Skip to main content
Download PDF
  • Systematic Review
  • Open access
  • Published:

Systematic review and meta-analysis on the carbapenem-resistant hypervirulent Klebsiella pneumoniae isolates

BMC Pharmacology and Toxicology volume 26, Article number: 25 (2025) Cite this article

Abstract

Background

The global dissemination of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) poses a critical threat to public health. However, comprehensive data on the prevalence and resistance rates of CR-hvKp are limited. This systematic review and meta-analysis aim to estimate the pooled prevalence of carbapenem resistance among hvKp strains and assess the distribution of carbapenemase genes.

Materials and methods

A systematic search of ISI Web of Science, PubMed, and Google Scholar was conducted to identify studies reporting carbapenem resistance rates in hvKp strains. The pooled prevalence of carbapenem resistance and carbapenemase genes was calculated using event rates with 95% confidence intervals.

Results

A total of 36 studies encompassing 1,098 hvKp strains were included. The pooled resistance rates were 49% for imipenem, 53.2% for meropenem, and 38.2% for ertapenem. Carbapenemase gene prevalence was 19.1% for blaVIM, 22.0% for blaNDM, 43.4% for blaOXA-48, and 58.8% for blaKPC.

Conclusion

The high prevalence of carbapenem resistance and the widespread distribution of carbapenemase genes among hvKp strains underscore their significant threat to global health. These findings highlight the urgent need for enhanced surveillance, rapid diagnostic tools, and stringent infection control measures to mitigate the spread of CR-hvKp. Future research should focus on understanding resistance mechanisms and developing targeted therapeutic strategies to address this critical challenge.

Peer Review reports

Introduction

Klebsiella pneumoniae is one the most important omnipresent opportunistic bacteria that belongs to Enterobacterales [1]. This bacterium commonly colonized in the human colon can cause multiple infections including blood-stream infections (BSI), surgical-site infections, urinary tract infections (UTIs), ventilator-associated pneumonia, abscesses, and wound infections [2, 3]. The literature identifies two phenotypes of Klebsiella pneumoniae: classical K. pneumoniae (cKp) and hypervirulent K. pneumoniae (hvKp) [4]. cKp strains primarily cause infections in immunocompromised individuals, while hvKp strains can cause severe, invasive infections, including multiple-site infections, even in healthy individuals [5, 6]. HvKp strains possess additional virulence factors such as the hypermucoviscosity phenotype (e.g., rmpA and rmpA2) and siderophores, contributing to their ability to cause severe infections in healthy hosts, whereas cKp strains typically harbor antimicrobial resistance (AMR) genes and affect those with weakened immunity [7, 8]. HvKp strains can acquire virulence plasmids, leading to complicated infections in both immune-deficient and healthy individuals [9]. As a result, hvKp is associated with higher mortality rates compared to cKp [10, 11]. HvKp is linked to life-threatening community-acquired infections, such as liver abscesses, endophthalmitis, meningitis, and necrotizing fasciitis, while cKp generally causes hospital-acquired infections, including pneumonia, bloodstream infections, and urinary tract infections [12]. HvKp is more common in Asian countries but has been increasingly reported worldwide, whereas cKp is a leading cause of nosocomial infections globally [13]. The emergence of hybrid strains (CR-hvKp), which combine hvKp virulence traits and cKp resistance traits, poses significant concerns, as these strains exhibit enhanced fitness, multidrug resistance, and increased ability to cause severe disease, complicating treatment and infection control efforts [14]. Furthermore, multidrug-resistant hvKp strains are associated with poor clinical outcomes, including higher mortality rates [15].

Carbapenems are one of the important classes of antibiotics that first choice therapy for infections caused by multiple drug-resistant pathogens [16]. Yigit et al. (1996) reported the first case of carbapenem-resistant K. pneumoniae infection from Carolina [17]. Nowadays, there is a continuous increase in the trends of carbapenem-resistant gram-negative bacilli in the world [18]. The World Health Organization (WHO) declared K. pneumoniae as the pathogen of critical threat in the global priority list in 2017 [19]. Currently, carbapenem-resistant pathogens have gained international attention due to their challenges in human health situations [20]. Some limited antimicrobial agents remain effective against carbapenem-resistant infections, antibiotic options for carbapenem-resistant infections are less effective and more toxic for humans [21]. Furthermore, there are several evidence regarding the increase in poor clinical outcomes e.g., the mortality rate in carbapenem-resistant pathogens than susceptible pathogens [22].

There are two main mechanisms for resistance to carbapenem including (1) acquisition of carbapenemase e.g., KPC-type enzymes, metallo-β-lactamases (VIM, IMP, NDM), as well as OXA-48 type enzymes, (2) alternations of porin expression [23]. Unfortunately, carbapenemase-related genes are identified in bacterial strains that already have resistance to other multiple drugs [24, 25]. The emergence and global dissemination of carbapenem-resistant hvKp strains can cause a major challenge to the world. There are several reports regarding the presence of carbapenem-resistant hypervirulent K. pneumoniae infections [26,27,28]. The presence of carbapenem-resistant hvKp strains leads to fatal clinical outcomes, particularly in intensive care units. There is a need for global surveillance efforts to track antimicrobial resistance; However, a significant gap exists in the accurate reporting and monitoring of carbapenem resistance in hypervirulent Klebsiella pneumoniae (hvKp) strains, which are underrepresented in various regions, thereby hindering effective containment and treatment strategies. In this relation, there are no comprehensive documents to underscore the prevalence of carbapenem-resistant hvKp infections. Herein, this systematic review and meta-analysis examined the pooled prevalence of carbapenem-resistant hvKp burden throughout the world.

Materials and methods

Search strategy

A computer-assisted search was performed in electronic databases e.g., ISI Web of Science, PubMed, and Google Scholar. All potential relevant studies that examine the prevalence of carbapenem-resistant hvKp strains in patients hospitalized in intensive care units were collected. The medical terms including “Klebsiella pneumoniae”, “carbapenem-resistant Klebsiella pneumoniae”, “Carbapenem”, “hypervirulent K. pneumoniae”, “antibiotic resistance”, “intensive care unit”, as well as “ICU” were chosen as relevant keywords to identify potential articles from inception to November 2024. Furthermore, the bibliography of relevant studies was manually checked by the authors to avoid losing any possible articles. This process was performed by two independent authors.

Study selection

To identify eligible studies, we included original research articles such as cross-sectional, case-control, and cohort studies that reported on the prevalence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (hvKp) strains. Studies on clinical samples and those that assessed antimicrobial drug susceptibility testing using Clinical Laboratory Standard Institute (CLSI) guidelines were also included. Additionally, only articles published in the English language were considered. Whereas, exclusion criteria consisted of case reports, letters, editorials, congress abstracts, studies based on non-clinical specimens, articles with repetitive samples, studies published in languages other than English, duplicate studies, and studies with unclear or incomplete methodologies. The selection process was carried out by two independent authors, and any discrepancies were resolved through consultation with a third author to ensure consistency and accuracy in the study inclusion.

Data extraction

After applying inclusion and exclusion criteria, the required information such as first author, publication year, country, the number of hvKp strains, number of carbapenem-resistance genes i.e., blaVIM, blaKPC, blaNDM, blaOXA-48, mortality rates, resistance rate to Carbapenems such as imipenem, meropenem, ertapenem, resistance rate to colistin, ESBL-positive rate was extracted and summarized in Table 1. This section was also performed by two independent authors and inconsistency was decided through discussion.

Table 1 Characteristics of included studies
Full size table

Statistical analysis

We pooled the data using Comprehensive Meta-Analysis (CMA) software version 2.2 (Biostat, Englewood, NJ). The pooled prevalence of carbapenem-resistance rates among hvKp strains was expressed using event rate with corresponding 95% confidence intervals. We used the Cochrane Q-test (p-value < 0.05) and I-squared (I2) index to estimate the heterogeneity among eligible studies. The random-effects model was used in the presence of considerable heterogeneity. Publication bias was also assessed using Egger’s p-value and asymmetry of the funnel plot.

Results

Characteristics of included studies

A total of 1101 records were identified through searching databases, duplicates were omitted. Subsequently, the title and abstracts of the remaining articles were evaluated. 153 articles were selected for detailed full-text evaluation. After applying the selection criteria, 36 eligible studies were included in a systematic review and quantitative synthesis (Fig. 1).

Fig. 1
figure 1

Flowchart of the studies included in the analysis

Full size image

The main reason for rejection was (1) studies that were not conducted on K. pneumoniae, (2) studies that did not evaluate hypervirulent K. pneumoniae, (3) studies that did not evaluate carbapenem resistance in clinical isolates of hvKP strain, (4) studies that did not report carbapenem-resistance genes, (5) studies on non-human subjects, 5) review articles, (6) studies that did not have full-text available, and (7) studies with unclear methods and results. There are 36 eligible studies to underscore the carbapenem-resistance rate among hvKp strains [29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64]. The included studies were from China (n = 21), Iran (n = 6), Egypt (n = 2), India (n = 5), Russia (n = 1), and Sudan (n = 1) between 2014 and 2023. In the current study, the data of 5,667 K. pneumoniae strains were included. Of these, there are 1,098 hypervirulent K. pneumoniae strains which were assessed to pooled carbapenem-resistance rates.

The prevalence of hvKp infections among total K. pneumoniae strains was approximately 17.7% (95%CI: 12.8–24.0; I2: 95.4; p-value: 0.01; Egger’s p-value: 0.1) (Fig. 2). In addition, the pooled prevalence of ESBL rate as well as resistance burden to colistin in hvKp strains was 38.3% (95%CI: 26.0-52.3; I2: 83.5; p-value: 0.01; Egger’s p-value: 0.09) and 13.1% (95%CI: 3.0-42.3; I2: 73.7; p-value: 0.01; Egger’s p-value: 0.9), respectively (appendix). The pooled mortality rate was also assessed as 28.0% (95%CI: 20.2–37.4; I2: 69.5; p-value: 0.01; Egger’s p-value: 0.4).

Fig. 2
figure 2

Forest plot of the meta-analysis on the prevalence of hypervirulent Klebsiella pneumoniae (hvKp) infections

Full size image

The pooled prevalence of imipenem was 49.0% (95%CI: 32.7–65.5; I2: 87.7; p-value: 0.01; Egger’s p-value: 0.3), 53.2% (95%CI: 35.6–70.1; I2: 88.8; p-value: 0.01; Egger’s p-value: 0.2) for meropenem, as well as 38.2% (95%CI: 5.4–87.0; I2: 90.9; p-value: 0.01; Egger’s p-value: 0.4) for mertapenem. Our findings reveal the presence of considerable resistance to carbapenem antibiotics among clinical hvKp strains (Fig. 3).

Fig. 3
figure 3

Forest plot of the meta-analysis on the resistance rates of hypervirulent Klebsiella pneumoniae (hvKp) strains to Imipenem, Meropenem, and Ertapenem

Full size image

In the next stage, the prevalence of carbapenem-resistance genes was measured among hvKp clinical strains. The pooled prevalence of blaVIM was 19.1% (95%CI: 5.0–91.0; I2: 80.9; p-value: 0.01; Egger’s p-value: 0.2), 22.0% (95%CI: 13.4–33.8; I2: 73.4; p-value: 0.01; Egger’s p-value: 0.4) for blaNDM, 43.4% (95%CI: 24.9–63.9; I2: 78.9; p-value: 0.01; Egger’s p-value: 0.3) for blaOXA-48, as well as 58.8% (95%CI: 25.3–85.8; I2: 90.6; p-value: 0.01; Egger’s p-value: 0.6) for blaKPC.

In the subgroup analyses, an increasing trend in colistin resistance rates among hvKp strains over time was observed, whereas unstable trends were noted for carbapenem-resistant and ESBL-producing hvKp strains (Fig. 4). However, the uneven distribution of studies across regions poses significant challenges to the reliability of conclusions regarding global trends in carbapenem resistance. This underrepresentation may result in an incomplete understanding of the global burden and regional variability in resistance mechanisms. Therefore, the results should be interpreted with more caution. Furthermore, we pooled the prevalence of carbapenem-resistance rates in hvKp strains based on WHO region classification (Fig. 5). The details of carbapenem-resistance rates in WHO regions are listed in Table 2. There is a considerably high pooled prevalence of carbapenem-resistance rate of hvKp strains among all of the WHO-West Pacific region, Eastern Mediterranean region, South-East Asian Region, European Region, as well as the African region. Our results showed that blaKPC is common in the West Pacific region. BlaOXA-48 is more common in both South-East Asian as well as African regions, while blaNDM, and blaVIM is popular in the Eastern Mediterranean region as well as the South-East Asian Region (Table 2).

Fig. 4
figure 4

Global trends in antibiotic resistance patterns of hypervirulent Klebsiella pneumoniae (hvKp) Strains

Full size image
Fig. 5
figure 5

Global distribution of carbapenemase variants in hypervirulent Klebsiella pneumoniae (hvKp) strains

Full size image
Table 2 Summary of event rates with confidence intervals (CIs) for carbapenem-resistant hvKp strains
Full size table

Publication bias

There are several items to underscore the presence of publication bias in the eligible studies. Both Egger’s plot and symmetry in the funnel plot confirmed the lack of publication bias in the included studies (Fig. 6).

Fig. 6
figure 6

Funnel plot of the meta-analysis on the prevalence of Carbapenem-resistant hypervirulent Klebsiella pneumoniae (hvKp) strains

Full size image

Discussion

According to the literature, carbapenem-resistant K. pneumoniae is one of the top seven leading death pathogens. More than 50,000 human deaths are attributed to this pathogen annually [26]. Carbapenem-resistant pathogens are considered one of the most serious human threats, mostly leading to clinical outcomes i.e., high mortality rates, prolonged hospitalization, as well as high medical costs [65].

Carbapenem-resistant K. pneumoniae is considered a global challenge so limited therapeutic options remain against these pathogens [66]. Unfortunately, the rate of carbapenem resistance in recent years has significantly increased in recent years as studies have shown that the rate of carbapenem-resistant K. pneumoniae has increased from 3 to 23.1% from 2005 to 2021. In addition, carbapenem-resistant A. baumannii has been reported from 31.0 to 71.5% [67]. This analysis included 36 eligible studies regarding the carbapenem-resistant K. pneumoniae rate. To the best of our knowledge, this is the first document, that investigated the pooled prevalence of carbapenem-resistant K. pneumoniae throughout the world. In this analysis, we evaluated data of 5,667 K. pneumoniae strains from 36 included studies that were performed between 2014 and 2023.

The pooled prevalence of ESBL-producing hvKp strains and colistin resistance rate was 38.3% (95%CI: 26.0-52.3) and 13.1% (95%CI: 3.0-42.3) measured. Furthermore, mortality rates in hvKp infections was also measured at 28.0% (95%CI: 20.2–37.4). In this relation, Xu et al. (2017) showed that infection with carbapenem-resistant K. pneumoniae strains significantly increased the risk of mortality compared with carbapenem-susceptible strains [65]. However, some studies have also shown no association between infection with carbapenem-resistant pathogens and death [68, 69]. According to the literature, drug-resistant pathogen infections in individuals with underlying diseases and comorbidities tend to increase mortality rates [70, 71]. Our results showed that the carbapenem-resistance rate including imipenem was 49.0%, meropenem was 53.2%, and ertapenem was about 38.2%. Tesfa et al. (2022) reported the pooled prevalence of colonization with carbapenem-resistant K. pneumoniae at about 5.43% [20]. Vaez et al. (2018) reported the prevalence of CR K. pneumoniae in Iranian populations was about 11.3% [16]. The carbapenem-resistance rate is more common in hvKp strains. In line with these results, Beig et al. (2024) estimated the carbapenem-resistant rate among hvKp strains such as imipenem (45.7%), meropenem (51.0%), and ertapenem (40.6%) [72].

Various mechanisms contribute to carbapenem resistance, including Ambler class A beta-lactamases (e.g., KPC, GES, IBC, SFC enzymes), metallo-beta-lactamases (VIM, IMP, NDM, SPM, GIM, and AIM), and Ambler class D enzymes (OXA-type enzymes). Among these, KPC, VIM, IMP, and NDM are the most prevalent carbapenemases with widespread distribution [73, 74]. The mechanisms underlying carbapenem resistance involve enzymatic properties, genetic organization, and modes of dissemination. In this context, the blaKPC gene encodes Klebsiella pneumoniae carbapenemase (KPC), a class A beta-lactamase capable of hydrolyzing carbapenems. It is typically carried on Tn4401 transposons, embedded within conjugative plasmids, and is endemic in North and South America [75]. Conversely, the blaOXA-48 gene encodes OXA-48 carbapenemase, a class D beta-lactamase with restricted hydrolytic activity against carbapenems. It is generally carried on Tn1999 transposons, often harbored on cryptic plasmids, and is predominantly found in the Middle East, North Africa, and parts of Southern Europe [76]. The regional dominance of carbapenemases is influenced by various aspects, including antibiotic usage patterns, horizontal gene transfers dynamics, geographic variability in infection control measures, as well as international travel [77, 78].

Our findings suggested that blaKPC and blaVIM were the most common and least common genes associated with carbapenem resistance among hvKp strains, respectively. Consistent with our results, KPC enzymes are the most frequent carbapenemase hydrolyzing enzymes that are predominant throughout the world [79]. KPC-producing K. pneumoniae has been reported from various WHO regions in the United States, Latin America, European, and Asian countries [80]. Previous studies revealed that KPC-producing K. pneumoniae is not only resistant to all β-lactam antibiotics but also has convergence resistance to other antimicrobial agents such as aminoglycosides and fluoroquinolones [81]. These findings could be explained by higher mortality rates of KPC-encoding K. pneumoniae [82]. Thus, infection with KPC-positive K. pneumoniae infections can be considered an independent risk factor for mortality [67, 68].

Based on our sub-group analysis, the carbapenem resistance rate in hvKp strains was relatively high across WHO regions, particularly the West Pacific region as well as the Southeast Asian region. The carbapenem resistance rate in Europe and Africa was reported to be over 50%. The studies that reported carbapenem-resistant hvKp strains are limited in African and European countries. Therefore, this picture does not represent the resistance rate in these regions. In this relation, the previous epidemiological studies reported high carbapenem-resistant K. pneumoniae rates in India (22%), China (21%), Egypt (19%), Spain (16%), and the USA (15%) [17]. The results of studies could be varied due to different backgrounds such as previous hospitalization, ICU admission, previous exposure to antibiotics, and distribution of resistance genes in various geographical regions [83, 84]. We found that the pooled prevalence of blaKPC and blaOXA-48 was higher than other carbapenemases. BlaKPC and blaOXA are carried by multiple plasmids such as IncFIIK1, FIIK2, FIA, I2, X, and A/C [85]. Early studies have shown a widespread global distribution of blaKPC and blaOXA-48 beta-lactamases [86, 87]. Consistent with our results, carbapenemases such as blaKPC, blaNDM, and blaOXA-48 are present in most eastern countries [78, 88,89,90]. Furthermore, North Africa and the Middle East are reservoirs for the global dissemination of blaOXA-48 and blaNDM-1 [91,92,93,94]. Research literature suggests that carbapenem-resistant K. pneumoniae dissemination in European counters has polyclonal from blaKPC-encoding pathogens [95]. However, there is no comprehensive data regarding these carbapenemases because blaIMP and blaVIM are challenging to trace [96].

Carbapenem-resistant hvKp strains present significant clinical challenges due to their dual threat of multidrug resistance and hypervirulence, which often leads to invasive infections particularly liver abscesses, endophthalmitis, and meningitis [97]. Current treatment options are severely limited, particularly as traditional last-line agents like carbapenems are rendered ineffective [98]. Combination therapies involving polymyxins, tigecycline, and ceftazidime-avibactam have shown some efficacy, but their success is inconsistent and constrained by factors such as suboptimal pharmacokinetics and emerging resistance [99]. In addition, reliance on polymyxins is associated with considerable nephrotoxicity, further complicating patient management [100]. The emergence of novel β-lactamase inhibitors, such as cefiderocol and combinations like meropenem-vaborbactam, offers some promise but remains limited in regions where blaOXA−48-like carbapenemases predominate, as these agents are less effective against OXA-48-producing strains [101, 102]. This geographical variation in resistance mechanisms necessitates a tailored therapeutic approach, highlighting the importance of rapid diagnostic tools to guide targeted therapy [103]. Future strategies should focus on developing agents capable of addressing both resistance and hypervirulence. Furthermore, optimizing combination regimens and investigating the role of adjunctive therapies, such as bacteriophage therapy, immunomodulators, and novel antimicrobials, could provide new hope in managing these challenging infections [104, 105]. To address these gaps, policymakers and researchers should prioritize investments in diagnostic advancements to enhance the detection of resistant pathogens and enable timely, precise interventions. Additionally, strengthening antimicrobial stewardship programs is essential to curb the emergence and spread of resistance, with an emphasis on optimizing antibiotic use and promoting adherence to evidence-based treatment guidelines.

This meta-analysis has several limitations. First, the small number of included studies reduces the robustness of the conclusions and limits the generalizability of the findings. Second, the eligible studies only provided unadjusted data, making it impossible to account for potential confounding factors that could influence the results. Third, considerable heterogeneity persisted across the included studies despite sensitivity analyses, likely due to differences in study design, population characteristics, and methodologies that could not be fully addressed. This heterogeneity complicates the synthesis of results and diminishes the precision of the pooled estimates. Furthermore, restricting the analysis to English-language articles introduces a language bias, potentially excluding valuable data from non-English publications and contributing to the observed heterogeneity. Lastly, we did not measure the prevalence of variants of carbapenem-resistance genes in hvKp strains. To overcome these limitations, future research should include a larger and more diverse set of high-quality studies with adjusted data to address confounding variables. Efforts to standardize study methodologies and population characteristics are essential to reduce heterogeneity. Additionally, expanding the analysis to include studies published in other languages would help mitigate language bias and enhance the comprehensiveness of the findings.

Conclusion

The current analysis highlights an alarming surge in carbapenem-resistant hvKp strains across most regions of the world, underscoring the urgent need for robust control and prevention strategies. These strategies should prioritize the implementation of advanced diagnostic methods and the establishment of comprehensive surveillance systems to monitor and curb the dissemination of these highly resistant pathogens. However, the uneven distribution of studies across regions presents a critical challenge, limiting the generalizability of findings and potentially overlooking resistance trends in underrepresented areas such as Africa and American regions. This gap emphasizes the importance of expanding research efforts and surveillance to ensure a more accurate global representation. Moreover, the considerable heterogeneity observed among the included studies complicates the synthesis of data and highlights the need for standardized methodologies and reporting practices in future research. Further investigations led by clinicians should focus on addressing these gaps, including exploring regional variations in resistance mechanisms, optimizing antimicrobial therapies, and identifying effective treatment regimens for carbapenem-resistant hvKp infections. By tackling these issues, the global research and medical communities can develop more targeted and equitable strategies to combat this growing public health threat.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

hvkp:

Hypervirulent Klebsiella pneumoniae

hypervirulent K. pneumoniae :

Hypervirulent Klebsiella pneumoniae

BSI:

Blood-stream infections

UTI:

Urinary tract infections

WHO:

World Health Organization

CLSI:

Clinical Laboratory Standard Institute guidelines

References

  1. Daikos GL, Markogiannakis A, Souli M, Tzouvelekis LS. Bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae: a clinical perspective. Expert Rev anti-infective Therapy. 2012;10(12):1393–404.

    Article  CAS  PubMed  Google Scholar 

  2. Chew KL, Lin RT, Teo JW. Klebsiella pneumoniae in Singapore: hypervirulent infections and the carbapenemase threat. Front Cell Infect Microbiol. 2017;7:515.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Podschun R, Ullmann U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev. 1998;11(4):589–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Russo TA, Marr CM. Hypervirulent klebsiella pneumoniae. Clin Microbiol Rev. 2019;32(3):00001–19. https://doiorg.publicaciones.saludcastillayleon.es/10.1128/cmr.

    Article  Google Scholar 

  5. Magill SS, O’Leary E, Janelle SJ, Thompson DL, Dumyati G, Nadle J, et al. Changes in prevalence of health care–associated infections in US hospitals. N Engl J Med. 2018;379(18):1732–44.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Chen Y-T, Lai Y-C, Tan M-C, Hsieh L-Y, Wang J-T, Shiau Y-R, et al. Prevalence and characteristics of pks genotoxin gene cluster-positive clinical Klebsiella pneumoniae isolates in Taiwan. Sci Rep. 2017;7(1):43120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Struve C, Roe CC, Stegger M, Stahlhut SG, Hansen DS, Engelthaler DM, et al. Mapping the evolution of Hypervirulent Klebsiella pneumoniae. mBio. 2015;6(4). https://doiorg.publicaciones.saludcastillayleon.es/10.1128/mbio.00630-15.

  8. Guo M, Gao B, Su J, Zeng Y, Cui Z, Liu H, et al. Phenotypic and genetic characterization of hypervirulent Klebsiella pneumoniae in patients with liver abscess and ventilator-associated pneumonia. BMC microbiology [Internet]. 2023 2023/11//; 23(1):338. Available from: http://europepmc.org/abstract/MED/37957579. https://biomedcentral-bmcmicrobiol.publicaciones.saludcastillayleon.es/counter/pdf/10.1186/s12866-023-03022-5. https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12866-023-03022-5. https://europepmc.org/articles/PMC10644596. https://europepmc.org/articles/PMC10644596?pdf=render

  9. Choby J, Howard-Anderson J, Weiss D. Hypervirulent Klebsiella pneumoniae–clinical and molecular perspectives. J Intern Med. 2020;287(3):283–300.

    Article  CAS  PubMed  Google Scholar 

  10. Chen J, Zhang H, Liao X. Hypervirulent Klebsiella pneumoniae. Infect Drug Resist. 2023:5243–9.

  11. Xu Q, Xie M, Liu X, Heng H, Wang H, Yang C, et al. Molecular mechanisms underlying the high mortality of hypervirulent Klebsiella pneumoniae and its effective therapy development. Signal Transduct Target Therapy. 2023;8(1):221.

    Article  Google Scholar 

  12. Shon AS, Bajwa RPS, Russo TA. Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: a new and dangerous breed. Virulence. 2013;4(2):107–18.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Nakamura-Silva R, Cerdeira L, Oliveira-Silva M, da Costa KRC, Sano E, Fuga B, et al. Multidrug-resistant Klebsiella pneumoniae: a retrospective study in Manaus, Brazil. Arch Microbiol. 2022;204(4):202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Du P, Liu C, Fan S, Baker S, Guo J. The role of plasmid and resistance gene acquisition in the emergence of ST23 multi-drug resistant, hypervirulent Klebsiella pneumoniae. Microbiol Spectr. 2022;10(2):e01929–21.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Bialek-Davenet S, Criscuolo A, Ailloud F, Passet V, Jones L, Delannoy-Vieillard A-S, et al. Genomic definition of hypervirulent and multidrug-resistant Klebsiella pneumoniae clonal groups. Emerg Infect Dis. 2014;20(11):1812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Vaez H, Sahebkar A, Khademi F. Carbapenem-resistant Klebsiella pneumoniae in Iran: a systematic review and meta-analysis. J Chemother. 2019;31(1):1–8.

    Article  PubMed  Google Scholar 

  17. Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW, Steward CD, et al. Novel carbapenem-hydrolyzing β-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother. 2001;45(4):1151–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Tuhamize B, Bazira J. Carbapenem-resistant Enterobacteriaceae in the livestock, humans and environmental samples around the globe: a systematic review and meta-analysis. Sci Rep. 2024;14(1):16333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Roque-Borda CA, da Silva PB, Rodrigues MC, Azevedo RB, Di Filippo L, Duarte JL, et al. Challenge in the discovery of new drugs: antimicrobial peptides against WHO-list of critical and high-priority bacteria. Pharmaceutics. 2021;13(6):773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tesfa T, Mitiku H, Edae M, Assefa N. Prevalence and incidence of carbapenem-resistant K. pneumoniae colonization: systematic review and meta-analysis. Syst Reviews. 2022;11(1):240.

    Article  Google Scholar 

  21. Karaiskos I, Giamarellou H. Multidrug-resistant and extensively drug-resistant Gram-negative pathogens: current and emerging therapeutic approaches. Expert Opin Pharmacother. 2014;15(10):1351–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Falagas ME, Tansarli GS, Karageorgopoulos DE, Vardakas KZ. Deaths attributable to carbapenem-resistant Enterobacteriaceae infections. Emerg Infect Dis. 2014;20(7):1170.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Nordmann P, Dortet L, Poirel L. Carbapenem resistance in Enterobacteriaceae: here is the storm! Trends Mol Med. 2012;18(5):263–72.

    Article  CAS  PubMed  Google Scholar 

  24. Satlin MJ, Chen L, Patel G, Gomez-Simmonds A, Weston G, Kim AC, et al. Multicenter clinical and molecular epidemiological analysis of bacteremia due to carbapenem-resistant Enterobacteriaceae (CRE) in the CRE epicenter of the United States. Antimicrob Agents Chemother. 2017;61(4):02349–16. https://doiorg.publicaciones.saludcastillayleon.es/10.1128/aac.

    Article  Google Scholar 

  25. Wang Q, Wang X, Wang J, Ouyang P, Jin C, Wang R, et al. Phenotypic and genotypic characterization of carbapenem-resistant Enterobacteriaceae: data from a longitudinal large-scale CRE study in China (2012–2016). Clin Infect Dis. 2018;67(suppl2):S196–205.

    Article  CAS  PubMed  Google Scholar 

  26. Pajand O, Darabi N, Arab M, Ghorbani R, Bameri Z, Ebrahimi A, et al. The emergence of the hypervirulent Klebsiella pneumoniae (hvKp) strains among circulating clonal complex 147 (CC147) harbouring bla NDM/OXA-48 carbapenemases in a tertiary care center of Iran. Ann Clin Microbiol Antimicrob. 2020;19:1–9.

    Article  Google Scholar 

  27. Lin Y-T, Cheng Y-H, Juan C-H, Wu P-F, Huang Y-W, Chou S-H, et al. High mortality among patients infected with hypervirulent antimicrobial-resistant capsular type K1 Klebsiella pneumoniae strains in Taiwan. Int J Antimicrob Agents. 2018;52(2):251–7.

    Article  CAS  PubMed  Google Scholar 

  28. Ahmed MAE-GE-S, Yang Y, Yang Y, Yan B, Chen G, Hassan RM, et al. Emergence of hypervirulent carbapenem-resistant Klebsiella pneumoniae coharboring a bla NDM-1-carrying virulent plasmid and a bla KPC-2-carrying plasmid in an Egyptian hospital. Msphere. 2021;6(3). https://doiorg.publicaciones.saludcastillayleon.es/10.1128/msphere. 00088– 21.

  29. Liu YM, Li BB, Zhang YY, Zhang W, Shen H, Li H, et al. Clinical and molecular characteristics of emerging hypervirulent Klebsiella pneumoniae bloodstream infections in mainland China. Antimicrob Agents Chemother. 2014;58(9):5379–85.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Shah RK, Ni ZH, Sun XY, Wang GQ, Li F. The determination and correlation of various virulence genes, ESBL, serum bactericidal effect and biofilm formation of clinical isolated classical and hypervirulent from respiratory tract infected patients. Pol J Microbiol. 2017;66(4):501–8.

    Article  PubMed  Google Scholar 

  31. Tabrizi AMA, Badmasti F, Shahcheraghi F, Azizi O. Outbreak of hypervirulent Klebsiella pneumoniae harbouring blaVIM-2 among mechanically-ventilated drug-poisoning patients with high mortality rate in Iran. J Global Antimicrob Resist. 2018;15:93–8.

    Article  Google Scholar 

  32. Lu Y, Feng Y, McNally A, Zong Z. The occurence of colistin-resistant hypervirulent Klebsiella pneumoniae in China. Front Microbiol. 2018;9:2568.

    Article  PubMed  PubMed Central  Google Scholar 

  33. El-Mahdy R, El-Kannishy G, Salama H. Hypervirulent Klebsiella pneumoniae as a hospital-acquired pathogen in the intensive care unit in Mansoura, Egypt. Germs. 2018;8(3):140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Remya P, Shanthi M, Sekar U. Occurrence and characterization of hyperviscous K1 and K2 serotype in Klebsiella pneumoniae. J Lab Physicians. 2018;10:283–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Li J, Ren J, Wang W, Wang G, Gu G, Wu X, et al. Risk factors and clinical outcomes of hypervirulent Klebsiella pneumoniae induced bloodstream infections. Eur J Clin Microbiol Infect Dis. 2018;37:679–89.

    Article  PubMed  Google Scholar 

  36. Liu C, Guo J. Characteristics of ventilator-associated pneumonia due to hypervirulent Klebsiella pneumoniae genotype in genetic background for the elderly in two tertiary hospitals in China. Antimicrob Resist Infect Control. 2018;7:1–8.

    Article  Google Scholar 

  37. Liu Z, Gu Y, Li X, Liu Y, Ye Y, Guan S, et al. Identification and characterization of NDM-1-producing hypervirulent (hypermucoviscous) Klebsiella pneumoniae in China. Annals Lab Med. 2019;39(2):167–75.

    Article  CAS  Google Scholar 

  38. Hao Z, Duan J, Liu L, Shen X, Yu J, Guo Y, et al. Prevalence of community-acquired, hypervirulent Klebsiella pneumoniae isolates in Wenzhou, China. Microb Drug Resist. 2020;26(1):21–7.

    Article  CAS  PubMed  Google Scholar 

  39. Rastegar S, Moradi M, Kalantar-Neyestanaki D, Hosseini-Nave H. Virulence factors, capsular serotypes and antimicrobial resistance of hypervirulent Klebsiella pneumoniae and classical Klebsiella pneumoniae in Southeast Iran. Infect Chemother. 2019;51.

  40. Li J, Huang Z-Y, Yu T, Tao X-Y, Hu Y-M, Wang H-C, et al. Isolation and characterization of a sequence type 25 carbapenem-resistant hypervirulent Klebsiella pneumoniae from the mid-south region of China. BMC Microbiol. 2019;19:1–10.

    Article  Google Scholar 

  41. Liu C, Guo J. Hypervirulent Klebsiella pneumoniae (hypermucoviscous and aerobactin positive) infection over 6 years in the elderly in China: antimicrobial resistance patterns, molecular epidemiology and risk factor. Ann Clin Microbiol Antimicrob. 2019;18:1–11.

    Article  Google Scholar 

  42. Lin Z-w, Zheng J-x, Bai B, Xu G-j, Lin F-j, Chen Z, et al. Characteristics of hypervirulent Klebsiella pneumoniae: does low expression of rmpA contribute to the absence of hypervirulence? Front Microbiol. 2020;11:436.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Taraghian A, Nasr Esfahani B, Moghim S, Fazeli H. Characterization of hypervirulent extended-spectrum β-lactamase-producing Klebsiella pneumoniae among urinary tract infections: the first report from Iran. Infect Drug Resist. 2020:3103–11.

  44. Tang Y, Liu H, Zhao J, Yi M, Yuan Y, Xia Y. Clinical and microbiological prognostic factors of in-hospital mortality caused by hypervirulent Klebsiella pneumoniae infections: a retrospective study in a tertiary hospital in Southwestern China. Infect Drug Resist. 2020:3739–49.

  45. Vasilyev I, Nikolaeva I, Siniagina M, Kharchenko A, Shaikhieva G. Multidrug-resistant hypervirulent Klebsiella pneumoniae found persisting silently in infant gut microbiota. Int J Microbiol. 2020;2020(1):4054393.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Albasha AM, Osman EH, Abd-Alhalim S, Alshaib EF, Al-Hassan L, Altayb HN. Detection of several carbapenems resistant and virulence genes in classical and hyper-virulent strains of Klebsiella pneumoniae isolated from hospitalized neonates and adults in Khartoum. BMC Res Notes. 2020;13:1–7.

    Article  Google Scholar 

  47. Kong Y, Sun Q, Chen H, Draz MS, Xie X, Zhang J, et al. Transmission dynamics of carbapenem-resistant klebsiella pneumoniae sequence type 11 strains carrying capsular loci KL64 and rmpA/rmpA2 genes. Front Microbiol. 2021;12:736896.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Shankar C, Basu S, Lal B, Shanmugam S, Vasudevan K, Mathur P, et al. Aerobactin seems to be a promising marker compared with unstable RmpA2 for the identification of hypervirulent carbapenem-resistant Klebsiella pneumoniae: in silico and in vitro evidence. Front Cell Infect Microbiol. 2021;11:709681.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Shao C, Jin Y, Wang W, Jiang M, Zhao S. An outbreak of carbapenem-resistant Klebsiella pneumoniae of K57 capsular serotype in an emergency intensive care unit of a teaching hospital in China. Front Public Health. 2021;9:724212.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Sanikhani R, Moeinirad M, Solgi H, Hadadi A, Shahcheraghi F, Badmasti F. The face of hypervirulent Klebsiella pneumoniae isolated from clinical samples of two Iranian teaching hospitals. Ann Clin Microbiol Antimicrob. 2021;20(1):58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Shankar C, Vasudevan K, Jacob JJ, Baker S, Isaac BJ, Neeravi AR, et al. Hybrid plasmids encoding antimicrobial resistance and virulence traits among hypervirulent Klebsiella pneumoniae ST2096 in India. Front Cell Infect Microbiol. 2022;12:875116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ouyang P, Jiang B, Peng N, Wang J, Cai L, Wu Y, et al. Characteristics of ST11 KPC-2‐producing carbapenem‐resistant hypervirulent Klebsiella pneumoniae causing nosocomial infection in a Chinese hospital. J Clin Lab Anal. 2022;36(6):e24476.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Liu S, Ding Y, Xu Y, Li Z, Zeng Z, Liu J. An outbreak of extensively drug-resistant and hypervirulent Klebsiella pneumoniae in an intensive care unit of a teaching hospital in Southwest China. Front Cell Infect Microbiol. 2022;12:979219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Saki M, Amin M, Savari M, Hashemzadeh M, Seyedian SS. Beta-lactamase determinants and molecular typing of carbapenem-resistant classic and hypervirulent Klebsiella pneumoniae clinical isolates from southwest of Iran. Front Microbiol. 2022;13:1029686.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Wei T, Zou C, Qin J, Tao J, Yan L, Wang J, et al. Emergence of hypervirulent ST11-K64 Klebsiella pneumoniae poses a serious clinical threat in older patients. Front Public Health. 2022;10:765624.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Shoja S, Ansari M, Bengar S, Rafiei A, Shamseddin J, Alizade H. Bacteriological characteristics of hypervirulent Klebsiella pneumoniae rmpA gene (hvKp-rmpA)-harboring strains in the south of Iran. Iran J Microbiol. 2022;14(4):475.

    PubMed  PubMed Central  Google Scholar 

  57. Liu C, Du P, Yang P, Yi J, Lu M, Shen N. Emergence of extensively drug-resistant and hypervirulent KL2-ST65 Klebsiella pneumoniae harboring bla KPC-3 in Beijing, China. Microbiol Spectr. 2022;10(6):e03044–22.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Raj S, Sharma T, Pradhan D, Tyagi S, Gautam H, Singh H, et al. Comparative analysis of clinical and genomic characteristics of hypervirulent Klebsiella pneumoniae from hospital and community settings: experience from a tertiary healthcare center in India. Microbiol Spectr. 2022;10(5):e00376–22.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Li J, Li Y, Tang M, Xia F, Min C, Hu Y, et al. Distribution, characterization, and antibiotic resistance of hypervirulent Klebsiella pneumoniae isolates in a Chinese population with asymptomatic bacteriuria. BMC Microbiol. 2022;22(1):29.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Osama DM, Zaki BM, Khalaf WS, Mohamed MYA, Tawfick MM, Amin HM. Occurrence and molecular study of hypermucoviscous/hypervirulence trait in gut commensal K. pneumoniae from healthy subjects. Microorganisms. 2023;11(3):704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Mukherjee S, Bhadury P, Mitra S, Naha S, Saha B, Dutta S, et al. Hypervirulent Klebsiella pneumoniae causing neonatal bloodstream infections: emergence of NDM-1-producing hypervirulent ST11-K2 and ST15-K54 strains possessing pLVPK-associated markers. Microbiol Spectr. 2023;11(2):e04121–22.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Dan B, Dai H, Zhou D, Tong H, Zhu M. Relationship between drug resistance characteristics and biofilm formation in Klebsiella pneumoniae strains. Infect Drug Resist. 2023:985–98.

  63. Tang M, Li J, Liu Z, Xia F, Min C, Hu Y, et al. Clonal transmission of polymyxin B-resistant hypervirulent Klebsiella pneumoniae isolates coharboring bla NDM-1 and bla KPC-2 in a tertiary hospital in China. BMC Microbiol. 2023;23(1):64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Pei N, Liu X, Jian Z, Yan Q, Liu Q, Kristiansen K, et al. Genome sequence and genomic analysis of liver abscess caused by hypervirulent Klebsiella pneumoniae. 3 Biotech. 2023;13(3):76.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Xu L, Sun X, Ma X. Systematic review and meta-analysis of mortality of patients infected with carbapenem-resistant Klebsiella pneumoniae. Ann Clin Microbiol Antimicrob. 2017;16:1–12.

    Article  Google Scholar 

  66. Trecarichi EM, Tumbarello M. Therapeutic options for carbapenem-resistant Enterobacteriaceae infections. Virulence. 2017;8(4):470–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Zeng M, Xia J, Zong Z, Shi Y, Ni Y, Hu F, et al. Guidelines for the diagnosis, treatment, prevention and control of infections caused by carbapenem-resistant gram-negative bacilli. J Microbiol Immunol Infect. 2023;56(4):653–71.

    Article  CAS  PubMed  Google Scholar 

  68. Bhavnani SM, Ambrose PG, Craig WA, Dudley MN, Jones RN. Outcomes evaluation of patients with ESBL-and non–ESBL-producing Escherichia coli and Klebsiella species as defined by CLSI reference methods: report from the SENTRY Antimicrobial Surveillance Program. Diagn Microbiol Infect Dis. 2006;54(3):231–6.

    Article  PubMed  Google Scholar 

  69. Kim B-N, Woo J-H, Kim M-N, Ryu J, Kim Y. Clinical implications of extended-spectrum β-lactamase-producing Klebsiella pneumoniae bacteraemia. J Hosp Infect. 2002;52(2):99–106.

    Article  PubMed  Google Scholar 

  70. Mouloudi E, Protonotariou E, Zagorianou A, Iosifidis E, Karapanagiotou A, Giasnetsova T, et al. Bloodstream infections caused by metallo-β-lactamase/Klebsiella pneumoniae carbapenemase–producing K. pneumoniae among intensive care unit patients in Greece: risk factors for infection and impact of type of resistance on outcomes. Infect Control Hosp Epidemiol. 2010;31(12):1250–6.

    Article  PubMed  Google Scholar 

  71. Vardakas KZ, Rafailidis PI, Konstantelias AA, Falagas ME. Predictors of mortality in patients with infections due to multi-drug resistant Gram negative bacteria: the study, the patient, the bug or the drug? J Infect. 2013;66(5):401–14.

    Article  PubMed  Google Scholar 

  72. Beig M, Majidzadeh N, Asforooshani MK, Rezaie N, Abed S, Khiavi EHG, et al. Antibiotic resistance rates in hypervirulent Klebsiella pneumoniae strains: a systematic review and meta-analysis. J Global Antimicrob Resist. 2024.

  73. Poirel L, Potron A, Nordmann P. OXA-48-like carbapenemases: the phantom menace. J Antimicrob Chemother. 2012;67(7):1597–606.

    Article  CAS  PubMed  Google Scholar 

  74. Meletis G. Carbapenem resistance: overview of the problem and future perspectives. Therapeutic Adv Infect Disease. 2016;3(1):15–21.

    Article  CAS  Google Scholar 

  75. Papagiannitsis CC, Di Pilato V, Giani T, Giakkoupi P, Riccobono E, Landini G, et al. Characterization of KPC-encoding plasmids from two endemic settings, Greece and Italy. J Antimicrob Chemother. 2016;71(10):2824–30.

    Article  CAS  PubMed  Google Scholar 

  76. Martínez-Martínez L, González-López JJ. Carbapenemases in Enterobacteriaceae: types and molecular epidemiology. Enferm Infecc Microbiol Clin. 2014;32:4–9.

    Article  PubMed  Google Scholar 

  77. Ma J, Song X, Li M, Yu Z, Cheng W, Yu Z, et al. Global spread of carbapenem-resistant Enterobacteriaceae: epidemiological features, resistance mechanisms, detection and therapy. Microbiol Res. 2023;266:127249.

    Article  CAS  PubMed  Google Scholar 

  78. Logan LK, Weinstein RA. The epidemiology of carbapenem-resistant Enterobacteriaceae: the impact and evolution of a global menace. J Infect Dis. 2017;215(suppl1):S28–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Codjoe FS, Donkor ES. Carbapenem resistance: a review. Med Sci. 2017;6(1):1.

    Google Scholar 

  80. Castanheira M, Huband MD, Mendes RE, Flamm RK. Meropenem-Vaborbactam tested against contemporary Gram-negative isolates collected worldwide during 2014, including carbapenem-resistant, KPC-producing, multidrug-resistant, and extensively drug-resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2017;61(9). https://doiorg.publicaciones.saludcastillayleon.es/10.1128/aac.00567-17.

  81. Chen L, Mathema B, Chavda KD, DeLeo FR, Bonomo RA, Kreiswirth BN. Carbapenemase-producing Klebsiella pneumoniae: molecular and genetic decoding. Trends Microbiol. 2014;22(12):686–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Villegas MV, Lolans K, Correa A, Kattan JN, Lopez JA, Quinn JP. First identification of Pseudomonas aeruginosa isolates producing a KPC-type carbapenem-hydrolyzing β-lactamase. Antimicrob Agents Chemother. 2007;51(4):1553–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Ling ML, Tee YM, Tan SG, Amin IM, How KB, Tan KY, et al. Risk factors for acquisition of carbapenem resistant Enterobacteriaceae in an acute tertiary care hospital in Singapore. Antimicrob Resist Infect Control. 2015;4:1–7.

    Article  Google Scholar 

  84. Yamamoto N, Asada R, Kawahara R, Hagiya H, Akeda Y, Shanmugakani R, et al. Prevalence of, and risk factors for, carriage of carbapenem-resistant Enterobacteriaceae among hospitalized patients in Japan. J Hosp Infect. 2017;97(3):212–7.

    Article  CAS  PubMed  Google Scholar 

  85. Gaibani P, Galea A, Fagioni M, Ambretti S, Sambri V, Landini MP. Evaluation of matrix-assisted laser desorption ionization–time of flight mass spectrometry for identification of KPC-producing Klebsiella pneumoniae. J Clin Microbiol. 2016;54(10):2609–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Boyd SE, Holmes A, Peck R, Livermore DM, Hope W. OXA-48-like β-lactamases: global epidemiology, treatment options, and development pipeline. Antimicrob Agents Chemother. 2022;66(8):e00216–22.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Lee Y-L, Wang W-Y, Ko W-C, Hsueh P-R. Global epidemiology and antimicrobial resistance of Enterobacterales harbouring genes encoding OXA-48-like carbapenemases: insights from the results of the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme 2018–2021. J Antimicrob Chemother. 2024:dkae140.

  88. Mathers AJ, Peirano G, Pitout JD. The role of epidemic resistance plasmids and international high-risk clones in the spread of multidrug-resistant Enterobacteriaceae. Clin Microbiol Rev. 2015;28(3):565–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Netikul T, Kiratisin P. Genetic characterization of carbapenem-resistant Enterobacteriaceae and the spread of carbapenem-resistant Klebsiella pneumonia ST340 at a university hospital in Thailand. PLoS ONE. 2015;10(9):e0139116.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Villa L, Feudi C, Fortini D, Brisse S, Passet V, Bonura C, et al. Diversity, virulence, and antimicrobial resistance of the KPC-producing Klebsiella pneumoniae ST307 clone. Microb Genomics. 2017;3(4):e000110.

    Article  Google Scholar 

  91. Nordmann P, Naas T, Poirel L. Global spread of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis. 2011;17(10):1791.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Manenzhe RI, Zar HJ, Nicol MP, Kaba M. The spread of carbapenemase-producing bacteria in Africa: a systematic review. J Antimicrob Chemother. 2015;70(1):23–40.

    Article  CAS  PubMed  Google Scholar 

  93. Shibl A, Al-Agamy M, Memish Z, Senok A, Khader SA, Assiri A. The emergence of OXA-48- and NDM-1-positive Klebsiella pneumoniae in Riyadh, Saudi Arabia. Int J Infect Diseases: IJID: Official Publication Int Soc Infect Dis. 2013;17(12):e1130–3.

    CAS  Google Scholar 

  94. Xu ZQ, Flavin MT, Flavin J. Combating multidrug-resistant Gram-negative bacterial infections. Expert Opin Investig Drugs. 2014;23(2):163–82.

    Article  CAS  PubMed  Google Scholar 

  95. Di Pilato V, Errico G, Monaco M, Giani T, Del Grosso M, Antonelli A, et al. The changing epidemiology of carbapenemase-producing Klebsiella pneumoniae in Italy: toward polyclonal evolution with emergence of high-risk lineages. J Antimicrob Chemother. 2021;76(2):355–61.

    Article  CAS  PubMed  Google Scholar 

  96. Yamamoto N, Kawahara R, Akeda Y, Shanmugakani RK, Yoshida H, Hagiya H, et al. Development of selective medium for IMP-type carbapenemase-producing Enterobacteriaceae in stool specimens. BMC Infect Dis. 2017;17(1):229.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Serban D, Popa Cherecheanu A, Dascalu AM, Socea B, Vancea G, Stana D, et al. Hypervirulent Klebsiella pneumoniae endogenous endophthalmitis—a global emerging disease. Life. 2021;11(7):676.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Di Pilato V, Pollini S, Miriagou V, Rossolini GM, D’Andrea MM. Carbapenem-resistant Klebsiella pneumoniae: the role of plasmids in emergence, dissemination, and evolution of a major clinical challenge. Expert Rev Anti Infect Ther. 2024;22(1–3):25–43.

    Article  PubMed  Google Scholar 

  99. Chen J, Zhang H, Liao X. Hypervirulent Klebsiella pneumoniae/i. Infection and drug resistance [Internet]. 2023;16:5243–9. Available from: http://europepmc.org/abstract/MED/37589017 https://www.dovepress.com/getfile.php?fileID=91918 https://doiorg.publicaciones.saludcastillayleon.es/10.2147/IDR.S418523 https://europepmc.org/articles/PMC10426436 https://europepmc.org/articles/PMC10426436?pdf=render

  100. Marchaim D, Chopra T, Pogue JM, Perez F, Hujer AM, Rudin S, et al. Outbreak of Colistin-Resistant, Carbapenem-Resistant < i > Klebsiella pneumoniae in Metropolitan Detroit, Michigan. Antimicrob Agents Chemother. 2011;55(2):593–9.

    Article  CAS  PubMed  Google Scholar 

  101. Lupia T, Corcione S, Shbaklo N, Montrucchio G, De Benedetto I, Fornari V, et al. Meropenem/Vaborbactam and Cefiderocol as Combination or Monotherapy to treat Multi-drug resistant gram-negative infections: a Regional Cross-sectional Survey from Piedmont Infectious Disease Unit Network (PIDUN). J Funct Biomaterials. 2022;13(4):174.

    Article  CAS  Google Scholar 

  102. Zhao J, Pu D, Li Z, Liu X, Zhang Y, Wu Y, et al. <i > in vitro activity of cefiderocol, a siderophore cephalosporin, against carbapenem-resistant hypervirulent < i > Klebsiella pneumoniae in China</i >. Antimicrob Agents Chemother. 2023;67(12):e00735–23.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Bouzid D, Zanella MC, Kerneis S, Visseaux B, May L, Schrenzel J, et al. Rapid diagnostic tests for infectious diseases in the emergency department. Clin Microbiol Infect. 2021;27(2):182–91.

    Article  CAS  PubMed  Google Scholar 

  104. Souza EBd, Pinto AR, Fongaro G. Bacteriophages as potential clinical Immune modulators. Microorganisms. 2023;11(9):2222.

    Article  Google Scholar 

  105. Streicher LM. Exploring the future of infectious disease treatment in a post-antibiotic era: a comparative review of alternative therapeutics. J Global Antimicrob Resist. 2021;24:285–95.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to the authors of the included studies and the enrolled patients.

Funding

There is no financial support for this manuscript.

Author information

Authors and Affiliations

  1. Paramedical Faculty of Iranshahr, Iranshahr, Iran

    Motahareh Sabaghi Qala Nou

  2. Department of Surgery, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

    Zahra Amirian

  3. Department of Pediatrics, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran

    Fatemeh Dehghani

  4. Department of General Surgery, Imam Ali Hospital, Zahedan University of Medical Sciences, Zahedan, Iran

    Amir-Kazem Vejdan

  5. Critical Care Nursing, Department of Nursing, School of Nursing and Midwifery, Iranshahr University of Medical Sciences, Iranshahr, Iran

    Roghayeh Rooin

  6. Medical Surgical Nursing, Department of Nursing, School of Nursing and Midwifery, Iranshahr University of Medical Sciences, Iranshahr, Iran

    Sadegh Dehghanmehr

Authors
  1. Motahareh Sabaghi Qala Nou
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Zahra Amirian
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Fatemeh Dehghani
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Amir-Kazem Vejdan
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Roghayeh Rooin
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Sadegh Dehghanmehr
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

Study conception and design: MQN. Acquisition of data: MQN, ZA, and FD. Statistical analysis: MK. Drafting of the manuscript: FD and ZA. Critical revision of the manuscript: SD and AKV. Supervision: SD and RR. All authors contributed to the article and approved the submitted version. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Sadegh Dehghanmehr.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qala Nou, M.S., Amirian, Z., Dehghani, F. et al. Systematic review and meta-analysis on the carbapenem-resistant hypervirulent Klebsiella pneumoniae isolates. BMC Pharmacol Toxicol 26, 25 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s40360-025-00857-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s40360-025-00857-8

Keywords

BMC Pharmacology and Toxicology

ISSN: 2050-6511

Contact us