Katherine Young

• Merck & Co.

Background Imipenem/relebactam (IMR) combines imipenem with the β-lactamase inhibitor relebactam, an inhibitor of class A and C β-lactamases. We assessed the activity of IMR and comparators against Pseudomonas aeruginosa collected in 9 countries in the Asia/Pacific region as part of the global SMART surveillance program, with a focus on the increas...

Background Enterobacterales with multidrug-resistance (MDR) or difficult-to-treat resistance (DTR) present clinicians with limited treatment options. Imipenem/relebactam (IMR) is a combination of imipenem with relebactam, a β-lactamase inhibitor of class A and C β-lactamases. We examined the activity of IMR and comparators against isolates of non-M...

Background The proliferation of carbapenemases in many geographies has compromised the effectiveness of the carbapenem class of antimicrobials and constitutes a major clinical problem. However, carbapenems paired with β-lactamase inhibitors, like imipenem/relebactam (IMR), can restore their activity against isolates carrying some types of carbapene...

Background Hospital ward and patient age are factors that can guide in the selection of empiric therapy. Imipenem/relebactam (IMR) is a combination of imipenem with the β-lactamase inhibitor relebactam, an inhibitor of class A and C β-lactamases. Ceftolozane/tazobactam (C/T) combines ceftolozane, an anti-pseudomonal cephalosporin, with tazobactam....

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...

Objectives To assess the in vitro 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...

Objectives To investigate the activities of ceftolozane/tazobactam and imipenem/relebactam against Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa isolated from hospitalized patients in Mexico in 2017–2021. Methods MICs were determined by CLSI broth microdilution and interpreted using CLSI M100 breakpoints. β-Lactamase genes wer...

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 consecut...

Background Ongoing national and international surveillance efforts are critical components of antimicrobial stewardship, resistance monitoring, and drug development programs. In this report, we summarize the results of ceftolozane/tazobactam, imipenem/relebactam, ceftazidime/avibactam and comparator agent testing against 10 509 Enterobacterales and...

Objectives To evaluate the in vitro susceptibility of recent Gram-negative pathogens collected in South Korean medical centres to imipenem/relebactam and comparator agents. Methods From 2018 to 2021, six hospitals in South Korea each collected up to 250 consecutive, aerobic or facultative Gram-negative pathogens per year from patients with bloodst...

Background Imipenem/relebactam (IMI/REL) is a combination of imipenem/cilastatin with relebactam, an inhibitor of class A and C β-lactamases. IMI/REL is not active against metallo-β-lactamases (MBLs) or OXA-48-like carbapenemases. Using non-Morganellaceae Enterobacterales (NME) isolates collected in 9 countries in Latin America as part of the SMART...

Background Antimicrobial resistance among Pseudomonas aeruginosa is challenging with limited treatment options. Ceftolozane/tazobactam (C/T) maintains activity against P. aeruginosa resistant to commonly used β-lactams. Imipenem/relebactam (IMI/REL) can restore the activity of IMI against P. aeruginosa. C/T and IMI/REL can be affected by different...

Background Imipenem/relebactam (IMI/REL) is a combination of imipenem/cilastatin with the β-lactamase inhibitor relebactam, an inhibitor of class A and C β-lactamases. We evaluated the activity of IMI/REL and comparators against AmpC- and extended-spectrum β-lactamase (ESBL)-producing E. coli and K. pneumoniae as well as against isolates of intrins...

Background Antimicrobial resistance has been increasing among gram-negative pathogens. Carbapenem resistance is especially concerning, as carbapenems are a mainstay of therapy for resistant infections. KPC production is the most common cause of carbapenem resistance in the US, but it can also be mediated by mechanisms such as porin loss or efflux....

Objectives: To evaluate the in vitro 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 Gra...

Objectives: To determine the in vitro activities of ceftolozane/tazobactam (C/T) and comparators against Pseudomonas aeruginosa isolates cultured from hospitalized patient samples in Taiwan from 2012 to 2021 with additional focus on temporal and geographical prevalence of carbapenem-resistant P. aeruginosa (CRPA). Methods: P. aeruginosa isolates...

Objectives: To determine susceptibility profiles and β-lactamase content for ceftolozane/tazobactam-resistant and imipenem/relebactam-resistant Pseudomonas aeruginosa 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 p...

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. We report analyses of relebactam enhancement of imipenem activity against both imipenem-nonsusceptible (NS) and imipenem-susceptible (S) Pseu...

Objectives: To provide the initial description of 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 t...

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 hos...

Objectives: 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 P. aeruginosa (ICU, n=35; non-ICU, n=264) and Enterobacterales (ICU, n=129; non-ICU, n=1390) were collected in four Hong Kong hospi...

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 (23.1% from a total of 4086 P. aeruginosa isolates) collected at 32 clinical laboratories in six countrie...

Introduction. 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 Enterobacterales and Pseudomonas aeruginosa ; new agents with improved activity are needed. Gap Statement. Publication o...

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. IMI/R...

Objectives To describe the in vitro activity of imipenem/relebactam against non-Morganellaceae Enterobacterales (NME) and Pseudomonas aeruginosa 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 particip...

Background Ceftolozane is a cephalosporin specifically developed to have enhanced antibacterial activity against P. aeruginosa. Combined with tazobactam, it was approved by FDA and EMA for hospital-acquired/ventilator-associated bacterial pneumonia. We evaluated trends in the activity of ceftolozane/tazobactam (C/T) against P. aeruginosa isolates c...

Background Gram-negative pathogens with multidrug resistance (MDR) or difficult-to-treat resistance (DTR) are increasingly common, resulting in limited treatment options. These resistant pathogens are often isolated from the respiratory tract or bloodstream and can result in significant patient morbidity and mortality. Imipenem/relebactam is a comb...

Background Metallo-beta (β)-lactamases (MBLs) are in the class B group of β-lactamases due to zinc ions in the active site that are required for enzymatic activity. MK-3866 is a small molecule MBL inhibitor (MBLi) that restores antibacterial activity against resistant MBL-expressing gram-negative bacteria. Efflux is an important mechanism of antibi...

Background The Beta-Lactamase Inhibitors (BLIs) Relebactam (REL) and Avibactam (AVI) both inhibit class A and C beta-lactamases and are approved in combination with the beta-lactam antibiotics imipenem (IMI/REL) and ceftazidime (CAZ/AVI), respectively. Our goal was to evaluate the effect of these BLIs on susceptibility of Pseudomonas aeruginosa iso...

Background Antimicrobial resistance of P. aeruginosa to commonly used β-lactams is typically higher in isolates collected from ICU patients and those with hospital-acquired infections. P. aeruginosa with multidrug-resistance (MDR) or difficult-to-treat resistance (DTR) is especially challenging as clinicians have limited treatment options. Ceftoloz...

Background Imipenem/relebactam (IMR) is a combination of imipenem/cilastatin with the β-lactamase inhibitor relebactam, an inhibitor of class A and C β-lactamases. We evaluated the activity of IMR and comparators against AmpC- and extended-spectrum β-lactamase (ESBL)-producing E. coli and K. pneumoniae as well as against isolates of intrinsic AmpC-...

With the emergence and rapid spreading of NDM-1 and existence of clinically relevant VIM-1 and IMP-1, discovery of pan inhibitors targeting metallo-beta-lactamases (MBLs) became critical in our battle against bacterial infection. Concurrent with our fragment and high-throughput screenings, we performed a knowledge-based search of known metallo-beta...

Objectives: We evaluated the activity of ceftolozane/tazobactam and comparators against clinical Pseudomonas aeruginosa isolates collected for the global SMART surveillance program in ten countries in the Middle East and Africa to augment scarce standardized surveillance data in this region. Methods: MICs were determined using CLSI broth microdi...

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...

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

Rising antimicrobial resistance challenges our ability to combat bacterial infections. The problem is acute for tuberculosis (TB), the leading cause of death from infection before COVID-19. Here, we developed a framework for multiple pharmaceutical companies to share proprietary information and compounds with multiple laboratories in the academic a...

Natural products provide a rich source of potential antimicrobials for treating infectious diseases for which drug resistance has emerged. Foremost among these diseases is tuberculosis. Assessment of the antimycobacterial activity of nargenicin, a natural product that targets the replicative DNA polymerase of Staphylococcus aureus, revealed that it...

Objectives . To determine the prevalence of ESBL non-CRE (carbapenem-resistant Enterobacterales) phenotype isolates among clinical isolates of Escherichia coli and Klebsiella pneumoniae collected in 2018-2019 for the SMART global surveillance program and to review trends in prevalence over 5 years (2015-2019). Methods . MICs were determined by CLS...

Background Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor approved by FDA and EMA for complicated urinary tract (cUTI) and complicated intraabdominal infections (cIAI), as well as hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) in patients ≥18 years. Clinical trials stu...

Background Ceftolozane/tazobactam (C/T), an antipseudomonal cephalosporin combined with a β-lactamase inhibitor, was approved for treatment of complicated urinary tract (cUTI) and intraabdominal infections (cIAI), and hospital-acquired/ventilator-associated bacterial pneumonia (HAP/VAP). Imipenem/relebactam (IMI/REL) is a combination of imipenem/ci...

Background Ceftolozane is a cephalosporin specifically developed to have enhanced antibacterial activity against P. aeruginosa. Combined with tazobactam, it was approved by FDA and EMA for complicated urinary tract and intraabdominal infections, as well as hospital-acquired/ventilator-associated bacterial pneumonia. We evaluated the activity of cef...

Background Relebactam (REL) inhibits class A and C β-lactamases (BLs) and is approved in the US in the combination imipenem/cilastatin/REL (IMI/REL) for hospital acquired bacterial pneumonia (HABP) and ventilator associated bacterial pneumonia (VABP), and also in patients with limited treatment options for complicated urinary tract infections and c...

Background ICUs are considered hotspots of antimicrobial resistance. Treatment of ICU patients with infections caused by P. aeruginosa (Pa) is especially challenging. When patients fail to improve on therapy with first-line antipseudomonal agents such as piperacillin/tazobactam (P/T) or cefepime (FEP), clinicians often escalate to a carbapenem. Cef...

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...

In the phase III RESTORE‐IMI 2 study (ClinicalTrials.gov: NCT02493764), the combination antibacterial agent imipenem/cilastatin/relebactam (IMI/REL) demonstrated noninferiority to piperacillin/tazobactam for the end points of all‐cause mortality at day 28 and favorable clinical response at the early follow‐up visit in adult participants with gram‐n...

Natural products provide a rich source of potential antimicrobials for use in treating infectious diseases for which drug resistance has emerged. Foremost among these is tuberculosis. Assessment of the antimycobacterial activity of nargenicin, a natural product that targets the replicative DNA polymerase of Staphylococcus aureus, revealed that it i...

Background Carbapenem-nonsusceptible and multidrug-resistant (MDR) P. aeruginosa, which are more common in patients with lower respiratory tract infections (LRTIs) and in patients in ICUs, pose difficult treatment challenges and may require new therapeutic options. Two β-lactam/β-lactamase-inhibitor combinations, ceftolozane/tazobactam (C/T) and im...

Bloodstream infections (BSI) are often caused by drug-resistant pathogens, and novel antimicrobials are needed. We examined the activity of imipenem/relebactam against BSI pathogens from US and Canada: >99% of non-Morganellaceae Enterobacterales, including 100% of MDR isolates, and >94% of Pseudomonas aeruginosa were imipenem/relebactam-susceptible...

Background Ceftolozane/tazobactam (C/T) is approved in 70 countries, including the United States, for the treatment of patients with hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible Gram-negative pathogens. C/T is of particular importance as an agent for the treatment of multidrug-resistant (MDR) Pseudomonas aer...

Background Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor approved by FDA and EMA for complicated urinary tract and intraabdominal infections, and hospital-acquired and ventilator-associated bacterial pneumonia. We evaluated the activity of C/T against isolates collected from patients ≥65 year...

Background Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor approved by FDA and EMA for hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). Elevated antimicrobial resistance rates have been reported among pathogens collected in ICUs. Using isolates collected in Asia/Paci...

Background HABP/VABP are serious infections associated with high mortality. Critically ill patients (pts) are at particularly high risk of adverse clinical outcomes. In the RESTORE-IMI 2 trial, IMI/REL was non-inferior to PIP/TAZ in primary and key secondary endpoints. We evaluated outcomes specifically in critically ill pts, according to several d...

Background Relebactam (REL) is an inhibitor of class A and C β-lactamases approved in the USA in combination with imipenem (IMI) and cilastatin for the treatment of complicated intraabdominal and urinary tract infections. Elevated antimicrobial resistance rates have been reported in ICUs. Using isolates collected in Asia/Pacific for the SMART surve...

Background IMI/REL is a combination of IMI and the novel class A and class C β-lactamase inhibitor REL. Here we present per-pathogen outcomes from a recent phase 3 clinical trial (RESTORE-IMI 2), in which IMI/REL was shown to be non-inferior to piperacillin/tazobactam (PIP/TAZ) for empiric therapy of HABP/VABP, in both primary and key secondary end...

Background Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor. C/T has been approved by the FDA and EMA for complicated urinary tract infections, complicated intraabdominal infections, and hospital-acquired and ventilator-associated bacterial pneumonia. Using isolates collected in the United State...

Background Recent data have shown high rates of resistance and co-resistance of P. aeruginosa (PsA) to traditional first-line β-lactam antibiotics (piperacillin/tazobactam, ceftazidime, cefepime, and meropenem), with < 45% susceptibility to the others when resistance to one agent is present, driving a large medical need for newer agents. We compare...

Background Relebactam (REL) inhibits class A and C β-lactamases, including KPC, and was approved in the United States combined with imipenem (IMI) and cilastatin for complicated urinary tract and intraabdominal infections. We evaluated the activity of IMI/REL against non-Morganellaceae (NME) and P. aeruginosa collected as part of the global SMART s...

Background Relebactam (REL) inhibits class A and C β-lactamases and was approved in the US combined with imipenem (IMI) and cilastatin for complicated urinary tract and intraabdominal infections. Using isolates collected as part of the global SMART surveillance program in the US, we evaluated the activity of IMI/REL against gram-negative pathogens...

Background Relebactam (REL) inhibits class A and C β-lactamases and was approved in the USA in combination with imipenem (IMI) and cilastatin for the treatment of complicated intraabdominal and urinary tract infections. We evaluated the activity of IMI/REL against clinical isolates collected in Asia/Pacific as part of the global SMART surveillance...

Background In the RESTORE-IMI 2 trial, imipenem/cilastatin/relebactam (IMI/REL) was non-inferior to PIP/TAZ for treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) in the primary endpoint of Day 28 all-cause mortality (D28 ACM) and the key secondary endpoint of clinical response (CR) at early follow-up (EFU; 7-14 d afte...

Our hollow-fiber infection model simulated the projected steady-state pharmacokinetics of ceftolozane and tazobactam in lung epithelial lining fluid of patients with pneumonia receiving 3 g ceftolozane/tazobactam q8h. Results confirmed previously established in vitro activity of ceftolozane/tazobactam at and above approved breakpoints against multi...

Background: Imipenem combined with the β-lactamase inhibitor relebactam has broad antibacterial activity, including against carbapenem-resistant gram-negative pathogens. We evaluated efficacy and safety of imipenem/cilastatin/relebactam in treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP). Methods: This was a rando...

Background: Studies describing the activity of imipenem/relebactam against gram-negative bacilli (GNB) isolated from pediatric patients are lacking in the peer-reviewed literature. We address this deficiency by reporting on GNB tested against imipenem/relebactam as part of the Study for Monitoring Antimicrobial Resistance Trends global surveillanc...

Background: The RESTORE-IMI 1 phase 3 trial (NCT02452047) demonstrated efficacy and safety of imipenem/cilastatin (IMI) combined with relebactam (REL) for treating imipenem-nonsusceptible infections. The objective of this analysis was to compare outcomes among patients meeting eligibility requirements based on central laboratory susceptibility vers...

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 which focuses on treatment-limiting...

Introduction. Infections attributable to carbapenem-resistant Gram-negative bacilli are increasing globally. New antimicrobial agents are urgently needed to treat patients with these infections.Aim. To describe susceptibility to the novel carbapenem-β-lactamase inhibitor combination imipenem-relebactam and comparators of clinical isolates of non-Pr...

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. For this report, the activity of imipenem-relebactam was assessed against Gram-negative bacilli from intraabdominal infections (IAIs) and urinary tract...

β-lactam- and multidrug-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 United States Food and Drug A...

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 surve...

Background Ceftolozane–tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor. The combination was cleared by FDA and EMA and is approved in the United States and over 60 countries worldwide. Using clinical isolates collected in the United States and Canada as part of the global SMART surveillance program, we com...

Background Ceftolozane-tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor. The combination was cleared by FDA and EMA and is approved in the United States and over 60 countries worldwide. Relebactam (REL) is an inhibitor of class A and C β-lactamases that is in clinical development in combination with imipene...

Relebactam is a small‐molecule β‐lactamase inhibitor developed as a fixed‐dose combination with imipenem/cilastatin. The pharmacokinetics of relebactam and imipenem across 10 clinical studies were analyzed using data from adult healthy volunteers and patients with bacterial infections. Renal function estimated by creatinine clearance significantly...

Background: The β-lactamase inhibitor relebactam can restore imipenem activity against imipenem-nonsusceptible gram-negative pathogens. We evaluated imipenem/relebactam for treating imipenem-nonsusceptible infections. Methods: Randomized, controlled, double-blind, phase 3 trial. Hospitalized patients with hospital-acquired/ventilator-associated...

Objectives: Relebactam is a small molecule β-lactamase inhibitor under clinical investigation for use as a fixed-dose combination with imipenem/cilastatin. Here we present a translational pharmacokinetic/pharmacodynamic mathematical model to support optimal dose selection of relebactam. Methods: Data derived from in vitro checkerboard and hollow...

Background: The prevalence of antibiotic resistance is increasing, and multidrug-resistant Pseudomonas aeruginosa has been identified as a serious threat to human health. The production of β-lactamase is a key mechanism contributing to imipenem resistance in P. aeruginosa. Relebactam is a novel β-lactamase inhibitor, active against class A and C β...

Objectives: Infections caused by Pseudomonas aeruginosa are often difficult to treat. Knowledge of the risk of infection with resistant P. aeruginosa would allow more discriminatory prescribing of broad-spectrum antimicrobials. Using clinical isolates collected as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART), we examine...

Objectives: Relebactam is a diazabicyclooctane non-β-lactam inhibitor of Ambler class A and C β-lactamases that is in clinical development in combination with imipenem/cilastatin. The current study evaluated the in vitro activity of imipenem/relebactam against 5447 isolates of Pseudomonas aeruginosa submitted to the SMART global surveillance progr...

A total of 2732 isolates of Pseudomonas aeruginosa collected at 26 United States clinical laboratories in 2015–2017 were tested for susceptibility to imipenem-relebactam. Imipenem-relebactam MICs were interpreted using 2018 CLSI M100 imipenem breakpoints for P. aeruginosa. A total of 93.9% of P. aeruginosa isolates were susceptible to imipenem-rele...

Objective Our aim was to identify natural products with anti-tubercular activity. ResultsA set of ~ 500 purified natural product compounds was screened for inhibition against the human pathogen Mycobacterium tuberculosis. A series of cyclic hexapeptides with anti-tubercular activity was identified. Five analogs from a set of sixteen closely related...

Background Clinical trials of new antibacterial agents in patients with carbapenem-resistant infections are critical but challenging to conduct. One challenge is identifying the study population by microbiological (micro) criteria; patients need to be identified locally to initiate effective treatment rapidly, but data standardization requires cent...

Background Relebactam (REL), formerly MK-7655, is a β-lactamase inhibitor of class A and C β-lactamases that is in clinical development in combination with imipenem (IMI). In this study, we evaluated the activity of IMI/REL against Gram-negative bacilli and resistant phenotypes collected in the United States as part of the SMART surveillance progra...

Background Relebactam (REL), formerly MK-7655, is a β-lactamase inhibitor of class A and C β-lactamases that is in development in combination with imipenem (IMI). In this study, we evaluated the activity of IMI/REL against recent clinical isolates of Gram-negative bacilli (GNB) collected globally as part of the SMART surveillance program. Methods...

Antimicrobial resistance among Enterobacteriaceae has been increasing globally especially due to extended-spectrum-β-lactamases (ESBLs), which typically necessitate the use of carbapenems for treatment of serious infections. Emerging carbapenem-resistant Enterobacteriaceae further complicate therapy. As part of the Study for Monitoring Antimicrobia...

The World Health Organization has identified antimicrobial resistance as a global public health threat as the prevalence and spread of antibiotic resistance among bacterial pathogens worldwide are staggering. Carbapenems, such as imipenem and meropenem have been used to treat multidrug-resistant bacteria; however, since the development of resistanc...

Objectives: Relebactam inhibits Ambler class A and C β-lactamases. Imipenem-relebactam has completed one Phase III clinical study of patients infected with imipenem-nonsusceptible gram-negative bacilli. Two more Phase III clinical studies are in progress for the treatment of patients with hospital-acquired and ventilator-associated bacterial pneum...

Relebactam is a non-β-lactam, bicyclic diazabicyclooctane β-lactamase inhibitor of class A and class C β-lactamases, including Klebsiella pneumoniae carbapenemases (KPCs). It is in phase 3 clinical development in combination with imipenem/cilastatin. The in vitro activities of imipenem-relebactam, imipenem, and comparators were determined using the...

Objectives: Antimicrobial resistance is increasing worldwide and is especially problematic in intensive care units (ICUs). Relebactam is a new bicyclic diazabicyclooctane β-lactamase-inhibitor of class A and C β-lactamases that is in development in combination with imipenem. This study describes geographical resistance patterns among isolates from...

Resistance to antibiotics among bacterial pathogens is rapidly spreading and therapeutic options against multidrug-resistant bacteria are limited. There is an urgent need for new drugs, especially those that can circumvent the broad array of resistance pathways that bacteria have evolved. In this study, we assessed the pharmacokinetic/pharmacodynam...

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...

A set of ∼500 purified natural product compounds was screened for inhibition against the human pathogen Mycobacterium tuberculosis. A series of cyclic hexapeptides with anti-tubercular activity was identified. Five analogs from a set of sixteen closely related compounds were active, with minimum inhibitory concentrations ranging from 2.3-8.9 μM. El...

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 Klebsiel...