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

Pearls and pitfalls of oral carbapenem/penem agents: the promise of a new era or the risk of amplified resistance? (PubMed, Expert Opin Pharmacother) - "This review examines the chemistry, pharmacokinetics/pharmacodynamics, and phase 3 trial evidence for tebipenem and sulopenem, recently FDA-approved for urinary tract infections (UTI). This risk requires strict resistance surveillance and formulary restriction to confirmed MDR infections lacking oral alternatives. Their clinical trajectory will depend less on intrinsic activity than on the rigor of AMS frameworks governing their use."

Journal • Infectious Disease • Nephrology

In vitro activity and in vivo efficacy of sulopenem against Bacillus anthracis in inhalational anthrax mouse and rabbit models. (PubMed, Antimicrob Agents Chemother) - "Fluoroquinolones and tetracyclines are common antibiotics used for post-exposure prophylaxis and treatment in the United States (U.S.), whereas penicillin is the drug of choice throughout the rest of the world...Using human-equivalent dosing regimens, we show that sulopenem is highly protective in both the mouse and rabbit inhalational anthrax models. Together, these results support continued evaluation of this oral penem as a countermeasure for inhalational anthrax."

Journal • Preclinical • Infectious Disease • Nephrology

The changing picture of community acquired urinary tract infections in the US: a daunting prospect. (PubMed, Expert Rev Anti Infect Ther) - "Resistance to fluoroquinolones and trimethoprim-sulfamethoxazole exceeding 40% among uropathogenic Escherichia coli - driven largely by multidrug-resistant and extended‑spectrum β‑lactamase (ESBL) - producing Enterobacterales strains such as ST131-are fueling increased reliance on parenteral agents, emergency department visits, and hospitalizations...It highlights oral agents approved or under review in the US, including pivmecillinam, sulopenem, and gepotidacin, each approved for uncomplicated UTI, as well as tebipenem pivoxil hydrobromide, which if approved, would represent the first oral carbapenem option for selected complicated UTIs, and discusses antimicrobial stewardship principles for community UTI management...Pharmacoeconomic analyses incorporating avoided admissions and patient convenience will be essential. Judiciously deployed within stewardship frameworks, these agents have potential to reduce the clinical and economic burden of multidrug-resistant UTI,..."

Journal • Review • Infectious Disease • Nephrology

Sulopenem Etzadroxil/Probenecid: A Comprehensive Review of an Oral Thiopenem. (PubMed, Ann Pharmacother) - "Sulopenem etzadroxil/probenecid provides an additional oral treatment option for uUTI in adult women with limited or no alternative options."

Journal • Review • Infectious Disease • Nephrology

Targeted Use of Sulopenem in Multidrug-Resistant Uncomplicated Urinary Tract Infections. (PubMed, Int J Antimicrob Agents) - No abstract available

Journal • Infectious Disease • Nephrology

Pivmecillinam (Pivya) for uncomplicated UTI. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Infectious Disease • Nephrology

Evidentiary Standards for Newly Approved Antibiotics for Uncomplicated Urinary Tract Infections. (PubMed, Antibiotics (Basel)) - "Interventions: Sulopenem/probenecid was compared to ciprofloxacin and to amoxicillin/clavulanate and gepotidacin was compared to nitrofurantoin. Pivotal clinical trials for sulopenem/probenecid and gepotidacin for uUTI had significant design limitations and relied on surrogate endpoints of limited clinical interpretability, undermining reliability and clinical relevance. Future antibiotic development for uUTI should prioritize representative populations, standard-of-care comparators, clinically meaningful outcomes and robust, well-controlled trial designs to ensure meaningful clinical evidence of safety and efficacy."

Clinical • Journal • Infectious Disease • Nephrology

Pharmacokinetics of Sulopenem Etzadroxil Plus Probenecid in Adolescents (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Iterum Therapeutics, International Limited | Trial completion date: Jul 2026 ➔ Oct 2026 | Initiation date: Jan 2026 ➔ Apr 2026 | Trial primary completion date: Jul 2026 ➔ Oct 2026

Trial completion date • Trial initiation date • Trial primary completion date • Infectious Disease

Comparison of in vitro antimicrobial activity of tebipenem, sulopenem, meropenem, and ertapenem against cefotaxime-resistant Enterobacterales (ESCMID Global 2026) - No abstract available

Preclinical

A systematic review of data on the resistance of uropathogens to sulopenem. (PubMed, Eur J Clin Microbiol Infect Dis) - No abstract available

Journal • Review

Understanding Pharmacokinetic-Drug Interactions With Drugs Approved by the US Food and Drug Administration in 2024 to Better Manage the Risk of Drug Interactions With Concomitant Medications: A Review of Clinical Data From New Drug Applications. (PubMed, Curr Ther Res Clin Exp) - "Of these, 7 drugs were substrates of CYP3A, 3 of CYP2C9, one of CYP1A2, and one of CYP2C8, including the sensitive substrates vanzacaftor (CYP3A) and vorasidenib (CYP1A2). As precipitants, 6 drugs (acoramidis, cefepime/enmetazobactam, givinostat, lazertinib, mavorixafor, and resmetirom) were clinical inhibitors of CYP enzymes (2C8, 2C9, 2D6, 2E1, and 3A), with mavorixafor being a CYP2D6 strong inhibitor. Two drugs (elafibranor and tovorafenib) showed weak induction of CYP3A. Regarding transporter data, 3 drugs were substrates of transporters, including seladelpar (BCRP and OAT3), sulopenem (OAT3), and vadadustat (OAT1/3), and 8 drugs (arimoclomol, danicopan, givinostat, lazertinib, mavorixafor, resmetirom, vadadustat, and vazacaftor/tezacaftor/deutivacaftor) were inhibitors of transporters...Several DDIs with an AUC change <2 also had labeling recommendations, pertaining most often to the concomitant use of drugs with a narrow therapeutic index. Mechanistic DDI..."

Clinical data • FDA event • Journal • NDA • PK/PD data • Review • CYP1A2 • CYP2C9

Gepotidacin (Blujepa) - a new antibiotic for uncomplicated UTI. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Infectious Disease • Nephrology

Exploring the activity of a novel orally bioavailable β-lactam-β-lactamase inhibitor combination, ceftibuten-ledaborbactam, against Enterobacterales-carrying blaOXA-48. (PubMed, Microbiol Spectr) - "In this study, we compared the in vitro antimicrobial activity of ceftibuten-ledaborbactam with that of other oral antibiotics, including tebipenem, sulopenem, ceftibuten-clavulanic acid, amoxicillin-clavulanic acid, and levofloxacin, against OXA-48-producing Enterobacterales. Our results show that ceftibuten-ledaborbactam has the most potent activity, with an MIC90 of 0.5 mg/L."

Journal

Sulopenem for the Treatment of Uncomplicated Urinary Tract Infections in Women (ASHP 2025) - No abstract available

Clinical • Infectious Disease • Nephrology

Evaluative Review of Sulopenem Etzadroxil/Probenecid for Urinary Tract Infections: Clinical Evidence, Efficacy, and Safety Outcomes (ASHP 2025) - No abstract available

Clinical • Review • Infectious Disease • Nephrology

Sulopenem: Rolling the Dice with Antibiotic Resistance? (ASHP 2025) - "Learning Objectives: Describe the antimicrobial stewardship concerns associated with availability of an oral carbapenem in the outpatient setting."

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