Evolutionary trajectories of β-lactam resistance in strains.

Unlabelled: Resistance to ampicillin and imipenem in is infrequent. However, the evolution of resistance can occur through prolonged antibiotic exposure during the treatment of chronic infections. In this study, we conducted a long-term evolution experiment using four genetically diverse strains of with varying susceptibilities to ampicillin and imipenem.

Evolutionary trajectories of β-lactam resistance in strains.

Unlabelled: Resistance to ampicillin and imipenem in is infrequent. However, the evolution of resistance can occur through prolonged antibiotic exposure during the treatment of chronic infections. In this study, we conducted a Long-Term Evolution Experiment (LTEE) using four genetically diverse strains of with varying susceptibilities to ampicillin and imipenem.

Molecular basis of β-lactam antibiotic resistance of ESKAPE bacterium E. faecium Penicillin Binding Protein PBP5.

Penicillin-binding proteins (PBPs) are essential for the formation of the bacterial cell wall. They are also the targets of β-lactam antibiotics. In Enterococcus faecium, high levels of resistance to β-lactams are associated with the expression of PBP5, with higher levels of resistance associated with distinct PBP5 variants.

Penicillin-Binding Proteins and Alternative Dual-Beta-Lactam Combinations for Serious Enterococcus faecalis Infections with Elevated Penicillin MICs.

Ampicillin-ceftriaxone has become a first-line therapy for Enterococcus faecalis endocarditis. We characterized the penicillin-binding protein (PBP) profiles of various E. faecalis strains and tested for synergy to better inform beta-lactam options for the treatment of E.

Meropenem plus Ceftaroline Is Active against Enterococcus faecalis in an Pharmacodynamic Model Using Humanized Dosing Simulations.

The standard of care for serious Enterococcus faecalis infections is ampicillin plus ceftriaxone. Ampicillin's inconvenient dosing schedule, drug instability, allergy potential, along with ceftriaxone's high risk for Clostridioides difficile infection and its promotion of vancomycin-resistant enterococci (VRE), led our team to explore alternative options. This work aimed to understand the role of carbapenems in combination with cephalosporins in these infections.

Houston, We Have a Problem: Reports of Clostridioides difficile Isolates With Reduced Vancomycin Susceptibility.

During the past 4 decades, oral vancomycin has been a mainstay of Clostridioides difficile infection (CDI) therapy with no reports of treatment failure due to emergence of vancomycin resistance. However, C. difficile isolates with high-level phenotypic resistance to vancomycin have recently been reported in 3 distinct geographic regions.

Enterococcal Physiology and Antimicrobial Resistance: The Streetlight Just Got a Little Brighter.

differs from many other common human pathogens in its physiology and in its susceptibility to antimicrobial agents. Multiresistant strains owe their phenotypes to a combination of intrinsic and acquired antimicrobial resistance determinants. Acquired resistance is due to frequenting multicultural environments, its capacity to mate with different species, and the nullification of its own defense mechanisms in some lineages.

An Updated History of : 2000-2020.

Since its inaugural issue nearly half a century ago, has served as a premier source for reports on scientific and clinical advances in the field of antimicrobial chemotherapy. As a follow-up to the previous "History of from 1972 to 1998" written by George A. Jacoby (Antimicrob Agents Chemother 43:999-1002, 1999, https://doi.

Resistance in Vancomycin-Resistant Enterococci.

Serious infections owing to vancomycin-resistant enterococci have historically proven to be difficult clinical cases, requiring combination therapy and management of treatment-related toxicity. Despite the introduction of new antibiotics with activity against vancomycin-resistant enterococci to the therapeutic armamentarium, significant challenges remain. An understanding of the factors driving the emergence of resistance in vancomycin-resistant enterococci, the dynamics of gastrointestinal colonization and microbiota-mediated colonization resistance, and the mechanisms of resistance to the currently available therapeutics will permit clinicians to be better prepared to tackle these challenging hospital-associated pathogens.

Fosfomycin for Injection (ZTI-01) Versus Piperacillin-tazobactam for the Treatment of Complicated Urinary Tract Infection Including Acute Pyelonephritis: ZEUS, A Phase 2/3 Randomized Trial.

Background: ZTI-01 (fosfomycin for injection) is an epoxide antibiotic with a differentiated mechanism of action (MOA) inhibiting an early step in bacterial cell wall synthesis. ZTI-01 has broad in vitro spectrum of activity, including multidrug-resistant Gram-negative pathogens, and is being developed for treatment of complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) in the United States.

Methods: Hospitalized adults with suspected or microbiologically confirmed cUTI/AP were randomized 1:1 to 6 g ZTI-01 q8h or 4.

The Enterococcus: a Model of Adaptability to Its Environment.

The genus comprises a ubiquitous group of Gram-positive bacteria that are of great relevance to human health for their role as major causative agents of health care-associated infections. The enterococci are resilient and versatile species able to survive under harsh conditions, making them well adapted to the health care environment. Two species cause the majority of enterococcal infections: and Both species demonstrate intrinsic resistance to common antibiotics, such as virtually all cephalosporins, aminoglycosides, clindamycin, and trimethoprim-sulfamethoxazole.

Antimicrobial Stewardship and Antimicrobial Resistance.

Antimicrobial stewardship programs aim to reduce costs, optimize therapeutic outcomes, and reduce antimicrobial resistance. Reductions of antimicrobial resistance are the most elusive because emergence and spread of resistant bacteria involves antimicrobial selective pressure and lapses in infection control techniques. The relationship between antimicrobial usage and resistance is not always direct.

Structural and Regulatory Changes in PBP4 Trigger Decreased β-Lactam Susceptibility in Enterococcus faecalis.

strains resistant to penicillin and ampicillin are rare and have been associated with increases in quantities of low-affinity penicillin-binding protein 4 (PBP4) or with amino acid substitutions in PBP4. We report an strain (LS4828) isolated from a prosthetic knee joint that was subjected to long-term exposure to aminopenicillins. Subsequent cultures yielded with MICs of penicillins and carbapenems higher than those for wild-type strain JH2-2.

A Review of Combination Antimicrobial Therapy for Enterococcus faecalis Bloodstream Infections and Infective Endocarditis.

Enterococci, one of the most common causes of hospital-associated infections, are responsible for substantial morbidity and mortality. Enterococcus faecalis, the more common and virulent species, causes serious high-inoculum infections, namely infective endocarditis, that are associated with cardiac surgery and mortality rates that remained unchanged for the last 30 years. The best cures for these infections are observed with combination antibiotic therapy; however, optimal treatment has not been fully elucidated.

High-Level Fosfomycin Resistance in Vancomycin-Resistant Enterococcus faecium.

Of 890 vancomycin-resistant Enterococcus faecium isolates obtained by rectal screening from patients in Pittsburgh, Pennsylvania, USA, 4 had MICs >1,024 μg/mL for fosfomycin. These isolates had a Cys119Asp substitution in the active site of UDP-N-acetylglucosamine enolpyruvyl transferase. This substitution increased the fosfomycin MIC >4-fold and rendered this drug inactive in biochemical assays.

Factors essential for L,D-transpeptidase-mediated peptidoglycan cross-linking and β-lactam resistance in .

The target of β-lactam antibiotics is the D,D-transpeptidase activity of penicillin-binding proteins (PBPs) for synthesis of 4→3 cross-links in the peptidoglycan of bacterial cell walls. Unusual 3→3 cross-links formed by L,D-transpeptidases were first detected in more than four decades ago, however no phenotype has previously been associated with their synthesis. Here we show that production of the L,D-transpeptidase YcbB in combination with elevated synthesis of the (p)ppGpp alarmone by RelA lead to full bypass of the D,D-transpeptidase activity of PBPs and to broad-spectrum β-lactam resistance.

Homologous Recombination within Large Chromosomal Regions Facilitates Acquisition of β-Lactam and Vancomycin Resistance in Enterococcus faecium.

The transfer of DNA between Enterococcus faecium strains has been characterized both by the movement of well-defined genetic elements and by the large-scale transfer of genomic DNA fragments. In this work, we report on the whole-genome analysis of transconjugants resulting from mating events between the vancomycin-resistant E. faecium C68 strain and the vancomycin-susceptible D344RRF strain to discern the mechanism by which the transferred regions enter the recipient chromosome.

Vancomycin-Resistant Enterococci: Therapeutic Challenges in the 21st Century.

Vancomycin-resistant enterococci are serious health threats due in part to their ability to persist in rugged environments and their propensity to acquire antibiotic resistance determinants. Enterococci have now established a home in our hospitals and possess mechanisms to defeat most currently available antimicrobials. This article reviews the history of the struggle with this pathogen, what is known about the traits associated with its rise in the modern medical environment, and the current understanding of therapeutic approaches in severe infections caused by these microorganisms.

Draft Genome Sequence of Vancomycin-Susceptible, Ampicillin-Intermediate Enterococcus faecium Strain D344RRF.

Enterococcus faecium is an important nosocomial pathogen, causing a substantial health burden due to high resistance to antibiotics and its ability to colonize the gastrointestinal tract. Here, we present the draft genome of vancomycin-susceptible, ampicillin-intermediate strain D344RRF, a rifampicin/fusidic acid-resistant and commonly used laboratory strain, which is useful in studying the transfer of antibiotic resistance.

Genome Sequence of the Multiantibiotic-Resistant Enterococcus faecium Strain C68 and Insights on the pLRM23 Colonization Plasmid.

Enterococcus faecium infections are a rising concern in hospital settings. Vancomycin-resistant enterococci colonize the gastrointestinal tract and replace nonresistant strains, complicating the treatment of debilitated patients. Here, we present a polished genome of the multiantibiotic-resistant strain C68, which was obtained as a clinical isolate and is a useful experimental strain.