The role of universal stress protein Usp1413 in meropenem adaptive resistance and environmental stress responses in .

Although various mechanisms of carbapenem-resistance have been identified in the nosocomial pathogen , the critical process of resistance evolution and the factors involved in are not well understood. Herein, we identified a universal stress protein Usp1413 which played an important role in adaptive resistance of to meropenem (MEM). Based on RNA-Seq and genome sequencing, Usp1413 was not only one of the most downregulated USPs, but also the bare one having mutation of tyrosine and glycine inserted at the site of 229-230 (YG229-230) under the stimulation of MEM.

The role of type VI secretion system genes in antibiotic resistance and virulence in clinical isolates.

Introduction: The type VI secretion system (T6SS) is a crucial virulence factor in the nosocomial pathogen . However, its association with drug resistance is less well known. Notably, the roles that different T6SS components play in the process of antimicrobial resistance, as well as in virulence, have not been systematically revealed.

The optimized carbapenem inactivation method for objective and accurate detection of carbapenemase-producing .

The modified carbapenem inactivation method (mCIM) recommended by the Clinical and Laboratory Standards Institute is not applicable for detecting carbapenemases in . Four currently reported phenotypic detection methods, namely, the modified Hodge test, the mCIM, the adjusted mCIM, and the simplified carbapenem inactivation method (sCIM), did not perform well in our 90 clinical isolates. Thus, the minimal inhibitory concentrations (MICs) of carbapenems and the existence and expression of carbapenemase-encoding genes were detected to explain the results.

Programmed Cell Death Protein 1/Programmed Cell Death Ligand 1 Signaling Pathway Mediated Interleukin-10 and Bacterial Biofilm Formation to Drug Resistance Mechanism of Pneumoniae Meningitis.

It aimed to explore the resistance and biofilm formation characteristics of pneumococcal meningitis (PM) and the mechanism of programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) signaling pathway (SPW). Firstly, the drug susceptibility test of 32 Streptococcus pneumoniae strains isolated from patients with PM and the biofilm semi-quantitative determination was performed. Then, the PM mouse model was constructed.

Hemorrhagic Fever with Renal Syndrome Complicated with Rhino Mucormycosis: A Case Report.

Mucormycosis (MCR) is a rare but aggressive fungal disease. Rhino-orbito-cerebral mucormycosis is the most common clinical form of MCR infection, and sinonasal inoculation is the primary site of infection. The morbidity and mortality rates associated with MCR remain high.

Discovery and therapeutic implications of bioactive dihydroxylated phenolic acids in patients with severe heart disease and conditions associated with inflammation and hypoxia.

Our initial studies detected elevated levels of 3,4-dihydroxyphenyllactic acid (DHPLA) in urine samples of patients with severe heart disease when compared with healthy subjects. Given the reported anti-inflammatory properties of DHPLA and related dihydroxylated phenolic acids (DPAs), we embarked on an exploratory multi-centre investigation in patients with no urinary tract infections to establish the possible pathophysiological significance and therapeutic implications of these findings. Chinese and Caucasian patients being treated for severe heart disease or those conditions associated with inflammation (WBC ≥ 10 ×10/L or hsCRP ≥ 3.

Clinical Efficacy and Cost-Effectiveness of β-Lactam/β-Lactamase Inhibitor Combinations and Carbapenems in Liver Cirrhosis Patients with Gram-Negative Bacteria Bloodstream Infection.

Background: Gram-negative bacteria bloodstream infection (GNB-BSI) results in considerable mortality and hospitality costs in cirrhotic patients. β-lactam/β-lactamase inhibitor combinations (BLBLIs) and carbapenems (CARs) are widely recommended for treating GNB-BSI in cirrhotic patients, while the efficacy and cost-effectiveness of two strategies have never been evaluated. Therefore, we conducted a retrospective cohort study to evaluate the efficacy and the cost-effectiveness of BLBLIs and CARs.

The assemblage of covalent and metal binding dual functional scaffold for cross-class metallo-β-lactamases inhibition.

The discovery and development of novel broad-spectrum MβLs inhibitors are urgent to overcome antibiotic resistance mediated by MβLs. Herein, the synthesized 21 compounds exhibited potent inhibition to the clinically important MβLs (NDM-1, IMP-1 and ImiS) and effectively restored the antibacterial efficacy of cefazolin and imipenem against harboring MβLs. was first identified to be dual functional broad-spectrum MβLs inhibitor through assemblage of covalent and metal binding scaffold, which irreversibly inhibited B1, B2 MβLs via forming a Se-S covalent bond, and competitively inhibited B3 MβLs by coordinating the metals at active site.

Antibiotic consumption versus the prevalence of carbapenem-resistant Gram-negative bacteria at a tertiary hospital in China from 2011 to 2017.

Purpose: China launched a 3-year rectification scheme on the clinical use of antibiotics in 2011, and a specific scheme on carbapenem use in February 2017. This study investigated the trends in and correlations between antibiotic consumption and the prevalence of carbapenem-resistant Gram-negative bacteria (CRGN) at a tertiary hospital during these years, particularly in carbapenem consumption.

Methods: The data were collected calculated per quarter from 2011 to 2017.

Real-Time Monitoring of NDM-1 Activity in Live Bacterial Cells by Isothermal Titration Calorimetry: A New Approach To Measure Inhibition of Antibiotic-Resistant Bacteria.

The "superbug" infection caused by New Delhi metallo-β-lactamase (NDM-1) has become an emerging threat. Monitoring NDM-1 has proven challenging due to its shuttling between pathogenic bacteria. Here, we report an isothermal titration calorimetry (ITC) method that can monitor activity and inhibition of NDM-1 in live bacterial cells in real time.

Label-Free Visualization of Carbapenemase Activity in Living Bacteria.

Evaluating enzyme activity intracellularly on natural substrates is a significant experimental challenge in biomedical research. We report a label-free method for real-time monitoring of the catalytic behavior of class A, B, and D carbapenemases in live bacteria based on measurement of heat changes. By this means, novel biphasic kinetics for class D OXA-48 with imipenem as substrate is revealed, providing a new approach to detect OXA-48-like producers.

A strategy for designing voriconazole dosage regimens to prevent invasive pulmonary aspergillosis based on a cellular pharmacokinetics/pharmacodynamics model.

Background: Invasive pulmonary aspergillosis (IPA) is a life-threatening disease in immunosuppressed patients. Voriconazole is commonly used to prevent and treat IPA in the clinic, but the optimal prophylactic antifungal regimen is unknown. The objective of this study was to clarify the mechanism underlying how voriconazole prevents IPA based on a target cellular pharmacokinetics/pharmacodynamics model, with the aim of identifying a way to design an optimal prophylactic antifungal regimen.

Voriconazole therapeutic drug monitoring: Factors associated with supratherapeutic and subtherapeutic voriconazole concentrations.

Objective: The voriconazole trough concentration (C) varies widely, and C outside the therapeutic range (COTR) is associated with response failure and toxicity. The objective of this study was to identify potential factors associated with COTR in patients, and specifically the population at a high risk of COTR.

Materials And Methods: We performed a retrospective study of patients who received voriconazole from 2009 to 2016.

Characterization of β-lactamase activity using isothermal titration calorimetry.

Background: Hydrolysis of β-lactam antibiotic by β-lactamase is the most common mechanism of β-lactam resistance in clinical isolates. Timely detection and characterization of β-lactamases are therefore of utmost biomedical importance. Conventional spectrophotometric method is time-consuming and cannot provide thermodynamic information on β-lactamases.

Uptake and efflux kinetics, and intracellular activity of voriconazole against Aspergillus fumigatus in human pulmonary epithelial cells: a new application for the prophylaxis and early treatment of invasive pulmonary aspergillosis.

Invasive pulmonary aspergillosis (IPA), most caused by Aspergillus fumigatus, is a serious life-threatening infection in immunocompromised patients. Voriconazole is used to prevent and treat IPA. However, little is known about the pharmacological characteristics of voriconazole in pulmonary epithelial cells, which are the target site for the prophylaxis and early treatment of IPA.

Extensively drug-resistant Acinetobacter baumannii outbreak cross-transmitted in an intensive care unit and respiratory intensive care unit.

Background: Extensively drug-resistant Acinetobacter baumannii (XDRAB) is a great threat in intensive care units (ICUs). The aim of this study was to describe an XDRAB outbreak which was cross-transmitted in the ICU and respiratory intensive care unit (RICU) in a tertiary care hospital from January-March 2013.

Methods: Patient and environmental surveillances were performed.

In vitro activities of tedizolid compared with other antibiotics against Gram-positive pathogens associated with hospital-acquired pneumonia, skin and soft tissue infection and bloodstream infection collected from 26 hospitals in China.

To evaluate the in vitro antimicrobial activities of tedizolid, linezolid and other comparators against clinically significant Gram-positive cocci isolates from hospital-acquired pneumonia (HAP), skin and soft tissue infection (SSTI) and bloodstream infection (BSI), 2140 nonduplicate isolates (23.7 % isolated from HAP, 46.8 % from SSTI and 29.

Optimization of voriconazole dosage regimen to improve the efficacy in patients with invasive fungal disease by pharmacokinetic/pharmacodynamic analysis.

Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in hospitalized patients. To maximize the efficacy of voriconazole treatment, the study established the relationship between voriconazole pharmacokinetic/pharmacodynamic (PK/PD) and probability of response and optimized voriconazole dosage regimen in patients with IFD based on Monte Carlo simulation. Forty-four patients proven with IFD were involved in this study.

Photodynamic inactivation of Klebsiella pneumoniae biofilms and planktonic cells by 5-aminolevulinic acid and 5-aminolevulinic acid methyl ester.

The treatment of Klebsiella pneumoniae, particularly extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae, is currently a great challenge. Photodynamic antimicrobial chemotherapy is a promising approach for killing antibiotic-resistant bacteria.

Photodynamic inactivation of antibiotic-resistant bacteria and biofilms by hematoporphyrin monomethyl ether.

The worldwide increase in bacterial antibiotic resistance has led to a search for alternative antibacterial therapies. A promising approach to killing antibiotic-resistant bacteria is photodynamic antimicrobial chemotherapy, which uses light in combination with a photosensitizer to induce a phototoxic reaction. We evaluated the photodynamic inactivation (PDI) efficiency of hematoporphyrin monomethyl ether (HMME) on antibiotic-resistant bacteria and biofilms.

Pharmacokinetic and Pharmacodynamic Properties of Oral Voriconazole in Patients with Invasive Fungal Infections.

Study Objectives: To assess the pharmacokinetic and pharmacodynamic (PK/PD) properties of voriconazole and to investigate the relationship between PK/PD parameters and the efficacy of a fixed-dose oral regimen in the treatment of invasive fungal infections (IFIs).

Design: Prospective and observational PK/PD study.

Setting: A university-affiliated medical center.

Factors on trough teicoplanin levels, associations between levels, efficacy and safety in patients with gram-positive infections.

Objective: The objective of this study was to identify the factors influencing trough teicoplanin concentrations (C(min)), to investigate the relationship between teicoplanin C(min) with efficacy and safety, and to determine a target therapeutic concentration.

Methods: An analysis was performed on 95 serum concentrations from 50 patients with gram-positive infections who received teicoplanin treatment. Teicoplanin serum concentrations were measured by high-performance liquid chromatography.

Mechanistic aspects of the photodynamic inactivation of vancomycin-resistant Enterococci mediated by 5-aminolevulinic acid and 5-aminolevulinic acid methyl ester.

Vancomycin-resistant Enterococci (VRE) is a serious concern for public health. Serious infections with VRE have very limited effective antimicrobial therapy, and alternative treatment approaches are highly desirable. One promising approach might be the photodynamic antimicrobial chemotherapy.

Phenotypic and genotypic characteristic of invasive pneumococcal isolates from both children and adult patients from a multicenter surveillance in China 2005-2011.

Streptococcus pneumoniae is an important pathogen in both children and the elderly, but previous studies in China have provided limited information about invasive pneumococcal disease (IPD). A total of 240 IPD S. pneumoniae strains (from 105 children and 135 adults) were collected from 12 cities in China in 2005-2011.