinion. DISCUSSION AND CONCLUSIONS: Despite strong policy guidance encouraging PPI at the international and national levels, and anecdotal accounts of PPI taking place, evidence for the extent, quality and impact of PPI in antimicrobial drug development research has not yet appeared in the peer-reviewed literature.

Cost-effectiveness of rapid laboratory-based mass-spectrometry diagnosis of bloodstream infection: evidence from the RAPIDO randomised controlled trial.

OBJECTIVES AND INTERVENTION: Bloodstream infection, the presence of viable micro-organisms in the blood, is a prevalent clinical event associated with substantial mortality. Patient outcomes may be improved when the causative micro-organism is identified quickly. We assessed the cost-effectiveness of rapid microbial identification by matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry. DESIGN: Economic evaluation alongside a randomised multicentre trial (RAPIDO: RAPId Diagnosis on Outcome) assessing the impact of rapid identification by MALDI-TOF spectrometry. SETTING: Adult inpatients with bloodstream infections at seven National Health Service hospital trusts in England and Wales. PRIMARY OUTCOME: Net monetary benefit, estimated as incremental costs compared with incremental 28-day survival, of rapid identification by MALDI-TOF spectrometry compared with conventional identification. METHODS: Patients were randomised (1:1) to receive diagnosis by conventional methods of microbial identification (conventional arm) only or by MALDI-TOF spectrometry in addition to conventional identification (RAPIDO arm). RESULTS: Data from 5550 patients were included in primary analysis. Mean imputed costs in 2018/2019 prices per patient were lower by £126 in the RAPIDO arm (95% CI -£784 to £532) but the proportion of patients alive at day 28 was lower (81.4% vs 82.3%). The probability of cost-effectiveness of MALDI-TOF was <0.5 at cost-effectiveness thresholds between £20 000 and £50 000. CONCLUSIONS: Adjunctive MALDI-TOF diagnosis was unlikely to be cost-effective when measured as cost per death avoided at 28 days. However, the differences between arms in cost and effect were modest, associated with uncertainty and may not accurately reflect 'real-world' routine use of MALDI-TOF technology in this patient group. TRIAL REGISTRATION NUMBERS: ISRCTN97107018/UKCRN 11978.

Finding and engaging patients and the public to work collaboratively on an acute infection microbiology research public panel.

PLAIN ENGLISH SUMMARY: In 2015 a microbiology team in Bristol joined a European research project that aims to develop new antibiotics to fight drug resistant infections. The microbiology team were convinced of the benefits of patient and public involvement, but had found it difficult to find former patients to work with on earlier microbiology research. This paper describes how the team overcame this challenge to successfully recruit a PPI panel to develop PPI within the European project.The advice from people with experience in public involvement was to decide what criteria were desirable for panel membership, think about what the work of the panel might involve and how long the project will go on. The team decided that experience of suffering a serious acute infection would qualify people to comment on this project. Next, the team needed to identify ways of finding people to join the PPI panel.The microbiology research team tried different ways to approach potential panel members. These included distributing flyers at public research events, sending emails to potentially interested people, posting a message on the hospital Facebook page and approaching eligible people known to the team. A direct approach was the most successful method - either by email, mail or in person. Ultimately 16 people were selected to form the panel. Key factors for success were planning what the work of the panel might be, perseverance despite early lack of success, and one person having overall responsibility for setting up the panel, with the support of the whole team. ABSTRACT: Background In 2015 the microbiology research team became involved in a large European programme of research aiming to bring new antimicrobial drugs onto the market to combat the increasing problem of multi-drug resistant infection. With the purpose of developing patient and public involvement (PPI) in this project, the team decided to recruit a PPI panel to work with. The microbiology team had previously worked with a PPI panel on other research, but had found it difficult to recruit members. Methods Steps taken to recruit the panel were as follows:Advice was sought from people experienced in co-ordinating public involvement in research.One person in the team had overall responsibility but the whole research team was committed and met regularly.Two of the team undertook training in group facilitation and connecting with the public.Decisions were made about the criteria for inclusion into the panel, what tasks we envisaged for the panel, the length of and frequency of meetings.Advertising the involvement opportunity through flyers, social media, emails and direct contact with possible panel recruits known to the research team.Relevant documents such as a Role Profile and expression of interest form were drafted.An initial public meeting was planned for all who had shown interest in the panel.The expression of interest form was used for us to select as broad a group as possible.. Results Two out of three people who were approached directly and known by team members expressed interest in joining the panel (66%). Three out of seven members of a former panel were next (43%), then 10 out of 25 spinal infection clinic patients (40%), and finally 12 people responded to an email sent to 1261 foundation trust members (1%). No-one who was approached by indirect methods e.g. flyers or advertising on Facebook, expressed interest in the panel. Sixteen people were eventually selected for the panel. Conclusions It is possible to recruit a patient and public involvement panel for research in a discipline as challenging as microbiology. Good planning and the commitment of the research team were key to success.

Predictive factors for multidrug-resistant gram-negative bacteria among hospitalised patients with complicated urinary tract infections.

Background: Patients with complicated urinary tract infections (cUTIs) frequently receive broad-spectrum antibiotics. We aimed to determine the prevalence and predictive factors of multidrug-resistant gram-negative bacteria in patients with cUTI. Methods: This is a multicenter, retrospective cohort study in south and eastern Europe, Turkey and Israel including consecutive patients with cUTIs hospitalised between January 2013 and December 2014. Multidrug-resistance was defined as non-susceptibility to at least one agent in three or more antimicrobial categories. A mixed-effects logistic regression model was used to determine predictive factors of multidrug-resistant gram-negative bacteria cUTI. Results: From 948 patients and 1074 microbiological isolates, Escherichia coli was the most frequent microorganism (559/1074), showing a 14.5% multidrug-resistance rate. Klebsiella pneumoniae was second (168/1074) and exhibited the highest multidrug-resistance rate (54.2%), followed by Pseudomonas aeruginosa (97/1074) with a 38.1% multidrug-resistance rate. Predictors of multidrug-resistant gram-negative bacteria were male gender (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.20-2.29), acquisition of cUTI in a medical care facility (OR, 2.59; 95%CI, 1.80-3.71), presence of indwelling urinary catheter (OR, 1.44; 95%CI, 0.99-2.10), having had urinary tract infection within the previous year (OR, 1.89; 95%CI, 1.28-2.79) and antibiotic treatment within the previous 30 days (OR, 1.68; 95%CI, 1.13-2.50). Conclusions: The current high rate of multidrug-resistant gram-negative bacteria infections among hospitalised patients with cUTIs in the studied area is alarming. Our predictive model could be useful to avoid inappropriate antibiotic treatment and implement antibiotic stewardship policies that enhance the use of carbapenem-sparing regimens in patients at low risk of multidrug-resistance.

Cost of hospitalised patients due to complicated urinary tract infections: a retrospective observational study in countries with high prevalence of multidrug-resistant Gram-negative bacteria: the COMBACTE-MAGNET, RESCUING study.

OBJECTIVE: Complicated urinary tract infections (cUTIs) impose a high burden on healthcare systems and are a frequent cause of hospitalisation. The aims of this paper are to estimate the cost per episode of patients hospitalised due to cUTI and to explore the factors associated with cUTI-related healthcare costs in eight countries with high prevalence of multidrug resistance (MDR). DESIGN: This is a multinational observational, retrospective study. The mean cost per episode was computed by multiplying the volume of healthcare use for each patient by the unit cost of each item of care and summing across all components. Costs were measured from the hospital perspective. Patient-level regression analyses were used to identify the factors explaining variation in cUTI-related costs. SETTING: The study was conducted in 20 hospitals in eight countries with high prevalence of multidrug resistant Gram-negative bacteria (Bulgaria, Greece, Hungary, Israel, Italy, Romania, Spain and Turkey). PARTICIPANTS: Data were obtained from 644 episodes of patients hospitalised due to cUTI. RESULTS: The mean cost per case was €5700, with considerable variation between countries (largest value €7740 in Turkey; lowest value €4028 in Israel), mainly due to differences in length of hospital stay. Factors associated with higher costs per patient were: type of admission, infection source, infection severity, the Charlson comorbidity index and presence of MDR. CONCLUSIONS: The mean cost per hospitalised case of cUTI was substantial and varied significantly between countries. A better knowledge of the reasons for variations in length of stays could facilitate a better standardised quality of care for patients with cUTI and allow a more efficient allocation of healthcare resources. Urgent admissions, infections due to an indwelling urinary catheterisation, resulting in septic shock or severe sepsis, in patients with comorbidities and presenting MDR were related to a higher cost.

Retrospective observational study to assess the clinical management and outcomes of hospitalised patients with complicated urinary tract infection in countries with high prevalence of multidrug resistant Gram-negative bacteria (RESCUING).

INTRODUCTION: The emergence of multidrug resistant (MDR) Gram-negative bacteria (GNB), including carbapenemase-producing strains, has become a major therapeutic challenge. These MDR isolates are often involved in complicated urinary tract infection (cUTI), and are associated with poor clinical outcomes. The study has been designed to gain insight into the epidemiology, clinical management, outcome and healthcare cost of patients with cUTI, especially in countries with high prevalence of MDR GNB. METHODS AND ANALYSIS: This multinational and multicentre observational, retrospective study will identify cases from 1 January 2013 to 31 December 2014 in order to collect data on patients with cUTI as a cause of hospital admission, and patients who develop cUTI during their hospital stay. The primary end point will be treatment failure defined as the presence of any of the following criteria: (1) signs or symptoms of cUTI present at diagnosis that have not improved by days 5-7 with appropriate antibiotic therapy, (2) new cUTI-related symptoms that have developed within 30 days of diagnosis, (3) urine culture taken within 30 days of diagnosis, either during or after completion of therapy, that grows ≥10(4) colony-forming unit/mL of the original pathogen and (4) death irrespective of cause within 30 days of the cUTI diagnosis. SAMPLE SIZE: 1000 patients afford a power of 0.83 (α=0.05) to detect an absolute difference of 10% in the treatment failure rate between MDR bacteria and other pathogens. This should allow for the introduction of about 20 independent risk factors (or their interaction) in a logistic regression model looking at risk factors for failure. ETHICS AND DISSEMINATION: Approval will be sought from all relevant Research Ethics Committees. Publication of this study will be considered as a joint publication by the participating investigator leads, and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE). TRIAL REGISTRATION NUMBER: NCT02641015; Pre-results.