scholarly journals 207. Ineffective Initial Antibiotics for Enteric Bacteremia: Does Every Hour Count with Rapid Diagnostics and Stewardship Intervention?

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S211-S212
Author(s):  
Maggie Box ◽  
Samantha Bagsic ◽  
Shaina Saiki
Keyword(s):  
Blood Culture ◽  
Treatment Success ◽  
Clinical Treatment ◽  
Rapid Diagnostics ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Mortality Difference ◽  
Mortality Incidence ◽  
Secondary Endpoints ◽  
Related Mortality

Abstract Background It has been a long-standing practice to administer broad-spectrum antibiotics early for sepsis as each hour delay is associated with increase in mortality. With increasing rates of antibiotic resistance fueled by unnecessary use of antibiotics, it is delicate to balance the benefits vs consequences of empiric carbapenem therapy. With rapid molecular blood culture diagnostics available, identification of extended-spectrum beta-lactamase (ESBL) producing bacteremia can occur within hours and therapy optimized with active stewardship intervention. With rapid diagnostics, does each hour of ineffective antibiotic therapy really count? Methods This multicenter, retrospective, cohort study compared adult inpatients with E. coli bacteremia from a urinary source who received initial effective (EA) vs ineffective antibiotics (IA). The primary outcome was clinical treatment success at day 4. Secondary endpoints included length of stay (LOS), infection-related mortality, incidence of C. difficile infection (CDI), and subgroup analysis of outcomes by ESBL (CTX-M type) vs non-ESBL. Associations with endpoints were assessed using Fisher’s Exact tests using R v. 4.0.3. Results Clinical treatment success at day 4 was higher in the EA (n = 488) vs IA (n = 119) groups (93.7% vs 86.6%, p = 0.01) and median LOS was shorter (5 [IQR 4-6] vs 5 [IQR 5-7] days, p < 0.01). There were no differences in infection-related mortality (3.1% vs 3.4%, p = 0.8), 30-day mortality (2.5% vs 2.5%, p > 0.9), or incidence of CDI (1.8% vs 0%, p = 0.3) in the EA vs IA groups, respectively. For patients on IA < 24 h vs > 24 h, there was no difference in clinical improvement at day 4 (86.7% vs 90.5%, p > 0.9) nor 30-day mortality (2.4% vs 4.8%, p = 0.4). Clinical treatment success at day 4 was higher among non-CTX-M (n = 476) vs CTX-M (n = 131) patients (93.9% vs 86.3%, p = 0.01) even among those that received initial EA (94.5% vs 83.3%, p = 0.02). Median LOS was also shorter in CTX-M vs non CTX-M (5 [IQR 4-6] vs 5 [IQR 4-8] days, p < 0.01). Conclusion There was no mortality difference among patients receiving initial EA vs IA for E. coli bacteremia with rapid molecular blood culture diagnostics with active stewardship. Therapy for patients on IE is rapidly corrected and stewardship programs can use this intervention to promote judicious use of carbapenems. Disclosures All Authors: No reported disclosures

scholarly journals Carbapenem Therapy for Bacteremia Due to Extended-Spectrum-β-Lactamase-Producing Escherichia coli or Klebsiella pneumoniae: Implications of Ertapenem Susceptibility

2012 ◽  
Vol 56 (6) ◽  
pp. 2888-2893 ◽  
Author(s):  
Nan-Yao Lee ◽  
Ching-Chi Lee ◽  
Wei-Han Huang ◽  
Ko-Chung Tsui ◽  
Po-Ren Hsueh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Content Type ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Medical Centers ◽  
Extended Spectrum ◽  
Appropriate Therapy ◽  
Related Mortality

ABSTRACTA retrospective study was conducted at two medical centers in Taiwan to evaluate the clinical characteristics, outcomes, and risk factors for mortality among patients treated with a carbapenem for bacteremia caused by extended-spectrum-beta-lactamase (ESBL)-producing organisms. A total of 251 patients with bacteremia caused by ESBL-producingEscherichia coliandKlebsiella pneumoniaeisolates treated by a carbapenem were identified. Among these ESBL-producing isolates, rates of susceptibility to ertapenem (MICs ≤ 0.25 μg/ml) were 83.8% and 76.4%, respectively; those to meropenem were 100% and 99.3%, respectively; and those to imipenem were 100% and 97.9%, respectively. There were no significant differences in the critical illness rate (P= 0.1) or sepsis-related mortality rate (P= 0.2) for patients with bacteremia caused by ESBL-producingK. pneumoniae(140 isolates, 55.8%) andE. coli(111 isolates, 44.2%). Multivariate analysis of variables related to sepsis-related mortality revealed that the presence of severe sepsis (odds ratio [OR], 15.9; 95% confidence interval [CI], 5.84 to 43.34;P< 0.001), hospital-onset bacteremia (OR, 4.65; 95% CI, 1.42 to 15.24;P= 0.01), and ertapenem-nonsusceptible isolates (OR, 5.12; 95% CI, 2.04 to 12.88;P= 0.001) were independent risk factors. The patients receiving inappropriate therapy had a higher sepsis-related mortality than those with appropriate therapy (P= 0.002), irrespective of ertapenem, imipenem, or meropenem therapy. Infections due to the ertapenem-susceptible isolates (MICs ≤ 0.25 μg/ml) were associated with a more favorable outcome than those due to ertapenem-nonsusceptible isolates (MICs > 0.25 μg/ml), if treated by a carbapenem. However, the mortality for patients with bacteremic episodes due to isolates with MICs of ≤0.5 μg/ml was similar to the mortality for those whose isolates had MICs of >0.5 μg/ml (P= 0.8). Such a finding supports the rationale of the current CLSI 2011 criteria for carbapenems forEnterobacteriaceae.

scholarly journals Minimizing Time to Optimal Antimicrobial Therapy for Enterobacteriaceae Bloodstream Infections: A Retrospective, Hypothetical Application of Predictive Scoring Tools vs Rapid Diagnostics Tests

2020 ◽  
Vol 7 (8) ◽  
Author(s):  
Laura N Cwengros ◽  
Ryan P Mynatt ◽  
Tristan T Timbrook ◽  
Robert Mitchell ◽  
Hossein Salimnia ◽  
...  
Keyword(s):  
Medical Center ◽  
Bloodstream Infections ◽  
Beta Lactamase ◽  
Rapid Diagnostics ◽  
Early Therapy ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Risk Patients ◽  
Appropriate Therapy ◽  
Scoring Tools

Abstract Background Bloodstream infections (BSIs) due to ceftriaxone (CRO)-resistant Enterobacteriaceae are associated with delays in time to appropriate therapy and worse outcomes compared with infections due to susceptible isolates. However, treating all at-risk patients with empiric carbapenem therapy risks overexposure. Strategies are needed to appropriately balance these competing interests. The purpose of this study was to compare 4 methods for achieving this balance. Methods This was a retrospective hypothetical observational study of patients at the Detroit Medical Center with monomicrobial BSIs due to E. coli, K. oxytoca, K. pneumoniae, or P. mirabilis. This study compared the effectiveness of 4 methods to predict CRO resistance at the time of organism isolation. Three methods were based on applying published extended-spectrum beta-lactamase (ESBL) scoring tools. The fourth method was based on the presence or absence of the CTX-M marker from Verigene. Results Four hundred fifty-one Enterobacteriaceae BSIs were included, 73 (16%) of which were CRO-resistant. Verigene accurately predicted ceftriaxone susceptibility for 97% of isolates, compared with 70%–81% using the scoring tools (P &lt; .001). Verigene was associated with fewer cases of treatment with CRO when the isolate was CRO-resistant (15% vs 63%–71% with scoring tools) and fewer cases of overtreatment with a carbapenem for CRO-susceptible strains (0.3% vs 10%–12%). Conclusions Verigene significantly outperformed published ESBL scoring tools for identifying CRO-resistant Enterobacteriaceae BSI. Institutions should validate scoring tools before implementation. Stewardship programs should consider adoption of rapid diagnostic tests to optimize early therapy.

scholarly journals 115. Influence of Antimicrobial Stewardship and Molecular Rapid Diagnostic Test on Antimicrobial Prescribing for Extended-spectrum Beta-lactamase and Carbapenemase-producing Bacteria in Bloodstream Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S71-S72
Author(s):  
Ashlan Kunz Coyne ◽  
Anthony Casapao ◽  
Carmen Isache ◽  
James Morales ◽  
Yvette McCarter ◽  
...  
Keyword(s):  
Blood Culture ◽  
Antimicrobial Stewardship ◽  
Antimicrobial Therapy ◽  
Bloodstream Infections ◽  
Beta Lactamase ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum ◽  
Kaplan Meier ◽  
Baseline Characteristics

Abstract Background Molecular rapid diagnostic tests (mRDT) may help expedite the time to optimal antimicrobial therapy (TTOT) for extended-spectrum beta-lactamase (ESBL)- and carbapenemase-producing bacteria in bloodstream infections (BSI). The greatest impact of mRDT appears to occur when combined with antimicrobial stewardship program (ASP) intervention. The purpose of this study was to evaluate if mRDT + ASP influences the TTOT for patients with ESBL- and carbapenemase-producing E. coli and K. pneumoniae in BSI compared to conventional microbiological methods with ASP (CONV + ASP). Methods Multicenter, retrospective, cohort study evaluating five years of patients that had a positive E. coli or K. pneumoniae blood culture determined to be ESBL- or carbapenemase-producing by mRDT and/or CONV. Patients were excluded if they had polymicrobial BSI, transferred–in with previously identified positive blood cultures, were immunosuppressed, or died before culture results. Primary outcome was TTOT defined as time from blood culture draw to start of carbapenem therapy for ESBL-producing BSI and ceftazidime-avibactam, meropenem-vaborbactam, or at least one drug active in-vitro with the most-narrow spectrum for carbapenemase-producing BSI. Secondary outcomes were time to microbial clearance (TTMC) defined as the time from index blood culture draw to the time of first negative blood culture or hospital discharge, all-cause hospital mortality, 30-, 60- and 90-day readmission rates, and Clostridioides difficile rates. Results A total of 378 patients were included for analysis. Baseline characteristics were balanced between mRDT + ASP (n=164) and CONV + ASP (n=214). Infectious diseases consults were significantly greater for CONV + ASP compared to mRDT + ASP (82.2% vs 34.8%; p&lt; 0.001). The mRDT + ASP demonstrated a statistically significant decrease in TTOT (20.5 hrs [(IQR 17.0–42.2 hrs)] vs 50.1 hrs [(IQR 27.6–77.9 hrs)]; p&lt; 0.001) and TTMC (71.9 hrs [(IQR 54.1–108.5 hrs)] vs 91.2 hrs [(IQR 64.6–134.3 hrs)]; p=0.007). Other secondary endpoints were similar between groups. Table 1. Comparison of baseline characteristics for the mRDT+ASP and CONV+ASP groups Graph 1. Kaplan Meier time to optimal antimicrobial therapy Graph 2. Kaplan Meier time to microbial clearance Conclusion Our study supports the additional benefit of mRDT to ASP on shortening the TTOT and TTMC in patients with ESBL- or carbapenemase-producing E. coli and K. pneumoniae in BSI compared to CONV + ASP. Disclosures All Authors: No reported disclosures

scholarly journals 305. Prevalence of Ceftriaxone Susceptible, Piperacillin-tazobactam Non-susceptible Escherichia coli Bacteremia in Patients with Hematologic Malignancy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S150-S150
Author(s):  
Sarah L Spitznogle ◽  
Caitlin R Rausch ◽  
Micah M Bhatti ◽  
Samuel A Shelburne ◽  
Samuel L Aitken
Keyword(s):  
Escherichia Coli ◽  
Blood Culture ◽  
Hematologic Malignancy ◽  
Cancer Center ◽  
Cell Transplant ◽  
Extended Spectrum Beta Lactamase ◽  
Adult Age ◽  
University Of Texas ◽  
E Coli ◽  
Md Anderson

Abstract Background Piperacillin-tazobactam (TZP) is common empiric and targeted therapy for gram-negative bacteremia in patients with hematologic malignancy. Resistance to TZP tends to occur concurrently with ceftriaxone (CRO) resistance; however, the prevalence of TZP nonsusceptibility in CRO susceptible Escherichia coli (E. coli) in patients with hematologic malignancy is unknown. Therefore, we sought to determine the prevalence of TZP nonsusceptible, CRO susceptible E. coli bacteremia at a cancer center. Methods This is a retrospective cohort study of adult (age &gt; 18) patients with E. coli bacteremia admitted to the Leukemia or Stem Cell Transplant (SCT) services at The University of Texas MD Anderson Cancer Center (MDACC) between 8/2016 and 7/2019. Isolates were categorized according to current CLSI resistance breakpoints. A first isolate was defined as the first positive blood culture and subsequent episodes of bacteremia were defined as any E. coli isolate obtained at least 24 hours after the first negative blood culture. Results The overall prevalence of TZP resistant CRO susceptible E. coli from 404 isolates was 7.7% and varied by service. There was a higher prevalence in the Leukemia service compared to SCT, 9.8% vs 2.5%, respectively (p &lt; 0.01). 46% of isolates were CRO nonsusceptible, of which 91% were extended-spectrum beta-lactamase (ESBL) producers, identified by Vitek 2 or Accelerate Pheno. The TZP MIC50 was 4ug/ml, MIC90 was 128ug/ml, with an MIC range of 3ug/ml to ≥ 256ug/ml. The TZP MIC distribution varied based upon CRO phenotype. In CRO susceptible isolates the MIC50 and MIC90 were 4ug/ml and 64ug/ml, respectively, compared to 8ug/ml and 128ug/ml in CRO nonsusceptible isolates (p &lt; 0.01). TZP resistance was more common in CRO nonsusceptible isolates (31.6% vs 12.0%, p &lt; 0.01) and was more frequent with subsequent episodes of bacteremia compared to the first (39.5% vs 20.1%, p &lt; 0.01). Conclusion In patients with hematologic malignancy and E. coli bacteremia, TZP resistance is common with significant variations by CRO phenotype. TZP resistance becomes more common with subsequent episodes of bacteremia compared to the first. The clinical implications and genetic cause of this phenotype is currently unknown and warrants further investigation. Disclosures All Authors: No reported disclosures

scholarly journals Multidrug-Resistant, Including Extended-Spectrum Beta Lactamase-Producing and Quinolone-Resistant, Escherichia coli Isolated from Poultry and Domestic Pigs in Dar es Salaam, Tanzania

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 406
Author(s):  
Zuhura I. Kimera ◽  
Fauster X. Mgaya ◽  
Gerald Misinzo ◽  
Stephen E. Mshana ◽  
Nyambura Moremi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Multidrug Resistant ◽  
Antibiotics Resistance ◽  
Beta Lactamase ◽  
Domestic Pigs ◽  
Extended Spectrum Beta Lactamase ◽  
Phenotypic Profile ◽  
E Coli ◽  
Extended Spectrum ◽  
Esbl Producers

We determined the phenotypic profile of multidrug-resistant (MDR) Escherichia coli isolated from 698 samples (390 and 308 from poultry and domestic pigs, respectively). In total, 562 Enterobacteria were isolated. About 80.5% of the isolates were E. coli. Occurrence of E. coli was significantly higher among domestic pigs (73.1%) than in poultry (60.5%) (p = 0.000). In both poultry and domestic pigs, E. coli isolates were highly resistant to tetracycline (63.5%), nalidixic acid (53.7%), ampicillin (52.3%), and trimethoprim/sulfamethoxazole (50.9%). About 51.6%, 65.3%, and 53.7% of E. coli were MDR, extended-spectrum beta lactamase-producing enterobacteriaceae (ESBL-PE), and quinolone-resistant, respectively. A total of 68% of the extended-spectrum beta lactamase (ESBL) producers were also resistant to quinolones. For all tested antibiotics, resistance was significantly higher in ESBL-producing and quinolone-resistant isolates than the non-ESBL producers and non-quinolone-resistant E. coli. Eight isolates were resistant to eight classes of antimicrobials. We compared phenotypic with genotypic results of 20 MDR E. coli isolates, ESBL producers, and quinolone-resistant strains and found 80% harbored blaCTX-M, 15% aac(6)-lb-cr, 10% qnrB, and 5% qepA. None harbored TEM, SHV, qnrA, qnrS, qnrC, or qnrD. The observed pattern and level of resistance render this portfolio of antibiotics ineffective for their intended use.

scholarly journals Applicability and performance of EUCAST’s rapid antimicrobial susceptibility testing (RAST) on primarily sterile body fluids in blood culture bottles in laboratory routine with total lab automation

2021 ◽  
Author(s):  
Jasmin Kaur Jasuja ◽  
Stefan Zimmermann ◽  
Irene Burckhardt
Keyword(s):  
Blood Culture ◽  
Susceptibility Testing ◽  
Reference Method ◽  
Body Fluids ◽  
E Coli ◽  
Mueller Hinton ◽  
Mueller Hinton Agar ◽  
And Performance ◽  
Sterile Body Fluids ◽  
Better Than

AbstractOptimisation of microbiological diagnostics in primarily sterile body fluids is required. Our objective was to apply EUCAST’s RAST on primarily sterile body fluids in blood culture bottles with total lab automation (TLA) and to compare results to our reference method Vitek2 in order to report susceptibility results earlier. Positive blood culture bottles (BACTEC™ Aerobic/Anaerobic/PEDS) inoculated with primarily sterile body fluids were semi-automatically subcultured onto Columbia 5% SB agar, chocolate agar, MacConkey agar, Schaedler/KV agar and Mueller-Hinton agar. On latter, cefoxitin, ampicillin, vancomycin, piperacillin/tazobactam, meropenem and ciprofloxacin were added. After 6 h, subcultures and RAST were imaged and MALDI-TOF MS was performed. Zone sizes were digitally measured and interpreted following RAST breakpoints for blood cultures. MIC values were determined using Vitek2 panels. During a 1-year period, 197 Staphylococcus aureus, 91 Enterococcus spp., 38 Escherichia coli, 11 Klebsiella pneumoniae and 8 Pseudomonas aeruginosa were found. Categorical agreement between RAST and MIC was 96.5%. Comparison showed no very major errors, 2/7 (28.6%) and 1/7 (14.3%) of major errors for P. aeruginosa and meropenem and ciprofloxacin, 1/9 (11.1%) for K. pneumoniae and ciprofloxacin, 4/69 (7.0%) and 3/43 (5.8%) for Enterococcus spp. and vancomycin and ampicillin, respectively. Minor errors for P. aeruginosa and meropenem (1/8; 12.8%) and for E. coli and ciprofloxacin (2/29; 6.5%) were found. 30/550 RAST measurements were within area of technical uncertainty. RAST is applicable and performs well for primarily sterile body fluids in blood culture bottles, partially better than blood-based RAST. Official EUCAST evaluation is needed.

scholarly journals Phenotypic and Genotypic Properties of Fluoroquinolone-Resistant, qnr-Carrying Escherichia coli Isolated from the German Food Chain in 2017

2021 ◽  
Vol 9 (6) ◽  
pp. 1308
Author(s):  
Katharina Juraschek ◽  
Carlus Deneke ◽  
Silvia Schmoger ◽  
Mirjam Grobbel ◽  
Burkhard Malorny ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Point Mutations ◽  
Beta Lactamase ◽  
Resistance Development ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
German Food ◽  
Sequence Types ◽  
Ammonium Compounds ◽  
Additional Point

Fluoroquinolones are the highest priority, critically important antimicrobial agents. Resistance development can occur via different mechanisms, with plasmid-mediated quinolone resistance (PMQR) being prevalent in the livestock and food area. Especially, qnr genes, commonly located on mobile genetic elements, are major drivers for the spread of resistance determinants against fluoroquinolones. We investigated the prevalence and characteristics of qnr-positive Escherichia (E.) coli obtained from different monitoring programs in Germany in 2017. Furthermore, we aimed to evaluate commonalities of qnr-carrying plasmids in E. coli. We found qnr to be broadly spread over different livestock and food matrices, and to be present in various sequence types. The qnr-positive isolates were predominantly detected within selectively isolated ESBL (extended spectrum beta-lactamase)-producing E. coli, leading to a frequent association with other resistance genes, especially cephalosporin determinants. Furthermore, we found that qnr correlates with the presence of genes involved in resistance development against quaternary ammonium compounds (qac). The detection of additional point mutations in many isolates within the chromosomal QRDR region led to even higher MIC values against fluoroquinolones for the investigated E. coli. All of these attributes should be carefully taken into account in the risk assessment of qnr-carrying E. coli from livestock and food.

scholarly journals Antimicrobial Resistance Genes and Diversity of Clones among ESBL- and Acquired AmpC-Producing Escherichia coli Isolated from Fecal Samples of Healthy and Sick Cats in Portugal

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 262
Author(s):  
Isabel Carvalho ◽  
Nadia Safia Chenouf ◽  
Rita Cunha ◽  
Carla Martins ◽  
Paulo Pimenta ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Public Health Problem ◽  
Phylogenetic Groups ◽  
Disk Diffusion Test ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Specific Pcr ◽  
Flight Mass Spectrometry ◽  
Antimicrobial Resistance Genes ◽  
Esbl Producers

The aim of the study was to analyze the mechanisms of resistance in extended-spectrum beta-lactamase (ESBL)- and acquired AmpC (qAmpC)-producing Escherichia coli isolates from healthy and sick cats in Portugal. A total of 141 rectal swabs recovered from 98 sick and 43 healthy cats were processed for cefotaxime-resistant (CTXR) E. coli recovery (in MacConkey agar supplemented with 2 µg/mL cefotaxime). The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) method was used for E. coli identification and antimicrobial susceptibility was performed by a disk diffusion test. The presence of resistance/virulence genes was tested by PCR sequencing. The phylogenetic typing and multilocus sequence typing (MLST) were determined by specific PCR sequencing. CTXRE. coli isolates were detected in seven sick and six healthy cats (7.1% and 13.9%, respectively). Based on the synergy tests, 11 of 13 CTXRE. coli isolates (one/sample) were ESBL-producers (ESBL total rate: 7.8%) carrying the following ESBL genes: blaCTX-M-1 (n = 3), blaCTX-M-15 (n = 3), blaCTX-M-55 (n = 2), blaCTX-M-27 (n = 2) and blaCTX-M-9 (n = 1). Six different sequence types were identified among ESBL-producers (sequence type/associated ESBLs): ST847/CTX-M-9, CTX-M-27, CTX-M-1; ST10/CTX-M-15, CTX-M-27; ST6448/CTX-M-15, CTX-M-55; ST429/CTX-M-15; ST101/CTX-M-1 and ST40/CTX-M-1. Three of the CTXR isolates were CMY-2-producers (qAmpC rate: 2.1%); two of them were ESBL-positive and one ESBL-negative. These isolates were typed as ST429 and ST6448 and were obtained in healthy or sick cats. The phylogenetic groups A/B1/D/clade 1 were detected among ESBL- and qAmpC-producing isolates. Cats are carriers of qAmpC (CMY-2)- and ESBL-producing E. coli isolates (mostly of variants of CTX-M group 1) of diverse clonal lineages, which might represent a public health problem due to the proximity of cats with humans regarding a One Health perspective.

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