1590 - Activity of Meropenem-Vaborbactam and Single-Agent Comparators against Enterobacterales Isolates Including KPC-Producing Isolates, from European Patients Hospitalized with Pneumonia Including Ventilator-Associated Pneumonia (2014-2019)

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Presenting Author(s)

Dee Shortridge

Senior Director
JMI Laboratories
North Liberty, Iowa
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Co-Author(s)

LD

Lalitagauri M. Deshpande

Research Scientist
JMI Laboratories
North Liberty, Iowa
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Leonard R. Duncan

Associate Director
JMI Laboratories
North Liberty, IA
Disclosure: A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Dept of Health and Human Services (Research Grant or Support)
JS

Jennifer M. Streit

Surveillance Manager
JMI Laboratories
North Liberty, Iowa
Disclosure: A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)
Mariana Castanheira

Chief Scientific Officer
JMI Laboratories
North Liberty, Iowa
Disclosure: 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)

Background: Meropenem-vaborbactam (MVB) was recently approved in Europe for the treatment of complicated UTIs, including acute pyelonephritis, complicated intra-abdominal infections, hospital-acquired bacterial pneumonia, ventilator-associated pneumonia (VAP), and bacteremia. KPC-producing Enterobacterales (ENT) isolates have disseminated worldwide. We analysed the activity of MVB and single-agent comparators against 6,846 ENT isolates from patients hospitalised with pneumonia (PHP) including VAP in European hospitals (2014–2019).

Methods: Among 6,846 ENT clinical isolates from PHP collected in 40 European hospitals located in 20 countries that were susceptibility (S) tested using reference broth microdilution methods. Of the carbapenem-resistant isolates submitted to whole genome sequencing, 75 carried bla_KPC. ENT isolates were also characterized for an extended spectrum beta-lactamase (ESBL) phenotype as described (CLSI, 2020). EUCAST (2020) interpretive criteria were used. %S from patients in the intensive care unit (ICU), ICU patients with VAP, and non-ICU isolates were also analysed.

Results: The most common ENT pathogens isolated from PHP were Klebsiella pneumoniae (KPN; n=1,877) and Escherichia coli (EC; n=1,646). The %S of MVB and comparators to ENT, ICU, ICU/VAP, and non-ICU are shown in the table. Overall, 98.2% of ENT were S to MVB. For 3,218 ENT isolates from ICU patients, MVB %S was 96.6% and for 2,627 non-ICU isolates MVB %S was 98.5%. The %S of comparators for ICU vs non-ICU isolates were similar, except for levofloxacin. 29 KPC-producing isolates were from ICU (11 from VAP), 46 were from non-ICU. Most KPC-producing isolates were KPN (n=71; 54 bla_KPC-3, 16 bla_KPC-2 and 1 bla_KPC-12). 4 EC contained bla_KPC-3. KPC were from 7 countries, Italy had the highest number of KPC-producing isolates at 42 (56%). MVB inhibited 100% of KPC-producing isolates. Amikacin was the most active comparator against all ENT (94.2%S); colistin was the most active comparator against KPC-producing isolates (79.7%S).

Conclusion: These results demonstrate MVB has potent activity against ENT isolates from PHP including those producing KPC enzymes and suggest MVB is a useful treatment option for ICU and non-ICU PHP including VAP.Table 1