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Objectives: Meropenem/vaborbactam has been approved in Europe for the treatment of hospital-acquired bacterial pneumonia, ventilator-associated pneumonia (VAP) and bacteraemia among other indications. Vaborbactam is an inhibitor of class A and C β-lactamases, including Klebsiella pneumoniae carbapenemase (KPC) enzymes, but not class B or D carbapenemases. We analysed the activity of meropenem/vaborbactam and comparators against 6846 Enterobacterales and 3567 Pseudomonas aeruginosa isolates from patients hospitalized with pneumonia (PHP), including VAP.Methods: Isolates from PHP were consecutively collected during 2014-19 from 42 European hospitals located in 21 countries and susceptibility tested using the broth microdilution method. Carbapenem-resistant Enterobacterales (CRE) isolates were molecularly characterized to identify their carbapenem-resistance mechanisms. EUCAST (2020) interpretive criteria were used.Results: The most common Gram-negative pathogens isolated from PHP were P. aeruginosa (n = 3567), K. pneumoniae (n = 1877) and Escherichia coli (n = 1646). Overall, 98.0% of Enterobacterales and 82.1% of P. aeruginosa were susceptible to meropenem/vaborbactam, with 99.8% of Enterobacterales and 89.7% of P. aeruginosa in Western Europe (WE) and 92.7% of Enterobacterales and 69.1% of P. aeruginosa in Eastern Europe (EE). CRE were more common in EE (15.1%) than WE (2.1%). KPC was the most common carbapenemase in WE, while OXA-48-like was the most common carbapenemase in EE. Meropenem/vaborbactam susceptibility was 63.0% for all CRE (92.2% in WE and 51.5% in EE). Meropenem/vaborbactam inhibited 99.1% of KPC-producing isolates and 40.5% of OXA-48-like-producing isolates.Conclusions: These in vitro data demonstrate that meropenem/vaborbactam has potent activity against isolates from PHP, including isolates producing KPC, and may be a useful treatment option for PHP, including VAP. [ABSTRACT FROM AUTHOR]

Background: The Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) monitors the in vitro activity of ceftolozane/tazobactam and numerous antimicrobial agents against Gram-negative bacteria worldwide.Objectives: To evaluate the activity of ceftolozane/tazobactam and resistance trends among Pseudomonas aeruginosa and Enterobacterales isolates in Europe between 2012 and 2018.Methods: P. aeruginosa (7503) and Enterobacterales (30 582) isolates were collected from 53 medical centres in 26 countries in Europe and the Mediterranean region and tested for susceptibility by reference broth microdilution method in a central laboratory. MIC results were interpreted using EUCAST criteria.Results: Ceftolozane/tazobactam was the most active compound tested against P. aeruginosa isolates after colistin, with overall susceptibility rates of 94.1% in Western Europe and 80.9% in Eastern Europe. Moreover, ceftolozane/tazobactam retained activity against 75.2% and 59.2% of meropenem-non-susceptible P. aeruginosa isolates in Western and Eastern Europe, respectively. Tobramycin was the third most active compound tested against P. aeruginosa, with susceptibility rates of 88.6% and 70.9% in Western and Eastern Europe, respectively. Ceftolozane/tazobactam was active against 94.5% of all Enterobacterales and 96.1% of meropenem-susceptible isolates from Western Europe. In Eastern Europe, ceftolozane/tazobactam was active against 79.4% of Enterobacterales overall and 86.2% of meropenem-susceptible isolates.Discussion: Antimicrobial susceptibility rates for agents commonly used to treat serious systemic infections varied widely among nations and geographic regions and were generally lower in Eastern Europe compared with Western Europe. Ceftolozane/tazobactam demonstrated potent activity against P. aeruginosa, including MDR strains, and retained activity against most meropenem-susceptible Enterobacterales causing infection in European medical centres. [ABSTRACT FROM AUTHOR]

• Gram-positive pathogens are a major cause of infections. • The dissemination of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) has reduced the therapeutic options. • Antimicrobial activity of dalbavancin and other comparators was evaluated against recent clinical isolates of Gram-positive pathogens from several European countries and Russia. • The activity of dalbavancin against Gram-positive pathogens, including MRSA, was high [ minimum concentration inhibiting 90% of isolates tested (MIC 90) ≤0.12 mg/L for all isolates except vanA- harbouring enterococci, which had MIC 90 >2 mg/L] and remained unchanged over the years. • MRSA circulating inside and between countries revealed considerable clonal heterogeneity • These data support the efficacy of dalbavancin against Gram-positive pathogens, including MRSA and uncommon species. Gram-positive pathogens remain a major cause of healthcare- and community-associated infections. In particular, the dissemination of methicillin-resistant staphylococci, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), have significantly reduced the therapeutic options, making the management of these infections even more challenging. Dalbavancin is a second-generation lipoglycopeptide approved for the treatment of moderate to severe acute bacterial skin and skin structure infections (ABSSSIs) caused by Gram-positive organisms, showing a bactericidal effect and a low propensity towards the selection of resistance over time. To evaluate the antimicrobial activity of dalbavancin and other comparators against recent clinical isolates of Gram-positive pathogens obtained from different sources and from several European countries, including countries of Southern and Eastern Europe, and Russia, where resistance rates are typically high. This study also aimed to describe the clonal relationship of MRSA strains circulating in Southern and Eastern Europe and Russia. In total, 1478 isolates were collected. Study results demonstrated the excellent and stable activity of dalbavancin against Gram-positive microorganisms, including MRSA. Interestingly, dalbavancin has retained unaltered minimum inhibitory concentration (MIC 50 and MIC 90) values over the years, and seems to have a low propensity towards the selection of resistance. These data support the potential efficacy of dalbavancin against Gram-positive bacteria and uncommon Gram-positive pathogens in patients with ABSSSIs. Of note, few coagulase - negative staphylococci (CoNS) isolates were resistant to dalbavancin and susceptible to vancomycin, highlighting the importance of testing for susceptibility to dalbavancin before its administration for CoNS infections. [ABSTRACT FROM AUTHOR]