beta-lactamase inhibitor

UNLABELLED: Complications associated with pelvic organ prolapse (POP) surgery using a synthetic non-absorbable mesh are uncommon (<5%) but may be severe and may hugely diminish the quality of life of some women. In drawing up these multidisciplinary clinical practice recommendations, the French National Authority for Health (Haute Autorité de santé, HAS) conducted an exhaustive review of the literature concerning the diagnosis, prevention, and management of complications associated with POP surgery using a synthetic mesh...

OBJECTIVES: The occurrence of metallo-beta-lactamase-producing Pseudomonas aeruginosa (MBL-PA) isolates is increasing globally, including in Switzerland. The aim of this study was to characterise, phenotypically and genotypically, the MBL-PA isolates submitted to the Swiss National Reference Center for Emerging Antibiotic Resistance (NARA) reference laboratory over a 12-month period from July 2022 to July 2023. METHODS: Thirty-nine non-duplicate MBL-PA Isolates were submitted to NARA over the study period from across Switzerland...

INTRODUCTION: Novel hemoperfusion systems are emerging for the treatment of sepsis. These devices can directly remove pathogens, pathogen-associated molecular patterns, cytokines, and other inflammatory markers from circulation. However, significant safety concerns such as potential antibiotic clearance need to be addressed prior to these devices being used in large, clinical studies. METHODS: Prospective, observational study of 34 participants undergoing treatment with the Seraph 100® Microbind Affinity Blood Filter (Seraph 100) device at 6 participating sites in the United States...

The inoculum effect, characterized by diminished antibacterial activity at high bacterial inocula, is studied in the context of beta-lactam and beta-lactamase inhibitor combinations against beta-lactamase-producing Enterobacterales. The inhibition of ESBL + OXA-48 and KPC enzymes, in combination with ceftazidime, demonstrates encouraging results. In this study, 20 Klebsiella pneumoniae isolates were tested with different inocula (1-5 × 105 and 1-5 × 107  cfu/ml) using broth microdilution methods...

Allostery is the mechanism by which information and control are propagated in biomolecules. It regulates ligand binding, chemical reactions, and conformational changes. An increasing level of experimental resolution and control over allosteric mechanisms promises a deeper understanding of the molecular basis for life and powerful new therapeutics. In this review, we survey the literature for an up-to-date biological and theoretical understanding of protein allostery. By delineating five ways in which the energy landscape or the kinetics of a system may change to give rise to allostery, we aim to help the reader grasp its physical origins...

Salmonella spp. are known to persist in the environment. Wild animals are believed to act as important reservoirs, with antimicrobial resistance frequently occurring in the environment. However, little is known about the role of the wildlife in Bahia as a reservoir for Salmonella in Brazil. This study aimed to isolate and characterize Salmonella spp. from wildlife in the Atlantic Forest and Caatinga biomes considering indicators such as the animal species, degree of anthropization, sampling area, and feeding habits...

Children and adolescents with severe neurological impairment (SNI) require specialized care due to their complex medical needs. In particular, these patients are often affected by severe and recurrent lower respiratory tract infections (LRTIs). These infections, including viral and bacterial etiology, pose a significant risk to these patients, often resulting in respiratory insufficiency and long-term impairments. Using expert consensus, we developed clinical recommendations on the management of LRTIs in children and adolescents with SNI...

BACKGROUND: Burn injury causes profound pathophysiological changes in the pharmacokinetic/pharmacodynamic (PK/PD) properties of antibiotics. Infections are among the principal complications after burn injuries, and broad-spectrum beta-lactams are the cornerstone of treatment. The aim of this study was to review the evidence for the best regimens of these antibiotics in the burn patient population. METHODS: We performed a systematic review of evidence available on MEDLINE (from its inception to 2023) of pharmacology studies that focused on the use of 13 broad-spectrum beta-lactams in burn patients...

The emergence of bacteria resistant to beta-lactam/beta-lactamase inhibitor combinations is insufficiently studied, wherein the role of the inoculum effect (IE) in decreased efficacy is unclear. To address these issues, 5-day treatments with doripenem and doripenem/relebactam combination at different ratios of the agents were simulated in a hollow-fiber dynamic model against carbapenemase-producing K. pneumoniae at standard and high inocula. Minimal inhibitory concentrations (MICs) of doripenem alone and in the presence of relebactam at two inocula were determined...

BACKGROUND: Denmark has a low level of antimicrobial resistance (AMR). Patients hospitalized with suspected infection often present with unspecific symptoms. This challenges the physician between using narrow-spectrum antibiotics in accordance with guidelines or broad-spectrum antibiotics to compensate for diagnostic uncertainty. The aim of this study was to investigate adherence to a restrictive antibiotic guideline for the most common infection in emergency departments (EDs), namely community-acquired pneumonia (CAP)...

Antimicrobial resistance has emerged as a serious issue for physicians and health-care workers treating infections that could lead to the next pandemic. One of the key resistance mechanisms is beta-lactamases. Although several beta-lactamase inhibitors in combination with antibiotics have been created and are being utilized in clinical settings, resistance to these formulations has also been evolving in the bacterial population due to their distinct targets. In this study we used effective combination of antibiotic as an approach to inhibit multidrug resistance bacteria...

The design of inhibitors against metallo-β-lactamases (MBLs), the largest family of carbapenemases, has been a strategic goal in designing novel antimicrobial therapies. In this regard, the development of bicyclic boronates, such as taniborbactam (TAN) and xeruborbactam, is a major achievement that may help in overcoming the threat of MBL-producing and carbapenem-resistant Gram-negative pathogens. Of concern, a recent report has shown that New Delhi MBL-9 (NDM-9) escapes the inhibitory action of TAN by a single amino acid substitution with respect to New Delhi MBL-1 (NDM-1), the most widely disseminated MBL...

The complications of wound infections caused by animal related trauma are well known and explored. Of the numerous polymicrobial etiologies, Neisseria animaloris and Pasteurella canis oralis have been reported only in a limited number of cases. This manuscript explores the rare finding of these species in the case of an 83-year-old male with a diabetic foot wound complicated by infection from the saliva of his pet dog. The case highlights the first instance of P. canis oralis without the setting of a penetrating animal bite, emphasizing the vulnerability of open lesions in patients whose comorbidities impair proper wound healing...

(1) Objectives: To describe the attainment of optimal pharmacokinetic/pharmacodynamic (PK/PD) targets in orthotopic liver transplant (OLT) recipients treated with continuous infusion (CI) beta-lactams optimized using a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program during the early post-surgical period. (2) Methods: OLT recipients admitted to the post-transplant intensive care unit over the period of July 2021-September 2023, receiving empirical or targeted therapy with CI meropenem, piperacillin-tazobactam, meropenem-vaborbactam, or ceftazidime-avibactam optimized using a real-time TDM-guided ECPA program, were retrospectively retrieved...

Increasing antimicrobial resistance among multidrug-resistant (MDR), extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Enterobacterales (CPE), in particular metallo-β-lactamase (MBL)-positive strains, has led to limited treatment options in these isolates. This study evaluated the activity of aztreonam-avibactam (ATM-AVI) and comparator antimicrobials against Enterobacterales isolates and key resistance phenotypes stratified by wards, infection sources and geographic regions as part of the ATLAS program between 2016 and 2020...

Multidrug-resistant Gram-negative bacterial infections are exponentially increasing, posing one of the most urgent global healthcare and economic threats. Due to the lack of new therapies, the World Health Organization classified these bacterial species as priority pathogens in 2017, known as ESKAPE pathogens. This classification emphasizes the need for urgent research and development of novel targeted therapies. The majority of these priority pathogens are Gram-negative species, which possess a structurally dynamic cell envelope enabling them to resist multiple antibiotics, thereby leading to increased mortality rates...

In recent years, new antimicrobials have been introduced in therapeutics, including new beta-lactam-beta-lactamase inhibitor combinations and cefiderocol in response to therapeutic needs in the face of increasing resistance. There are also different treatment guidelines for infections caused by these microorganisms that have been approved by different professional societies, including those of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Disease Society of America (IDSA) and the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC)...

INTRODUCTION: Critically ill patients with cirrhosis admitted to the intensive care unit (ICU) are usually on broad-spectrum antibiotics because of suspected infection or as a hospital protocol. It is unclear if additional rifaximin has any synergistic effect with broad-spectrum antibiotics in ICU patients with acute overt hepatic encephalopathy (HE). METHODS: In this double-blind trial, patients with overt HE admitted to ICU were randomized to receive antibiotics (ab) alone or antibiotics with rifaximin (ab + r)...

The detection rate of carbapenem-resistant nontyphoidal Salmonella (NTS) is relatively low. However, carbapenem-sensitive and carbapenem-resistant Salmonella enterica serovar Typhimurium ( S. enterica serovar Typhimurium) were isolated from a clinical outpatient within a span of 10 days, named 1104-65 and 1104-75. We aimed to reveal the mechanism of carbapenem resistance in S. enterica serovar Typhimurium isolates in this case. The resistance phenotype of S. enterica serovar Typhimurium was analyzed by the VITEK-2 Compact equipment and Kirby-Bauer disc diffusion method...

Pseudomonas aeruginosa is a common multidrug-resistant pathogen in patients with cystic fibrosis (CF). The in vitro activity of imipenem/relebactam and imipenem was compared with other antipseudomonal antibiotics against 105 isolates from patients with CF from three US hospitals. Imipenem/relebactam, imipenem, meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam susceptibilities were 77%, 55%, 58%, 90%, and 92%, respectively. Relebactam potentiates imipenem against CF P. aeruginosa by fourfold leading imipenem/relebactam to retain susceptibility against most isolates in this cohort...