Early empiric antibiotic therapy in patients can improve clinical outcomes in Gram-negative bacteraemia. However, the widespread prevalence of antibiotic-resistant pathogens compromises our ability ...to provide adequate therapy while minimizing use of broad antibiotics. We sought to determine whether readily available electronic medical record data could be used to develop predictive models for decision support in Gram-negative bacteraemia.
We performed a multi-centre cohort study, in Canada and the USA, of hospitalized patients with Gram-negative bloodstream infection from April 2010 to March 2015. We analysed multivariable models for prediction of antibiotic susceptibility at two empiric windows: Gram-stain-guided and pathogen-guided treatment. Decision-support models for empiric antibiotic selection were developed based on three clinical decision thresholds of acceptable adequate coverage (80%, 90% and 95%).
A total of 1832 patients with Gram-negative bacteraemia were evaluated. Multivariable models showed good discrimination across countries and at both Gram-stain-guided (12 models, areas under the curve (AUCs) 0.68–0.89, optimism-corrected AUCs 0.63–0.85) and pathogen-guided (12 models, AUCs 0.75–0.98, optimism-corrected AUCs 0.64–0.95) windows. Compared to antibiogram-guided therapy, decision-support models of antibiotic selection incorporating individual patient characteristics and prior culture results have the potential to increase use of narrower-spectrum antibiotics (in up to 78% of patients) while reducing inadequate therapy.
Multivariable models using readily available epidemiologic factors can be used to predict antimicrobial susceptibility in infecting pathogens with reasonable discriminatory ability. Implementation of sequential predictive models for real-time individualized empiric antibiotic decision-making has the potential to both optimize adequate coverage for patients while minimizing overuse of broad-spectrum antibiotics, and therefore requires further prospective evaluation.
Readily available epidemiologic risk factors can be used to predict susceptibility of Gram-negative organisms among patients with bacteraemia, using automated decision-making models.
Appropriate empiric antibiotic therapy in patients with bloodstream infections due to Gram-negative pathogens can improve outcomes. We evaluated the utility of prior microbiologic results for guiding ...empiric treatment in Gram-negative bloodstream infections.
We conducted a multicentre observational cohort study in two large health systems in Canada and the United States, including 1832 hospitalized patients with Gram-negative bloodstream infection (community, hospital and intensive care unit acquired) from April 2010 to March 2015.
Among 1832 patients with Gram-negative bloodstream infection, 28% (n = 504) of patients had a documented prior Gram-negative organism from a nonscreening culture within the previous 12 months. A most recent prior Gram-negative organism resistant to a given antibiotic was strongly predictive of the current organism's resistance to the same antibiotic. The overall specificity was 0.92 (95% confidence interval (CI) 0.91–0.93), and positive predictive value was 0.66 (95% CI 0.61–0.70) for predicting antibiotic resistance. Specificities and positive predictive values ranged from 0.77 to 0.98 and 0.43 to 0.78, respectively, across different antibiotics, organisms and patient subgroups. Increasing time between cultures was associated with a decrease in positive predictive value but not specificity. An heuristic based on a prior resistant Gram-negative pathogen could have been applied to one in four patients and in these patients would have changed therapy in one in five.
In patients with a bloodstream infection with a Gram-negative organism, identification of a most recent prior Gram-negative organism resistant to a drug of interest (within the last 12 months) is highly specific for resistance and should preclude use of that antibiotic.
Summary Background Extended-spectrum β-lactamase (ESBL)-producing bacteria are important sources of infection; however, Canadian data evaluating the impact of ESBL-associated infection are lacking. ...Aim To determine whether patients infected with ESBL-producing Escherichia coli or Klebsiella species (ESBL-EcKs) exhibit differences in clinical outcome, microbiological outcome, mortality, and/or hospital resource use compared to patients infected with non-ESBL-producing strains. Methods A retrospective case–control study of 75 case patients with ESBL-EcKs matched to controls infected with non-ESBL-EcKs who were hospitalized from June 2010 to April 2013 was conducted. Patient-level cost data were provided by the institution's business office. Clinical data were collected using the electronic databases and paper charts. Findings Median infection-related hospitalization costs per patient were greater for cases than controls (C$10,507 vs C$7,882; median difference: C$3,416; P = 0.04). The primary driver of increased costs was prolonged infection-related hospital length of stay (8 vs 6 days; P = 0.02) with patient location (ward, ICU) and indirect care costs (including costs associated with infection prevention and control) as the leading cost categories. Cases were more likely to experience clinical failure (25% vs 11%; P = 0.03), with a higher all-cause mortality (17% vs 5%; P = 0.04). Less than half of case patients were prescribed appropriate empiric antimicrobial therapy, whereas controls received adequate initial treatment in nearly all circumstances (48% vs 96%; P < 0.01). Conclusion Patients with infection caused by ESBL-EcKs are at increased risk for clinical failure and mortality, with additional cost to the Canadian healthcare system of C$3,416 per patient.
To evaluate the current state of evidence for antimicrobial stewardship interventions in the critical care unit.
We performed a systematic search of OVID MEDLINE, Embase and Cochrane electronic ...databases from 1996-2010. Studies were included if they involved any experimental intervention to improve antimicrobial utilization in the critical care setting.
Thirty-eight studies met the inclusion criteria, of which 24 met our quality inclusion criteria. The quality of research was poor, with only 3 randomized controlled trials, 3 interrupted time series and 18 (75%) uncontrolled before-and-after studies. We identified six intervention types: studies of antibiotic restriction or pre-approval (six studies); formal infectious diseases physician consultation (five); implementation of guidelines or protocols for de-escalation (two); guidelines for antibiotic prophylaxis or treatment in intensive care (two); formal reassessment of antibiotics on a pre-specified day of therapy (three); and implementation of computer-assisted decision support (six). Stewardship interventions were associated with reductions in antimicrobial utilization (11%-38% defined daily doses/1000 patient-days), lower total antimicrobial costs (US$ 5-10/patient-day), shorter average duration of antibiotic therapy, less inappropriate use and fewer antibiotic adverse events. Stewardship interventions beyond 6 months were associated with reductions in antimicrobial resistance rates, although this differed by drug-pathogen combination. Antibiotic stewardship was not associated with increases in nosocomial infection rates, length of stay or mortality.
More rigorous research is needed, but available evidence suggests that antimicrobial stewardship is associated with improved antimicrobial utilization in the intensive care unit, with corresponding improvements in antimicrobial resistance and adverse events, and without compromise of short-term clinical outcomes.
Cefazolin plus tobramycin have been determined to be effective for community-acquired FN, but have not been evaluated in the treatment of nosocomial FN. This study compared the incidence of mortality ...from 2002 to 2004 with 2008 to 2009 in patients with nosocomial FN treated with cefazolin plus tobramycin and compared characteristics of patients with nosocomially acquired FN to community acquired FN. A retrospective chart review of 45 nosocomial FN episodes from 2008 to 2009, and 54 episodes from 2002 to 2004 treated with cefazolin plus tobramycin was conducted. Data on the community acquired FN episodes was obtained from our previous research. Nosocomial FN mortality increased from 4% in 2002–2004 to 13% in 2008–2009 (
p
= 0.08). The nosocomial cohort was at higher risk of medical complications and mortality than the community-acquired cohort based on several variables (neutrophil nadir, duration of neutropenia and fever, hematological malignancy, MASCC and Talcott score;
p
< 0.05). As a result, the nosocomial cohort was treated with longer courses of antibiotic therapy (14 days vs 7 days;
p
< 0.0001) and were more likely to require broader spectrum antibiotics (64 out of 99 vs 34 out of 96;
p
< 0.0001). There was an observed increased risk of mortality from 2002 to 2004 compared with 2008 to 2009 in patients treated with cefazolin plus tobramycin for nosocomial FN, this was notable despite not attaining statistical significance. Therefore, this regimen is not appropriate for nosocomial FN.
Our objective was to rigorously evaluate the impact of an antimicrobial stewardship audit-and-feedback intervention, via a stepped-wedge randomized trial. An effective intensive care unit (ICU) ...audit-and-feedback program was rolled out to 6 non-ICU services in a randomized sequence. The primary outcome was targeted antimicrobial utilization, using a negative binomial regression model to assess the impact of the intervention while accounting for secular and seasonal trends. The intervention was successfully transitioned, with high volumes of orders reviewed, suggestions made, and recommendations accepted. Among patients meeting stewardship review criteria, the intervention was associated with a large reduction in targeted antimicrobial utilization (-21%, P = .004); however, there was no significant change in targeted antibiotic use among all admitted patients (-1.2%, P = .9), and no reductions in overall costs and microbiologic outcomes. An ICU day 3 audit-and-feedback program can be successfully expanded hospital-wide, but broader benefits on non-ICU wards may require interventions earlier in the course of treatment.
We sought to prevent the initiation of antimicrobial therapy for asymptomatic bacteriuria (ASB) by providing audit and feedback of newly reported positive urine cultures to test whether this could ...empower providers to leave ASB untreated. Despite success in providing feedback before antibiotics could be initiated in most cases, these recommendations only reduced treatment duration, without affecting antibiotic initiation. This study highlights the limitations of educational initiatives in overcoming engrained beliefs about bacteriuria even when advice is provided in real time.
This paper summarizes work carried out in a project supported by the European Communities' Bureau of Reference (BCR) to develop reference software for finding best-fit geometric elements, under ...specified criteria, to coordinate data. The geometric elements considered are the line, plane, circle, sphere, cylinder, and cone. The criteria for determining the elements are, generally, minimum zone (MZ) and, where appropriate, minimum circumscribed (MC) and maximum inscribed (Ml). The software developed implements methods founded on optimization theory. Two approaches are described. the first implements mathematical programming methods that exploit the particular structure of the problems considered and provide a unified approach to their solution; the second, applicable to the MZ and, where appropriate, MC problems for the line (in two-dimensions (2-D), plane, circle (in 2-D) and sphere, implements a combinatorial method that returns all global solutions.
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