Optimizing empiric therapy for Gram-negative bloodstream infections in children

2018 ◽  
Vol 99 (2) ◽  
pp. 145-147 ◽  
Author(s):  
Y. Chao ◽  
C. Reuter ◽  
L.K. Kociolek ◽  
R. Patel ◽  
X. Zheng ◽  
...  
Keyword(s):  
Bloodstream Infections ◽  
Empiric Therapy ◽  
Gram Negative

scholarly journals 2143. Attempting to Add Clarity to “Indeterminates” on a Deployed Rapid Diagnostic with Antimicrobial Stewardship Program (ASP) Intervention

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S726-S726
Author(s):  
Heather L Cox ◽  
April E Attai ◽  
Allison M Stilwell ◽  
Kasi B Vegesana ◽  
Frankie Brewster ◽  
...  
Keyword(s):  
Pasteurella Multocida ◽  
Diagnostic Testing ◽  
Bloodstream Infections ◽  
Empiric Therapy ◽  
Central Line ◽  
Blood Cultures ◽  
University Hospital ◽  
Salmonella Spp ◽  
Gram Negative ◽  
Stewardship Program

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.

Clinical Experience with Aminoglycosides in Dialysis-Dependent Patients: Risk Factors for Mortality and Reassessment of Current Dosing Practices

2011 ◽  
Vol 45 (11) ◽  
pp. 1338-1345 ◽  
Author(s):  
Brett H Heintz ◽  
George R Thompson ◽  
William E Dager
Keyword(s):  
Risk Factors ◽  
Average Duration ◽  
Bloodstream Infections ◽  
Optimal Dose ◽  
Empiric Therapy ◽  
Multidrug Resistant ◽  
Gram Negative ◽  
Factors Associated ◽  
Aminoglycoside Therapy ◽  
Increased Risk

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.

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

2020 ◽  
Author(s):  
Marion Elligsen ◽  
Ruxandra Pinto ◽  
Jerome A Leis ◽  
Sandra A N Walker ◽  
Nick Daneman ◽  
...  
Keyword(s):  
Prediction Models ◽  
Tertiary Care ◽  
Intervention Group ◽  
Bloodstream Infections ◽  
Empiric Therapy ◽  
Clinical Implementation ◽  
Gram Negative ◽  
Empiric Antibiotics ◽  
Adequate Therapy ◽  
Empiric Antibiotic

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.

scholarly journals Healthcare-Associated Laboratory-Confirmed Bloodstream Infections—Species Diversity and Resistance Mechanisms, a Four-Year Retrospective Laboratory-Based Study in the South of Poland

2021 ◽  
Vol 18 (5) ◽  
pp. 2785
Author(s):  
Agnieszka Chmielarczyk ◽  
Monika Pomorska-Wesołowska ◽  
Dorota Romaniszyn ◽  
Jadwiga Wójkowska-Mach
Keyword(s):  
Bloodstream Infections ◽  
Diagnostic Techniques ◽  
Resistance Mechanisms ◽  
Infection Prevention And Control ◽  
The South ◽  
Coagulase Negative Staphylococci ◽  
Aminoglycoside Resistance ◽  
Gram Negative ◽  
Maldi Tof ◽  
Carbapenem Resistant

Introduction: Regardless of the country, advancements in medical care and infection prevention and control of bloodstream infections (BSIs) are an enormous burden of modern medicine. Objectives: The aim of our study was to describe the epidemiology and drug-resistance of laboratory-confirmed BSI (LC-BSIs) among adult patients of 16 hospitals in the south of Poland. Patients and methods: Data on 4218 LC-BSIs were collected between 2016–2019. The identification of the strains was performed using MALDI-TOF. Resistance mechanisms were investigated according to European Committee on Antimicrobial Susceptibility Testing, EUCAST recommendations. Results: Blood cultures were collected from 8899 patients, and LC-BSIs were confirmed in 47.4%. The prevalence of Gram-positive bacteria was 70.9%, Gram-negative 27.8% and yeast 1.4%. The most frequently isolated genus was Staphylococcus (50% of all LC-BSIs), with a domination of coagulase-negative staphylococci, while Escherichia coli (13.7%) was the most frequent Gram-negative bacterium. Over 4 years, 108 (2.6%) bacteria were isolated only once, including species from the human microbiota as well as environmental and zoonotic microorganisms. The highest methicillin resistant Staphylococcus aureus (MRSA) prevalence was in intensive care units (ICUs) (55.6%) but S. aureus with resistance to macrolides, lincosamides and streptogramins B (MLSB) in surgery was 66.7%. The highest prevalence of E. faecalis with a high-level aminoglycoside resistance (HLAR) mechanism was in ICUs, (84.6%), while E. faecium-HLAR in surgery was 83.3%. All cocci were fully glycopeptide-sensitive. Carbapenem-resistant Gram-negative bacilli were detected only in non-fermentative bacilli group, with prevalence 70% and more. Conclusions: The BSI microbiology in Polish hospitals was similar to those reported in other studies, but the prevalence of MRSA and enterococci-HLAR was higher than expected, as was the prevalence of carbapenem-resistant non-fermentative bacilli. Modern diagnostic techniques, such as MALDI-TOF, guarantee reliable diagnosis.

#43: Monotherapy Experience in Pediatric Patients with High-risk Febrile Neutropenia

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S19-S19
Author(s):  
Valentina Gutiérrez ◽  
Ximena Claverie
Keyword(s):  
High Risk ◽  
Febrile Neutropenia ◽  
Fungal Infections ◽  
Clinical Signs ◽  
Empiric Therapy ◽  
Fourth Generation ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Third Line ◽  
Clinical Worsening

Abstract Background Fever during neutropenia is a common occurrence in children with cancer. In a systematic review of RCTs of pediatric febrile neutropenia, compared monotherapy with aminoglycoside-containing combination therapy found no significant differences in failure rates, infection-related mortality, or overall mortality. The updated pediatric-specific guidelines recommend initiation of empirical antibiotic monotherapy using an antipseudomonal β-lactam, a fourth-generation cephalosporin, or a carbapenem for pediatric high-risk febrile neutropenia. However, local epidemiology and resistance patterns should be evaluated regularly. Our local hospital epidemiology does not have Pseudomonas aeruginosa isolates, therefore, we used ceftriaxone as monotherapy in patients with high-risk febrile neutropenia without other risk factors. The goal of our investigation is to describe the experience of using third-generation cephalosporins in these patients. Methods Descriptive study of high-risk febrile neutropenia episodes in patients admitted to the Pediatric Oncology Unit of Hospital Dr. Sótero del Río, Santiago, Chile. We included patients ≤15 years from June 2016 until November 2019. Results We found a total of 133 high-risk febrile neutropenia episodes corresponding to 50 patients, 78% were leukemia and 22% were solid tumor patients. Of the 133 episodes, 92 (69%) had clinical signs at admission, mostly respiratory in 46 (50%) of the cases, 18 (29%) had mucositis and 13 (14%) had diarrhea. Of 133 episodes, 41 (31%) did not have any source at clinical examination. Eighty-six (65%) cases started ceftriaxone at admission, 28 (33%) maintained ceftriaxone for 7 days of treatment with good clinical response. Of this group 58 (67%) patients changed treatment: 32 (37%) cases started second-line antibiotics for clinical worsening, 19 (22%) cases required second- and third-line antibiotics for persistent fever and clinical worsening, and 7 (8%) received third-line antibiotics from the start for past microbiological history. Sixteen (12%) cases of total evolved with sepsis requiring intensive care unit management. We had 30 (23%) episodes with positive blood culture, 11 (37%) due to gram-positive bacteria, 16 (53%) gram-negative bacteria, and 3 (10%) cases of fungal infections. Of the gram-negative bacteria, 7 (44%) were ESBL producers, without P. aeruginosa isolates. One case died (0.7%) for refractory sepsis due to gram-negative bacteria. Conclusion Although we did not have P. aeruginosa isolates, due to the spread of ESBL strains, monotherapy with ceftriaxone is not a good option as initial therapy for high-risk febrile neutropenia patients. The empiric therapy has to be evaluated regularly and should always be based on local epidemiology.

scholarly journals Implementation of a Rapid Phenotypic Susceptibility Platform for Gram-Negative Bloodstream Infections With Paired Antimicrobial Stewardship Intervention: Is the Juice Worth the Squeeze?

2021 ◽  
Author(s):  
Evan D Robinson ◽  
Allison M Stilwell ◽  
April E Attai ◽  
Lindsay E Donohue ◽  
Megan D Shah ◽  
...  
Keyword(s):  
Median Time ◽  
Antimicrobial Stewardship ◽  
A Priori ◽  
Bloodstream Infections ◽  
Standard Of Care ◽  
Post Intervention ◽  
Gram Negative ◽  
Stewardship Program ◽  
Days Of Therapy ◽  
The Impact

Abstract Background Implementation of the Accelerate PhenoTM Gram-negative platform (RDT) paired with antimicrobial stewardship program (ASP) intervention projects to improve time to institutional-preferred antimicrobial therapy (IPT) for Gram-negative bacilli (GNB) bloodstream infections (BSIs). However, few data describe the impact of discrepant RDT results from standard of care (SOC) methods on antimicrobial prescribing. Methods A single-center, pre-/post-intervention study of consecutive, nonduplicate blood cultures for adult inpatients with GNB BSI following combined RDT + ASP intervention was performed. The primary outcome was time to IPT. An a priori definition of IPT was utilized to limit bias and to allow for an assessment of the impact of discrepant RDT results with the SOC reference standard. Results Five hundred fourteen patients (PRE 264; POST 250) were included. Median time to antimicrobial susceptibility testing (AST) results decreased 29.4 hours (P &lt; .001) post-intervention, and median time to IPT was reduced by 21.2 hours (P &lt; .001). Utilization (days of therapy [DOTs]/1000 days present) of broad-spectrum agents decreased (PRE 655.2 vs POST 585.8; P = .043) and narrow-spectrum beta-lactams increased (69.1 vs 141.7; P &lt; .001). Discrepant results occurred in 69/250 (28%) post-intervention episodes, resulting in incorrect ASP recommendations in 10/69 (14%). No differences in clinical outcomes were observed. Conclusions While implementation of a phenotypic RDT + ASP can improve time to IPT, close coordination with Clinical Microbiology and continued ASP follow up are needed to optimize therapy. Although uncommon, the potential for erroneous ASP recommendations to de-escalate to inactive therapy following RDT results warrants further investigation.

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