Infection and Drug Resistance最新文献

Antimicrobial resistance poses a serious threat to human health. Polymyxins, as cyclic polypeptide antibiotics, include polymyxin B (PMB) and polymyxin E. Although they have different metabolic pathways, their antibacterial activities are similar. Polymyxins exert their effects through mechanisms such as disrupting bacterial cell membranes, neutralizing endotoxins, and impairing the respiratory chain. In clinical practice, polymyxins are often used in combination with other drugs to treat infections caused by carbapenem-resistant gram-negative bacteria (CRGNB). No difference in efficacy has been demonstrated between PMB and polymyxin E. An increasing amount of evidence suggests that combination therapy is not superior to monotherapy. The combination of intravenous administration and nebulization can help improve microbial clearance. Compared with other antibiotics, polymyxins have not shown obvious survival benefit. Polymyxins are associated with nephrotoxicity and neurotoxicity, and it is essential to closely monitor for related adverse events during the course of treatment.

Objective: To examine the species distribution, clinical prevalence, antimicrobial profiles, and carbapenemase phenotypes of carbapenem-resistant Enterobacterales (CRE) isolated from a tertiary hospital over the past two years, thereby providing a reference for clinical anti-infection strategies and hospital infection control measures.

Methods: A retrospective analysis was performed to examine the distribution of CRE strains isolated from inpatients at a tertiary hospital between 2023 and 2024, their resistance profiles to commonly used antibiotics and carbapenemase phenotypes.

Results: A total of 239 distinct CRE strains were identified between 2023 and 2024, predominantly in sputum, urine, and blood samples. The primary species of CRE include Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis. These CRE strains were mainly isolated from departments such as geriatrics, intensive care units (ICU), and respiratory medicine. Among the 239 CRE isolates, there was a notably high resistance rate to cephalosporins, enzyme inhibitor combinations, aminoglycosides, and quinolones, exceeding 85%, with carbapenems exhibiting a resistance rate of over 90%. Conversely, the resistance rates to tigecycline, ceftazidime/avibactam, and polymyxin B were 1.26%, 24.24%, and 5.43%, respectively. The majority of strains (74.06%) produced class A serine carbapenemases, specifically the KPC type.

Conclusion: The CRE isolation and resistance rates in this hospital are similar to international trends, both showing an upward trend, and comparison with domestic data reveals significant regional differences. CRE infections are difficult to treat and have a high mortality rate. Therefore, to meet the needs of Infection Prevention and Control, it is necessary to strengthen the monitoring of CRE resistance in this institution, contributing to the prevention, control, and clinical management capabilities for infections.

Purpose: This study aimed to evaluate the clinical effectiveness and safety of high-dose versus standard-dose cefoperazone-sulbactam in patients with severe infections, particularly those caused by multidrug-resistant organisms (MDROs).

Patients and methods: A multicenter retrospective cohort study was conducted across four hospitals from January 2020 to October 2024. Adult patients who received cefoperazone-sulbactam for severe infections, defined as admission to the intensive care unit (ICU), requirement for mechanical ventilation, or an increase in Sequential Organ Failure Assessment (SOFA) score of more than 2, or MDROs were categorized into high-dose (2 g-2 g q8h) and standard-dose (2 g-2 g q12h) groups. The primary outcome was clinical cure at day 14. Secondary outcomes included microbiological eradication, in-hospital mortality, and adverse events (AEs). Multivariate logistic regression and subgroup analyses were performed to identify treatment-associated factors.

Results: A total of 383 patients were included: 141 in the high-dose group and 242 in the standard-dose group. The high-dose group demonstrated significantly higher clinical cure rates (49.7% vs 38.8%; adjusted odds ratio [aOR]: 1.61, 95% CI: 1.05-2.50) and microbiological eradication rates (46.1% vs 20.3%; aOR: 3.85, 95% CI: 2.37-6.26). There was no significant difference in in-hospital mortality (17.7% vs 21.1%, aOR: 0.71; 95% CI: 0.41-1.25). Subgroup analyses showed greater benefit of high-dose therapy in patients with pneumonia, acute respiratory failure, ICU admission, and Charlson Comorbidity Index >4. Changes in liver function tests, renal function (serum creatinine), and coagulation parameters over the course of therapy did not differ significantly between the high-dose and standard-dose groups.

Conclusion: High-dose cefoperazone-sulbactam showed superior clinical and microbiological efficacy compared to the standard dose without increased safety concerns. These findings support the use of high-dose regimens in critically ill patients or those with MDRO infections.

Background: This study aimed to compare the efficacy and safety of colistimethate sodium (CMS) and polymyxin B (PMB) in treating carbapenem-resistant Gram-negative bacteria (CR-GNB)-induced bloodstream infection (BSI) based on real-world data. While international studies on CMS and PMB have yielded conflicting results, there is a lack of direct comparative data from Chinese cohorts, where the pathogen distribution may influence outcomes.

Methods: A retrospective analysis was conducted on 373 Chinese patients with CR-GNB-induced BSI who received CMS-containing therapy (n=132) or PMB-containing therapy (n=241) between Dec 2021 and Dec 2023. Propensity score matching was used to balance the two groups at a ratio of 1:2. The primary outcome was clinical success. The secondary outcomes included inpatient days, in-hospital mortality, 28-day all-cause mortality, and incidence of adverse events. Statistical analysis was performed with Wilcoxon rank sum test, Student's t-test, chi-square test, and Fisher's exact test as appropriate.

Results: In this cohort, Acinetobacter baumannii was the predominant pathogen (53.4%). No significant differences were observed in efficacy outcomes between the two groups (p>0.05). For safety, the difference in hyperpigmentation incidences between the two groups was statistically significant (CMS vs PMB: 0.0% vs 6.36%, p=0.04). Incidences of hypersensitivity, neurotoxicity, and nephrotoxicity were similar between groups (p>0.05). A longer treatment course (>12 days), while associated with a higher incidence of hyperpigmentation, was linked to significantly improved clinical outcomes, including higher success rate, reduced in-hospital mortality, and lower 28-day all-cause mortality (p<0.05).

Conclusion: This study provides the first large, real-world comparative evidence from a Chinese cohort with CR-GNB BSIs. In this setting, CMS and PMB demonstrated comparable efficacy. The critical difference lay in the safety profile, with CMS associated with a markedly lower incidence of hyperpigmentation. This finding provides a tangible basis for antibiotic stewardship, positioning CMS as a valuable first-line polymyxin option.

Introduction: The objective of the current investigation was to develop a clinical predictive model for virological treatment failure in HIV patients with low level viremia.

Methods: The study included 786 patients with HIV-associated low-level viremia (LLV). Using Lasso and multivariable logistic regression, we developed a predictive model from clinical and laboratory variables to identify significant predictors. This predictive model was presented as a nomogram and subsequently transformed into a scoring system. Following model construction, internal validation was performed to evaluate the model's calibration capability and clinical utility.

Results: The final model incorporated five predictors (HLLV, NVP/3TC/AZT, WHO stage 1, ART delay, triglyceride) into a point-based scoring system. Using the Youden index, a threshold of 6 points was determined. The model demonstrated good performance, with training and internal validation AUCs of 0.762 and 0.759, respectively, and satisfactory calibration and diagnostic accuracy.

Conclusion: New scoring system predicts virological failure in low-level viremia, supporting early clinical intervention.

Background: Talaromyces marneffei (T. marneffei) is a thermally dimorphic fungus traditionally associated with HIV-related immunosuppression. However, increasing reports have described infections in HIV-negative patients with hematologic malignancies, particularly those receiving novel immunosuppressive therapies.

Case presentation: We report a case of disseminated T. marneffei in an HIV-negative 55-year-old woman with T-prolymphocytic leukaemia (T-PLL) undergoing chemotherapy and targeted therapy with chidamide and golidocitinib. The patient presented with fever, pancytopenia, and signs of systemic infection. Blood cultures confirmed T. marneffei, with identification supported by dual-phase morphology and internal transcribed spacer (ITS) sequencing. Due to unavailability of amphotericin B, the patient was treated successfully with voriconazole, achieving rapid clinical improvement and negative follow-up cultures.

Discussion: This case adds to the growing evidence that T. marneffei can cause invasive infections in non-HIV immunocompromised hosts. Through a review of 10 published cases, we identify common features such as neutropenia, kinase inhibitor use, and diagnostic delays. We emphasize the importance of early fungal culture and phase-specific morphology for diagnosis, and highlight voriconazole as a viable alternative therapy when amphotericin B is inaccessible.

Conclusion: Clinicians should maintain high suspicion for talaromycosis in immunosuppressed hematologic patients in endemic regions, regardless of HIV status. Prompt recognition and appropriate antifungal therapy are essential to improve outcomes.

Background: Q fever is a globally distributed zoonotic disease caused by Coxiella burnetii (C. burnetii). As an obligate intracellular bacterium, C. burnetii is primarily transmitted from domestic animals to humans, with ticks also serving as potential vectors. The clinical manifestations of Q fever are often nonspecific and highly variable, making its diagnosis particularly challenging.

Case presentation: Two male pneumonia patients were hospitalized in Deqing People's Hospital, one was 73 years old, and the other one was 30 years old, both of them presented with hyperpyrexia without a clear epidemiological history. However, initial empirical treatment was ineffective and microbiological cultures were all negative, then bronchoscopy was conducted for them and bronchoalveolar lavage fluid (BALF) was sent for metagenomic next-generation sequencing (mNGS) test. Ultimately, two patients were diagnosed with Q fever pneumonia, and the symptoms of patients were significantly improved after timely treatment with the special drug doxycycline and moxifloxacin, and lung inflammation in both patients were effectively absorbed in the subsequent follow-up examination.

Conclusion: Two cases of Q fever pneumonia were diagnosed through mNGS. As a new detection method, mNGS has advantages in the diagnosis of unknown infectious pathogens. As a zoonotic pathogen, C. burnetii should not be ignored. The One Health approach may be suitable for Q fever prevention and control.

A novel bacterial strain, designated as L3024hy, was isolated from the fecal matter of a patient suffering from diarrhea in China. Whole-genome sequencing has identified this strain as a member of the genus Achromobacter. Comparative genomic analyses, including Average Nucleotide Identity (ANI) and digital DNA-DNA hybridization (dDDH), indicated that L3024hy constitutes a distinct lineage within this genus, as evidenced by ANI and dDDH values falling below established thresholds for species demarcation. This strain harbors multiple virulence genes associated with host colonization, suggesting its potential clinical significance. This study underscores the increasing diversity of the genus Achromobacter and emphasizes the necessity for further research on its role in human infections.

Pseudomonas aeruginosa (P. aeruginosa), traditionally regarded as a nosocomial pathogen, has emerged as an increasingly recognized etiologic agent in community-acquired pneumonia (CAP). Cavitary lung lesions-a severe complication of CAP characterized by parenchymal necrosis and cavity formation-are exceptionally rare in P. aeruginosa-associated CAP. We report a 64-year-old male with CAP complicated by P. aeruginosa infection (OXA-positive genotype carrying the virulence factors exoU and lasA), which rapidly progressed to cavitary lesions in the right upper lobe. This case highlights the aggressive clinical trajectory and antimicrobial resistance challenges inherent to community-acquired P. aeruginosa infections. Furthermore, it underscores the imperative for serial radiographic monitoring to detect cavitary evolution and the critical role of comprehensive antimicrobial susceptibility testing in guiding precision therapy.

Introduction: This study evaluated the prevalence of P. aeruginosa in cystic fibrosis(CF) patients, assessed its resistance patterns to commonly used antibiotics with an emphasis on fosfomycin, and examined the presence of resistance genes (glpT, fosA3, blaCTX-M) in these isolates.

Material and methods: A cross-sectional study was conducted at Shahid Beheshti University of Medical Sciences, Tehran, from January to June 2022. Sixty sputum samples from CF-confirmed patients were collected and cultured. Antibiotic susceptibility testing (AST) was performed using the Kirby-Bauer disk diffusion method according to CLSI guidelines. Minimum inhibitory concentrations (MICs) of fosfomycin were determined using E-test strips. PCR was employed to detect the presence of glpT, fosA3, and blaCTX-M resistance genes. Data were analyzed using SPSS version 21.

Results: P. aeruginosa was isolated from 71.6% (43/60) of samples. Based on AST, significant antibiotic resistance was observed, particularly against fosfomycin (77.2%), imipenem, and amikacin (53.5%). Using the combined disk diffusion test (CDDT), 46% of isolates were identified as ESBL producers. PCR analysis revealed the presence of glpT gene in all isolates, fosA3 gene in 39.5%, and blaCTX-M gene in 30.2%.

Discussion: The fosA3 gene showed a strong correlation with fosfomycin resistance, while blaCTX-M was associated with beta-lactam resistance. Molecular diagnostics targeting resistance genes such as glpT, fosA3, and blaCTX-M are essential for guiding antibiotic therapy. The resistance patterns observed, particularly against fosfomycin, highlight the need for innovative therapeutic approaches.

Conclusion: This study reveals a high rate of multidrug resistance in P. aeruginosa isolates from CF patients, particularly to fosfomycin, imipenem, and amikacin. The presence of resistance genes suggests a genetic basis for these patterns, emphasizing the importance of developing new strategies to manage P. aeruginosa infections effectively. Future studies should focus on targeted inhibitors for these genes to overcome resistance and improve clinical outcomes.