meropenem
PharmacologyPharmacodynamics of the Novel Metallo-β-Lactamase Inhibitor ANT2681 in Combination with Meropenem for the Treatment of Infections Caused by NDM-Producing EnterobacteriaceaeEnterobacteriaceae that produce metallo-β-lactamases (MBLs) are an emerging threat to public health. The metallo-β-lactamase inhibitor (MBLi) ANT2681 inhibits the enzymatic activity of MBLs through interaction with the dinuclear zinc ion cluster present in the active site that is common to these enzymes. ANT2681 is being codeveloped, with meropenem as the partner β-lactam, as a novel combination therapy for infections caused by...
PharmacologyReappraisal of the Optimal Dose of Meropenem in Critically Ill Infants and Children: a Developmental Pharmacokinetic-Pharmacodynamic AnalysisData of developmental pharmacokinetics (PK) of meropenem in critically ill infants and children with severe infections are limited. We assessed the population PK and defined the appropriate regimen to optimize treatment in this population based on developmental PK-pharmacodynamic (PD) analysis. Blood samples were collected from pediatric intensive care unit patients with severe infection treated with standard dosage regimens for...
Clinical TherapeuticsSafety and Pharmacokinetic Characterization of Nacubactam, a Novel β-Lactamase Inhibitor, Alone and in Combination with Meropenem, in Healthy VolunteersNacubactam is a novel β-lactamase inhibitor with dual mechanisms of action as an inhibitor of serine β-lactamases (classes A and C and some class D) and an inhibitor of penicillin binding protein 2 in Enterobacteriaceae. The safety, tolerability, and pharmacokinetics of intravenous nacubactam were evaluated in single- and multiple-ascending-dose, placebo-controlled studies. Healthy participants received single ascending doses...
PharmacologyPharmacodynamics of Meropenem against Acinetobacter baumannii in a Neutropenic Mouse Thigh Infection ModelAcinetobacter baumannii infections are difficult to treat and have limited treatment options. Carbapenems, including meropenem, are currently considered the first-line agents for the treatment of infections caused by Acinetobacter spp. The percentage of a 24-hour period that the concentration of...
PharmacologyActivity of Antibiotics against Pseudomonas aeruginosa in an In Vitro Model of Biofilms in the Context of Cystic Fibrosis: Influence of the Culture MediumPseudomonas aeruginosa is a major cause of respiratory biofilm-related infections in patients with cystic fibrosis. We developed an in vitro pharmacodynamic model to study the activity of antipseudomonal antibiotics against PAO1 biofilms grown in artificial sputum medium with agar [ASM(+)] versus that against biofilms grown in Trypticase soy broth...
Mechanisms of ResistanceCTX-M-33 Is a CTX-M-15 Derivative Conferring Reduced Susceptibility to CarbapenemsCTX-M-type extended-spectrum β-lactamases (ESBLs) are widespread among Enterobacterales strains worldwide. The most common variant is CTX-M-15, which hydrolyzes ceftazidime at a high rate but spares carbapenems. Here, we identified CTX-M-33, a point mutation derivative of CTX-M-15 (Asp to Ser substitution at Ambler position 109) that exhibited low carbapenemase activity.
Mechanisms of ResistanceA Large-Scale Whole-Genome Comparison Shows that Experimental Evolution in Response to Antibiotics Predicts Changes in Naturally Evolved Clinical Pseudomonas aeruginosaPseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of acute and chronic infections. An increasing number of isolates have mutations that make them antibiotic resistant, making treatment difficult. To identify resistance-associated mutations, we experimentally evolved the antibiotic-sensitive strain...
Clinical TherapeuticsMeropenem versus Cefotaxime and Ampicillin as Empirical Antibiotic Treatment in Adult Bacterial Meningitis: a Quality Registry Study, 2008 to 2016Cefotaxime, alone or with ampicillin, is frequently used in empirical treatment of acute bacterial meningitis (ABM). Meropenem is a less extensively investigated alternative. The aim of the study was to investigate the effects of empirical treatment with meropenem compared to cefotaxime plus ampicillin on outcome in ABM. The study was based on data from the Swedish quality register for ABM collected between January 2008 and December...
Mechanisms of ResistanceSpheroplast-Mediated Carbapenem Tolerance in Gram-Negative PathogensAntibiotic tolerance, the ability to temporarily sustain viability in the presence of bactericidal antibiotics, constitutes an understudied and yet potentially widespread cause of antibiotic treatment failure. We have previously shown that the Gram-negative pathogen Vibrio cholerae can tolerate exposure to the typically bactericidal β-lactam antibiotics by assuming a...
SusceptibilityNew β-Lactamase Inhibitors Nacubactam and Zidebactam Improve the In Vitro Activity of β-Lactam Antibiotics against Mycobacterium abscessus Complex Clinical IsolatesThe new diazabicyclooctane-based β-lactamase inhibitors avibactam and relebactam improve the in vitro activity of β-lactam antibiotics against bacteria of the Mycobacterium abscessus complex (MABC). Here, we evaluated the in vitro activities of two newer diazabicyclooctane-based β-lactamase inhibitors in clinical development, nacubactam and...