Effectiveness of an Electronic Automated Antibiotic Time Out Alert in the Setting of Gram-Negative Bacteremia.
Ontology highlight
ABSTRACT:
SUBMITTER: Mohayya SM
PROVIDER: S-EPMC8466937 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Although timely treatment of sepsis improves outcomes, delays in administering evidence-based therapies are common.To determine whether automated real-time electronic sepsis alerts can: (1) accurately identify sepsis and (2) improve process measures and outcomes.We systematically searched MEDLINE, Embase, The Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature from database inception through June 27, 2014.Included studies that empirically evaluated 1 or both of the prespecified objectives.Two independent reviewers extracted data and assessed the risk of bias. Diagnostic accuracy of sepsis identification was measured by sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio (LR). Effectiveness was assessed by changes in sepsis care process measures and outcomes.Of 1293 citations, 8 studies met inclusion criteria, 5 for the identification of sepsis (n?=?35,423) and 5 for the effectiveness of sepsis alerts (n?=?6894). Though definition of sepsis alert thresholds varied, most included systemic inflammatory response syndrome criteria?±?evidence of shock. Diagnostic accuracy varied greatly, with PPV ranging from 20.5% to 53.8%, NPV 76.5% to 99.7%, LR+ 1.2 to 145.8, and LR- 0.06 to 0.86. There was modest evidence for improvement in process measures (ie, antibiotic escalation), but only among patients in non-critical care settings; there were no corresponding improvements in mortality or length of stay. Minimal data were reported on potential harms due to false positive alerts.Automated sepsis alerts derived from electronic health data may improve care processes but tend to have poor PPV and do not improve mortality or length of stay.
| S-EPMC4477829 | biostudies-literature
Project description:Bacteremic trauma victims have a higher risk of death than their nonbacteremic counterparts. The role that altered immunity plays in the development of bacteremia is unknown. Using an existing dataset, we sought to determine if differences in early postinjury immune-related gene expression are associated with subsequent Gram-negative bacteremia.Retrospective cohort study, a secondary analysis of the Glue Grant database.Seven level I trauma centers across the United State.Severely injured blunt trauma patients.None.Total leukocyte gene expression was compared between the subjects in whom Gram-negative bacteremia developed and those in whom it did not develop. We observed that Gram-negative bacteremia was an independent risk factor for death (odds ratio, 1.86; p = 0.015). We then compared gene expression at 12 and 96 hours after injury in 10 subjects in whom subsequently Gram-negative bacteremia developed matched to 26 subjects in whom it did not develop. At 12 hours, expression of 64 probes differed more than or equal to 1.5-fold; none represented genes related to innate or adaptive immunity. By 96 hours, 102 probes were differentially expressed with 20 representing 15 innate or adaptive immunity genes, including down-regulation of IL1B and up-regulation of IL1R2, reflecting suppression of innate immunity in Gram-negative bacteremia subjects. We also observed down-regulation of adaptive immune genes in the Gram-negative bacteremia subjects.By 96 hours after injury, there are differences in leukocyte gene expression associated with the development of Gram-negative bacteremia, reflecting suppression of both innate and adaptive immunity. Gram-negative bacteremia after trauma is, in part, consequence of host immunity failure and may not be completely preventable by standard infection-control techniques.
| S-EPMC4515113 | biostudies-literature
Project description:BackgroundClinical decision support systems, including electronic alerts, ideally provide immediate and relevant patient-specific information to improve clinical decision-making. Despite the growing capabilities of such alerts in conjunction with an expanding electronic medical record, there is a paucity of information regarding their perceived usefulness. We surveyed healthcare providers' opinions concerning the practicality and efficacy of a specific text-based automated electronic alert for acute kidney injury (AKI) in a single hospital during a randomized trial of AKI alerts.MethodsProviders who had received at least one electronic AKI alert in the previous 6 months, as part of a separate randomized controlled trial (clinicaltrials.gov #01862419), were asked to complete a survey concerning their opinions about this specific AKI alert system. Individual approval of the alert system was defined by a provider's desire to continue receiving the alert after termination of the trial.ResultsA total of 98 individuals completed the survey, including 62 physicians, 27 pharmacists and 7 non-physician providers. Sixty-nine percent of responders approved the alert, with no significant difference among the various professions (P = 0.28). Alert approval was strongly correlated with the belief that the alerts improved patient care (P < 0.0001), and negatively correlated with the belief that alerts did not provide novel information (P = 0.0001). With each additional 30 days of trial duration, odds of approval decreased by 20% (3-35%) (P = 0.02).ConclusionsThe alert system was generally well received, although approval waned with time. Approval was correlated with the belief that this type of alert improved patient care. These findings suggest that perceived efficacy is critical to the success of future alert trials.
| S-EPMC4957729 | biostudies-literature
Project description:What is known and objectiveGram-negative bacteremia remains a major health problem around the world. The optimal duration of antibiotic treatment has been poorly defined, and there are significant differences of opinion between clinicians. We conducted this systematic review and meta-analysis to compare the clinical outcomes of short-course and long-course treatments in patients with uncomplicated gram-negative bacteremia.MethodsWe searched public databases (PubMed, EMBASE and Cochrane Library) to identify eligible studies. The primary outcomes were all-cause mortality and the incidence of recurrent bacteremia through day 30. We used the Cochrane risk of bias assessment tool to evaluate the risk of bias for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale for non-RCTs.Results and discussionSix studies involving 2689 patients were included in the systematic review and meta-analysis. No significant difference was found between short-course and long-course antibiotic treatments in 30-day mortality (risk ratio [RR] 0.85; 95% confidence interval [CI] 0.65-1.13; P = .26), 30-day recurrent bacteremia (RR 1.07; 95% CI 0.68-1.67; P = .78), 90-day mortality (RR 0.84; 95% CI 0.57-1.24; P = .38), 90-day recurrent bacteremia (RR 0.98; 95% CI 0.50-1.89; P = .94), adverse events (RR 1.14; 95% CI 0.89-1.45; P = .30), Clostridium difficile infection (RR 0.86; 95% CI 0.40-1.86; P = .71) or resistance development (RR 1.19; 95% CI 0.66-2.14; P = .57).What is new and conclusionShort-course was non-inferior to long-course antibiotic treatments for patients with uncomplicated gram-negative bacteremia. Considering the drug-related side effects and cost-effectiveness, a shorter duration of antibiotic treatment may be preferable for this particular population. However, additional high-quality RCTs are needed to further assess whether a shorter course of antibiotic treatment is of greater benefit for patients with uncomplicated gram-negative bacteremia.
| S-EPMC7820952 | biostudies-literature
Project description:Antibody autoreactivity against bactericidal/permeability-increasing protein (BPI) is strongly associated with Pseudomonas aeruginosa infection in cystic fibrosis (CF), non-CF bronchiectasis (BE), and chronic obstructive pulmonary disease (COPD). We examined the pathogen-specific nature of this autoreactivity by examining antibodies to BPI in bacteremia patients. Antibodies to BPI and bacterial antigens were measured in sera by ELISA from five patient cohorts (n = 214). Antibody avidity was investigated. Bacteremic patient sera (n = 32) exhibited IgG antibody autoreactivity against BPI in 64.7% and 46.7% of patients with positive blood cultures for P. aeruginosa and Escherichia coli, respectively. Autoantibody titers correlated with IgG responses to bacterial extracts and lipopolysaccharide (LPS). A prospective cohort of bacteremic patient sera exhibited anti-BPI IgG responses in 23/154 (14.9%) patients with autoreactivity present at the time of positive blood cultures in patients with Gram-negative and Gram-positive bacteria, including 8/60 (13.3%) patients with Staphylococcus aureus Chronic tissue infection with S. aureus was associated with BPI antibody autoreactivity in 2/15 patients (13.3%). Previously, we demonstrated that BPI autoreactivity in CF patient sera exhibits high avidity. Here, a similar pattern was seen in BE patient sera. In contrast, sera from patients with bacteremia exhibited low avidity. These data indicate that low-avidity IgG responses to BPI can arise acutely in response to bacteremia and that this association is not limited to P. aeruginosa This is to be contrasted with chronic respiratory infection with P. aeruginosa, suggesting that either the chronicity or the site of infection selects for the generation of high-avidity responses, with biologic consequences for airway immunity.
| S-EPMC7504969 | biostudies-literature
Project description:A declining pipeline of clinically useful antibiotics has made it imperative to develop more effective antimicrobial therapies, particularly against difficult-to-treat Gram-negative pathogens. Silver has been used as an antimicrobial since antiquity, yet its mechanism of action remains unclear. We show that silver disrupts multiple bacterial cellular processes, including disulfide bond formation, metabolism, and iron homeostasis. These changes lead to increased production of reactive oxygen species and increased membrane permeability of Gram-negative bacteria that can potentiate the activity of a broad range of antibiotics against Gram-negative bacteria in different metabolic states, as well as restore antibiotic susceptibility to a resistant bacterial strain. We show both in vitro and in a mouse model of urinary tract infection that the ability of silver to induce oxidative stress can be harnessed to potentiate antibiotic activity. Additionally, we demonstrate in vitro and in two different mouse models of peritonitis that silver sensitizes Gram-negative bacteria to the Gram-positive-specific antibiotic vancomycin, thereby expanding the antibacterial spectrum of this drug. Finally, we used silver and antibiotic combinations in vitro to eradicate bacterial persister cells, and show both in vitro and in a mouse biofilm infection model that silver can enhance antibacterial action against bacteria that produce biofilms. This work shows that silver can be used to enhance the action of existing antibiotics against Gram-negative bacteria, thus strengthening the antibiotic arsenal for fighting bacterial infections.
| S-EPMC3771099 | biostudies-literature
Project description:Diminished antibiotic susceptibility of bacterial pathogens is an increasingly serious threat to human and animal health. Alternative strategies are required to combat antibiotic refractory bacteria. Bacterial metabolic state has been shown to play a critical role in its susceptibility to antibiotic killing. However, the adjuvant potential of nucleotides in combination with antibiotics to kill Gram-negative pathogens remains unknown. Herein, we found that thymine potentiated ciprofloxacin killing against both sensitive and resistant-E. coli in a growth phase-independent manner. Similar promotion effects were also observed for other bactericidal antibiotics, including ampicillin and kanamycin, in the fight against four kinds of Gram-negative bacteria. The mechanisms underlying this finding were that exogenous thymine could upregulate bacterial metabolism including increased TCA cycle and respiration, which thereby promote the production of ATP and ROS. Subsequently, metabolically inactive bacteria were converted to active bacteria and restored its susceptibility to antibiotic killing. In Galleria mellonella infection model, thymine effectively improved ciprofloxacin activity against E. coli. Taken together, our results demonstrated that thymine potentiates bactericidal antibiotics activity against Gram-negative pathogens through activating bacterial metabolism, providing a universal strategy to overcome Gram-negative pathogens.
| S-EPMC7875874 | biostudies-literature
Project description:The current need for novel antibiotics is especially acute for drug-resistant Gram-negative pathogens1,2. These microorganisms have a highly restrictive permeability barrier, which limits the penetration of most compounds3,4. As a result, the last class of antibiotics that acted against Gram-negative bacteria was developed in the 1960s2. We reason that useful compounds can be found in bacteria that share similar requirements for antibiotics with humans, and focus on Photorhabdus symbionts of entomopathogenic nematode microbiomes. Here we report a new antibiotic that we name darobactin, which was obtained using a screen of Photorhabdus isolates. Darobactin is coded by a silent operon with little production under laboratory conditions, and is ribosomally synthesized. Darobactin has an unusual structure with two fused rings that form post-translationally. The compound is active against important Gram-negative pathogens both in vitro and in animal models of infection. Mutants that are resistant to darobactin map to BamA, an essential chaperone and translocator that folds outer membrane proteins. Our study suggests that bacterial symbionts of animals contain antibiotics that are particularly suitable for development into therapeutics.
| S-EPMC7188312 | biostudies-literature
Project description:Beta-lactam antibiotics form the backbone of treatment for Gram-negative pneumonia in mechanically ventilated patients in the intensive care unit. However, this beta-lactam antibiotic backbone is increasingly under pressure from emerging resistance across all geographical regions, and health-care professionals in many countries are rapidly running out of effective treatment options. Even in regions that currently have only low levels of resistance, the effects of globalization are likely to increase local pressures on the beta-lactam antibiotic backbone in the near future. Therefore, clinicians are increasingly faced with a difficult balancing act: the need to prescribe adequate and appropriate antibiotic therapy while reducing the emergence of resistance and the overuse of antibiotics. In this review, we explore the burden of Gram-negative pneumonia in the critical care setting and the pressure that antibiotic resistance places on current empiric therapy regimens (and the beta-lactam antibiotic backbone) in this patient population. New treatment approaches, such as systemic and inhaled antibiotic alternatives, are on the horizon and are likely to help tackle the rising levels of beta-lactam antibiotic resistance. In the meantime, it is imperative that the beta-lactam antibiotic backbone of currently available antibiotics be supported through stringent antibiotic stewardship programs.
| S-EPMC4731981 | biostudies-literature
Project description:Rapid identification of microorganisms and antimicrobial resistance is paramount for targeted treatment in serious bloodstream infections (BSI). The Verigene Gram-negative blood culture nucleic acid test (BC-GN) is a multiplex, automated molecular diagnostic test for identification of eight Gram-negative (GN) organisms and resistance markers from blood culture with a turnaround time of approximately 2 h. Clinical isolates from adult patients at the University Maryland Medical Center with GN bacteremia from 1 January 2012 to 30 June 2012 were included in this study. Blood culture bottles were spiked with clinical isolates, allowed to incubate, and processed by BC-GN. A diagnostic evaluation was performed. In addition, a theoretical evaluation of time to effective and optimal antibiotic was performed, comparing actual antibiotic administration times from chart review ("control") to theoretical administration times based on BC-GN reporting and antimicrobial stewardship team (AST) review ("intervention"). For organisms detected by the assay, BC-GN correctly identified 95.6% (131/137), with a sensitivity of 97.1% (95% confidence interval [CI], 90.7 to 98.4%) and a specificity of 99.5% (95% CI, 98.8 to 99.8%). CTX-M and OXA resistance determinants were both detected. Allowing 12 h from Gram stain for antibiotic implementation, the intervention group had a significantly shorter duration to both effective (3.3 versus 7.0 h; P < 0.01) and optimal (23.5 versus 41.8 h; P < 0.01) antibiotic therapy. BC-GN with AST intervention can potentially decrease time to both effective and optimal antibiotic therapy in GN BSI.
| S-EPMC4325795 | biostudies-literature