Abstract Carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa are being isolated from patient specimens with increasing frequency in Latin America and worldwide. The current study provides an initial description of the in vitro activity of imipenem/relebactam (IMR) against non-Morganellaceae Enterobacterales (NME) and P. aeruginosa infecting hospitalized patients in Latin America. From 2018 to 2020, 37 clinical laboratories in nine Latin American countries participated in the SMART global surveillance program and contributed 15,466 NME and 3408 P aeruginosa isolates. MICs for IMR and seven comparators were determined using CLSI broth microdilution and interpreted by CLSI M100 (2022) breakpoints. β-lactamase genes were identified in selected isolate subsets. IMR (96.9% susceptible), amikacin (95.9%), meropenem (90.7%), and imipenem (88.7%) were the most active agents against NME. Among piperacillin/tazobactam-nonsusceptible NME (n= 4124), 90.4% of isolates were IMR-susceptible (range by country, 97.2 [Chile] to 67.0% [Guatemala]) and among meropenem-nonsusceptible NME isolates (n= 1433), 74.0% were IMR-susceptible (94.1% [Puerto Rico] to 5.1% [Guatemala]). Overall, 6.3% of all collected NME isolates carried a KPC (metallo-β-lactamase [MBL]-negative), 1.8% an MBL, 0.4% an OXA-48-like carbapenemase (MBL-negative), and 0.1% a GES carbapenemase (MBL-negative). Amikacin (85.2% susceptible) and IMR (80.1%) were the most active agents against P. aeruginosa; only 56.5% of isolates were imipenem-susceptible. Relebactam increased susceptibility to imipenem by 22.0% (from 23.9% to 45.9%) in piperacillin/tazobactam-nonsusceptible isolates (n= 1031) and by 35.5% (from 5.5% to 41.0%) in meropenem-nonsusceptible isolates (n= 1128). Overall, 7.6% of all collected P. aeruginosa isolates were MBL-positive and 0.7% carried a GES carbapenemase. In conclusion, in 2018‒2020, almost all NME (97%) and most P. aeruginosa(80%) isolates from Latin America were IMR-susceptible. Continued surveillance of the in vitro activities of IMR and comparator agents against Gram-negative pathogens, and monitoring for β-lactamase changes (in particular for increases in MBLs), is warranted. Carbapenemresistant Carbapenem resistant worldwide imipenemrelebactam relebactam (IMR nonMorganellaceae non Morganellaceae (NME 201 2020 3 15466 15 466 15,46 340 M M10 2022 (2022 breakpoints βlactamase β lactamase subsets 96.9% 969 96 9 (96.9 susceptible, susceptible , 95.9%, 959 95.9% 95 (95.9%) 90.7%, 907 90.7% 90 7 (90.7%) 88.7% 887 88 (88.7% piperacillin/tazobactamnonsusceptible piperacillintazobactamnonsusceptible piperacillin/tazobactam nonsusceptible piperacillin tazobactam n= n (n 4124, 4124 4124) 904 4 90.4 IMRsusceptible range country 972 97 2 97. Chile [Chile 670 67 0 67.0 Guatemala [Guatemala] meropenemnonsusceptible 1433, 1433 1433) 740 74 74.0 94.1% 941 94 1 (94.1 Puerto Rico 51 5 5.1 Guatemala. . Overall 63 6 6.3 metalloβlactamase metallo MBLnegative, MBLnegative MBL negative [MBL]-negative) 18 8 1.8 04 0.4 OXA48like OXAlike OXA 48 like (MBL-negative) 01 0.1 MBLnegative. 85.2% 852 85 (85.2 80.1% 801 80 (80.1% 565 56 56.5 imipenemsusceptible. imipenemsusceptible susceptible. imipenem-susceptible 220 22 22.0 239 23 23.9 45.9% 459 45 1031 355 35 35.5 55 5.5 41.0% 410 41 1128. 1128 1128) 76 7.6 MBLpositive positive 07 0.7 conclusion 20182020 2018‒2020 97% (97% aeruginosa80% aeruginosa80 80% aeruginosa(80% IMRsusceptible. Gramnegative Gram pathogens MBLs, MBLs MBLs) warranted 20 202 1546 46 15,4 34 M1 (202 96.9 (96. 95.9 (95.9% 90.7 (90.7% 88.7 (88.7 tazobactamnonsusceptible piperacillintazobactam 412 90. 67. [Guatemala 143 74. 94.1 (94. 5. 6. [MBL]-negative 1. 0. (MBL-negative 85.2 (85. 80.1 (80.1 56. 22. 23. 45.9 103 35. 41.0 112 7. 2018202 2018‒202 (97 aeruginosa8 aeruginosa(80 154 15, (20 96. (96 95. (95.9 (90.7 88. (88. 14 94. (94 85. (85 80. (80. 45. 10 41. 11 201820 2018‒20 (9 aeruginosa(8 (2 (95. (90. (88 (8 (80 20182 2018‒2 ( aeruginosa( (95 (90 2018‒

Abstract Introduction The incidence of antimicrobial resistance is increasing in many parts of the world. The focus of this report is to examine changes in antimicrobial resistance epidemiology among clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected in six Latin American countries as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program from 2015 to 2020, with a focus on the in vitro activity of ceftazidime-avibactam against Multidrug-Resistant (MDR) isolates. Methods Non-duplicate, clinical isolates of Enterobacterales (n= 15,215) and P. aeruginosa (n= 4,614) collected by 40 laboratories in Argentina, Brazil, Chile, Colombia, Mexico, and Venezuela, from 2015 to 2020, underwent centralized Clinical Lab Standards Institute (CLSI) broth microdilution susceptibility testing. Minimum Inhibitory Concentration (MIC) values were interpreted using 2022 CLSI breakpoints. An MDR phenotype was defined by resistance to ≥ 3 of seven sentinel agents. Results In total, 23.3% of Enterobacterales and 25.1% of P. aeruginosa isolates were MDR. Annual percent MDR values for Enterobacterales were stable from 2015 to 2018 (21.3% to 23.7% year) but markedly increased in 2019 (31.5%) and 2020 (32.4%). Annual percent MDR values for P. aeruginosa were stable from 2015 to 2020 (23.0% to 27.6% year). Isolates were divided into two 3-year time-periods, 2015‒2017 and 2018‒2020, for additional analyses. For Enterobacterales, 99.3% of all isolates and 97.1% of MDR isolates from 2015‒2017 were ceftazidime-avibactam-susceptible compared to 97.2% and 89.3% of isolates, respectively, from 2018‒2020. For P. aeruginosa, 86.6% of all isolates and 53.9% of MDR isolates from 2015‒2017 were ceftazidime-avibactam-susceptible compared to 85.3% and 45.3% of isolates, respectively, from 2018‒2020. Among individual countries, Enterobacterales and P. aeruginosa collected in Venezuela showed the greatest reductions in ceftazidime-avibactam susceptibility over time. Conclusion MDR Enterobacterales increased in Latin America from 22% in 2015 to 32% in 2020 while MDR P. aeruginosa remained constant at 25%. Ceftazidime-avibactam remains highly active against all clinical isolates of both Enterobacterales (97.2% susceptible, 2018‒2020) and P. aeruginosa (85.3%), and inhibited more MDR isolates (Enterobacterales, 89.3% susceptible, 2018‒2020; P. aeruginosa, 45.3%) than carbapenems, fluoroquinolones, and aminoglycosides. world ATLAS (ATLAS 201 ceftazidimeavibactam ceftazidime avibactam MultidrugResistant Multidrug Resistant (MDR Nonduplicate, Nonduplicate Non duplicate, duplicate Non-duplicate n= n (n 15,215 15215 15 215 P 4,614 4614 4 614 Argentina Brazil Chile Colombia Mexico (CLSI testing MIC (MIC 202 breakpoints agents total 233 23 23.3 251 25 1 25.1 21.3% 213 21 (21.3 237 7 23.7 year 31.5% 315 31 5 (31.5% 32.4%. 324 32.4% . 32 (32.4%) 23.0% 230 0 (23.0 276 27 6 27.6 year. 3year timeperiods, timeperiods time periods, periods time-periods 20152017 2017 2015‒201 20182020 2018‒2020 analyses 993 99 99.3 971 97 97.1 ceftazidimeavibactamsusceptible susceptible 972 2 97.2 893 89 89.3 respectively 866 86 86.6 539 53 9 53.9 853 85 85.3 453 45 45.3 22 25% Ceftazidimeavibactam Ceftazidime (97.2 85.3%, , (85.3%) (Enterobacterales carbapenems fluoroquinolones aminoglycosides 20 15,21 1521 4,61 461 61 23. 25. 21.3 (21. 31.5 (31.5 32.4 (32.4% 23.0 (23. 27. 2015201 2015‒20 2018202 2018‒202 99. 97. 8 89. 86. 53. 85. 45. (97. (85.3% 15,2 152 4,6 46 21. (21 31. (31. 32. (32.4 (23 201520 2015‒2 201820 2018‒20 (97 (85.3 15, 4, (2 (31 (32. 20152 2015‒ 20182 2018‒2 (9 (85. ( (3 (32 2018‒ (85 (8

ABSTRACT Gram-negative ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are important etiologic agents of nosocomial infection that are frequently resistant to broad-spectrum antimicrobial agents. Gram-negative ESKAPE pathogens were collected from hospitalized patients in 11 Latin American countries from 2013 to 2015 as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program. In total, 2113 isolates from intra-abdominal infections (IAI) and 970 isolates from urinary tract infections (UTI) were tested against antimicrobial agents using standardized CLSI broth microdilution methodology. Of the agents tested, amikacin demonstrated the highest rates of susceptibility (%) for K. pneumoniae (92.2, 92.3), Enterobacter spp. (97.5, 92.1), and P. aeruginosa (85.3, 75.2) isolates from both IAI and UTI, respectively. Ertapenem (68.5, 62.6) and imipenem (79.2, 75.9) showed substantially higher rates of susceptibility (%) than other β-lactams, including piperacillin-tazobactam (35.9, 37.4) against ESBL-positive isolates of K. pneumoniae from IAI and UTI, respectively. Rates of susceptibility to all agents tested against A. baumannii were ≤30.9%. Gram-negative ESKAPE pathogens isolated from Latin America demonstrated compromised in vitro susceptibility to commonly prescribed broad-spectrum, parenteral antimicrobial agents. Continued surveillance is warranted. New antimicrobial agents with potent activity against Gram-negative ESKAPE pathogens are urgently needed.

ABSTRACT As part of the Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) surveillance program in 2012 the in vitro activity of ceftaroline and relevant comparator antimicrobials was evaluated in six Latin American countries (Argentina, Brazil, Chile, Colombia, Mexico and Venezuela) against pathogens isolated from patients with hospital associated skin and soft tissue infections (SSTIs). The study documented that ceftaroline was highly active (MIC90 0.25 mg/L/% susceptible 100%) against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus (MIC90 2 mg/L/% susceptible 83.3%) and ß-hemolytic streptococci (MIC90 0.008-0.015 mg/L/% susceptible 100%). The activity of ceftaroline against selected species of Enterobacteriaceae was dependent upon the presence or absence of extended-spectrum ß-lactamases (ESBLs). Against ESBL screen-negativeEscherichia coli, Klebsiella pneumoniae, andKlebsiella oxytoca the MIC90 and percent susceptible for ceftaroline were (0.5 mg/L/94.1%), (0.5 mg/L/99.0%) and (0.5 mg/L/91.5%), respectively. Ceftaroline demonstrated potent activity against a recent collection of pathogens associated with SSTI in six Latin American countries in 2012.

The in vitro antimicrobial susceptibility of the respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis to commonly tested and prescribed agents was investigated during 1999-2000 and compared with results obtained during a previous 1997-1998 study. Of 448 isolates of S. pneumoniae collected and tested in 1999-2000, 77.2% were susceptible, 19.9% were intermediate, and 2.9% were resistant to penicillin, demonstrating that there were no major changes in susceptibility to penicillin from 1997-1998 (77.1% susceptible, 18.7% intermediate, 4.2% resistant). All S. pneumoniae isolates from 1999-2000 were susceptible to levofloxacin and vancomycin, and >90% were susceptible to the beta-lactams (amoxicillin-clavulanate, ceftriaxone, and cefuroxime) and macrolides (azithromycin and clarithromycin), showing that susceptibility to these agents also remained unchanged since 1997-1998. The most notable increase in resistance between the two studies was demonstrated by trimethoprim-sulfamethoxazole, which increased from 23.4% to 38.6%. Penicillin resistance correlated with resistance to beta-lactams, macrolides, and trimethoprim-sulfamethoxazole in both studies. In H. influenzae, the prevalence of beta-lactamase-producing isolates remained unchanged (10.6% in 1999-2000; 11.0% in 1997-1998). All H. influenzae isolates were susceptible to levofloxacin, ceftriaxone, cefuroxime, and azithromycin, and showed no change between the two studies. Trimethoprim-sulfamethoxazole resistance was present in 40.1% of isolates in 1999-2000, and in 45.2% in 1997-1998. In M. catarrhalis, the prevalence of beta-lactamase-producing isolates was unchanged (97.9% in 1999-2000; 98.0% in 1997-1998). The most active agents against M. catarrhalis were azithromycin (MIC90, <0.03 mug/ml) and levofloxacin (MIC90, 0.03 mug/ml). Overall, these results suggest that, in Brazil, between 1999-2000 and 1997-1998, there have been no significant changes in the susceptibility of respiratory pathogens to any of the commonly tested and prescribed agents with the exception of trimethoprim-sulfamethoxazole for S. pneumoniae.