In vitro 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

2017 ◽  
Vol 88 (2) ◽  
pp. 171-176 ◽  
Author(s):  
Sibylle H. Lob ◽  
Meredith A. Hackel ◽  
Krystyna M. Kazmierczak ◽  
Daryl J. Hoban ◽  
Katherine Young ◽  
...  
Keyword(s):  
United States ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
The United States ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Lower Respiratory Tract Infections ◽  
Gram Negative ◽  
Tract Infections

scholarly journals 709. Activity of Key β-Lactam Agents Against Gram-Negative Bacilli From ICU Patients with Lower Respiratory Tract Infections, SMART United States 2015–2017

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S255-S255
Author(s):  
Sibylle Lob ◽  
Krystyna Kazmierczak ◽  
Daryl Hoban ◽  
Meredith Hackel ◽  
Katherine Young ◽  
...  
Keyword(s):  
United States ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
The United States ◽  
Surveillance Program ◽  
Lower Respiratory Tract Infections ◽  
Icu Patients ◽  
Gram Negative ◽  
Tract Infections

Abstract 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 program from patients with lower respiratory tract infections (RTI) in ICUs, where antimicrobial resistance is typically higher than in non-ICU wards. Methods In 2015–2017, 26 hospitals in the United States each collected up to 100 consecutive Gram-negative pathogens from RTI per year. Antimicrobial susceptibility was determined for 1,298 non-Proteeae Enterobacteriaceae (NPE) and 638 P. aeruginosaisolates collected in ICUs, using CLSI broth microdilution and breakpoints; for comparison purposes, the IMI susceptible breakpoint was applied to IMI/REL. Proteeae were excluded due to intrinsic nonsusceptibility to IMI. Susceptibility was calculated for the 4 United States census regions and overall. Results Susceptibility of NPE was lowest in the Midwest to ceftazidime (81%) and cefepime (87%) and highest in the Northeast (88% and 94%, respectively); susceptibility to imipenem (89–93%) and piperacillin–tazobactam (86–90%) showed less variability across regions. Susceptibility of P. aeruginosa to the four agents was lowest in the West region (57–65%) and highest in the Northeast (68–76%). Susceptibilities to IMI/REL of NPE and P. aeruginosa as well as of phenotypes nonsusceptible (NS) to β-lactams are shown below. Conclusion The studied β-lactams showed some variability in activity against pathogens from RTI patients in ICUs across census regions, whereas IMI/REL maintained activity in all regions against NPE (>96%) and P. aeruginosa (90–95%). IMI/REL remained active against ≥98% of resistant phenotypes of NPE, except the imipenem-NS subset (67.5% susceptible), which was composed mainly of Serratia spp., and remained active against 77–82% of resistant phenotypes of P. aeruginosa, including 77.2% of imipenem-NS isolates. IMI/REL may provide a valuable therapeutic option for the treatment of ICU patients with respiratory tract infections caused by organisms resistant to commonly used β-lactams. Disclosures S. Lob, IHMA, Inc.: Employee, Salary. Merck: Consultant, Consulting fee. K. Kazmierczak, Merck: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary. D. Hoban, IHMA, Inc.: Employee, Salary. Merck: Consultant, Consulting fee. M. Hackel, IHMA, Inc.: Employee, Salary. Merck: Consultant, Consulting fee. K. Young, Merck: Employee and Shareholder, Dividends and Salary. M. Motyl, Merck: Employee and Shareholder, Dividends and Salary. D. Sahm, IHMA, Inc.: Employee, Salary. Merck: Consultant, Consulting fee.

scholarly journals 1587. Activity of Ceftolozane/Tazobactam against Gram-Negative Isolates from Lower Respiratory Tract Infections – SMART United States 2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S790-S791
Author(s):  
Sibylle Lob ◽  
Meredith Hackel ◽  
Daryl DePestel ◽  
Katherine Young ◽  
Mary Motyl ◽  
...  
Keyword(s):  
United States ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
The United States ◽  
Lower Respiratory Tract Infections ◽  
Independent Contractor ◽  
Gram Negative ◽  
The Us ◽  
Tract Infections

Abstract 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 States as part of the global SMART surveillance program, we evaluated the activity of C/T and comparators against gram-negative pathogens collected from patients with lower respiratory tract infections (LRTI). Methods In 2018, 24 hospitals in the US each collected up to 100 consecutive aerobic or facultative gram-negative bacilli (GNB) from LRTI for a total of 1773 isolates. MICs were determined using CLSI broth microdilution and breakpoints. C/T-nonsusceptible (NS) Enterobacterales and P. aeruginosa isolates were screened by PCR and sequencing for genes encoding β-lactamases. Results The 3 most common species collected from LRTI were P. aeruginosa (35.0% of all collected GNB), K. pneumoniae (10.4%), and E. coli (9.6%). Enterobacterales and P. aeruginosa combined comprised 86.3% of all collected LRTI GNB. The activity of C/T and comparators against GNB from LRTI is shown in the table. C/T was active against 93% of Enterobacterales isolates from LRTI (activity only exceeded by meropenem and amikacin), as well as against 97% of P. aeruginosa and 94% of all Enterobacterales and P. aeruginosa combined (activity only exceeded by amikacin). C/T maintained activity against 69-83% of β-lactam-NS subsets of Enterobacterales and P. aeruginosa combined. Among 67 molecularly characterized C/T-NS Enterobacterales isolates, 19.4% carried KPC, 1.5% acquired AmpC, and 16.4% only extended-spectrum β-lactamases. No acquired β-lactamases were detected in the remaining 62.7% of isolates, of which 92.9% were species with intrinsic AmpC. Among 21 molecularly characterized C/T-NS P. aeruginosa, one isolate carried an IMP-type metallo-β-lactamase, and in the remaining isolates no acquired β-lactamases were detected. Table Conclusion With its broad coverage of Enterobacterales and P. aeruginosa, C/T can provide an important empiric therapy option for patients with LRTI in the US. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Daryl DePestel, PharmD, BCPS-ID, Merck & Co, Inc (Employee) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

scholarly journals 1609. Epidemiology and Susceptibility to Imipenem/Relebactam of Gram-Negative Pathogens from Patients with Lower Respiratory Tract Infections – SMART United States 2017-2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S799-S799
Author(s):  
Sibylle Lob ◽  
Meredith Hackel ◽  
Katherine Young ◽  
Mary Motyl ◽  
Daniel F Sahm
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Surveillance Program ◽  
Lower Respiratory Tract Infections ◽  
Independent Contractor ◽  
Gram Negative ◽  
The Us ◽  
Tract Infections

Abstract 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 (GNP) from patients with lower respiratory tract infections (LRTI), including a comparison of isolates from ICU and non-ICU wards. Methods In 2017-2018, 27 US hospitals each collected up to 100 consecutive aerobic or facultative GNP from LRTI patients per year. MICs were determined using CLSI broth microdilution and breakpoints. Results Among 3878 GNP isolates from LRTI, the most common species collected were P. aeruginosa (Psa, 33.3%), K. pneumoniae (10.9%), E. coli (10.4%), and S. marcescens (6.9%). Susceptibility of GNP is shown in the table. IMI/REL inhibited 93% of Psa and Enterobacterales, which included 174 isolates of Morganellaceae that are not expected to be susceptible to IMI or IMI/REL. S. marcescens also showed low susceptibility to IMI, with improved but still reduced activity upon addition of REL. IMI/REL inhibited 83% of all GNP combined, 7-18 percentage points higher than the comparator β-lactams. Of the tested comparators, only amikacin exceeded the activity of IMI/REL. Only Psa showed substantial differences in susceptibility between isolates from ICU (n=486) and non-ICU wards (n=611), with 63.4% and 70.2%, respectively, susceptible to IMI, 71.6/78.7% to cefepime, and 64.2/73.3% to piperacillin/tazobactam (P/T). Susceptibility to IMI/REL was high in both settings (91.4/93.6%). Among Enterobacterales, susceptibility was generally similar in ICU and non-ICU wards (IMI/REL, 92.5% in both settings; IMI, 86.3 and 87.1%, respectively; cefepime, 89.9/89.0%; P/T, 88.7/87.4%). Table Conclusion Although resistance rates have frequently been reported to be higher in ICU than non-ICU wards, this pattern was seen in the current study only among Psa isolates. IMI/REL showed activity >90% against both Enterobacterales and Psa from both ward types. These in vitro data suggest that IMI/REL could provide an important treatment option for patients with LRTI in the US, including those in ICUs. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

scholarly journals Activity of ceftolozane/tazobactam against Gram-negative isolates from patients with lower respiratory tract infections – SMART United States 2018–2019

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
James A. Karlowsky ◽  
Sibylle H. Lob ◽  
Katherine Young ◽  
Mary R. Motyl ◽  
Daniel F. Sahm
Keyword(s):  
United States ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
The United States ◽  
Lower Respiratory Tract Infections ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Broth Microdilution Method ◽  
Tract Infections

Abstract 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 aeruginosa infections. The current study summarizes 2018–2019 data from the United States on lower respiratory tract isolates of Gram-negative bacilli from the SMART global surveillance program. The CLSI reference broth microdilution method was used to determine in vitro susceptibility of C/T and comparators against isolates of P. aeruginosa and Enterobacterales. Results C/T inhibited 96.0% of P. aeruginosa (n = 1237) at its susceptible MIC breakpoint (≤4 μg/ml), including > 85% of meropenem-nonsusceptible and piperacillin/tazobactam (P/T)-nonsusceptible isolates and 76.2% of MDR isolates. Comparator agents demonstrated lower activity than C/T against P. aeruginosa: meropenem (74.8% susceptible), cefepime (79.2%), ceftazidime (78.5%), P/T (74.4%), and levofloxacin (63.1%). C/T was equally active against ICU (96.0% susceptible) and non-ICU (96.7%) isolates of P. aeruginosa. C/T inhibited 91.8% of Enterobacterales (n = 1938) at its susceptible MIC breakpoint (≤2 μg/ml); 89.5% of isolates were susceptible to cefepime and 88.0% susceptible to P/T. 67.1 and 86.5% of extended-spectrum β-lactamase (ESBL) screen-positive isolates of Klebsiella pneumoniae (n = 85) and Escherichia coli (n = 74) and 49.6% of MDR Enterobacterales were susceptible to C/T. C/T was equally active against ICU (91.3% susceptible) and non-ICU (92.6%) Enterobacterales isolates. Conclusion Data from the current study support the use of C/T as an important treatment option for lower respiratory tract infections including those caused by MDR P. aeruginosa.

scholarly journals In Vitro Activity of AR-709 against Streptococcus pneumoniae

2008 ◽  
Vol 52 (3) ◽  
pp. 1182-1183 ◽  
Author(s):  
W. T. M. Jansen ◽  
A. Verel ◽  
J. Verhoef ◽  
D. Milatovic
Keyword(s):  
Streptococcus Pneumoniae ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Lower Respiratory Tract Infections ◽  
Excellent Activity ◽  
Tract Infections

ABSTRACT We investigated the in vitro activity of AR-709, a novel diaminopyrimidine antibiotic currently in development for treatment of community-acquired upper and lower respiratory tract infections, against 151 Streptococcus pneumoniae strains from various European countries. AR-709 showed excellent activity against both drug-susceptible and multidrug-resistant pneumococci.

scholarly journals 1353. In Vitro Activity of Lefamulin (LEF) Against Bacterial Pathogens Commonly Causing Community-Acquired Bacterial Pneumonia (CABP): 2016 SENTRY Data From the United States

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S414-S414 ◽  
Author(s):  
Susanne Paukner ◽  
Robert K Flamm ◽  
Steven P Gelone ◽  
Helio S Sader
Keyword(s):  
United States ◽  
Ribosomal Subunit ◽  
The United States ◽  
Vitro Activity ◽  
Surveillance Program ◽  
Respiratory Pathogens ◽  
In Vitro Activity ◽  
Medical Centers ◽  
Tract Infections

Abstract Background LEF, the first pleuromutilin antibiotic for IV and oral use in humans, is in Phase 3 clinical trials for the treatment of CABP in adults. In the first of these to be completed, LEF demonstrated noninferiority to moxifloxacin ± linezolid. LEF inhibits bacterial translation by binding the 50S ribosomal subunit at the A- and P-sites in the peptidyl transferase center. CABP is a leading cause of infectious diseases in the United States and increasing antibacterial resistance complicates its treatment. This study investigated the in vitro activity of LEF and comparators against a contemporary set of bacterial respiratory pathogens collected in the United States. Methods Isolates (n = 1674, 1/patient) were collected from 32 medical centers in the United States as part of the SENTRY Surveillance Program. LEF and comparators were tested by CLSI broth microdilution methods, and susceptibility was determined using the CLSI (2018) breakpoints. Results LEF was the most active compound against Streptococcus pneumoniae (MIC50/90 of 0.12/0.12 µg/mL), and its activity was not affected by resistance to other antibiotic classes. S. pneumoniae isolates were susceptible to levofloxacin (99.1%) and ceftriaxone (97.7%), whereas only 53.9%, 63.9%, and 80.4% of isolates were susceptible to macrolides, penicillin (oral), and tetracycline, respectively. LEF also showed potent activity against Staphylococcus aureus (MIC50/90 of 0.06/0.12 µg/mL), including methicillin-resistant (MRSA) isolates (MIC50/90 of 0.06/0.12 µg/mL, 87.1% resistant to erythromycin), Haemophilus influenzae, (MIC50/90 of 0.5/1 µg/mL, 26.9% β-lactamase producing), and Moraxella catarrhalis (MIC50/90 0.06/0.06 µg/mL, 96.5% β-lactamase positive) (figure). Conclusion LEF displayed potent in vitro activity against a contemporary collection of respiratory pathogens from the United States. LEF was active regardless of resistance phenotype to other antibiotic classes including β-lactams, tetracyclines, or macrolides. These results further support the clinical development of lefamulin for the treatment of CABP or other respiratory tract infections. Disclosures S. Paukner, Nabriva: Employee and Shareholder, Salary. R. K. Flamm, Nabriva: Research Contractor, Research grant. S. P. Gelone, Nabriva Therapeutics: Employee, Equity, Shareholder and Salary. Achaogen: Shareholder, Equity, Shareholder. H. S. Sader, Nabriva Therapeutics: Research Contractor, Research support.

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