Development and implementation of a short duration antibiotic therapy algorithm for uncomplicated gram-negative bloodstream infections

2021 ◽  
pp. 1-3
Author(s):  
Esther Y. Bae ◽  
Kathryn Dzintars ◽  
Fidelia Bernice ◽  
Pranita D. Tamma ◽  
Sara E. Cosgrove ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Short Duration ◽  
Bloodstream Infections ◽  
Therapy Algorithm ◽  
Gram Negative

scholarly journals 131. Duration of Therapy for the Treatment of Gram-Negative Bloodstream Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S94-S95
Author(s):  
Stephanie Shulder ◽  
Matthew O’Connell ◽  
Kaitlyn J Agedal ◽  
Kelly M Conn ◽  
Kelly E Pillinger
Keyword(s):  
Short Duration ◽  
Bloodstream Infections ◽  
Oral Antibiotic ◽  
In Vitro Susceptibility ◽  
Clinical Resolution ◽  
Gram Negative ◽  
Prior Therapy ◽  
Source Of Infection ◽  
Long Duration

Abstract Background While current guidelines suggest a total treatment duration of 7 to 14 days for gram-negative bloodstream infections (GN-BSI), there is mounting evidence to suggest that shorter durations may be sufficient. This study compared the treatment outcomes of patients who received short duration therapy (6–10 days) with those who received long durations (11–15 days). Methods This was a retrospective study of adult patients who grew an aerobic gram-negative organism from a blood culture while admitted at Strong Memorial Hospital between May 2016 and May 2018. The primary outcome was a composite of mortality and relapsed GN-BSI with the same organism within 90 days of index culture. Secondary outcomes included clinical resolution at end of therapy (EOT), length of stay (LOS), 30-day readmission rate, Clostridoides difficile infection (CDI), development of recurrent GN-BSI resistant to prior antibiotic therapy, and development of multi-drug-resistant (MDR) GN-BSI within 90 days. Appropriate therapy was defined as an antibiotic with confirmed in vitro susceptibility that was either parenteral or a highly bioavailable oral antibiotic (fluoroquinolones or sulfamethoxazole–trimethoprim). Results Of 600 patients screened, 116 were included in the long duration group and 34 patients in the short-duration group. The majority of patients had a urinary source of infection (59.3%). The primary composite outcome occurred in 11.8% of the short duration group compared with 10.3% in the long (P > 0.999). There was no difference in clinical resolution at EOT, LOS, or rates of CDI, MDR GN-BSI, recurrent GN-BSI resistant to prior therapy, or 30-day readmission. Patients in the long duration group were discharged with longer appropriate outpatient courses (8 days vs. 0.5 days, P < 0.001), which remained significant when including lower bioavailability agents (e.g., oral β lactams) (8 days vs. 5 days, P < 0.001). Conclusion There was no difference in clinical outcomes between the long and short duration therapy for treatment of GN-BSI. This study may support shorter treatment durations for uncomplicated GN-BSI, but should be interpreted cautiously given the smaller sample size. Disclosures All authors: No reported disclosures.

scholarly journals 194. Description of Positive Blood Culture Results not Identified by Verigene Informs Empiric Antibiotic Selection

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S116-S117
Author(s):  
Connor Deri ◽  
Whitney Nesbitt ◽  
George Nelson ◽  
Jessica Keefe
Keyword(s):  
Antibiotic Therapy ◽  
Resistance Mechanism ◽  
Bloodstream Infections ◽  
Blood Cultures ◽  
Aerobic Bacteria ◽  
Gram Positive ◽  
Antibiotic Selection ◽  
Gram Negative ◽  
Empiric Antibiotic ◽  
Gram Negative Organisms

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.

scholarly journals A Decision Tree Using Patient Characteristics to Predict Resistance to Commonly Used Broad-Spectrum Antibiotics in Children With Gram-Negative Bloodstream Infections

2019 ◽  
Vol 9 (2) ◽  
pp. 142-149 ◽  
Author(s):  
Anna C Sick-Samuels ◽  
Katherine E Goodman ◽  
Glenn Rapsinski ◽  
Elizabeth Colantouni ◽  
Aaron M Milstone ◽  
...  
Keyword(s):  
High Risk ◽  
Decision Tree ◽  
Antibiotic Therapy ◽  
Broad Spectrum ◽  
Tertiary Care ◽  
Bloodstream Infections ◽  
Intestinal Transplantation ◽  
Empiric Antibiotic Therapy ◽  
Gram Negative ◽  
Broad Spectrum Antibiotics

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.

scholarly journals Management of Gram-Negative Bloodstream Infections in the Era of Rapid Diagnostic Testing: Impact With and Without Antibiotic Stewardship

2020 ◽  
Vol 7 (10) ◽  
Author(s):  
Kimberly C Claeys ◽  
Emily L Heil ◽  
Stephanie Hitchcock ◽  
J Kristie Johnson ◽  
Surbhi Leekha
Keyword(s):  
Antibiotic Therapy ◽  
Proportional Hazards ◽  
Diagnostic Testing ◽  
Bloodstream Infections ◽  
Cox Proportional Hazards ◽  
Gram Negative ◽  
Optimal Therapy ◽  
Kaplan Meier ◽  
Quasi Experimental

Abstract Background Verigene Blood-Culture Gram-Negative is a rapid diagnostic test (RDT) that detects gram-negatives (GNs) and resistance within hours from gram stain. The majority of the data support the use of RDTs with antimicrobial stewardship (AMS) intervention in gram-positive bloodstream infection (BSI). Less is known about GN BSI. Methods This was a retrospective quasi-experimental (nonrandomized) study of adult patients with RDT-target GN BSI comparing patients pre-RDT/AMS vs post-RDT/pre-AMS vs post-RDT/AMS. Optimal therapy was defined as appropriate coverage with the narrowest spectrum, accounting for source and co-infecting organisms. Time to optimal therapy was analyzed using Kaplan-Meier and multivariable Cox proportional hazards regression. Results Eight-hundred thirty-two patients were included; 237 pre-RDT/AMS vs 308 post-RDT/pre-AMS vs 237 post-RDT/AMS, respectively. The proportion of patients on optimal antibiotic therapy increased with each intervention (66.5% vs 78.9% vs 83.2%; P &lt; .0001). Time to optimal therapy (interquartile range) decreased with introduction of RDT: 47 (7.9–67.7) hours vs 24.9 (12.4–55.2) hours vs 26.5 (10.3–66.5) hours (P = .09). Using multivariable modeling, infectious diseases (ID) consult was an effect modifier. Within the ID consult stratum, controlling for source and ICU stay, compared with the pre-RDT/AMS group, both post-RDT/pre-AMS (adjusted hazard ratio [aHR], 1.34; 95% CI, 1.04–1.72) and post-RDT/AMS (aHR, 1.28; 95% CI, 1.01–1.64), improved time to optimal therapy. This effect was not seen in the stratum without ID consult. Conclusions With the introduction of RDT and AMS, both proportion and time to optimal antibiotic therapy improved, especially among those with an existing ID consult. This study highlights the beneficial role of RDTs in GN BSI.

scholarly journals 52. Development and Implementation of a Short Duration of Antibiotic Therapy Algorithm for Uncomplicated Gram-Negative Bacteremia

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S48-S48
Author(s):  
Esther Y Bae ◽  
Fidelia Bernice ◽  
Kathryn Dzintars ◽  
Sara E Cosgrove ◽  
Pranita D Tamma ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Clinical Outcomes ◽  
Median Duration ◽  
Intervention Period ◽  
Therapy Algorithm ◽  
Gram Negative ◽  
Duration Of Therapy ◽  
Number Of Patients ◽  
Gram Negative Bacteremia ◽  
The Impact

Abstract Background Recent literature suggests no difference in clinical outcomes between short (7 days) and prolonged course (14 days) antibiotic therapy for the treatment of uncomplicated Gram-negative bacteremia (GNB). Methods The objectives of the study were to develop and implement a treatment algorithm that identifies patients who are eligible for 7-day therapy for uncomplicated GNB and evaluate its impact on patient outcomes at The Johns Hopkins Hospital (JHH) in Baltimore. The algorithm was developed and implemented at JHH on 11/11/2019. From 11/11/2019 to 3/31/2020, the Infectious Diseases (ID) Pharmacy Resident and ID pharmacists reviewed cases of GNB on weekdays and contacted teams to provide algorithm-compliant treatment recommendations. To quantify the impact of the intervention on clinical outcomes, data from the same time period during the previous year (baseline) were collected and compared to those collected during the intervention. The primary outcome was duration of antibiotic therapy for GNB. Secondary outcomes included: duration of intravenous (IV) antibiotics, length of hospital stay (LOS), and recurrent bacteremia. Results A total of 345 patients with GNB were identified (142 baseline; 203 intervention) of which 59 and 55 patients met criteria for 7-day therapy, respectively. The Pitt bacteremia score (median 1), bacteremia source [urinary (43%), abdominal (23%)], and organisms [E. coli (48%) and Klebsiella spp. (33%)] were similar between the periods. More patients in the intervention period were treated for ≤8 days (60.0% vs. 37.3%; p=0.015), and the median duration of therapy was 2 days shorter (8 vs. 10 days; p=0.04). Median duration of IV antibiotic therapy (4 vs. 7 days; p=0.004) and median LOS (4 vs. 7 days; p=0.029) were also shorter in the intervention period. There were no differences in the rate of 30-day recurrent bacteremia between the periods (3.4% baseline vs. 1.8% intervention; p=0.60). Conclusion Our pharmacist-led intervention successfully shortened the duration of therapy, increased conversion from IV to PO therapy, and reduced LOS, without negatively impacting the number of patients with recurrent GNB. Disclosures All Authors: No reported disclosures

scholarly journals 1360. Variation in Duration of Antibiotic Therapy for Central-line Associated Blood Stream Infections Caused by Gram Negative Bacilli in Hospitalized Children

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S691-S691
Author(s):  
Grant R Whitmer ◽  
Tonya Scardina ◽  
Shan Sun ◽  
Xiaotian Zheng ◽  
Sameer Patel
Keyword(s):  
Antibiotic Therapy ◽  
Median Duration ◽  
Positive Culture ◽  
Bloodstream Infections ◽  
Venous Catheter ◽  
Central Line ◽  
Effective Therapy ◽  
Severe Neutropenia ◽  
Solid Organ ◽  
Gram Negative

Abstract Background Central-line associated bloodstream infections (CLABSIs) are associated with increased morbidity, mortality, and duration of hospitalization in children. Existing guidelines recommend a broad range (7-14 days) for duration of antibiotic therapy. Unnecessarily prolonged therapy may be associated with emergence of antibiotic resistance and adverse events. Methods We performed a retrospective review of all patients diagnosed with CLABSIs caused by Gram negative bacilli (GNB) at our institution from August 2009 to April 2019. CLABSI was defined as isolation of a GNB from the blood &gt;48 hours after hospital admission with presence of a central venous catheter. Children who died before completion of treatment were excluded. Data collection variables included severe neutropenia (defined as absolute neutrophil count &lt; 500), immunocompromised status (defined as receipt of bone marrow transplant, solid organ transplant, or immunosuppressive medication), and catheter removal. The duration of effective antibiotic therapy was calculated from the date of last positive culture to discontinuation. Effective therapy was defined as use of an agent to which the isolated organism was susceptible by antimicrobial susceptibility testing. The primary outcome was microbiological recurrence of the same organism and/or all-cause mortality within 30 days of discontinuation. Results Overall, 95 CLABSIs were included. Of 92 patients, 46 (50%) were immunocompromised. For patients with catheters removed prior to the end of therapy (n=48), the median duration of effective therapy was 13.5 days (IQR: 8.75-16 days). For patients who retained catheters throughout treatment (n=47), the median duration of effective therapy was 13 days (IQR: 9-15 days). Of these 95 CLABSIs, one patient (retained catheter) had microbiological recurrence within 30 days. Seven patients died (without microbiological recurrence), with range of duration of therapy of 6-14 days. Conclusion There was a wide variation in length of therapy for CLABSIs caused by GNB in children. Microbiological recurrence was rare, and mortality was unrelated to microbiological recurrence. Future studies should evaluate standardization of shorter duration therapy to avoid unnecessarily prolonged antibiotic exposure. Disclosures Sameer Patel, MD MPH, Merck (Grant/Research Support)Nexogen (Consultant)

scholarly journals Optimizing the Management of Uncomplicated Gram-Negative Bloodstream Infections: Consensus Guidance Using a Modified Delphi Process

2021 ◽  
Vol 8 (10) ◽  
Author(s):  
Emily L Heil ◽  
Jacqueline T Bork ◽  
Lilian M Abbo ◽  
Tamar F Barlam ◽  
Sara E Cosgrove ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Antibiotic Therapy ◽  
Bloodstream Infections ◽  
Blood Cultures ◽  
Oral Antibiotic ◽  
Gram Negative ◽  
Modified Delphi ◽  
Oral Antibiotic Therapy ◽  
Consensus Statements ◽  
Definition Of

Abstract Background Guidance on the recommended durations of antibiotic therapy, the use of oral antibiotic therapy, and the need for repeat blood cultures remain incomplete for gram-negative bloodstream infections. We convened a panel of infectious diseases specialists to develop a consensus definition of uncomplicated gram-negative bloodstream infections to assist clinicians with management decisions. Methods Panelists, who were all blinded to the identity of other members of the panel, used a modified Delphi technique to develop a list of statements describing preferred management approaches for uncomplicated gram-negative bloodstream infections. Panelists provided level of agreement and feedback on consensus statements generated and refined them from the first round of open-ended questions through 3 subsequent rounds. Results Thirteen infectious diseases specialists (7 physicians and 6 pharmacists) from across the United States participated in the consensus process. A definition of uncomplicated gram-negative bloodstream infection was developed. Considerations cited by panelists in determining if a bloodstream infection was uncomplicated included host immune status, response to therapy, organism identified, source of the bacteremia, and source control measures. For patients meeting this definition, panelists largely agreed that a duration of therapy of ~7 days, transitioning to oral antibiotic therapy, and forgoing repeat blood cultures, was reasonable. Conclusions In the absence of professional guidelines for the management of uncomplicated gram-negative bloodstream infections, the consensus statements developed by a panel of infectious diseases specialists can provide guidance to practitioners for a common clinical scenario.

scholarly journals Gram-negative bacilli bacteremia: a 7 year retrospective study in a referral Brazilian tertiary-care teaching hospital

2020 ◽  
Author(s):  
Maria Clara Bisaio Quillici ◽  
Daiane Silva Resende ◽  
Iara Rossi Gonçalves ◽  
Sabrina Royer ◽  
Sebastiana Silva Sabino ◽  
...  
Keyword(s):  
Septic Shock ◽  
Antibiotic Therapy ◽  
Bloodstream Infection ◽  
Teaching Hospital ◽  
Type Species ◽  
Bloodstream Infections ◽  
Gram Negative ◽  
Content Type ◽  
Link Type ◽  
Initial Antibiotic Therapy

Introduction. Bloodstream infection is one of the most frequent and challenging hospital-acquired infections and it is associated with high morbidity, mortality and additional use of healthcare resources. Hypothesis/Gap Statement: Bloodstream infections have consequences for the patient, such as the evolution to mortality and inappropriate empirical antibiotic prescription, especially when caused by multidrug-resistant Gram-negative bacilli. Objective. To assess the impact of bloodstream infection and the status of multidrug resistance (MDR) in the evolution of patients who received inappropriate initial antibiotic therapy. Methods. A retrospective surveillance was conducted on nosocomial bloodstream infections caused by Gram-negative bacilli (GNB) from January 2012 to December 2018 in an adult intensive care unit of a Brazilian tertiary teaching hospital. Results. We identified 270 patients with GNB nosocomial bacteremia. Non-survivors were older (with an average age of 58.8 years vs 46.9 years, P=<0.0001), presented more severe illnesses, were immunosuppressed (73.7 vs 37.6%, P=<0.0001), were more likely to have septic shock (55.8 vs 22.4%, P=<0.0001) and had an increased usage of mechanical ventilators (98.6 vs 89.6%, P=0.0013) than survivors. In a logistic regression model, inappropriate empirical antibiotic therapy was not an independent predictor of mortality, different from mechanical ventilator (P=<0.0001; OR=28.0; 95% CI=6.3–123.6), septic shock (P=0.0051; OR=2.5; 95% CI=1.3–4.9) and immunosuppression (P=0.0066; OR=2.6; 95% CI=1.3–5.2). In contrast, in a separate model, MDR was strongly associated with the prescription of inappropriate initial antibiotic therapy (P=0.0030; OR=5.3; 95% CI=1.7–16.1). The main isolated pathogens were Acinetobacter baumannii (23.6 %) and Klebsiella pneumoniae (18.7 %). The frequency of MDR organisms was high (63.7 %), especially among non-fermenting bacilli (60.9 %), highlighting A. baumannii (81.6 %) and Pseudomonas aeruginosa (41.8 %). Conclusion. Illness severity (septic shock and immunosuppression) and mechanical ventilation were identified as predictors of mortality. Additionally, MDR was a major determinant of inappropriate antibiotic empirical therapy, but not associated with mortality, and both characteristics were not statistically associated with death.

scholarly journals 1050. Oral Antibiotics for the Treatment of Gram-Negative Bloodstream Infections: Prescribing Practices and Outcomes at a Large Academic Medical Center

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S313-S314
Author(s):  
Kimberly Claeys ◽  
Nora Loughry ◽  
Sanjay Chainani ◽  
Surbhi Leekha ◽  
Emily Heil
Keyword(s):  
Antibiotic Therapy ◽  
Medical Center ◽  
Academic Medical Center ◽  
Bloodstream Infections ◽  
Antibiotic Use ◽  
Optimal Time ◽  
Oral Antibiotics ◽  
Prescribing Practices ◽  
Gram Negative ◽  
Academic Medical

Abstract Background There is limited data to guide the use of oral (PO) antibiotics for the treatment of Gram-negative (GN) bloodstream infection (BSI). The objective of this study was to describe the characteristics and outcomes at a large academic medical center. Methods Retrospective observational cohort of adult patients (age ≥18 years) with at least one blood culture positive for aerobic Gram-negative organism(s) treated with antibiotic therapy (IV or oral [PO]) at University of Medical Center from November 2015 to May 2017. Oral antibiotics were described based on bioavailability. The primary outcome of interest was 30-day infection-related readmission. Secondary objectives included evaluation of patient characteristics associated with PO antibiotic use. Results During the defined study period 310 patients met inclusion; 113 (36.5%) were switched to PO antibiotic therapy for the treatment of GN BSI within a median of 5 (IQR 3–11) days. Oral antibiotics were initiated at discharge for 50 (44%) of patients switched. Patients switched to PO were less likely to have has a stay in the ICU (24.8% vs. 47.7%, P &lt; 0.0001) and were less likely to have an ID consult (57.5% vs. 71.1%, P = 0.034). There was no difference in median Charlson Comorbidity Score (2, IQR 0–4). The most common sources of infection among those switched to PO agents were urinary (50, 44.2%) and intra-abdominal (25, 22.1%). The majority of patients were placed on a PO agent with high bioavailability (61, 54%), which included levofloxacin and moxifloxacin. There was a slightly higher proportion of use of high (vs. low) bioavailable antibiotics in patients with ID consult compared with those without (59% vs. 41%, P = 0.053). PO antibiotics were more frequently prescribed for patients discharged home (78, 69%) compared with patients discharged to Rehab/Short-term facility (28, 24.8%). Thirty-day hospital readmission was more common among the patients treated with PO antibiotics (18.6 vs. 8.1%, P = 0.006); however, ID-related readmission was rare (0.9% vs. 1%, P = 0.91). Conclusion Urinary and intra-abdominal sources and home discharge were common among those with PO antibiotic use. ID-related outcomes were similar among those treated with IV vs. PO agents. More research is necessary to determine optimal time to PO antibiotic switch. Disclosures K. Claeys, Nabriva: Scientific Advisor, Consulting fee. Melinta: Scientific Advisor, Consulting fee. E. Heil, ALK-Abelló: Grant Investigator, Research grant.

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