Cefepime-Taniborbactam and Ceftibuten-Ledaborbactam Maintain Activity Against KPC Variants that Lead to Ceftazidime-Avibactam Resistance DOI Creative Commons
Cullen L. Myers,

Annie Stevenson,

Brittany Miller

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 11, 2024

Abstract Klebsiella pneumoniae carbapenemases (KPCs) are widespread β-lactamases that a major cause of clinical non-susceptibility Gram-negative bacteria to carbapenems and other β-lactam antibiotics. Ceftazidime combined with the β-lactamase inhibitor avibactam (CAZ-AVI) has been effective for treating infections by KPC-producing bacteria, but emergent KPC variants confer resistance combination. Taniborbactam ledaborbactam bicyclic boronate inhibitors under development cefepime ceftibuten, respectively, treat carbapenem-resistant bacterial infections. Here, we assessed effects clinically important KPC-2 KPC-3 (V240G, D179Y, D179Y T243M) on antibacterial activity cefepime-taniborbactam (FEP-TAN) ceftibuten-ledaborbactam (CTB-LED) examined catalytic inhibition these variants. FEP-TAN CTB-LED were highly active against CAZ-AVI-resistant engineered E. coli strains expressing Purified catalyzed more efficient CAZ hydrolysis than wild-type enzymes, D179Y-containing additionally FEP KPC-3. All poorly hydrolyzed CTB, demonstrated significantly higher affinity or CTB. Second-order rate constants ( k 2 / K ) reduced relative KPC-2, AVI most impacted. was less affected variants, reflected robust TAN, LED AVI. Together, findings illustrate biochemical basis greater in variant expression backgrounds CAZ-AVI, whereby have sufficient inhibitory activity, whilst CTB poorer substrates bind enzymes compared CAZ.

Language: Английский

Whole genome sequencing characterization of the new KPC-245 variant-carrying Klebsiella pneumoniae strain isolated from a transplanted patient and resistant to ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam DOI Creative Commons

Claudia Vaiana,

Roberta Vazzana, Salvatore Castelbuono

et al.

Journal of Global Antimicrobial Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Meropenem–Vaborbactam for Treatment of Carbapenem-Resistant Enterobacterales: A Narrative Review of Clinical Practice Evidence DOI Creative Commons
Matteo Bassetti, Daniele Roberto Giacobbe, Antonio Vena

et al.

Infectious Diseases and Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 12, 2025

Among drug-resistant bacteria, carbapenem-resistant Enterobacterales (CRE) are a major clinical challenge with limited options for treatment. In the last several years, new treatment have emerged CRE, including meropenem-vaborbactam (MVB). MVB was studied clinically in TANGO-I and TANGO-II trials, which evaluated combination complicated urinary tract infections different types of CRE infections, respectively. To date, data on efficacy remain limited, but needed to understand drug routine practice. Eight retrospective studies investigated use CRE. these analyses, overall success rate varied from 60 75%, while mortality rates at 30 days ranged about 15 30%. Most investigations involved patients KPC-producing strains, also Gram-negative 80% were addition, number small case series reports describing MVB. both series/reports, there appeared be no safety concerns. Collectively, shown that can considered promising severe Klebsiella pneumoniae carbapenemase (KPC)-producing-CRE is safe well tolerated.

Language: Английский

Citations

0
In vivo development of resistance to novel β-lactam/β-lactamase inhibitor combinations in KPC-producing Klebsiella pneumoniae infections: a case series DOI Creative Commons
Matteo Boattini, Gabriele Bianco,

Sara Comini

et al.

European Journal of Clinical Microbiology & Infectious Diseases, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 10, 2024

Understanding the dynamics that may characterize emergence of KPC variants with resistance to novel β-lactam/β-lactamase inhibitor combinations (βL/βLICs) represents a challenge be overcome in appropriate use recently introduced antibiotics.

Language: Английский

Citations

3
Real-world effectiveness and safety of meropenem–vaborbactam in the treatment of carbapenem-resistant enterobacterales (CRE) infections: a systematic review and meta-analysis DOI Creative Commons
Dongcai Jin, Danyang Hu, Yu Jin

et al.

Journal of Chemotherapy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 9

Published: Feb. 13, 2025

This study aimed to evaluate the effectiveness and safety of Meropenem-Vaborbactam(M-V) for treating carbapenem-resistant Enterobacterales (CRE) infections based on real-world data. A systematic search PubMed, Embase, Cochrane Library, Web Science was conducted, considering studies up October 31, 2024. Real-world evidence from registries nonselected case series involving 10 or more adult patients treated with Meropenem-Vaborbactam CRE included. Meta-analyses using a random-effects model were performed, primary outcomes being clinical efficacy survival, including 30-day 90-day survival rates. Out 1862 potentially relevant publications, six included in meta-analysis. The pooled success rate 75% (95% CI, 66%–82%), rates 71%–78%) 69% 61%–76%), respectively. Importantly, no serious adverse effects reported. In conclusion, demonstrated both settings. registered PROSPERO (CRD42022370880).

Language: Английский

Citations

0
Systematic Review and Meta-Analysis of Clinical Efficacy and Safety of Meropenem-Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections DOI Open Access

Alexandra Bucătaru,

Adina Turcu-Știolică, Daniela Călina

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9574 - 9574

Published: Sept. 4, 2024

Antimicrobial resistance is increasingly concerning, causing millions of deaths and a high cost burden. Given that carbapenemase-producing Enterobacterales are particularly concerning due to their ability develop structural modifications produce antibiotic-degrading enzymes, leading levels, we sought summarize the available data on efficacy safety regarding combination meropenem-vaborbactam (MV) versus best therapy (BAT). Articles related our objective were searched in PubMed Scopus databases inception July 2024. To assess quality studies, used Cochrane risk-of-bias tool, RoB2. The outcomes pooled as risk ratio (RR) 95% confidence interval (95%CI). A total four published studies involved: one retrospective cohort study three phase 3 trials, including 432 patients treated with MV 426 BAT (mono/combination polymyxins, carbapenems, aminoglycosides, colistin, tigecycline; or ceftazidime-avibactam; piperacillin-tazobactam). No significant difference clinical response rate was observed between comparators at TOC (RR = 1.29, 95%CI [0.92, 1.80], p 0.14) EOT 1.66, [0.58, 4.76], 0.34) visits. associated similar microbiological 1.63, [0.85, 3.11], assessment 1.16, [0.88, 1.54], 0.14). In analysis 28-day all-cause mortality lower for than control groups 0.47, [0.24, 0.92], 0.03). adverse events (AEs) 0.79, [0.53, 1.17], 0.23). Additionally, fewer renal-related AEs 0.32, [0.15, 0.66], 0.002). treatment discontinuation 0.76, [0.38, 1.49], 0.42) drug-related 0.56, [0.28, 1.10], 0.09) comparators. conclusion, presents promising therapeutic option treating CRE infections, demonstrating responses other comparators, potential advantages AEs.

Language: Английский

Citations

2
Recent updates in treating carbapenem-resistant infections in patients with hematological malignancies DOI
Abdullah Tarık Aslan, Murat Akova

Expert Review of Anti-infective Therapy, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 17

Published: Sept. 24, 2024

Patients with hematological malignancies (PHMs) are at increased risk for infections caused by carbapenem-resistant organisms (CROs) due to frequent exposure broad-spectrum antibiotics and prolonged hospital stays. These result in high mortality morbidity rates along delays chemotherapy, longer hospitalizations, health care costs.

Language: Английский

Citations

1
Meropenem-vaborbactam as intrathecal-sparing therapy for the treatment of carbapenem-resistant K. pneumoniae shunt-related ventriculitis: two case reports and review of the literature DOI
Gabriele Giuliano,

Margherita Sambo,

Patrizia Castellani

et al.

European Journal of Clinical Microbiology & Infectious Diseases, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

Language: Английский

Citations

1
Cefepime-Taniborbactam and Ceftibuten-Ledaborbactam Maintain Activity Against KPC Variants that Lead to Ceftazidime-Avibactam Resistance DOI Creative Commons
Cullen L. Myers,

Annie Stevenson,

Brittany Miller

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 11, 2024

Abstract Klebsiella pneumoniae carbapenemases (KPCs) are widespread β-lactamases that a major cause of clinical non-susceptibility Gram-negative bacteria to carbapenems and other β-lactam antibiotics. Ceftazidime combined with the β-lactamase inhibitor avibactam (CAZ-AVI) has been effective for treating infections by KPC-producing bacteria, but emergent KPC variants confer resistance combination. Taniborbactam ledaborbactam bicyclic boronate inhibitors under development cefepime ceftibuten, respectively, treat carbapenem-resistant bacterial infections. Here, we assessed effects clinically important KPC-2 KPC-3 (V240G, D179Y, D179Y T243M) on antibacterial activity cefepime-taniborbactam (FEP-TAN) ceftibuten-ledaborbactam (CTB-LED) examined catalytic inhibition these variants. FEP-TAN CTB-LED were highly active against CAZ-AVI-resistant engineered E. coli strains expressing Purified catalyzed more efficient CAZ hydrolysis than wild-type enzymes, D179Y-containing additionally FEP KPC-3. All poorly hydrolyzed CTB, demonstrated significantly higher affinity or CTB. Second-order rate constants ( k 2 / K ) reduced relative KPC-2, AVI most impacted. was less affected variants, reflected robust TAN, LED AVI. Together, findings illustrate biochemical basis greater in variant expression backgrounds CAZ-AVI, whereby have sufficient inhibitory activity, whilst CTB poorer substrates bind enzymes compared CAZ.

Language: Английский

Citations

0