OBJECTIVES:To characterise the phylogenetic structure and clinical implications of carbapenemase-aerobactin (iuc) convergence among respiratory Klebsiella pneumoniae isolates. METHODS:We performed whole-genome sequencing of 707 non-duplicate respiratory K. pneumoniae isolates collected at a tertiary hospital in China from 2017 to 2023 and linked the genomic data to blinded clinical adjudication. Isolates were grouped by carbapenemase gene carriage and iuc status. Core-genome SNP phylogenies were constructed for ST11 and ST23, and reference-plasmid mapping to pK2044 was performed in a targeted subset. Within the carbapenemase-positive subset, logistic regression was used to test the incremental contribution of iuc beyond age, Charlson Comorbidity Index, and ICU admission during hospitalisation. All-cause mortality at 14, 28, and 90 days was assessed among infection cases. RESULTS:Overall, 548/707 isolates (77.5%) were adjudicated as infection, including 280 community-acquired pneumonia and 268 hospital-acquired pneumonia cases. Seventy-nine isolates (11.2%) were classified as carb+/iuc+, and 74/79 (93.7%) belonged to ST11. Phylogenetic analysis showed that convergence was concentrated in lineage-restricted ST11 branches, particularly KL64/KL47-associated backgrounds, whereas ST23 formed a more dispersed classical iuc-positive lineage background. Carb-/iuc+ ST23 retained a conserved hypervirulence-associated module and showed high compatibility with pK2044, whereas carb+/iuc+ ST11 showed a more fragmented virulence profile and heterogeneous, incomplete pK2044 coverage. Within the carbapenemase-positive subset, adding iuc to a model including age, Charlson Comorbidity Index, and ICU admission during hospitalisation did not improve infection attribution (adjusted OR 0.93, 95% CI 0.33-2.68; likelihood ratio test P = 0.892; ΔAIC = 1.98). Among infection cases, carb+/iuc+ and carb+/iuc- groups showed broadly similar all-cause mortality at 14, 28, and 90 days. CONCLUSIONS:Carbapenemase-aerobactin convergence among respiratory K. pneumoniae was concentrated in dominant ST11 backgrounds and occurred in distinct lineage-specific virulence contexts. However, within the carbapenemase-positive respiratory subset, iuc added limited value for infection attribution and did not clearly separate short- to intermediate-term mortality beyond host and care-setting factors.

Non-HIV Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic fungal pneumonia that may progress rapidly in immunocompromised hosts. Broad bronchoalveolar lavage fluid (BALF) molecular testing supports microbiologic recognition, but additional organisms often require bedside adjudication. We conducted a single-center observational study of 49 HIV-negative adults with clinically confirmed PJP, routine BALF metagenomic next-generation sequencing support, and complete 30-day follow-up. Diagnosis required compatible symptoms and chest computed tomography findings, microbiologic support for P. jirovecii, and infectious disease specialist exclusion of isolated colonization. The primary endpoint was ICU-level care requirement, defined as ICU admission, invasive mechanical ventilation, or 30-day all-cause mortality. Recent immunosuppressive exposure was present in 48 patients (98.0%). ICU-level care was required in 15 patients (30.6%); all ventilation and death events occurred in this group, and 30-day mortality was 10.2%. Baseline PaO2/FiO2 < 200 mmHg was associated with higher proportions of ICU admission, mechanical ventilation, and death. Chronic kidney disease, lower creatinine clearance, higher lactate dehydrogenase, and bacterial co-pathogen context showed exploratory signals, whereas overall co-pathogen positivity was heterogeneous. These findings support integrating oxygenation status, host vulnerability, and conservative co-pathogen adjudication to guide escalation and antimicrobial decisions after BALF testing.

BACKGROUND AND OBJECTIVE:Chlamydia psittaci and Legionella pneumophila are common atypical pathogens that cause severe community-acquired pneumonia (CAP). This study aimed to compare the clinical features and outcomes of Chlamydia psittaci pneumonia (CPP) and Legionella pneumophila pneumonia (LPP) identified using next-generation sequencing (NGS) for accurate identification. METHODS:This retrospective study included 68 patients with CPP and 42 patients with LPP. All cases were confirmed by metagenomic or targeted next-generation sequencing (mNGS/tNGS) of bronchoalveolar lavage fluid, serum, or sputum samples. RESULTS:Patients with LPP had a higher prevalence of diabetes and were predominantly male. Poultry contact was common in CPP (64.7% vs. 14.3%), whereas recent travel was associated with LPP (47.6% vs. 2.9%). LPP presented with increased extrapulmonary symptoms. Inflammatory marker levels were higher in LPP, including leukocytosis, neutrophilia, C-reactive protein, and procalcitonin (all p < 0.05). Organ dysfunction was more frequent in LPP, with higher creatinine levels. Patients with LPP had more severe hypoxemia, required more respiratory support, and had higher intensive care admission rates. Targeted therapy guided by NGS was effective, with no significant differences in mortality or hospital stay between the two groups. CONCLUSION:LPP demonstrated greater initial clinical and laboratory severity compared to CPP. Under NGS-guided targeted therapy, both groups achieved comparable outcomes. The observational finding that both pathogens respond to azithromycin and cause severe disease when left undetected underscore the value of guideline-recommended β-lactams/macrolide combination therapy in CAP settings, particularly where these intracellular pathogens remain undiagnosed without NGS.

Acute Q fever manifests sporadically in mainland China, where its clinical spectrum and optimal diagnostic strategies remain under-recognized. This study aimed to delineate the clinical phenotype and antimicrobial prescribing patterns of sporadic acute Q fever diagnosed via metagenomic next-generation sequencing (mNGS). We conducted a retrospective, single-center cohort study of adult patients with sporadic acute Q fever. A comprehensive literature review of all published sporadic cases across China was subsequently performed to delineate the national clinical spectrum of sporadic Q fever. The cohort comprised 22 male patients (mean age 36.7±13.5 years). All patients presented with high-grade pyrexia (>39°C) accompanied by a characteristic symptom constellation of headache, fatigue, myalgia, and hepatic involvement (100

Clonorchiasis, caused by Clonorchis sinensis, often evades early diagnosis in non-endemic regions due to its nonspecific presentation and the delayed appearance of eosinophilia. We report an informative case of a 56-year-old male with acute fever, abdominal pain, and hepatitis, where conventional diagnostics and initial antimicrobial therapy failed. In this case, metagenomic next-generation sequencing (mNGS) of blood identified C. sinensis-specific reads, and cytokine profiling revealed a marked elevation in interleukin-5 (IL-5) before the onset of peripheral eosinophilia. Targeted treatment with praziquantel led to rapid clinical resolution. This case suggests the potential of integrating mNGS and IL-5 monitoring as early diagnostic tools for clonorchiasis, which can allow for intervention prior to classical biomarker emergence.

OBJECTIVES:Hypervirulent ceftazidime/avibactam (CAZ/AVI)-resistant Klebsiella pneumoniae (Kp) has emerged; however, its dynamic within-host evolution and competitive features are uncharacterized. This study aimed to clarify the systematic microevolution characteristics of the rapid transformation of blaKPC variants during long-term infection. METHODS:Thirty-nine Kp strains were isolated from a single patient with severe recurrent osteomyelitis during a 2-year period. Whole-genome sequencing and in vitro evolution assay was performed. Microbiological characteristics were examined through antimicrobial susceptibility testing, plasmid stability, growth curve, in vitro competition and Galleria mellonella larvae lethality assays. RESULTS:Among all the clinical Kp isolates, 37 were carbapenem-resistant Kp (CRKP), including 25 CAZ-/AVI-resistant Kp. All isolates belonged to the ST11-K47. During in vivo evolution, the blaKPC variant and its amplification emerged. Twenty-four isolates (24/39, 61.5%) harboured a novel blaKPC variant, blaKPC-144. All five Kp isolates carried blaKPC-2 in 2021. Surprisingly, 24 blaKPC-144-harbouring isolates (70.6%, 24/34) and 10 blaKPC-2-harboring isolates were identified in 2023, indicating rapid changing of blaKPC. Kp4 carried two copies of blaKPC-2, and Kp10-1 exhibited a 1.94-fold increase in the blaKPC-144 copy number. Similarly, in vitro, the blaKPC copy number increased upon exposure to low CAZ/AVI concentrations. However, at higher concentrations (4/1 mg/L), the blaKPC copy number increased significantly, and blaKPC mutations emerged simultaneously. The competition assay indicated that the blaKPC-144-harboring isolates exhibited a superior competitive capacity. CONCLUSIONS:The blaKPC amplification and mutation emerged simultaneously or sequentially during in vivo and in vitro evolution. Kp isolates harbouring blaKPC-144, conferring resistance to CAZ/AVI, exhibited a competitive advantage, promoting the rapid replacement of blaKPC-2.

OBJECTIVES:The tmexCD1-toprJ1 RND efflux pump gene cluster is predominantly identified among Klebsiella pneumoniae (K. pneumoniae) from humans and food animals. However, the mechanism of the long and rapid dissemination of such resistance determinant among strains from humans, food animals, and the environment is unclear. METHODS:K. pneumoniae isolates were collected from two surveillance projects among patients and food animals. Whole-genome sequencing for phylogenetically close-related tmexCD1-toprJ1-positive and negative isolates, and phylogenic, plasmid stability, and fitness cost analyses were performed. RESULTS:Among 2592 clinical K. pneumoniae isolates and 243 K. pneumoniae isolates from food animals, the minimum inhibitory concentrations (MICs) of tigecycline (TGC) were 2 to 32 mg/L. The tmexCD1-toprJ1-positive isolates belonged to five sequence types (STs) and exhibited TGC resistance. By phylogenetic analyses, we have shown that tmexCD1-toprJ1-positive ST22 may have derived from tmexCD1-toprJ1-negative isolates in our hospital, whereas tmexCD1-toprJ1-positive ST726 showed a long-distance transmission among human and food animals. Different types of plasmids harbouring tmexCD1-toprJ1 were identified, which have been disseminated among bacteria from humans, food animals, and the environment. Interestingly, low fitness costs of the tmexCD1-torpJ1-positive isolates compared to the phylogenetically close tmexCD1-toprJ1-negative isolates. CONCLUSIONS:The long and rapid transmission of tmexCD1-toprJ1 was predominantly caused by plasmids. In One Health, systematic surveillance and studies of isolates from different sources are urgently needed to understand the mechanism of resistance genes dissemination.

Objective: In older populations admitted for diabetes, limited evidence suggests that influenza vaccination protects against hospitalization outcomes. Methods: This study pooled 27,620 hospitalizations recorded for elderly diabetes patients from the Beijing Elderly Influenza Vaccination Information Registration Database (2013-2018) and the Beijing Urban Employee Basic Medical Insurance Database (2013-2018). Generalized linear regression and propensity score matching were conducted to estimate the effects of influenza vaccination on hospitalization outcomes (in-hospital all-cause mortality, readmission, length and costs of hospitalization), adjusting for measurable confounding factors. The low influenza period (May-July) was used as a reference period to adjust for unmeasured confounding factors during the peak influenza period (November-January). Results: In propensity score matching, influenza vaccination in peak influenza period could reduce the risk of inhospital death (OR: 0.47[0.22,0.97]) and readmission (OR: 0.70[0.60,0.81]), length of hospitalization (beta: -1.32 [-1.47, -1.17]) and medical costs (GMR: 0.90[0.88,0.92]). After adjusting for unmeasured confounding factors, influenza vaccination was associated with 17% (ratio of ORs: 0.83 [0.69, 1.02]) lower risk of readmission and shorter length of hospitalization (difference in beta: -0.23 [-0.62, 0.16]). The subgroup analyses showed that male patients with older age and poorer health conditions could benefit more after influenza vaccination. Conclusion: Influenza vaccination could significantly improve hospitalization outcomes in elderly diabetic patients. This provides evidence supporting free influenza vaccination policies for vulnerable populations in lowand middle-income countries.

BackgroundNeutrophil plays a pivotal role in the management of Klebsiella pneumoniae infection. Delineate the clinical characteristics and prognostic utility of neutrophil in severe patients with K. pneumoniae infection are crucial for clinical management and prognostic assessment.MethodsK. pneumoniae patients with different infection sites were enrolled from Medical Information Mart for Intensive Care IV and eICU Collaborative Research Database. Temporal variations of neutrophil counts within 30 days of clinical onset were examined using locally weighted scatterplot smoothing curves. Logistic regression analysis was performed to assess the relationship between neutrophil counts and hospital mortality.ResultsA total of 1,705 patients caused by K. pneumonia were included in the study. The non-survivor group exhibited a comparatively older age and a higher proportion of K. pneumoniae infections originating from respiratory and bloodstream sources compared to the survivor group (38.4% vs 21.1%, p<0.0001, and 15.1% vs 10.3%, p=0.021). Patients combined with multiple drug resistance strains, respiratory infection, liver disease, and above 60 years exhibited a specific dynamic process of neutrophil levels. Neutrophils counts peaked at admission and 1-2 weeks later. There was a ‘U’-shaped relationship between neutrophil counts and hospital mortality.ConclusionsNeutrophils in K. pneumoniae infected patients have distinctive features and dynamic clinical trajectories. Close monitoring of severe patients infected with K. pneumoniae upon admission and during the first 1-2 weeks after admission is of utmost importance, particularly for patients with a neutrophil count exceeding 8.0×109/L.

Pneumonia is the most common complication of varicella infections. Although previous studies have tended to focus mainly on immunocompromised patients, varicella pneumonia can also occur in healthy adults. Therefore, in this study, we aimed to assess the progression of varicella pneumonia in immunocompetent hosts. This retrospective study involved immunocompetent adult outpatients with varicella who attended the adult Fever Emergency facility of Peking University Third Hospital from April 1, 2020, to October 31, 2022. Varicella pneumonia was defined as a classic chickenpox-type rash in patients with infiltrates on chest computed tomography. The study included 186 patients, 57 of whom had a contact history of chickenpox exposure. Antiviral pneumonia therapy was administered to 175 patients by treating physicians. Computed tomography identified pneumonia in 132 patients, although no deaths from respiratory failure occurred. Seventy of the discharged patients were subsequently contacted, all of whom reported being well. Follow-up information, including computed tomography findings, was available for 37 patients with pneumonia, among whom 24 reported complete resolution whereas the remaining 13 developed persistent calcifications. Notably, we established that the true incidence of varicella pneumonia is higher than that previously reported, although the prognosis for immunocompetent hosts is generally good.

Hypervirulent Klebsiella pneumoniae(hvKp) has a unique ability to cause organ or life-threatening tissue invasive infection in multiple sites. This case highlights that classical hvKp resulted in multiple abscesses in every body site, especially in the necrotizing fasciitis and osteomyelitis. The combination of antibiotics, drainage and debridement is essential for cure.

We identified a novel ceftazidime/avibactam (CAZ/AVI) resistance mechanism in endemic sequence type 11 hypervirulent and carbapenem-resistant Klebsiella pneumoniae isolated from a patient who had not been exposed CAZ/AVI. Overexpression of blaSHV-12 caused by tandem gene amplification contributed to CAZ/AVI resistance instead of the carriage of blaKPC-2. Enhanced genomic surveillance is essential to identify emerging variants.

Introduction and Objectives:Kikuchi-Fujimoto disease (KFD) is self-limiting, has an unknown origin, and predominantly affects the lymph nodes. KFD with aseptic meningitis is rare and diagnostically challenging. This retrospective observational study aimed to elucidate the clinical features and treatment outcomes of KFD, particularly in cases with aseptic meningitis. Methods:We conducted this retrospective study to describe KFD to determine the characteristics of the disease, with a particular focus on cases involving aseptic meningitis. Results:Our study comprised 103 patients (33 men, 70 women) diagnosed with KFD at Peking University Third Hospital between January 2013 and March 2024. Diagnosis was based on histological examination of lymph node biopsies. The mean age was 25 (range: 16-66) years. Clinical manifestations included fever (100%), cervical pain (79.6%), fatigue (49.5%), headache (44.7%), myalgia (26.2%), and hepatosplenomegaly (23.3%). Biological signs included leukopenia (66.0%) and elevated lactate dehydrogenase (>250 U/L, 83.5%) and ferritin (>300 ng/mL, 44.6%) levels. Forty-three cases improved with nonsteroidal anti-inflammatory drugs (NSAIDs) as monotherapy, whereas 24 required corticosteroid therapy. Four of the 46 patients with headache underwent cerebrospinal fluid analysis, confirming aseptic meningitis. Notably, all four responded well to nonsteroidal anti-inflammatory drugs. Conclusion:Our findings highlight the features and outcomes of KFD, particularly its association with aseptic meningitis, which has a favorable prognosis in the absence of corticosteroid therapy.

Background The occurrence of multidrug-resistant and hypervirulent Klebsiella pneumoniae (MDR-hvKp) worldwide poses a great challenge for public health. Few studies have focused on ST218 MDR-hvKp. Methods Retrospective genomic surveillance was conducted at the Peking University Third Hospital from 2017 and clinical information was obtained. To understand genomic and microbiological characteristics, antimicrobial susceptibility testing, plasmid conjugation and stability, biofilm formation, serum killing, growth curves and whole-genome sequencing were performed. We also assessed the clinical and microbiological characteristics of ST218 compared with ST23. Results A total of eleven ST218 Kp isolates were included. The most common infection type was lower respiratory tract infection (72.7%, 8/11) in our hospital, whereas ST23 hvKp (72.7%, 8/11) was closely associated with bloodstream infection. Notably, nosocomial infections caused by ST218 (54.5%, 6/11) was slightly higher than ST23 (36.4%, 4/11). All of the ST218 and ST23 strains presented with the virulence genes combination of iucA + iroB + peg344 + rmpA + rmpA2 . Interestingly, the virulence score of ST218 was lower than ST23, whereas one ST218 strain (pPEKP3107) exhibited resistance to carbapenems, cephalosporins, β-lactamase/inhibitors and quinolones and harbored an ~ 59-kb IncN type MDR plasmid carrying resistance genes including bla NDM-1 , dfrA14 and qnrS1 . Importantly, bla NDM-1 and qnrS1 were flanked with IS 26 located within the plasmid that could successfully transfer into E. coli J53 . Additionally, PEKP2044 harbored an ~ 41-kb resistance plasmid located within tetA indicating resistance to doxycycline. Conclusion The emergence of bla NDM-1 revealed that there is great potential for ST218 Kp to become a high-risk clone for MDR-hvKp, indicating the urgent need for enhanced genomic surveillance.

The rural revitalization strategy represents a quantum leap in both the theory and practice of rural development in China, and serves as a crucial solution to address the array of challenges facing rural areas. Multi-dimensionally, the rural revitalization strategy sets out the general requirements of “building rural areas with thriving businesses, pleasant living environments, good social civility, effective governance, and prosperity,” which echo the measures of new urbanization: efficient, green, humanistic, well-governed, and inclusive. Specifically, “building rural areas with prosperity” aligns with the development requirement of urban-rural dual structure theory; “building rural areas with thriving businesses” meets the development requirement of the industrial division of labor and integration theory; “building rural areas with pleasant living environments and good social civility” follows the development requirement of sustainable development theory; and “building rural areas with effective governance” tallies with the development requirement of rural governance theory. Urbanization theory, urban-rural dual structure theory, the industrial division of labor and integration theory, sustainable development theory, and rural governance theory serve as crucial theoretical references for the rural revitalization strategy, helping make clear its conceptual underpinnings.

Pandrug-resistant (PDR) Klebsiella pneumoniae poses a great challenge to public health, and tigecycline is an essential choice for antimicrobial treatment. In this study, we reported the emergence of PDR K. pneumoniae coharboring tmexCD1-toprJ1 , bla NDM-1 , and bla KPC-2 , which belongs to ST22 and ST3691.

Objective:To report our experience with early recognition of mild Chlamydia psittaci pneumonia in fever clinic.Methods:Clinical data of 13 cases of mild Chlamydia psittaci pneumonia who visited the Fever Clinic of Peking University Third Hospital from June 2021 to August 2022 were retrospectively analyzed. The diagnosis was confirmed by metagenomic next generation sequencing (mNGS) after admission. Clinical data collected included history of exposure to poultry and birds, clinical symptoms, routine blood tests, and chest CT images.Results:All the patients (100%) had a history of direct exposure to parrots or pigeons and fever, with 6 cases (46.2%) complicated with dry cough and 8 (61.5%) with obvious headache. The median time from symptoms to the visit of fever clinic was 3 days. The median white blood cell count was 6.92×109/L (range, 5.04×109/L-8.42×109/L), and the median percentage of neutrophils was 76.4% (range, 71.2%-84.8%). Chest CT findings consisted of consolidation (7 cases, 53.8%), nodules (4 cases, 30.8%), and mass (2 cases, 15.4%), which were mainly found in the periphery (10 cases, 76.9%) of one lobe (12 cases, 92.3%) in a single lung (100%) and were often accompanied by surrounding ground glass shadows (11 cases, 84.6%) and internal air bronchogram (11 cases, 84.6%). Bronchial wall thickening (1 case, 7.7%), centrilobular nodules (1 case, 7.7%), and pleural fluid (1 case, 7.7%) was infrequently observed.Conclusion:Chlamydia psittaci pneumonia should be considered when patients visit fever clinic with a history of exposure to parrots or pigeons, fever with nonproductive cough or prominent headache, normal white blood cell count, and consolidation in the periphery of the lower lobe of a single lung on chest CT images.