Screening and comparison of -induced resistant and clinically resistant strains for eravacycline resistance-related genes.

Objective: To identify genes related to eravacycline resistance in () and to provide a theoretical basis for the study of eravacycline resistance mechanisms in and the development of new antibiotics.

Methods: The study employed an integrated omics approach: (1) antimicrobial susceptibility profiling via broth microdilution to determine baseline MICs for eravacycline and comparator drugs; (2) Induction of resistance in clinical isolates (WJ_4, WJ_14, WJ_18) with low eravacycline MICs through serial passage in escalating drug concentrations; (3) Transcriptome sequencing (RNA-seq) and whole-genome sequencing (WGS) of -induced resistant strains (WJ_4a, WJ_14a, WJ_18a) and a clinical high-MIC isolate (WJ_97); (4) Bioinformatics analyses, including differential gene expression screening (with |log2(fold change)| > 2 and FDR-adjusted p < 0.05), SNP detection via GATK, and copy number variation (CNV) quantification using CCNE-acc to identify and compare resistance-related genetic alterations.

The Role of OXA-101 and OXA-573 in Extensively Drug-Resistant/ Pan Drug-Resistant (XDR/PDR) Resistance to Ceftazidime-Avibactam.

Objective: To explore the association of the resistance of extensively drug-resistant/ pan-drug-resistant (XDR/PDR-PA) to ceftazidime-avibactam (CZA) with various class D β-lactamase genes.

Methods: Twofold dilution was used to determine the minimum inhibitory concentration (MIC) of CZA against XDR/PDR-PA. Whole genome sequencing and bioinformatics analysis were used to determine the drug-resistant genes of each isolate.

Clinical Outcomes of Hospitalized Immunocompromised Patients With COVID-19 and the Impact of Hyperinflammation: A Retrospective Cohort Study.

Purpose: Immunocompromised patients are at increased risk for severe outcomes from COVID-19 due to their altered immune responses, yet their inflammatory profiles and the interplay between immunosuppression remain poorly understood. We aimed to illustrate the inflammation profile and clinical outcomes of hospitalized immunocompromised patients with COVID-19.

Methods: We conducted a retrospective study using a multicenter database and included adult hospitalized patients with Corona virus disease 2019 (COVID-19) in China's late 2022 COVID-19 wave.

Pharmacodynamic target attainment of the synergism of ceftazidime-avibactam in combination with amikacin against OXA-producing extensively drug-resistant or pan drug-resistant (XDR/PDR) Pseudomonas aeruginosa.

To investigate the pharmacodynamic target attainment of ceftazidime-avibactam (CZA) in combination with amikacin against OXA-producing extensively drug-resistant/ pan-drug-resistant Pseudomonas aeruginosa (XDR/PDR-PA). The minimum inhibitory concentrations (MICs) of CZA and amikacin against OXA-producing XDR/PDR-PA were determined by the checkerboard method, and the combined inhibitory index (FICI) was calculated to evaluate whether the combination of the two antimicrobials has a synergistic effect on OXA-producing XDR/PDR-PA in vitro. The pharmacokinetic (PK) and pharmacodynamic (PD) parameters of CZA and amikacin were combined by Monte Carlo simulation (MCS) to evaluate the cumulative fraction of response (CFR) of the two antimicrobials for the treatment of OXA-producing XDR/PDR-PA infection.

Associations of nirmatrelvir-ritonavir treatment with death and clinical improvement in hospitalized patients with COVID-19 during the Omicron wave in Beijing, China: a multicentre, retrospective cohort study.

Background: The effectiveness of nirmatrelvir-ritonavir has mainly been shown in non-hospitalized patients with mild-to-moderate coronavirus disease 2019 (COVID-19). The real-world effectiveness of nirmatrelvir-ritonavir urgently needs to be determined using representative in-hospital patients with COVID-19 during the Omicron wave of the pandemic.

Methods: We performed a multicentre, retrospective study in five Chinese PLA General Hospital medical centers in Beijing, China.

Real-world effectiveness of nirmatrelvir-ritonavir versus azvudine in hospitalized patients with COVID-19 during the omicron wave in Beijing: a multicenter retrospective cohort study.

Background And Aim: Two oral antivirals (Nirmatrelvir- ritonavir and Azvudine) are widely used in China practice during the Omicron wave of the pandemic. However, little evidence regarding the real-world effectiveness of these two oral antivirals in in-hospital patients. We aimed to evaluate the clinical effectiveness of nirmatrelvir-ritonavir versus azvudine among adult hospitalized patients with COVID-19.

In vitro Antimicrobial Activity and Dose Optimization of Eravacycline and Other Tetracycline Derivatives Against Levofloxacin-Non-Susceptible and/or Trimethoprim-Sulfamethoxazole-Resistant .

Purpose: To better guide clinical use, we determined the in vitro antimicrobial activity of the new drug eravacycline and other tetracycline derivatives against levofloxacin (LVFX)-non-susceptible and/or trimethoprim-sulfamethoxazole (TMP-SMZ)-resistant and evaluated their dosing regimens.

Methods: Seventy-seven unique strains of were isolated from sputa samples and airway aspirate samples that were either LVFX-non-susceptible and/or TMP-SMZ-resistant. Monte Carlo simulations were performed for different dosing regimens according to the population pharmacokinetic parameters of antibiotics in patients with respiratory tract infections at the minimum inhibitory concentration (MIC).

Optimal treatment of ceftazidime-avibactam and aztreonam-avibactam against bloodstream infections or lower respiratory tract infections caused by extensively drug-resistant or pan drug-resistant (XDR/PDR) .

Objective: To evaluate the efficacy of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections (BSIs) or lower respiratory tract infections (LRTIs) - caused by extensive drug-resistant or pan drug-resistant (XDR/PDR)

Method: The two-fold dilution method was used to determine the minimum inhibitory concentrations (MICs) of CZA/AZA against XDR/PDR . Whole-genome sequencing was used to analyze the resistance determinants of each isolate. Monte Carlo simulations (MCSs) were used to evaluate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of each CZA/AZA dosing regimen traditional infusion (TI)/optimized two-step-administration therapy (OTAT).

Compassionate Use of Contezolid for the Treatment of Tuberculous Pleurisy in a Patient with a Leadless Pacemaker.

We report the case of an 87-year-old woman with tuberculous pleurisy. She developed adverse effects in the form of thrombocytopenia and gastrointestinal hemorrhage with isoniazid, and thrombocytopenia with linezolid. Her treatment was switched to contezolid plus cycloserine for a 4-week antibiotic duration, with a favorable outcome.

Evaluation of the Efficacy of Optimized Two-Step-Administration Therapy with Ceftazidime/Avibactam for Treating Extensively Drug-Resistant Pseudomonas aeruginosa Pulmonary Infections: a Pharmacokinetic/Pharmacodynamic Analysis.

The objective of this pharmacokinetic (PK)/pharmacodynamic (PD) analysis was to evaluate the efficacy of different dosing regimens of ceftazidime/avibactam (CZA) for the treatment of pulmonary infections by extensively drug-resistant (XDR) Pseudomonas aeruginosa using optimized two-step administration therapy (OTAT) and traditional infusion (TI). We used Monte Carlo simulations (MCS) to integrate PK parameters with PD parameters to assess the adequacy of CZA dosing in critically ill patients with XDR P. aeruginosa pulmonary infections.

Evaluation of ceftazidime/avibactam alone and in combination with amikacin, colistin and tigecycline against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae by in vitro time-kill experiment.

Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) poses a major threat to human health worldwide. Combination therapies of antibiotics with different mechanisms have been recommended in literatures.

Pharmacokinetic/pharmacodynamic modelling to evaluate the efficacy of various dosing regimens of ceftazidime/avibactam in patients with pneumonia caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae: a multicentre study in northern China.

Objectives: The objective of this study was to evaluate the efficacy of different dosing regimens of ceftazidime/avibactam (CZA) in patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) pulmonary infections.

Methods: A total of 70 KPC-Kp strains were isolated from sputum and bronchoalveolar lavage samples of patients with pulmonary infections in three hospitals in northern China from April 2015 to October 2015.

In vitro and in vivo synergistic effects of tigecycline combined with aminoglycosides on carbapenem-resistant Klebsiella pneumoniae.

Objectives: Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections represent severe threats to public health worldwide. The aim of this study was to assess potential synergistic interaction between tigecycline and aminoglycosides via in vitro and in vivo studies.

Methods: Antibiotic resistance profiles and molecular characteristics of 168 CR-KP clinical isolates were investigated by susceptibility testing, PCR and MLST.

In vitro activity of minocycline combined with aminoglycosides against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae.

This study assessed the in vitro antibacterial activity of minocycline-aminoglycoside combination against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. Seventy non-duplicate clinical isolates of KPC-producing K.

Use of Monte Carlo simulation to evaluate the efficacy of tigecycline and minocycline for the treatment of pneumonia due to carbapenemase-producing Klebsiella pneumoniae.

Background: Pneumonia caused by carbapenemase-producing Klebsiella pneumoniae (CP-KP) are increasingly encountered in hospitals worldwide, causing high mortality due to lack of treatment options. The goal of this study was to assess the efficacy of tigecycline and minocycline for CP-KP hospital-acquired pneumonia (HAP) by using Monte Carlo simulation.

Methods: A total of 164 non-duplicated CP-KP strains were collected from sputum or blood in patients with HAP.

Pharmacodynamics of tigecycline alone and in combination with colistin against clinical isolates of multidrug-resistant Acinetobacter baumannii in an in vitro pharmacodynamic model.

The objectives of this study, which were based on the hypothesis of mutant prevention concentration (MPC), were to compare tigecycline and colistin monotherapy and combination therapy against multidrug-resistant Acinetobacter baumannii (MDR-AB) and to identify changes in the susceptibility of the organism using an in vitro pharmacodynamic model. Human free-drug concentration profiles of colistin and tigecycline used alone and in combination were simulated against four clinical MDR-AB isolates over 24 h. Pharmacodynamic activity was measured as log CFU/mL and as the area under the bactericidal curve (AUBC).

Penetration of Ciprofloxacin and Amikacin into the Alveolar Epithelial Lining Fluid of Rats with Pulmonary Fibrosis.

We determined the concentration-time profiles of ciprofloxacin and amikacin in serum and alveolar epithelial lining fluid (ELF) of rats with or without pulmonary fibrosis and investigated the effect of pulmonary fibrosis on the capacity for penetration of antimicrobials into the ELF of rats. Pulmonary fibrosis was induced in rats with a single intratracheal instillation of bleomycin. After intravenous injection of ciprofloxacin or amikacin, blood and bronchoalveolar lavage fluid samples were collected.

Serum soluble urokinase-type plasminogen activator receptor as a biological marker of bacterial infection in adults: a systematic review and meta-analysis.

The serum concentration of soluble urokinase-type plasminogen activator receptor (suPAR) reflects immune activation. We performed a meta-analysis to evaluate the usefulness of suPAR for the diagnosis and prognosis of bacterial infections. PubMed, Embase and Cochrane Library databases were searched for studies reporting the detection of suPAR in adult patients with bacterial infections.

Tigecycline-Amikacin Combination Effectively Suppresses the Selection of Resistance in Clinical Isolates of KPC-Producing Klebsiella pneumoniae.

By far, only tigecycline, colistin, and some aminoglycosides still show favorable in vitro activities against carbapenem-resistant Enterobacteriaceae. However, rapid emergence of resistance often occurs during long-term treatment in clinic, challenging these last resort antimicrobials. In this study, we measured mutant prevention concentration (MPC) and mutant selection window (MSW) of tigecycline, colistin and amikacin alone and in combination for clinical isolates of KPC-producing K.

Evaluation of Trimethoprim/Sulfamethoxazole (SXT), Minocycline, Tigecycline, Moxifloxacin, and Ceftazidime Alone and in Combinations for SXT-Susceptible and SXT-Resistant Stenotrophomonas maltophilia by In Vitro Time-Kill Experiments.

Background: The optimal therapy for infections caused by Stenotrophomonas maltophilia (S. maltophilia) has not yet been established. The objective of our study was to evaluate the efficacy of trimethoprim/sulfamethoxazole (SXT), minocycline, tigecycline, moxifloxacin, levofloxacin, ticarcillin-clavulanate, polymyxin E, chloramphenicol, and ceftazidime against clinical isolated S.

Tigecycline Treatment for Carbapenem-Resistant Enterobacteriaceae Infections: A Systematic Review and Meta-Analysis.

Carbapenem-resistant Enterobacteriaceae (CRE) infections are prevalent worldwide; they have few effective treatments and this jeopardizes public health. Clinicians often use tigecycline to combat CRE, but its clinical efficacy remains controversial. Therefore, to compare the efficacy and safety of tigecycline in treating CRE infections compared with that of other antimicrobial agents, and to evaluate whether combination therapy and high-dose regimens are beneficial, we performed a systematic review and meta-analysis.

Effects of Efflux Pump Inhibitors on Colistin Resistance in Multidrug-Resistant Gram-Negative Bacteria.

We tested the effects of various putative efflux pump inhibitors on colistin resistance in multidrug-resistant Gram-negative bacteria. Addition of 10 mg/liter cyanide 3-chlorophenylhydrazone (CCCP) to the test medium could significantly decrease the MICs of colistin-resistant strains. Time-kill assays showed CCCP could reverse colistin resistance and inhibit the regrowth of the resistant subpopulation, especially in Acinetobacter baumannii and Stenotrophomonas maltophilia These results suggest colistin resistance in Gram-negative bacteria can be suppressed and reversed by CCCP.

Tigecycline treatment experience against multidrug-resistant Acinetobacter baumannii infections: a systematic review and meta-analysis.

The role of tigecycline in treating multidrug-resistant Acinetobacter baumannii (MDR-AB) infections remains controversial. A systematic review and meta-analysis was performed to assess the efficacy and safety of tigecycline in treating MDR-AB infections. PubMed, Embase and Cochrane Library databases were searched up to 20 September 2015.

Healthcare-associated Pneumonia: Clinical Features and Retrospective Analysis Over 10 Years.

Background: Healthcare-associated pneumonia (HCAP) is associated with drug-resistant pathogens and high mortality, and there is no clear evidence that this is due to inappropriate antibiotic therapy. This study was to elucidate the clinical features, pathogens, therapy, and outcomes of HCAP, and to clarify the risk factors for drug-resistant pathogens and prognosis.

Methods: Retrospective observational study among hospitalized patients with HCAP over 10 years.

A Monte Carlo pharmacokinetic/pharmacodynamic simulation to evaluate the efficacy of minocycline, tigecycline, moxifloxacin, and levofloxacin in the treatment of hospital-acquired pneumonia caused by Stenotrophomonas maltophilia.

Background: Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen in recent years. Increasing antimicrobial resistance and other contraindications have greatly compromised trimethoprim/sulfamethoxazole (SXT) as the first-line therapeutic option. The objective of this study was to explore other options for treating hospital-acquired pneumonia (HAP) caused by S.