Jones Microbiology Institute, Inc.

- No Emergence of Resistance was Observed- Additional Years of Surveillance are Under Way BOSTON, July 31, 2024 (GLOBE NEWSWIRE) -- Paratek Pharmaceuticals, Inc., a biopharmaceutical company focused on providing innovative medical therapies that create positive patient stories in the hospital, community and public health settings, today shared overall findings from the company’s five-year post-approval microbiologic surveillance study of NUZYRA® (omadacycline), its broad-spectrum, oral and IV antibiotic. Surveillance studies are required by U.S. Food and Drug Administration (FDA) for all antibiotics as post-approval commitments and are intended to monitor for minimum inhibitory concentration (MIC) shifts as an indicator of potential resistance development. The surveillance study, timed to the market introduction of NUZYRA in early 2019, was designed to monitor the in vitro activity of omadacycline and relevant standard-of-care comparator antibiotics against Gram-positive and Gram-negative clinical bacterial isolates recovered from patients in the United States with different infection types. In addition, the program was designed to track the potential emergence of resistance to omadacycline as well as monitor the susceptibility patterns of comparator drugs. A total of 35,000 clinical isolates collected between 2019 and 2023 were evaluated. Omadacycline demonstrated consistent in vitro potency against the isolates evaluated with no emergence of resistance reported (i.e. MIC values remained unchanged with no year-on-year increases). “Since its commercial introduction in 2019 and its increased use across the United States, these in vitro results further support that NUZYRA remains an effective treatment option against the different bacterial pathogens that cause community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections, for which NUZYRA is indicated to treat,” said Randy Brenner, chief development and regulatory officer of Paratek. “Although this post-approval commitment with the FDA is complete, we have elected to extend this important microbiologic surveillance program for additional years, as part of Paratek’s continued commitment to address antimicrobial resistance.” The five-year study was conducted by JMI Laboratories in collaboration with Paratek. The results from this study will be presented and published later this year and have been submitted to the FDA, thus completing the post-approval commitment. The data are publicly available at paratek-keystone.com or can be requested via the AMR register on Vivli at vivli.org/amr-data-register/. The microbiologic surveillance study was funded as part of the company's Project BioShield contract (75A50120C00001) with the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services. About Paratek Pharmaceuticals, Inc. Paratek Pharmaceuticals, Inc. is a commercial-stage biopharmaceutical company focused on providing innovative medical therapies that create positive patient stories in the hospital, community and public health settings. The company's lead commercial product, NUZYRA® (omadacycline), is a once-daily oral and intravenous antibiotic available in the United States for the treatment of adults with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). Paratek has a collaboration agreement with Zai Lab Limited for the development and commercialization of omadacycline in the greater China region and retains all remaining global rights. Zai Lab received approval of both IV and oral NUZYRA as a Category 1 innovative drug by the National Medical Products Administration of China for the treatment of CABP and ABSSSI in December 2021 and in Macao for the treatment of CABP and ABSSSI in May 2023. Paratek is also conducting a Phase 2b study with NUZYRA in a rare disease, non-tuberculous mycobacterial (NTM) pulmonary disease, caused by Mycobacterium abscessus complex. In December 2019, BARDA awarded Paratek a contract (75A50120C00001) that is now valued at up to approximately $304 million. In addition to supporting the development of NUZYRA for both the treatment and prophylaxis of pulmonary anthrax, this contract supports the U.S. onshoring of NUZYRA and manufacturing security requirements; FDA post-marketing requirements associated with the initial NUZYRA approval; and the procurement of up to 10,000 treatment courses of NUZYRA for the treatment of anthrax. For more information, visit www.ParatekPharma.com or follow us on LinkedIn and Twitter. About NUZYRA®NUZYRA® (omadacycline) is a novel antibiotic with both once-daily oral and intravenous (IV) formulations for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). A modernized tetracycline, NUZYRA is specifically designed to overcome tetracycline resistance and exhibits activity across a spectrum of bacteria, including Gram-positive, Gram-negative, atypicals and other drug-resistant strains. IMPORTANT SAFETY INFORMATIONCONTRAINDICATIONSNUZYRA is contraindicated in patients with known hypersensitivity to omadacycline or tetracycline-class antibacterial drugs, or to any of the excipients. WARNINGS AND PRECAUTIONSMortality imbalance was observed in the CABP clinical trial with eight deaths (2%) occurring in patients treated with NUZYRA compared to four deaths (1%) in patients treated with moxifloxacin. The cause of the mortality imbalance has not been established. All deaths, in both treatment arms, occurred in patients > 65 years of age; most patients had multiple comorbidities. The causes of death varied and included worsening and/or complications of infection and underlying conditions. Closely monitor clinical response to therapy in CABP patients, particularly in those at higher risk for mortality. The use of NUZYRA during tooth development (last half of pregnancy, infancy and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown) and enamel hypoplasia. The use of NUZYRA during the second and third trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth. Hypersensitivity reactions have been reported with NUZYRA. Life-threatening hypersensitivity (anaphylactic) reactions have been reported with other tetracycline-class antibacterial drugs. NUZYRA is structurally similar to other tetracycline-class antibacterial drugs and is contraindicated in patients with known hypersensitivity to tetracycline-class antibacterial drugs. Discontinue NUZYRA if an allergic reaction occurs. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs. NUZYRA is structurally similar to tetracycline-class antibacterial drugs and may have similar adverse reactions. Adverse reactions, including photosensitivity, pseudotumor cerebri, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, hyperphosphatemia, pancreatitis, and abnormal liver function tests), have been reported for other tetracycline-class antibacterial drugs, and may occur with NUZYRA. Discontinue NUZYRA if any of these adverse reactions are suspected. Prescribing NUZYRA in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. ADVERSE REACTIONSThe most common adverse reactions (incidence ≥2%) are nausea, vomiting, infusion site reactions, alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyl transferase increased, hypertension, headache, diarrhea, insomnia, and constipation. DRUG INTERACTIONSPatients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage while taking NUZYRA. Absorption of tetracyclines, including NUZYRA is impaired by antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate and iron containing preparations. USE IN SPECIFIC POPULATIONSLactation: Breastfeeding is not recommended during treatment with NUZYRA. See full prescribing information here. MEDIA CONTACT: Christine Fanelle Scient PR Christine@ScientPR.com215-595-5211

Eight presentations on antibiotic ceftobiprole providing further evidence for its activity against methicillin-resistant Staphylococcus aureus (MRSA) and other clinically relevant pathogens Allschwil, Switzerland, October 17, 2023 Basilea Pharmaceutica Ltd, Allschwil (SIX: BSLN), a commercial-stage biopharmaceutical company committed to meeting the needs of patients with severe bacterial and fungal infections, announced today that scientific presentations with new data on its antibiotic ceftobiprole (Zevtera®) have been presented at Infectious Disease Week (IDWeek) 2023, highlighting its utility for the treatment of severe bacterial infections. IDWeek is the annual meeting of the Infectious Diseases Society of America (IDSA), jointly held with other infectious diseases societies in the US, and took place in Boston, Massachusetts (USA) from 11 to 15 October 2023. Dr. Marc Engelhardt, Chief Medical Officer of Basilea, stated: “The data presented at IDWeek provide further evidence for the potent antimicrobial activity of ceftobiprole against MRSA and other clinically relevant pathogens. It also provides results of pharmacokinetic-pharmacodynamic modeling supporting the dosing regimens to treat severe bacterial infections from the successful clinical phase 3 studies. These studies were conducted in patients with Staphylococcus aureus bacteremia (SAB), acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). These are the three indications included in our New Drug Application, which is currently under priority review with the US FDA, with a Prescription Drug User Fee Act (PDUFA) goal date of 03 April 2024.” Data from four presentations, building on pharmacokinetic-pharmacodynamic modeling, provided evidence that the exposure achieved with the applied dosing regimens was efficacious for the treatment of Staphylococcus aureus bacteremia (SAB) in the ERADICATE phase 3 study.1 The same was also shown in analyses for the ceftobiprole phase 3 studies in acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP).2, 3 Four additional abstracts included data from large in-vitro susceptibility studies testing bacterial isolates from US patients, which confirmed that ceftobiprole exhibits potent in-vitro activity against methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA, MRSA), as well as against Streptococcus pneumoniae and Enterococcus faecalis, and retained its potency over the surveillance period of several years against these clinically relevant pathogens. The presented data were generated in collaboration with the Institute for Clinical Pharmacodynamics, Schenectady, New York (USA), JMI Laboratories, North Liberty, Iowa, (USA) and the Duke Clinical Research Institute, Durham, North Carolina (USA). Basilea’s ceftobiprole phase 3 program is funded in part with federal funds from the US Department of Health and Human Services (HHS); Administration for Strategic Preparedness and Response (ASPR); Biomedical Advanced Research and Development Authority (BARDA), under contract number HHSO100201600002C. Basilea has been awarded approximately USD 112 million, or approximately 75 percent of the costs related to the phase 3 studies in SAB and acute bacterial skin and skin structure infections (ABSSSI), regulatory activities and non-clinical work. Ceftobiprole data presented at IDWeek 2023 Abstract #1946 – In Vitro Activity of Ceftobiprole against Staphylococcus aureus Bacteremia Isolates from the United States (2018–2020) – L. Duncan, M. Castanheira, J. I. Smart, M. E. Jones, R. E. Mendes Abstract #2162 – In Vitro Antimicrobial Activity of Ceftobiprole against Streptococcus pneumoniae Isolates from the United States (2016–2020) – L. Duncan, M. Castanheira, J. I. Smart, M. E. Jones, R. E. Mendes Abstract #2173 – Activity of Ceftobiprole Against Enterococcus faecalis Clinical Isolates From the United States (2016–2020), Including Those From Difficult-to-Treat Infections – R. E. Mendes, L. Duncan, H. S. Sader, J. I. Smart, M. E. Jones, M. Castanheira Abstract #2530 – Pharmacokinetic-Pharmacodynamic (PK-PD) Target Attainment Analyses to Support Ceftobiprole Dose Selection for the Treatment of Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) and Community-Acquired Bacterial Pneumonia (CABP) – S. M. Bhavnani, J. P. Hammel, A. J. Rinaldo, J. I. Smart, K. Litherland, L. Duncan, M. E. Jones, M. Engelhardt, P. G. Ambrose, C. M. Rubino Abstract #2531 – Pharmacokinetic-Pharmacodynamic (PK-PD) Target Attainment Analyses to Support Ceftobiprole Dosing Regimens for Patients with Staphylococcus aureus Bacteremia (SAB) – S. M. Bhavnani, J. P. Hammel, A. J. Rinaldo, J. I. Smart, K. Litherland, L. Duncan, M. E. Jones, M. Engelhardt, P. G. Ambrose, C. M. Rubino Abstract #2532 – Pharmacokinetic-Pharmacodynamic Analyses for Ceftobiprole Efficacy Based on Phase 3 Data from Patients with Staphylococcus aureus Bacteremia – S. M. Bhavnani, J. P. Hammel, K. Liolios, A. P. Cammarata, M. Saulay, C. M. Rubino, M. Engelhardt, J. I. Smart, M. E. Jones, P. G. Ambrose, K. Litherland Abstract #2561 – Population Pharmacokinetic Analyses for Ceftobiprole Using Data from Phase 1 and 3 Studies – A. P. Cammarata, K. Litherland, M. C. Safir, S. M. Bhavnani, M. Saulay, J. I. Smart, M. E. Jones, M. Engelhardt, C. M. Rubino Abstract #2785 - Characterization of Methicillin-resistant Staphylococcus aureus Bloodstream Isolates Recovered from Patients Enrolled in a Randomized, Double-blind, Multi-center Study to Establish the Efficacy and Safety of Ceftobiprole for Treatment of Bacteremia, Including Infective Endocarditis – R. E. Mendes, L. Duncan, J. H. Kimbrough, T. L. Holland, V. G. Fowler Jr, M. E. Jones, M. Engelhardt, J. I. Smart, M. Castanheira About ceftobiprole Ceftobiprole, the active moiety of the prodrug ceftobiprole medocaril, is an advanced generation cephalosporin antibiotic for intravenous administration, with rapid bactericidal activity against a wide range of Gram-positive bacteria such as Staphylococcus aureus, including methicillin-resistant strains (MRSA), and Gram-negative bacteria.4 The brand is currently approved and marketed as Zevtera® and Mabelio® in several countries in Europe and beyond for the treatment of adult patients with hospital-acquired bacterial pneumonia (HABP), excluding ventilator-associated bacterial pneumonia (VABP), and for the treatment of community-acquired bacterial pneumonia (CABP). Basilea has entered into license and distribution agreements covering more than 80 countries. Ceftobiprole is currently not approved or partnered in the US. Ceftobiprole was designated a Qualified Infectious Disease Product (QIDP) by the US Food and Drug Administration (FDA) for SAB, ABSSSI and CABP. Therefore, if approved, ceftobiprole would be eligible to receive ten years of market exclusivity in the US from the date of approval. About Basilea Basilea is a commercial-stage biopharmaceutical company founded in 2000 and headquartered in Switzerland. We are committed to discovering, developing and commercializing innovative drugs to meet the needs of patients with severe bacterial and fungal infections. We have successfully launched two hospital brands, Cresemba for the treatment of invasive fungal infections and Zevtera for the treatment of bacterial infections. In addition, we have preclinical anti-infective assets in our portfolio. Basilea is listed on the SIX Swiss Exchange (SIX: BSLN). Please visit basilea.com. Disclaimer This communication expressly or implicitly contains certain forward-looking statements, such as "believe", "assume", "expect", "forecast", "project", "may", "could", "might", "will" or similar expressions concerning Basilea Pharmaceutica Ltd, Allschwil and its business, including with respect to the progress, timing and completion of research, development and clinical studies for product candidates. Such statements involve certain known and unknown risks, uncertainties and other factors, which could cause the actual results, financial condition, performance or achievements of Basilea Pharmaceutica Ltd, Allschwil to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Basilea Pharmaceutica Ltd, Allschwil is providing this communication as of this date and does not undertake to update any forward-looking statements contained herein as a result of new information, future events or otherwise. For further information, please contact: Peer Nils Schröder, PhDHead of Corporate Communications & Investor RelationsBasilea Pharmaceutica International Ltd, Allschwil Hegenheimermattweg 167b4123 AllschwilSwitzerlandPhone+41 61 606 1102E-mailmedia_relations@basilea.cominvestor_relations@basilea.com This press release can be downloaded from www.basilea.com. References ERADICATE (SAB): ClinicalTrials.gov identifier NCT03138733T. L. Holland, S. E. Cosgrove, S. B. Doernberg et al. Ceftobiprole for treatment of complicated Staphylococcus aureus bacteremia. New England Journal of Medicine 2023 (389), 1390-1401; DOI: 10.1056/NEJMoa2300220TARGET (ABSSSI): ClinicalTrials.gov identifier NCT03137173J. S. Overcash, C. Kim, R. Keech R et al. Ceftobiprole compared with vancomycin plus aztreonam in the treatment of acute bacterial skin and skin structure infections: Results of a phase 3, randomized, double-blind trial (TARGET). Clinical Infectious Diseases 2021 (73), e1507-e1517CABP study: ClinicalTrials.gov identifier NCT00326287S. C. Nicholson, T. Welte, T. M. File Jr. et al. A randomised, double-blind trial comparing ceftobiprole medocaril with ceftriaxone with or without linezolid for the treatment of patients with community-acquired pneumonia requiring hospitalization. International Journal of Antimicrobial Agents 2012 (39), 240-246Summary of Product Characteristics (SmPC) Zevtera: https://www.medicines.org.uk/emc/product/9164/smpc [Accessed October 16, 2023] Press release (PDF)

Growing Global Incidence of Carbapenem-Resistant Enterobacterales Metallo-beta-lactamases were the most frequently identified carbapenem resistance mechanism among Enterobacterales isolates in IHMA global surveillance MALVERN, Pa.--(BUSINESS WIRE)-- Venatorx Pharmaceuticals, a private, pre-commercial pharmaceutical company focused on improving health outcomes for patients with difficult-to-treat drug resistant gram-negative bacterial infections and viral infections, today highlights two recent publications that provide important updates on the changing epidemiology of carbapenem-resistant Enterobacterales (CRE) globally and in the United States (US). According to a recent global surveillance publication from International Health Management Associates (IHMA), the proportion of carbapenem resistance among Enterobacterales increased from 3.3% of isolates from 2012-2017 to 5.7% in 2018-2019, a 72% increase[1]. When looking deeper at the specific contribution from carbapenemase families, metallo-beta-lactamases (MBLs) were the most frequently identified carbapenem resistance mechanism. In the publication from IHMA[1], data from participating global hospitals in 2018-2019 demonstrated that the majority of carbapenem resistance mechanisms identified among CRE isolates collected were MBLs (36.7%). MBLs were the most frequently seen carbapenemase in isolates from Asia/Pacific (59.4%) and Africa and Middle East (49%) and were as frequently detected as Klebsiella pneumoniae carbapenemases (KPCs) in Europe (both at approximately 28%). In the U.S. and Canada, MBLs were found in 15.5% of all CRE isolates in 2018-2019, or approximately 1 out of every 7 CRE isolates. This represents a 300% increase from the 2012-17 period when only 5% of CRE isolates expressed MBLs in the US and Canada.[2] This frequency is also consistent with JMI Laboratories’ 2021 US CRE surveillance in the US and Canada reporting 18.4% of CRE isolates carrying MBLs.[3] In a second publication, Tamma et al.[4] of Johns Hopkins University analyzed consecutive CRE clinical isolates collected from unique patients at 3 US hospitals from 2016-2021. Of the 603 total CRE isolates, 276 expressed carbapenemases and 29 of those isolates, approximately 4.8% of all cases and 15.4% of carbapenemase-positive cases, produced MBLs. In response to growing awareness of MBL occurrence in the US, 2023 US Infectious Diseases Society of America (IDSA) guidance [5] recommends that patients with gram-negative infections that are suspected or confirmed to contain MBLs be treated with the sub-set of CRE treatment regimens whose coverage includes both MBLs and serine beta-lactamases (SBLs). “Since MBLs were the most frequent resistance mechanism identified globally within CRE isolates and identified in a growing proportion of US CRE isolates in the IHMA surveillance, it is essential that the next generation of antibiotics are available to combat the evolving landscape of multi-drug resistant gram-negative bacterial infections,” said Christopher J. Burns, Ph.D., Chief Executive Officer of Venatorx. “Development of new antibiotics with comprehensive MBL coverage is necessary to address global critical unmet medical needs and provide hope for patients and healthcare providers alike to effectively treat appropriate patients with these gram-negative resistant infections.” About Gram-Negative Infections and Antimicrobial Resistance (AMR) In a recent report on AMR, the U.S. Centers for Disease Control and Prevention (CDC) reported rates of resistance have increased significantly in the U.S. among bacterial pathogens including those commonly causing cUTI, pyelonephritis, and bacteremia. The CDC also cited that there are more than 2.8 million AMR infections annually in the U.S., which are directly related to more than 35,000 deaths.[6] Between 2014 and 2019, an analysis of U.S. UTI patients determined that 4.4% of cases were carbapenem resistant (CR) and 24.5% of U.S. UTI patients were bacteremic with 1.7% of cases caused by a CR pathogen. Patients with CR infections had a significantly longer hospital length of stay (LOS), were less likely to be discharged home, had a higher readmission rate, and had greater LOS-associated charges than patients with carbapenem-susceptible infections. Additionally, patients with bacteremia (urosepsis) due to CR pathogens had a significantly higher rate of mortality than those with carbapenem susceptible pathogens.[7] Gram-negative bacteria have multiple AMR mechanisms that continue to adapt in response to increases in antibiotic usage. Carbapenems are broad-spectrum antibiotics that have been widely used to treat infections caused by multidrug-resistant gram-negative bacteria, including Enterobacterales. With the increased global use of carbapenems, CRE have emerged, which have limited treatment options and are associated with increased morbidity and mortality. Resistance to carbapenems among Enterobacterales is primarily achieved by production of carbapenemases, which are enzymes capable of hydrolyzing carbapenem antibiotics and most other beta-lactams and fall into two distinct families: serine beta-lactamases and metallo-beta-lactamases (MBLs). Common variants of MBLs include New Delhi MBL (NDM) and Verona Integron-encoded MBL (VIM). According to an IHMA surveillance study in 2018-2019 and JMI US Surveillance study from 2021, MBLs were the most commonly identified carbapenem resistance mechanism globally among Enterobacterales isolates, with ~16 to 18% of US CRE isolates carrying MBLs. [1,3] While carbapenem-resistant Pseudomonas aeruginosa (CRPA) is also increasing in some geographies due to emergence of MBLs, multidrug-resistant P. aeruginosa (MDR-PA), which may exhibit resistance to carbapenems, represents an increasing challenge for clinicians and their patients in the US and globally due to the paucity of treatment options for this primarily hospital-associated pathogen. Especially outside the US, CRPA may carry carbapenemases including MBLs (i.e., VIM); however, non-carbapenemase resistance mechanisms (i.e., efflux pumps, porins) also contribute to the growing global resistance of MDR-PA and CRPA.[8] If AMR infections continue on this trajectory, it has been projected that an estimated 10 million people will die per year of resistant infections by 2050—a number that surpasses the projected annual number of deaths (8.2 million) caused by cancer—and the cumulative cost to the global economy could be as high as US$100 trillion.[9] In the U.S., estimates have reached as high as US$20 billion in excess direct healthcare costs, with an additional US$35 billion associated with lost productivity.[10] By 2050, the world is at risk of losing up to 3.8% of its annual gross domestic product with an annual shortfall of up to US$3.4 trillion by 2030, a figure on par with losses attributable to the 2008 global financial crisis.[11] The Infectious Disease Society of America (IDSA) maintains updated guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections online at .[5] For those patients who do not respond to current treatment, new antibiotic therapies are needed to combat AMR. About Venatorx Pharmaceuticals, Inc. Venatorx is a private, pre-commercial pharmaceutical company focused on improving health outcomes for patients with difficult-to-treat drug resistant gram-negative bacterial infections and viral infections. Venatorx’s lead asset, cefepime-taniborbactam, is an investigational antibiotic that completed a Phase 3 study (NCT03840148) in adults with complicated urinary tract infections (cUTI), including pyelonephritis. In October 2022, BARDA awarded a contract of up to $318M to Venatorx for development and procurement of cefepime-taniborbactam for the treatment of melioidosis and multidrug-resistant infections. As part of its broader pipeline, Venatorx is also developing an oral antibacterial, ceftibuten-ledaborbactam etzadroxil, that is currently in Phase 1 clinical studies. For more information about Venatorx and its anti-infectives portfolio, please visit . References [1] Estabrook et al. Epidemiology of Resistance Determinants Identified in Meropenem-Nonsusceptible Enterobacterales Collected as Part of a Global Surveillance Study, 2018 to 2019. Antimicrobial Agents and Chemotherapy; May 2023, Vol. 67, Issue 5 [2] Kazmierczak Antimicrob Agents Chemother. 2021 Jun 17;65(7):e0200020. doi: 10.1128/AAC.02000-20. Epub 2021 Jun 17. [3] Castanheira et al. Increase in the Occurrence of Carbapenem-Resistant Enterobacterales in United States Hospitals from 2019 to 2021 and Activity of Novel Beta-Lactams/Beta-Lactamase Inhibitor Combinations Against these Isolates, 2022 ID Week Abstract #664. Open Forum Infectious Diseases, Volume 9, Issue Supplement_2, December 2022, ofac492.716 [4] Tamma et al. Comparing the activity of novel antibiotic agents against carbapenem-resistant Enterobacterales clinical isolates Infection Control & Hospital Epidemiology (2023), 44, 762–767 [5] Infectious Disease Society of America maintains updated guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections posted online at accessed July 2023 [6] Antibiotic Resistance Threats in the United States 2019, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. [7] Shields et al. Burden of illness in U.S. hospitals due to carbapenem-resistant gram-negative urinary tract infections in patients with or without bacteremia. BMC Infectious Diseases (2021) 21:572. [8] Jean S-S, Harnod D and Hsueh P-R (2022) Global Threat of Carbapenem Resistant Gram-Negative Bacteria. Front.Cell. Infect.Microbiol.12:823684. doi:10.3389/fcimb.2022.823684 [9] O’Neill, J. ‘Tackling Drug-Resistant Infections Globally: Final Report and Recommendations’. Review on Antimicrobial Resistance. May 2016. [10] Antibiotic Resistance Threats in the United States 2013, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. [11] World Bank. Final Report Drug Resistant Infections: A Threat to Our Economic Future. Mar 2017.