Serum metabolomics profile identifies patients with community-acquired pneumonia infected by bacteria, fungi, and viruses.

PURPOSE: Patients with bacterial, fungal, and viral community-acquired pneumonia (CAP) were studied to determine their metabolic profiles. METHODS: Loop-mediated isothermal amplification technology and nucleic acid sequence-dependent amplification combined with microfluidic chip technology were applied to screen multiple pathogens from respiratory tract samples. Eighteen patients with single bacterial infection (B-CAP), fifteen with single virus infection (V-CAP), twenty with single fungal infection (F-CAP), and twenty controls were enrolled. UHPLC-MS/MS analysis of untargeted serum samples for metabolic profiles. Multiple linear regression and Spearman's rank correlation analysis were used to determine associations between metabolites and clinical parameters. The sensitivity and specificity of the screened metabolites were also examined, along with their area under the curve. RESULTS: The metabolic signatures of patients with CAP infected by bacteria, viruses, and fungi were markedly different from those of controls. The abundances of 45, 56, and 79 metabolites were significantly unbalanced. Among these differential metabolites, 11, 13, and 29 were unique to the B-CAP, V-CAP, and F-CAP groups, respectively. Bacterial infections were the only known causes of disturbances in the pentose and glucuronate and aldarate and ascorbate metabolism interconversions metabolic pathway. CONCLUSIONS: Serum metabolomic techniques based on UHPLC-MS/MS may identify differences between individuals with CAP who have been infected by various pathogens, and they can also build a metabolite signature for early detection of the origin of infection and prompt care.

Pneumocystis jirovecii and Nocardia pneumonia in a middle-aged male with Nephrotic syndrome: a case report and literature review.

INTRODUCTION: Nephrotic syndrome (NS) is a common chronic kidney disease that is often accompanied by a state of immunodeficiency. Immunosuppression increases the risk of infections, with Pneumocystis jirovecii and Nocardia brasiliensis being two opportunistic pathogens that can cause severe infections in patients with compromised immune function. This study presents a case of a middle-aged male patient with NS concurrently infected with Pneumocystis jirovecii and Nocardia brasiliensis. It aims to synthesize the pertinent diagnostic approaches and treatment experiences. Notably, there have been no reported cases of NS occurring simultaneously with both Pneumocystis jirovecii pneumonia and Nocardia pneumonia. CASE PRESENTATION: A 58-year-old male farmer presented to the hospital with a one-week history of persistent fever, cough, and sputum production. His maximum body temperature was recorded at 39 °C, and he produced yellow viscous sputum. This patient had a one-year history of NS, managed with long-term oral corticosteroid and cyclophosphamide therapy. Admission chest computed tomography displayed interstitial changes in both lungs. After failing to detect any pathogens through routine etiological tests, we successfully identified Nocardia brasiliensis, Pneumocystis jirovecii, and Lodderomyces elongisporus using bronchoscopy-guided sputum samples through metagenomic next-generation sequencing (mNGS) technology. Subsequently, we initiated a combined treatment regimen for the patient using trimethoprim-sulfamethoxazole, meropenem, and moxifloxacin, which yielded remarkable therapeutic outcomes. CONCLUSION: The adoption and promotion of mNGS technologies have significantly resolved the difficulty in early pathogen detection, guiding clinicians from empirical to genomic diagnosis, achieving prevention before treatment, and thereby enhancing patient survival rates.

Atypical pneumonia caused by Chlamydia abortus in HIV patient: a case report.

BACKGROUND: Chlamydia abortus, as a pathogen of atypical pneumonia, is rare in humans, especially in HIV infection patients. CASE PRESENTATION: We present the case of a 48-year-old man with a history of HIV infection who started high fever and developed pneumonia. The pathogen-targeted next-generation sequencing (ptNGS) results of bronchial lavage fluid showed Chlamydia abortus infection. CONCLUSION: This is the first report of Chlamydia abortus infection presented as atypical pneumonia in an AIDS patient.

Hypermucoviscous Klebsiella Pneumoniae Caused Community-Acquired Pneumonia in Gondar, Northwest Ethiopia.

BACKGROUND: The incidence of hypermucoviscous Klebsiella pneumoniae (hmvKp), which complicates community-acquired pneumonia, has been increasing recently. This study aimed to detect hypermucoviscous K. pneumoniae and determine its antimicrobial susceptibility pattern in adult patients with community-acquired pneumonia in Northwest Ethiopia. METHODS: This cross-sectional study included 39 K. pneumoniae isolates identified by using Gram stain, culture, and biochemical tests from 312 adult patients with community-acquired pneumonia at the University of Gondar Comprehensive Specialized Referral Hospital from April to June 2021. The hypermucoviscous strains were identified by using the string test. Antimicrobial susceptibility testing was performed by using the Kirby-Bauer disk dif-fusion method. Data were entered by using EPI data version 4.6 and were analyzed by using SPSS version 20. A p-value ≤ 0.05 at a 95% confidence interval was considered statistically significant. RESULTS: Overall, 35.9% (n = 14) of the 39 K. pneumoniae isolates were hypermucoviscous phenotype. The mean age of the hmvKp group was lower than of the cKp group (36.93 ± 12.573 vs. 53.52 ± 19.556 years, p = 0.007). All hmvKp isolates were resistant to amoxicillin-clavulanic acid and trimethoprim-sulfamethoxazole. Azithromycin resistance in the hmvKp strains was significantly higher than in the cKp group (p = 0.012). CONCLUSIONS: This study demonstrates that the hmvKp phenotype causes community-acquired pneumonia and a full resistance to amoxicillin-clavulanic acid and trimethoprim-sulfamethoxazole. Antimicrobial resistance was higher in the hmvKp strain than in the classic strains. Further detection of resistance genes, capsular serotypes, hypermucoviscosity-related genes, and virulence genes is necessary.

Bacterial pneumonia patients with elevated globulin levels did not get infected with SARS-CoV-2: two case reports.

Background: COVID-19 began in December 2019, rapidly spreading worldwide. China implemented a dynamic zero-COVID strategy and strict control measures after the outbreak. However, Guangzhou city ended closed-off management by the end of November 2022, leading to exposure to SARS-CoV-2. Despite most hospitalized patients being infected or co-infected with SARS-CoV-2, some remained uninfected. We report two cases of bacterial pneumonia with elevated globulin levels not infected with SARS-CoV-2, aiming to identify protection factors of SARS-CoV-2 infection and provide a scientific basis for SARS-CoV-2 prevention. Case presentation: Case 1, a 92-year-old male, admitted on October 21, 2022, developed worsening cough and sputum after aspiration, diagnosed with bacterial pneumonia with Pseudomonas aeruginosa, Escherichia coli (CRE) and carbapenem-resistant Acinetobacter baumannii (CRAB) infections. He was treated with imipenem anti-infective therapy and mechanical ventilation, then switched to a combination of meropenem, voriconazole and amikacin anti-infective therapy due to recurrent infections and septic shock, and died of sepsis on 8 January 2023. Case 2 is an 82-year-old male admitted on 30 September 2022, with recurrent cough, sputum, and shortness of breath, diagnosed with bacterial pneumonia with carbapenem-resistant Klebsiella pneumoniae (CRKP) and Mycobacterium pneumoniae infections. He was treated with ventilator-assisted ventilation, meropenem, amikacin, tigecycline and mucomycin nebulization and discharged with improvement on 26 October. He was readmitted on 21 November 2022 and diagnosed with bacterial pneumonia. He was treated with cefoperazone sulbactam, amikacin, meropenem and fluconazole and discharged on 31 December. Neither patient was infected with SARS-CoV-2 during hospitalization. Notably, their globulin levels were elevated before SARS-CoV-2 exposure, gradually decreasing afterward. Conclusions: Patients with bacterial pneumonia with high globulin levels likely have large amounts of immunoglobulin, and that immunoglobulin cross-reactivity causes this protein to be involved in clearing SARS-CoV-2 and preventing infection. Therefore, bacterial pneumonia patients with high globulin levels included in this study were not infected with SARS-CoV-2. After exposure to SARS-CoV-2, the amount of globulin in the patient's body was reduced because it was used to clear SARS-CoV-2. The results of this study are expected to provide a theoretical basis for the study of the mechanism of prevention and treatment of SARS-CoV-2 infection.

Pathogen kinetics and detection by next-generation sequencing in pediatric complicated pneumonia.

Pediatric pneumonia can be severe and result in empyema. Next-generation sequencing (NGS) may broadly detect pathogens though, optimal timing and impact of sample type on diagnostic yield is unknown. This is a prospective, single-center pilot study of children aged 3 months through 17 years admitted to the PICU with a primary diagnosis of complicated pneumonia. Plasma, endotracheal, nasopharyngeal, and pleural fluid samples were collected at three time points during hospitalization. After nucleic acid extraction, combined libraries were enriched with an NGS enrichment panel kit (RPIP, Illumina), sequenced and quantitative organism detections were analyzed. NGS identified the same bacterial pathogen as traditional testing in all samples, regardless of antibiotic pre-treatment or time collected. Conventional culture methods only identified the pathogen reliably in invasively obtained pleural fluid or endotracheal aspirates. Future application of NGS may allow for non-invasive pathogen detection at a broader range of time points and more targeted antibiotic coverage.

Combining Gram stain and 16S qPCR improved diagnostic accuracy for suspected pneumonia and could become a new metric in the rapid diagnosis of lower respiratory tract infections.

Introduction. The frequency of multidrug-resistant organisms (MDROs) in hospitals and the risk of delaying effective treatment result in the culture of respiratory secretions for nearly all patients with suspected pneumonia. Culture delays contribute to over prescribing and use of broader spectrum antibiotics.Gap statement. The need for improved rapid diagnostics for early assessment of suspected hospital pneumonia.Aim. To validate a new metric, enhanced Gram stain (EGS), to provide a rapid diagnostic test of high diagnostic accuracy that could be assessed in clinical trials of the use of antibiotics in suspected pneumonia.Methodology. Ninety-two residual lower respiratory samples previously tested by culture and Gram stain were re-tested by 16S ribosomal DNA real-time polymerase chain reaction (16S qPCR) and reported as a combined metric with Gram stain termed EGS. The EGS was assessed for diagnostic accuracy, standard performance measurements and correlation against culture. For samples with discordance between culture and EGS, 16S ribosomal DNA whole operon sequencing (16S rDNA WOS) was used for test resolution. An amended EGS (A-EGS was reassessed against culture.Results. Gram stain, 16S qPCR, EGS and A-EGS had respective diagnostic accuracies of 77.01 %, 82.76 %, 84.04 % and 94.19 %. The same platforms had respective correlation with culture of r = 0.67, r = 0.71, r = 0.81 and r = 0.89. EGS had the highest negative predictive value (NPV) of 93.18 % (81.99 %-97.62 %). Adding an 16S qPCR result is achievable in most routine laboratories and, combined with Gram stain, could improve early decision-making in patients with suspected hospital pneumonia.Conclusion. EGS could improve early decision-making in patients with suspected hospital pneumonia and could be assessed in clinical trials. The 16S rDNA WOS results in the A-EGS also supported the use of pathogen genomic sequencing in early decision making of suspected pneumonia.

Pneumonia in an elderly Tibetan male caused by Shewanella algae: A case report.

RATIONALE: Shewanella algae are Gram-negative bacteria that are widely found in aquatic habitats and rarely cause lung infections in inland areas. PATIENT CONCERNS: Cough with light-yellow phlegm for 2 weeks. DIAGNOSES: The final diagnosis was bacterial pneumonia. INTERVENTIONS: The patient was treated with ceftazidime (2 g, every 12 h) for 1 week. OUTCOMES: The patient's lung infection improved and he was discharged. LESSONS: This case highlights a rare occurrence of lung infection caused by Shewanella algae in elderly Tibetan men residing in non-marine environments.

Predictive signature of murine and human host response to typical and atypical pneumonia.

BACKGROUND: Pneumonia due to typical bacterial, atypical bacterial and viral pathogens can be difficult to clinically differentiate. Host response-based diagnostics are emerging as a complementary diagnostic strategy to pathogen detection. METHODS: We used murine models of typical bacterial, atypical bacterial and viral pneumonia to develop diagnostic signatures and understand the host's response to these types of infections. Mice were intranasally inoculated with Streptococcus pneumoniae, Mycoplasma pneumoniae, influenza or saline as a control. Peripheral blood gene expression analysis was performed at multiple time points. Differentially expressed genes were used to perform gene set enrichment analysis and generate diagnostic signatures. These murine-derived signatures were externally validated in silico using human gene expression data. The response to S. pneumoniae was the most rapid and robust. RESULTS: Mice infected with M. pneumoniae had a delayed response more similar to influenza-infected animals. Diagnostic signatures for the three types of infection had 0.94-1.00 area under the receiver operator curve (auROC). Validation in five human gene expression datasets revealed auROC of 0.82-0.96. DISCUSSION: This study identified discrete host responses to typical bacterial, atypical bacterial and viral aetiologies of pneumonia in mice. These signatures validated well in humans, highlighting the conserved nature of the host response to these pathogen classes.

Legionella maceachernii pneumonia: a case report and literature review.

BACKGROUND: Legionella maceachernii pneumonia is a severe respiratory infection with low incidence but high mortality. However, the optimal treatment for this disease remains unclear. We report a case of successful treatment of Legionella maceachernii pneumonia, which is the first report of such a case in China. CASE PRESENTATION: An 87-year-old man with concomitant chronic obstructive pulmonary disease, liver cirrhosis, and history of left nephrectomy was diagnosed with Legionella maceachernii pneumonia using Dano-seq pathogen metagenomic testing. After two weeks of treatment with cefoperazone/sulbactam combined with quinolone antibiotics, the patient showed improvement and was discharged. The patient continued to take oral quinolone antibiotics for one week after discharge and recovered during outpatient follow-up. CONCLUSIONS: Dano-seq pathogen metagenomic testing can rapidly diagnose Legionella maceachernii pneumonia, and taking quinolone antibiotics is an effective treatment.

Intracranial dissemination of Klebsiella pneumoniae originating from pulmonary infection: a case report.

BACKGROUND: Metastatic brain abscesses caused by Klebsiella pneumoniae are extremely rare but life-threatening conditions. To depict a unique case of the middle-aged hypertensive man with an unusual presentation of metastatic brain abscesses originating from a pleural abscess caused by Klebsiella pneumoniae and subsequently leading to loss of consciousness (LOC). CASE REPORT: A 52-year-old Iranian man with a history of hypertension presented to the emergency department with a five-day history of worsening cough, high-grade fever, shortness of breath, chest pain, fatigue, and a productive cough. Laboratory tests revealed leukocytosis, elevated C-reactive protein, and respiratory alkalosis. A chest computed tomography scan confirmed pneumonia, and a brain scan revealed multiple hypodense lesions. Despite antibiotic therapy, the patient's condition worsened, leading to confusion, disorientation, and loss of consciousness. Magnetic resonance imaging revealed multiple ring-enhancing lesions, suggesting an abscess formation. Bronchial washings and BAL samples confirmed a lower respiratory tract infection. Cultures from the bronchial washings grew Klebsiella pneumoniae. CONCLUSIONS: Metastatic brain abscesses caused by Klebsiella pneumoniae are exceedingly rare but life-threatening conditions. Timely diagnosis and effective antimicrobial treatment are critical for patient outcomes. This case underscores the significance of recognizing atypical presentations of bacterial infections, as early detection and appropriate management can significantly impact patient outcomes.

Tropheryma whipplei pneumonia revealed by Metagenomic next-generation sequencing: Report of two cases.

Tropheryma whipplei is the causative agent of Whipple's disease, which is a rare multiorgan systemic disease. We report two cases of Tropheryma whipplei infection, all routine tests were negative and it was finally detected by mNGS. This may help clinicians increase awareness of the diagnosis and treatment of acute severe pneumonia and interstitial pneumonia caused by Tropheryma whipplei.

Fulminant fatal pneumonia and bacteremia due to Aeromonas dhakensis in an immunocompetent man: a case report and literature review.

Background: Aeromonas dhakensis is associated with soft tissue infection, bacteremia and gastroenteritis. Involvement of respiratory system in adults is extremely rare. We report a case of fulminant pneumonia and bacteremia due to A. dhakensis in a patient without underlying diseases. Case presentation: A 26-year-old man became ill suddenly with pneumonia after swimming in a river. Despite intensive support measures in the intensive care unit, he died 13 hours after admission and 4 days after his first symptoms. Autopsy showed abundant Gram-negative bacteria, massive inflammatory cell infiltration, edema, necrosis and hemorrhage in lung tissue. A. dhakensis was isolated from blood culture taken at admission and bronchoalveolar lavage fluid (BALF) after intubation. Moreover, A. dhakensis was also detected in lung tissue by metagenomic next-generation sequencing (mNGS) assay. The infection may have come from river water. Conclusion: In patients who develop a fulminant pneumonia after contacting an aquatic environment, A. dhakensis should be alerted and mNGS may aid in the detection of aquatic pathogens by being more sensitive and specific versus traditional bacterial culture.

Acute Q fever pneumonia diagnosed by metagenomic next-generation sequencing.

INTRODUCTION: Q fever, a zoonotic disease caused by Coxiella burnetii (C. burnetii), presents diagnostic challenges due to its clinical and radiological nonspecificity, which often mimics community-acquired pneumonia, coupled with the limitations of traditional diagnostic methods. Metagenomic next-generation sequencing (mNGS) has become an indispensable tool in clinical diagnostics for its high-throughput pathogen identification capabilities. Herein, we detail a case of acute Q fever pneumonia diagnosed with mNGS. CASE PRESENTATION: The patient exhibited symptoms of fever, cough, expectoration, and diarrhea for three days, with the pathogen undetected in initial laboratory assessments. Bronchoscopy and bronchoalveolar lavage (BAL) were conducted, leading to the identification of C. burnetii in the lavage fluid via mNGS. Consequently, the patient was promptly initiated on a treatment regimen of 100 mg doxycycline, administered orally every 12 hours. RESULTS: Post-treatment, the patient's temperature normalized, and a full recovery was observed. The follow-up chest CT scan revealed complete resolution of the right lower lobe consolidation. CONCLUSIONS: The clinical presentation of Q fever pneumonia lacks specificity, making diagnosis based solely on symptoms and imaging challenging. mNGS offers a superior alternative for identifying elusive or rarely cultured pathogens.

Metagenomic next-generation sequencing reveals co-infection with Legionella pneumophila and Fusobacterium necrophorum in a patient with severe pneumonia: a case report.

BACKGROUND: Legionella pneumonia is one of the most severe types of atypical pneumonia, impairing multiple organ systems, posing a threat to life. Diagnosing Legionella pneumonia is challenging due to difficulties in culturing the bacteria and limitations in immunoassay sensitivity and specificity. CASE PRESENTATION: This paper reports a rare case of sepsis caused by combined infection with Legionella pneumophila and Fusobacterium necrophorum, leading to respiratory failure, acute kidney injury, acute liver injury, myocardial damage, and electrolyte disorders. In addition, we systematically reviewed literature on patients with combined Legionella infections, analyzing their clinical features, laboratory results and diagnosis. CONCLUSIONS: For pathogens that require prolonged incubation periods and are less sensitive to conventional culturing methods, metagenomic next-generation sequencing (mNGS) can be a powerful supplement to pathogen screening and plays a significant role in the auxiliary diagnosis of complex infectious diseases.

Burkholderia semiarida as Cause of Recurrent Pulmonary Infection in Immunocompetent Patient, China.

Burkholderia semiarida was previously identified solely as a plant pathogen within the Burkholderia cepacia complex. We present a case in China involving recurrent pneumonia attributed to B. semiarida infection. Of note, the infection manifested in an immunocompetent patient with no associated primary diseases and endured for >3 years.