Vabomere (meropenem/vaborbactam) / Melinta Therap, Menarini - LARVOL DELTA

Case Report of Treatment of Polymicrobial Bacteremia Caused by Carbapenem-Resistant Klebsiella pneumoniae, and Bacillus Species in an Immunocompetent Patient With Meropenem-Vaborbactam. (PubMed, J Pharm Pract) - "The Infectious Disease Society of America (IDSA) recommends meropenem-vaborbactam, ceftazidime-avibactam, or imipenem-cilastatin-relebactam as preferred options with cefiderocol as an alternative, all of which are also alternative options for CTX-M Enterobacterales...This case report illustrates the treatment course of CTX-M and KPC-producing Klebsiella pneumoniae, and Bacillus species bacteremia that included cefiderocol, followed by vancomycin and meropenem-vaborbactam, and then meropenem-vaborbactam monotherapy...In our report, an immunocompetent patient developed a polymicrobial bloodstream infection caused by an MDR Klebsiella pneumoniae, and Bacillus species, which was successfully treated with meropenem-vaborbactam. This unusual infection and treatment course also serves to promote awareness of another treatment option for invasive Bacillus species infection and furthermore encourages providers to request testing & sensitivities to consolidate therapy,..."

Journal • Infectious Disease • Pneumonia

Emergence of mutH V76G among longitudinal carbapenem resistant Klebsiella pneumoniae causing long-term colonization and recurrent infection disrupts DNA mismatch repair and results in a hypermutator phenotype. (PubMed, bioRxiv) - "Clinical mutH V76G isolates and CRISPR-engineered mutH V76G mutants were hypermutators based on rifampin mutational frequencies...Both clinical and lab-engineered mutH V76G mutant strains rapidly acquire resistance or reduced susceptibility to new antibiotics like ceftazidime-avibactam, meropenem-vaborbactam and cefiderocol, due to mutations in carbapenemase ( bla KPC-3 ), porin ( ompK36 ) and other genes. mutH V76G -driven hypermutation also enhances horizontal transfer of resistance plasmids and improves K. pneumoniae fitness during mouse infections. This study is important for understanding K. pneumoniae hypermutation as a potent mediator of antibiotic resistance and other phenotypes relevant to human infections."

Journal • Mismatch repair • Infectious Disease • Pneumonia

Antimicrobial Activity of Aztreonam-Avibactam and Other β-Lactamase Inhibitor Combinations Tested Against Enterobacterales Isolates from Pediatric Patients from United States Medical Centers (2019-2023). (PubMed, Antibiotics (Basel)) - "Susceptibility to imipenem-relebactam varied from 97.1% (ceftriaxone-nonsusceptible) to 100.0% (ESBL producers). Ceftolozane-tazobactam showed good activity against ESBL producers (91.8% susceptible), but limited activity against ceftriaxone-nonsusceptible (75.8% susceptible) and MDR isolates (80.9% susceptible)...ESBL-producing Enterobacterales, mainly CTX-M, remain an important cause of infection in children. Aztreonam-avibactam, ceftazidime-avibactam, and meropenem-vaborbactam were highly active against isolates from both pediatric and adult population."

Journal • Infectious Disease • Nephrology • Pediatrics • Pneumonia • Respiratory Diseases

Use of Aztreonam-Avibactam with Rapid Eravacycline Step-Down Therapy for a Tibial Septic Non-Union by NDM-Producing Enterobacter cloacae. (PubMed, Antibiotics (Basel)) - "Cultures grew Enterobacter cloacae complex resistant to meropenem, ceftazidime-avibactam, meropenem-vaborbactam, and cefiderocol, as well as Candida parapsilosis...The patient was treated with ATM-AVI plus micafungin, achieving clinical stability within three days...At eight-week follow-up, the patient remained clinically improved without relapse or adverse effects. This case highlights ATM-AVI as a critical therapy for NDM-producing orthopedic infections involving hardware and supports eravacycline as a feasible step-down option in outpatient management."

Journal • Infectious Disease • Musculoskeletal Diseases • Orthopedics

Treatment Options for Critically Ill Patients with Infections Caused by Metallo-Beta-Lactamase-Producing Klebsiella pneumoniae. (PubMed, Antibiotics (Basel)) - "The emergence of metallo-beta-lactamases (MBLs) has contributed to the protection of pathogens against all current beta-lactam/beta-lactamase inhibitors (BL/BLIs), including the newer ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam, and imipenem-relebactam...In vitro and clinical data suggest that combinations of CAZ-AVI with aztreonam (ATM) and the use of two different carbapenems (double carbapenem therapy, DCT) may be an option for MBL-producing pathogens... Treatment with CAZ-AVI + ATM or DCT presented similar efficacy with appropriate antibiotic therapy for infections caused by MBL-producing K. pneumoniae strains. Larger studies are required to confirm the findings."

Journal • Critical care • Infectious Disease • Pneumonia

β-Lactam/β-Lactamase Inhibitor Combinations in Sepsis-Associated Acute Kidney Injury and Renal Replacement Therapy. (PubMed, Antibiotics (Basel)) - "This review summarizes PK/PD features, extracorporeal clearance, and practical dosing considerations about ceftolozane-tazobactam, ceftazidime-avibactam, aztreonam-avibactam, cefiderocol, meropenem-vaborbactam, imipenem-relebactam, and newer agents including sulbactam-durlobactam, cefepime-enmetazobactam, and cefepime-taniborbactam. Full-dose initiation during the first 24-48 h, followed by careful adjustment, appears prudent. Therapeutic drug monitoring should be used when available, and institution-specific protocols should be integrated into stewardship programs to improve efficacy and minimize resistance."

Journal • Review • Acute Kidney Injury • Infectious Disease • Nephrology • Pediatrics • Renal Disease • Septic Shock

New Drugs, Old Problems: A Narrative Review of Antibiotic Stewardship Program in the era of novel Gram-negative antibiotics. (PubMed, Clin Microbiol Infect) - "Effective stewardship of new Gram-negative antibiotics requires combining enablement, personalized pharmacology, and selective restriction within multidisciplinary ASPs. Strengthening real-world evidence, digital infrastructure, and standardized outcome measures is essential to guide equitable and sustainable implementation."

Journal • Review • Infectious Disease

Unlocking potentials: the impact of meropenem, meropenem-vaborbactam, and ceftazidime-avibactam in combating carbapenem-resistant Enterobacter cloacae. (PubMed, Antimicrob Agents Chemother) - "Resistance development was observed following treatment with meropenem monotherapy (minimum inhibitory concentrations increasing to >32 µg/mL for the non-CP isolate with extended infusion and to >32 µg/mL for the CP isolate with bolus and extended-infusion treatments) and ceftazidime-avibactam (minimum inhibitory concentration increase from 2 to 16 μg/mL with bolus dosing against the CP isolate). Meropenem-vaborbactam exposure did not result in the emergence of antimicrobial resistance in any of the tested models."

Journal

In vivo evolution of resistance to novel β-lactam/β-lactamase inhibitor combinations through overproduction of the horizontally acquired extended-spectrum AmpC β-lactamase FOX-14 and porin disruption in Serratia marcescens. (PubMed, Eur J Clin Microbiol Infect Dis) - "We tested the susceptibility of the isolates to ceftazidime/avibactam, aztreonam/avibactam, imipenem/relebactam and meropenem/vaborbactam. Purified FOX-14 displayed marked cephalosporinase activity against ceftazidime and cefepime, with low Km values, while negligible turnover for aztreonam and ertapenem and a low avibactam IC50. In S. marcescens, in vivo resistance in clinical isolates emerged from FOX-14 overproduction combined with reduced outer-membrane permeability, predominantly due to OmpF disruption. These findings elucidate resistance to newer β-lactam/β-lactamase inhibitor combinations and warrant close monitoring of antimicrobial activity during carbapenem-based therapy for S. marcescens infections."

Journal • Preclinical • Infectious Disease

Imipenem/Relebactam Plus Aztreonam: First Reported Use in MDR Klebsiella pneumoniae Sternal Infection Complicated by Bacteremia. (PubMed, Antibiotics (Basel)) - "Sternal swab and mediastinal liquid culture results highlighted CRKP harboring blaNDM and blaKPC genes, while the blood isolate showed blaCTX and blaKPC, indicating phenotypic resistance to ceftazidime-avibactam. All the strains exhibited phenotypic susceptibility to meropenem-vaborbactam (MEV), despite having a high minimum inhibitory concentration. Following clinical failure of MEV-based therapy, combination treatment with aztreonam (ATM) and imipenem/cilastatin/relebactam (IMI/REL), plus gentamicin, was initiated...The patient completed 49 days of ATM and IMI/REL without relapse over a 3-month follow-up period. This is, to the best of our knowledge, the first reported case of IMI/REL being used in combination with ATM."

Journal • Infectious Disease • Pneumonia

Therapeutic challenges in treating ESBL- and/or AmpC-producing non-carbapenemase-producing Enterobacterales: an in vitro evaluation of novel β-lactam/β-lactamase inhibitor combinations and cefiderocol. (PubMed, J Antimicrob Chemother) - "CR non-CPE exhibit heterogeneous resistance profiles, especially in ESBL/AmpC co-producers and CTX-M-33-producing isolates. While cefepime-zidebactam, imipenem-relebactam, and cefiderocol were the most active agents, susceptibility testing remains essential to guide therapy in this emerging and neglected bacterial group."

Journal • Preclinical

Significant Prevalence of Dual KPC/NDM Carbapenemase-Producing Klebsiella pneumoniae in an ICU Cohort in Thessaloniki (2023), Including an ST512 Isolate Co-Harboring blaNDM-1 and blaKPC-3. (PubMed, Antibiotics (Basel)) - "Bacterial identification and Antimicrobial susceptibility testing (AST) were performed by VITEK-2; Minimum inhibitory concentrations (MICs) for ceftazidime/avibactam (CAZ/AVI), meropenem/vaborbactam (MER/VAB), and imipenem/relebactam (IMI/REL) were determined by E-tests...Tigecycline showed the highest retained activity; colistin remained active in a minority... Half of CRKP isolates in this ICU-predominant series co-produced KPC and NDM, severely limiting β-lactam/β-lactamase inhibitor options. These data support routine screening for carbapenemases, strict infection prevention, antimicrobial stewardship, and access to agents active against MBLs."

Journal • Critical care • Infectious Disease • Pneumonia

Characterizing the MDR Klebsiella pneumoniae from Ghanaian Hospital Isolates. (ASTMH 2025) - "The resistance rate was highest for Cefotaxime (89%) followed by trimethoprim-sulfamethoxazole (87.5%). Meropenem-vaborbactam (98%), amikacin (81%), and ceftazidime-avibactam (76%) exhibited high susceptibility levels...The dominance ST15 and ST147, coupled with bla-CTX-M-15, bla-NDM-1 underscores a threat to antimicrobial efficacy. The findings Highlights the need for targeted infection control and genomic surveillance in low-resource settings."

Clinical • Late-breaking abstract • Infectious Disease • Pneumonia

Antimicrobial susceptibility of Enterobacterales causing infection in the elderly: focus on aztreonam-avibactam and recently approved β-lactamase inhibitor combinations. (PubMed, JAC Antimicrob Resist) - "Ceftazidime-avibactam and meropenem-vaborbactam were very active against Enterobacterales overall (≥99.7% susceptible) but exhibited limited activity against CRE (70.4%-71.6% susceptible). The most active agents against CRE were aztreonam-avibactam (98.8% susceptible), cefiderocol (96.3% susceptible) and tigecycline (96.3% susceptible)...The most common carbapenemase among CREs from elderly patients were Klebsiella pneumoniae carbapenemases (55.6% of CRE) and NDM (24.7%); a metallo-β-lactamase was identified in 28.4% of CRE isolates. Enterobacterales causing infections in the elderly population showed a similar antimicrobial resistance profile but a lower frequency of CRE and MDR isolates to those causing infection in the adults."

Journal • Infectious Disease • Pneumonia

Novel KPC-2 plasmid in a clinical Salmonella Rissen selected by antibiotic pressure. (PubMed, J Infect Dis) - "The pSEay-KPC conferred broad-spectrum antimicrobial resistance, allowing the pathogen to survive two consecutive antibiotic therapies with ceftriaxone and ciprofloxacin. Effective treatment was ultimately achieved with meropenem-vaborbactam, a last-resort agent. These findings highlight IncN2 plasmids as potent vectors for the spread of clinically significant resistance genes, enabling bacteria to evade frontline antimicrobials and complicating infection management."

Journal • Infectious Disease

Global susceptibility profiles and potential resistance mechanisms of ceftazidime-avibactam-resistant, non-carbapenemase-producing carbapenem-resistant Enterobacterales: 2020-23 data from the Antimicrobial Testing Leadership and Surveillance. (PubMed, J Antimicrob Chemother) - "Based on the data from this study, poor in vitro susceptibility rates for amikacin and meropenem-vaborbactam against contemporary ceftazidime-avibactam-resistant non-CP-CRE were observed. In contrast, aztreonam-avibactam, colistin and tigecycline appear to be reasonable options for the management of infections caused by ceftazidime-avibactam-resistant non-CP-CRE."

Journal • Infectious Disease • Pneumonia

VABOR-KIDS-01: A Study to Assess How Vaborem® is Taking up in the Body and Tolerated in Paediatric Patients With Gram Negative Infections, Including But Not Restricted to Complicated Urinary Tract Infections (clinicaltrials.gov) - P2 | N=44 | Recruiting | Sponsor: Menarini Group | N=32 ➔ 44

Enrollment change • Infectious Disease • Nephrology • Pediatrics

In vitro activity of meropenem-vaborbactam combinations and eravacycline against carbapenem-resistant Acinetobacter baumannii. (PubMed, Sci Rep) - "Extensively drug-resistant (XDR) CRAB isolates were selected for evaluating colistin, eravacycline and the in vitro synergy of antimicrobial combinations via gradient strips for meropenem-vaborbactam, gentamicin, and ceftazidime. All CRAB isolates were sensitive to tigecycline and were either multidrug resistant or XDR...Our findings suggest that eravacycline, as well as combination therapies involving meropenem-vaborbactam with either gentamicin or ceftazidime, may offer promising therapeutic potential for CRAB infections pending further clinical evaluation. These agents demonstrated notable in vitro activity, including potential synergistic effects, particularly against isolates harboring carbapenemase enzymes."

Journal • Preclinical • Infectious Disease

Molecular and pharmacodynamic insights into β-lactam therapy for high-inoculum Enterobacter cloacae complex infections. (PubMed, Antimicrob Agents Chemother) - "We evaluated the pharmacodynamic efficacy of cefepime, meropenem, ertapenem, meropenem-vaborbactam, and ceftazidime-avibactam against three high-inoculum (10⁹ colony-forming unit [CFU]/g) ECC isolates (0008, 0032, and 0060) harboring diverse β-lactamases using a 96 h simulated endocardial vegetation (SEV) model with humanized exposures. Meropenem-vaborbactam showed consistent activity, and prolonged meropenem infusion benefited select isolates. Variable ceftazidime-avibactam efficacy reinforces aligning β-lactam selection with underlying β-lactamase mechanisms."

Journal • PK/PD data • Infectious Disease

Antimicrobial Activity of Aztreonam-Avibactam and Molecular Characterization of Enterobacterales Resistant to Ceftazidime-Avibactam and/or Meropenem-Vaborbactam from United States Medical Centers (2016-2024) (IDWeek 2025) - No abstract available

Infectious Disease

Real-World Efficacy and Safety of Meropenem-Vaborbactam in Patients with Moderate to Severe Renal Impairment (IDWeek 2025) - No abstract available

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Infectious Disease

A Comparative Analysis of Ceftazidime-avibactam and Meropenem-vaborbactam in the Treatment of Carbapenem-resistant Enterobacterales Infections (IDWeek 2025) - No abstract available

Infectious Disease

Beta-lactams and beta-lactamase inhibitors-current developments (PubMed, Inn Med (Heidelb)) - "These included MRSA-active cephalosporins (ceftaroline and ceftobiprole), new, broadly effective combinations of beta-lactams with beta-lactamase inhibitors, and cefiderocol, a new siderophore cephalosporin that uses the bacteria's own iron uptake systems of gram-negative bacteria to better reach the site of action through the outer membrane.In addition to cefiderocol, the most important active ingredients or fixed combinations already available on the German market include ceftazidime-avibactam, ceftolozane-tazobactam, and aztreonam-avibactam. Imipenem-relebactam and meropenem-vaborbactam are also available; Cefepim-enmetazobactam was recently added...However, interesting new combinations, such as ceftibutene-avibactam for oral use, are in development. Such combinations could also enable the oral treatment of infections by some carbapenemase producers in the future."

Journal • Review • Infectious Disease

Characterization of ertapenem-resistant Enterobacterales in Canadian hospitals: 17 years of the CANWARD study (2007-23). (PubMed, J Antimicrob Chemother) - "In Canada, ertapenem-resistant Enterobacterales remain uncommon (0.7%). CPE isolates demonstrated higher percent resistant values for multiple antimicrobial classes and harboured more antimicrobial resistance genes than non-CPE isolates. Continued monitoring for ertapenem-resistant Enterobacterales, particularly CPE, is important given their associated multidrug resistance to both established and newer agents."

Journal • Infectious Disease • Pneumonia

Gram-negative pathogens from Canadian hospitals: 17 years of results from the CANWARD study (2007-23). (PubMed, J Antimicrob Chemother) - "The CANWARD surveillance study has provided 17 years of reference antimicrobial susceptibility testing data."

Journal • Infectious Disease • Pneumonia