Outbreak of Multidrug-Resistant OXA-232-Producing ST15 Klebsiella pneumoniae in a Teaching Hospital in Wenzhou, China

Abstract

Background OXA-232-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) has the potential to become the “third epidemic” of carbapenem-resistant Klebsiella strain after KPC-2 and NDM in China. We investigated the first outbreak of CRKP in the First Affiliated Hospital of Wenzhou Medical University. Methods We collected 610 clinical isolates of CRKP from the First Affiliated Hospital of Wenzhou Medical University between January 2019 and September 2020 and screened them by Polymerase Chain Reaction (PCR). The multilocus sequence typing and pulsed-field gel electrophoresis were used to determine the genetic relatedness of the strains. The antimicrobial susceptibility test was performed to determine the drug resistance of the clinical isolates. The molecular mechanism underlying carbapenem resistance was elucidated by performing PCR and conjugation experiments. The virulence potential of the strains was determined by the string test, detection of virulence-associated genes and capsular serotypes, and Galleria mellonella larval infection model. Results Between September 2019 and May 2020, 26 OXA-232-producing CRKP were obtained from 12 patients in our hospital. Ten patients were hospitalized in the intensive care units (ICU) and the overall mortality of the inpatients involved in the outbreak was 50% (6/12). Epidemiological investigations reported that all the OXA-232-producing CRKP strains belonged to the sequence type ST15 and can be clonally transmitted among the inpatients in the ICU. All the strains had low virulence and were resistant to commonly used clinical antibiotics except for ceftazidime/avibactam, colistin, and tigecycline. The OXA-232-producing CRKP was sensitive to triclosan and chlorhexidine, and its eradication from our hospital can be achieved by the use of disinfectants in the ICU. Conclusion In our study, OXA-232-producing CRKP isolates appeared to be clonally transmitted and the sequence type ST15 was responsible for the outbreak. Therefore, effective measurements for the infection control of CRKP are urgently needed to prevent its epidemic in the nearby region in the future.

Epidemiological Characteristics of OXA-232-Producing Carbapenem-Resistant Klebsiella pneumoniae Strains Isolated during Nosocomial Clonal Spread Associated with Environmental Colonization

“…The rates of resistance to colistin and tigecycline were 5.13% and 8.55%, respectively (see Table S2). The antibiotic resistance experiment suggested that the OXA-232-CRKP isolates presented a multidrug-resistant profile with different levels of resistance to carbapenems, as reported previously ( 23 ).…”

“…Qin et al reported that the infection incidence of patients who had CRKP colonization in the intestinal tract and nasopharyngeal tract was almost 45.9% in the ICU at Huashan Hospital (Shanghai, China), which posed a true threat to public health because antimicrobial agents are rarely used to treat multidrug- resistant pathogens ( 21 ). Although the environment has been considered a reservoir for pathogens in the ICU and nosocomial outbreaks of OXA-232-CRKP have increased in recent years, there is limited literature reporting on the relationship and transmission of OXA-232-CRKP between the environment and patients ( 9 , 22 , 23 ). In this study, we focused on the OXA-232-CRKP that was first reported by Potron et al in 2013 and then spread throughout the world in recent years ( 12 ), whereas limited literature focuses on colonization in hospitals and patient infections.…”

“…According to previous reports, the infectious diseases caused by OXA-232-CRKP included pneumonia, urinary tract infections, and even septicemia ( 15 , 23 ). Yang et al reported an OXA-232-CRKP outbreak that was probably associated with endoscopic retrograde cholangiopancreatography procedures in a single institution in the United States, and 6 of 11 patients with OXA-232-CRKP infection died ( 24 ).…”

Resistance Phenotype and Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Isolated from Nanjing Children’s Hospital in Jiangsu Province, China

“…The OXA-48 enzyme has been reported in Beijing, 24 Shanghai 25 and Taiwan. 26 In recent years, OXA-232-producing (a variant of OXA-48 family, and the third most common OXA-48-like carbapenemase worldwide) Enterobacteriaceae began to appear in China, while OXA-232-producing Klebsiella pneumoniae is the most common in Shanghai, 27 Zhejiang 28 and other regions. According to the above reports, the OXA-48-like enzyme has begun to spread in China.…”

Whole genome sequencing of OXA-232-producing wzi93-KL112-O1 carbapenem-resistant Klebsiella pneumoniae in human bloodstream infection co-harboring chromosomal ISEcp1-based blaCTX-M-15 and one rmpA2-associated virulence plasmid

“…OXA-232-producing K. pneumoniae strains have been reported in Zhejiang and Shanghai, China (Shen et al, 2020b;Shi et al, 2020;Jia et al, 2021), but to our knowledge, no comprehensive phylogenetic analysis for ST15 K. pneumoniae isolates collected from various countries has been performed before. Moreover, a study by Zhu et al in Yancheng, China reported clonal dissemination of ST15 OXA-232-producing K. pneumoniae strains (Zhu et al, 2021).…”