Ceftazidime/Avibactam Resistance in Carbapenemase-Producing Klebsiella pneumoniae.

We identified a novel ceftazidime/avibactam resistance mechanism in sequence type 11 Klebsiella pneumoniae carbapenemase 2-producing K. pneumoniae. Plasmid recombination and chromosomal integration formed a novel virulence plasmid and provided an additional promoter for blaSHV-12, leading to blaSHV-12 overexpression and ceftazidime/avibactam resistance. Genetic rearrangement contributed to convergence of hypervirulence and ceftazidime/avibactam resistance.

ST11 Carbapenem-Resistant Klebsiella pneumoniae Clone Harboring blaNDM Replaced a blaKPC Clone in a Tertiary Hospital in China.

The nosocomial spread of carbapenem-resistant Enterobacterales (CRE) is extremely common, resulting in severe burdens on healthcare systems. In particular, the high-risk Klebsiella pneumoniae ST11 strain has a wide endemic area in China. The current study describes the results of continuous monitoring of CRE genotypes and phenotypes in a tertiary hospital in North China from 2012 to 2020. A total of 160 isolates were collected, including 109 Klebsiella. pneumoniae (68.13%), 29 Escherichia coli (26.60%), 12 Enterobacter cloacae (7.50%), and 10 other strains (6.25%). A total of 149 carbapenemase genes were detected, of which blaKPC-2 (51.0%) was the most common, followed by blaNDM-1 (22.82%), and blaNDM-5 (23.49%). Based on multi-locus sequence typing, the ST11 strain (66.1%) dominates K. pneumoniae, followed by ST15 (13.8%). Interestingly, the proportion of blaNDM (22.2%, 16/72) in ST11 K. pneumoniae was significantly increased in 2018−2019. Hence, whole-genome sequencing was performed on ST11 K. pneumoniae. Growth curves and in vitro competition experiments showed that K. pneumoniae carrying blaNDM exhibited a stronger growth rate (p < 0.001) and competition index (p < 0.001) than K. pneumoniae carrying blaKPC. Moreover, K. pneumoniae carrying blaNDM had a stronger biofilm-forming ability than K. pneumoniae carrying blaKPC (t = 6.578; p < 0.001). K. pneumoniae carrying blaKPC exhibited increased defense against bactericidal activity than K. pneumoniae carrying blaNDM. Thus, ST11 K. pneumoniae carrying blaNDM has strong adaptability and can locally replace K. pneumoniae carrying blaKPC to become an epidemic strain. Based on these findings, infection control and preventive measures should focus on the high-risk ST11-K. pneumoniae strain.

Epidemiology and Antimicrobial Resistance Profiles of the Nocardia Species in China, 2009 to 2021.

The genus Nocardia includes ubiquitous environmental saprophytes and the most frequently isolated aerobic actinomycete human pathogen responsible for localized or disseminated infection. Herein, the species distribution and antimicrobial susceptibility profiles of 441 nonrepetitive Nocardia strains are reported, collected from 21 provinces/cities in China over 13 years (from 2009 to 2021). These isolates were identified to species level by mass spectrometry or targeted DNA sequencing. The susceptibility profiles of Nocardia species for 15 antibiotics were determined by the broth microdilution method. Among these Nocardia isolates, Nocardia farcinica was the most commonly isolated species (39.9%, 176 of 441), followed by Nocardia cyriacigeorgica (28.6%, 126), Nocardia abscessus (6.6%, 29), and Nocardia otitidiscaviarum (5.9%, 26). Furthermore, 361 Nocardia strains (81.9%) were collected from lower respiratory tract (sputum, lung tissue, and bronchoalveolar lavage fluid), 50 (11.3%) were collected from skin and soft tissues, 9 were collected from blood, 9 were collected from eye, 4 were collected from cerebrospinal fluid and brain abscesses, and 2 were collected from pleural effusion. All of the Nocardia strains were susceptible to linezolid, followed by amikacin (99.3%) and trimethoprim-sulfamethoxazole (TMP-SMX) (99.1%). The antibiotic resistance profiles of other antibiotics varied tremendously among different Nocardia species. This demonstrated that accurate species identification and/or antibiotic susceptibility testing should be performed before the usage of these antibiotics. In summary, this is the largest study on the species and antibiotic resistance profiles of the genus Nocardia circulating in China, and our data will contribute to a better understanding of clinical nocardiosis. IMPORTANCE The genus Nocardia has the potential to cause nocardiosis, which might be underrecognized and underdiagnosed. Herein, the demographical features of 441 nonrepetitive nocardiosis cases and species distribution of their Nocardia strains in China, 2009 to 2021, are summarized. The susceptibility profiles for 15 antibiotics against all of the above Nocardia strains were also determined by the broth microdilution method. To date, this is the largest study on the genus Nocardia contributing to nocardiosis in China. Our study will be helpful for understanding the species diversity of Nocardia isolates distributed in China and for decision-making in the context of nocardiosis diagnosis and treatment.