scholarly journals 1265. In Vitro Activity of Aztreonam-Avibactam against Klebsiella pneumoniae Isolates Analyzed by Epidemic Lineage and Hypervirulence Factors Collected in China as Part of the ATLAS Global Surveillance Study in 2019

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S721-S721
Author(s):  
Mark Estabrook ◽  
Krystyna Kazmierczak ◽  
Francis Arhin ◽  
Daniel F Sahm
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Surveillance Study ◽  
In Vitro Activity ◽  
Independent Contractor ◽  
Illumina Hiseq ◽  
Carbapenem Resistant ◽  
Class D

Abstract Background Hypervirulent Klebsiella pneumoniae (hvKp), unlike classical K. pneumoniae (cKp), are often responsible for community-acquired infections in otherwise healthy individuals. The acquisition of hypervirulence genes by sequence type 11 (ST11) carbapenem-resistant (CR) Kp endemic in Asia is a grave threat. Aztreonam-avibactam (ATM-AVI) is a monobactam combined with a β-lactamase inhibitor for the treatment of infections caused by Enterobacterales isolates that carry Class A, B, C and some Class D β-lactamases. Methods 487 K. pneumoniae isolates were collected from 17 sites in China in 2019 as a part of the ATLAS global surveillance study. 220 isolates with MICs >1 µg/ml to meropenem (MEM), ceftazidime or ATM were selected for whole genome sequencing (Illumina Hiseq 2x150 bp reads). Analyses were carried out using the CLC Genomics Workbench (Qiagen). Presence of the aerobactin synthesis locus differentiated hvKp and cKp. Antimicrobial susceptibility was determined by CLSI broth microdilution. Results Of the 487 isolates, MIC90 values for ATM-AVI (0.5 µg/ml; Table) were lower than those for any comparator tested, with only two isolates testing with MIC >4 µg/ml. Of the isolates sequenced, 82/220 (37.3%) were ST11. 53/82 (64.6%) of these ST11 isolates were hvKp (ATM-AVI, MIC90 1 µg/ml; range, 0.25-4 µg/ml) and showed percentages of susceptibility < 90% to three last-line agents (0% MEM-susceptible (S); 18.9% amikacin (AMK)-S; 88.7% tigecycline (TGC)-S). Isolates of other STs (Non-ST11) were less frequently identified as hvKp (24/138, 17.4%) and more Non-ST-11 hvKp and cKp alike were S to MEM and AMK relative to isolates of ST11 (75.0-86.8% MEM-S; 83.3-96.5% AMK-S). Likewise, the ATM-AVI MIC90 value (0.25 µg/ml) was 4-fold lower for Non-ST11 isolates. Results Table Conclusion CR ST11 hvKp represented at least 10.9% of the collected Kp isolates. ATM-AVI retained potent in vitro activity against these isolates which displayed resistance to a range of last-line agents. CST and TGC also displayed some activity but are limited in utility due to nephrotoxicity and poor accumulation in blood, respectively. The spread of virulence factors leading to the complicated clinical presentation of hvKp infection into multidrug-resistant lineages warrants continued surveillance. Disclosures Mark Estabrook, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Francis Arhin, PhD, Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

scholarly journals 203. Activity of Cefepime in Combination with Taniborbactam (formerly VNRX-5133) Against Pseudomonas aeruginosa from a Global 2018-2020 Surveillance Collection

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S124-S124
Author(s):  
Meredith Hackel ◽  
Mark G G Wise ◽  
Daniel F Sahm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Efflux Pump ◽  
Active Agent ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Independent Contractor ◽  
Carbapenem Resistant ◽  
New Treatment

Abstract Background Taniborbactam is a novel cyclic boronate-based broad-spectrum β-lactamase inhibitor (BLI) with potent and selective inhibitory activity against both serine- and metallo-β-lactamases (MBLs). Taniborbactam restores the activity of cefepime (FEP) against many multidrug resistant organisms, including cephalosporin- and carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa (PA). We evaluated the in vitro activity of the investigational combination cefepime-taniborbactam and comparators against clinical isolates of PA collected during a 2018-2020 surveillance. Methods MICs of FEP with taniborbactam fixed at 4 µg/mL (FTB) and comparators were determined against 3,219 PA collected from 221 sites in 52 countries in 2018-2020. Resistant phenotypes were based on 2021 CLSI breakpoints. Acquired β-lactamase (BL) genes were identified via PCR/Sanger sequencing or whole-genome sequencing (WGS) for 516 isolates with meropenem (MEM) MIC ≥8 µg/mL, and for 94 randomly selected isolates with FEP or ceftazidime MIC ≥16 µg/mL. 186 isolates with FTB MIC ≥16 µg/mL, 16 with FTB MIC=8 µg/mL and one with FTB MIC=4 µg/mL were subjected to WGS. Results Overall, 28.7%, 26.2% and 20.3% of PA isolates were nonsusceptible (NS) to piperacillin-tazobactam (TZP), MEM or FEP, respectively (Table). FTB demonstrated potent activity (MIC50/90, 2/8 µg/mL; 94.2% inhibited at ≤8 µg/mL) against PA overall and inhibited between 63.4% (ceftazidime-avibactam [CZA] NS) and 82.1% (TZP NS) of isolates in the NS subsets compared to 0% to 69.1% S for comparators. Against the 111 strains carrying VIM or NDM MBL genes, 67.6% had FTB MICs ≤8 µg/mL, with 11.7% having FTB MICs of 16 µg/mL. Plausible explanations for elevated FTB MICs included IMP MBL genes, penicillin binding protein 3 variations, and/or possible efflux pump up-regulation. Conclusion FTB demonstrated potent in vitro activity against PA with different resistance profiles, including NS to FEP, MEM, and TZP, and to the BL/BLI combinations CZA, ceftolozane-tazobactam, and meropenem-vaborbactam. FTB was the most active agent tested against PA harboring VIM and NDM MBLs. These findings support the continued development of FTB as a potential new treatment option for challenging infections due to MDR PA. Disclosures Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Mark G G. Wise, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

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.

scholarly journals 1348. In vitro Activity of Plazomicin, a Next-Generation Aminoglycoside, Against Carbapenemase-Producing Klebsiella pneumoniae

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S412-S413
Author(s):  
Michael R Jacobs ◽  
Caryn E Good ◽  
Ayman M Abdelhamed ◽  
Daniel D Rhoads ◽  
Kristine M Hujer ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Next Generation ◽  
Aminoglycoside Resistance ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Research Grant

Abstract Background Plazomicin is a next-generation aminoglycoside with in vitro activity against multidrug-resistant Gram-negative species, including carbapenem-resistant isolates. The Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE) is a federally funded, prospective multicenter consortium of 20 hospitals from nine US healthcare systems to track carbapenem-resistant Enterobacteriaceae. Methods Minimum inhibitory concentrations (MICs) of plazomicin were determined by broth microdilution according to current CLSI guidelines against a collection of 697 carbapenem-resistant Klebsiella pneumoniae with defined carbapenem resistance mechanisms, including KPC and OXA carbapenemases. Isolates were submitted by participating CRACKLE centers. Results Carbapenemases present in study isolates included KPC-2 (n = 323), KPC-3 (n = 364), KPC-4 (n = 2), OXA-48 like (n = 7), and NDM (n = 1). Plazomicin MICs ranged from ≤0.12 to >32 mg/L, with MIC50 and MIC90 values of 0.25 and 1 mg/L, respectively (figure). MICs of 689 (98.8%) isolates were ≤4 mg/L, while MICs of the remaining eight isolates were >32 mg/L. Plazomicin MICs were related to specific carbapenemases present in isolates: of eight isolates with MICs >32 mg/L, seven contained OXA-48 like and one contained KPC-3, suggesting that these isolates possess an aminoglycoside-resistance mechanism on the same plasmid as their carbapenemase gene, such as a 16S ribosomal RNA methyltransferase, against which plazomicin is not active. Conclusion Plazomicin has good in vitro potency against a collection of carbapenemase-producing K. pneumoniae, with MIC90 value of 1 mg/L and MICs of ≤4 mg/L for 98.9% of isolates. Disclosures M. R. Jacobs, Achaogen: Investigator, Research grant. Shionogi: Investigator, Research grant. L. Connolly, Achaogen, Inc.: Consultant, Consulting fee. K. M. Krause, Achaogen: Employee, Salary. S. S. Richter, bioMerieux: Grant Investigator, Research grant. BD Diagnostics: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Hologic: Grant Investigator, Research grant. Diasorin: Grant Investigator, Research grant. Accelerate: Grant Investigator, Research grant. Biofire: Grant Investigator, Research grant. D. Van Duin, achaogen: Scientific Advisor, Consulting fee. shionogi: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Astellas: Scientific Advisor, Consulting fee. Neumedicine: Scientific Advisor, Consulting fee. Roche: Scientific Advisor, Consulting fee. T2 Biosystems: Scientific Advisor, Consulting fee.

scholarly journals Fluopsin C for Treating Multidrug-Resistant Infections: In vitro Activity Against Clinically Important Strains and in vivo Efficacy Against Carbapenemase-Producing Klebsiella pneumoniae

2019 ◽  
Vol 10 ◽  
Author(s):  
Miguel Octavio Pérez Navarro ◽  
Ane Stefano Simionato ◽  
Juan Carlos Bedoya Pérez ◽  
André Riedi Barazetti ◽  
Janaina Emiliano ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
In Vivo Efficacy

Comparison of in vitro activities of plazomicin and other aminoglycosides against clinical isolates of Klebsiella pneumoniae and Escherichia coli

2021 ◽  
Author(s):  
Gizem İnce ◽  
Hasan Cenk Mirza ◽  
Aylin Üsküdar Güçlü ◽  
Hale Gümüş ◽  
Çiğdem Erol ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Resistance Rate ◽  
Vitro Activity ◽  
Diffusion Method ◽  
In Vitro Activity ◽  
Carbapenem Resistant ◽  
Gradient Diffusion ◽  
Susceptibility Rate

Abstract Objectives To compare the in vitro activity of plazomicin and two older aminoglycosides (gentamicin and amikacin) against 180 isolates of Escherichia coli and Klebsiella pneumoniae, including subsets of 60 non-ESBL-producing, 60 ESBL-producing and 60 carbapenem-resistant (46 carrying blaOXA-48, 11 carrying blaNDM and 3 carrying blaOXA-48 and blaNDM) strains. Methods MICs of plazomicin, gentamicin and amikacin were determined by a gradient diffusion method. Gentamicin and amikacin MICs were interpreted according to CLSI criteria and EUCAST breakpoint tables. Plazomicin MICs were interpreted using FDA-defined breakpoints. Results All non-ESBL-producing and ESBL-producing isolates were susceptible to plazomicin. The plazomicin susceptibility rate (71.7%) in carbapenem-resistant isolates was significantly higher than those observed for gentamicin (45%) and amikacin (56.7% and 51.7% according to CLSI and EUCAST breakpoints, respectively). Gentamicin, amikacin and plazomicin susceptibility rates (35.6% for gentamicin; 44.4% and 37.8% for amikacin according to CLSI and EUCAST breakpoints, respectively; 64.4% for plazomicin) in carbapenem-resistant K. pneumoniae were significantly lower than those observed for carbapenem-resistant E. coli isolates (73.3% for gentamicin; 93.3% for amikacin and plazomicin). Gentamicin, amikacin and plazomicin susceptibility rates for blaNDM-positive isolates were lower than those observed for blaOXA-48-positive isolates, but differences were not statistically significant. Among the isolates that were non-susceptible to both gentamicin and amikacin, the plazomicin susceptibility rate was less than 30%. Conclusions Although plazomicin showed excellent in vitro activity against carbapenem-susceptible isolates, the plazomicin resistance rate increased to 35.6% among carbapenem-resistant K. pneumoniae and further increased to 45.5% among blaNDM-positive isolates.

scholarly journals ACHN-490, a Neoglycoside with Potent In Vitro Activity against Multidrug-Resistant Klebsiella pneumoniae Isolates

2009 ◽  
Vol 53 (10) ◽  
pp. 4504-4507 ◽  
Author(s):  
Andrea Endimiani ◽  
Kristine M. Hujer ◽  
Andrea M. Hujer ◽  
Eliana S. Armstrong ◽  
Yuvraj Choudhary ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
In Vitro Activity

ABSTRACT The in vitro activity of ACHN-490, a novel aminoglycoside (“neoglycoside”), was evaluated against 102 multidrug-resistant (MDR) Klebsiella pneumoniae strains, including a subset of 25 strains producing the KPC carbapenemase. MIC50 values for gentamicin, tobramycin, and amikacin were 8 μg/ml, 32 μg/ml, and 2 μg/ml, respectively; MIC90 values for the same antimicrobials were ≥64 μg/ml, ≥64 μg/ml, and 32 μg/ml, respectively. ACHN-490 showed an MIC50 of 0.5 μg/ml and an MIC90 of 1 μg/ml, which are significantly lower than those of comparator aminoglycosides. ACHN-490 represents a promising aminoglycoside for the treatment of MDR K. pneumoniae isolates, including those producing KPC β-lactamase.

scholarly journals In Vitro Activity of Cefotetan against ESBL-Producing Escherichia coli and Klebsiella pneumoniae Bloodstream Isolates from the MERINO Trial

2021 ◽  
Author(s):  
Adam G. Stewart ◽  
Kyra Cottrell ◽  
Andrew Henderson ◽  
Kanthi Vemuri ◽  
Michelle J. Bauer ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Severe Infection ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Carbapenem Resistant

Carbapenem antibiotics remain the treatment of choice for severe infection due to ESBL- and AmpC-producing Enterobacterales . The use of carbapenems is a major driver of the emergence of carbapenem-resistant Gram-negative bacilli, which are often resistant to most available antimicrobials.

scholarly journals 1244. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against MDR Enterobacterales and Pseudomonas aeruginosa Collected in Latin America During the ATLAS Global Surveillance Program 2018-2019

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S711-S711
Author(s):  
Sibylle Lob ◽  
Meredith Hackel ◽  
Gregory Stone ◽  
Daniel F Sahm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Latin America ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Effective Treatment Option ◽  
Independent Contractor ◽  
Class D ◽  
In Vitro Data

Abstract Background Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination that can inhibit class A, C, and some class D β-lactamases. Resistance caused by these β-lactamases often results in multidrug-resistance (MDR). This study evaluated the in vitro activity of CAZ-AVI and comparators against MDR Enterobacterales and Pseudomonas aeruginosa isolates collected from patients in Latin America. Methods Non-duplicate clinical isolates were collected in 2018-2019 in 10 countries in Latin America. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2021 and FDA (tigecycline) breakpoints. MDR was defined as resistant (R) to ≥3 of 7 sentinel drugs: amikacin (AMK), aztreonam (ATM), cefepime (FEP), colistin (CST), levofloxacin (LVX), meropenem (MEM), and piperacillin-tazobactam (TZP). Results The activity of CAZ-AVI and comparators against all isolates and MDR subsets is shown in the table. MDR rates for the studied species ranged from 16.3% among E. cloacae to 35.7% among K. pneumoniae. CAZ-AVI was active against 98% of Enterobacterales isolates and maintained activity against 74-98% of MDR isolates of the examined Enterobacterales species. Only tigecycline showed higher activity. Among P. aeruginosa, CAZ-AVI was active against 87% of all isolates and 47% of MDR isolates; no other studied drug was more active. The three most common MDR phenotypes among Enterobacterales were 1) R to ATM, FEP, and LVX (n=544, 44.8% of all MDR Enterobacterales; 100% susceptible (S) to CAZ-AVI), 2) R to ATM, FEP, LVX, and TZP (n=150, 12.4% of all MDR Enterobacterales; 99.3% S to CAZ-AVI), and 3) R to all sentinel drugs except AMK and CST (n=145, 11.9% of all MDR isolates; 78.6% S to CAZ-AVI). The three most common MDR phenotypes among P. aeruginosa were 1) R to all sentinel drugs except CST (n=85, 19.7% of all MDR isolates; 24.7% S to CAZ-AVI), 2) R to all sentinel drugs except AMK and CST (n=42, 9.7% of all MDR isolates; 66.7% S to CAZ-AVI), and 3) R to AMK, LVX, and MEM (n=37, 8.6% of all MDR isolates; 24.3% S to CAZ-AVI). Conclusion These in vitro data suggest that CAZ-AVI can be an effective treatment option for infections caused by MDR Enterobacterales and P. aeruginosa collected in Latin America. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

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