scholarly journals 679. In vitro Activity of Cefiderocol (CFDC), a Novel Siderophore Cephalosporin, Against Difficult-to-Treat-Resistant (DTR) Gram-Negative Bacterial Pathogens From the Multi-National Sentinel Surveillance Study, SIDERO-WT (2014–2017)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S309-S310 ◽  
Author(s):  
Christopher Longshaw ◽  
Masakatsu Tsuji ◽  
Meredith M Hackel ◽  
Daniel F Sahm ◽  
Yoshinori Yamano
Keyword(s):  
Treatment Options ◽  
Vitro Activity ◽  
Surveillance Study ◽  
Line Treatment ◽  
In Vitro Activity ◽  
First Line ◽  
Gram Negative ◽  
Acinetobacter Spp ◽  
First Line Treatment

Abstract Background DTR organisms are defined as nonsusceptible to all high-efficacy, low-toxicity antibiotics (penicillins, cephalosporins, carbapenems, and quinolones), leaving physicians with limited first-line treatment options. Analyses of electronic health records have shown that patients with DTR Gram-negative bacterial infections are more likely to receive inappropriate antibiotic therapy, have longer hospital stay and increased risk of mortality. CFDC is a novel parenteral siderophore cephalosporin with potent activity against aerobic Gram-negative pathogens, including carbapenem-resistant strains. We evaluated the in vitro activity of CFDC and comparators against DTR pathogens collected by the SIDERO-WT surveillance study. Methods A total of 30,459 clinical isolates of Gram-negative bacilli were systematically collected from United States, Canada, and 11 EU countries during 2014–2017. MICs were determined by broth microdilution for a panel of 7 antibiotics, including CFDC, ceftazidime–avibactam (CZA), ceftolozane–tazobactam (C/T), colistin (CST), cefepime (FEP), meropenem (MEM), and ciprofloxacin (CIP) according to CLSI guidelines. All antibiotics were tested in cation-adjusted Mueller–Hinton broth (CAMHB) except CFDC, for which iron-depleted CAMHB was used. Susceptibility was determined according to CLSI interpretive breakpoints except CST, where EUCAST breakpoints were used. DTR pathogens were defined as being nonsusceptible to FEP, MEM, and CIP according to CLSI breakpoints. Results Among 30,459 Gram-negative isolates collected between 2014 and 2017, 9.3% were nonsusceptible to FEP, MEM, and CIP and could be defined as DTR. DTR was most frequently observed in Acinetobacter spp. (55.5%), followed by Burkholderia spp. (19%), Pseudomonas aeruginosa (9.5%), and Enterobacterales (2.7%). Of the 1,173 Stenotrophomonas maltophilia tested, 97% had MEM MIC of ≥8 mg/L; however, only 2.9% could be defined as DTR. Cefiderocol was the most active antibiotic tested against DTR isolates with 94.5% DTR-Acinetobacter spp., 98.3% DTR-P. aeruginosa, and 99.8% DTR-Enterobacterales susceptible (Table 1). Conclusion CFDC demonstrated potent activity against DTR Gram-negative pathogens with limited first-line treatment options. Disclosures All authors: No reported disclosures.

scholarly journals In Vitro Activity of Cefepime against Multidrug-Resistant Gram-Negative Bacilli, Viridans Group Streptococci andStreptococcus pneumoniaefrom a Cross-Canada Surveillance Study

1999 ◽  
Vol 10 (2) ◽  
pp. 122-127 ◽  
Author(s):  
Donald E Low ◽  
Joyce de Azavedo ◽  
Canadian Bacterial Surveillance Network ◽  
Ross Davidson
Keyword(s):  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Surveillance Study ◽  
National Committee ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Resistance Rates ◽  
Viridans Group Streptococci

OBJECTIVE: To determine the in vitro activity of cefepime against multidrug-resistant Gram-negative bacilli and Gram-positive cocci obtained from an ongoing cross-Canada surveillance study.DESIGN: Clinical isolates of aerobic Gram-negative bacilli with inducible and constitutive chromosomally mediated cephalosporinases, viridans group streptococci andStreptococcus pneumoniaewere collected from laboratories serving hospitals, nursing homes and physician offices in the community from across Canada during 1996 and 1997. Laboratories were asked to submit only clinically relevant nonduplicate isolates for susceptibility testing. In vitro antimicrobial susceptibility testing was carried out on all isolates of Gram-negative and viridans group streptococci.S pneumoniaewere characterized as penicillin susceptible, intermediately resistant or highly resistant. Nonsusceptible isolates were defined as being intermediately or highly resistant (minimal inhibitory concentrations [MIC] greater than 0.06 mg/L). Only isolates ofS pneumoniaethat were nonsusceptible to penicillin were selected for further study. MICs were determined using a microbroth dilution technique according to the National Committee of Clinical Laboratory Standards.RESULTS: A total of 727 Gram-negative bacilli samples were collected. No resistance to cefepime was detected withCitrobacter freundii,Serratia marcescens,Morganella morganiiandEnterobacterspecies. Of these strains,Enterobacterspecies andC freundiiwere the most resistant to ceftazidime, cefotaxime and ceftriaxone with MIC90Sof 32 mg/L or greater and resistance rates of 6% or greater. Resistance rates ofPseudomonas aeruginosaandAcinetobacterspecies to cefepime were 4.8% and 3%, respectively. The two organisms had similar rates of resistance to ceftazidime. Less than 3% of the Gram-negative bacilli were resistant to imipenem and meropenem. There were 153 viridans group streptococci, of which 22 (14.4%) were resistant to penicillin. Of 1287S pneumoniaesamples, 193 (15%) were nonsusceptible to penicillin. Cefepime, ceftriaxone and cefotaxime had comparable activity against all isolates of viridans group streptococci andS pneumoniae.CONCLUSIONS: Cefepime demonstrated excellent in vitro activity against Gram-negative bacilli with inducible and constitutive chromosomally mediated cephalosporinases, and had equal or superior activity versus comparator beta-lactams against all isolates of viridans group streptococci andS pneumoniae.

In Vitro Activity of Imipenem/Relebactam and Ceftolozane/Tazobactam Against Clinical Isolates of Gram-negative Bacilli With Difficult-to-Treat Resistance and Multidrug-resistant Phenotypes—Study for Monitoring Antimicrobial Resistance Trends, United States 2015–2017

2020 ◽  
Author(s):  
James A Karlowsky ◽  
Sibylle H Lob ◽  
Janet Raddatz ◽  
Daryl D DePestel ◽  
Katherine Young ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
First Line ◽  
Clin Microbiol Infect ◽  
Gram Negative ◽  
Novel Approach ◽  
The Us ◽  
Urinary Isolates

Abstract Background Multidrug-resistant (MDR) bacteria are frequently defined using the criteria established by Magiorakos et al [Clin Microbiol Infect 2012;18:268–81]. Difficult-to-treat resistance (DTR) [Kadri et al, Clin Infect Dis 2018;67:1803–14] is a novel approach to defining resistance in gram-negative bacilli focusing on treatment-limiting resistance to first-line agents (all β-lactams and fluoroquinolones). Methods Clinical and Laboratory Standards Institute–defined broth microdilution minimum inhibitory concentrations (MICs) were determined for imipenem/relebactam, ceftolozane/tazobactam, and comparators against respiratory, intraabdominal, and urinary isolates of Enterobacterales (n = 10 516) and Pseudomonas aeruginosa (n = 2732) collected in 26 US hospitals in 2015–2017. Results Among all Enterobacterales, 1.0% of isolates were DTR and 15.6% were MDR; 8.4% of P. aeruginosa isolates were DTR and 32.4% were MDR. MDR rates for Enterobacterales and DTR and MDR rates for P. aeruginosa were significantly higher (P < .05) in isolates collected in intensive care units (ICUs) than in non-ICUs and in respiratory tract isolates than in intraabdominal or urinary tract isolates. In addition, 82.4% of DTR and 92.1% of MDR Enterobacterales and 62.2% of DTR and 82.2% of MDR P. aeruginosa were imipenem/relebactam-susceptible, and 1.5% of DTR and 65.8% of MDR Enterobacterales and 67.5% of DTR and 84.0% of MDR P. aeruginosa were ceftolozane/tazobactam-susceptible. Conclusions MDR phenotypes defined using the Magiorakos criteria may overcall treatment-limiting resistance in gram-negative bacilli. In the US, DTR Enterobacterales were infrequent, while MDR Enterobacterales isolates and DTR and MDR P. aeruginosa were common. Imipenem/relebactam (Enterobacterales, P. aeruginosa) and ceftolozane/tazobactam (P. aeruginosa) retained in vitro activity against most DTR and MDR isolates.

scholarly journals Collective assessment of antimicrobial susceptibility among the most common Gram-negative respiratory pathogens driving therapy in the ICU

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Pamela A Moise ◽  
Marcela Gonzalez ◽  
Irina Alekseeva ◽  
Diego Lopez ◽  
Brune Akrich ◽  
...  
Keyword(s):  
Respiratory Infections ◽  
Vitro Activity ◽  
Surveillance Program ◽  
Antibiotic Prescribing ◽  
Respiratory Pathogens ◽  
In Vitro Activity ◽  
First Line ◽  
Icu Patients ◽  
Gram Negative

Abstract Objectives To describe the pathogen predominance and to evaluate the probability of covering the most common Gram-negative pathogens collectively in both empirical and early adjustment prescribing scenarios in ICU patients with respiratory infections. Methods Data were collected from an international cohort of hospitals as part of the SMART Surveillance Program (2018). Susceptibility testing (mg/L) was performed by broth microdilution methods. Results 7171 Gram-negative respiratory isolates from adult ICU patients across 209 hospitals from 56 different countries were studied. Overall, the most common ICU respiratory pathogens isolated were Pseudomonas aeruginosa (25%), Klebsiella pneumoniae (18%), Acinetobacter baumannii (14%), and Escherichia coli (11%), with inter-regional differences among these pathogens. Among Enterobacterales, 36% were ESBL positive. When the collective susceptibility profile of this set of pathogens (P. aeruginosa plus Enterobacterales; comprising 78% of all organisms isolated) was performed, ceftolozane/tazobactam (84%), followed by meropenem (81%), provided the most reliable in vitro activity in the empirical prescribing scenario compared with other β-lactam antibiotics. P. aeruginosa co-resistance was common among first-line β-lactam antibiotics. If P. aeruginosa was non-susceptible to piperacillin/tazobactam, less than one-third were susceptible to meropenem or ceftazidime. In contrast, ceftolozane/tazobactam offered in vitro coverage in over two-thirds of these resistant pathogens. Conclusions Ceftolozane/tazobactam demonstrated high cumulative susceptibility levels and in vitro activity in both empirical and adjustment antibiotic prescribing scenarios. High frequency of co-resistance undermines reliable coverage for Gram-negative pathogens already resistant to first-line agents. Ceftolozane/tazobactam would offer additional coverage in this setting.

scholarly journals Prevalence and regional variation in meticillin-resistant Staphylococcus aureus (MRSA) in the USA and comparative in vitro activity of tigecycline, a glycylcycline antimicrobial

2007 ◽  
Vol 56 (9) ◽  
pp. 1189-1193 ◽  
Author(s):  
Debra A. Goff ◽  
Michael J. Dowzicky
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
New Hampshire ◽  
Regional Variation ◽  
Vitro Activity ◽  
Surveillance Study ◽  
In Vitro Activity ◽  
Gram Negative ◽  
The Usa

The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) is a surveillance study established in 2004 to monitor the activity of tigecycline, the first glycylcycline, and comparator agents [β-lactams (including penicillins, cephalosporins and carbapenems), glycopeptides, tetracyclines, fluoroquinolones and oxazolidinones] against Gram-positive and Gram-negative pathogens worldwide. This report examines 1692 isolates of Staphylococcus aureus collected in the continental United States between January 2004 and September 2005. Meticillin-resistant S. aureus (MRSA) accounted for 52.0 % of isolates. Prevalence of MRSA by state ranged from 12.5 % in New Hampshire to 100 % in Kentucky. All isolates were susceptible to tigecycline, linezolid and vancomycin. In vitro, tigecycline was potent against both meticillin-susceptible S. aureus (MSSA) (MIC50 and MIC90=0.12 μg ml−1) and MRSA (MIC50=0.12 μg ml−1; MIC90=0.25 μg ml−1). Only a single isolate was resistant to three or more antimicrobial classes. Ninety-six isolates (5.7 %) were susceptible to the complete antimicrobial panel.

scholarly journals Patient profiles as an aim to optimize selection in the second line setting: the role of aflibercept

2021 ◽  
Author(s):  
B. González Astorga ◽  
F. Salvà Ballabrera ◽  
E. Aranda Aguilar ◽  
E. Élez Fernández ◽  
P. García-Alfonso ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Option ◽  
Scientific Evidence ◽  
Treatment Options ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Effective Therapeutic Option ◽  
Line Setting ◽  
First Line Treatment

AbstractColorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient’s profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment.

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