scholarly journals 1243. Eravacycline in Bacteremia: A Case Series

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S710-S711
Author(s):  
Justin A Andrade ◽  
Robert Kosalka ◽  
James Truong ◽  
Joshua R Rosenberg

Abstract Background Eravacycline (ERV) is FDA-approved for the treatment of complicated intra-abdominal infections, but there is limited experience for non-FDA approved indications. Methods We present five cases that utilized ERV for treatment of bacteremia. Results Patient 1 in septic shock (SS) started on vancomycin (VAN) and ceftazidime-avibactam (CZA). Blood culture (BC) finalized to E. coli and regimen narrowed to CZA. On day 9, gram-positive cocci in chains in BC grew and VAN was added. BC finalized to VRE faecium and regimen was modified to ERV on day 12. Repeat BC on day 15 finalized to no growth with no recurrence of bacteremia until discharged (day 78). Patient 2 treated for MSSA bacteremia with cefazolin and subsequent K. pneumoniae VAP treated with ceftriaxone (CRO) (day 18-26). On day 27, meropenem (MEM) was initiated for gram-negative bacteremia and started on IV trimethoprim/sulfamethoxazole (TMP/SMX) the following day for pneumonia caused by TMP/SMX-susceptible S. maltophila. BC finalized on day 29 to S. maltophila resistant to TMP/SMX, regimen modified to ERV. Repeat BC on day 30 finalized to no growth and ERV was continued until day 42 with no recurrence of bacteremia; however, patient died on day 45. Patient 3 with renal failure and on day 11, CRO started for SBP prophylaxis. On day 13, switched to daptomycin and cefepime (FEP) as patient was febrile and BC repeated. BC finalized to VRE faecium and was started on ERV on day 17 and completed a 7-day course with no recurrence of bacteremia; however, patient died on day 34. Patient 4 initially treated for bacterial superinfection with CRO and azithromycin, and subsequent worsening pneumonia treated with VAN and MEM (day 10-17). On day 19, patient was febrile and treated with VAN and FEP until day 27. Repeat BC on day 29 finalized to VRE species and modified to ERV on day 32. ERV continued for a 7-day course and was discharged with no repeat BC obtained to confirm clearance. Patient 5 in SS started on VAN and MEM. On day 3, BC on admission finalized to VRE faecium and therapy switched to ERV. Repeat BC taken on day 3 after ERV initiation were negative. Discharged to complete two-week course of ERV. Conclusion ERV may be an option for bacteremia as demonstrated by clearance in four of five cases. More studies must be conducted as these reports show variable clinical outcomes. Disclosures Joshua R. Rosenberg, MD, Allergan/Abbvie (Consultant)La Jolla/Tetraphase (Consultant)Melinta (Consultant)Merck (Consultant)Paratek (Consultant)Sanofi (Consultant)Shionogi (Consultant)

2006 ◽  
Vol 50 (7) ◽  
pp. 2478-2486 ◽  
Author(s):  
Andrea Giacometti ◽  
Oscar Cirioni ◽  
Roberto Ghiselli ◽  
Federico Mocchegiani ◽  
Fiorenza Orlando ◽  
...  

ABSTRACT Sepsis remains a major cause of morbidity and mortality in hospitalized patients, despite intense efforts to improve survival. The primary lead for septic shock results from activation of host effector cells by endotoxin, the lipopolysaccharide (LPS) associated with cell membranes of gram-negative bacteria. For these reasons, the quest for compounds with antiendotoxin properties is actively pursued. We investigated the efficacy of the amphibian skin antimicrobial peptide temporin L in binding Escherichia coli LPS in vitro and counteracting its effects in vivo. Temporin L strongly bound to purified E. coli LPS and lipid A in vitro, as proven by fluorescent displacement assay, and readily penetrated into E. coli LPS monolayers. Furthermore, the killing activity of temporin L against E. coli was progressively inhibited by increasing concentrations of LPS added to the medium, further confirming the peptide's affinity for endotoxin. Antimicrobial assays showed that temporin L interacted synergistically with the clinically used β-lactam antibiotics piperacillin and imipenem. Therefore, we characterized the activity of temporin L when combined with imipenem and piperacillin in the prevention of lethality in two rat models of septic shock, measuring bacterial growth in blood and intra-abdominal fluid, endotoxin and tumor necrosis factor alpha (TNF-α) concentrations in plasma, and lethality. With respect to controls and single-drug treatments, the simultaneous administration of temporin L and β-lactams produced the highest antimicrobial activities and the strongest reduction in plasma endotoxin and TNF-α levels, resulting in the highest survival rates.


Author(s):  
Julieta Madrid-Morales ◽  
Aditi Sharma ◽  
Kelly Reveles ◽  
Carolina Velez-Mejia ◽  
Teri Hopkins ◽  
...  

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.


2019 ◽  
Vol 47 (Suppl. 3) ◽  
pp. 51-53 ◽  
Author(s):  
Marcus Ewert Broman ◽  
Mikael Bodelsson

Background: Lipopolysaccharide (endotoxin) from the outer Gram-negative bacterial wall can induce a harmful immunologic response, involving hemodynamic deprivation, and is one important motor driving the septic cascade. The positively charged poly-imine ethylene layer on the oXiris membrane is capable of adsorbing negatively charged endotoxin molecules and removing them from the blood compartment. Endotoxin is detrimental and should be removed from blood. Summary: The adsorbable endotoxin fraction in blood arises from a tight balance between seeding from an infectious focus and removal by an overwhelmed immune system. The net sum of remaining endotoxin in blood is available for an adsorption process in the oXiris filter. Endotoxin data from 2 patients with severe Gram-negative septic shock and endotoxemia in this case series, speaks for a considerable share of the adsorption of the oXiris filter in the endotoxin net removal over time. Key Messages: Analysis of combined in vitro and in vivo data speaks for an effect of the oXiris filter in lowering endotoxin.


2010 ◽  
Vol 59 (9) ◽  
pp. 1050-1054 ◽  
Author(s):  
Stephen P. Hawser ◽  
Robert E. Badal ◽  
Samuel K. Bouchillon ◽  
Daryl J. Hoban ◽  

A total of 542 clinical isolates of aerobic Gram-negative bacilli from intra-abdominal infections were collected during 2008 from seven hospitals in India participating in the Study for Monitoring Antimicrobial Resistance Trends (SMART). Isolates were from various infection sources, the most common being gall bladder (30.1 %) and peritoneal fluid (31.5 %), and were mostly hospital-associated isolates (70.8 %) as compared to community-acquired (26.9 %). The most frequently isolated pathogens were Escherichia coli (62.7 %), Klebsiella pneumoniae (16.7 %) and Pseudomonas aeruginosa (5.3 %). Extended-spectrum β-lactamase (ESBL) rates in E. coli and K. pneumoniae were very high, at 67 % and 55 %, respectively. Most isolates exhibited resistance to one or more antibiotics. The most active drugs were generally ertapenem, imipenem and amikacin. However, hospital-acquired isolates in general, as well as ESBL-positive isolates, exhibited lower susceptibilities than community-acquired isolates. Further surveillance monitoring of intra-abdominal isolates from India is recommended.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S93-S93
Author(s):  
Andrew Walkty ◽  
Heather Adam ◽  
Melanie Baxter ◽  
Amina Henni ◽  
Philippe Lagace-Wiens ◽  
...  

Abstract Background Inadequate empiric antimicrobial therapy for Gram-negative bacteremia is associated with adverse clinical outcomes. The purpose of this study was to evaluate the proportion of Gram-negative bacterial isolates recovered from the bloodstream of patients attending Canadian emergency rooms (ERs) that remain susceptible to commonly prescribed antimicrobials. Methods Annually from 2007 to 2018, sentinel hospitals across Canada collected bloodstream isolates from patients attending ERs as part of the CANWARD study. Susceptibility testing was performed using broth microdilution as described by CLSI (data analysis limited to Gram-negative bacteria in the top 10 pathogens), with current CLSI breakpoints applied. Extended-spectrum β-lactamase (ESBL)-producing isolates were confirmed using the CLSI disk diffusion method. Results Gram-negative bacteria among the top 10 bloodstream pathogens for patients seen at ERs across Canada were: Escherichia coli (n = 2,414), Klebsiella pneumoniae (n = 573), Pseudomonas aeruginosa (n = 211), Proteus mirabilis (n = 119), and Enterobacter cloacae (n = 114). Aggregate susceptibility of these isolates to common antimicrobials was as follows (% susceptible [S]): meropenem 99.4% S, piperacillin–tazobactam 98.5% S, gentamicin 93.3% S, ceftriaxone 88.1% S, ciprofloxacin 81.4% S, TMP-SMX 73.5% S. The most active antimicrobials evaluated vs. E. coli were meropenem (100% S), piperacillin–tazobactam (98.8% S), and ceftriaxone (93.3% S). Ceftriaxone susceptibility among E. coli isolates declined from 95.4% in 2007 to 89.8% in 2018. The average proportion of E. coli isolates that harbored an ESBL enzyme increased from 3.4% in the first three study years to 8.4% in the last three study years. The most active antimicrobials evaluated vs. K. pneumoniae isolates were meropenem (99.7% S), piperacillin–tazobactam (98.8% S), gentamicin (97.7% S), and ceftriaxone (96.9% S). Conclusion The most consistently active antimicrobials for empiric treatment of patients at Canadian ERs with Gram-negative bacteremia are meropenem and piperacillin–tazobactam. Ceftriaxone susceptibility among E. coli has declined over the last 12 years, mostly related to an increase in ESBL-producing isolates. Disclosures All authors: No reported disclosures.


1960 ◽  
Vol 58 (4) ◽  
pp. 357-366 ◽  
Author(s):  
Leonard Colebrook ◽  
E. J. L. Lowbury ◽  
L. Hurst

Six strains of Str. pyogenes and four strains of Staph. aureus were found to grow well from large or small inocula in fresh human serum; four strains of E. coli failed to grow from large inocula and were killed when the inocula were small. Ps. pyocyanea, Proteus and Str. viridans sometimes grew and sometimes failed to grow in fresh serum.In serum which had been treated with trypsin or heated at 56° C. for 1 hr. the Gram-negative bacilli grew readily, and growth was still better in serum which had been heated and then trypsinized. Heating at 56° C. and treatment with proteolytic enzymes were shown to destroy complement and to inactivate the bactericidal activity of fresh serum against a Shigella highly sensitive to the properdin system. It is suggested that these changes might be enough to explain the conversion of serum by proteolytic enzymes into a suitable medium for the growth of coliform bacilli. This change might be brought about by bacterial or leucocytic enzymes. Fibrinolytic serum from a cadaver was found to retain at least a part of its complement and bactericidal activity.Strains of E. coli, Ps. pyocyanea, Proteus, Staph. aureus and Str. pyogenes were tested for growth in burn slough suspension and blister fluid. In slough suspension all strains grew well, but the Gram-negative bacilli grew rather more vigorously than the Gram-positive cocci. In blister fluid E. coli was killed and other strains grew.These findings are discussed in relation to wound sepsis.


2015 ◽  
Vol 60 (1) ◽  
pp. 245-251 ◽  
Author(s):  
Hui Zhang ◽  
Qiwen Yang ◽  
Kang Liao ◽  
Yuxing Ni ◽  
Yunsong Yu ◽  
...  

ABSTRACTTo evaluate the antimicrobial susceptibility of Gram-negative bacilli that caused hospital-acquired and community-acquired intra-abdominal infections (IAIs) in China between 2012 and 2013, we determined the susceptibilities to 12 antimicrobials and the extended-spectrum β-lactamase (ESBL) statuses of 3,540 IAI isolates from seven geographic areas in China in a central laboratory using CLSI broth microdilution and interpretive standards. Most infections were caused byEscherichia coli(46.3%) andKlebsiella pneumoniae(19.7%). Rates of ESBL-producingE. coli(P= 0.031),K. pneumoniae(P= 0.017), andProteus mirabilis(P= 0.004) were higher in hospital-acquired IAIs than in community-acquired IAIs. Susceptibilities of enterobacteriaceae to ertapenem, amikacin, piperacillin-tazobactam, and imipenem were 71.3% to 100%, 81.3% to 100%, 64.7% to 100%, and 83.1% to 100%, respectively, but imipenem was ineffective againstP. mirabilis(<20%). Although most ESBL-positive hospital-acquired isolates were resistant to third- and fourth-generation cephalosporins, the majority were susceptible to cefoxitin (47.9% to 83.9%). Susceptibilities of ESBL-positive isolates to ampicillin-sulbactam (<10%) were low, whereas susceptibilities to ciprofloxacin (0% to 54.6%) and levofloxacin (0% to 63.6%) varied substantially. The prevalences of cephalosporin-susceptibleE. coliandK. pneumoniaewere higher in the northeastern and southern regions than in the central and eastern regions, reflecting the ESBL-positive rates in these areas, and were lowest in the Jiangsu-Zhejiang (Jiang-Zhe) area where the rates of carbapenem resistance were also highest. Ertapenem, amikacin, piperacillin-tazobactam, and imipenem are the most efficacious antibiotics for treating IAIs in China, especially those caused byE. coliorK. pneumoniae. Resistance to cephalosporins and carbapenems is more common in the Jiang-Zhe area than in other regions in China.


2020 ◽  
Vol 7 (11) ◽  
Author(s):  
Jean Carlet ◽  
Vincent Jarlier ◽  
Jacques Acar ◽  
Olivier Debaere ◽  
Patrick Dehaumont ◽  
...  

Abstract Background Antimicrobial resistance (AMR) is a serious threat to humanity. This paper describes the French efforts made since 2001 and presents data on antimicrobial consumption (AC) and AMR. Methods We gathered all data on AC and AMR recorded since 2001 from different national agencies, transferred on a regular basis to standardized European data on AC and resistance in both humans and animals. Results After a large information campaign implemented in France from 2001 to 2005 in humans, AC in the community decreased significantly (18% to 34% according to the calculation method used). It remained at the same level from 2005 to 2010 and increased again from 2010 to 2018 (8%). Contrasting results were observed for AMR. The resistance of Staphylococcus aureus decreased significantly. For gram-negative bacilli, the results were variable according to the microorganism. The resistance of Enterobacteriaceae to third-generation cephalosporins increased, remaining moderate for Escherichia coli (12% in 2017) but reaching 35% in the same year for Klebsiella pneumoniae. Resistance to carbapenems in those 2 microorganisms remained below 1%. Both global AC and resistance to most antibiotics decreased significantly in animals. Conclusions Antibiotic consumption decreased significantly in France after a large public campaign from 2001 to 2005, but this positive effect was temporary. The effect on AMR varied according to the specific microorganism: The effect was very impressive for gram-positive cocci, variable for gram-negative bacilli, and moderate for E. coli, but that for K. pneumoniae was of concern. The consumption of and resistance to antibiotics decreased significantly in animals.


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