RESUMO
Acinetobacter baumannii is one of the main pathogens causing nosocomial and community-acquired infections. Tigecycline is an important antibiotic for the treatment of multidrug-resistant A. baumannii infections, but strains resistant to tigecycline have also emerged. There are still many unclear questions concerning the mechanism of tigecycline resistance in A. baumannii. In this study, tigecycline-susceptible and tigecycline-intermediate strains were gradually cultured with sub-minimum inhibitory concentrations of tigecycline to select for tigecycline-resistant mutants, and a tigecycline-resistant strain was cultured under 42 °C to select for tigecycline-susceptible mutants. We found that the acquisition of tigecycline resistance affected the susceptibility of the strains to other antibiotics. Resistance to ampicillin-sulbactam is negatively correlated with tigecycline resistance. The strains will experience fitness costs along with the acquisition of tigecycline resistance. Tigecycline resistance in the strains was not related to 16S rRNA target variation or outer membrane integrity alteration. By constructing a transposon mutation library, we found that transposon insertion of the adeL gene reduced the sensitivity of A. baumannii to tigecycline. This study provides important clues for understanding the mechanism of tigecycline resistance in A. baumannii.
RESUMO
OBJECTIVES: To develop classification criteria for early rheumatoid arthritis (ERA) based on a large cohort of early inflammatory arthritis patients and to evaluate the performance of these criteria. METHODS: The study population comprised a cohort of early inflammatory arthritis patients with symptom duration less than one year. Classification criteria of ERA were developed by incorporating the most sensitive or specific variables. Performance of the ERA criteria, 1987 ACR and 2010 ACR/EULAR criteria were evaluated. RESULTS: A total of 803 patients were enrolled in this study. By the end of the one year follow-up, 514 patients were diagnosed with RA, 251 with other rheumatic diseases, and 38 patients with undifferentiated arthritis. The ERA criteria are as follows: 1) morning stiffness ≥30 minutes; 2) arthritis of 3 or more joint areas; 3) arthritis of hand joints; 4) positive RF; 5) positive anti-CCP antibody. Rheumatoid arthritis is defined by the presence of 3 or more of the criteria. The sensitivity (84.4%) of the ERA classification criteria was much higher than the 1987 ACR criteria (58.0%). In a validation cohort of early inflammatory arthritis patients, the area under the ROC curves (AUC) showed a better performance for the ERA criteria (0.906, 95%CI 0.866 to 0.945) than the 1987 ACR criteria (0.786, 95%CI 0.725 to 0.848) and the 2010 ACR/EULAR criteria (0.745, 95%CI 0.677 to 0.814). CONCLUSIONS: A set of ERA classification criteria has been developed with good performance for early RA. It is applicable in clinical practice and research.