sulopenem etzadroxil/probenecid (CP-70429) / Iterum - LARVOL DELTA

Pharmacokinetics of Sulopenem Etzadroxil Plus Probenecid in Adolescents (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Iterum Therapeutics, International Limited | Initiation date: Sep 2025 ➔ Jan 2026 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial initiation date • Infectious Disease

Cost-Effectiveness of Sulopenem vs. Ciprofloxacin for the Treatment of Uncomplicated Urinary Tract Infections in Women: A Decision Analysis (ISPOR-EU 2025) - P3 | "Ciprofloxacin was found to be the cost-effective choice for treating uncomplicated UTIs in women under typical clinical scenarios."

Clinical • Cost effectiveness • HEOR • Infectious Disease • Nephrology

Sulopenem etzadroxil/probenecid (Orlynvah) for uncomplicated UTIs. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Infectious Disease • Nephrology

Redefining uUTI therapy: Orlynvah as a promising oral alternative (sulopenem etzadroxil and probenecid). (PubMed, Ann Med Surg (Lond)) - "The efficacy of Orlynvah was established through two large multicenter trials, which demonstrated superior outcomes compared to amoxicillin-clavulanate and improved efficacy over ciprofloxacin in cases involving resistant pathogens. The drug was generally well-tolerated, with few serious adverse events reported. Orlynvah offers a promising oral alternative in the era of rising antimicrobial resistance and represents a significant advancement in the management of uUTIs."

Journal • Infectious Disease • Nephrology

Targeting Mycobacterium abscessus: Dual mechanisms and enhanced killing by optimized β-Lactam/β-Lactamase inhibitor combinations (NACFC 2025) - "Among 18 β-lactams tested with or without BLIs (avibactam and durlobactam), the imipenemdurlobactam combination exhibited the strongest Mab killing, surpassing the standard-of-care regimen (amikacin, clarithromycin, and imipenem or cefoxitin) (Fig...β-lactams and BLIs binding to PBP-lipo—such as sulopenem, imipenem, durlobactam, and amoxicillin—induced filamentous cell morphology (Fig... The combination of imipenem and durlobactam demonstrated potent Mab killing with minimal regrowth, attributable to robust β-lactamase inhibition and targeting of multiple LDTs and PBPs. These results highlight the potential of this combination as a promising therapeutic strategy for Mab infections in CF patients, warranting further clinical investigation."

Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Respiratory Diseases

The Drug Update: Recent drug approvals, summer 2025 edition. (PubMed, Nurse Pract) - "This article highlights the following new medications: donanemab-azbt (Kisunla), nalmefene injection (Zurnai), epinephrine nasal spray (neffy), palopegteriparatide (Yorvipath), xanomeline and trospium chloride (Cobenfy), and sulopenem etzadroxil/probenecid (Orlynvah). Additionally, this article highlights the recent approval of obstructive sleep apnea as a new indication for tirzepatide (Zepbound) and chronic obstructive pulmonary disease as a new indication for dupilumab (Dupixent)."

Journal • Addiction (Opioid and Alcohol) • Allergy • Alzheimer's Disease • Chronic Obstructive Pulmonary Disease • CNS Disorders • Endocrine Disorders • Hypoparathyroidism • Immunology • Obstructive Sleep Apnea • Psychiatry • Pulmonary Disease • Respiratory Diseases • Schizophrenia • Sleep Disorder

The oral penems and carbapenems. (PubMed, Clin Microbiol Rev) - "The majority of available carbapenems can only be administered parenterally, but two orally administered penems (faropenem and sulopenem) and one orally administered carbapenem (tebipenem) are in increased use due to approvals in new markets. These oral agents have a spectrum of activity similar to widely used parenteral carbapenems but are simpler to administer than intravenous agents and will likely experience rapid increases in their rates of use as they are approved in new markets. In this review, we discuss their spectra of activity, pharmacokinetics, pharmacodynamics, clinical efficacy, toxicity, antimicrobial stewardship considerations, and potential clinical applications."

Journal • Review

An evaluation of antibiotic options for the treatment of biothreat pathogens. (PubMed, Front Antibiot) - "This review includes finafloxacin, levofloxacin, delafloxacin, omadacycline, gepotidacin, tebipenem and sulopenem. The selection criteria of these antibiotics were 1) the availability of an oral formulation, 2) the regulatory status (licensed by a regulatory authority or in an advanced stage of development) and 3) the availability of publicly available information on the biodefence pathogens of concern. We hope to highlight approved or advanced clinical candidates that have significant and unique potential in the biodefense space which may be deployed to protect both the public and warfighter against these bacterial infections."

Journal • Review • Infectious Disease

In Vitro Activity of Sulopenem and Comparator Agents Against U.S. Enterobacterales Clinical Isolates, SENTRY Antimicrobial Surveillance Program, 2023 (IDWeek 2025) - No abstract available

Preclinical • Infectious Disease

An Overview of Urinary Tract Infection in Adult Women: Focus on Oral Sulopenem (IDWeek 2025) - "Supported By Iterum Therapeutics"

Clinical • Infectious Disease

Sulopenem Etzadroxil and Probenecid: A Drug Review of a Novel Oral Penem Active Against Extended-Spectrum Beta-Lactamase (ESBL) Producing Bacteria. (PubMed, Am J Health Syst Pharm) - "Sulopenem is an effective and safe treatment option for the treatment of uUTI in adult women, however current research lacks the evidence to confidently recommend sulopenem for other infectious diseases."

Journal • Infectious Disease • Nephrology

SUSCEPTIBILITY OF MULTI-DRUG RESISTANT ESCHERICHIA COLI AND KLEBSIELLA PNEUMONIAE TO ORAL ANTIBIOTICS IN AUSTRALIA. (PubMed, J Glob Antimicrob Resist) - "The favourable results support the use of mecillinam, tebipenem, sulopenem, faropenem, fosfomycin and omadacycline against multi-drug resistant E. coli. Mecillinam, sulopenem and fosfomycin may be useful for multi-drug resistant K. pneumoniae in Australia."

Journal • Infectious Disease • Nephrology • Pneumonia

Pharmacokinetics of Sulopenem Etzadroxil Plus Probenecid in Adolescents (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Iterum Therapeutics, International Limited

New P1 trial • Infectious Disease

The Role of Sulopenem in the Treatment of Uncomplicated Urinary Tract Infections: A Systematic Review and Meta-Analysis. (PubMed, Cureus) - "So, first-line agents such as nitrofurantoin and trimethoprim-sulfamethoxazole are losing their beneficial effects. Sulopenem/probenecid was equal or superior to amoxicillin/clavulanate, including among resistant strains. PK/PD modeling confirmed bactericidal concentrations for a sustained duration."

Journal • Retrospective data • Review • Infectious Disease • Nephrology

In vitro activity of sulopenem and comparator agents against U.S. Enterobacterales clinical isolates collected during the SENTRY antimicrobial surveillance program in 2023. (PubMed, J Glob Antimicrob Resist) - "The potent in vitro activity of sulopenem against this large collection of contemporary Enterobacterales clinical isolates from multiple infection types supports its use in the treatment of uncomplicated urinary tract infection, as well as its further clinical evaluation in the treatment of other common bacterial infections demonstrating resistant phenotypes."

Journal • Preclinical • Infectious Disease • Nephrology • Pneumonia

Sulopenem versus Amoxicillin/Clavulanate for the Treatment of Uncomplicated Urinary Tract Infection. (PubMed, NEJM Evid) - P3 | "Sulopenem was noninferior to amoxicillin/clavulanate for the treatment of adult women with uncomplicated urinary tract infection, but was associated with more frequent mild adverse events. (Funded by Iterum Therapeutics; REASSURE ClinicalTrials.gov number, NCT05584657.)."

Clinical • Journal • Infectious Disease • Nephrology • Pain

Optimized β-Lactam/β-Lactamase Inhibitor Combinations for Mycobacterium abscessus: Dual Mechanisms of Action and Enhanced Killing (ASM Microbe 2025) - "Durlobactam alone caused a ~2 log10 reduction and achieved near-complete eradication when combined with imipenem or dual β-lactams, surpassing the standard-of-care regimen (amikacin, clarithromycin, and imipenem or cefoxitin). Sulopenem, imipenem, durlobactam, and amoxicillin induced filamentous cell morphology through PBP-lipo inhibition, a phenomenon corroborated by DSF-derived melting temperature shifts. The combination of imipenem and durlobactam demonstrated potent Mab killing with minimal regrowth, attributable to robust β-lactamase inhibition and dual targeting of LDTs and PBPs. These results highlight the potential of this combination as a promising therapeutic strategy for Mab infections, warranting further clinical investigation."

Infectious Disease • Respiratory Diseases

Recent Developments in Penem Antibiotics: Structural and Therapeutic Perspectives. (PubMed, Molecules) - "Notable representatives such as sulopenem and faropenem are discussed...The review also highlights the challenges and future possibilities in penem research, including the need for improved oral bioavailability and the potential for combination therapies with β-lactamase inhibitors. Overall, penems are valuable antibacterial agents in the antimicrobial arsenal, offering hope in the ongoing battle against multidrug-resistant pathogens."

Journal • Review • Infectious Disease • Nephrology

Sulopenem Etzadroxil/Probenecid. (PubMed, Hosp Pharm) - "Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433."

Journal • Review

Characterization of sulopenem antimicrobial activity using in vitro time-kill kinetics, synergy, post-antibiotic effect, and sub-inhibitory MIC effect methods against Escherichia coli and Klebsiella pneumoniae isolates. (PubMed, Microbiol Spectr) - "The oral dosing regimen of sulopenem etzadroxil/probenecid 500 mg/500 mg administered every 12 hours was recently evaluated in two phase 3 clinical trials where sulopenem demonstrated efficacy against amoxicillin-clavulanate in uncomplicated urinary tract infection (uUTI) and against ciprofloxacin in fluoroquinolone-resistant uUTI.IMPORTANCESulopenem is an oral and intravenous penem antibiotic in clinical development for treatment of urinary tract and intra-abdominal infections caused by multidrug-resistant pathogens. This study evaluated sulopenem via broth microdilution susceptibility testing, PAE, sub-inhibitory MIC PAE effect, checkerboard testing, and time-kill testing. The results of this study-interpreted along with recent pharmacodynamic in vitro one-compartment and hollow-fiber infection model work-provide insight into the in vitro activity of sulopenem."

Journal • Preclinical • Infectious Disease • Nephrology • Pneumonia

Durlobactam in combination with β-lactams to combat Mycobacterium abscessus. (PubMed, Antimicrob Agents Chemother) - "Imipenem demonstrated high binding affinity to LDTs and PBPs, with extremely low inhibition constants (Ki,app; ≤0.002 mg/L for LDT1-2, ≤0.6 mg/L for PBPs), while cephalosporins, sulopenem, tebipenem, and amoxicillin exhibited moderate to low binding affinity...Durlobactam alone showed ~2 log10 reduction, and when combined with imipenem or two β-lactams, durlobactam achieved near-eradication of Mab, surpassing the current therapy (amikacin + clarithromycin + imipenem/cefoxitin). Inactivation of PBP-lipo by sulopenem, imipenem, durlobactam, and amoxicillin (with avibactam) led to morphological changes, showing filaments. This study demonstrates the mechanistic basis of combinations therapy, particularly imipenem + durlobactam, in overcoming β-lactam resistance in Mab."

Journal

A phase 3 randomized trial of sulopenem vs. ertapenem in patients with complicated intraabdominal infections. (PubMed, Clin Microbiol Infect) - P3 | "Sulopenem IV followed by oral sulopenem etzadroxil/probenecid was not noninferior to ertapenem followed by oral step-down in treating cIAI in the micro-MITT population. This finding should be interpreted in the context of country regulations, as endpoint timing, primary analysis population and noninferiority margin may vary regionally. Both IV and oral sulopenem were well-tolerated; the oral formulation allowed patients with resistant pathogens to step down from IV therapy."

Journal • P3 data • Infectious Disease

Sulopenem is Efficacious in a Rabbit Model of Inhalational Anthrax (IDWeek 2024) - No abstract available

Preclinical • Infectious Disease

Oral Sulopenem/probenecid for Uncomplicated Urinary Tract Infections (uUTI): Results from the REASSURE Trial (IDWeek 2024) - No abstract available

Infectious Disease

β-Lactam and β-Lactamase Inhibitor Combination Combating Mycobacterium abscessus: Synergistic Effects of Imipenem and Durlobactam Revealed Through β-Lactamase Inhibition and Multi-Target Receptor Inactivation (ASM Microbe 2024) - "The current therapies have significant toxicities (such as amikacin), emphasizing the need for a safer option...Using Mab ATCC19977, we conducted time kill studies over 10 days to evaluate the effects of BL/BLI using avibactam (AVI), durlobactam (DUR) + sulbactam (SUL), imipenem (IPM), sulopenem (SULO), ceftaroline, cefuroxime, and amoxicillin (AMX) (inoc.: 6.0 log10 CFU/mL)...This outcome can be attributed to β-lactamase inhibition and the inactivation of multiple targets (LDTs and PBPs), highlighting the notion of target redundancy. This combination strategy holds promise for enhanced safety and efficacy against Mab, necessitating further study in animal models and subsequent clinical trials.$$graphic_{00A83904-230A-43BC-A26E-2C07450F2202}$$$$graphic_{EE21A07B-B039-42FD-BCAF-3253E2F36605}$$"

Pulmonary Disease • Respiratory Diseases