Study For Monitoring Antimicrobial Resistance Trends Research Articles

Epidemiology and antimicrobial susceptibility profiles of Enterobacterales causing bloodstream infections before and during COVID-19 pandemic: Results of the Study for Monitoring Antimicrobial Resistance Trends (SMART) in Taiwan, 2018–2021

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has contributed to the spread of antimicrobial resistance, including carbapenem-resistant Enterobacterales. MethodsThis study utilized data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in Taiwan. Enterobacterales from patients with bloodstream infections (BSIs) were collected and subjected to antimicrobial susceptibility testing and β-lactamase gene detection using a multiplex PCR assay. Statistical analysis was conducted to compare susceptibility rates and resistance genes between time periods before (2018–2019) and during the COVID-19 pandemic (2020–2021). ResultsA total of 1231 Enterobacterales isolates were collected, predominantly Escherichia coli (55.6%) and Klebsiella pneumoniae (29.2%). The proportion of nosocomial BSIs increased during the COVID-19 pandemic (55.5% vs. 61.7%, p < 0.05). Overall, susceptibility rates for most antimicrobial agents decreased, with Enterobacterales from nosocomial BSIs showing significantly lower susceptibility rates than those from community-acquired BSIs. Among 123 Enterobacterales isolates that underwent molecular resistance mechanism detection, ESBL, AmpC β-lactamase, and carbapenemase genes were detected in 43.1%, 48.8% and 16.3% of the tested isolates, respectively. The prevalence of carbapenemase genes among carbapenem-resistant Enterobacterales increased during the pandemic, although the difference was not statistically significant. Two novel β-lactamase inhibitor combinations, imipenem-relebactam and meropenem-vaborbactam, preserved good efficacy against Enterobacterales. However, imipenem-relebactam showed lower in vitro activity against imipenem-non-susceptible Enterobacterales than that of meropenem-vaborbactam. ConclusionsThe COVID-19 pandemic appears to be associated with a general decrease in antimicrobial susceptibility rates among Enterobacterales causing BSIs in Taiwan. Continuous surveillance is crucial to monitor antimicrobial resistance during the pandemic and in the future.

1698. Activity of ceftolozane/tazobactam in vitro against Gram-negative isolates from pediatric patients: SMART 2017-2021

Abstract Background The study aims to evaluate the in vitro activity of ceftolozane/tazobactam (C/T) and other common-used antibiotics against clinical Gram-negative bacterial (GNB) isolates obtained from Chinese pediatric patients using data from The Study for Monitoring Antimicrobial Resistance Trends (SMART). Methods From 2017-2021, 554 Gram-negative isolates were collected from 16 pediatric departments across China. GNB isolates from pediatric departments were mainly derived from bloodstream (n = 135), intraperitoneal (n = 129), lower respiratory tract (n = 198) and urinary tract (n = 92) infections (Figure 1). The minimum inhibitory concentrations (MICs) were tested using a Trek Diagnostic System (Thermo Fisher Scientific). Susceptibility was determined by CLSI broth microdilution and interpreted with CLSI M100 (2021) breakpoints. Results E. coli (34.30%) and K. pneumoniae (27.62%) were the most common pathogens, followed by P. aeruginosa (15.34%). Susceptibility of species with more than 20 isolates were showed in Table 1. The susceptibility of P. aeruginosa to C/T was 89.41%, which was the highest among beta-lactams and was second only to amikacin. The susceptibilities of E. coli and K. pneumoniae isolates to C/T were 92.63% and 58.17%, respectively. When exclude carbapenem-resistant E. coli and K. pneumoniae, the susceptibility to C/T increased to 96.17% and 86.14%. C/T showed similar activities to E. coli and K. pneumoniae isolated from pediatric patients &amp;lt; 1 year (Table 2). Thirteen P. aeruginosa isolates were collected from patients &amp;lt; 1 year and 13/13 were susceptible to C/T (Table 3). Conclusion P. aeruginosa and E. coli obtained from pediatric patients in China showed a high susceptibility to C/T. When excluding carbapenem resistant isolates, C/T also showed good activities against K. pneumoniae. Disclosures Pengcheng Li, M.D., MSD China: Employee of MSD China

Antimicrobial surveillance: A 20-year history of the SMART approach to addressing global antimicrobial resistance into the future

Antimicrobial resistance (AMR) is a major global public health threat, particularly affecting patients in resource-poor settings. Comprehensive surveillance programmes are essential to reducing the high mortality and morbidity associated with AMR and are integral to informing treatment decisions and guidelines, appraising the effectiveness of intervention strategies, and directing development of new antibacterial agents. Various surveillance programmes exist worldwide, including those administered by government bodies or funded by the pharmaceutical industry. One of the largest and longest running industry-sponsored AMR surveillance programme is the Study for Monitoring Antimicrobial Resistance Trends (SMART), which recently completed its 20th year. The SMART database has grown to almost 500000 isolates from over 200 sites in more than 60 countries, encompassing all major geographic regions and including many sites in low- and middle-income countries. The SMART surveillance programme has evolved in scope over time, including additional antibacterial agents, pathogens and infection sites, in line with changing epidemiology and medical need. Surveillance data from SMART and similar programmes have been used successfully to detect emerging resistance threats and AMR patterns in specific countries and regions, thus informing national and local clinical treatment guidelines. The SMART database can be accessed readily by physicians and researchers globally, which may be especially valuable to those from countries with limited healthcare resources, where surveillance and resistance data are rarely collected. Continued participation from as many sites as possible worldwide and maintenance of adequate funding are critical factors to fully realising the potential of large-scale AMR surveillance programmes into the future.

A nested cohort 5-year Canadian surveillance of Gram-negative antimicrobial resistance for optimized antimicrobial therapy

We analyzed 5 years (2016–2020) of nested Canadian data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) to identify pathogen predominance and antimicrobial resistance (AMR) patterns of adult Gram-negative infections in Canadian health care and to complement other public surveillance programs and studies in Canada. A total of 6853 isolates were analyzed from medical (44%), surgical (18%), intensive care (22%) and emergency units (15%) and from respiratory tract (36%), intra-abdominal (25%), urinary tract (24%) and bloodstream (15%) infections. Overall, E. coli (36%), P. aeruginosa (18%) and K. pneumoniae (12%) were the most frequent isolates and P. aeruginosa was the most common respiratory pathogen. 18% of Enterobacterales species were ESBL positive. Collective susceptibility profiles showed that P. aeruginosa isolates were highly susceptible (> 95%) to ceftolozane/tazobactam and colistin, though markedly less susceptible (58–74%) to other antimicrobials tested. Multi-drug resistance (MDR) was present in 10% of P. aeruginosa isolates and was more frequent in those from respiratory infections and from ICU than non-ICU locations. Of P. aeruginosa isolates that were resistant to combinations of ceftazidime, piperacillin/tazobactam and meropenem, 73–96% were susceptible to ceftolozane/tazobactam over the period of the study. These national data can now be combined with clinical prediction rules and genomic data to enable expert antimicrobial stewardship applications and guide treatment policies to optimize adult patient care.

Antimicrobial Susceptibility of E. coli Isolates from Intra-Abdominal Infections in the Asia-Pacific Region: Trends in Ciprofloxacin, Ceftriaxone, Cefepime, and Piperacillin/Tazobactam Susceptibility.

To investigate the antibiotic susceptibility of Escherichia coli isolates in patients diagnosed with intra-abdominal infections (IAIs) in the Asia-Pacific region. This study was conducted at 50 medical hospitals across 9 countries/regions as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program from 2014 to 2018. Nonduplicate isolates of aerobic and facultative gram-negative bacilli were collected and processed for further antimicrobial susceptibility testing. A total of 10,709 isolates were collected, with E. coli (n=4737, 44.2%) being the leading pathogen causing IAIs, followed by Klebsiella pneumoniae (n=2429, 22.7%) and Pseudomonas aeruginosa (n=931, 8.7%). Community-associated (CA) E. coli isolates generally exhibited higher susceptibility rates for most antibiotics than hospital-associated (HA) isolates. In countries/regions other than Hong Kong, South Korea, and Singapore, HA isolates displayed lower susceptibility rates for multiple classes (≥4) of antibiotics. Among the commonly used antibiotics in IAIs, the overall susceptibility rate for ciprofloxacin was low, with an average of 41.3%. Ceftriaxone susceptibility rates in all selected countries were below 80% starting in 2018, ranging from 23.3% to 75.8%. The cefepime susceptibility rates varied across regions, with consistently reduced susceptibility ranging from 45.5% to 57.8% in India, Thailand, and Vietnam. Piperacillin/tazobactam demonstrated effectiveness against E. coli isolates in almost all countries except India, with a downward trend observed in the Philippines and Taiwan. Carbapenems remained effective against more than 90% of E. coli isolates, except in India. Prudent use of fluoroquinolones and ceftriaxone is advised when treating both CA and HA IAIs in the Asia-Pacific region. The low susceptibility rate of cefepime in India, Thailand, and Vietnam needs careful consideration in its administration. Moreover, the increase in nonsusceptibility to piperacillin/tazobactam in the Philippines and Taiwan poses a potential risk that should be closely monitored.

In vitro activity of imipenem/relebactam, meropenem/vaborbactam and comparators against Enterobacterales causing urinary tract infection in Taiwan: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART), 2020

ObjectivesAntimicrobial resistance due to β-lactamase production is a worldwide issue, and β-lactamase inhibitors have been developed to overcome the growing problem. This study aimed to evaluate the in vitro activities of two recently introduced carbapenem/β-lactamase inhibitor combinations – imipenem/relebactam and meropenem/vaborbactam – and their comparators against Enterobacterales from patients with urinary tract infections (UTIs). MethodsEnterobacterales isolates from patients with UTIs in Taiwan and participating in the Study for Monitoring Antimicrobial Resistance Trends (SMART) in 2020 were included. Minimum inhibitory concentrations (MICs) for various antibiotics were determined using the broth microdilution method. Susceptibility was interpreted based on the MIC breakpoints of the Clinical and Laboratory Standards Institute 2022. Genes encoding common β-lactamases, including extended-spectrum β-lactamases, AmpC β-lactamases and carbapenemases, were detected using multiplex polymerase chain reaction. ResultsA total of 309 Enterobacterales isolates were included, against which both imipenem/relebactam and meropenem/vaborbactam exerted excellent efficacy (275 of 309, 95% and 288 of 309, 99.3%, respectively). Among imipenem non-susceptible isolates, 17 of 43 (39.5%) and 39 of 43 (90.7%) were susceptible to imipenem/relebactam and meropenem/vaborbactam, respectively. ConclusionImipenem/relebactam and meropenem/vaborbactam may be appropriate choices for treating UTIs due to Enterobacterales resistant to commonly used antibiotics. Continuous monitoring of antimicrobial resistance is crucial.

In vitro activity of ceftolozane/tazobactam against Pseudomonas aeruginosa collected in the Study for Monitoring Antimicrobial Resistance Trends (SMART) between 2016-2019 in China.

Ceftolozane/tazobactam is an antipseudomonal cephalosporin combined with a well-established β-lactamase inhibitor which has not been approved to datein clinical practice in China. The aim of the study was to evaluate the in vitro activity of ceftolozane/tazobactam and comparator agents against Pseudomonas aeruginosa which demonstrated various resistance patterns. P. aeruginosa (n = 2,178) specimens were collected from multiple sources in seven geographic regions of China from 2016 to 2019. All isolates were identified by MALDI-TOF MS (Bruker Daltonics, MS, USA), and minimum inhibitory concentrations (MICs) of antimicrobial agents including ceftolozane/tazobactam, amikacin, tobramycin, ceftazidime, cefepime, colistin, levofloxacin, aztreonam, meropenem, imipenem, and piperacillin-tazobactam were determined using the CLSI broth microdilution method (BMD). P. aeruginosa demonstrated a considerably higher rate of multidrug-resistant (57.3%), extensive drug-resistant (43.5%) and in being difficult-to-treat (16.8%). The overall susceptibility of P. aeruginosa to ceftolozane/tazobactam was 81.9%, and ceftolozane/tazobactam showed diverse activities against various resistance patterns ranging from 28.5% (difficult-to-treat resistance) to 68.9% (MDR). P. aeruginosa and various resistance patterns derived from the east (Jiangzhe) area maintained a significantly lower susceptibility to ceftolozane/tazobactam than from other areas. The susceptibility rates of P. aeruginosa isolated from diverse sources to ceftolozane/tazobactam were similar to isolates from bloodstream infections (BSI), the highest being88.6%. Compared with comparator antimicrobial agents, ceftolozane/tazobactam was more active than tested β-lactams, while being slightly less active than amikacin, which in turn demonstrated the best activity against P. aeruginosa and multiple resistant subsets. Ceftolozane/tazobactam demonstrated considerable in vitro activity against P. aeruginosa including multiple resistance patterns, indicating that it could be an optional therapeutic agent against P. aeruginosa.

Activity of imipenem/relebactam against Enterobacterales and Pseudomonas aeruginosa in Spain. SMART 2016-2020.

To determine susceptibility to the novel β-lactam/β-lactamase inhibitor combination imipenem/relebactam in clinical isolates recovered from intra-abdominal (IAI), urinary (UTI), respiratory (RTI) and bloodstream (BSI) infections in the SMART (Study for Monitoring Antimicrobial Resistance Trends) study in SPAIN during 2016 - 2020. Broth microdilution MICs for imipenem/relebactam and comparators were determined by a central laboratory against isolates of Enterobacterales and Pseudomonas aeruginosa. MICs were interpreted using EUCAST-2021 breakpoints. In total, 5,210 Enterobacterales and 1,418 P. aeruginosa clinical isolates were analyzed. Imipenem/relebactam inhibited 98.8% of Enterobacterales. Distinguishing by source of infection susceptibility was 99.1% in BSI, 99.2% in IAI, 97.9% in RTI, and 99.2% in UTI. Of intensive care unit isolates (ICU) 97.4% were susceptible and of non-ICU isolates 99.2% were susceptible. In Enterobacterales, activity against Class A, Class B and Class D carbapenemases was 96.2%, 15.4% and 73.2%, respectively. In P. aeruginosa, imipenem/relebactam was active in 92.2% of isolates. By source of infection it was 94.8% in BSI, 92.9% in IAI, 91.7% in RTI, and 93.1% in UTI. An 88.7% of ICU isolates and 93.6% of non-ICU isolates were susceptible to imipenem/relebactam. Imipenem/relebactam remained active against P. aeruginosa ceftazidime-resistant (76.3%), cefepime-resistant (73.6%), imipenem-resistant (71.5%) and piperacillin-resistant (78.7%) isolates. Of all multidrug-resistant or difficult-to-treat resistance P. aeruginosa isolates, 75.1% and 46.2%, respectively, were susceptible to imipenem/relebactam. Imipenem/relebactam showed high rates of susceptibility in Enterobacterales and P. aeruginosa isolates from different sources of infection as well as depending on patients' location (ICU or non-ICU scenarios).

In vitro activity of ceftolozane/tazobactam against multidrug-resistant Pseudomonas aeruginosa from patients in Western Europe: SMART 2017-2020

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections compromise both empirical and definitive antimicrobial therapies. The Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program identified 943 MDR P. aeruginosa (from a total of 4086 P. aeruginosa isolates [23.1%]) collected at 32 clinical laboratories in six countries in Western Europe from 2017 to 2020. Minimum inhibitory concentrations (MICs) for ceftolozane/tazobactam and 10 comparator agents were determined by broth microdilution and interpreted using 2021 EUCAST breakpoints. β-lactamase genes were identified in selected isolate subsets. Most isolates of P. aeruginosa in Western Europe (93.3%) were ceftolozane/tazobactam-susceptible. A total of 23.1% of P. aeruginosa isolates were MDR. Of these, 72.0% were ceftolozane/tazobactam-susceptible, which is similar to that for ceftazidime/avibactam (73.6%) but >40% higher than for carbapenems, piperacillin/tazobactam, third- and fourth-generation cephalosporins, and levofloxacin. Metallo-β-lactamases (MBLs) were carried by 8.8% of molecularly characterized MDR P. aeruginosa, and 7.6% of molecularly characterized MDR isolates carried Guiana Extended Spectrum (GES) carbapenemases. MBLs were identified in isolates from all six countries, ranging from 3.2% of all P. aeruginosa isolates from Italy to 0.4% of all isolates from the United Kingdom. Acquired β-lactamases were not identified in 80.0% of molecularly characterized MDR P. aeruginosa isolates. Percentages of MDR isolates without detected β-lactamases were higher in the United Kingdom (97.7%), Spain (88.2%), France (88.1%), and Germany (84.7%) than in Portugal (63.0%) and Italy (61.3%), where carbapenemases were more prevalent. Ceftolozane/tazobactam is an important treatment option for patients infected with MDR P. aeruginosa that are not susceptible to first-line antipseudomonal agents.

In vitro activity of imipenem/relebactam, meropenem/vaborbactam and comparators against Enterobacterales from patients with intra-abdominal infections: Results of the study for Monitoring Antimicrobial Resistance Trends (SMART) in Taiwan, 2020

Multi-drug resistant Enterobacterales is a growing health threat. Imipenem/relebactam and meropenem/vaborbactam, are not clinically used in Taiwan and the susceptibility is lack from routine laboratory tests. Broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) and interpreted according to the Clinical and Laboratory Standards Institute (CLSI) breakpoints criteria. Isolates that were not susceptible to imipenem (MIC ≥ 2 mg/L), imipenem/relebactam (MIC ≥ 2 mg/L), or ceftolozane-tazobactam (MIC ≥ 4 mg/L) were selected for further molecular testing for genes encoding extended-spectrum beta-lactamases (ESBLs), AmpC β-lactamases, and carbapenemases by multiplex PCR assays. A total of 290 Enterobacterales isolates from 9 participating hospitals were collected in 2020. Escherichia coli (n=135, 46.6%) and Klebsiella pneumoniae (n=88, 30.3%) were two leading pathogens of all Enterobacterales isolates. The antimicrobial agents with susceptibility rates more than 90% included amikacin (99.3%, 288/290), ertapenem (90.0%, 261/290), meropenem (97.2%, 282/290), imipenem/relebactam (94.8%, 275/290) and meropenem/vaborbactam (99.3%, 288/290). K. pneumoniae isolates were less susceptible to ertapenem, imipenem, meropenem, piperacillin-tazobactam and ceftozolane/tazobactam than E. coli (all p <0.05). ESBL, AmpC, and carbapenemase were detected in 40.5% (17/42), 45.2% (19/42) and 11.9% (5/42) among tested isolates, respectively. The 5 carbapenemase genes included 4 bla KPC and 1 bla IMP . The imipenem-non-susceptible isolates (n = 30) had higher susceptibility rates to meropenem/vaborbactam (93.3%, 28/30) than imipenem/relebactam (50%, 12/30) ( p < 0.05). Imipenem/relebactam and meropenem/vaborbactam had excellent efficacy against Enterobacterales isolates . Meropenem/vaborbactam allowed better salvage therapy for carbapenem-resistant Enterobacterales infections.

Activity of ceftolozane/tazobactam against clinical isolates of Pseudomonas aeruginosa from patients in the Middle East and Africa – Study for Monitoring Antimicrobial Resistance Trends (SMART) 2017-2020

ObjectivesWe evaluated the activity of ceftolozane/tazobactam (C/T), and comparators against clinical Pseudomonas aeruginosa isolates collected for the global Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in ten countries in the Middle East and Africa to augment scarce standardized surveillance data in this region. MethodsMinimum inhibitory concentrations (MICs) were determined using Clinical and Laboratory Standards Institute broth microdilution and interpreted with European Committee on Antimicrobial Susceptibility Testing breakpoints. P. aeruginosa isolates testing with C/T MIC >4 mg/l or imipenem MIC >2 mg/l were screened for β-lactamase genes. ResultsC/T was active against 91.4% and 87.0% of P. aeruginosa isolates from the Middle East and Africa, respectively (14-21 and 7-16 percentage points higher than most β-lactam comparators, respectively). Considerable variation in susceptibility was seen across countries, which largely correlated with the observed prevalence of carbapenemases and/or extended-spectrum β-lactamases. Differences across countries were smaller for C/T than for the β-lactam comparators, ranging from 81% C/T-susceptible among isolates from Jordan to 95% for Qatar. Among subsets resistant to meropenem, ceftazidime, or piperacillin/tazobactam, C/T maintained activity against 51-73% of isolates from the Middle East and against 27-54% from Africa (where metallo-β-lactamase and GES carbapenemase rates were higher). ConclusionGiven the desirability of β-lactam use among clinicians, C/T represents an important option in the treatment of infections caused by P. aeruginosa.

In Vitro Activity of Ceftolozane-Tazobactam, Imipenem-Relebactam, Ceftazidime-Avibactam, and Comparators against Pseudomonas aeruginosa Isolates Collected in United States Hospitals According to Results from the SMART Surveillance Program, 2018 to 2020.

Ceftolozane-tazobactam (C/T), imipenem-relebactam (IMR), and ceftazidime-avibactam (CZA) were tested against 2,531 P. aeruginosa strains isolated from patients in the United States from 2018 to 2020 as part of the SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance program. MICs were determined by CLSI broth microdilution and interpreted using CLSI M100 (2021) breakpoints. Imipenem-, IMR-, or C/T-nonsusceptible isolates were screened for β-lactamase genes: 96.4% of all isolates and ≥70% of multidrug-resistant (MDR), pan-β-lactam-nonsusceptible, and difficult-to-treat resistance (DTR) isolates were C/T-susceptible; 52.2% of C/T-nonsusceptible isolates remained susceptible to IMR compared to 38.9% for CZA; and 1.7% of isolates tested were nonsusceptible to both C/T and IMR versus 2.2% of isolates with a C/T-nonsusceptible and CZA-resistant phenotype (a difference of 12 isolates). C/T and IMR modal MICs for pan-β-lactam-nonsusceptible isolates remained at or below their respective susceptible MIC breakpoints from 2018 to 2020, while the modal MIC for CZA increased 2-fold from 2018 to 2019 and exceeded the CZA-susceptible MIC breakpoint in both 2019 and 2020. Only six of 802 molecularly characterized isolates carried a metallo-β-lactamase, and two isolates carried a GES carbapenemase. Most P. aeruginosa isolates were C/T-susceptible, including many with MDR, pan-β-lactam-nonsusceptible, DTR, CZA-resistant, and IMR-nonsusceptible phenotypes. While C/T was the most active antipseudomonal agent, IMR demonstrated greater activity than CZA against isolates nonsusceptible to C/T.

127. Living on the Edge: The Impact of MIC Distributions on Empiric Antibiotic Selection

BackgroundDue to variability in the precision of an MIC, concern may exist in optimizing PK/PD using standard doses when the MIC is at the susceptibility breakpoint (SBP). This is notable when treating infections in critically ill patients. Evaluating MIC distributions among commonly used antibiotics and accounting for isolates at the SBP represents an additional enhancement to inform empiric therapy. The aim of the study was to evaluate antibiotic susceptibility for commonly used β-lactams against Pseudomonas aeruginosa (PA) in a syndromic antibiogram, incorporating MIC distribution. Methods20 US institutions submitted yearly up to 250 consecutive targeted Gram-negative pathogens from hospitalized patients as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) in 2016-2019. MICs were determined by broth microdilution and interpreted using 2021 CLSI breakpoints. The syndromic antibiogram included PA from a blood or respiratory source based on patient location. Based on CLSI guidance, an empiric antibiotic susceptibility threshold of ≥ 90% was deemed optimal. Results2,500 PA blood (n=680) and respiratory (n=1,820) isolates were evaluated; piperacillin/tazobactam (P/T), cefepime (FEP), meropenem (MEM), and ceftolozane/tazobactam (C/T) susceptibilities were 69.6%, 74.2%, 75.3%, and 95%, respectively (Figure 1). Isolates with MICs at the SBP were observed in 12.1%, 18.7%, 7.5%, and 6.5% for P/T, FEP, MEM, and C/T, respectively. Susceptibilities were lower when stratified by ICU, 64.8%, 71.2%, 70.7%, and 93.7% for P/T, FEP, MEM, and C/T, respectively with a similar frequency of SBP isolates (Figure 2).Figure 1. Syndromic antibiogram evaluating P. aeruginosa blood and respiratory isolates. Figure 2. Syndromic antibiogram evaluating Pseudomonas aeruginosa blood and respiratory isolates stratified by ICU. *MIC breakpoints used to determine susceptibility included: P/T MIC ≤ 16/4 µg/ml, FEP ≤ 8 µg/ml, MEM ≤ 2 µg/ml, C/T ≤ 4 µg/ml ConclusionOur analysis demonstrated that first line antipseudomonal agents, P/T and FEP, have susceptibility rates lower than the CLSI recommended threshold. A significant portion of the MICs within the susceptible range are at the SBP. Due to the frequency of baseline resistance and challenge in achieving adequate PK/PD in critically ill patients, clinicians may be concerned with relying on certain antibiotics when the MIC is at the SBP. Antimicrobial stewardship programs should consider incorporating MIC distributions into syndromic antibiograms to better inform empiric therapy recommendations. Disclosures Karri A. Bauer, PharmD, Merck & Co., Inc. (Employee, Shareholder) Levita K. Hidayat, PharmD BCIDP, Merck & Co., Inc. (Employee, Shareholder) Kenneth Klinker, PharmD, Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder)

631. Economic Analysis of Imipenem/Cilastatin/Relebactam Compared to Piperacillin/Tazobactam for Treating Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia

Abstract Background Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) is associated with high rates of morbidity and mortality; this is often worse among patients who experience a delay in receiving appropriate therapy. Initial treatment choice and early adjustment occurs prior to pathogen susceptibility results and may be based on suspicion of a resistant infection and/or clinical deterioration. This study assesses the cost effectiveness of Imipenem/cilastatin/relebactam (IMI/REL) in an early adjustment prescribing scenario compared to PIP/TAZ for patients with high risk of resistant infection from a US perspective. Methods Although early adjustment data was not directly available, pathogen susceptibility data derived from 2017-19 Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program was applied to estimate patients who may have clinical worsening, likely due to a resistant infection. The efficacy and safety data for IMI/REL and PIP/TAZ were informed by the modified intent-to-treat population of a phase III trial (RESTORE-IMI 2). Our analysis comprised a decision tree (reflecting hospitalization period) followed by a yearly Markov model (capturing lifetime impact). The decision tree captured short-term outcomes (clinical cure, all-cause mortality, and hospital resource use). The Markov model translated short term outcomes into quality-adjusted life years (QALYs). Results were expressed as an incremental cost-effectiveness ratio (ICER). Sensitivity analyses were conducted to test the robustness of model results. Results Compared with PIP/TAZ, IMI/REL in the early adjustment setting was associated with increased costs (&amp;10,087 per patient) but a higher cure (+7%) and lower mortality (-3%) rate. The resulting ICER (&amp;12,173/QALY) falls well below typical US willingness to pay thresholds. Model drivers were the SMART-based susceptibility profiles and RESTORE-IMI 2 response and mortality rates. Conclusion Our results suggest that IMI/REL, used as an early adjustment option, could be considered cost effective for patients with worsening HABP/VABP in a US setting, when compared against PIP/TAZ. Disclosures Jaesh Naik, MSc, BresMed Health Solutions (Employee) Lewis Ralph, MSc, Bresmed (Employee) Ryan J. Dillon, MSc, Merck &amp; Co. Inc., (Employee, Shareholder) Joe Yang, Ph.D., Merck &amp; Co (Employee)

Antimicrobial activity of ceftolozane-tazobactam against Enterobacterales and Pseudomonas aeruginosa recovered during the Study for Monitoring Antimicrobial Resistance Trends (SMART) program in Spain (2016-2018).

ABSTRACTObjectiveTo analyse the susceptibility to ceftolozane-tazobactam and comparators in Enterobacterales and Pseudomonas aeruginosa isolates recovered from intraabdominal (IAI), urinary (UTI), respiratory (RTI) and bloodstream infection (BSI) in the SMART (Study for Monitoring Antimicrobial Resistance Trends) study.Methods. The susceptibility of 5,351 isolates collected in 11 Spanish hospitals (2016-2018) were analysed (EUCAST-2020 criteria) by broth microdilution and were phenotypically studied for the presence of extended-spectrum beta-lactamases (ESBL). Ceftolozane-tazobactam and/or carbapenem resistant isolates were genetically characterized for ESBL and carbapenemases.ResultsEscherichia coli was the most frequent pathogen (49.3% IAI, 54.9% UTI, 16.7% RTI and 50% BSI), followed by Klebsiella pneumoniae (11.9%, 19.1%, 13.1% and 15.4%, respectively). P. aeruginosa was isolated in 9.3%, 5.6%, 32% and 9%, respectively. The frequency of isolates with ESBLs (2016-2017) was: 30.5% K. pneumoniae, 8.6% E. coli, 2.3% Klebsiella oxytoca and 0.7% Proteus mirabilis. Ceftolozane-tazobactam was very active against non-ESBL-(99.3% susceptible) and ESBL-(95.2%) producing E. coli being less active against K. pneumoniae (98% and 43.1%, respectively) isolates. CTX-M-15 was the most prevalent ESBL in E. coli (27.5%) and K. pneumoniae (51.9%) frequently associated with OXA-48-like carbapenemase. Overall, 93% of P. aeruginosa isolates were susceptible to ceftolozane-tazobactam, preserving this activity (>75%) in isolates resistant to other beta-lactams except in those resistant to meropenen or ceftazidime-avibactam. GES-5, PER-1, VIM-1/2 were the most prevalent enzymes in isolates resistant to ceftolozane-tazobactam.ConclusionsCeftolozane-tazobactam showed high activity rates against isolates recovered in the SMART study although it was affected in K. pneumoniae and P. aeruginosa isolates with ESBL and/or carbapenemases.

103. Empiric Antibiotic Susceptibility Using a Traditional vs. Syndromic Antibiogram-Implications for Antimicrobial Stewardship Programs

BackgroundA primary tenet of antimicrobial stewardship programs (ASPs) is to establish empiric antibiotic treatment recommendations. While traditional antibiograms are useful, intrinsic variability in susceptibility exists when stratifying by source and/or location. In contrast, a syndromic antibiogram displays the likelihood of adequate coverage for a specific infection syndrome, considering the weighted incidence of pathogens causing that syndrome. The aim of the study was to compare antibiotic susceptibilities using a traditional versus syndromic antibiogram.MethodsBetween 2016–2019, 20 US institutions per year submitted up to 250 consecutive targeted gram-negative pathogens from hospitalized patients as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). MICs were determined by broth microdilution and interpreted using 2020 CLSI breakpoints, except for imipenem/relebactam (I/R) for which FDA breakpoints were used. The traditional antibiogram included the 3 most common Gram-negative pathogens from all sources and represented critical organisms considered for empiric antibiotic coverage; the syndromic antibiogram included the 3 most commonly isolated Gram-negative pathogens from a respiratory source based on patient location.Results17,561 Gram-negative isolates, including 6,654 lower respiratory isolates were evaluated. The top 3 most common Gram-negative organisms included: E. coli (n=6095, 44%), Klebsiella spp. (n=4097, 30%), P. aeruginosa (n=3649, 26%). Cumulative susceptibilities were comparable using a traditional vs. syndromic antibiogram (Figure 1); however, cefepime (FEP), piperacillin/tazobactam (TZP), and meropenem (MEM) susceptibilities were 5 – 8% lower when stratified by patient location (Figure 2) and ≥10% for P. aeruginosa (Figure 3). Ceftolozane/tazobactam (C/T) and I/R demonstrated ≥90% susceptibility regardless of respiratory source or patient location.Figure 1. Cumulative susceptibility of E. coli, Klebsiella spp, and P. aeruginosa for traditional vs. syndromic antibiogram Figure 2. Syndromic antibiogram evaluating cumulative susceptibility of E. coli (n = 637), Klebsiella spp. (n = 1190) and P. aeruginosa (n = 1997) respiratory isolates stratified by patient location Figure 3. Syndromic antibiogram evaluating susceptibility of P. aeruginosa (n = 1997) respiratory isolates stratified by patient location ConclusionOur analysis demonstrated that susceptibilities were lower for first-line agents when stratified by ICU and P. aeruginosa. ASPs should consider syndromic antibiograms based on source and patient location to optimize empiric antibiotic therapy recommendations.DisclosuresKenneth Klinker, PharmD, Merck & Co, Inc (Employee) Karri A. Bauer, PharmD, Merck Research Laboratories (Employee) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Levita K. Hidayat, PharmD BCIDP, Merck & Co (Employee)

In Vitro Activity of Imipenem/Relebactam Against Enterobacteriaceae Isolates Obtained from Intra-abdominal, Respiratory Tract, and Urinary Tract Infections in China: Study for Monitoring Antimicrobial Resistance Trends (SMART), 2015-2018.

Considering the increasing incidence of carbapenem-resistant Enterobacteriaceae in China, this study aimed to establish the in vitro effectiveness of imipenem/relebactam (IMI/REL) on clinical Enterobacteriaceae isolates derived from intra-abdominal infections (IAIs), respiratory tract infections (RTIs), and urinary tract infections (UTIs) in China between 2015 and 2018. In total, 8781 Enterobacteriaceae isolates from IAI, RTI, and UTI samples were collected from 22 hospitals across 7 geographic regions of China. Susceptibility to antimicrobial drugs was tested using the Clinical and Laboratory Standards Institute broth microdilution and breakpoints, and IMI/REL activity was assessed using United States Food and Drug Administration guidelines. In 2015-2018, the most frequently identified Enterobacteriaceae species was Escherichia coli (n = 4676 [53.3%]), followed by Klebsiella pneumoniae (n = 2949 [33.6%]) and Enterobacter cloacae (n = 542 [6.2%]). The Enterobacteriaceae isolates showed 95.2% overall susceptibility to IMI/REL, of which the susceptibility rates in isolates from IAI, RTI, and UTI were 95.8%, 91.4%, and 96.6%, respectively. Overall, the susceptibilities of both intensive care unit (ICU) and non-ICU Enterobacteriaceae isolates to colistin were 92.9%, followed by IMI/REL (90.7% [95.9%]) and amikacin (83.3% [92.3%]). In addition, IMI/REL restored 66.3% susceptibility in imipenem-nonsusceptible Enterobacteriaceae. Given their high in vitro susceptibility, Enterobacteriaceae infections in China should be considered for IMI/REL treatment, especially with isolates that are not susceptible to carbapenems.

Antimicrobial susceptibility and distribution of extended-spectrum β-lactamases, AmpC β-lactamases and carbapenemases among Proteus, Providencia and Morganella isolated from global hospitalised patients with intra-abdominal and urinary tract infections: Results of the Study for Monitoring Antimicrobial Resistance Trends (SMART), 2008–2011

ObjectivesThe increasing trend of β-lactam resistance among Enterobacteriaceae is a worldwide problem. This study investigated isolates of the tribe Proteeae (Proteus, Providencia and Morganella) causing intra-abdominal and urinary tract infections from the worldwide Study for Monitoring Antimicrobial Resistance Trends (SMART) collected from 2008–2011. MethodsAntimicrobial susceptibility testing was performed on isolates with an ertapenem minimum inhibitory concentration >0.5mg/L or those phenotypically producing extended-spectrum β-lactamases (ESBLs). ESBLs, AmpC β-lactamases and carbapenemases were detected by multiplex PCR. ResultsA total of 142 isolates, including Proteus mirabilis (n=121), Proteus vulgaris (n=3), Providencia stuartii (n=5), Providencia rettgeri (n=6) and Morganella morganii (n=7), were analysed. Proteus mirabilis was generally susceptible to ertapenem (∼90%) compared with imipenem (≤25%). The most common ESBLs were CTX-M types (n=64), followed by TEM (n=27) and SHV (n=7). CTX-M-1, CTX-M-2 and CTX-M-15 were the dominant CTX-M-type ESBLs in P. mirabilis isolates. CMY (n=14), which included CMY-2 (n=6), was the most common AmpC β-lactamase, followed by DHA (n=6) and FOX (n=4). NDM (n=7), which included NDM-1 (n=4), was the most common carbapenemase, followed by KPC (n=2). Isolates from hospital-associated infections had more complicated β-lactamase combinations than isolates from community-acquired infections. ConclusionThe global emergence and spread of β-lactamase-producing Proteeae isolates are major issues in tackling antimicrobial resistance. Continuous monitoring of antimicrobial resistance trends and developing further resistance surveillance are necessary.

In vitro activity of imipenem/relebactam against Enterobacteriaceae and Pseudomonas aeruginosa isolated from intraabdominal and urinary tract infection samples: SMART Surveillance United States 2015–2017

ObjectivesAntimicrobial resistance, including multidrug-resistance (MDR), is increasing, especially among Gram-negative bacilli. New agents are needed to treat infections caused by these pathogens. This report assessed the activity of imipenem/relebactam against Gram-negative bacilli from intraabdominal infections (IAIs) and urinary tract infections (UTIs) submitted to the SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance programme in the United States from 2015 to 2017. MethodsBroth microdilution MICs for imipenem/relebactam and comparators were determined by a central laboratory against isolates of non-Proteeae Enterobacteriaceae (NPE) and Pseudomonas aeruginosa (P. aeruginosa). Imipenem/relebactam MICs were interpreted using United States Food and Drug Administration (FDA) breakpoints. Results99.5% of NPE isolates collected from patients with IAIs (n=3633) and UTIs (n=3038) were susceptible to imipenem/relebactam, as were 77.9% of imipenem-nonsusceptible, 96.3% of Klebsiella pneumoniae carbapenemase (KPC)-positive, and 98.7% of MDR isolates from IAIs and UTIs combined. A total of 96.7% of IAI isolates (n=486) and 96.4% of UTI isolates (n=360) of P. aeruginosa were susceptible to imipenem/relebactam, as were 85.0% of imipenem-nonsusceptible and 87.3% of MDR isolates from IAIs and UTIs combined. Percent susceptibility to imipenem/relebactam for cefepime-, ceftazidime-, and piperacillin-tazobactam-nonsusceptible isolates was 98.3–98.8% for NPE and 87.3–90.0% for P. aeruginosa. ConclusionsImipenem/relebactam demonstrated potent in vitro activity against NPE and P. aeruginosa isolates from IAIs and UTIs, including against resistant subsets, and will provide important coverage for IAIs and UTIs caused by β-lactam-resistant, MDR, and KPC-positive Gram-negative bacilli.

2477. Antimicrobial Resistance patterns of Enterobacteriaceae and Pseudomonas aeruginosa from Colombian clinical isolates. 2017–2018

BackgroundThe Study for Monitoring Antimicrobial Resistance Trends (SMART) is a worldwide initiative to monitor in vitro susceptibility of clinical Gram-negative isolates to several antimicrobial agents. Surveillance initiatives are essential to provide real-world evidence to support local guidelines development. Colombia has participated since 2012 with isolates from complicated intrabdominal infections (cIAI), complicated urinary tract infections (cUTI) and respiratory tract infections (RTI). This study describes resistant patterns of Escherichia coli (Eco), Klebsiella pneumoniae (Kpn) and Pseudomonas aeruginosa (Pae) clinical isolates collected in Colombian hospitals in a 2 years period (2017–2018).MethodsIsolates from patients with cIAI, cUTI and RTI were collected. Identification confirmation was done in central laboratory. Minimum inhibitory concentrations (MIC) were performed by broth microdilution and interpreted according to 2018 CLSI guidelines, same criteria for Extended-spectrum β-lactamase (ESBL) classification. The antimicrobial activity was evaluated for aztreonam (ATM), ceftolozane/tazobactam (C/T), ceftazidime (CAZ), colistin (COL), ertapenem (ETP), cefepime (FEP), imipenem (IMP), meropenem (MEM) and piperacillin–tazobactam (TZP).ResultsDuring 2017–2018, 1492 isolates were collected. The main organism was Eco (51%) followed by Kpn (29%) and Pae (20%). In vitro susceptibility activity is presented in Table 1. COL, C/T, ETP, MEM and IPM exhibited over 95% susceptibility in Eco. ESBL prevalence was 18% for Eco (53/314) and 22% for Kpn (36/165). COL and C/T were the most active agents against Pae isolates. For Kpn, MIC50/90 values were: MEM (0.12 / 8), C/T (0.5 / 8) and for TZP (8 / > 64), meanwhile for Pae were MEM (0.5 / 32), C/T (0.5 / 32) and for TZP (8 / > 64).ConclusionContinued antimicrobial resistance surveillance initiatives are critical to guide the empiric treatments decision in a multidrug resistance era. This study shows that Ceftolozane/Tazobactam, MEM and COL have the best susceptibility profile against Eco, Kpn and Pae of cIAI, cUTI and RTI cases in Colombia. The C/T susceptibility rates and low MIC distribution provide evidence to support its use as a non-carbapenem therapeutic alternative for Gram-negative infections. Disclosures All authors: No reported disclosures.