702: AMINOGLYCOSIDE PHARMACODYNAMIC TARGETS AND CLINICAL SUCCESS IN TREATING GRAM-NEGATIVE BACTEREMIA

2016 ◽  
Vol 44 (12) ◽  
pp. 251-251
Author(s):  
Emily McCleary ◽  
Frank Tverdek ◽  
Jeffrey Bruno
Keyword(s):  
Clinical Success ◽  
Gram Negative ◽  
Gram Negative Bacteremia

scholarly journals 1596. Ceftolozane/tazobactam (Zerbaxa) for the Treatment of Pseudomonas aeruginosa (PSA) Bacteremia: A Systematic Literature Review (SLR)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S794-S794
Author(s):  
Ryan J Dillon ◽  
Zarmina S Khankhel ◽  
Carisa De Anda ◽  
Christopher Bruno ◽  
Laura A Puzniak
Keyword(s):  
Clinical Outcomes ◽  
Clinical Success ◽  
Complicated Urinary Tract Infection ◽  
Clinical Trial Data ◽  
Empiric Therapy ◽  
Multidrug Resistant ◽  
Eligibility Criteria ◽  
Published Evidence ◽  
Gram Negative Bacteremia ◽  
Intra Abdominal Infection

Abstract Background Bacteremia is a significant cause of morbidity and mortality. Several studies have shown this burden to increase among patients with multidrug resistant (MDR) PSA, and in those treated with inappropriate empiric therapy. Ceftolozane/tazobactam (C/T) is a combination of a novel antipseudomonal cephalosporin and an established β-lactamase inhibitor approved for the treatment of complicated urinary tract infection, complicated intra-abdominal infection and hospital-acquired and ventilator-associated bacterial pneumonia. In the absence of specific bacteremia clinical trial data; the aim of this study is to describe all published evidence relating to C/T for the treatment of Gram negative bacteremia. Methods This SLR includes all published evidence from December 2015 to March 2020 searched via the OVID platform: EMBASE, MEDLINE, and MEDLINE In-Process. In addition, data published (2018-2019) from the European Society of Clinical Microbiology and Infectious Diseases and Infectious Disease Week Congresses were included. Eligible publications were on adult patients treated with C/T reporting any clinical outcome where data were reported specifically for the bacteremia population. Results The SLR identified 1,455 citations, of which 24 publications representing 23 unique studies met eligibility criteria. This included primary and secondary bacteremia. Ten studies included patients with primary bacteremia, only 7 of which reported results specific to primary bacteremia patients. Despite heterogeneity in study design, patient and treatment characteristics, and a lack of detailed reporting; the majority of studies focused on MDR/ extensively drug resistant (XDR) infections (range: 68.3%-100%). Clinical success/ cure ranged from 33%-100%, with 6/7 studies at >85%; 30-day mortality from 0%-67%, with 3/7 studies at 0% (Table 1). Table 1. Clinical Outcomes reported among Primary Bacteremia population(s) Conclusion Although the number of C/T treated patients was small, favorable clinical outcomes were observed, even among highly resistant PSA infections. Heterogeneity was ubiquitous, with diverse and complex patient profiles identified. Further studies where outcomes are stratified by bacteremia status and by timing of C/T treatment are needed. Disclosures Ryan J. Dillon, MSc, Merck & Co., Inc., (Employee) Carisa De Anda, PharMD, Merck & Co Inc, (Employee) Christopher Bruno, MD, Merck & Co., Inc. (Employee) Laura A. Puzniak, PhD, Merck (Employee)

scholarly journals 1608. Efficacy of Ceftolozane/Tazobactam for Multidrug-Resistant Gram-Negative Infections in Multiple Urban Hospitals

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S798-S799
Author(s):  
Nicolo Cabrera ◽  
Truc T Tran ◽  
Travis J Carlson ◽  
Faris Alnezary ◽  
William R Miller ◽  
...  
Keyword(s):  
Research Study ◽  
Clinical Success ◽  
Significant Proportion ◽  
Scientific Research ◽  
Panel Member ◽  
Multidrug Resistant ◽  
Outcome Data ◽  
Research Support ◽  
Gram Negative ◽  
Study Investigator

Abstract Background Ceftolozane/tazobactam (C/T) is a novel cephalosporin/beta-lactamase inhibitor combination developed for use against multidrug-resistant (MDR) Gram-negative infections, particularly Pseudomonas aeruginosa (PA). C/T is approved for complicated urinary tract and intraabdominal infections as well as hospital-acquired/ventilator-associated bacterial pneumonias. However, comprehensive clinical characterization of patients treated with C/T in non-FDA-approved indications is limited. Methods Patients ≥18 years who received C/T for ≥48 hours while hospitalized in 9 acute care centers in Houston, TX from January 2016 through September 2018 were included. Demographic, microbiologic, treatment and clinical outcome data were retrospectively collected by chart review. In patients who received multiple inpatient courses of C/T, only the first course with C/T was assessed. Results 210 patients met inclusion criteria: 58% were non-white, 35% were female and 13% were immunocompromised. Median age was 61 years (IQR, 48 to 69). Median Charlson comorbidity index was 5 (IQR, 2 to 6). At the onset of the index episode, a significant proportion of patients required intensive care unit admission (44%), mechanical ventilation (37%) and pressor support (22%). Respiratory sources were the most common (50%) followed by urine (15%). Positive cultures were documented in 93% of the cases and PA was found in 86%. Majority (95%) of PA which were MDR. C/T use was guided by susceptibility testing of the index isolate in ca. 52%. In 5.7% of cases, C/T was used to escalate therapy without any documented C/T-susceptible organism. Half (51%) of the cohort received initial dosing appropriate for renal function while 36% receiving a lower than recommended dose. Clinical success (i.e., recovery from infection-related signs and symptoms) occured in 77%. The in-hospital mortality rate in our cohort was 15% with 26 of 31 deaths deemed infection-related. Conclusion We report a large multicenter observational cohort that received C/T. A 77% clinical success with the use of C/T was documented. These data support the use of C/T in critically ill patients infected with MDR PA. Disclosures William R. Miller, MD, Entasis Therapeutics (Scientific Research Study Investigator)Merck (Grant/Research Support)Shionogi (Advisor or Review Panel member) Laura A. Puzniak, PhD, Merck (Employee) Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)

Optimizing Rapid Diagnostics and Diagnostic Stewardship in Gram‐Negative Bacteremia

2021 ◽  
Author(s):  
Jamie L. Wagner ◽  
Kylie C. Markovich ◽  
Katie E. Barber ◽  
Kayla R. Stover ◽  
Lauren R. Biehle
Keyword(s):  
Rapid Diagnostics ◽  
Gram Negative ◽  
Gram Negative Bacteremia

Pathogenesis of Gram-Negative Bacteremia

2021 ◽  
Vol 34 (2) ◽  
Author(s):  
Caitlyn L. Holmes ◽  
Mark T. Anderson ◽  
Harry L. T. Mobley ◽  
Michael A. Bachman
Keyword(s):  
Immune Responses ◽  
Global Economy ◽  
Human Infection ◽  
Model Systems ◽  
Small Subset ◽  
Gram Negative ◽  
Content Type ◽  
Capsule Production ◽  
Gram Negative Bacteremia ◽  
Species Specific

SUMMARY Gram-negative bacteremia is a devastating public health threat, with high mortality in vulnerable populations and significant costs to the global economy. Concerningly, rates of both Gram-negative bacteremia and antimicrobial resistance in the causative species are increasing. Gram-negative bacteremia develops in three phases. First, bacteria invade or colonize initial sites of infection. Second, bacteria overcome host barriers, such as immune responses, and disseminate from initial body sites to the bloodstream. Third, bacteria adapt to survive in the blood and blood-filtering organs. To develop new therapies, it is critical to define species-specific and multispecies fitness factors required for bacteremia in model systems that are relevant to human infection. A small subset of species is responsible for the majority of Gram-negative bacteremia cases, including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. The few bacteremia fitness factors identified in these prominent Gram-negative species demonstrate shared and unique pathogenic mechanisms at each phase of bacteremia progression. Capsule production, adhesins, and metabolic flexibility are common mediators, whereas only some species utilize toxins. This review provides an overview of Gram-negative bacteremia, compares animal models for bacteremia, and discusses prevalent Gram-negative bacteremia species.

scholarly journals Cytokine screening identifies NICU patients with Gram-negative bacteremia

2012 ◽  
Vol 71 (3) ◽  
pp. 261-266 ◽  
Author(s):  
Laura L. Raynor ◽  
Jeffrey J. Saucerman ◽  
Modupeola O. Akinola ◽  
Douglas E. Lake ◽  
J. Randall Moorman ◽  
...  
Keyword(s):  
Gram Negative ◽  
Gram Negative Bacteremia

scholarly journals Combination antibiotic therapy versus monotherapy in the treatment of acute exacerbations of chronic obstructive pulmonary disease: an open-label randomized trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Phuong Nguyen Thi Thu ◽  
Minh Ngo Thị Huong ◽  
Ngan Tran Thi ◽  
Hoi Nguyen Thanh ◽  
Khue Pham Minh
Keyword(s):  
Clinical Success ◽  
Chronic Obstructive ◽  
Gram Negative Bacteria ◽  
Beta Lactam ◽  
Open Label ◽  
Obstructive Pulmonary Disease ◽  
Gram Negative ◽  
Copd Exacerbations ◽  
Beta Lactam Antibiotics ◽  
Acute Exacerbations

Abstract Background The role of antibiotics in the treatment of chronic obstructive pulmonary disease (COPD) exacerbations and their effectiveness in combination have not been clearly established. To determine whether using a combination of fluoroquinolones and beta-lactams improves the clinical and microbiological efficacy of antibiotics on day 20 of treatment, we conducted an open-label randomized trial based on clinical outcomes, microbiological clearance, spirometry tests, and signs of systemic inflammation in patients hospitalized with acute exacerbations of COPD. Methods We enrolled 139 subjects with COPD exacerbations, defined as acute worsening of respiratory symptoms leading to additional treatment. Patients were divided randomly into two groups: 79 patients using beta-lactam antibiotics alone and 60 using beta-lactam antibiotics plus fluoroquinolones. Clinical and microbiological responses, spirometry tests, symptom scores, and serum C-reactive protein (CRP) levels were evaluated. Results Clinical success, lung function, and symptoms were similar in patients with or without fluoroquinolone administration on days 10 and 20. Combination therapy was superior in terms of microbiological outcomes and reduction in serum CRP value. Although equivalent to monotherapy in terms of clinical success, the combination showed superiority in terms of microbiological success and a decrease in CRP. The combination therapy group had a higher microbiological success rate with gram-negative bacteria than the monotherapy group with Pseudomonas aeruginosa (100% vs. 33.3%, respectively) and Acinetobacter baumanii (100% vs. 20%, respectively) (P < 0.05). Conclusions Concomitant use of fluoroquinolone and beta-lactam antibiotics for bacterial infections during COPD exacerbations caused by gram-negative bacteria appear to be effective and should be applied in clinical practice.

scholarly journals Validation of Available Extended Spectrum Beta-Lactamase (ESBL) Clinical Scoring Models in Predicting Drug Resistance in Patients with Enteric Gram- Negative Bacteremia, Treated at South Texas Veterans Health Care System (STVHCS).

2021 ◽  
Author(s):  
Julieta Madrid-Morales ◽  
Aditi Sharma ◽  
Kelly Reveles ◽  
Carolina Velez-Mejia ◽  
Teri Hopkins ◽  
...  
Keyword(s):  
Health Care ◽  
Prediction Models ◽  
South Texas ◽  
Beta Lactamase ◽  
Veterans Health ◽  
Discriminatory Ability ◽  
Gram Negative ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Gram Negative Bacteremia

Background: Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are increasingly common; however, predicting which patients are likely to be infected with an ESBL pathogen is challenging, leading to increased use of carbapenems. To date, five prediction models have been developed to distinguish between patients infected with ESBL pathogens. The aim of this study was to validate and compare each of these models, to better inform antimicrobial stewardship. Methods: This was a retrospective cohort study of patients with gram-negative bacteremia treated at the South Texas Veterans Health Care System over 3 months from 2018 to 2019. We evaluated isolate, clinical syndrome, and score variables for the five published prediction models/scores: Italian “Tumbarello”, Duke, University of South Carolina (USC), Hopkins Clinical Decision Tree, and Modified Hopkins. Each model was assessed using the receiver-operating-characteristic curve (AUROC) and Pearson correlation. Results: 145 patients were included for analysis, of which 20 (13.8%) were infected with an ESBL E. coli or Klebsiella spp. The most common sources of infection were genitourinary (55.8%) and gastrointestinal/intraabdominal (24.1%) and the most common pathogen was E. coli (75.2%). The prediction model with the strongest discriminatory ability (AUROC) was Tumbarello (0.7556). Correlation between prediction model score and percent ESBL was strongest with Modified Hopkins (R2=0.74). Conclusions: In this veteran population, the Modified Hopkins and Duke prediction models were most accurate in discriminating between gram-negative bacteremia patients when considering both AUROC and correlation. However, given the moderate discriminatory ability, many patients with ESBL Enterobacteriaceae (at least 25%) may still be missed empirically.

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