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. blaKPC-2 was the most common CEG found in IMI-resistant KPN, followed by blaKPC-3, in most LATAM countries (Figure 1). MBL encoding genes were detected in 92/415 (22.2%) IMI-resistant PSA. blaVIM-2 was detected in 79.3% of these isolates, followed by IMP variants (20.6%). blaGES-5, -19, -20, and -26 were only detected in PSA isolated from Mexico, while blaSPM-1 was only observed in five Brazilian PSA. IMI/REL showed excellent activity against EC [MIC50/90, 0.12/0.5 µg/mL; 99.6% susceptible (S)], KPN (MIC50/90, 0.25/.05 µg/mL; 96.5%, %S), and ECL (MIC50/90, 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.
Disclosures
Ana Cristina Gales, Medical Doctor, CRISTALIA (Consultant)EUROFARMA (Consultant)INFECTOPHARM (Consultant)MSD (Consultant, Grant/Research Support, Scientific Research Study Investigator)PFIZER (Consultant, Scientific Research Study Investigator)ZAMBON (Consultant) Elisa Beirao, Medical Doctor, MSD (Consultant, Grant/Research Support, Scientific Research Study Investigator)PFIZER (Consultant) Felipe Tuon, Medical Doctor, MSD (Consultant, Grant/Research Support, Scientific Research Study Investigator)PFIZER (Consultant)TEVA (Consultant) Thales Polis, Medical Doctor, MSD (Employee) Suellen Rodrigues, MPharm, MSD (Employee) Marina Della Negra, Medical Doctor, MSD (Employee) Tarik Andrade, Bsc Pharm, MSD (Employee) Fernando Serra, MD, MSD Brazil (Employee)
