Multicenter Genomic Analysis of Carbapenem-Resistant Klebsiella pneumoniae from Bacteremia in China

Cienfuegos-Gallet, Astrid V.; Zhou, Ying; Ai, Wenxiu; Kreiswirth, Barry N.; Yu, Fangyou; Chen, Liang

doi:10.1128/spectrum.02290-21

Cited by 24 publications

(23 citation statements)

References 49 publications

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“… 30 Another study reported that genes encoding yersiniabactin were identified in 83.7% (123/147) of the CRKP isolates. 31 Sherif et al found that yersiniabactin was the most common virulence factor (69.2%) in 39 randomly selected, geographically diverse MDR Kp isolates. 32 Furthermore, aerobactin was the dominant siderophore produced by the hvKp strains and the critical siderophore that enhances virulence ex vivo and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Clinical Outcomes, Microbiological Characteristics and Risk Factors for Difficult-to-Treat Resistance to Klebsiella pneumoniae Infection

Yang¹,

Liu²,

Wu³

et al. 2022

IDR

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Purpose This study aimed to identify the clinical outcomes, microbiological features and risk factors for difficult-to-treat resistance (DTR) Klebsiella pneumoniae (Kp) infection. Materials and Methods A retrospective study was conducted at Peking University Third Hospital from January 2020 to March 2021. DTR was defined as resistance to ≥1 carbapenem, ≥1 extended-spectrum cephalosporin, and ≥1 fluoroquinolone. Hypervirulent Kp (HvKp) was defined as peg-344-, iroB-, iucA-, rmpA- , or rmpA2 -positive. Clinical data were collected. Antimicrobial susceptibility testing and string tests were performed to determine resistance and hypermucoviscosity phenotype. Whole genome sequencing was performed to analyze the sequence type (ST), capsular serotypes, resistance and virulence genes. Risk factors for 30-day mortality were analyzed. Results Fifty DTR-Kp (50.0%) strains were identified among 100 patients. Compared to non-DTR-Kp group, a significant number of patients with DTR-Kp infection experienced ICU admission (44.0% versus 10.0%, P<0.001) and mechanical ventilation after Kp detection (26.0% versus 10.0%, P=0.037). Notably, the percentage of hvKp among the DTR-Kp isolates increased consistently over the 15 months evaluated. Most DTR-Kp strains belonged to ST11 (82.0%), followed by ST15 (12.0%), ST86 (2.0%), ST996 (2.0%), and ST3157 (2.0%). DTR-Kp isolates possessed various resistance genes, such as bla KPC-2 , bla TEM-1D and fosA3 (90.0%, 80.0% and 72.0%, respectively). Importantly, the yersiniabactin genes were significantly clustered in DTR group (48/50, 96.0%). The 30-day mortality was significantly higher in patients with DTR-Kp infection than non-DTR-Kp group (38.0% versus 8.2%, P=0.001). DTR-Kp infection (odds ratio [OR] = 4.196) was an independent risk factor for the 30-day mortality of Kp-infected patients. Additionally, cerebrovascular disease (OR = 2.780) and Charlson comorbidity index (OR= 1.584) were independent risk factors for DTR-Kp infections. Conclusion DTR-hvKp is rapidly emerging. The DTR-Kp strains harbored various resistance genes and high rates of yersiniabactin siderophore genes. DTR-Kp infection was an independent risk factor for mortality, suggesting that enhanced awareness essential.

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Section: Discussionmentioning

confidence: 99%

Clinical Outcomes, Microbiological Characteristics and Risk Factors for Difficult-to-Treat Resistance to Klebsiella pneumoniae Infection

Yang¹,

Liu²,

Wu³

et al. 2022

IDR

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“…For virulence factors, we found that ST15 CRKP carried genes encoding aerobactin, enterobactin, and yersiniabactin, including iutA, ybt, irp1, irp2, fyuA, ent, fepA , that are essential for bacterial growth. According to previous studies, siderophores systems, such as aerobactin, yersiniabactin, and enterobactin, are more common in invasive isolates than in non-invasive isolates [ 38 ]. Although yersiniabactin was detected in nearly 30% of the non-invasive isolates and almost 80% of the bacteraemia isolates, we detected it in 100% of the ST15 CRKP.…”

Section: Discussionmentioning

confidence: 99%

Epidemiology of carbapenem-resistant Klebsiella pneumoniae ST15 of producing KPC-2, SHV-106 and CTX-M-15 in Anhui, China

Zhao

et al. 2022

BMC Microbiol

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Background: It is well known that carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a more problematic public health issue due to its widespread spread worldwide. In China, ST11-type CRKP is the most prevalent CRKP, but ST15-type CRKP, a recently prevalent high-risk clone, has emerged widely throughout China, posing a serious public health risk. Therefore, we conducted an epidemiological of an outbreak of ST15 CRKP of producing CTX-M-15, KPC-2 and SHV-106 in a tertiary hospital in Anhui, China, to Understanding the potential risks of the current STT15 CRKP outbreak. Results: From July 2021 to December 2021, 13 ST15 CRKP isolates were identified by collecting non-repeated clinical multidrug-resistant isolates, with all capsular typing of serotype KL19. All ST15 CRKP isolates were resistant to cephalosporins, carbapenems and quinolones, but were sensitive to amikacin, tigecycline and polymyxin B. In addition, isolates carried blaSHV−106 (100%), blaKPC−2 (69%), blaCTX−M−15 (69%), blaTEM−1B (69%), blaOXA−1 (62%) and blaLAP−2 (8%), as well as iron chelators (iutA, ybt, fyuA, ent, fepA, irp1, irp2, 100%) were detected. In phenotyping experiments, all ST15 CRKP exhibited lower growth rates than NTUH-K2044, and all ST15 CRKP did not exhibit mucoviscositty characteristics. However, in the Galleria mellonella infection model, isolates 21081212, 21081241 and 21091216 were more lethal than the hypervirulent isolates NTUH-K2044. Sequencing results showed that the genetic environment surrounding the genes blaSHV−106, blaKPC−2, blaCTX−M−15, blaOXA−1 and blaTEM−1B were all identical in the ST15 CRKP isolates. Phylogenetic analysis showed that 13 ST15 CRKP isolates were divided into three subgroups, and when placed in global analysis, 10 of them were highly homologous to isolates from Jiangsu, two were highly homologous to isolates from Zhejiang, and one was homologous to an isolate from an unlabelled region. Conclusion: Our research shows that ST15 CRKP, which carries multiple β-lactamases genes and siderophores-encoding genes, may be evolving to hypervirulence and may have spread widely in localised areas. Therefore, environmental surveillance and clinical infection control in hospitals should be strengthened to prevent further spread of ST15 CRKP.

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“…Currently K. pneumoniae is the most common cause of nosocomial infections in Russia, accounting for almost 30% of cases in 2020 according to the AMRmap database [ 20 ] ( , accessed on 23 August 2022). The isolates studied belonged to the ST395 group, which is known as a high-risk clone with high capacity of drug resistance acquisition [ 21 ] and was revealed in different countries, for example, in France [ 22 ], Hungary [ 23 ] and China [ 24 ]. Additionally, ST395/KL39 isolates carrying the blaOXA-48 gene were recently revealed in Russia, including CriePir234 (GCA_009661195.1) described earlier by us [ 25 ], as well as in Finland in the same year, and were also obtained in 2013–2016 in such distant regions of the world as China, Germany and the USA.…”

Section: Discussionmentioning

confidence: 99%

Long-Read Whole Genome Sequencing Elucidates the Mechanisms of Amikacin Resistance in Multidrug-Resistant Klebsiella pneumoniae Isolates Obtained from COVID-19 Patients

et al. 2022

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Klebsiella pneumoniae is a Gram-negative, encapsulated, non-motile bacterium, which represents a global challenge to public health as one of the major causes of healthcare-associated infections worldwide. In the recent decade, the World Health Organization (WHO) noticed a critically increasing rate of carbapenem-resistant K. pneumoniae occurrence in hospitals. The situation with extended-spectrum beta-lactamase (ESBL) producing bacteria further worsened during the COVID-19 pandemic, due to an increasing number of patients in intensive care units (ICU) and extensive, while often inappropriate, use of antibiotics including carbapenems. In order to elucidate the ways and mechanisms of antibiotic resistance spreading within the K. pneumoniae population, whole genome sequencing (WGS) seems to be a promising approach, and long-read sequencing is especially useful for the investigation of mobile genetic elements carrying antibiotic resistance genes, such as plasmids. We have performed short- and long read sequencing of three carbapenem-resistant K. pneumoniae isolates obtained from COVID-19 patients in a dedicated ICU of a multipurpose medical center, which belonged to the same clone according to cgMLST analysis, in order to understand the differences in their resistance profiles. We have revealed the presence of a small plasmid carrying aph(3′)-VIa gene providing resistance to amikacin in one of these isolates, which corresponded perfectly to its phenotypic resistance profile. We believe that the results obtained will facilitate further elucidating of antibiotic resistance mechanisms for this important pathogen, and highlight the need for continuous genomic epidemiology surveillance of clinical K. pneumoniae isolates.

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Multicenter Genomic Analysis of Carbapenem-Resistant Klebsiella pneumoniae from Bacteremia in China

Cited by 24 publications

References 49 publications

Clinical Outcomes, Microbiological Characteristics and Risk Factors for Difficult-to-Treat Resistance to Klebsiella pneumoniae Infection

Clinical Outcomes, Microbiological Characteristics and Risk Factors for Difficult-to-Treat Resistance to Klebsiella pneumoniae Infection

Epidemiology of carbapenem-resistant Klebsiella pneumoniae ST15 of producing KPC-2, SHV-106 and CTX-M-15 in Anhui, China

Long-Read Whole Genome Sequencing Elucidates the Mechanisms of Amikacin Resistance in Multidrug-Resistant Klebsiella pneumoniae Isolates Obtained from COVID-19 Patients

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