841 - Frequency of carbapenemase-encoding genes among Imipenem-Resistant Gram-negative Bacilli isolated from Latin America: Is there a Role for Imipenem/Relebactam? Results from SMART 2017-2018

Background: New beta-lactamase inhibitors in combination with beta-lactams such as imipenem /relebactam (IMI/REL) were recently developed and approved for clinical use to overcome the emergence and spread of carbapenemase-producing Gram-negative bacilli (GNB). We evaluated the frequency of carbapenemase-encoding genes (CEG) among imipenem-resistant GNB isolated from Latin America through the SMART Program (2017-2018), in order to gain insight to the possible therapeutic role of IMI/REL in this region.

Methods: 13,843 GNB isolates including Enterobacterales (ENT) and P. aeruginosa (PSA), were collected consecutively from 10 Latin American countries during 2017-2018. GNB were recovered from patients diagnosed with distinct body site infections including bloodstream and respiratory tract infections. MICs were determined and interpreted according to CLSI broth microdilution recommendations. IMI-resistant isolates were selected for characterization of carbapenemase content by PCR followed by DNA sequencing.

Results: IMI resistance rates for E. coli (EC; N= 4,877), K. pneumoniae (KPN; N=2,718), P. aeruginosa (PSA; 2,108), Acinetobacter spp. (N=711), and E. cloacae (ECL; N=578) were 1.0%, 17.9%, 31.7%, 71.3% and 6.4%, respectively. These species accounted for 79.4% of all collected isolates. Detection of CEG was carried out in nearly 62.5% of the IMI-resistant ENT and PSA isolates. bla_KPC-2 was the most common CEG found in IMI-resistant KPN, followed by bla_KPC-3, in most LATAM countries (Figure 1). MBL encoding genes were detected in 92/415 (22.2%) IMI-resistant PSA. bla_VIM-2 was detected in 79.3% of these isolates, followed by IMP variants (20.6%). bla_{GES-5, -19, -20, and -26} were only detected in PSA isolated from Mexico, while bla_SPM-1 was only observed in five Brazilian PSA. IMI/REL showed excellent activity against EC [MIC_50/90, 0.12/0.5 µg/mL; 99.6% susceptible (S)], KPN (MIC_50/90, 0.25/.05 µg/mL; 96.5%, %S), and ECL (MIC_50/90, 0.25/0.5 µg/mL; 96.7%S).Most frequent carbapenemase encoding genes detected among IMI-resistant Enterobacterales (Panel A) and P. aeruginosa (Panel B) in Latin American countries
Species distribution by infection site


Conclusion: Important local variations were observed for some CEG variants detected only in specific countries. IMI/REL showed relevant in vitro activity against IMI-resistant ENT and MBL-negative PSA; and seems to be an important option for treatment of infections in LATAM.