Activity of ceftolozane/tazobactam and imipenem/relebactam against Gram-negative clinical isolates collected in Mexico-SMART 2017-2021.

Objectives: To investigate the activities of ceftolozane/tazobactam and imipenem/relebactam against Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa isolated from hospitalized patients in Mexico in 2017-2021. Methods: MICs were determined by CLSI broth microdilution and interpreted using CLSI M100 breakpoints. ß-Lactamase genes were identified in ceftolozane/tazobactam-, imipenem/relebactam-, and/or imipenem-non-susceptible isolates. Results: Ceftolozane/tazobactam and imipenem/relebactam inhibited 89% and 99% of E. coli isolates (n = 2337), and 87% and 94% of K. pneumoniae isolates (n = 1127). Sixty-four percent of E. coli and 47% of K. pneumoniae had an ESBL non-carbapenem-resistant Enterobacterales (ESBL non-CRE) phenotype. Eighty-six percent and 91% of ESBL non-CRE E. coli and K. pneumoniae were ceftolozane/tazobactam susceptible, and 99.9% and 99.8% were imipenem/relebactam susceptible. Ceftolozane/tazobactam was the most active agent studied against P. aeruginosa (n = 1068; 83% susceptible), 9-28 percentage points higher than carbapenems and comparator ß-lactams excluding imipenem/relebactam (78% susceptible). Ceftolozane/tazobactam remained active against 35%-58%, and imipenem/relebactam against 32%-42%, of P. aeruginosa in meropenem-, piperacillin/tazobactam-, and cefepime-non-susceptible subsets. The majority of isolates of ceftolozane/tazobactam-non-susceptible E. coli carried an ESBL, whereas among ceftolozane/tazobactam-non-susceptible K. pneumoniae and P. aeruginosa, the majority carried carbapenemases. The most prevalent carbapenemase observed among E. coli (estimated at 0.7% of all isolates), K. pneumoniae (4.8%) and P. aeruginosa (10.0%) was an MBL. Almost all imipenem/relebactam-non-susceptible E. coli and K. pneumoniae carried MBL or OXA-48-like carbapenemases, whereas among imipenem/relebactam-non-susceptible P. aeruginosa, 56% carried MBL or GES carbapenemases. Conclusions: Ceftolozane/tazobactam and imipenem/relebactam may provide treatment options for patients infected with ß-lactam-non-susceptible Gram-negative bacilli, excluding isolates carrying an MBL- or OXA-48-like carbapenemase.

In vitro activity of imipenem/relebactam against non-Morganellaceae Enterobacterales and Pseudomonas aeruginosa in Latin America: SMART 2018‒2020.

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. ß-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-ß-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 ß-lactamase changes (in particular for increases in MBLs), is warranted.

Epidemiology and in vitro activity of ceftazidime-avibactam and comparator agents against multidrug-resistant isolates of Enterobacterales and Pseudomonas aeruginosa collected in Latin America as part of the ATLAS surveillance program in 2015‒2020.

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.

In vitro activity of imipenem/relebactam against non-Morganellaceae Enterobacterales and Pseudomonas aeruginosa in Latin America: SMART 2018‒2020

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.

Epidemiology and in vitro activity of ceftazidime-avibactam and comparator agents against multidrug-resistant isolates of Enterobacterales and Pseudomonas aeruginosa collected in Latin America as part of the ATLAS surveillance program in 2015‒2020

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.

In vitro activity of ceftazidime-avibactam against Enterobacterales and Pseudomonas aeruginosa isolates collected in Latin America as part of the ATLAS global surveillance program, 2017-2019.

The Antimicrobial Testing Leadership and Surveillance (ATLAS) global surveillance program collected clinical isolates of Enterobacterales (n = 8416) and Pseudomonas aeruginosa (n = 2521) from 41 medical centers in 10 Latin American countries from 2017 to 2019. In vitro activities of ceftazidime-avibactam and comparators were determined using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. Overall, 98.1% of Enterobacterales and 86.9% of P. aeruginosa isolates were susceptible to ceftazidime-avibactam. When isolates were analyzed by country of origin, susceptibility to ceftazidime-avibactam for Enterobacterales ranged from 97.8% to 100% for nine of 10 countries (except Guatemala, 86.3% susceptible) and from 75.9% to 98.4% for P. aeruginosa in all 10 countries. For Enterobacterales, 100% of AmpC-positive, ESBL- and AmpC-positive, GES-type carbapenemase-positive, and OXA-48-like-positive isolates were ceftazidime-avibactam-susceptible as were 99.8%, 91.8%, and 74.7% of ESBL-positive, multidrug-resistant (MDR), and meropenem-nonsusceptible isolates. Among meropenem-nonsusceptible isolates of Enterobacterales, 24.4% (139/570) carried a metallo-ß-lactamase (MBL); 83.3% of the remaining meropenem-nonsusceptible isolates carried another class of carbapenemase and 99.4% of those isolates were ceftazidime-avibactam-susceptible. Among meropenem-non-susceptible isolates of P. aeruginosa (n = 835), 25.6% carried MBLs; no acquired ß-lactamase was identified in the majority of isolates (64.8%; 87.2% of those isolates were ceftazidime-avibactam-susceptible). Overall, clinical isolates of Enterobacterales collected in Latin America from 2017 to 2019 were highly susceptible to ceftazidime-avibactam, including isolates carrying ESBLs, AmpCs, and KPCs. Country-specific variation in susceptibility to ceftazidime-avibactam was more common among isolates of P. aeruginosa than Enterobacterales. The frequency of MBL-producers among Enterobacterales from Latin America was low (1.7% of all isolates; 146/8,416), but higher than reported in previous surveillance studies.

Resistance among Gram-negative ESKAPE pathogens isolated from hospitalized patients with intra-abdominal and urinary tract infections in Latin American countries: SMART 2013-2015

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.

Resistance among Gram-negative ESKAPE pathogens isolated from hospitalized patients with intra-abdominal and urinary tract infections in Latin American countries: SMART 2013-2015.

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 ß-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.

Phenotypic and genotypic analysis of levofloxacin-resistant clinical isolates of Streptococcus pneumoniae collected in 13 countries during 1999-2000.

During 1999-2000, 5015 isolates were collected from 13 countries and tested against levofloxacin. Overall, levofloxacin resistance minimum inhibitory concentration (MIC>or =8 mg/l) was found in 40 isolates (0.8%). The highest resistance rates were in Hong Kong (8.0%), China (3.3%) and Spain (1.6%). Levofloxacin retained an MIC(90) of 1 mg/l in all countries. Pulsed-field gel electrophoresis analysis of resistant isolates demonstrated the presence of clones in countries where levofloxacin resistance exceeded 1%, suggesting that the elevated resistance rates could result from resistant clones within participating hospitals. DNA-sequence analysis of the quinolone-resistance-determining regions of gyrA, gyrB, parC and parE genes showed that the most common mutations were in GyrA (Ser81Phe), ParC (Ser79Phe, Lys137Asn) and ParE (Ile460Val), accounting for 40% of the isolates tested. Levofloxacin-resistant isolates were generally non-susceptible to other fluoroquinolones tested. Future studies to characterise resistant isolates by other molecular methods may ensure that the appropriate counter-measures can be taken to control the spread of resistant isolates.

Antimicrobial resistance in respiratory pathogens isolated in Brazil during 1999-2000

The in vitro antimicrobial susceptibility of the respiratory pathogens Streptococcus Pneumoniae, Hemophilus 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 B-lactams (amoxicillin-clavulanate, ceftriaxone, and cefuroxime) and macrolides (axithyromycin 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 B-lactams, macrolides, and trimethoprim-sulfamethoxazole in both studies. In H. influenzae, the prevalence of B-lactamase-producing isolates remained unchanged (10.6 in 1999-2000; 11.0 in 1997-1998). All H. influenzae isolates were susceptible to levofloxacine, 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 B-lactamase-producing isolates was unchanged (97.9 in 1999-2000;98.0 in 1997-1998). The most active agents against M. catarrhalis were azithromycin (MIC(90),< or = 0.03 microg/ml) and levofloxacin (MIC(90),< or = 0.03 microg/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.