Polymyxin B

The main objective of this study was to assess the effect of rich artificial cation adjusted Mueller-Hinton broth (CAMHB), on the growth of three Acinetobacter baumannii strains, ATCC 19606 and two clinical A. baumannii strains, either susceptible or resistant to polymyxin B (PMB), and on the PMB bactericidal activity. A pharmacokinetic (PK) / pharmacodynamic (PD) modelling approach was then used to characterize the effect of PMB in various conditions. Time-kill experiments were performed using undiluted CAMHB or diluted at 50%, 25% and 10%, with or without Ca2+ and Mg2+ compensation (known to affect PMB activity), and with PMB concentrations ranging from 0...

BACKGROUND: Liver transplantation (LT) is the only curative treatment for end-stage liver disease. However, LT recipients are susceptible to infection, which is the leading cause of early mortality after LT. Klebsiella pneumoniae infections (KPIs) in the bloodstream are common in LT recipients. We hypothesized that KPIs and carbapenem-resistant Klebsiella pneumoniae (CRKP) infections may affect the outcomes of LT recipients. AIM: To assess KPI incidence, timing, distribution, drug resistance, and risk factors following LT and its association with outcomes...

Benzalkonium chloride (BAC) is a disinfectant with broad-spectrum antibacterial properties, yet despite its widespread use and detection in the environment, the effects of BAC exposure on microorganisms remain poorly documented. Herein, the impacts of BAC on a Pseudomonas aeruginosa strain Jade-X were systematically investigated. The results demonstrated that the minimum inhibitory concentration (MIC) of BAC against strain Jade-X was 64 mg L-1 . Exposure to BAC concentrations of 8, 16, 32, and 64 mg L-1 significantly augmented biofilm formation by 2...

Background Typhoid fever presents a significant challenge in developing nations, exacerbated by the emergence of antibiotic-resistant strains due to widespread prevalence and overuse of antibiotics. This study seeks to assess the antibiogram profiles of Salmonella species isolated from blood cultures of patients hospitalized at two prominent tertiary care hospitals in Peshawar, Pakistan: Khyber Teaching Hospital (KTH) and Hayatabad Medical Complex (HMC). By examining these profiles, the research aims to provide valuable insights into the evolving landscape of antibiotic resistance in the context of typhoid fever management...

BACKGROUND: Morganella spp are opportunistic pathogens involved in various infections. Intrinsic resistance to multiple antibiotics (including colistin) combined with the emergence of carbapenemase producers reduces the number of active antimicrobials. The aim of this study was to characterise genetic features related to the spread of carbapenem-resistant Morganella spp. METHODS: This comparative genomic study included extensively drug-resistant Morganella spp isolates collected between Jan 1, 2013, and March 1, 2021, by the French National Reference Center (NRC; n=68) and European antimicrobial resistance reference centres in seven European countries (n=104), as well as one isolate from Canada, two reference strains from the Pasteur Institute collection (Paris, France), and two colistin-susceptible isolates from Bicêtre Hospital (Kremlin-Bicêtre, France)...

BACKGROUND: Polymyxins, including both colistin and polymyxin B (PMB), have regained clinical attention as last-line treatment options for treating infections caused by multidrug-resistant (MDR) gram-negative bacteria. Nonetheless, concerns persist regarding the toxicity associated with polymyxins. The objective of this study was to explore the potential severe adverse events (AEs) associated with polymyxins and compare the disparities in AEs between these two agents. METHODS: Records of AEs associated with colistin and PMB were retrieved from the U...

MRX-8 is a novel polymyxin for carbapenem-resistant Gram-negative infections that has been recently evaluated in Phase I clinical trials. Herein, its pharmacokinetics (PK) and nephrotoxicity in rats are reported for the first time. This study aimed at pre-clinical PK and safety assessments. An LC-MS/MS method was developed to determine concentrations of MRX-8 and its major deacylation metabolite, MRX-8039, in rat plasma. Animals were administered a single dose of MRX-8 (2, 4, 6, and 8 mg/kg) or comparator polymyxin B (PMB) (4 and 8 mg/kg) to compare the kidney injury known for the polymyxin drug class...

Microbial biofilm formation creates a persistent and resistant environment in which microorganisms can survive, contributing to antibiotic resistance and chronic inflammatory diseases. Increasingly, biofilms are caused by multi-drug resistant microorganisms, which, coupled with a diminishing supply of effective antibiotics, is driving the search for new antibiotic therapies. In this respect, antimicrobial peptides (AMPs) are short, hydrophobic, and amphipathic peptides that show activity against multidrug-resistant bacteria and biofilm formation...

UNLABELLED: Acinetobacter baumannii is highly resistant to antimicrobial agents, and XDR strains have become widespread. A. baumannii has developed resistance to colistin, which is considered the last resort against XDR Gram-negative bacteria, mainly caused by lipooligosaccharide (LOS) phosphoethanolamine (pEtN) and/or galactosamine (GalN) modifications induced by mutations that activate the two-component system (TCS) pmrAB . Although PmrAB of A. baumannii has been recognized as a drug resistance factor, its function as TCS, including its regulatory genes and response factors, has not been fully elucidated...

BACKGROUND: This study aimed to evaluate the effect of polymyxin B hemoperfusion (PMX-HP) in patients with peritonitis-induced septic shock who still required high dose vasopressors after surgical source control. METHODS: This retrospective study included adult patients admitted to the surgical intensive care unit (ICU) at Seoul National University Hospital between July 2014 and February 2021 who underwent major abdominal surgery to control the source of sepsis...

Introduction Comparison of the marker kinetics procalcitonin, presepsin and endotoxin during extracorporeal hemoperfusion with polymyxin B adsorbing cartridge (PMX-HA) have never been described in abdominal sepsis. We aim to compare the trend of three biomarkers in septic post-surgical abdominal patients in Intensive care Unit (ICU) treated with PMX-HA and their prognostic value. Methods Ninety abdominal postsurgical patients were enrolled into different groups according to the evidence of postoperative sepsis or not...

Diabetic wounds are characterized by chronic trauma, with long-term non-healing attributed to persistent inflammation and recurrent bacterial infections. Exacerbation of the inflammatory response is largely due to increased levels of reactive oxygen species (ROS). In this study, catalase (CAT) was used as a biological template to synthesize nanozyme-supported natural enzymes (CAT-Mn(SH)x ) using a biomimetic mineralization method. Subsequently, polymyxin B (CAT-Mn(SH)x @PMB) was immobilized on its surface through electrostatic assembly...

UNLABELLED: Antimicrobial resistance (AMR) poses a significant worldwide public health crisis that continues to threaten our ability to successfully treat bacterial infections. With the decline in effectiveness of conventional antimicrobial therapies and the lack of new antibiotic pipelines, there is a renewed interest in exploring the potential of metal-based antimicrobial compounds. Antimony-based compounds with a long history of use in medicine have re-emerged as potential antimicrobial agents...

Cutaneous T-cell lymphomas (CTCL) are a group of lymphoproliferative disorders of skin-homing T cells causing chronic inflammation. These disorders cause impairment of the immune environment, which leads to severe infections and/or sepsis due to dysbiosis. In this study, we elucidated the host-microbial interaction in CTCL that occurs during the phototherapeutic treatment regime and determined whether modulation of the skin microbiota could beneficially affect the course of CTCL. EL4 T-cell lymphoma cells were intradermally grafted on the back of C57BL/6 mice...

OBJECTIVE: To investigate the clinical characteristics and molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolated from patients with bloodstream infections in a large tertiary-care general hospital in Southwest China. METHODS: A total of 131 strains of non-repeating CRKP were collected from the blood cultures of patients who had bloodstream infections in 2015-2019. The strains were identified by VITEK-2, a fully automated microbial analyzer, and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry...

Drug-induced acute renal failure (ARF) is a public health concern that hinders optimal drug therapy. However, pathological mechanisms of drug-induced ARF remain to be elucidated. Here, we show that a pathological process of drug-induced ARF is mediated by proinflammatory cross-talk between kidney tubular cells and macrophages. Both polymyxin B and colistin, polypeptide antibiotics, frequently cause ARF, stimulated the ERK and NF-κB pathways in kidney tubular cells, and thereby upregulated M-CSF and MCP-1, leading to infiltration of macrophages into the kidneys...

The rapid discrimination of bacteria is currently an emerging trend in the fields of food safety, medical detection, and environmental observation. Traditional methods often require lengthy culturing processes, specialized analytical equipment, and bacterial recognition receptors. In response to this need, we have developed a paper-based fluorescence sensor array platform for identifying different bacteria. The sensor array is based on three unique carbon quantum dots (CQDs) as sensing units, each modified with a different antibiotic (polymyxin B, ampicillin, and gentamicin)...

BACKGROUND: Urinary tract infection (UTI) associated with Klebsiella pneumoniae poses a serious threat for inpatients. This study aimed to describe the genomic characteristics of K. pneumoniae causing UTI in a tertiary-care hospital in Beijing, China. METHODS: A total of 20 K. pneumoniae strains collected from 2020 to 2021 were performed whole-genome sequencing. The Antibiotic susceptibility of 19 common antimicrobial agents was tested against all strains. The multi-locus sequence types (MLSTs) and serotypes were determined from the WGS data...

Polymyxin B (PMB) is considered a last-line treatment for multidrug-resistant (MDR) gram-negative bacterial infections. Model-informed precision dosing with population pharmacokinetics (PopPK) models could help to individualize PMB dosing regimens and improve therapy. However, the external prediction ability of the established PopPK models has not been fully elaborated. This study aimed to systemically evaluate eleven PMB PopPK models from ten published literature based on a new independent population, which was divided into four different populations, patients with liver dysfunction, kidney dysfunction, liver and kidney dysfunction, and normal liver and kidney function...

Pseudomonas aeruginosa is the main pathogen associated with pulmonary exacerbation in patients with cystic fibrosis (CF). CF is a multisystemic genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene, which mainly affects pulmonary function. P. aeruginosa isolated from individuals with CF in Brazil is not commonly associated with multidrug resistance (MDR), especially when compared to global occurrence, where the presence of epidemic clones, capable of expressing resistance to several drugs, is often reported...