Treatment of multidrug-resistant (MDR) Gram-negative bacteria (GNB) infections has led to a global public health challenging due to the bacterial resistance and limited choices of antibiotics. Cefiderocol (CFDC), a novel siderophore cephalosporin possessed unique drug delivery systems and stability to β-lactamases, has the potential to become first-line therapy for most aggressive MDR Gram-negative pathogens infection. However, there have been reports of drug resistance in the course of using CFDC. This study provides an overview of the in-vitro and in-vivo activity of CFDC and potential resistance mechanism was also summarized. In general, CFDC shows excellent activity against a broad range of MDR GNB pathogens including Enterobacteriaceae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. The expressions of metallo-β-lactamases such as inosine 5'-monophosphate (IMP), Verona integron-mediated metallo-β-lactamase (VIM), and New Delhi metallo-β-lactamase (NDM) are associated with a higher resistance rate of CFDC. Carbapenem-resistant phenotype has little effect on the resistance rate, although the acquisition of a particular carbapenemase may affect the susceptibility of the pathogens to CFDC. For potential resistance mechanism, mutations in β-lactamases and TonB-dependent receptors, which assist CFDC entering bacteria, would increase a minimum inhibitory concentration (MIC)90 value of CFDC against MDR pathogens. Since the development of CFDC, resistance during its utilization has been reported thus, prudent clinical applications are still necessary to preserve the activity of CFDC.

Chronic obstructive pulmonary disease (COPD) has the highest mortality rate among chronic respiratory diseases [1]. COPD patients often show incomplete reversibility of airflow obstruction caused by emphysema and chronic bronchitis. It can eventually develop into severe diseases, such as pulmonary heart disease and respiratory failure. Currently, there is no good way to prevent development of […]

One of the major limitations in the clinical use of existing oxazolidinone antibiotics is their characteristic adverse reactions, in particular thrombocytopenia. In anti-infective treatment, if patients are suspected of having drug-induced thrombocytopenia, the first step is to immediately discontinue the offending drug. Even in patients with severe infections, the antibacterial drug may need to be changed or the antibacterial treatment may need to be discontinued because thrombocytopenia may have a more serious clinical prognosis. In addition, if the patient needs to continue antibacterial treatment after discharge, the lack of conditions for monitoring platelet levels may also pose hidden dangers to the patient. Contezolid is an orally administered oxazolidinone antibacterial agent approved by the National Medical Products Administration of China in 2021. We found that contezolid may have an improved safety profile with a significantly reduced potential for myelosuppression based on the results of our observational clinical study. In this article, we review the advantages of contezolid as a new oxazolidinone antibiotic and describe three typical clinical cases of patients who experienced drug-induced thrombocytopenia after using linezolid. The platelet levels of these different patients were all significantly improved to varying degrees after initiation of contezolid treatment.

Background: Drug-drug interactions (DDIs) are factors of adverse drug reactions and are more common in elderly patients. Identifying potential DDIs can prevent the related risks. Fewer studies of potential DDIs in prescribing for elderly patients in outpatient clinics. This study aimed to investigate the prevalence and associated factors with potential DDIs and potentially clinically significant DDIs (csDDIs) among elderly outpatients based on 3 DDIs databases. Methods: A cross-sectional study was carried out on outpatients (≥65 years old) of a tertiary care hospital in China between January and March 2022. Patients’ prescriptions, including at least 1 systemic drug, were consecutively collected. The potential DDIs were identified by Lexicomp^®, Micromedex^®, and DDInter. Patient-related clinical parameter recorded at the prescriptions and DDIs with higher risk rating was analyzed. Variables showing association in univariate analysis (P<0.2) were included in logistic regression analysis. Weighted kappa analysis was used to analyze the consistencies of different databases. Results: A total of 19,991 elderly outpatients were involved in the study, among whom 21,527 drug combinations including 486 drugs occurred. Lexicomp^®, Micromedex^®, and DDInter respectively identified 32.22%, 32.93%, and 22.62% of patients have at least one potential DDIs, meanwhile, 9.16%, 14.53%, and 4.56% of patients have at least one potential csDDIs. Under any evaluation criteria, polypharmacy and neurology visits were risk factors for csDDIs. Lexicomp^® has the highest coverage rate (87.86%) for drugs. Micromedex^® identified the most csDDIs (740 drug combinations). Drugs used in diabetes and psycholeptics were frequently found in the csDDIs of 2 commercial databases. The consistency between Lexicomp^® and Micromedex^® was moderate (weighted kappa 0.473). DDInter had fair consistencies with the other databases. Conclusions: This study showed the prevalence of potential DDIs is high in elderly outpatients and potential csDDIs were prevalent. Considering the relative risk, pre-warning of potential DDIs before outpatient prescribing is necessary. As the consistencies among identification criteria are not good, more research is needed to focus on actual adverse outcomes to promote accurate prevention of csDDIs.

As a heterogeneous and wide inflammation, osteoarticular infection (OAI) shows an increasing incidence in recent years. Staphylococcus aureus is the most important pathogen causing OAI. The antibiotic treatment will affect the outcomes of OAI patients, and the drug selection and dosage regimen highly rely on patients’ variability, pathogen susceptibility, and drug property like bone permeability. Model-informed precision dosing (MIPD) provides options to describe and quantify the pharmacokinetic (PK) variability of the OAI population using different models, such as the population pharmacokinetic (PPK) model and physiological-based pharmacokinetic (PB/PK) model. In the present review, we highlighted that the MIPD of antibiotics played a critical role in OAI and listed the dose regimen recommended by the model. Collectively, our current study provided a valuable reference for the treatment of patients and improved the safety and efficiency of drug use.