Activity of meropenem/vaborbactam and comparators against Gram-negative isolates from Eastern and Western European patients hospitalized with pneumonia including ventilator-associated pneumonia (2014–19)

Abstract

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.

Meropenem-Vaborbactam Activity against U.S. Multidrug-Resistant Enterobacterales Strains, Including Carbapenem-Resistant Isolates

“…The primary carbapenemase in the present study was KPC (81.1%); the presence of MBLs (NDM and VIM) or OXA-48-like carbapenemases was uncommon (4.5% of isolates produced MBLs and 1.4% produced OXA-48-like carbapenemases). This is in contrast to findings for Europe, where MBL- and OXA-48-producing isolates are increasingly observed, particularly in Eastern European countries, where OXA-48 is becoming as common as KPC ( 6 , 23 – 25 ).…”

“…It is possible that the high nonCP CRE rate reported by Tamma et al ( 26 ) represents a local clonal spread. The nonCP CRE rate for European CRE strains was 17.7% in the study by Sader et al ( 23 ), with Poland having a greater number than other European countries in additional recent studies ( 24 , 27 ).…”

Novel Antimicrobial Agents for Gram-Negative Pathogens

“…Regarding HAP/VAP isolates, the drug was active against >90% of KPC-producing Enterobacterales and 70–80% of P. aeruginosa [ 74 , 75 ]. KPC-producing K. pneumoniae strains that develop resistance to CAZ/AVI often leads to MER/VARB cross-resistance through increased KPC expression, although some isolates remained susceptible to MER/VARB [ 76 , 77 ].…”

Epidemiology, Mechanisms of Resistance and Treatment Algorithm for Infections Due to Carbapenem-Resistant Gram-Negative Bacteria: An Expert Panel Opinion

“…In fact, in vitro studies showed very low MICs of the MEV combination for all tested Enterobacterales, which were known to be KPC-positive, OXA-48-negative and MBL-negative [ 67 ]. On the contrary, MEV showed little efficacy against MBL-producing CRE, DTR P. aeruginosa , S. maltophilia and A. baumannii in in vitro study [ 68 , 69 , 70 ]. The clinical efficacy of MER/VAB was evaluated in two phase 3 RCTs: TANGO I and TANGO II.…”

“…MEV was specifically developed to target KPC-producing CRE [ 126 ]. A European survey among clinical isolates of inpatients with pneumonia showed that most isolated Enterobacterales were susceptible to MEV (98%; MIC50: 0.03 µg/mL; MIC90: 0.06 µg/mL) [ 68 ]. However, susceptibility to MER/VAB dropped to 63.0% (MIC50: 4 µg/mL; MIC90: >32 µg/mL) due to the presence of OXA-48- and MBL-producing strains of Enterobacterales.…”