scholarly journals 274. Comparison of Cefazolin Susceptibilities of Enterobacterales with an Automated Susceptibility Testing Platform versus In Vitro Antimicrobial Testing

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S138-S138
Author(s):  
Mandee Noval ◽  
Emily Heil ◽  
Paula Williams ◽  
J Kristie Johnson ◽  
Kimberly C Claeys
Keyword(s):  
Treatment Failure ◽  
Susceptibility Testing ◽  
Recurrent Infection ◽  
Bloodstream Infections ◽  
Infectious Complications ◽  
Disk Diffusion ◽  
Source Control ◽  
Testing Methods ◽  
Definitive Therapy

Abstract Background The Clinical and Laboratory Standards Institute (CLSI) revised breakpoints for cefazolin (CFZ) may be difficult to implement with current automated susceptibility testing (AST) platforms and Enterobacterales may be falsely reported as susceptible to CFZ. The possibility remains that CFZ may then be inappropriately used as definitive therapy. Methods This was a retrospective observational cohort of adult patients with Enterobacterales bloodstream infections (BSI) reported CFZ susceptible per Vitek®2 (bioMerieux, Durham NC). The primary outcome was the percentage of CFZ susceptible Enterobacterales isolates using three different susceptibility testing methods: Vitek®2 automated testing, ETEST® (bioMerieux, Durham NC), and disk diffusion. Secondary outcomes included treatment failure defined as a composite outcome of 30-day all-cause inpatient mortality, 30-day recurrent BSI, 60-day recurrent infection, or infectious complications. Results In 195 isolates reported CFZ susceptible per Vitek®2, 84 (43.1%) were CFZ susceptible using E-test vs.119 (61%) using disk diffusion (Figure 1). Rates of treatment failure were similar in both CFZ and non-CFZ groups (33.3% vs. 38.5% respectively; p=0.57). Both groups had high rates of ID consult involvement (>60%) and source control (>80%) with urinary tract being the most reported source. No difference was noted in 30-day all-cause mortality, secondary infectious complications, 30-day readmissions, or 60-day recurrent infections. A subgroup analysis of patients receiving CFZ vs. ceftriaxone suggests treatment failure was significantly less likely to occur in the setting of source control (adjusted OR 0.06; 95% CI, 0.13–0.32) and ID consult Figure 1: CFZ Susceptibilities by Testing Method Conclusion There was a large discrepancy among testing methods; additional confirmatory CFZ susceptibility testing beyond AST platforms should be considered prior to definitive use of CFZ for systemic Enterobacterales infections. Disclosures All Authors: No reported disclosures

scholarly journals 710. In Vitro Activity and Performance of Available Susceptibility Testing Methods for Eravacycline Against Carbapenem-Resistant Enterobacteriaceae (CRE)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S319-S320
Author(s):  
Chelsea E Jones ◽  
Ellen G Kline ◽  
Minh-Hong Nguyen ◽  
Cornelius J Clancy ◽  
Ryan K Shields
Keyword(s):  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Disk Diffusion ◽  
In Vitro Activity ◽  
Testing Methods ◽  
And Performance ◽  
Susceptibility Breakpoint

Abstract Background Eravacycline (ERV) is a recently-approved, fully synthetic fluorocycline agent that demonstrates broad in vitro activity against multidrug-resistant pathogens. We sought to compare the activity of ERV with minocycline (MIN) and tigecycline (TGC) against diverse CRE clinical isolates, and to evaluate the performance of commercially-available susceptibility testing methods. Methods ERV, MIN, and TGC minimum inhibitory concentrations (MICs) were determined in triplicate by broth microdilution against previously characterized CRE isolates. ERV susceptibility was also measured by disk diffusion (20 µg disk; Mast Group) and MIC test strips (MTS; Liofilchem) according to manufacturer instructions. Results 148 CRE were tested, including 92 K. pneumoniae, 32 Enterobacter spp, 11 E. coli, 5 C. freundii, 4 K. oxytoca, and 4 S. marcescens. 72% of isolates harbored blaKPC, which encoded KPC-2 (n = 33), KPC-3 (n = 48), and other KPC variants (n = 22). 77% and 19% of isolates were resistant to meropenem and ceftazidime–avibactam, respectively. By BMD, the ERV, MIN, and TGC MIC range, MIC50 and MIC90 for shown in the Table. ERV MICs were ≥2-fold lower than MIN and TGC against 99% and 43% of isolates, respectively. ERV MICs did not vary by species or KPC-subtype. ERV MICs determined by BMD and MTS were well-correlated showing 89% essential agreement (MIC within one 2-fold dilution; Figure). The rate of categorical agreement (CA) was 73%. By comparison, the CA rate between BMD and disk diffusion was 78%. By both MTS and disk diffusion methods, susceptibility results clustered on either side of the susceptibility breakpoint. 50% of disk diffusion zones clustered between 14 and 16 millimeters (mm), which is 1 mm on either side of the susceptibility breakpoint (≥15 mm). Conclusion This study confirms the in vitro activity of ERV against CRE clinical isolates, which is comparable to TGC. ERV MTS demonstrated high rates of EA, but lower rates of CA. Clinicians should be aware of the nuances of ERV susceptibility testing and recognize that the modal distribution of ERV MICs against CRE lies on either side of the susceptibility breakpoint. Disclosures All authors: No reported disclosures.

scholarly journals 165. Comparative Effectiveness of Oral Fluoroquinolones vs. β-Lactams for the Treatment of Patients with Enterobacteriaceae Bloodstream Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S107-S107
Author(s):  
Lauren Bjork ◽  
Teri Hopkins ◽  
Linda Yang ◽  
Christopher R Frei ◽  
Xavier Jones ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Primary Outcome ◽  
Adverse Drug Events ◽  
Total Duration ◽  
Bloodstream Infections ◽  
Source Control ◽  
Definitive Treatment ◽  
Oral Antibiotic ◽  
Oral Agents ◽  
Definitive Therapy

Abstract Background Fluoroquinolones (FQ) are associated with unacceptable rates of adverse drug events (ADE) and drug resistance. Safe and effective alternative oral agents are needed for definitive treatment of Enterobacteriaceae bloodstream infections (BSI). This study aims to determine whether treatment failure rates were similar in patients who received FQ or β-lactams (BL) for stepdown treatment of Enterobacteriaceae BSI. Methods We conducted a retrospective cohort study comparing oral BL vs. FQ as definitive therapy for patients with BSI due to Escherichia coli, Klebsiella spp., or Proteus spp. Eligible patients were ≥18 years old with a monomicrobial BSI treated with a single definitive oral antibiotic. Patients with a total antibiotic treatment duration of <6 or >21 days were excluded. Groups were matched based on age and gender. The primary outcome was treatment failure defined as recurrence or all-cause mortality within 90 days with a 10% non-inferiority margin. Secondary outcomes were death or recurrence within 30 and 90 days, symptomatic urinary tract infection (UTI) or BSI within 30 days, and the safety outcome of antibiotic-related ADE. Results The average age was 68 years, with 94% males. In the BL group, 80% had a urinary source of infection vs. 69% of the FQ group. The majority of patients had source control (88% of BL group vs. 83% of FQ group). The most common pathogens were E. coli (66%) and K. pneumoniae (24%). Cefpodoxime (71%) and ciprofloxacin (85%) were the most commonly used oral antibiotics. The average duration of oral therapy was 9.2 vs. 9.6 days and total duration was 14.4 vs. 13.9 days in the BL vs. FQ group, respectively. The primary outcome occurred in 15.4% of the BL group vs. 12.3% of the FQ group (P = 0.8002, RR = 0.80, 95% CI = 0.33–1.90). No deaths were directly attributed to infection. Symptomatic UTI or BSI within 30 days occurred in 20% of BL patients vs. 21.5% of FQ patients (P = 1.0000, RR = 1.07, 95% CI = 0.55–2.11). Mortality or recurrence at 30 days were similar between groups (4.6% of BL group vs. 9.2% of FQ group, P = 0.4920, RR = 2.00, 95% CI = 0.52–7.66). One FQ patient experienced an antibiotic-related ADE (C. difficile infection). Conclusion BL are non-inferior to FQ and appear to be as effective for oral step-down treatment of Enterobacteriaceae BSI without the associated risks. Disclosures All authors: No reported disclosures.

scholarly journals Comparing Quantitative and Qualitative Methods for Detecting the In Vitro Activity of Colistin against Different Gram-Negative Bacilli

2021 ◽  
Vol 8 (5) ◽  
Author(s):  
Shams N ◽  
◽  
AlHiraky H ◽  
Moulana N ◽  
Riahi M ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Susceptibility Testing ◽  
High Sensitivity ◽  
Multidrug Resistant ◽  
Disk Diffusion ◽  
Broth Microdilution ◽  
Testing Methods ◽  
Gram Negative ◽  
Phenotypic Profile

The surge in the prevalence of Multidrug-Resistant (MDR) Gram-negative bacterial infections with limited treatment led to colistin reusing to treat MDR infections. This study aimed to determine economical, simple, and reliable colistin susceptibility testing methods as an alternative to the microdilution technique. We compared seven colistin susceptibility testing methods, including quantitative and qualitative, namely: Disk diffusion, E-test, ComASPTM SensiTest Colistin, Colistin broth disk elution, and colistin agar test CHROMagarTM COL-APSE, and BD Phoenix ID/AST automated identification and susceptibility testing system to the gold standard Broth Microdilution (BMD). Whole-genome sequencing was performed on all isolates to determine if the genetic resistant factors affect the phenotypic profile of the colistin resistance. Our results revealed that disk diffusion is still an ineffective method for measuring colistin susceptibility in Gram-negative Bacilli with the highest major error (31.75%), the lowest Kappa 0 (0%), and categorical agreement (68.25%) values. Phoenix, and CompASPTM SensiTest colistin methods have remained superior in reproducibility, sturdiness, and simplicity of use, similar to the currently recommended broth microdilution procedure; with high sensitivity of 95.56%, and 97.73%, specificity of 95.24, and 100%, and Kappa values of 0.89 and 0.95, respectively. This study revealed that Phoenix, and ComASPTM SensiTest colistin methods are recommended for routine microbiology laboratories with a large workload.

scholarly journals DelafloxacinIn VitroBroth Microdilution and Disk Diffusion Antimicrobial Susceptibility Testing Guidelines: Susceptibility Breakpoint Criteria and Quality Control Ranges for an Expanded-Spectrum Anionic Fluoroquinolone

2018 ◽  
Vol 56 (8) ◽  
Author(s):  
M. A. Pfaller ◽  
R. K. Flamm ◽  
S. P. McCurdy ◽  
C. M. Pillar ◽  
D. Shortridge ◽  
...  
Keyword(s):  
Quality Control ◽  
Susceptibility Testing ◽  
Test Methods ◽  
Susceptibility Test ◽  
Disk Diffusion ◽  
Surveillance Program ◽  
Broth Microdilution ◽  
Testing Methods ◽  
Content Type

ABSTRACTDelafloxacin, a recently approved anionic fluoroquinolone, was tested within an international resistance surveillance program. Thein vitrosusceptibilities of 7,914 indicated pathogens causing acute bacterial skin and skin structure infections (ABSSSI) were determined using Clinical and Laboratory Standards Institute (CLSI) broth microdilution MIC testing methods. The U.S. Food and Drug Administration (FDA) susceptibility testing breakpoints and quality control ranges for routine broth microdilution and disk diffusion methods were confirmed. The delafloxacin MIC50/90(% susceptibility) results were as follows:Staphylococcus aureus, including methicillin-resistantS. aureus(MRSA), 0.008/0.25 μg/ml (92.8%);Staphylococcus lugdunensis, 0.016/0.03 μg/ml (99.3%);Streptococcus pyogenes, 0.016/0.03 μg/ml (100.0%);Streptococcus anginosusgroup, 0.008/0.016 μg/ml (100.0%);Enterococcus faecalis, 0.12/1 μg/ml (66.2%); andEnterobacteriaceae, 0.12/4 μg/ml (69.5%). The FDA clinical breakpoints were used to assess intermethod test agreement between delafloxacin MIC and disk diffusion methods for the indicated pathogens. The intermethod susceptibility test categorical agreement for delafloxacin was acceptable, with only 0.4% very major, false-susceptible errors amongS. aureusstrains. Across all FDA-indicated species, the selected breakpoints produced only 0.0 to 1.7% rates of serious (very major and major errors) intermethod error. Quality control ranges for these standardized delafloxacin susceptibility test methods were calculated from three multilaboratory (12 total sites) studies for six control organisms. In conclusion, the application of FDA MIC breakpoints for delafloxacin against contemporary (2014 to 2016) isolates of ABSSSI pathogens provides additional support for the use of delafloxacin in the treatment of adults with ABSSSI. Delafloxacin MIC and disk diffusion susceptibility testing methods have been standardized for clinical application, achieving high intermethod categorical agreement.

scholarly journals Effect of Obesity on Clinical Failure of Patients Treated with Beta-Lactams

2021 ◽  
Author(s):  
Nathan A Pinner ◽  
Natalie G Tapley ◽  
Katie E Barber ◽  
Kayla R Stover ◽  
Jamie L Wagner
Keyword(s):  
Treatment Failure ◽  
Clinical Outcomes ◽  
Hospital Length Of Stay ◽  
Source Control ◽  
Definitive Treatment ◽  
Therapeutic Drug ◽  
Obese Patients ◽  
Definitive Therapy ◽  
All Cause Mortality ◽  
The Impact

Abstract Background Altered pharmacokinetics in obese patients raise concerns over worse clinical outcomes. This study assessed whether obese patients receiving a beta-lactam (BL) have worse clinical outcomes compared to non-obese patients and to identify if therapeutic drug monitoring (TDM) may be beneficial. Methods This multi-center, retrospective cohort included hospitalized adults admitted from July 2015-July 2017 treated with a BL as definitive monotherapy against a Gram-negative bacilli for ≥72 hours. Patients were excluded if there was lack of source control or if polymicrobial infections required &gt;1 antibiotic for definitive therapy. Patients were classified based on body mass index (BMI): non-obese (BMI ≤29.9 kg/m 2) and obese (BMI ≥30.0 kg/m 2). The primary outcome was clinical treatment failure, and secondary were hospital length of stay (LOS), inpatient all-cause mortality, and 30-day all-cause readmission. Results There were 257 (43.6%) obese patients and 332 (56.4%) non-obese patients included. The most common infections were urinary (50.9%) and respiratory (31.4%). Definitive treatment was driven by 3 rd generation cephalosporins (46.9%) and cefepime (44.7%). Treatment failure occurred in 131 (51%) obese patients and 109 (32.8%) non-obese patients (p&lt;0.001). Obesity and respiratory source were independently associated with increased likelihood of treatment failure. Obese patients were hospitalized longer than non-obese patients (p=0.002), but no differences were found for all-cause mortality (p=0.117) or infection-related readmission (0=0.112). Conclusions Obese patients treated with BLs have higher rates of treatment failure and longer hospitalization periods than non-obese patients. Future studies are needed to assess the impact of TDM and specific dosing recommendations for targeted infection types.

scholarly journals Minimum Inhibitory Concentration Breakpoints and Disk Diffusion Inhibitory Zone Interpretive Criteria for Tilmicosin Susceptibility Testing against Pasteurella Spp. Associated with Bovine Respiratory Disease

1996 ◽  
Vol 8 (3) ◽  
pp. 337-344 ◽  
Author(s):  
Thomas R. Shryock ◽  
Donald W. White ◽  
J. Mitchell Staples ◽  
Carolyn S. Werner
Keyword(s):  
Respiratory Disease ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
Bovine Respiratory Disease ◽  
Disk Diffusion ◽  
National Committee ◽  
Pharmacokinetic Data ◽  
In Vitro Test ◽  
Disk Diffusion Testing

Tilmicosin is a novel macrolide antibiotic developed for exclusive use in veterinary medicine. The first tilmicosin-containing product was approved to treat bovine respiratory disease associated with pasteurellae. The development of antimicrobial susceptibility testing guidelines for tilmicosin was predicated on the relationship of clinical efficacy studies that demonstrated a favorable therapeutic outcome, on pharmacokinetic data, and on in vitro test data, as recommended by the National Committee for Clinical Laboratory Standards (NCCLS). The NCCLS-approved breakpoints for the MIC dilution testing are resistant ‡ 32 g/ml, intermediate 16 g/ml, and susceptible £ 8 g/ml. The zone of inhibition interpretive criteria for disk diffusion testing with a 15- g disk are resistant £ 10 mm, intermediate 11–13 mm, and susceptible ‡ 14 mm.

scholarly journals Aerococcus urinae and Aerococcus sanguinicola: Susceptibility Testing of 120 Isolates to Six Antimicrobial Agents Using Disk Diffusion (EUCAST), Etest, and Broth Microdilution Techniques

2017 ◽  
Vol 11 (1) ◽  
pp. 160-166 ◽  
Author(s):  
Derya Carkaci ◽  
Xiaohui C. Nielsen ◽  
Kurt Fuursted ◽  
Robert Skov ◽  
Ole Skovgaard ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Susceptibility Testing ◽  
Treatment Options ◽  
Disk Diffusion ◽  
Broth Microdilution ◽  
Testing Methods ◽  
European Committee ◽  
Aerococcus Urinae ◽  
Background Data ◽  
Tract Infections

Background: Aerococcus urinae and Aerococcus sanguinicola are relatively newcomers and emerging organisms in clinical and microbiological practice. Both species have worldwide been associated with urinary tract infections. More rarely cases of bacteremia/septicemia and infective endocarditis have been reported. Treatment options are therefore important. Just recently, European recommendations on susceptibility testing and interpretive criteria have been released. Objective: In this investigation 120 A. urinae and A. sanguinicola isolates were tested for susceptibility to six antimicrobial agents: Penicillin, cefotaxime, meropenem, vancomycin, linezolid, and rifampicin. Methods: Three susceptibility testing methods were used; disk diffusion according to The European Committee on Antimicrobial Susceptibility Testing (EUCAST) standardized disk diffusion methodology and MIC determination with Etest and broth microdilution (BMD). All testing was performed with EUCAST media for fastidious organisms. Results: Data obtained in this study were part of the background data for establishing EUCAST breakpoints. MIC values obtained by Etest and BMD were well correlated with disk diffusion results. Conclusion: All isolates were found susceptible to all six antimicrobial agents: penicillin, cefotaxime, meropenem, vancomycin, linezolid, and rifampicin.

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