The ongoing spread of antimicrobial resistance has complicated the treatment of bacterial hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). Gram-negative pathogens, especially those with multidrug-resistant profiles, including Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Pseudomonas aeruginosa, and Acinetobacter spp., are an important culprit in this type of infections. Understanding the determinants of resistance in pathogens causing pneumonia is ultimately stressing, especially in the shadows of the COVID-19 pandemic, when bacterial lung infections are considered a top priority that has become urgent to revise. Globally, the increasing prevalence of these pathogens in respiratory samples represents a significant infection challenge, with major limitations of treatment options and poor clinical outcomes. This review will focus on the epidemiology of HAP and VAP and will present the roles and the antimicrobial resistance patterns of implicated multidrug-resistant (MDR) Gram-negative pathogens like carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Enterobacterales (CRE), as well as colistin-resistant Gram-negative pathogens and extended-spectrum β-lactamase (ESBL)-producing Enterobacterales. While emerging from the COVID-19 pandemic, perspectives and conclusions are drawn from findings of HAP and VAP caused by MDR Gram-negative bacteria in patients with COVID-19.

BACKGROUND: Respiratory infections have long been recognized as a primary cause of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). Additionally, the emergence of antimicrobial resistance has led to an urgent and critical situation in developing countries, including Vietnam. This study aimed to investigate the distribution and antimicrobial resistance of bacteria in patients with AE-COPD using both conventional culture and multiplex real-time PCR. Additionally, associations between clinical characteristics and indicators of pneumonia in these patients were examined.
METHODS: This cross-sectional prospective study included 92 AE-COPD patients with pneumonia and 46 without pneumonia. Sputum specimens were cultured and examined for bacterial identification, and antimicrobial susceptibility was determined for each isolate. Multiplex real-time PCR was also performed to detect ten bacteria and seven viruses.
RESULTS: The detection rates of pathogens in AE-COPD patients with pneumonia were 92.39%, compared to 86.96% in those without pneumonia. A total of 26 pathogenic species were identified, showing no significant difference in distribution between the two groups. The predominant bacteria included Klebsiella pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, followed by Acinetobacter baumannii and Streptococcus mitis. There was a slight difference in antibiotic resistance between bacteria isolated from two groups. The frequency of H. influenzae was notably greater in AE-COPD patients who experienced respiratory failure (21.92%) than in those who did not (9.23%). S. pneumoniae was more common in patients with stage I (44.44%) or IV (36.36%) COPD than in patients with stage II (17.39%) or III (9.72%) disease. ROC curve analysis revealed that C-reactive protein (CRP) levels could distinguish patients with AE-COPD with and without pneumonia (AUC = 0.78).
CONCLUSIONS: Gram-negative bacteria still play a key role in the etiology of AE-COPD patients, regardless of the presence of pneumonia. This study provides updated evidence for the epidemiology of AE-COPD pathogens and the appropriate selection of antimicrobial agents in Vietnam.

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.
METHODS: 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.

BACKGROUND: 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.
METHODS: 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.

UNASSIGNED: Pneumonia is a common infection in the intensive care unit (ICU), and gram-negative bacilli are the most common bacterial cause. The purpose of the study was to investigate the risk factors for 30-day mortality in patients with gram-negative bacillary pneumonia in the ICU, construct a predictive model, and stratify patients based on risk to assess their short-term survival.
UNASSIGNED: Patients admitted to the ICU with gram-negative bacillary pneumonia at Fujian Medical University Affiliated First Hospital between January 2018 and September 2020 were selected. Patients were divided into deceased and survivor groups based on whether death occurred within 30 days. Multifactorial logistic regression analysis was used to identify independent risk factors for 30-day mortality in these patients, and a predictive nomogram model was constructed based on these factors. Patients were categorized into low-, medium-, and high-risk groups according to the model\'s predicted probability, and Kaplan-Meier survival curves were plotted to assess short-term survival.
UNASSIGNED: The study included 305 patients. Lactic acid (odds ratio [OR], 1.524, 95% CI: 1.057-2.197), tracheal intubation (OR: 4.202, 95% CI: 1.092-16.169), and acute kidney injury (OR:4.776, 95% CI: 1.632-13.978) were identified as independent risk factors for 30-day mortality. A nomogram prediction model was established based on these three factors. Internal validation of the model showed a Hosmer-Lemeshow test result of X2=5.770, P=0.834, and an area under the ROC curve of 0.791 (95% CI: 0.688-0.893). Bootstrap resampling of the original data 1000 times yielded a C-index of 0.791, and a decision curve analysis indicated a high net benefit when the threshold probability was between 15%-90%. The survival time for low-, medium-, and high-risk patients was 30 (30, 30), 30 (16.5, 30), and 17 (11, 27) days, respectively, which were significantly different.
UNASSIGNED: Lactic acid, tracheal intubation, and acute kidney injury were independent risk factors for 30-day mortality in patients in the ICU with gram-negative bacillary pneumonia. The predictive model constructed based on these factors showed good predictive performance and helped assess short-term survival, facilitating early intervention and treatment.

The occurrence of clonal hematopoiesis of indeterminate potential (CHIP), in which advantageous somatic mutations result in the clonal expansion of blood cells, increases with age, as do an increased risk of mortality and detrimental outcomes associated with CHIP. However, the role of CHIP in susceptibility to pulmonary infections, which also increase with age, is unclear. In this issue of the JCI, Quin and colleagues explored the role of CHIP in bacterial pneumonia. Using characterization of immune cells from human donors and mice lacking tet methylcytosine dioxygenase 2 (Tet2), the authors mechanistically link myeloid immune cell dysfunction to CHIP-mediated risk of bacterial pneumonia. The findings suggest that CHIP drives inflammaging and immune senescence, and provide Tet2 status in older adults as a potential prognostic tool for informing treatment options related to immune modulation.

BACKGROUND: A. baumannii is an important and common clinical pathogen, especially in the intensive care unit (ICU). This study aimed to characterize one hypervirulent A. baumannii strain in a patient with community-acquired pneumonia and herpes simplex type 1 virus infection.
METHODS: Minimum inhibitory concentrations (MICs) were determined using the Kirby-Bauer (K-B) and broth microdilution methods. Galleria mellonella infection model experiment was conducted. Whole-genome sequencing (WGS) was performed using the Illumina and Nanopore platforms. The resistance and virulence determinants were identified using the ABRicate program with ResFinder and the VFDB database. The capsular polysaccharide locus (K locus) and lipooligosaccharide outer core locus (OC locus) were identified using Kleborate with Kaptive. Phylogenetic analyses were conducted using the BacWGSTdb server.
RESULTS: A. baumannii XH2146 strain belongs to ST10Pas and ST447Oxf. The strain was resistant to cefazolin, ciprofloxacin, and trimethoprim/sulfamethoxazole (TMP-SMX). Bautype and Kaptive analyses showed that XH2146 contains OCL2 and KL49. WGS analysis revealed that the strain harbored blaADC-76, blaOXA-68, ant(3\'\')-IIa, tet(B), and sul2. Notably, tet(B) and sul2, both were located within a 114,700-bp plasmid (designated pXH2146-1). Virulence assay revealed A. baumannii XH2146 possessed higher virulence than A. baumannii AB5075 at 12 h. Comparative genomic analysis showed that A. baumannii ST447 strains were mainly isolated from the USA and exhibited a relatively close genetic relationship. Importantly, 11 strains were observed to carry blaOXA-58; blaOXA-23 was identified in 11 isolates and three ST447 A. baumannii strains harbored blaNDM-1.
CONCLUSIONS: Early detection of community-acquired hypervirulent Acinetobacter baumannii strains is recommended to prevent their extensive spread in hospitals.

BACKGROUND: Community-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis.
METHODS: We conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced.
RESULTS: The sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections.
CONCLUSIONS: Collectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients.

OBJECTIVE: To assess differences in the sputum microbiota of community-acquired pneumonia (CAP) patients with either COPD or asthma, specifically focusing on a patient population in Turkey.
METHODS: This retrospective study included hospitalized patients > 18 years of age with a diagnosis of pneumonia between January of 2021 and January of 2023. Participants were recruited from two hospitals, and three patient groups were considered: CAP patients with asthma, CAP patients with COPD, and CAP patients without COPD or asthma.
RESULTS: A total of 246 patients with CAP were included in the study, 184 (74.8%) and 62 (25.2%) being males and females, with a mean age of 66 ± 14 years. Among the participants, 52.9% had COPD, 14.2% had asthma, and 32.9% had CAP but no COPD or asthma. Upon analysis of sputum cultures, positive sputum culture growth was observed in 52.9% of patients. The most commonly isolated microorganisms were Pseudomonas aeruginosa (n = 40), Acinetobacter baumannii (n = 20), Klebsiella pneumoniae (n = 16), and Moraxella catarrhalis (n = 8). CAP patients with COPD were more likely to have a positive sputum culture (p = 0.038), a history of antibiotic use within the past three months (p = 0.03), utilization of long-term home oxygen therapy (p < 0.001), and use of noninvasive ventilation (p = 0.001) when compared with the other patient groups. Additionally, CAP patients with COPD had a higher CURB-65 score when compared with CAP patients with asthma (p = 0.004).
CONCLUSIONS: This study demonstrates that CAP patients with COPD tend to have more severe presentations, while CAP patients with asthma show varied microbial profiles, underscoring the need for patient-specific management strategies in CAP.

Cold-inducible RNA-binding protein (CIRP) is a damage-associated molecular pattern that plays a critical role in triggering inflammatory responses. It remains unknown whether CIRP is strongly associated with bacterial load, inflammatory response, and mortality in sepsis model. Pneumonia was induced in specific pathogen-free 8-9-week old male rats by injecting bacteria via puncture of the tracheal cartilage. The expressions of CIRP and proinflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β] in lung tissues, alveolar macrophages (AMs), plasma, and bronchoalveolar lavage fluid (BALF) were determined by reverse transcription-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The numbers of bacteria recovered from the lungs were correlated with the bacterial loads injected and mortality. The expressions of CIRP increased sharply as the bacterial loads increased in the lung tissues and AMs. The amounts of TNF-α, IL-6 and IL-1β proteins synthesized were dependent on the bacterial load in the lung tissues. Releases of CIRP, TNF-α, IL-6, and IL-1β increased with the bacterial load in the blood plasma. The proteins confirmed similar patterns in the BALF. CIRP was strongly associated with the releases of TNF-α, IL-6, and IL-1β in the lung tissues, blood plasma, and BALF, and showed a close correlation with mortality. CIRP demonstrated a strong association with bacterial load, which is new evidence, and close correlations with proinflammatory cytokines and mortality of pneumonia in rats, suggesting that it might be an interesting pneumonic biomarker for monitoring host response and predicting mortality, and a promising target for immunotherapy.