Infection and Drug Resistance最新文献

Antifungal therapy for invasive pulmonary aspergillosis (IPA) can be challenging in cancer patients due to interpatient variability in pharmacokinetic properties of antifungals and potential drug-drug interactions (DDIs). This case report describes a 14-year-old boy with advanced osteosarcoma diagnosed with invasive pulmonary aspergillosis (IPA) after chemotherapy. Initial treatment of voriconazole showed poor improvement, as therapeutic drug monitoring (TDM) revealed exceptionally low trough concentration (0.28 μg/mL) even after dose increase. When voriconazole was switched to isavuconazole, favorable antifungal response was observed with isavuconazole trough concentrations ranging from 2.43 μg/mL to 4.12 μg/mL. Moreover, TDM also detected no obvious pharmacokinetic DDI between isavuconazole and apatinib but potential DDI between voriconazole and anlotinib in this patient. This case highlights the importance of individualized pharmacokinetic considerations in antifungal therapy in cancer patients. TDM may be a useful aid for therapeutic regimen decision and optimization.

Advances in diagnostic technologies have led to the identification of an increasing number of viruses associated with pneumonia, thereby drawing significant attention to viral pneumonia. The primary viral pathogens implicated in pneumonia include influenza virus, respiratory syncytial virus, coronavirus, adenovirus, parainfluenza virus, human metapneumovirus, and enterovirus. Post-translational modifications, especially phosphorylation, are pivotal in the lifecycle of these viruses. Phosphorylation affects key processes such as viral replication, transcription, assembly, and release, thereby influencing their propagation in host cells. Viral infection can also trigger kinase-associated pathways within host cells, activating host cell phosphatases and related signaling cascades. This results in alterations to host phosphorylation states, aggravating cellular pathology and facilitating viral proliferation. This review examines the common viral pathogens involved in pneumonia and highlights the role of phosphorylation in viral proliferation. Additionally, we explore the potential of phosphorylation inhibitors in controlling viral infections, with the aim of advancing our understanding of viral phosphorylation and promoting the use of these inhibitors in the treatment of viral pneumonia.

Background: Infections caused by daptomycin-resistant and vancomycin-resistant Enterococcus faecium (DRE) are a critical clinical challenge with limited therapeutic options. This study aimed to compare the efficacy of high-dose daptomycin monotherapy against combination therapies in a rat model of DRE infective endocarditis (IE).

Methods: A clinical DRE isolate (daptomycin MIC, 8 mg/L) was used to establish IE in Wistar rats. After 48  h, the animals were randomized to three-day regimens: saline control, daptomycin 90 mg/kg/day s.c. (D90), daptomycin 125 mg/kg/day s.c. (D125), D90 plus fosfomycin 500 mg/kg/day i.p. (D90F), or D90 plus ceftaroline 40 mg/kg q8 h i.m. (D90C). Efficacy was evaluated by quantifying colony-forming units (CFU) in excised cardiac vegetation.

Results: A strong correlation was observed between higher daptomycin exposure (Cmax/MIC and AUC_{0 -2 4}/MIC) and lower vegetation bacterial density (p < 0.01 for both). High-dose daptomycin monotherapy (D125) was the most effective regimen, resulting in the lowest mean vegetation bacterial load (4.75 log_{1 0} CFU/g). This was significantly lower than the bacterial load in the D90F group (5.62 log_{1 0} CFU/g; p = 0.02) and showed a trend towards superiority over the D90C group (5.87 log_{1 0} CFU/g; p = 0.05).

Conclusion: In this severe DRE infection model, escalating the daptomycin dose was more effective in clearing bacteria from the cardiac vegetation than combining a standard high dose with a synergistic agent. These findings suggest that higher daptomycin exposure may be a viable strategy for managing DRE infections, pending clinical validation.

Objective: To compare the clinical value of Group A Streptococcus (GAS) antigen detection and pathogen culture in the diagnosis and treatment of paediatric infections, providing a basis for the rational use of antibiotics.

Methods: This retrospective study included 310 paediatric patients with GAS infections admitted between January 2019 and January 2024. Patients were assigned to either the antigen-positive group (n = 156) or the culture-positive group (n = 154). Demographic characteristics, clinical features, treatment outcomes, and complications were compared between the two groups.

Results: There were no significant differences between the two groups in terms of demographic data (age, sex, weight) and clinical symptoms (such as fever, sore throat, and rash) (P > 0.05). The time to fever resolution (3.00 [3.00, 4.00] days vs 3.00 [2.00, 4.00] days, P = 0.103), time to sore throat resolution (3.00 [3.00, 5.00] days vs 4.00 [3.00, 5.00] days, P = 0.405), acute complication rates (6.41% vs 9.09%, P = 0.377), and late complications (none in either group) during the 3-month follow-up period showed no significant differences.

Conclusion: GAS antigen detection and pathogen culture have comparable clinical efficacy and can both effectively guide antibiotic treatment. Rapid antigen detection can be used as the preferred screening method in clinical practice, optimising early diagnosis and treatment.

Purpose: To examine the distribution of clinical pathogens and their antimicrobial resistance trends in a hospital in East China to provide evidence for rational antibiotic use and infection control.

Methods: We conducted a retrospective study of bacterial isolates from January 2020 to December 2024. Bacterial identification and antimicrobial susceptibility testing were performed using the VITEK 2 system. WHONET 5.6 and R software were used for data analysis. Statistical analyses included chi-square tests and trend tests.

Results: A total of 8680 pathogenic isolates were collected. Gram-negative bacteria predominated (74.7%) over Gram-positive bacteria (25.3%). The primary specimens were urine (33.7%), sputum (25.3%), and secretions (19.4%). The leading pathogens were E. coli (28.4%), K. pneumoniae (12.8%), and P. aeruginosa (11.5%). The carbapenem resistance rate was less than 1.9% in Escherichia coli strains over five years. The rate for carbapenem resistant K. pneumoniae (CRKP) showed a significant increasing trend, rising from 9.4% in 2022 to 16.7% in 2024 (p<0.05). CRKP rates were lower than national CHINET data. The imipenem resistance rate of Pseudomonas aeruginosa exhibited an upward trend from 2020 (24.2%) to 2023 (34.1%) (p<0.05). A. baumannii maintained high resistance to imipenem (>73%), exceeding national levels. The proportion of methicillin-resistant Staphylococcus aureus (MRSA) fluctuated over the course of the five years (26.9-44.8%). No vancomycin-resistant Enterococcus (VRE) was detected.

Conclusion: E. coli, K. pneumoniae, and P. aeruginosa were the predominant pathogens in this hospital. The rising and high resistance rates of CRKP and CRAB highlight the urgent need for enhanced antimicrobial stewardship. Β-lactamase, β-lactamase inhibitor combination preparations and carbapenems were recommended for susceptible strains of E. coli and K. pneumoniae. For CRKP infections and CRAB infections, tigecycline and colistin are recommended. Continuous surveillance and infection control are crucial to combat the evolving threat of multidrug-resistant organisms.

Objective: This study reports five clinical cases of adult Febrile Infection-Related Epilepsy Syndrome (FIRES) treated with a ketogenic diet (KD). The aim is to explore the clinical efficacy, safety, optimal initiation timing, and related efficacy factors of KD in adult FIRES through case analysis, and to provide reference for clinical decision-making.

Methods: We retrospectively reviewed the medical records of five FIRES patients treated with KD at Shanxi Bethune Hospital between October 2019 and January 2025.

Results: Among the five FIRES patients (2 males, 3 females), with a median age of 32 years [interquartile range (IQR) 25-34]. All patients presented with refractory status epilepticus following a febrile illness. EEG revealed slowed background activity with multifocal epileptiform discharges, and 60% (3/5) showed abnormal brain MRI findings. All patients received multidrug antiseizure therapy, anesthetics, and immunotherapy. KD was initiated at a median of 33 days (IQR 10-50) post-onset. Ketosis was achieved within a median of 2 days (IQR 2-3), followed by significant seizure reduction after a median of 3 days (IQR 3-4) of KD. At discharge, mRS scores were 2 (40%) or 4 (60%); by 3-month follow-up, all patients achieved an mRS score of 2. Common adverse effects included diarrhea (60%), hypoalbuminemia (100%), anemia (80%), fecal occult blood (60%), and hyperlipidemia (40%), all of which resolved with symptomatic management.

Conclusion: FIRES is a rare and devastating clinical syndrome with an unclear pathogenesis, high mortality, and poor prognosis, often accompanied by cognitive decline or severe neurological sequelae. KD appears effective in FIRES management; however, due to limited case data, further large-sample, prospective, or randomized controlled studies are needed to elucidate its short- and long-term efficacy in adult FIRES patients.

Purpose: It is well known that bacteria often acquire drug resistance genes through acquiring exogenous resistant plasmids. The tmexCD1-toprJ1-positive plasmid confers tigecycline resistance to bacterial strains.

Methods: Three sequence type (ST) 17 Klebsiella pneumoniae strains were isolated from two patients within 5 days. Experimental and comparative genomic analyses were performed to investigate potential transmission routes and antimicrobial resistance phenotype disparities.

Results: Strain HD9931 was tigecycline-sensitive, whereas HD9932 and HD10868 were tigecycline-resistant because of the presence of a tmexCD1-toprJ1-positive plasmid. HD10868 exhibited enhanced fitness and greater tigecycline resistance than HD9932 did. Comparative analysis revealed mutations in the AcrAB-TolC efflux pump and lamb in HD9932 and HD10868.

Conclusion: Our study highlights the complexity of resistance gene transfer and underscores the need for continued vigilance and research in this field.

Objective: This study aimed to analyze the distribution characteristics and changes in antimicrobial resistance of pathogens in the Pediatric Intensive Care Unit (PICU) of Beijing Children's Hospital from 2014 to 2023 to guide the rational use of antibiotics and provide a scientific basis for hospital infection prevention and control, as well as public health policy formulation.

Methods: A retrospective cohort design was used to systematically analyze the clinical data and antibiotic sensitivity results of 4,468 children aged 0-17 years who were admitted to the PICU of Beijing Children's Hospital between 2014 and 2023.

Results: 6,079 strains of pathogenic bacteria were cultured and isolated. There were 4,276 strains of Gram-negative bacteria, including Acinetobacter baumannii (20.0%), Pseudomonas aeruginosa (15.2%), and Klebsiella pneumoniae (12.9%); There were 1,803 Gram-positive bacteria, including Staphylococcus aureus (11.3%) and coagulase-negative Staphylococci (CoNS) (7.9%). Between 2014 and 2023, the number of detected Gram-negative and Gram-positive bacteria showed a fluctuating upward trend. A. baumannii showed a resistance rate of over 70% to most antibiotics, P. aeruginosa exhibited a relatively high resistance rate to carbapenems, and Escherichia coli demonstrated a high resistance rate to third-generation cephalosporins, but a low resistance rate to carbapenems. Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococci (MRCNS) were highly resistant to most antibiotics but remained highly sensitive to linezolid and vancomycin. Carbapenem-resistance (CR) and difficult-to-treat resistance (DTR) phenotypes of K. pneumoniae showed a marked upward trend. In contrast, E. coli, P. aeruginosa, and A. baumannii exhibited fluctuating or relatively stable resistance to extended-spectrum cephalosporins (ECR) and fluoroquinolones (FQR).

Conclusion: This study revealed the distribution and antibiotic resistance trends of pathogens in the PICU of Beijing Children's Hospital, providing important evidence for empirical anti-infective treatment in clinical practice.

Infectious complications still remain a major challenge in the treatment of children with hematological malignancies. Invasive mold infections such as invasive aspergillosis or mucormycosis have a significant and negative impact on overall outcome in pediatric cancer patients. Although severe prolonged neutropenia is the major risk factor for invasive mold infection, other factors such as steroid exposure and acute or chronic graft-versus-host disease have to be considered in increasing the risk for infection. As clinical signs and symptoms are unspecific, diagnosis of invasive mold infection is mainly based on imaging and microbiological evaluation. Non-culture based tests using biomarkers such as galactomannan are more sensitive than culture-based tests, and there is major development of molecular techniques including next generation sequencing and analysis of cell-free DNA in order to improve both specificity and sensitivity. Antifungal strategies can be divided in prophylaxis (indicated for patients with a natural incidence of fungal infection ≥10%), empirical (eg, prolonged neutopenic fever despite broad-spectrum antibiotics) and pre-emptive therapy and treatment of established infection. Although there are exciting potent novel-class antifungal agents in the pipeline, pediatric approval of antifungal compounds significantly lags that for adult patients. To this end, despite major improvements over the last three decades, invasive mold infection is still a major challenge for pediatric patients with hematological malignancies.

SARS-CoV-2 is a major global public health burden associated with significant morbidity, mortality, and complications, including respiratory, cardiovascular, neurological, and digestive disorders. COVID-19 may induce venous and arterial thromboembolic complications, including deep vein thrombosis, myocardial infarction and cerebral infarction. Simultaneous myocardial and cerebral infarction, termed cardio-cerebral infarction, is exceedingly rare. There is only limited case of concurrent cardio-cerebral infarction in patients with COVID-19. Although there is no standard treatment for the condition, antiplatelet and anticoagulation agents should be used. We emphasize the catastrophic coexistence of concurrent cardio-cerebral infarction in a patient co-infected with SARS-CoV-2 and influenza A. We described a 75-year-old woman was admitted for SARS-CoV-2 and influenza A coinfection. She received anti-viral agent treatment for the virus infection. The patient presented with right side limbs weakness and declined consciousness. The magnetic resonance imaging of brain revealed acute cerebral infarction over the left corona radiata and basal ganglion. Meanwhile, acute myocardial infarction was diagnosed using electrocardiogram and elevated cardiac enzymes. Percutaneous coronary intervention and dual-antiplatelet agents were applied for the arterial thrombosis. The patient survived and recovered with mild residual hemiparesis. In addition, this is the first reported case of concurrent cardio-cerebral infarction in patients with SARS-CoV-2 and influenza A coinfection. Coinfection with SARS-CoV-2 and influenza A is associated with more complications including thromboembolic complications. Management of concurrent cardio-cerebral infarction poses challenges, as timely intervention is critical to prevent disability or death, yet aggressive anticoagulation risks hemorrhagic complications. Optimal treatment strategies remain unclear, highlighting the need for further research. This case underscores the importance of vigilance in managing thrombotic complications in patients with SARS-CoV-2 and influenza coinfection. Despite the downgrading of the COVID-19 pandemic, clinicians must remain alert to complex presentations caused by coinfections with respiratory viruses.