Enterobacteriaceae
Mechanisms of ResistanceA Genotype-Phenotype Correlation Study of SHV β-Lactamases Offers New Insight into SHV Resistance ProfilesThe SHV β-lactamases (BLs) have undergone strong allele diversification that has changed their substrate specificities. Based on 147 NCBI entries for SHV alleles, in silico mathematical models predicted 5 positions as relevant for the β-lactamase inhibitor (BLI)-resistant (2br) phenotype, 12 positions as relevant for the extended-spectrum BL (ESBL) (2be) phenotype, and 2 positions as related solely to the narrow-spectrum (2b)...
Mechanisms of ResistanceComplex Response of the CpxAR Two-Component System to β-Lactams on Antibiotic Resistance and Envelope Homeostasis in EnterobacteriaceaeThe Cpx stress response is widespread among Enterobacteriaceae. We previously reported a mutation in cpxA in a multidrug-resistant strain of Klebsiella aerogenes isolated from a patient treated with imipenem. This mutation yields a single-amino-acid substitution (Y144N) located in the periplasmic sensor domain of CpxA. In this work, we sought to...
Epidemiology and SurveillanceComparison of Commensal and Clinical Isolates for Diversity of Plasmids in Escherichia coli and Klebsiella pneumoniaeIn this study, the plasmid content of clinical and commensal strains was analyzed and compared. The replicon profile was similar in both populations, except for L, M, A/C, and N (detected only in clinical strains) and HI1 (only in commensal strains). Although I1 and F were the most frequent replicons, only IncI1, sequence type 12 (ST12) was associated with blaCMY-2 in both populations. In contrast, the widespread...
Epidemiology and SurveillanceA Pilot Study of Chicago Waterways as Reservoirs of Multidrug-Resistant Enterobacteriaceae (MDR-Ent) in a High-Risk Region for Community-Acquired MDR-Ent Infection in ChildrenCommunity-acquired multidrug resistant Enterobacteriaceae (MDR-Ent) infections continue to increase in the United States. In prior studies, we identified neighboring regions in Chicago, Illinois, where children have 5 to 6 times greater odds of MDR-Ent infections. To prevent community spread of MDR-Ent, we need to identify the MDR-Ent reservoirs. A pilot study of 4 Chicago waterways for MDR-Ent and associated antibiotic...
Experimental TherapeuticsModel-Informed Drug Development, Pharmacokinetic/Pharmacodynamic Cutoff Value Determination, and Antibacterial Efficacy of Benapenem against EnterobacteriaceaeBenapenem is a novel carbapenem. The objective of this study was to determine the pharmacokinetic (PK)/pharmacodynamic (PD) cutoff values and evaluate the optimal administration regimens of benapenem for the treatment of bacterial infections via PK/PD modeling and simulation. Ertapenem was used as a control. Infected mice received an intravenous (i.v.) injection of benapenem or ertapenem of 14.6, 58.4, or 233.6 mg/kg of body weight, and...
Epidemiology and SurveillanceActivity of Meropenem-Vaborbactam against Bacterial Isolates Causing Pneumonia in Patients in U.S. Hospitals during 2014 to 2018Meropenem-vaborbactam is approved to treat hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), in Europe. Meropenem-vaborbactam activity was evaluated against 3,193 Pseudomonas aeruginosa and 4,790 Enterobacterales isolates causing pneumonia, including VAP, in hospitalized patients in the United States. Susceptibility testing...
Epidemiology and SurveillanceIn Vitro Activity of Eravacycline against Gram-Negative Bacilli Isolated in Clinical Laboratories Worldwide from 2013 to 2017Eravacycline is a novel, fully synthetic fluorocycline antibiotic developed for the treatment of serious infections, including those caused by multidrug-resistant (MDR) pathogens. Here, we evaluated the in vitro activities of eravacycline and comparator antimicrobial agents against a global collection of frequently encountered clinical isolates of Gram-negative bacilli. The CLSI broth microdilution method was used to determine...
Editor's Pick Clinical TherapeuticsHigh Heterogeneity of Multidrug-Resistant Enterobacteriaceae Fecal Levels in Hospitalized Patients Is Partially Driven by Intravenous β-LactamsMultidrug-resistant Enterobacteriaceae (MRE) colonize the intestine asymptomatically from where they can breach into the bloodstream and cause life-threatening infections, especially in heavily colonized patients. Despite the clinical relevance of MRE colonization levels, we know little about how they vary in hospitalized patients and the clinical factors that determine those levels.
Challenging Clinical Case in Antimicrobial ResistanceSimultaneous Infection with Enterobacteriaceae and Pseudomonas aeruginosa Harboring Multiple Carbapenemases in a Returning Traveler Colonized with Candida aurisWe report our clinical experience treating a critically ill patient with polymicrobial infections due to multidrug-resistant Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa in a 56-year-old woman who received...
Editor's Pick Clinical TherapeuticsEstimating the Size of the U.S. Market for New Antibiotics with Activity against Carbapenem-Resistant EnterobacteriaceaeNew antibiotics with activity against carbapenem-resistant Enterobacteriaceae (CRE) improve outcomes of CRE-infected patients. However, companies developing these drugs have faced financial difficulties. Sales of ceftazidime-avibactam, meropenem-vaborbactam, and plazomicin in the United States totaled $101 million from February 2018 to January 2019. We estimate that...