CLSI Broth Microdilution Method Research Articles

Activity of ceftolozane/tazobactam and imipenem/relebactam against clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected in Greece and Italy-SMART 2017-2021.

The current study evaluated the in vitro activities of ceftolozane/tazobactam (C/T), imipenem/relebactam (IMI/REL), and comparators against recent (2017-2021) clinical isolates of gram-negative bacilli from two countries in southern Europe. Nine clinical laboratories (two in Greece; seven in Italy) each collected up to 250 consecutive gram-negative isolates per year from lower respiratory tract, intraabdominal, urinary tract, and bloodstream infection samples. MICs were determined by the CLSI broth microdilution method and interpreted using 2022 EUCAST breakpoints. β-lactamase genes were identified in select β-lactam-nonsusceptible isolate subsets. C/T inhibited the growth of 85-87% of Enterobacterales and 94-96% of ESBL-positive non-CRE NME (non-Morganellaceae Enterobacterales) isolates from both countries. IMI/REL inhibited 95-98% of NME, 100% of ESBL-positive non-CRE NME, and 98-99% of KPC-positive NME isolates from both countries. Country-specific differences in percent susceptible values for C/T, IMI/REL, meropenem, piperacillin/tazobactam, levofloxacin, and amikacin were more pronounced for Pseudomonas aeruginosa than Enterobacterales. C/T and IMI/REL both inhibited 84% of P. aeruginosa isolates from Greece and 91-92% of isolates from Italy. MBL rates were estimated as 4% of Enterobacterales and 10% of P. aeruginosa isolates from Greece compared to 1% of Enterobacterales and 3% of P. aeruginosa isolates from Italy. KPC rates among Enterobacterales isolates were similar in both countries (7-8%). OXA-48-like enzymes were only identified in Enterobacterales isolates from Italy (1%) while GES carbapenemase genes were only identified in P. aeruginosa isolates from Italy (2%). We conclude that C/T and IMI/REL may provide viable treatment options for many patients from Greece and Italy.

7-Year (2015-21) longitudinal surveillance of lefamulin in vitro activity against bacterial pathogens collected worldwide from patients with respiratory tract infections including pneumonia and characterization of resistance mechanisms.

Lefamulin (Xenleta™), a pleuromutilin antibiotic, was approved for the oral and IV treatment of community-acquired bacterial pneumonia (CABP) in adults in 2019/2020. This study evaluated the in vitro activity of lefamulin and comparators against 19 584 unique bacterial isolates collected from patients with community-acquired respiratory tract infections and hospitalized patients with pneumonia within the global SENTRY Antimicrobial Surveillance Program during 2015-21. Isolates were susceptibility tested by the CLSI broth microdilution method, and resistance mechanisms were investigated in isolates with elevated lefamulin MICs. Lefamulin exhibited potent antibacterial activity against the most common and typical CABP pathogens tested, including Streptococcus pneumoniae [MIC50/90, 0.06/0.25 mg/L; 99.9% susceptible (S)], Staphylococcus aureus (MIC50/90, 0.06/0.12 mg/L; 99.6% S), Haemophilus influenzae (MIC50/90, 0.5/2 mg/L; 99.1% S) and Moraxella catarrhalis (MIC50/90, 0.06/0.12 mg/L; 100.0% S). Potent activity was also observed against the less common pneumonia pathogens: β-haemolytic (MIC50/90 of 0.03/0.06 mg/L) and viridans group Streptococcus spp. (MIC50/90 of 0.06/0.25 mg/L) and Haemophilus parainfluenzae (MIC50/90 of 1/4 mg/L). Lefamulin's activity was not adversely affected by resistance to macrolides, penicillin, tetracyclines, fluoroquinolones and other resistance phenotypes. Non-susceptibility/resistance to lefamulin was rare and primarily determined by ribosomal protection through vga(A) variants in S. aureus, overexpression of AcrAB-TolC efflux pump in H. influenzae or modifications in L3, L4 and 23SrRNA in Streptococcus spp. Based on the coverage of the most important CABP pathogens and lacking cross-resistance, lefamulin may represent a valuable empirical treatment option for ambulatory and hospitalized patients with CABP, particularly in settings with high prevalence of resistance.

2146. Antimicrobial Activity of Aztreonam-avibactam, Ceftazidime-avibactam, and Meropenem-vaborbactam against Enterobacterales causing Bloodstream Infection in US Medical Centers (2020–2022)

Abstract Background As the frequency of Enterobacterales (ENT) producing metallo-β-lactamase (MBL) and/or OXA-48 is increasing in some US medical centers, effective antimicrobials to treat the infections caused by these organisms are urgently needed. Aztreonam-avibactam (ATM-AVI) is under clinical development for treatment of infections caused by Gram-negative bacteria, including MBL producers. We evaluated the activities of ATM-AVI, ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MEM-VAB), and comparators against ENT isolated from patients with bloodstream infections (BSIs). Methods 4,802 ENT were consecutively collected (1/patient) from 72 US medical centers in 2020–2022 and susceptibility tested by CLSI broth microdilution method. ATM-AVI was tested with AVI at a fixed 4 mg/L. A pharmacokinetic/pharmacodynamic susceptible (S) breakpoint of ≤ 8 mg/L was applied for comparison. Carbapenem-resistant ENT (CRE) isolates were screened for carbapenemase (CPE) by whole genome sequencing. Results ATM-AVI was highly active against ENT (Table); only 2 isolates showed ATM-AVI MICs > 8 mg/L: 1 MEM-S E. coli and 1 E. aerogenes (CRE). All CPE producers and 98.0% of CREs were inhibited at an ATM-AVI MIC of ≤ 8 mg/L. CAZ-AVI and MEM-VAB were active against 81.6% and 65.3% of CREs, respectively. Ceftolozane-tazobactam (TOL-TAZ) was active against only 72.6% of ceftriaxone (CRO)-nonsusceptible (NS) isolates. ATM-AVI retained activity (MIC, ≤8 mg/L) against all MEM-VAB-NS and 90.0% of CAZ-AVI-NS isolates. The most common CPEs were KPC-2/3 (57.1% of CREs), OXA-48–like (16.3%), and NDM (12.2%). A CPE gene was not observed in 14.3% of CREs. CAZ-AVI and MEM-VAB were active against 100.0% of KPC producers, but CAZ-AVI showed limited activity against MBL producers and MEM-VAB showed limited activity against OXA-48–like and MBL producers. The most active comparators against CRE were tigecycline (95.9%S), gentamicin (49.0%S), and amikacin (44.9%S). Conclusion ATM-AVI demonstrated potent activity against a large collection ENT isolated from patients with BSI in US hospitals, including CREs and isolates resistant to recently approved β-lactamase inhibitor combinations. These results support further clinical development of ATM-AVI. Disclosures Helio S. Sader, MD, PhD, FIDSA, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support John H. Kimbrough, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support

Trends in the susceptibility of U.S. Acinetobacter baumannii-calcoaceticus species complex and Stenotrophomonas maltophilia isolates to minocycline, 2014-2021.

Acinetobacter baumannii-calcoaceticus species complex (ACB) and Stenotrophomonas maltophilia (SM) are opportunistic, non-fermentative organisms that can cause serious hospital-acquired infections in immunocompromised patients. These pathogens are inherently resistant to several common drug classes and often acquire other resistance mechanisms, making them difficult to treat. In this study, we analyzed the susceptibility of 1,029 contemporary ACB and 1,522 SM isolates to minocycline (MIN) and levofloxacin (LEV) as well as meropenem (MER) for ACB and trimethoprim-sulfamethoxazole (TMP/SMX) for SM using the CLSI broth microdilution method. Isolates were collected as a part of the SENTRY Antimicrobial Surveillance Program from 2014 to 2021. Pneumonia in hospitalized patients was the most common infection from which ACB (57.0%) and SM (73.9%) were isolated. MIN had the highest in vitro activity for ACB (86.2%) and SM (99.5%). The activity of ACB and SM to all three agents varied over the period studied. MIN activity to ACB decreased in 2020 (80.6%) but rebounded in 2021 (86.2%). LEV and MER showed an overall trend of increasing susceptibility for ACB, with slightly lower activity in 2020-2021. MIN and TMP/SMX (>98.3% and >93.7%, respectively) activities were stable against SM isolates. LEV activity decreased from 84.3% (2015) to 69.2% (2018). The activity of MIN remained stable and higher than other agents tested for both ACB and SM, pathogens that have limited therapeutic alternatives. These in vitro data suggest that MIN is a useful treatment option for infections caused by ACB or SM.IMPORTANCEAcinetobacter baumannii-calcoaceticus species complex and Stenotrophomonas maltophilia are opportunistic, non-fermentative Gram-negative organisms that can cause serious hospital-acquired infections in immunocompromised patients. These pathogens are inherently resistant to several common drug classes and often acquire other resistance mechanisms, making them difficult to treat. In this study, we analyzed the trends of susceptibility of over 2,500 U.S. bacterial isolates collected from hospitalized patients over an 8-year period to minocycline, which is used to treat infections caused by these pathogens. These in vitro data suggest that minocycline is a useful treatment option for infections caused by Acinetobacter baumannii-calcoaceticus species complex or Stenotrophomonas maltophilia.

Exploring synergy between azole antifungal drugs and statins for Candida auris.

Global emergence of rapidly developing resistance to multiple antifungal drugs and high mortality pose challenges to the treatment of invasive Candida auris infections. New therapeutic approaches are needed, such as repurposing drugs including combination with antifungals. Statins have been reported to exert antifungal effects against various Candida species. Our study investigated potential synergy between the statins (rosuvastatin and fluvastatin) and azoles (voriconazole, posaconazole and isavuconazole) on clinical isolates of C. auris. Twenty-one clinical isolates of C. auris were obtained. Chequerboard assays based on the CLSI broth microdilution method were used to assess synergy based on FIC index (FICI) calculations of MICs of individual drugs and in combinations. Single drug geometric mean (GM) MICs of fluvastatin and rosuvastatin were ≥128 mg/L in all 21 isolates. GM (range) MICs of posaconazole, voriconazole and isavuconazole were 0.259 (0.016-1 mg/L), 0.469 (0.016-2 mg/L) and 0.085 (0.004-1 mg/L), respectively. Combination of azoles with fluvastatin showed synergy in 70%-90% of C. auris isolates. In particular, voriconazole/fluvastatin resulted in 16-fold reduction in voriconazole MIC and synergy in 14/21 (67%) isolates. Posaconazole/fluvastatin resulted in 8-fold reduction in posaconazole MIC and synergy in 19/21 (90%) isolates.Combining rosuvastatin with the azoles also showed synergy against C. auris in 40%-60% of the isolates and additive effect in 40%-50%. None of the combinations was antagonistic. Our results provide a rationale for pursuing in vivo synergy tests as well as clinical studies to explore tolerability, treatment outcomes, optimal dose and exposure targets.

Oritavancin in vitro activity against Gram-positive organisms from European medical centers: a 10-year longitudinal overview from the SENTRY Antimicrobial Surveillance Program (2010–2019)

To assess oritavancin in vitro activity against clinically relevant Gram-positive pathogens in European (EU) hospitals, a total of 51,531 consecutive and unique clinical isolates collected in 2010–2019 were evaluated. All isolates were tested by CLSI broth microdilution methods. The key resistance phenotypes differed considerably between Eastern Europe (E-EU) and Western Europe (W-EU), respectively: methicillin-resistant (MR) Staphylococcus aureus 27.7%/22.9%; multidrug resistant (MDR) S. aureus, 19.7%/15.2%; MR coagulase-negative staphylococci, 77.3%/61.9%; vancomycin-resistant enterococci (E. faecium), 44.2%/20.9%; and MDR E. faecium, 63.8%/55.4%. There were no substantive differences in oritavancin minimum inhibitory concentration (MIC) values for the different species/organism groups over time or by EU region. Oritavancin inhibited 99.9% and 99.1% of all S. aureus and coagulase-negative staphylococci at 0.12 mg/L, respectively, and all isolates of E. faecalis and E. faecium at ≤0.5 mg/L. Oritavancin susceptibility rates against β-hemolytic and Viridans group streptococci isolates were 98.1% and 99.4%, respectively. Oritavancin had potent activity in vitro against this contemporary collection of European Gram-positive isolates from 2010 to 2019.

Terbinafine-Resistant Dermatophytes and the Presence of Trichophyton indotineae in North America.

Dermatophytes are common causes of skin, hair, and nail infections in humans. The most common species causing infections in humans are Trichophyton rubrum, Trichophyton mentagrophytes, and Trichophyton interdigitale. Outbreaks of recalcitrant dermatophytosis have been reported in parts of South Asia, including those caused by a hypervirulent and resistant species, Trichophyton indotineae. We evaluated the antifungal susceptibility profiles of dermatophytes received by our laboratory from institutions across North America between 2021 and 2022 and performed species identification for isolates deemed to demonstrate in vitro resistance. Susceptibility testing was performed by CLSI broth microdilution methods, and species identification was performed by DNA sequence analysis. During this 2-year period, 271 dermatophyte isolates were included, the majority of which demonstrated low MIC values for terbinafine (geometric mean [GM] and modal MIC, 0.031 μg/mL and 0.008 μg/mL, respectively) and the azoles itraconazole, posaconazole, and voriconazole (0.035 to 0.049 μg/mL and ≤0.03 μg/mL). However, 18.6% of the isolates tested were resistant to terbinafine (MIC ≥ 0.5 μg/mL), including 21 T. rubrum and 21 T. indotineae isolates. These isolates were received from several different states in the United States and two provinces in Canada. In contrast, resistance to itraconazole was relatively rare. We also searched our laboratory database for earlier isolates that were resistant to terbinafine and identified 3 additional T. indotineae isolates, the earliest of which was from 2017. These results demonstrate that terbinafine resistance in dermatophytes was relatively common over this 2-year period and that T. indotineae is present in multiple areas in North America. Continued surveillance is warranted.

Comparison of PCV10, PCV13, PCV15, PCV20 and PPSV23 vaccine coverage of invasive Streptococcus pneumoniae isolate serotypes in Canada: the SAVE study, 2011-20.

As pneumococci evolve under vaccine, antimicrobial and other selective pressures, it is important to track isolates covered by established (PCV10, PCV13 and PPSV23) and new (PCV15 and PCV20) vaccine formulations. To compare invasive pneumococcal disease (IPD) isolates from serotypes covered by PCV10, PCV13, PCV15, PCV20 and PPSV23, collected in Canada from 2011 to 2020, by demographic category and antimicrobial resistance phenotype. IPD isolates from the SAVE study were initially collected by members of the Canadian Public Health Laboratory Network (CPHLN) as part of a collaboration between the Canadian Antimicrobial Resistance Alliance (CARA) and the Public Health Agency of Canada (PHAC). Serotypes were determined by quellung reaction, and antimicrobial susceptibility testing was performed using the CLSI broth microdilution method. A total of 14 138 invasive isolates were collected from 2011 to 2020, with 30.7% of isolates covered by the PCV13 vaccine, 43.6% of isolates covered by the PCV15 vaccine (including 12.9% non-PCV13 serotypes 22F and 33F), and 62.6% of isolates covered by the PCV20 vaccine (including 19.0% non-PCV15 serotypes 8, 10A, 11A, 12F and 15B/C). Non-PCV20 serotypes 2, 9N, 17F and 20, but not 6A (present in PPSV23) represented 8.8% of all IPD isolates. Higher-valency vaccine formulations covered significantly more isolates by age, sex, region and resistance phenotype including MDR isolates. Coverage of XDR isolates did not significantly differ between vaccine formulations. When compared with PCV13 and PCV15, PCV20 covered significantly more IPD isolates stratified by patient age, region, sex, individual antimicrobial resistance phenotypes and MDR phenotype.

Isolation, identification and antifungal susceptibility of dermatophytes from clinical specimens in a tertiary care hospital in South Kerala

Dermatophtyosis is common, more prevalent in tropical and subtropical countries including India. Though not life threatening it can cause great discomfort, especially in immunocompromised conditions. In the last few years a number of new less toxic antifungal drugs have become available for clinical use. Lack of clinical response may occur in 20%.125 clinically suspected cases of dermatophytosis were studied.The samples were subjected to direct microscopy and culture. Identification of the causative pathogen was done by performing slide culture, lacto phenol cotton blue mount, hair perforation tests and urease tests. In this study we evaluated the efficacy of seven antifungal medications using CLSI broth microdilution method (M38-A). The antifungals used were sertaconazole, terbinafine, griseofulvin, fluconazole, itraconazole, voriconazole and amphotericin B.Out of 125 samples, dermatophytosis manifested clinically more in the age group of 21-30 yrs. In our study, KOH positivity rate was 60.8% and culture positivity rate was 32%. Dermatophytosis was more common in females. Tinea corporis was the most common lesion (54.4%) followed by Tinea cruris (25.6%), Tinea pedis (8%), Tinea unguium(7.2%) and Tinea faciei (0.8%). was the commonest aetiological agent (50%) followed by (35%), (7.5%), (5%) and (2.5%). The range of their minimum inhibitory concentration endpoint by broth microdilution technique for the seven antifungal drugs were as follows, sertoconazole <0.06-4 μg/ml , griseofulvin 0.25-1 μg/ml, terbinafine <0.06-2 μg/ml, voriconazole 0.06-0.5 μg/ml, itraconazole <0.06-1 μg/ml, fluconazole 2-8 μg/ml and amphotericin B 2-8 μg/ml. This study gives an insight about the aetiological agents of dermatophytosis in this part of South Kerala, India. Both direct microscopy and culture are important tools for diagnosis of the superficial fungal infections. Majority of strains in the study were inhibited by relatively low concentration of the antifungals tested.

Species Distribution and Antifungal Susceptibilities of Aspergillus Section Terrei Isolates in Clinical Samples from the United States and Description of Aspergillus pseudoalabamensis sp. nov.

Aspergillus section Terrei consists of numerous cryptic species in addition to A. terreus sensu stricto. The treatment of invasive infections caused by these fungi may pose a unique challenge prior to diagnosis and species identification, in that they are often clinically resistant to amphotericin B, with poor outcomes and low survival rates in patients treated with this polyene. Data on the species distributions and susceptibility profiles of isolates within section Terrei from the United States (U.S.) are limited. Here, we report the species distributions and susceptibility profiles for amphotericin B, isavuconazole, itraconazole, posaconazole, voriconazole, and micafungin against 278 clinical isolates of this section from institutions across the U.S. collected over a 52-month period. Species identification was performed by DNA sequence analysis and phenotypic characterization. Susceptibility testing was performed using the CLSI broth microdilution method. The majority of isolates were identified as Aspergillus terreus sensu stricto (69.8%), although several other cryptic species were also identified. Most were cultured from specimens collected from the respiratory tract. Posaconazole demonstrated the most potent activity of the azoles (MIC range ≤ 0.03-1 mg/L), followed by itraconazole (≤0.03-2 mg/L), voriconazole, and isavuconazole (0.125-8 mg/L for each). Amphotericin B demonstrated reduced in vitro susceptibility against this section (MIC range 0.25-8 mg/L), although this appeared to be species-dependent. A new species within this section, A. pseudoalabamensis, is also described. Our results, which are specific to the U.S., are similar to previous surveillance studies of the Aspergillus section Terrei.

Antifungal Resistance Profile of Fungal Isolates from Fungal Rhinosinusitis Patients: A Study from Tertiary Care Hospital.

Objective Fungal rhinosinusitis is on the rise worldwide and it is endemic especially in North India. The main purpose of this study was to determine the antifungal resistance profile of fungal isolates from the cases of fungal rhinosinusitis. Methods Antifungal susceptibility testing of isolated fungi to fluconazole, amphotericin B, itraconazole, and voriconazole was determined by standard CLSI broth microdilution method. Results Sixty-eight fungal isolates of Aspergillus spp . ( n = 49), Rhizopus spp. ( n = 9), Candida spp . ( n = 4), Penicillium spp . ( n = 2), Mucor spp . ( n = 2), Bipolaris spp . ( n = 1), and Alternaria spp . ( n = 1) were obtained from 60 different clinical samples as exudate from nasal mucosa ( n = 28), allergic mucin ( n = 8), nasal lavage ( n = 2), tissue biopsy from nasal polyps ( n = 14), and intraoperative nasal mucosa ( n = 8). Of the 68 isolates, 75% were resistant to fluconazole, 13.23% were resistant to itraconazole, 2.94% to amphotericin B, and none were resistant to voriconazole. Aspergillus flavus (5%) was the only fungi found resistant to amphotericin B, while against itraconazole, A. flavus (7.5%) and A. niger (100%) were found resistant. All the isolates of A. flavus , A. fumigatus , A. niger , and Penicillium spp. were resistant to fluconazole. Conclusion Although amphotericin B stills remains to be the most effective drug, more prospective studies are needed for the requirement of knowledge of the sensitivity pattern for optimal treatment and reduction in morbidity in the long run.

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.

In vitro activity of imipenem/relebactam against piperacillin/tazobactam-resistant and meropenem-resistant non-Morganellaceae Enterobacterales and Pseudomonas aeruginosa collected from patients with lower respiratory tract infections in Western Europe: SMART 2018-20.

To describe the in vitro activity of imipenem/relebactam against non-Morganellaceae Enterobacterales (NME) and Pseudomonas aeruginosa recently isolated from lower respiratory tract infection samples by hospital laboratories in Western Europe. From 2018 to 2020, 29 hospital laboratories in six countries in Western Europe participated in the SMART global surveillance programme and contributed 4414 NME and 1995 P. aeruginosa isolates. MICs were determined using the CLSI broth microdilution method and interpreted by EUCAST (2021) breakpoints. β-Lactamase genes were identified in selected isolate subsets (2018-20) and oprD sequenced in molecularly characterized P. aeruginosa (2020). Imipenem/relebactam (99.1% susceptible), amikacin (97.2%), meropenem (96.1%) and imipenem (95.9%) were the most active agents tested against NME; by country, relebactam increased imipenem susceptibility from <1% (France, Germany, UK) to 11.0% (Italy). A total of 96.0% of piperacillin/tazobactam-resistant (n = 990) and 81.1% of meropenem-resistant (n = 106) NME were imipenem/relebactam-susceptible. Only 0.5% of NME were MBL positive, 0.9% were OXA-48-like-positive (MBL negative) and 2.8% were KPC positive (MBL negative). Amikacin (91.5% susceptible) and imipenem/relebactam (91.4%) were the most active agents against P. aeruginosa; 72.3% of isolates were imipenem-susceptible. Relebactam increased susceptibility to imipenem by 34.4% (range by country, 39.1%-73.5%) in piperacillin/tazobactam-resistant and by 37.4% (3.1%-40.5%) in meropenem-resistant P. aeruginosa. Only 1.8% of P. aeruginosa isolates were MBL positive. Among molecularly characterized imipenem/relebactam-resistant P. aeruginosa isolates from 2020, 90.9% (30/33) were oprD deficient. Imipenem/relebactam appears to be a potential treatment option for lower respiratory tract infections caused by piperacillin/tazobactam- and meropenem-resistant NME and P. aeruginosa in Western Europe.

645. Trends in the Susceptibility of US Acinetobacter baumannii-calcoaceticus Species Complex and Stenotrophomonas maltophilia Isolates to Minocycline, 2014-2021

Abstract Background Acinetobacter baumannii-calcoaceticus species complex (ACB) and Stenotrophomonas maltophilia (SM) are opportunistic, non-fermentative organisms that can cause serious hospital-acquired infections in immunocompromised patients. These pathogens are inherently resistant to several common drug classes and often acquire other resistance mechanisms, making them difficult to treat. In this study, we analyzed the susceptibility of contemporary ACB and SM isolates to minocycline (MIN), levofloxacin (LEV), meropenem (MER) for ACB, and trimethoprim-sulfamethoxazole (T/S) for SM. Isolates were collected as a part of the SENTRY Antimicrobial Surveillance Program from 2014-2021. Susceptibilities of SM and ACB to MIN and comparators, 2014-2021 Methods Isolates were collected from hospitalized patients in 35 US medical centers. Hospitals submitted 1 isolate per patient per infection episode that met local criteria for being the likely causative pathogen. Identification was performed by the submitting laboratory and confirmed by JMI Laboratories with matrix-assisted laser desorption ionization-time of flight mass spectrometry or other standard methods as required. Isolates were tested for susceptibility (S) to MIN and comparators using the CLSI broth microdilution method. All infection types were included in the analysis. CLSI (2022) breakpoints were applied. Results A total of 1,029 ACB and 1,520 SM were tested. Pneumonia in hospitalized patients was the most common infection from which ACB (57.0%) and SM (73.9%) were isolated. The %S of the agents tested against the organisms in this study are shown in the table. MIN had the highest %S for ACB (86.2%S) and SM (99.5%S). The %S of ACB and SM to all 3 agents varied over the period studied. MIN %S to ACB decreased in 2020 (80.6%) but rebounded in 2021 (86.2%). LEV and MER showed an overall trend of increasing S for ACB, with slightly lower %S in 2020-2021. SM had stable %S to MIN and T/S ( &amp;gt;98.3% and &amp;gt;93.7%, respectively). LEV varied from 84.3%S (2015) to 69.2%S (2018). Conclusion %S to MIN remained stable and higher than other agents tested for both ACB and SM, pathogens which have limited therapeutic alternatives. ACB showed &amp;lt; 6% decrease in %S to all 3 agents in 2020-2021. These in vitro data suggest that MIN is a useful treatment option for infections caused by ACB or SM. Disclosures Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Jennifer M. Streit, BS, MT(ASCP), Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Shionogi: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.

1677. In vitro Activity of SPR206 and Comparator Compounds against Enterobacterales Isolates Responsible for Infections in United States Hospitals

Abstract Background SPR206 is a next generation polymyxin under clinical development to treat infections, such as pneumonia, bloodstream, and urinary tract infections caused by Gram-negative (GN) multidrug-resistant (MDR) pathogens. The in vitro activity of SPR206 and comparators was monitored against GN pathogens causing infection in US and European hospitals during 2021 as part of the SENTRY Antimicrobial Surveillance Program. This study reports the activity of SPR206 against Enterobacterales (ENT) from US hospitals. Methods A total of 1,614 ENT recovered from clinical samples during the SENTRY Program for 2021 were included in the study. Isolates were collected from medical centers in all 9 US Census Divisions and centrally tested for susceptibility using the CLSI broth microdilution method and interpretations. Results E. coli (EC; 425) and K. pneumoniae (KP; 425) were the most common pathogens included in this surveillance study, followed by E. cloacae (215), Citrobacter spp. (120), K. oxytoca (110), S. marcescens (104), K. aerogenes (65), P. mirabilis (60), M. morganii (60), and other 11 species (30). Overall, SPR206 and colistin (COL) had MIC50 of 0.06 and 0.25 mg/L against all ENT, respectively. Indole-positive Proteae, Proteus species and Serratia spp., which are intrinsically resistant to COL (MIC values, ≥8 mg/L), also had an elevated MIC for SPR206 (MIC, ≥8 mg/L). Excluding these organisms, SPR206 (MIC50/90, 0.06/0.12 mg/L) and meropenem (MIC50/90, 0.03/0.06 mg/L) showed the lowest MIC against this ENT subset, followed by COL (MIC50/90, 0.25/0.25 mg/L) and ceftazidime-avibactam (MIC50/90, 0.12/0.5 mg/L). SPR206 (MIC50/90, 0.06/0.12 mg/L) had MIC 2- to 4-fold lower than COL (MIC50/90, 0.25/0.25 mg/L) against EC and KP. Finally, SPR206 (MIC50/90, 0.06/0.25 mg/L) showed the lowest MIC against MDR and extremely drug-resistant (XDR) isolates. Conclusion SPR206 was consistently more potent than COL against ENT pathogens causing various infections in US hospitals. SPR206 remained active against the MDR and XDR subsets, where limited intravenous options were available. These SPR206 data, combined with its favorable safety and tolerability profiles in Phase 1 studies, support the continued clinical advancement and development of SPR206. Disclosures Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support SJ Ryan Arends, PhD, AbbVie: Grant/Research Support|GSK: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Shionogi: Grant/Research Support Ian A. Critchley, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Ian A. Critchley, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.

1836. Frequency and Antimicrobial Susceptibility of Gram-negative Bacteria Isolated from Patients with Bloodstream Infections in United States (US) Medical Centers (2020-2021)

Abstract Background Antimicrobial resistance among Gram-negative bacteria (GNB) is a major problem in US hospitals. The development of various β-lactamase inhibitor combinations (BLICs) markedly increased the armamentarium to treat infections caused by GNB in recent years. We evaluated the frequency and antimicrobial susceptibility of GNB causing bloodstream infection (BSI). Methods 5,796 organisms were consecutively collected (1/patient) from patients with BSI in 31 US medical centers in 2020-2021. The collection included 2,893 (49.9%) GNB, which were susceptibility tested against ceftazidime-avibactam (CAZ-AVI), ceftolozane-tazobactam (C-T), meropenem-vaborbactam (MEM-VAB), imipenem-relebactam (IMI-REL), and many comparators by CLSI broth microdilution method. Enterobacterales (ENT) isolates with an ESBL phenotype were screened for β-lactamase genes by whole genome sequencing. Results The most common GNBs were E. coli (41.9%), K. pneumoniae (16.1%), P. aeruginosa (10.2%), and E. cloacae (6.8%). Ceftriaxone susceptibility rates were 80.1%, 82.9%, and 74.0% for E. coli, K. pneumoniae, and E. cloacae, respectively. CAZ-AVI and MEM-VAB showed almost complete activity (≥ 99.7%) against ENT, whereas IMI-REL exhibited limited activity against P. mirabilis and indole-positive Proteeae isolates and C-T showed limited activity against E. cloacae, ESBL-phenotype, and multidrug-resistant (MDR) isolates (Table). CAZ-AVI, MEM-VAB, and IMI-REL were active against 84.2%, 57.9%, and 52.6% of carbapenem-resistant ENT (CRE) isolates, respectively. PSA susceptibility to PIP-TAZ, MEM, and CAZ were 86.1%, 88.5%, and 88.5%, respectively. CAZ-AVI (97.6% susceptible [S]), C-T (97.6%S), IMI-REL (99.0%S), and tobramycin (TOB; 98.3%S) were the most active agents against PSA and retained good activity against piperacillin-tazobactam (PIP-TAZ) nonsusceptible (NS), MEM-NS, and multidrug-resistant (MDR) isolates. Conclusion CAZ-AVI and MEM-VAB were the most active agents against ENT and CAZ-AVI; C-T and IMI-REL were the most active BLICs against PSA. The new BLICs represent valuable treatment options for infections caused by MDR GBNs. CAZ-AVI exhibited a more balanced spectrum against ENT and PSA when compared to other BLICs. Disclosures Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Michael D. Huband, BS, AbbVie: Grant/Research Support|Melinta: Grant/Research Support Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.

1684. Antimicrobial Activity of Aztreonam-Avibactam Against a Large Collection of Stenotrophomonas maltophilia and Burkholderia cepacia Species Complex Causing Infections in United States (US) Medical Centers (2016-2021)

Abstract Background S. maltophilia has become a major cause of hospital-associated pneumonia. Aztreonam (ATM) is a monobactam stable to hydrolysis by metallo-β-lactamases (MBLs), including those intrinsically produced by S. maltophilia. Avibactam (AVI) is a non-β-lactam β-lactamase inhibitor that inhibits serine β-lactamases such as ESBLs, KPCs, AmpCs, and some OXAs. ATM-AVI is being developed for treatment of serious infections caused by Gram-negative bacteria, including MBL producers. We evaluated the activity of ATM-AVI against S. maltophilia and B. cepacia from US hospitals. Methods 1,565 S. maltophilia and 219 B. cepacia were consecutively collected (1/patient) in 77 US medical centers in 2016-2021 and susceptibility tested by CLSI broth microdilution method. Only isolates determined to be the probable cause of infection were included. CLSI/US FDA breakpoints were applied when available. Results The isolate collection were recovered mainly from patients with pneumonia (73.3%) and bloodstream infection (BSI; 10.1%). ATM-AVI was very active against S. maltophilia, with MIC50/90s of 2/4 mg/L and 98.3% of isolates inhibited at ≤8 mg/L, including 100.0% of isolates from BSI and 97.9% of isolates from pneumonia. Trimethoprim-sulfamethoxazole (TMP-SMX; MIC50/90, ≤0.5/1 mg/L; 95.7% susceptible [S]) and minocycline (MIC50/90, 0.5/2 mg/L; 99.2%S) also were very active against S. maltophilia, while ceftazidime and levofloxacin were active against 21.3% and 76.2% of isolates per CLSI criteria, respectively (Table). ATM-AVI was also very active against B. cepacia, with MIC50/90s of 4/16 mg/L and 88.1% inhibited at ≤8 mg/L, including 93.3% and 87.3% of isolates from BSI and pneumonia, respectively. The most active comparators tested against B. cepacia were ceftazidime (84.9%S), meropenem (84.5%S), TMP-SMX (83.5%S), and minocycline (80.0%S). Conclusion ATM-AVI demonstrated potent in vitro activity against S. maltophilia and B. cepacia from US hospitals and may represent a valuable option to treat infections caused by these organisms. Clinical studies are urgently warranted to evaluate the efficacy of ATM-AVI as well as reevaluate the susceptibility breakpoints for antibiotics currently used to treat infections caused by these organisms. Disclosures Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support SJ Ryan Arends, PhD, AbbVie: Grant/Research Support|GSK: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Shionogi: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.

1676. Activity of SPR206 and Comparator Agents Against Pseudomonas aeruginosa and Acinetobacter baumannii Causing Infections in United States Hospitals

Abstract Background SPR206 is a next generation polymyxin being developed to treat serious infections caused by Gram-negative (GN) multidrug-resistant (MDR) pathogens. The in vitro activity of SPR206 and comparators were monitored against GN pathogens causing infection in US and European hospitals during 2021 as part of the SENTRY Antimicrobial Surveillance Program. This study reports the activity of SPR206 against A. baumannii-calcoaceticus species complex (ACB) and P. aeruginosa (PSA) recovered from patients hospitalized in the USA. Methods A total of 238 ACB and 450 PSA recovered from clinical samples during the SENTRY Program for 2021 were included in the study. Isolates were collected from sites in all 9 US Census Divisions and centrally tested for susceptibility by CLSI broth microdilution method and interpretations. Results A total of 34.9% (83/238) and 14.7% (35/238) ACB displayed an MDR or XDR phenotype, whereas 17.8% (80/450) and 8.0% (36/450) PSA had these phenotypes, respectively. Overall, SPR206 had MIC50/90 of 0.12/0.5 mg/L against all ACB, whereas colistin (COL) had MIC50/90 results of 0.5/1 mg/L. SPR206 and COL inhibited, respectively, 98.0% and 97.0% of ACB at MIC of ≤2 mg/L. Other agents tested against ACB showed MIC90 of &amp;gt;16 mg/L. SPR206 remained active against the MDR (MIC50/90, 0.12/1 mg/L) and XDR (MIC50/90, 0.12/0.25 mg/L) subsets of ACB, as did COL (MIC50/90, 0.5/1 mg/L). MIC50, MIC90, and MIC100 of 0.25 mg/L, 0.25 mg/L, and 2 mg/L were obtained for SPR206 against all PSA, respectively. COL (MIC50/90, 1/1 mg/L), ceftazidime-avibactam (MIC50/90, 2/8 mg/L; 94.9% susceptible), and ceftolozane-tazobactam (MIC50/90, 0.5/2 mg/L; 96.9% susceptible) were active against PSA. SPR206 (MIC50/90, 0.25/0.5 mg/L) and COL (MIC50/90, 1/1 mg/L) remained active against the MDR and XDR PSA subsets. Conclusion SPR206 showed potent in vitro activity against these recent collections of ACB and PSA from the USA. SPR206 potency was consistently greater than clinically available in-class and other comparator agents. These results, and favorable safety and tolerability profiles of SPR206 in Phase 1 studies, support the clinical development of SPR206 for the usually difficult-to-treat infections caused by these pathogens and their resistant subsets. Disclosures Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support SJ Ryan Arends, PhD, AbbVie: Grant/Research Support|GSK: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Shionogi: Grant/Research Support Ian A. Critchley, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Ian A. Critchley, PhD, Spero Therapeutics: Employee|Spero Therapeutics: Stocks/Bonds Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.

1686. Antimicrobial Activity of Aztreonam-avibactam, Ceftazidime-Avibactam, and Comparator Agents against Pseudomonas aeruginosa from Cystic Fibrosis Patients

Abstract Background Aztreonam-avibactam (ATM-AVI) is under clinical development for the treatment of serious infections caused by Gram-negative bacteria, including MBL producers. Four other β-lactamase inhibitor combinations (BL/BLI) have been recently approved by the US FDA: ceftazidime-avibactam (CAZ-AVI), ceftolozane-tazobactam (C-T), meropenem-vaborbactam (MEM-VAB), and imipenem-relebactam (IMI-REL). We evaluated the in vitro activity of these 5 BL/BLIs and comparators against P. aeruginosa (PSA) causing cystic fibrosis (CF) pulmonary exacerbation. Methods 383 PSA isolates (1/patient) were recovered from 35 medical centers in the US (n=187) and 12 European countries (EU; n=196) in 2018-2021 and susceptibility tested by CLSI broth microdilution method. Results ATM-AVI inhibited 83.4%/85.2% of isolates from US/EU at ≤8 mg/L. CAZ-AVI (MIC50/90, 2/8 mg/L; 96.3%/95.4% susceptible [S] in US/EU) was the most active agent, followed by IMI-REL (94.7%/92.5%S in US/EU) and C-T (89.8%/91.3%S in US/EU). MEM-VAB (not approved for PSA in the US) and MEM showed similar activity. Tobramycin (TOB)-S rates were 73.3%/85.7% in US/EU (Table 1). Among TOB-non-S (NS) isolates, 84.6% were CAZ-AVI-S and 73.1% were inhibited at ATM-AVI MIC of ≤8 mg/L. CAZ-AVI retained good activity against C-T-NS (61.1%S), IMI-REL-NS (62.1%S), piperacillin-tazobactam (PIP-TAZ)-NS (86.7%S), meropenem (MEM)-NS (86.6%S), and ciprofloxacin (CIP)-NS (92.1%S) isolates (Table 2). Multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes were observed among 40.1%/30.1% and 24.6%/16.8% of isolates from US/EU, respectively. Among MDR isolates, 90.7%/84.7% were CAZ-AVI-S, 65.3%/66.1% were inhibited at ≤8 mg/L of ATM-AVI, and 78.7%/76.3% were TOB-S in US/EU. CAZ-AVI and TOB retained activity against 87.0%/75.8% and 39.1%/63.6% of XDR isolates in US/EU, respectively. Conclusion ATM-AVI and CAZ-AVI exhibited potent activity against PSA isolated from CF patients in US and EU and retained good activity against isolates resistant to other antimicrobials, including MDR and XDR organisms; both compounds showed greater activity than TOB. ATM-AVI and CAZ-AVI may represent a valuable option to treat CF patients with pulmonary exacerbations due to PSA infection. Disclosures Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support Leonard R. Duncan, PhD, AbbVie: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.

In vitro activity of sulopenem against 1880 bacterial pathogens isolated from Canadian patients with urinary tract infections (CANWARD, 2014-21).

There are limited oral antimicrobial options for the treatment of urinary infections caused by ESBL-producing and MDR Enterobacterales. Sulopenem is an investigational thiopenem antimicrobial that is being developed as both an oral and IV formulation. The purpose of this study was to evaluate the in vitro activity of sulopenem versus bacterial pathogens recovered from the urine of patients admitted to or assessed at hospitals across Canada (CANWARD). The in vitro activity of sulopenem and clinically relevant comparators was determined for 1880 Gram-negative and Gram-positive urinary isolates obtained as part of the CANWARD study (2014 to 2021) using the CLSI broth microdilution method. Sulopenem demonstrated excellent in vitro activity versus members of the Enterobacterales, with MIC90 values ranging from 0.06 to 0.5 mg/L for all species tested. Over 90% of ESBL-producing, AmpC-producing and MDR (not susceptible to ≥1 antimicrobial from ≥3 classes) Escherichia coli were inhibited by ≤0.25 mg/L of sulopenem. Sulopenem had an identical MIC90 to meropenem for ESBL-producing and MDR E. coli. The MIC90 of sulopenem and meropenem versus MSSA was 0.25 mg/L. Sulopenem was not active in vitro versus Pseudomonas aeruginosa (similar to ertapenem), and it demonstrated poor activity versus Enterococcus faecalis (similar to meropenem). Sulopenem demonstrated excellent in vitro activity versus bacterial pathogens recovered from the urine of Canadian patients. These data suggest that sulopenem may have a role in the treatment of urinary infections caused by antimicrobial-resistant Enterobacterales, but additional clinical studies are required.