Metabolomics Method in Understanding and Sensitizing Carbapenem-Resistant Acinetobacter baumannii to Meropenem.

Carbapenem-resistant Acinetobacter baumannii (CRAB) strains are prevalent worldwide and represent a major threat to public health. However, treatment options for infections caused by CRAB are very limited as they are resistant to most of the commonly used antibiotics. Consequently, understanding the mechanisms underlying carbapenem resistance and restoring bacterial susceptibility to carbapenems hold immense importance. The present study used gas chromatography-mass spectrometry (GC-MS)-based metabolomics to investigate the metabolic mechanisms of antibiotic resistance in clinically isolated CRAB. Inactivation of the pyruvate cycle and purine metabolism is the most typical characteristic of CRAB. The CRAB exhibited a reduction in the activity of enzymes involved in the pyruvate cycle, proton motive force, and ATP levels. This decline in central carbon metabolism resulted in a decrease in the metabolic flux of the α-ketoglutarate-glutamate-glutamine pathway toward purine metabolism, ultimately leading to a decline in adenine nucleotide interconversion. Exogenous adenosine monophosphate (AMP) and adenosine triphosphate (ATP) enhance the killing efficacy of Meropenem against CRAB. The combination of ATP and Meropenem also has a synergistic effect on eliminating CRAB persisters and the biofilm, as well as protecting mice against peritonitis-sepsis. This study presents a novel therapeutic modality to treat infections caused by CRAB based on the metabolism reprogramming strategy.

Chlamydia psittaci pneumonia: a clinical analysis of 12 patients.

Background: We conducted a retrospective analysis to explore the clinical characteristics, laboratory examination, imaging features, treatment outcomes, and prognosis of the Chlamydia psittaci (C. psittaci) pneumonia, aiming to improve early diagnosis and treatment. Methods: The clinical data of 12 patients with C. psittaci pneumonia diagnosed by metagenomic next-generation sequencing (mNGS) in our hospital were retrospectively analyzed. These data included baseline information, epidemiological history, clinical symptoms and signs, laboratory and chest computed tomography (CT) examination findings, treatment schemes, and prognosis. Results: The average age of the 12 patients was 58.25±13.27 years, and there were 7 (58.3%) males and 5 (41.7%) females in this cohort. Five patients had clear exposure to poultry or birds. The main clinical manifestations included fever (12/12, 100.0%), cough (12/12, 100.0%), expectoration (10/12, 83.3%), and dyspnea (10/12, 83.3%). Laboratory examination showed marked elevation of the total white blood cell (WBC) count, neutrophil (NEUT) count, C-reactive protein (CRP), procalcitonin (PCT), D-dimer, aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine, and creatine kinase (CK) levels; as well as decreased hemoglobin (HGB), blood platelet (PLT), and albumin (ALB) levels. Arterial blood gas analysis showed that the average value of the oxygenation index (PO2/FiO2) was 290.9±83.1, which was less than 300 in 6 cases (50.0%). The main chest CT features were patchy or consolidation in the bilateral or unilateral lungs, and the boundary was not clear but showed a bronchial inflation sign. Also, some of the cases were accompanied by pleural effusion. Once the etiology was obtained, the patients were quickly treated with doxycycline combined with other antibiotics. All 12 patients improved and were discharged from the hospital. However, two severe patients were admitted to the intensive care unit (ICU) and received ventilation and monitoring treatment. There were no deaths. Conclusions: C. psittaci pneumonia is an atypical community-acquired pneumonia (CAP) caused by C. psittaci infection, with its own laboratory and imaging characteristics. In this study, diagnosis was established based on the application of mNGS owing to the absence of easily available conventional pathogenic evidence. In addition, an aggressive and precise treatment strategy can help achieve a favorable prognosis for patients.