The culture of follow-up blood cultures Wiggers, J.B.; Daneman, N.
Clinical microbiology and infection,
July 2020, 2020-Jul, 2020-07-00, 20200701, Letnik:
26, Številka:
7
Journal Article
Prediction of embolic events (EEs) in infective endocarditis (IE) could inform clinical decisions, such as surgical timing. We conducted a systematic review to more precisely define associations ...between risk factors and EEs.
We searched two bibliographic databases (1994–2018) for observational studies that reported EEs in IE patients and considered clinical, microbiological or echocardiographic risk factors. Studies that did not use Duke criteria or only investigated a subset of IE patients were excluded. Study quality was assessed using the Newcastle–Ottawa scale. A pooled risk ratio (RR) for each risk factor was estimated using random-effects models; statistical heterogeneity was estimated using I2.
Of 3862 unique citations, 47 cohort studies (11 215 IE cases) were included; 54 risk factors were analysed in at least two studies, with nine studies reporting other individual factors. Most studies were of high methodological quality. Major predictors of EEs were intravenous drug use (RR 1.69, 95% CI 1.32–2.17; I2 = 46%), Staphylococcus aureus infection (RR 1.64, 95% CI 1.45–1.86, I2 = 32%), mitral valve vegetation (RR 1.24, 95% CI 1.11–1.37, I2 = 30%), and vegetation size >10 mm (RR 1.87, 95% CI 1.57–2.21, I2 = 48%). EE risk was also higher with human immunodeficiency virus, chronic liver disease, elevated C-reactive protein, Staphylococcus spp. infection, vegetation presence, and multiple, mobile or prosthetic mechanical valve vegetation, and lower with Streptococcus spp. infection. Most findings were unchanged in sensitivity analyses that removed studies with pulmonary EEs from the outcome.
Given the serious consequences of embolism, surgical evaluation may be considered in patients with these risk factors.
Abstract
Introduction
This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the ...MERINO trial.
Methods
Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations.
Results
In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval CI 2.8–87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%–15%) and 8% (95% CI 2%–15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI −1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum β-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%–28%).
Conclusions
After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.
Piperacillin/tazobactam should be avoided for ceftriaxone nonsusceptible Escherichia coli and Klebsiella spp. bloodstream infections, especially when minimum inhibitory concentrations are > 16 mg/L. Further assessment of current testing is warranted given disparity between commonly used methods and broth microdilution.
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.
The rate of cardiac implantable electronic device (CIED) infection is increasing with time. We sought to determine the predictors, relative mortality, and cost burden of early-, mid- and late-onset ...CIED infections. We conducted a retrospective cohort study of all CIED implantations in Ontario, Canada between April 2013 and March 2016. The procedures and infections were identified in validated, population-wide health-care databases. Infection onset was categorized as early (0–30 days), mid (31–182 days) and late (183–365 days). Cox proportional hazards regression was used to assess the mortality impact of CIED infections, with infection modelled as a time-varying covariate. A generalized linear model with a log-link and γ distribution was used to compare health-care system costs by infection status. Among 17 584 patients undergoing CIED implantation, 215 (1.2%) developed an infection, including 88 early, 85 mid, and 42 late infections. The adjusted hazard ratio (aHR) of death was higher for patients with early (aHR 2.9, 95% CI 1.7–4.9), mid (aHR 3.3, 95% CI 1.9–5.7) and late (aHR 19.9, 95% CI 9.9–40.2) infections. Total mean 1-year health costs were highest for late-onset (mean Can$113 778), followed by mid-onset (mean Can$85 302), and then early-onset (Can$75 415) infections; costs for uninfected patients were Can$25 631. After accounting for patient and procedure characteristics, there was a significant increase in costs associated with early- (rate ratio (RR) 3.1, 95% CI 2.3–4.1), mid- (RR 2.8, 95% CI 2.4–3.3) and late- (RR 4.7, 95% CI 3.6–6.2) onset infections. In summary, CIED infections carry a tremendous clinical and economic burden, and this burden is disproportionately high for late-onset infections.
Background. Despite pneumococcal antibiotic resistance rates in excess of 25%, macrolides remain first-line agents for the treatment of community-acquired pneumonia. Methods. Prospective, ...population-based surveillance was conducted to identify cases of pneumococcal bacteremia in Toronto and Peel, Canada, between 2000 and 2004. "Macrolide failures" were defined as cases of bacteremia occurring during outpatient treatment with macrolide antibiotics or within 2 days after treatment. Macrolide susceptibility was determined according to Clinical Laboratory Standards Institute guidelines; common macrolide resistance mechanisms were determined by genotyping. Results. During the 5 years of surveillance, there were 1696 episodes of pneumococcal bacteremia (8.5 cases/100,000 population/year), of which 60 (3.5%) were failures of outpatient macrolide therapy. Resistant isolates were more common among cases of bacteremia after failure of macrolide therapy (37 64% of 58 cases) than among cases of bacteremia after failure of nonmacrolide antibiotics (16 22% of 74 cases; P < .001) or cases of bacteremia that occurred without prior antibiotic therapy (193 12% of 1569 cases; P < .001). Macrolide failures were significantly more common among cases of pneumococcal bacteremia with isolates exhibiting an erythromycin MIC of 1 µg/mL than among isolates exhibiting MICs ⩽0.25 µg/mL (3 38% of 8 cases vs. 21 1.5% of 1394 cases of bacteremia; P < .001). Increases in the MIC to 1 µg/mL were not associated with further increases in the likelihood of macrolide failure. Low-level resistance conferred by mefA and high-level resistance conferred by ermB were equally overrepresented among macrolide failures. Conclusions. Macrolide resistance contributes to an increased risk of macrolide failure, irrespective of the underlying resistance mechanism or of the degree of elevation in erythromycin MIC.
Our objective was to evaluate whether patients with bacteraemic urinary tract infection (UTI) who receive inadequate empirical therapy have worse outcomes than those with adequate therapy. This was a ...retrospective cohort study of patients with bacteraemic UTI. The exposure variable was adequate versus inadequate empirical antibiotic therapy (AEAT versus IEAT) within 24 h of culture collection. Primary endpoint was time to cure. The primary analysis used propensity score models with inverse probability of treatment weights. A secondary Cox proportional hazards modelling approach was used to test the robustness of this finding, and to evaluate other patient and pathogen predictors of time to cure. Of 469 patients with bacteraemic UTI, 368 (78.5%) received AEAT. There was no significant difference in mortality between those receiving AEAT and those receiving IEAT (adjusted OR 0.86, 95%CI 0.47–1.58). Receipt of AEAT had no association with time to cure (HR 0.93, 95%CI 0.73–1.19, p 0.55) or time to normalization of individual clinical variables. Cox proportional hazards modelling revealed that longer time to cure was associated with liver disease (HR 0.25, 95%CI 0.08–0.76, p 0.015), prior stroke (HR 0.73, 95%CI 0.54–0.99, p 0.044), empirical receipt of piperacillin–tazobactam (HR 0.77, 95%CI 0.59–0.99, p 0.044), qSOFA score >1 (HR 0.68, 95%CI 0.55–0.84, p < 0.001), and hospital-onset UTI (HR 0.53, 95%CI 0.39–0.71, p < 0.001). In conclusion, we found no association between AEAT and time to cure for patients with bacteraemic UTI. It may be appropriate to accept a higher risk threshold when choosing empirical antibiotic regimens, even in centres with high rates of resistant uropathogens.
Clostridioides difficile infection is the leading cause of healthcare-associated infectious diarrhoea. Several preventative and treatment interventions exist; however, decisions for their use are ...typically made independent of other interventions along the care pathway.
To assess how the scope of the decision problem is defined in economic evaluations of C. difficile interventions.
A scoping review was conducted following the Joanna Briggs Institute framework using a comprehensive literature search with C. difficile and economic evaluation as key search concepts. Study selection and extraction were performed independently by two reviewers. An in-depth analysis of all cost-utility and cost-effectiveness analyses was conducted. Care pathway domains (i.e. infection prevention and control, antimicrobial stewardship programmes, prevention, diagnostics, treatment) were defined iteratively, and each study was classified according to the scope of the decision problem: (i) one intervention, one domain; (ii) one intervention, multiple domains; (iii) multiple interventions, one domain; and (iv) multiple interventions, multiple domains.
In total, 3886 studies were identified. Of these, 116 studies were included in the descriptive overview, and 46 were included in the in-depth analysis. Most studies limited the scope of the decision problem to one intervention (43/46; 93%). Only three studies (3/46; 7%) assessed multiple interventions – either as bundled vs standalone interventions for prevention (i.e. a single domain), or as sequences of treatments for initial and recurrent infection (i.e. multiple domains). No study assessed multiple interventions across prevention and treatment domains.
Economic evaluations for C. difficile infection assess narrowly defined decision problems which may have implications for optimal healthcare resource allocation.
The United States Food & Drug Administration released an advisory in 2016 that fluoroquinolones be relegated to second-line agents for uncomplicated urinary tract infections (UTIs) given reports of ...rare but serious side effects; similar warnings have followed from Health Canada and the European Medicines Agency. The objective was to determine whether alternative non-fluoroquinolone agents are as effective as fluoroquinolones in the treatment of UTIs.
We conducted a retrospective population-based cohort study using administrative health data from six Canadian provinces. We identified women (n = 1 585 997) receiving antibiotic treatment for episodes of uncomplicated UTIs (n = 2 857 243) between January 1 2005 and December 31 2015. Clinical outcomes within 30 days from the initial antibiotic dispensation were compared among patients treated with a fluoroquinolone versus non-fluoroquinolone agents. High-dimensional propensity score adjustments were used to ensure comparable treatment groups and to minimize residual confounding.
Fluoroquinolone use for UTI declined over the study period in five of six Canadian provinces and accounted for 22.3–48.5% of treatments overall. The pooled effect across the provinces indicated that fluoroquinolones were associated with fewer return outpatient visits (OR 0.89, 95%CI 0.87–0.92), emergency department visits (OR 0.74, 95%CI 0.61–0.89), hospitalizations (OR 0.83, 95%CI 0.77–0.88), and repeat antibiotic dispensations (OR 0.77, 95%CI 0.75–0.80) within 30 days.
Fluoroquinolones are associated with improved clinical outcomes among women with uncomplicated UTIs. This benefit must be weighed against the risk of fluoroquinolone resistance and rare but serious fluoroquinolone side effects when selecting first-line treatment for these patients.
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.
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