This study reports on the characterization of two ceftazidime-avibactam (CZA)-resistant KPC-producing Klebsiella pneumoniae strains (KP-14159 and KP-8788) sequentially isolated from infections occurred in a patient never treated with CZA. Whole-genome sequencing characterization using a combined short- and long-read sequencing approach showed that both isolates belonged to the same ST258 strain, had altered outer membrane porins (a truncated OmpK35 and an Asp137Thr138 duplication in the L3 loop of OmpK36), and carried novel pKpQIL plasmid derivatives (pIT-14159 and pIT-8788, respectively) harboring two copies of the Tn4401a KPC-3-encoding transposon. Plasmid pIT-8788 was a cointegrate of pIT-14159 with a ColE replicon (that was also present in KP-14159) apparently evolved in vivo during infection. pIT-8788 was maintained at a higher copy number than pIT-14159 and, upon transfer to Escherichia coli DH10B, was able to increase the CZA MIC by 32-fold. The present findings provide novel insights about the mechanisms of acquired resistance to CZA, underscoring the role that the evolution of broadly disseminated pKpQIL plasmid derivatives may have in increasing the blaKPC gene copy number and KPC-3 expression in bacterial hosts. Although not self-transferable, similar elements, with multiple copies of Tn4401 and maintained at a high copy number, could mediate transferable CZA resistance upon mobilization.

Elena Pérez-Nadales and Belén Gutiérrez-Gutiérrez have contributed equally to this work.Investigators listed in Acknowledgments.

Objective To assess cardiac function in infants with bronchiolitis and the association with disease severity and outcomes. Working Hypothesis Cardiac function may be impaired in bronchiolitis and represent an early predictor of disease severity. Study Design A prospective cohort study. Patient Selection Infants with suspected bronchiolitis were included. Methodology All cases received antigen detection and viral genome detection from nasal lavage or swabs and echocardiography within 24 hours from admission. Systolic and diastolic function in left ventricle (LV) and right ventricle (RV) were assessed using longitudinal strain (LS), a measure of myocardial deformation. Pulmonary artery pressures were estimated using tricuspid regurgitation jet (TR), when present, and end‐systolic eccentricity index (EI ES). Main outcomes (duration of respiratory support, length of stay [LOS], and type of respiratory support) were collected. Data were compared to normative existing data, and a group of healthy infants, matched in age. Results Twenty‐eight infants with bronchiolitis and 10 healthy comparators were included. Cases with bronchiolitis showed significantly lower values of RV LS and LV LS compared to healthy comparators (LV: p0.04 and RV: P < .001). Ten infants (36%) had a normal biventricular function, nine (32%) had LV impairment, and nine (32%) had a biventricular impairment. No significant differences were found in TR and EI ES. Infants with biventricular impairment demonstrated a significant increase in LOS (p0.04) and higher levels of respiratory support compared to the healthy comparators (P = .03). Conclusions Bronchiolitis is associated with myocardial impairment. Cardiac function is related to disease severity and outcome.