Infection and Drug Resistance最新文献

Background: Bloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) pose a huge threat to global public health. The mortality rates are particularly high among older adults. However, few studies have focused on CRKP BSIs in older adults. This study aims to investigate the clinical and genomic characteristics of CRKP-BSIs in older adults.

Methods: This study collected all eligible older patients (age ≥65 years) with CRKP-BSIs from a national regional medical center in Changsha, China from 2020 to 2023. The identification of CRKP strains was performed using MALDI-TOF mass. The antimicrobial susceptibility testing was evaluated by VITEK 2 Compact system. Clinical data of the patients were collected and a binary logistic regression model was used to analyze the risk factors associated with 30-day mortality. The genomic characteristics of CRKP were characterized by whole-genome sequencing (WGS).

Results: A total of 77 older adults with CRKP-BSIs were ultimately included in this study, with an all-cause mortality rate as high as 64.9% (50/77). Mechanical ventilation (OR=8.851; 95% CI 1.503-52.127; p=0.016) is a risk factor for 30-day mortality. 97.4% (75/77) of the strains carried carbapenemase genes, with bla_KPC-2  alone (92.2%, 71/77) being the most common, followed by bla_KPC-2 + bla_NDM-1 (2.6%, 2/77). Up to 72.7% (56/77) of the isolates were identified as hypervirulent CRKP (Hv-CRKP). MLST revealed ST11 (96.1%,74/77) dominated absolutely. Five different capsular serotypes were detected, with KL64 (81.8%, 63/77) being the most common. Through phylogenetic relationship analysis, we speculated that there might have been 10 clonal transmission events of CRKP within the hospital.

Conclusion: CRKP-BSIs in older adults are primarily driven by a limited genetic lineage, ST11, in Changsha, China. Therefore, it is urgently necessary to strengthen the active screening and continuous monitoring of high-risk clone ST11 CRKP among older adults.

Klebsiella pneumoniae (KP), a clinically significant Gram-negative opportunistic pathogen, has emerged as one of the predominant causative agents of hospital-acquired infections (HAIs). This bacterium is responsible for various severe clinical manifestations, including pneumonia, urinary tract infections, bloodstream infections, and sepsis. In recent years, the global prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) K. pneumoniae strains has been escalating rapidly. Epidemiological surveillance data reveal a persistent upward trend in infections caused by MDR microorganisms worldwide, a phenomenon disproportionately prevalent in resource-limited developing countries. This trend presents formidable challenges to clinical infection management and constitutes a critical threat to global public health security. In the context of bacterial antibiotic resistance, the phenomenon of heteroresistance (HR) has attracted growing scientific attention due to its unique clinical significance. HR is characterized by the coexistence of subpopulations within a clonal (ie, genetically similar) bacterial population that exhibit divergent susceptibility profiles to an antimicrobial agent. This subtle phenotypic heterogeneity is considered a crucial precursor to the development of stable, high-level antibiotic resistance, representing a pivotal transitional phase in the evolution of MDR. The clinical importance of HR is twofold: first, the resistant subpopulations are often missed by conventional antimicrobial susceptibility testing, potentially leading to unexpected treatment failure. Second, HR serves as an early warning indicator for the impending emergence of complete resistance.

Introduction: Extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) pose a significant public health threat. While carbapenems are known to be superior in treating bacteremic infections, the evidence is unclear for non-bacteremic infections.

Objective: To assess the effectiveness of carbapenem-sparing therapies compared to carbapenems for non-bacteremic ESBL-E infections.

Methodology: This is a retrospective observational cohort study involving patients aged 18 years or older with confirmed diagnoses of ESBL-E non-bacteremic infections who received either carbapenems or carbapenem-sparing targeted therapy during the study period. The primary outcomes were clinical cure and 30-day all-cause mortality. Secondary outcomes included microbiological eradication, recurrence of ESBL-E infection within 6 months, and the 30-day incidence of new multidrug-resistant infections.

Results: The study included 216 patients: 117 in the carbapenem group and 99 in the carbapenem-sparing group. Both groups showed no significant differences in 30-day all-cause mortality and clinical resolution. However, notable statistical differences were observed in three secondary outcomes: the carbapenem group had a higher recurrence rate of ESBL infections (RR 1.65, 95% CI: 1.05-2.59, P = 0.025) and more secondary multidrug-resistant infections (RR 1.92, 95% CI: 1.11-3.31, P = 0.015), including carbapenem-resistant Enterobacterales infections (RR 2.26, 95% CI: 1.10-4.63, P = 0.020).

Conclusion: The study demonstrates that carbapenem-sparing therapies for ESBL-E nonbacteremic infections are non-inferior to carbapenems, with comparable 30-day all-cause mortality, clinical cure, and bacteriological resolution rates. Additionally, carbapenem-sparing options showed lower recurrence rates of ESBL-E infections and reduced development of secondary multidrug-resistant infections, including CRE infections.

Background: Klebsiella quasipneumoniae subsp. similipneumoniae is an emerging member of the K. pneumoniae complex that is often misidentified in routine diagnostics. Its clinical relevance and genomic characteristics remain poorly understood.

Methods: Four K. quasipneumoniae subsp. similipneumoniae isolates were collected from hospitalized patients in different wards and identified by whole-genome sequencing. Antimicrobial susceptibility testing was conducted using the broth microdilution method. Phylogenetic, comparative genomic, and plasmid transfer analyses were conducted to elucidate genetic relatedness and resistance mobility. Virulence phenotypes were assessed by measuring capsule production, biofilm formation, serum resistance, and in vivo pathogenicity in a Galleria mellonella infection model.

Results: All four isolates belonged to the novel ST1929-KL159 clonotype and exhibited an extensively drug-resistant phenotype, with resistance to β-lactams, carbapenems, fluoroquinolones, tigecycline, and trimethoprim-sulfamethoxazole. Amikacin was the only consistently active agent; one isolate showed high-level resistance to polymyxin B due to a premature stop mutation in mgrB (Gln30*). Genomic analysis revealed the coexistence of bla _NDM-1 and the tigecycline resistance cluster tmexC2D2-toprJ2 on a IncU plasmid, which transferred efficiently to E. coli recipients. Comparative genomics demonstrated strong similarity to multidrug-resistant plasmids from diverse Enterobacterales. Phylogenetic analysis confirmed the global distribution of K. quasipneumoniae subsp. similipneumoniae but highlighted the rarity of ST1929, with close relatedness among the four isolates suggesting recent nosocomial transmission. Despite the absence of classical virulence genes, ST1929 exhibited enhanced biofilm formation, moderate capsule production, and intermediate serum resistance, but low virulence in the G. mellonella model.

Conclusion: This study provides the first description of K. quasipneumoniae subsp. similipneumoniae ST1929, an extensively drug-resistant lineage harboring bla _NDM-1 and the tigecycline resistance cluster tmexC2D2-toprJ2 on a transferable IncU plasmid. The findings underscore the need for accurate detection and surveillance of this rare lineage.

Introduction: The increasing utilization of antiretroviral (ART) medications by people living with HIV(PLWH) poses a potential risk to the efficacy of standardized ART management protocols in resource-limited settings, particularly as it may accelerate the emergence of transmitted drug resistance (TDR). Our research aimed to elucidate the prevalence, risk factors, geographical variations, and transmission patterns of TDR to inform and enhance ART management strategies.

Methods: The study covered newly diagnosed PLWH in Sichuan from July 2022 to June 2023. We conducted sequencing - based resistance profiling and then analyzed TDR via the Stanford HIV Drug Resistance Database and logistic regression to identify associated factors via SPSS. ArcGIS and spatial statistics were used to create LISA maps showing the TDR distribution. HIV-TRACE's Tamura Nei 93 model was used to assess genetic clustering, and QGIS was used to analyze TDR intensity within and between cities.

Results: This study found that the prevalence of TDR in Sichuan had reached a moderate level, with a resistance rate of 10.91%. Resistance varied by drug class: 8.08% for NNRTIs, 1.34% for NRTIs, and 2.22% for PIs. Regions like LS, DY, SN, and LZ had higher TDR rates. Within NNRTIs, efavirenz (EFV) and nevirapine (NVP) resistance rates were 6.26% and 6.50%, respectively. Furthermore, risk factors for TDR included age under 15, HIV-1 subtypes, and residing in areas with high ART failure rates. In addition, spatial analysis showed significant clustering of TDR, especially for PIs and NNRTIs, with hotspots identified in certain regions. Among 1,486 drug-resistant PLWH, 52.76% formed resistance-linked networks, comprising 181 molecular clusters. Key resistance mutations included K103N, E138A, V179D, Y181C, and Q58E. The transmission intensity of TDR varied across regions, highlighting complex spatial dynamics.

Discussion: The prevalence of TDR in Sichuan had reached moderate epidemic levels, with certain cities already experiencing high epidemic rates. It is urgent that we urgently expand targeted genotypic drug resistance detection and implement interventions to improve medication adherence.

The mpox virus (MPXV) is a zoonotic pathogen that has been causing a worldwide pandemic outbreak since 2022, posing a significant threat to global public health security. During this outbreak, monkeypox has been more prevalent among immunocompromised individuals, particularly those infected with HIV (Human Immunodeficiency Virus). We report a case of a 21-year-old male patient with advanced AIDS in China who developed severe complications, including skin tissue infection, proctitis, and conjunctivitis, following monkeypox infection. Despite early aggressive treatment, the patient ultimately succumbed to infectious shock and multiple organ failure. This case strongly underscores that such patients experience severe skin infections and rapid disease progression, necessitating urgent early recognition and treatment.

Background: Antimicrobial resistance (AMR) is the number one cause of death globally, and Sub-Saharan Africa bears the most significant burden. Previous studies conducted in Uganda have revealed high rates of antimicrobial prescribing in hospitals, with evidence of widespread inappropriate use, which necessitates the development of targeted interventions. The inappropriate use of antimicrobials is a driver of AMR. We conducted point-prevalence surveys of antimicrobial prescribing in selected health facilities in central Uganda to identify areas for improvement.

Methods: The study utilised the Global Point Prevalence Survey (GPPS) to collect data on antimicrobial prescribing among eight public health facilities in Central Uganda from February to April 2024. Both inpatient and outpatient data were collected in three hospitals and five lower-level health facilities, respectively. The data collection tools adopted from GPPS were employed. Data were collected on patient demographics, antimicrobial therapy details, and compliance with standard treatment guidelines.

Results: The overall prevalence of antimicrobial use among inpatients at the hospitals was 87.2%, and ceftriaxone was the most frequently prescribed antimicrobial, accounting for 30.6% of the prescriptions. Prescriptions for prophylactic use were the most predominant, with prophylaxis for obstetric and gynaecological surgery accounting for 30.7% of the prescriptions. The prevalence of antimicrobial use among outpatients at lower-level health facilities was 60.7%. Amoxicillin was the most prescribed antimicrobial across the sites, accounting for 39.1% of the prescriptions. Upper respiratory tract infections accounted for most prescriptions (45.1%). Standard treatment guideline compliance was nearly half (50.5%) among hospitals, with variations observed among the different study sites.

Conclusion: A high prevalence of antimicrobial prescribing was observed, highlighting the need to enhance antimicrobial stewardship practices in health facilities. Compliance with standard treatment guidelines was average among hospitals but high among the lower-level health facilities. Some of the potential areas for stewardship interventions include broad-spectrum antibiotic prescriptions, prolonged antibiotic prophylactic courses, and inappropriate prescription of antibiotics for upper respiratory tract infections.

Kerstersia gyiorum (K. gyiorum) had been reported as a rare cause of human infections. In this study, we isolated an uncommon strain of K. gyiorum from swab specimens of a male patient with cerebral infarction. The identification was performed using VITEK MS in the RUO (Research Use Only) mode and 16s rRNA gene sequencing. We hereby report a case of chronic osteomyelitis caused by K. gyiorum in a patient with cerebral infarction and left-sided limb hemiplegia in China.

Purpose: This study investigated the role of copper metabolism MURR1 domain-containing 1 (COMMD1) in Talaromyces marneffei (TM)-induced osteomyelitis (OM) and its regulation of osteoclast differentiation via the NF-κB pathway.

Methods: A murine TM infection model was used to assess bone destruction and osteoclast activity via micro-CT, histological analysis, biomechanical testing, qPCR, and Western blot. RNA sequencing was performed to analyze differentially expressed genes. Functional validation was conducted using COMMD1 conditional knockout (cKO) mice and bone marrow-derived monocytes macrophages (BMMs). The NF-κB inhibitor JSH-23 was used to verify pathway dependency.

Results: TM infection significantly upregulated inflammatory cytokines (IL-10, IL-17, TNF-α) and induced severe bone structural damage, characterized by trabecular thinning and reduced mechanical strength. These changes were accompanied by increased osteoclast numbers and elevated expression of osteoclast differentiation-related genes (TRAP, NFATc1, Ctsk, FOS). RNA sequencing revealed downregulation of COMMD1 and activation of the NF-κB pathway in TM-infected mice. COMMD1 deficiency exacerbated bone destruction and osteoclast differentiation, while COMMD1 overexpression suppressed these effects. Mechanistic studies showed that COMMD1 deletion increased P65 phosphorylation and decreased IκBα expression, effects that were reversed by JSH-23 treatment.

Conclusion: COMMD1 protects against TM-induced OM by inhibiting the NF-κB pathway, suggesting it as a potential therapeutic target for bone infections.

Objective: To analyze and discuss the clinical characteristics of carbapenem-induced platelet abnormalities.

Methods: The databases of CNKI, Wanfang Data, Chinese VIP, Web of science, PubMed, Embase and Elsevier were searched (up to June 30,2025), and the case reports of carbapenem-induced platelet abnormalities were collected and descriptively analyzed.

Results: A total of 42 patients (21 males and 21 females) were included, with a median age of 64 years (range:0-96 years). Thrombocytosis was observed in 20 patients, while thrombocytopenia occurred in 22 patients. Platelet abnormality most often occurred in patients receiving meropenem (64.3%) followed by imipenem (26.2%). All cases occurred during carbapenem therapy. The median time to platelet count abnormality was 3 days (range 0.125-12), with 79.5% of cases occurring within one week. Specifically, the median time to carbapenem-induced thrombocytopenia was 2.5 days (range 0.125-9), while the median time to carbapenem-induced thrombocytosis was 3 days (range 3-12). The nadir of platelet count was reached at 5 days (range 1-10) after medication, with a median platelet count nadir of 21.5×10⁹ /L (range 0-136). The peak of platelet count was reached at 8 days (range 3-18), with a median platelet count peak of 900×10⁹ /L (range 570-1,440). Complications occurred in 10 thrombocytopenia cases, all of which were bleeding events. After discontinuation of the drug and symptomatic treatment, all cases showed significant improvement in platelet counts and resolution of complications, except for one patient who died from multiple organ dysfunction syndrome.

Conclusion: Carbapenem-induced platelet abnormalities appear to be more frequent than previously recognized, predominantly occurring within the first week of therapy. This potentially severe adverse drug reaction should be particularly considered in elderly patients receiving meropenem therapy.