Antimicrobial Activity of Imipenem/Relebactam and Comparator Agents Against Gram-Negative Isolates Collected From Pediatric Patients: SMART 2018-2022 Global Surveillance.

Objectives: To evaluate the in vitro susceptibility of recent Gram-negative pathogens collected from pediatric patients to imipenem/relebactam (IMI/REL) and comparator agents.

Methods: From 2018 to 2022 254 hospitals in 62 countries collected Enterobacterales or Pseudomonas aeruginosa isolates from patients <18 years old as part of the SMART global surveillance program. Minimum inhibitory concentrations (MIC)s were determined using CLSI broth microdilution and interpreted with 2024 CLSI breakpoints.

Susceptibility of Gram-negative pathogens collected in Israel to ceftolozane/tazobactam, imipenem/relebactam and comparators: SMART 2018-22.

Objectives: To assess the antimicrobial activity of ceftolozane/tazobactam, imipenem/relebactam and comparator agents against clinical isolates of Gram-negative bacilli collected in Israel from 2018 to 2022.

Methods: Six clinical laboratories each collected up to 250 consecutive Gram-negative isolates per year from patients with bloodstream, intra-abdominal, lower respiratory tract and urinary tract infections. MICs were determined by CLSI broth microdilution and interpreted with 2024 EUCAST breakpoints.

Activity of ceftolozane/tazobactam and imipenem/relebactam against clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected in Greece and Italy-SMART 2017-2021.

Purpose: The current study evaluated the in vitro activities of ceftolozane/tazobactam (C/T), imipenem/relebactam (IMI/REL), and comparators against recent (2017-2021) clinical isolates of gram-negative bacilli from two countries in southern Europe.

Methods: Nine clinical laboratories (two in Greece; seven in Italy) each collected up to 250 consecutive gram-negative isolates per year from lower respiratory tract, intraabdominal, urinary tract, and bloodstream infection samples. MICs were determined by the CLSI broth microdilution method and interpreted using 2022 EUCAST breakpoints.

Perspectives on the use of ceftolozane/tazobactam: a review of clinical trial data and real-world evidence.

Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are common healthcare-associated infections linked to high morbidity and mortality. Gram-negative pathogens, such as , exhibit multidrug resistance and are recognized as major public health concerns, particularly among critically ill patients with HABP/VABP. Ceftolozane/tazobactam is a novel combination antibacterial agent comprising ceftolozane (a potent antipseudomonal cephalosporin) and tazobactam (a β-lactamase inhibitor).

Activity of ceftolozane/tazobactam and imipenem/relebactam against clinical isolates of Enterobacterales and collected in central and northern Europe (Belgium, Norway, Sweden, Switzerland)-SMART 2017-21.

Objectives: To evaluate the activities of ceftolozane/tazobactam and imipenem/relebactam against clinical isolates of Gram-negative bacilli collected in four central and northern European countries (Belgium, Norway, Sweden, Switzerland) during 2017-21.

Methods: Participating clinical laboratories each collected up to 250 consecutive Gram-negative isolates per year from patients with bloodstream, intraabdominal, lower respiratory tract or urinary tract infections. MICs were determined by CLSI broth microdilution and interpreted using 2022 EUCAST breakpoints.

Susceptibility profile and β-lactamase content of global isolates resistant to ceftolozane/tazobactam and/or imipenem/relebactam-SMART 2016-21.

Objectives: To determine susceptibility profiles and β-lactamase content for ceftolozane/tazobactam-resistant and imipenem/relebactam-resistant isolates collected in eight global regions during 2016-21.

Methods: Broth microdilution MICs were interpreted using CLSI breakpoints. PCR to identify β-lactamase genes or WGS was performed on selected isolate subsets.

Participant- and Disease-Related Factors as Independent Predictors of Treatment Outcomes in the RESTORE-IMI 2 Clinical Trial: A Multivariable Regression Analysis.

Background: In the RESTORE-IMI 2 trial, imipenem/cilastatin/relebactam (IMI/REL) was noninferior to piperacillin/tazobactam in treating hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia. This post hoc analysis was conducted to determine independent predictors of efficacy outcomes in the RESTORE-IMI 2 trial, to assist in treatment decision making.

Methods: A stepwise multivariable regression analysis was conducted to identify variables that were independently associated with day 28 all-cause mortality (ACM), favorable clinical response at early follow-up (EFU), and favorable microbiologic response at end of treatment (EOT).

In vitro activity of imipenem/relebactam against non-Morganellaceae Enterobacterales and Pseudomonas aeruginosa in the Asia-Pacific region: SMART 2017-2020.

Objectives: To describe the in vitro activity of imipenem/relebactam (IMR) against non-Morganellaceae Enterobacterales (NME) and Pseudomonas aeruginosa, including piperacillin/tazobactam-nonsusceptible and meropenem-nonsusceptible isolates, infecting hospitalized patients in the Asia-Pacific region.

Methods: From 2017 to 2020, 49 clinical laboratories in nine countries in the Asia-Pacific region participated in the SMART global surveillance program and contributed 26 783 NME and 6383 P. aeruginosa.

Relebactam restores susceptibility of resistant Pseudomonas aeruginosa and Enterobacterales and enhances imipenem activity against chromosomal AmpC-producing species: analysis of global SMART 2018-2020.

Background: Carbapenem-resistant bacteria are an increasing problem in clinical practice; thus, it is important to identify β-lactamase inhibitors (e.g., relebactam) that can restore carbapenem susceptibility.

In vitro activity of imipenem/relebactam against non-Morganellaceae Enterobacterales and Pseudomonas aeruginosa in Latin America: SMART 2018‒2020.

Carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa are being isolated from patient specimens with increasing frequency in Latin America and worldwide. The current study provides an initial description of the in vitro activity of imipenem/relebactam (IMR) against non-Morganellaceae Enterobacterales (NME) and P. aeruginosa infecting hospitalized patients in Latin America.

Carbapenem resistance among Gram-negative isolates collected from patients in ICU and non-ICU hospital wards in Hong Kong: SMART 2017-2020.

Objectives: The aim of this study was to estimate carbapenem resistance in Pseudomonas aeruginosa and Enterobacterales isolated from infected patients in intensive care unit (ICU) and non-ICU hospital wards in Hong Kong.

Methods: Isolates of Pseudomonas aeruginosa (ICU, n = 35; non-ICU, n = 264) and Enterobacterales (ICU, n = 129; non-ICU, n = 1390) were collected in four Hong Kong hospitals in 2017-2020. Clinical and Laboratory Standards Institute broth microdilution minimum inhibitory concentrations (MICs) were interpreted according to Clinical and Laboratory Standards Institute 2021 M100 breakpoints.

Imipenem/cilastatin/relebactam efficacy, safety and probability of target attainment in adults with hospital-acquired or ventilator-associated bacterial pneumonia among patients with baseline renal impairment, normal renal function, and augmented renal clearance.

Objectives: To assess the relationship between renal function and efficacy/safety of imipenem/cilastatin/relebactam for the treatment of hospital-acquired/ventilator-associated pneumonia (HABP/VABP) from RESTORE-IMI 2 and determine the PTA.

Methods: Adults with HABP/VABP were randomized 1:1 to IV imipenem/cilastatin/relebactam 1.25 g or piperacillin/tazobactam 4.

In vitro activity of ceftolozane/tazobactam against multidrug-resistant Pseudomonas aeruginosa from patients in Western Europe: SMART 2017-2020.

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections compromise both empirical and definitive antimicrobial therapies. The Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program identified 943 MDR P. aeruginosa (from a total of 4086 P.

activity of imipenem/relebactam against piperacillin/tazobactam-resistant and meropenem-resistant non- and collected from patients with bloodstream, intra-abdominal and urinary tract infections in Western Europe: SMART 2018-2020.

Piperacillin/tazobactam and carbapenems are important agents for the treatment of serious Gram-negative infections in hospitalized patients. Resistance to both agents is a significant concern in clinical isolates of and ; new agents with improved activity are needed. Publication of current, region-specific data describing the activity of newer agents such as imipenem/relebactam (IMR) against piperacillin/tazobactam-resistant and carbapenem-resistant and are needed to support their clinical use.

activity of imipenem/relebactam against piperacillin/tazobactam-resistant and meropenem-resistant non-Morganellaceae Enterobacterales and collected from patients with lower respiratory tract infections in Western Europe: SMART 2018-20.

Objectives: To describe the activity of imipenem/relebactam against non-Morganellaceae Enterobacterales (NME) and recently isolated from lower respiratory tract infection samples by hospital laboratories in Western Europe.

Methods: From 2018 to 2020, 29 hospital laboratories in six countries in Western Europe participated in the SMART global surveillance programme and contributed 4414 NME and 1995 isolates. MICs were determined using the CLSI broth microdilution method and interpreted by EUCAST (2021) breakpoints.

Activity of ceftolozane/tazobactam and imipenem/relebactam against clinical gram-negative isolates from Czech Republic, Hungary, and Poland-SMART 2017-2020.

Antimicrobial susceptibility was determined for clinical gram-negative isolates from Czech Republic, Hungary, and Poland, where published data for ceftolozane/tazobactam (C/T) and imipenem/relebactam (IMI/REL) is scarce. C/T was active against 94.3% of Enterobacterales, 10-18% higher than the tested cephalosporins and piperacillin/tazobactam.

Activity of ceftolozane/tazobactam against clinical isolates of Pseudomonas aeruginosa from patients in the Middle East and Africa - Study for Monitoring Antimicrobial Resistance Trends (SMART) 2017-2020.

Objectives: We evaluated the activity of ceftolozane/tazobactam (C/T), and comparators against clinical Pseudomonas aeruginosa isolates collected for the global Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in ten countries in the Middle East and Africa to augment scarce standardized surveillance data in this region.

Methods: Minimum inhibitory concentrations (MICs) were determined using Clinical and Laboratory Standards Institute broth microdilution and interpreted with European Committee on Antimicrobial Susceptibility Testing breakpoints. P.

Use of Novel Antibiograms to Determine the Need for Earlier Susceptibility Testing and Administration for New β-Lactam/β-Lactamase Inhibitors in the United States.

Antimicrobial resistance is a global public health threat, and gram-negative bacteria, such as Enterobacterales and are particularly problematic with difficult-to-treat resistance phenotypes. To reduce morbidity and mortality, a reduction in the time to effective antimicrobial therapy (TTET) is needed, especially among critically ill patients. The antibiogram is an effective clinical tool that can provide accurate antimicrobial susceptibility information and facilitate early antimicrobial optimization, decrease TTET, and improve outcomes such as mortality, hospital length of stay, and costs.

Activity of Ceftolozane-Tazobactam, Imipenem-Relebactam, Ceftazidime-Avibactam, and Comparators against Pseudomonas aeruginosa Isolates Collected in United States Hospitals According to Results from the SMART Surveillance Program, 2018 to 2020.

Ceftolozane-tazobactam (C/T), imipenem-relebactam (IMR), and ceftazidime-avibactam (CZA) were tested against 2,531 P. aeruginosa strains isolated from patients in the United States from 2018 to 2020 as part of the SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance program. MICs were determined by CLSI broth microdilution and interpreted using CLSI M100 (2021) breakpoints.

Activity of ceftolozane/tazobactam against Gram-negative isolates among different infections in Hong Kong: SMART 2017-2019.

Ceftolozane/tazobactam was approved by the Drug Office, Department of Health, Government of the Hong Kong Special Administrative Region in 2017. Currently the activity of ceftolozane/tazobactam against Gram-negative pathogens isolated from patients in Hong Kong is undocumented. It would be prudent to document the activity of ceftolozane/tazobactam against and Enterobacterales isolated from hospitalized patients in Hong Kong.

Prevalence of ESBL non-CRE Escherichia coli and Klebsiella pneumoniae among clinical isolates collected by the SMART global surveillance programme from 2015 to 2019.

This study aimed to determine the prevalence of extended-spectrum β-lactamase (ESBL) non-carbapenem-resistant Enterobacterales (non-CRE) phenotype among clinical Escherichia coli and Klebsiella pneumoniae isolates collected in 2018-2019 for the SMART global surveillance programme and review trends in prevalence over 5 years (2015-2019). MICs were determined by CLSI reference broth microdilution. ESBL non-CRE phenotypes were defined as non-susceptible to ceftriaxone (MIC ≥ 2 μg/mL) and susceptible to ertapenem (MIC ≤ 0.

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.

Ceftolozane-tazobactam activity against clinical isolates of Pseudomonas aeruginosa from ICU patients with pneumonia: United States, 2015-2018.

Objectives: To report on the activity of ceftolozane-tazobactam and comparators against Pseudomonas aeruginosa isolates collected from hospitalized patients with pneumonia in US intensive care units (ICUs) between 2015 and 2018. Activity against all P. aeruginosa and common resistant phenotypes are described to better inform decision-making and support antimicrobial stewardship efforts.

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.

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

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.