Improving Decision Making in Empiric Antibiotic Selection (IDEAS) for Gram-negative Bacteremia: A Prospective Clinical Implementation Study

Author(s):  
Marion Elligsen ◽  
Ruxandra Pinto ◽  
Jerome A Leis ◽  
Sandra A N Walker ◽  
Nick Daneman ◽  
...  

Abstract Background Timely selection of adequate empiric antibiotics has become increasingly difficult due to rising resistance rates and the competing desire to apply antimicrobial stewardship (AMS) principles. Individualized clinical prediction models offer the promise of reducing broad-spectrum antibiotic use and preserving/improving adequacy of treatment, but few have been validated in the clinical setting. Methods Multivariable models were used to predict the probability of susceptibility for gram-negative (GN) bacteria in bloodstream infections (bacteremia) to ceftriaxone, ciprofloxacin, ceftazidime, piperacillin-tazobactam, and meropenem. The models were combined with existing resistance-prediction methods to generate optimized and individualized suggestions for empiric therapy that were provided to prescribers by an AMS pharmacist. De-escalation of empiric antibiotics and adequacy of therapy were analyzed using a quasi-experimental design comparing two 9-month periods (pre- and postintervention) at a large academic tertiary care institution. Results Episodes of bacteremia (n = 182) were identified in the preintervention and postintervention (n = 201) periods. Patients who received the intervention were more likely to have their therapy de-escalated (29 vs 21%; aOR = 1.77; 95% CI, 1.09–2.87; P = .02). The intervention also increased the proportion of patients who were on the narrowest adequate therapy at the time of culture finalization (44% in the control and 55% in the intervention group; aOR = 2.04; 95% CI, 1.27–3.27; P = .003). Time to adequate therapy was similar in the intervention and control groups (5 vs 4 hours; P = .95). Conclusions An AMS intervention, based on individualized predictive models for resistance, can influence empiric antibiotic selections for GN bacteremia to facilitate early de-escalation of therapy without compromising adequacy of antibiotic coverage.

Author(s):  
Marion Elligsen ◽  
Ruxandra Pinto ◽  
Jerome A Leis ◽  
Sandra A N Walker ◽  
Derek R MacFadden ◽  
...  

Abstract Background A patient’s prior cultures can inform the subsequent risk of infection from resistant organisms, yet prescribers often fail to incorporate these results into their empiric antibiotic selection. Given that timely initiation of adequate antibiotics has been associated with improved outcomes, there is an urgent need to address this gap. Methods In order to better incorporate prior culture results in the selection of empiric antibiotics, we performed a pragmatic, prospective, hospital-wide intervention: (1) empiric antibiotic prescriptions were assessed for clinically significant discordance with the most recent methicillin-resistant Staphylococcus aureus (MRSA) surveillance swab, previous cultures for extended-spectrum beta-lactamases (ESBLs), and the most recent culture for a Gram-negative (GN) organism; and (2) if discordant, an antimicrobial stewardship pharmacist provided recommendations for alternative therapy. The impact was analyzed using a quasi-experimental design comparing two 9-month periods (pre- and postintervention) at a large academic, tertiary care institution. Results Clinically significant discordance was identified 99 times in the preintervention period and 86 times in the intervention period. The proportion of patients that received concordant therapy increased from 73% (72/99) in the control group to 88% (76/86) in the intervention group (P = .01). The median time to concordant therapy was shorter in the intervention group than the control group (25 vs 55 hrs, respectively; P < .001; adjusted hazard ratio = 1.95 [95% confidence interval {CI}, 1.37–2.77; P < .001]). The median duration of unnecessary vancomycin therapy was reduced by 1.1 days (95% CI, .5–1.6 days; P < .001). Conclusions This intervention improved prescribing, with a shorter time to concordant therapy and an increased proportion of patients receiving empiric therapy concordant with prior culture results. The use of unnecessary vancomycin was also reduced.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S726-S726
Author(s):  
Heather L Cox ◽  
April E Attai ◽  
Allison M Stilwell ◽  
Kasi B Vegesana ◽  
Frankie Brewster ◽  
...  

Abstract Background Rapid diagnostic testing paired with ASP intervention optimizes therapy and improves outcomes but few data guide ASP response in the absence of organism identification (ID). We describe the microbiology for organisms unidentified by Accelerate Pheno™ Gram-negative platform (AXDX) in order to inform ASP-provider team communication (PTC). Methods Consecutive, non-duplicate inpatient blood cultures with Gram-negative bacilli (GNB) following AXDX implementation at a single university hospital between April 2018 and March 2019 were included. Standard of care (SOC) ID and susceptibility followed AXDX. Clinical Microbiology emailed AXDX results to the ASP in real time; results were released into the EMR paired with telephone PTC or withheld after ASP review. Bloodstream Infections (BSIs) and patient outcomes for organisms labeled no/indeterminate ID by the AXDX were characterized. Results AXDX was performed on 351 blood cultures. Among 52 (15%) labeled no/indeterminate ID, SOC methods revealed: Enterobacteriaceae (40%; 9 monomicrobial with AXDX targets), anaerobes (21%), non-lactose fermenters (NLFs) other than Pseudomonas aeruginosa (21%), and fastidious GNB (10%). Frequent organisms without AXDX targets included: Raoultella planticola (4); Bacteroides fragilis, Cupriavidus spp., Haemophilus spp., Prevotella spp., Providencia spp., non-aeruginosa Pseudomonas spp., Salmonella spp. (3 each); Pasteurella multocida, Stenotrophomonas maltophilia (2 each). BSI sources were most commonly intra-abdominal (21%), central line-associated (17%), or unknown (17%). CLABSIs were associated with immune suppression and/or substance abuse in all but 1 case. BSIs without active empiric therapy included: NDM-producing Providencia stuartii SSSI; OXA-48-producing R. planticola intraabdominal infection (IAI); Pandoraea spp. CLABSI after liver transplant; enteric fever; B. fragilis, Leptotrichia wadei, and S. maltophilia, each of unknown source. In-hospital mortality occurred in 4 of these cases. Conclusion When AXDX yields no/indeterminate ID, ASP chart review for possible anaerobic/IAI, unique environmental exposures, and travel history may assist in guiding empiric therapy. GNB with AXDX targets are not excluded. Disclosures All authors: No reported disclosures.


2018 ◽  
Vol 99 (2) ◽  
pp. 145-147 ◽  
Author(s):  
Y. Chao ◽  
C. Reuter ◽  
L.K. Kociolek ◽  
R. Patel ◽  
X. Zheng ◽  
...  

2020 ◽  
Author(s):  
Zhixin Liang ◽  
Qiang Zhu ◽  
Minghui Zhu ◽  
Chunyan Li ◽  
Lina Li ◽  
...  

Abstract Background Gram-negative bacterial bloodstream infections (BSIs) are serious diseases associated with high morbidity and mortality. The following study examines the incidence, clinical characteristics and microbiological features, drug resistance situations and mortality associated with gram-negative BSIs at a large Chinese tertiary-care hospital in Beijing, China. Methods A retrospective cohort study of patients with gram-negative BSIs was performed between January 1, 2010, and December 31, 2018, at the Chinese People's Liberation Army General Hospital. The patients’ data were collected and included in the reviewing electronic medical records. Results A total of 6867 episodes of gram-negative BSIs occurred among 3199 patients over 9 years, and there were 3032 significant BSI episodes 77% of these cases were healthcare-associated, while 23% were community-associated. The overall incidence of gram-negative BSIs fluctuated from 2.30 to 2.55 episodes per 1000 admissions over 9 years. Malignancy was the most common comorbidity and indwelling central intravenous catheter was the most common predisposing factor for gram-negative BSI. Escherichia coli were the major pathogen (34.3%), followed by Klebsiella pneumoniae (23.3%) and other bacterial pathogens (9.9%). The resistance rates of Escherichia coli and Klebsiella pneumoniae to penicillins were more than 90%. and the resistance rates of Acinetobacter baumannii to the most antibiotic were more than 70% include the Carbapenem. The resistance of ESBLs-producing Escherichia coli to the most antibiotic was higher than non-ESBLs producing Escherichia coli but to Carbapenems(0.7% VS 5.1%). The rates of Carbapenems resistance of ESBLs-producing Klebsiella pneumoniae and non-ESBLs producing Klebsiella pneumoniae were 32.8% and 8.1%. The rates of Carbapenems resistance of Enterobacter cloacae and Pseudomonas aeruginosa were 1.4% and 27.8% respectively. Between 2010 and 2018, the overall mortality of gram-negative BSIs decreased from 11.41–9.05%(X2 = 6.95, P = 0.434). Moreover, the mortality in the ICU decreased from 27.03–14.93%(X2 = 9.61, P = 0.212), while in the general ward fluctuated from 8.85–8.13% that without obvious decrease change(X2 = 9.29, P = 0.232). Conclusions The mortality of gram-negative BSIs have showed downward trends. carbapenem antibiotics is still consider the best treatment for patients with Gram-negative BSIs except Acinetobacter baumannii.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S116-S117
Author(s):  
Connor Deri ◽  
Whitney Nesbitt ◽  
George Nelson ◽  
Jessica Keefe

Abstract Background Bloodstream infections are a leading cause of mortality amongst hospitalized patients. Optimizing time to pathogen identification and receipt of appropriate antibiotic therapy significantly decreases mortality, morbidity, and length of hospitalization. Rapid diagnostic tests, such as Verigene, assist in the early identification of bacteria and resistance determinants from positive blood cultures; however, Verigene assays are limited to the detection of 13 gram-positive and 9 gram-negative bacteria. Methods The purpose of this study was to describe gram-negative and gram-positive aerobic bacteria identified from positive blood cultures with no Verigene target detected and to use the susceptibilities to create an antibiogram to assist in empiric antibiotic selection. A total of 2325 positive blood cultures resulted between January 2017 and October 2018 underwent Verigene testing. Results Of the 2325 isolates, 383 (16.5%), had no Verigene organism or resistance mechanism detected. Of these, there were 239 (62.4%) gram-positive isolates, 141 (36.8%) gram-negative isolates, and 3 yeast isolates with 96 unique organisms. Seventy-six (19.8%) of the organisms identified by standard culture, but not Verigene testing, are included on Verigene panel. We analyzed nine common antibiotics active against gram-negative organisms to determine percent susceptibilities against the isolated aerobic pathogens: amikacin (92.1%), cefepime (93.5%), ceftazidime (94.0%), ceftriaxone (79.7%), ciprofloxacin (88.5%), gentamicin (91.9%), levofloxacin (86.9%), piperacillin–tazobactam (83.8%), and tobramycin (85.5%). Additionally, four antibiotics active against gram-positive organisms were analyzed for gram-positive susceptibilities: cefotaxime (91.8%), ceftriaxone (98.1%), levofloxacin (82.5%), and vancomycin (91.8%). Conclusion The results of this study provide clinicians with antibiotic susceptibilities against organisms that were not identified through Verigene to better guide timely and appropriate antibiotic therapy against gram-negative and gram-positive aerobic bacteria. Disclosures All authors: No reported disclosures.


2011 ◽  
Vol 45 (11) ◽  
pp. 1338-1345 ◽  
Author(s):  
Brett H Heintz ◽  
George R Thompson ◽  
William E Dager

Background:: A resurgence of aminoglycoside use has followed the recent increase of multidrug-resistant gram-negative pathogens and is often needed even in the treatment of dialysis-dependent patients; however, studies evaluating the treatment of gram-negative infections with aminoglycosides, including the optimal dose, in the setting of dialysis are limited. Objective: To evaluate the current patterns of aminoglycoside use, including microbiologic and clinical indications, and identify risk factors associated with mortality in dialysis-dependent patients receiving aminoglycosides. Methods: Utilization, clinical, and microbiologic data were collected retrospectively over a 2-year period (July 2008-June 2010) for adults with a diagnosis of renal failure requiring dialysis and aminoglycoside therapy. Binary logistic and multivariate regression analyses were performed to identify risk factors for alt-cause 30-day mortality. Results: Ninety-five consecutive aminoglycoside courses in 88 patients met inclusion criteria for evaluation. A wide variety of clinical and microbiologic indications were documented. The average duration of aminoglycoside therapy was 5.2 days (range 1-42), the average duration of antimicrobial therapy was 13.5 days (1-60), and the all-cause 30-day mortality rate was 36.5%. Factors associated with all-cause 30-day mortality were gram-negative rod (GNR) bacteremia (OR 28.6; p = 0.035), advanced age (OR 8.5; p = 0.030), recent admission (OR 33.4; p = 0.038). and inadequate empiric therapy (OR 14.9; p = 0.024). Intravenous catheter removal was protective of all-cause 30-day mortality (OR 0.01; p = 0.005). A first pre-dialysis plasma concentration relative to the minimum inhibitory concentration (Cp:MIC) <6 mg/L (gentamicin/tobramycin) was associated with an increased risk of mortality (p = 0.026) upon subgroup analysis of dialysis-dependent patients with GNR bloodstream infections. Conclusions: Outcomes among dialysis-dependent patients who received aminoglycosides were below expectations. Various risk factors for mortality were identified, including retention of the catheter, inadequate empiric therapy, and a Cp:MIC <6 mg/L. Improved approaches to dosing of aminoglycosides in dialysis-dependent patients, including more aggressive dosing practices, should be urgently explored in attempts to maximize favorable patient outcomes.


2019 ◽  
Vol 9 (2) ◽  
pp. 142-149 ◽  
Author(s):  
Anna C Sick-Samuels ◽  
Katherine E Goodman ◽  
Glenn Rapsinski ◽  
Elizabeth Colantouni ◽  
Aaron M Milstone ◽  
...  

Abstract Background As rates of multidrug-resistant gram-negative infections rise, it is critical to recognize children at high risk of bloodstream infections with organisms resistant to commonly used empiric broad-spectrum antibiotics. The objective of the current study was to develop a user-friendly clinical decision aid to predict the risk of resistance to commonly prescribed broad-spectrum empiric antibiotics for children with gram-negative bloodstream infections. Methods This was a longitudinal retrospective cohort study of children with gram-negative bacteria cared for at a tertiary care pediatric hospital from June 2009 to June 2015. The primary outcome was a bloodstream infection due to bacteria resistant to broad-spectrum antibiotics (ie, cefepime, piperacillin-tazobactam, meropenem, or imipenem-cilastatin). Recursive partitioning was used to develop the decision tree. Results Of 689 episodes of gram-negative bloodstream infections included, 31% were resistant to broad-spectrum antibiotics. The decision tree stratified patients into high- or low-risk groups based on prior carbapenem treatment, a previous culture with a broad-spectrum antibiotic resistant gram-negative organism in the preceding 6 months, intestinal transplantation, age ≥3 years, and ≥7 prior episodes of gram-negative bloodstream infections. The sensitivity for classifying high-risk patients was 46%, and the specificity was 91%. Conclusion A decision tree offers a novel approach to individualize patients’ risk of gram-negative bloodstream infections resistant to broad-spectrum antibiotics, distinguishing children who may warrant even broader antibiotic therapy (eg, combination therapy, newer β-lactam agents) from those for whom standard empiric antibiotic therapy is appropriate. The constructed tree needs to be validated more widely before incorporation into clinical practice.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S351-S352
Author(s):  
Thomas P Lodise Jr. ◽  
Nicole G Bonine ◽  
J Michael Ye ◽  
Henry J Folse ◽  
Patrick Gillard

Abstract Background Identification of infections caused by antimicrobial-resistant microorganisms is critical to administration of early appropriate antibiotic therapy. We developed a clinical bedside tool to estimate the probability of carbapenem-resistant Enterobacteriaceae (CRE), extended spectrum β-lactamase-producing Enterobacteriaceae (ESBL), and multidrug-resistant Pseudomonas aeruginosa (MDRP) among hospitalized adult patients with Gram-negative infections. Methods A retrospective observational study of the Premier Hospital Database (PHD) was conducted. The study included adult hospitalized patients with complicated urinary tract infection (cUTI), complicated intraabdominal infection (cIAI), bloodstream infections (BSI), or hospital-acquired/ventilator-associated pneumonia (HAP/VAP) with a culture-confirmed Gram-negative infection in PHD from 2011 to 2015. Model development steps are shown in Figure 1. The study population was split into training and test cohorts. Prediction models were developed using logistic regression in the training cohort (Figure 1). For each resistant phenotype (CRE, ESBL, and MDRP), a separate model was developed for community-acquired (index culture ≤3 days of admission) and hospital-acquired (index culture &gt;3 days of admission) infections (six models in total). The predictive performance of the models was assessed in the training and test cohorts. Models were converted to a singular user-friendly interface for use at the bedside. Results The most important predictors of antibiotic-resistant Gram-negative bacterial infection were prior number of antibiotics, infection site, prior infection in the last 3 months, hospital prevalence of each resistant pathogen (CRE, ESBL, and MDRP), and age (Figure 2). The predictive performance was highly acceptable for all six models (Figure 3). Conclusion We developed a clinical prediction tool to estimate the probability of CRE, ESBL, and MDRP among hospitalized adult patients with community- and hospital-acquired Gram-negative infections. Our predictive model has been implemented as a user-friendly bedside tool for use by clinicians to predict the probability of resistant infections in individual patients, to guide early appropriate therapy. Disclosures T. P. Lodise Jr., Motif BioSciences: Board Member, Consulting fee. N. G. Bonine, Allergan: Employee, Salary. J. M. Ye, Allergan: Employee, Salary. H. J. Folse, Evidera: Employee, Salary. P. Gillard, Allergan: Employee, Salary.


2012 ◽  
Vol 137 (9) ◽  
pp. 1247-1254 ◽  
Author(s):  
Katherine K. Perez ◽  
Randall J. Olsen ◽  
William L. Musick ◽  
Patricia L. Cernoch ◽  
James R. Davis ◽  
...  

Context.—Early diagnosis of gram-negative bloodstream infections, prompt identification of the infecting organism, and appropriate antibiotic therapy improve patient care outcomes and decrease health care expenditures. In an era of increasing antimicrobial resistance, methods to acquire and rapidly translate critical results into timely therapies for gram-negative bloodstream infections are needed. Objective.—To determine whether mass spectrometry technology coupled with antimicrobial stewardship provides a substantially improved alternative to conventional laboratory methods. Design.—An evidence-based intervention that integrated matrix-assisted laser desorption and ionization time-of-flight mass spectrometry, rapid antimicrobial susceptibility testing, and near–real-time antimicrobial stewardship practices was implemented. Outcomes in patients hospitalized prior to initiation of the study intervention were compared to those in patients treated after implementation. Differences in length of hospitalization and hospital costs were assessed in survivors. Results.—The mean hospital length of stay in the preintervention group survivors (n = 100) was 11.9 versus 9.3 days in the intervention group (n = 101; P = .01). After multivariate analysis, factors independently associated with decreased length of hospitalization included the intervention (hazard ratio, 1.38; 95% confidence interval, 1.01–1.88) and active therapy at 48 hours (hazard ratio, 2.9; confidence interval, 1.15–7.33). Mean hospital costs per patient were $45 709 in the preintervention group and $26 162 in the intervention group (P = .009). Conclusions.—Integration of rapid identification and susceptibility techniques with antimicrobial stewardship significantly improved time to optimal therapy, and it decreased hospital length of stay and total costs. This innovative strategy has ramifications for other areas of patient care.


Author(s):  
Pankaj Katoch ◽  
Anil Kanga

Background: Vascular endothelial dysfunction plays a critical role in the evolution of sepsis there is an increase in vascular permeability leading to coagulation abnormalities and subsequent dysfunction of major organs.1 Bloodstream infections are a cause of life-threatening complications in all age groups of the population especially the extreme age groups who are very much prone to the risk. Antibiotic usage is associated with bacteremia, septicemia, and mortality through many factors. We are aware that Gram-negative bacteria due to many causes are becoming increasingly resistant to the currently used antimicrobial therapy. Here, in this study, we report the incidence and etiology and of the Gram-Negative bacterial isolates and their clinical significance from our tertiary care institute located in the Northern part of India. Materials and Methods: Prospective Observational Study conducted in the Department of Microbiology IGMC Shimla for a tenure of one year to determine the incidence and etiology of Gram-negative bacterial isolates and their antimicrobial resistance profile. All the blood culture samples received in the Department of Microbiology IGMC Shimla for culture by Bactec Bd fx from July 2015 to June 2016 were included in the study except for falling in the exclusion criteria. The blood culture was observed in the Bactec bd fx system for at least 5 days before they are reported as sterile. Results: Among the total 1275 cultures which were positive for bacteria, 931(73.02%) were positive for Gram-negative bacteria. Among the total of 931culture that were positive for Gram-negative bacteria, The Non-fermenter group of organisms was isolated in 292(31.36%) cultures, followed by E. coli 266(28.57%). Among the total of 931 cultures positive for GNB, a maximum of 335 (35.98%) belonged to 0-1 year. Among them, 574 (61.65%) were males while 357 (38.35%) were females. Conclusion: Nonfermenter group was the commonest organism among Gram-negative isolates. Infants were more commonly positive as compared to another age group. Males were more commonly culture positive as compared to females among gram-negative isolates.


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