In vitro activity of ceftolozane/tazobactam against Gram-negative isolates collected from ICU patients with lower respiratory tract infections in seven Asian countries-SMART 2017-2019.

Objectives: Antimicrobial resistance is one of the top 10 global public-health threats. Especially high rates of resistance have been reported for isolates from ICU patients, requiring expanded treatment options in this setting. We evaluated the activity of ceftolozane/tazobactam and comparators against Gram-negative isolates collected from patients with lower respiratory tract infections (LRTIs) in ICUs in seven Asian countries.

In vitro activity of ceftazidime-avibactam against Enterobacterales and Pseudomonas aeruginosa isolates collected in Latin America as part of the ATLAS global surveillance program, 2017-2019.

The Antimicrobial Testing Leadership and Surveillance (ATLAS) global surveillance program collected clinical isolates of Enterobacterales (n = 8416) and Pseudomonas aeruginosa (n = 2521) from 41 medical centers in 10 Latin American countries from 2017 to 2019. In vitro activities of ceftazidime-avibactam and comparators were determined using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. Overall, 98.

Ceftolozane/Tazobactam and Imipenem/Relebactam Cross-Susceptibility Among Clinical Isolates of From Patients With Respiratory Tract Infections in ICU and Non-ICU Wards-SMART United States 2017-2019.

Background: Carbapenem-nonsusceptible and multidrug-resistant (MDR) , which are more common in patients with lower respiratory tract infections (LRTIs) and in patients in intensive care units (ICUs), pose difficult treatment challenges and may require new therapeutic options. Two β-lactam/β-lactamase inhibitor combinations, ceftolozane/tazobactam (C/T) and imipenem/relebactam (IMI/REL), are approved for treatment of hospital-acquired/ventilator-associated bacterial pneumonia.

Methods: The Clinical and Laboratory Standards Institute-defined broth microdilution methodology was used to determine minimum inhibitory concentrations (MICs) against isolates collected from patients with LRTIs in ICUs (n = 720) and non-ICU wards (n = 914) at 26 US hospitals in 2017-2019 as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program.

strains possessing a four amino acid YRIN insertion in PBP3 identified as part of the SIDERO-WT-2014 surveillance study.

Background: In addition to carbapenemases, dissemination of recently reported lineages possessing a four amino acid insertion in PBP3 (encoded by ) that confers reduced susceptibility to PBP3-targeted β-lactams, such as ceftazidime, can pose a threat of antimicrobial resistance.

Objectives: To evaluate genotypic and phenotypic characteristics of possessing the mutated PBP3 collected during SIDERO-WT-2014 surveillance.

Methods: A subset of 65 clinical isolates with MICs ≥2 mg/L for ceftazidime/avibactam, ceftolozane/tazobactam or cefiderocol, among a total of 1529 isolates from the multinational surveillance study, were subjected to gene analysis and antimicrobial susceptibility testing.

Epidemiology of Carbapenem Resistance Determinants Identified in Meropenem-Nonsusceptible Collected as Part of a Global Surveillance Program, 2012 to 2017.

To estimate the incidence of carbapenem-resistant (CRE), a global collection of 81,781 surveillance isolates of collected from patients in 39 countries in five geographic regions from 2012 to 2017 was studied. Overall, 3.3% of isolates were meropenem-nonsusceptible (MIC ≥2 μg/ml), ranging from 1.

Molecular characterization of clinical isolates of Enterobacterales with elevated MIC values for aztreonam-avibactam from the INFORM global surveillance study, 2012-2017.

Objectives: While aztreonam-avibactam is a potent β-lactam-β-lactamase-inhibitor combination, reduced in vitro activity against some Enterobacterales isolates has been reported. In this study, globally collected clinical isolates of Enterobacterales with elevated minimum inhibitory concentrations (MICs) for aztreonam-avibactam were examined for potential resistance mechanisms.

Methods: Isolates with aztreonam-avibactam MICs ≥8 μg/mL (n = 55: Escherichia coli, n = 38; Enterobacter cloacae, n = 10; Klebsiella pneumoniae, n = 3; others, n = 4) and <8 μg/mL (n = 18) collected for the INFORM global surveillance programme were characterized by short read whole-genome sequencing.

Longitudinal analysis of ESBL and carbapenemase carriage among Enterobacterales and Pseudomonas aeruginosa isolates collected in Europe as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance programme, 2013-17.

Objectives: To determine the spread of ESBLs and carbapenemases in Enterobacterales and Pseudomonas aeruginosa in Europe.

Methods: 45 335 Gram-negative bacilli were collected in 18 European countries as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance programme from 2013 to 2017. Antimicrobial susceptibility was determined using broth microdilution, and 9546 isolates were screened for β-lactamase genes by PCR and sequencing.

In vitro activity of ceftolozane/tazobactam against phenotypically defined extended-spectrum β-lactamase (ESBL)-positive isolates of Escherichia coli and Klebsiella pneumoniae isolated from hospitalized patients (SMART 2016).

The Clinical and Laboratory Standards Institute (CLSI)-defined broth microdilution testing method (M07, 11th edition, 2018) was used to determine MICs for ceftolozane/tazobactam and eight comparator agents against 21,952 isolates of Enterobacteriaceae submitted by 161 clinical laboratories in 51 countries in 2016 as a part of the SMART global surveillance program. MICs were interpreted using CLSI breakpoints (M100 29th edition, 2019). 89.

In-vitro activity of imipenem/relebactam and key β-lactam agents against Gram-negative bacilli isolated from lower respiratory tract infection samples of intensive care unit patients - SMART Surveillance United States 2015-2017.

β-lactam- and multi-drug-resistant (MDR) Gram-negative bacilli frequently cause lower respiratory tract infections (LRTIs) in patients housed in intensive care units (ICUs). Relebactam, a novel diazabicyclooctane inhibitor of Ambler class A and C β-lactamases, in combination with imipenem-cilastatin was approved by the US Food and Drug Administration in July 2019 for the treatment of adults with complicated intra-abdominal infections and complicated urinary tract infections. A phase III study of imipenem/relebactam for the treatment of patients with respiratory tract infections, including antimicrobial-resistant Gram-negative infections, has also been completed.

In vitro activity of imipenem/relebactam against Enterobacteriaceae and Pseudomonas aeruginosa isolated from intraabdominal and urinary tract infection samples: SMART Surveillance United States 2015-2017.

Objectives: Antimicrobial resistance, including multidrug-resistance (MDR), is increasing, especially among Gram-negative bacilli. New agents are needed to treat infections caused by these pathogens. This report assessed the activity of imipenem/relebactam against Gram-negative bacilli from intraabdominal infections (IAIs) and urinary tract infections (UTIs) submitted to the SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance programme in the United States from 2015 to 2017.

Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Latin American Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015.

The International Network for Optimal Resistance Monitoring (INFORM) global surveillance program collected clinical isolates of ( = 7,665) and ( = 1,794) from 26 medical centers in six Latin American countries from 2012 to 2015. The activity of ceftazidime-avibactam and comparators was determined for the isolates using the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method. were highly susceptible (99.

In vitro activity of cefiderocol, a siderophore cephalosporin, against a recent collection of clinically relevant carbapenem-non-susceptible Gram-negative bacilli, including serine carbapenemase- and metallo-β-lactamase-producing isolates (SIDERO-WT-2014 Study).

Cefiderocol is a siderophore cephalosporin in development for treatment of infections caused by Gram-negative bacilli, including carbapenem-resistant and multidrug-resistant isolates. β-Lactamase carriage and in vitro activity of cefiderocol were determined against 1272 meropenem-non-susceptible isolates of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii collected as part of the SIDERO-WT-2014 surveillance study. Minimum inhibitory concentration (MIC) values for cefiderocol were ≤4 µg/mL against 97.

Activity of Ceftazidime-Avibactam and Aztreonam-Avibactam against OXA-48-Carrying Enterobacteriaceae Isolated as Part of the International Network for Optimal Resistance Monitoring (INFORM) Global Surveillance Program from 2012 to 2015.

producing the Ambler class D OXA-48 carbapenemase, combined with additional resistance mechanisms, such as permeability defects or cocarriage of class A, B, or C β-lactamases, can become highly resistant to most β-lactams currently in use, including carbapenems. A total of 45,872 clinical isolates collected in 39 countries as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance study in 2012 to 2015 were tested for susceptibility to β-lactams and comparator agents using the Clinical and Laboratory Standards Institute broth microdilution methodology and screened for the presence of β-lactamases. The and genes were detected in 333 isolates across 14 species of collected in 20 countries across the globe.

In vitro activity of ceftazidime/avibactam against isolates of Pseudomonas aeruginosa collected in European countries: INFORM global surveillance 2012-15.

Objectives: The activity of ceftazidime/avibactam was assessed against 5716 Pseudomonas aeruginosa isolates collected from 96 medical centres in 18 European countries as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance programme from 2012 to 2015. Activity was analysed against subsets of isolates based on resistance phenotypes and β-lactamase content.

Methods: Antimicrobial susceptibility testing was performed by broth microdilution and β-lactamase genes were detected by PCR screening and sequencing.

In vitro activity of ceftazidime/avibactam against isolates of Enterobacteriaceae collected in European countries: INFORM global surveillance 2012-15.

Objectives: The activity of ceftazidime/avibactam was assessed against 24 750 isolates of Enterobacteriaceae collected from 96 medical centres in 18 European countries as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance programme from 2012 to 2015. Activity was analysed against subsets of isolates based on resistant phenotypes and β-lactamase content.

Methods: Antimicrobial susceptibility testing was performed using broth microdilution and the presence of β-lactamase genes in isolates of interest was determined using PCR and sequencing.

Activity of Imipenem-Relebactam against Clinical Isolates of Gram-Negative Bacilli Isolated in Hospital Laboratories in the United States as Part of the SMART 2016 Program.

Relebactam is a non-β-lactam, bicyclic diazabicyclooctane β-lactamase inhibitor of class A and class C β-lactamases, including carbapenemases (KPCs). It is in phase 3 clinical development in combination with imipenem/cilastatin. The activities of imipenem-relebactam, imipenem, and comparators were determined using the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method for isolates of ( = 3,419) and ( = 896) collected in 2016 by 21 U.

Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Asia-Pacific Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015.

The activities of ceftazidime-avibactam and comparators against 9,149 isolates of and 2,038 isolates of collected by 42 medical centers in nine countries in the Asia-Pacific region from 2012 to 2015 were determined as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance program. Antimicrobial susceptibility testing was conducted by Clinical and Laboratory Standards Institute (CLSI) broth microdilution, and isolate subset analysis was performed on the basis of the resistant phenotypes and β-lactamase content. Ceftazidime-avibactam demonstrated potent activity (MIC, ≤8 μg/ml) against all tested (99.

In vitro activity of imipenem/relebactam against Gram-negative ESKAPE pathogens isolated in 17 European countries: 2015 SMART surveillance programme.

Objectives: Relebactam is an inhibitor of class A β-lactamases, including KPC β-lactamases, and class C β-lactamases, and is currently under clinical development in combination with imipenem. The objective of the current study was to evaluate the in vitro activity of imipenem/relebactam against Gram-negative ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) submitted by clinical laboratories in 17 European countries to the Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance programme in 2015.

Prevalence of mcr-type genes among colistin-resistant Enterobacteriaceae collected in 2014-2016 as part of the INFORM global surveillance program.

A set of 908 clinically derived colistin-resistant Enterobacteriaeae isolates collected worldwide in 2014-2016 were screened for the presence of the plasmid-borne mcr-1, mcr-2, mcr-3, mcr-4 and mcr-5 genes. In total 3.2% (29/908) of the collection were positive for mcr, including 27 Escherichia coli, 1 Klebsiella pneumoniae and 1 Enterobacter cloacae.

Global survey of Klebsiella pneumoniae major porins from ertapenem non-susceptible isolates lacking carbapenemases.

Purpose: To understand the diversity of porin disruption in Klebsiella pneumoniae, the major outer membrane protein (OMP) porins, OmpK35 and OmpK36, were examined in a set of isolates that did not harbour traditional carbapenem-hydrolysing enzymes, but nevertheless tested non-susceptible to ertapenem.

Methods: A world-wide collection of Klebsiella pneumoniae isolates that were part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance project over the years 2008-2014 were characterised with regard to their β-lactamase gene carriage and potential permeability defects. Four hundred and eighty-seven isolates that did not carry carbapenemase genes, but were non-susceptible to ertapenem, were investigated by sequence analysis of the genes encoding OmpK35 and OmpK36.

Activity of Aztreonam-Avibactam against Enterobacteriaceae and Pseudomonas aeruginosa Isolated by Clinical Laboratories in 40 Countries from 2012 to 2015.

The combination of the monobactam aztreonam and the non-β-lactam β-lactamase inhibitor avibactam is currently in clinical development for the treatment of serious infections caused by metallo-β-lactamase (MBL)-producing , a difficult-to-treat subtype of carbapenem-resistant for which therapeutic options are currently very limited. The present study tested clinically significant isolates of ( = 51,352) and ( = 11,842) collected from hospitalized patients in 208 medical center laboratories from 40 countries from 2012 to 2015 for susceptibility to aztreonam-avibactam, aztreonam, and comparator antimicrobial agents using a standard broth microdilution methodology. Avibactam was tested at a fixed concentration of 4 μg/ml in combination with 2-fold dilutions of aztreonam.

Activity of Imipenem-Relebactam against Gram-Negative ESKAPE Pathogens Isolated by Clinical Laboratories in the United States in 2015 (Results from the SMART Global Surveillance Program).

Relebactam (formerly MK-7655) is an inhibitor of class A and C β-lactamases, including carbapenemase (KPC), and is currently in clinical development in combination with imipenem-cilastatin. Using Clinical and Laboratory Standards Institute (CLSI)-defined broth microdilution methodology, we evaluated the activities of imipenem-relebactam, imipenem, and seven routinely tested parenteral antimicrobial agents against Gram-negative ESKAPE pathogens (including , = 689; , = 72; , = 845; and spp., = 399) submitted by 21 clinical laboratories in the United States in 2015 as part of the SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance program.

Activity of Imipenem against Carbapenemase-Positive Enterobacteriaceae Isolates Collected by the SMART Global Surveillance Program from 2008 to 2014.

The Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program collected 103,960 isolates of from 2008 to 2014. From this isolate collection, all ertapenem-nonsusceptible isolates (MIC, ≥1 μg/ml; = 3,428) and 9,371 isolates of , , , and with an ertapenem-susceptible extended-spectrum-β-lactamase (ESBL)-positive phenotype were assessed for the presence of common carbapenemase genes using a Check-MDR CT101 microarray (Check-Points, Wageningen, the Netherlands) and published multiplex PCR assays. Testing identified 1,493 isolates that harbored a carbapenemase gene (1,485 ertapenem-nonsusceptible isolates and 8 ertapenem-susceptible ESBL-positive isolates) and accounted for 1.

Invitro activity of imipenem-relebactam against gram-negative bacilli isolated from patients with lower respiratory tract infections in the United States in 2015 - Results from the SMART global surveillance program.

The β-lactamase inhibitor relebactam inactivates class A β-lactamases, including KPC-type carbapenemases, and class C β-lactamases. Relebactam combined with imipenem is in clinical development for several indications, including hospital-acquired and ventilator-associated pneumonia. Employing CLSI-defined broth microdilution methodology, we evaluated the activities of imipenem-relebactam (using imipenem MIC breakpoints) and comparators against non-Proteeae Enterobacteriaceae (n=853) and Pseudomonas aeruginosa (n=598) isolated from lower respiratory tract infection samples in 20 hospital laboratories in the United States participating in the 2015 SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance program.

Importance of Clonal Complex 258 and IncF Plasmids among a Global Collection of Klebsiella pneumoniae with .

This study was designed to determine the global distribution of clonal complex (CC) 258 and IncFII plasmids with among 522 global carbapenemase (KPC)-producing isolates. CC258 (i.e.