Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection poses a great threat to public health worldwide, and KPC-2-producing strains are the main factors responsible for resistance to carbapenems in China. Ceftazidime/avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor combination with good activity against KPC-2 carbapenemase and is becoming the most important option for treating KPC-producing CRKP infection. Here, we report the emergence of a novel KPC-2 variant, designated KPC-74, produced by K. pneumoniae strain KP55, that conferred CZA resistance in a patient after CZA exposure. The novel blaKPC–74 variant showed a deletion of 6 nucleotides at positions 712–717 compared with blaKPC–2, and this deletion resulted in the consequent deletion of glycine and valine at positions 239 and 240. Antimicrobial susceptibility testing showed that KP55 presents multidrug resistance, including resistance to CZA and ertapenem, but is susceptible to imipenem, meropenem, and colistin. The blaKPC–74 gene was located on a plasmid, as determined by S1-nuclease pulsed-field gel electrophoresis followed by southern blotting, and confirmed to be 133,766 bp in length by whole-genome sequencing on both the Illumina and MinION platforms. The CZA resistance phenotype of the novel KPC variant was confirmed by both transformation of the blaKPC–74-harboring plasmid and a blaKPC–74 gene cloning assay, showing a 64-fold higher CZA minimum inhibitory concentration (MIC) than the recipient strains. The G239_V240del observed in KPC-74 was outside the omega-loop region but was still close to the active site Ser70 and omega-loop in the protein tertiary structure. The enzyme kinetic parameters and IC50 values further indicated that the hydrolytic activity of the KPC-74 enzyme against ceftazidime was potentiated twofold and that the affinity between KPC-74 and avibactam was alleviated 17-fold compared with that of the KPC-2 allele. This CZA resistance mediated by KPC-74 could be selected after CZA therapy and evolved to be more diverse and heterogeneous. Surveillance of CZA resistance is urgently needed in clinical settings.
For the first time, we reported a KPC variant, KPC-90, in a clinical ST463 CRPA strain with CZA resistance. CZA resistance was mediated by a 2 amino acid insertion outside the KPC omega-loop region in CRPA.
In this study, we report an ST11-type clinical CRKP isolate that produces KPC-71, a novel plasmid backbone KPC variant that confers the development of CZA resistance during treatment. Furthermore, we reveal that resistance to CZA is mediated by the 182S insertion mutation in the KPC enzyme, which increases ceftazidime affinity and decreases avibactam inhibition.
Nontuberculous mycobacteria infections present mostly pulmonary characteristics. However, the incidence of skin and soft tissue infections caused by nontuberculous mycobacteria has increased in part due to the increased popularity of cosmetic and plastic surgery. Here, we report a case of Mycobacterium agri infection. The patient underwent a one-year course of anti-infection therapy. To the best of our knowledge, this is the first report of a previously healthy patient presenting a skin and soft tissue infection caused by Mycobacterium agri. Clinical personnel should be aware of possible causes of persistent skin and soft tissue infection after cosmetic and plastic surgery.
Introduction: Pyogenic liver abscess (PLA) is a serious infectious disease of the liver. PLA caused by Fusobacterium nucleatum is extremely rare. Here we report the first case of liver abscess caused by F. nucleatum in China. Case Presentation: The case was a 34-year-old female patient admitted to the hospital due to high fever. The diagnosis of liver abscess was confirmed by imaging studies and liver puncture. We finally confirmed the pathogen as F. nucleatum by next-generation sequencing (NGS). After the targeted anti-infective treatment, the patient recovered and discharged. Conclusions: As a new microbial detection method, NGS can still help in clinical practice. In addition, to improve the positive rate of anaerobic bacteria culture, we should pay attention to avoid contact with air in the process of specimen collection when the pathogenic bacteria are suspected to be anaerobic bacteria.
Psoas abscess (PA) is an uncommon disease that has been increasingly reported in recent years. We reviewed patients with PA and analysed their clinical characteristics to improve the understanding of this rare disorder. The study retrospectively reviewed the clinical presentations, microbiology, and outcomes of patients with PA between 2011 and 2021 in Zhejiang Provincial People’s Hospital in China. There were 35 cases out of 23057427 hospitalised adult patients; the mean age was 60 years, and 65.7% of the patients were male. Primary symptoms were typically nonspecific. In all, 17 abscesses were considered secondary, and the most common aetiology was infective spondylitis. The most common causative organism for primary PA was Staphylococcus aureus, followed by Escherichia coli, while for secondary abscesses, there were multiple bacterial species. The overall in-hospital mortality rate was 6%. Secondary PA patients had longer hospital stays (mean, 23 vs. 28 days). PAs, as a serious infectious condition, usually present with nonspecific symptoms and laboratory test results, making early diagnosis difficult. The aetiological profiles differed from those reported in our study. Initial clinical status and subsequent imaging studies can lead to favourable outcomes.
The rapidly increasing prevalence of Klebsiella pneumoniae carbapenemase 2 (KPC-2)-producing bacteria has become a serious challenge to public health. Currently, the blaKPC–2 gene is mainly disseminated through plasmids of different sizes and replicon types. However, the plasmids carrying the blaKPC–2 gene have not been fully characterized. In this study, we report the complete genome sequences of two novel blaKPC–2-harboring incompatibility group U (IncU) plasmids, pEC2341-KPC and pEC2547-KPC, from international high-risk clones of Escherichia coli isolated from Zhejiang, China. Two KPC-2-producing E. coli isolates (EC2341 and EC2547) were collected from clinical samples. Whole-genome sequencing (WGS) analysis indicated that EC2341 and EC2547 belonged to the ST410 and ST131 clones, respectively. S1-nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blot and conjugation experiments confirmed the presence of the blaKPC–2 gene on the pEC2341-KPC plasmid and that this was a conjugative plasmid, while the blaKPC–2 gene on the pEC2547-KPC plasmid was a non-conjugative plasmid. In addition, plasmid analysis further revealed that the two blaKPC–2-harboring plasmids have a close evolutionary relationship. To the best of our knowledge, this is the first report of E. coli strains carrying the blaKPC–2 gene on IncU plasmids. The emergence of the IncU-type blaKPC–2-positive plasmid highlights further dissemination of blaKPC–2 in Enterobacteriaceae. Therefore, effective measures should be taken immediately to prevent the spread of these blaKPC–2–positive plasmids.
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