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Review

Global Epidemiology and Antimicrobial Resistance of Klebsiella Pneumoniae Carbapenemase (KPC)-Producing Gram-Negative Clinical Isolates: A Review

by
Matthew E. Falagas
1,2,3,*,
Christina-Maria Asimotou
1,
Maria Zidrou
1,
Dimitrios S. Kontogiannis
1 and
Charalampos Filippou
2
1
Alfa Institute of Biomedical Sciences, 9 Neapoleos Street, Marousi, 151 23 Athens, Greece
2
School of Medicine, European University Cyprus, 6 Diogenous Str., Egkomi, Nicosia 2404, Cyprus
3
Department of Medicine, Tufts University School of Medicine, Boston, 145 Harrison Ave, Boston, MA 02111, USA
*
Author to whom correspondence should be addressed.
Microorganisms 2025, 13(7), 1697; https://doi.org/10.3390/microorganisms13071697 (registering DOI)
Submission received: 30 May 2025 / Revised: 27 June 2025 / Accepted: 17 July 2025 / Published: 19 July 2025
(This article belongs to the Special Issue ß-Lactamases, 3rd Edition)
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Abstract

Klebsiella pneumoniae carbapenemases (KPCs) are a group of class A β-lactamases of Gram-negative bacteria leading to difficult-to-treat infections. We evaluated the global epidemiology of KPC-producing Gram-negative clinical isolates. A systematic search of six databases (Cochrane Library, Embase, Google Scholar, PubMed, Scopus, and Web of Science) was conducted. Extracted data were tabulated and evaluated. After screening 1993 articles, 119 were included in the study. The included studies originated from Asia (n = 49), Europe (n = 29), North America (n = 14), South America (n = 11), and Africa (n = 3); 13 studies were multicontinental. The most commonly reported KPC-producing species were Klebsiella pneumoniae (96 studies) and Escherichia coli (52 studies), followed by Enterobacter cloacae (31), Citrobacter spp. (24), Klebsiella oxytoca (23), Serratia spp. (15), Enterobacter spp. (15), Acinetobacter baumannii complex (13), Providencia spp. (11), Morganella spp. (11), Klebsiella aerogenes (9), Pseudomonas aeruginosa (8), Raoultella spp. (8), Proteus spp. (8), and Enterobacter aerogenes (6). Among the studies with specific blaKPC gene detection, 52/57 (91%) reported the isolation of blaKPC-2 and 26/57 (46%) reported blaKPC-3. The antimicrobial resistance of the studied KPC-producing isolates was the lowest for ceftazidime–avibactam (0–4%). Resistance to polymyxins, tigecycline, and trimethoprim–sulfamethoxazole in the evaluated studies was 4–80%, 0–73%, and 5.6–100%, respectively. Conclusions: The findings presented in this work indicate that KPC-producing Gram-negative bacteria have spread globally across all continents. Implementing proper infection control measures, antimicrobial stewardship programs, and enhanced surveillance is crucial.

1. Introduction

Antimicrobial resistance increases the mortality of patients with various types of infections [1]. If no appropriate measures are taken to combat this problem, deaths due to infections with antimicrobial resistance will continue to rise globally in the coming years [2,3]. In addition, antimicrobial resistance considerably increases the length of hospital stay and healthcare-associated costs for all countries [2].
One of the basic microbial mechanisms contributing to the development of antimicrobial resistance is the production of β-lactamases [4]. Beta-lactamases hydrolyze the β-lactam ring of antibiotics. They are grouped as class A, B, C, and D based on the Ambler classification [4,5]. Classes A, C, and D use serine at their active site, whereas class B enzymes (metallo-β-lactamases) require zinc. A subset of class A β-lactamases, specifically Klebsiella pneumoniae carbapenemase (KPC), is significant due to its global dissemination and the increased incidence of opportunistic infections in immunocompromised patients caused by bacteria, mainly Klebsiella pneumoniae (K. pneumoniae) that harbor KPC [4,6]. The worldwide spread of KPC has been linked to the dissemination of a main clone of K. pneumoniae [sequence type (ST) 258] and a single-locus variant of ST258, specifically ST512 that is prevalent in Italy, Colombia, and Israel [7,8,9]. In Asia, most specifically in China, another variant of ST258, specifically ST11, is mostly reported among blaKPC-harboring K. pneumoniae isolates [8,10]. It is ultimately known that ST258 and its variants are the principal clones accounting for the majority of KPC-producing K. pneumoniae globally [9]. ST307 is another globally spread clone, which raises concerns among the scientific community [11]. This clone has been found in Greece, Italy, and Spain. In addition, the clones ST340 and ST437 have caused frequent clinical outbreaks in Brazil and Greece [9]. Other successfully KPC-producing pathogens nowadays include Enterobacterales, such as Escherichia coli, with the clone ST131 being the most dominant worldwide along with the ST258 K. pneumoniae [12]. Another E. coli clone, ST410, has been rising in China [12]. Other Enterobacterales that produce KPCs are Klebsiella oxytoca, Enterobacter spp., and Serratia spp., as well as lactose-non-fermenting Gram-negative bacilli, including Pseudomonas spp., and Acinetobacter baumannii [13].
Infections caused by KPC-producing pathogens are associated with considerable morbidity and mortality [14]. Two factors contribute to this result. First, a significant proportion of infections due to KPC-producing pathogens occur in patients in healthcare settings who already have considerable comorbidities. Second, the therapeutic options for patients with such infections are limited [15]. Subsequently, the outcome is often unfavorable, particularly for patients with severe infections and significant comorbidities.
Previous studies have evaluated the distribution of carbapenemase-producing isolates [16,17,18,19]; however, limited data exist regarding the global epidemiology of KPC-producing Gram-negative pathogens, particularly regarding recent developments. The scope of this review is to address the information gap by gathering and evaluating all relevant and recent bibliographical data on this topic.

2. Methods

2.1. Objectives

This review evaluated the global epidemiology of KPC-producing Gram-negative bacteria and their resistance to various antimicrobial agents.

2.2. Eligibility Criteria

Studies that included Gram-negative clinical pathogens in their analyses were eligible for inclusion in this study. There were no limitations regarding the language, date, geographical location, publication journal, age, gender, and patient settings (hospitalized or not). Reports from the gray literature, such as conference abstracts, were excluded from further analysis in the screening process. Studies that included fewer than five clinical isolates were excluded.
Only studies confirming the presence of KPC genes with the polymerase chain reaction (PCR) method and antimicrobial resistance based on the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations were eligible for inclusion.

2.3. Search Strategy

On 20 February 2025, specific search strings using combinations of the terms “Klebsiella pneumoniae carbapenemase”, “KPC-producing”, “carbapenemase”, “prevalence”, Gram-negative”, “worldwide”, and “global” were applied in six resources (Cochrane Library, Web of Science, Embase, PubMed, Google Scholar, and Scopus) for the identification of relevant articles. Supplementary Table S1 presents the detailed search strings used.

2.4. Selection Process

Identified studies from the six resources were deduplicated using the SR Accelerator software. Two reviewers (among CMA, MZ, and DSK) screened these studies, first by title and abstract, and then by full text. Discrepancies between the reviewers’ findings were resolved in meetings with a senior author (MEF). All the retrieved articles deemed relevant were included in the analysis. Additionally, one reviewer (CMA, MZ, or DSK) examined the references of pertinent review articles related to the topic to identify any additional reports that might have been missed.

2.5. Data Extraction

Two reviewers (among CMA, MZ, and DSK) tabulated the following data in a spreadsheet: first author, year, continent, country, period of isolation, population characteristics (age, hospital ward), samples used for bacterial detection, species of isolates, and gene types of KPC. The proportion of KPC-producing pathogens was evaluated according to the available data of each article and expressed in fractions and percentages. Discrepancies were resolved by consensus with a senior author (MEF). When reported, the proportion of KPC-producing bacteria resistant to various antimicrobial agents was recorded (as a percentage).

3. Results

3.1. Selection of Relevant Articles

Figure 1 presents the identification, screening, and inclusion of articles in the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram. After removing 3148 duplicates, 1993 articles remained for screening, and, finally, 119 articles were eligible for inclusion in this review.

3.2. Results of Individual Studies

In Table 1, a total of 119 studies were included. Of these, 103 were classified as observational or clinical outbreak studies, including 32 that were limited in scope (small sample size, studies conducted at a single institution, or restricted timeframe). Additionally, 12 studies were categorized as multi-country surveillance and 4 were categorized as systematic surveillance studies. These classifications highlight the methodological diversity in the reporting and monitoring of Klebsiella pneumoniae carbapenemase (KPC) detection globally. The data on the 119 included studies (first author, year, country, continent, period of isolation), the species identified, and the proportion of the detected blaKPC genes via PCR are presented. A total of 49 studies originated from Asia (25 from China [20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44], 4 from Israel [45,46,47,48], 3 from Nepal [49,50,51], 3 from Singapore [52,53,54], 3 from Taiwan [55,56,57], 2 from South Korea [58,59], and 2 from Vietnam [60,61]), while 1 study came from each of the following countries: Saudi Arabia [62], India [63], Iran [64], Iraq [64], Venezuela [65], Turkey [66], and Russia [67]. A total of 29 studies were from Europe (4 from Greece [68,69,70,71], 4 from Italy [72,73,74,75], 3 from Poland [76,77,78], and 2 from Hungary [79,80]), while 1 study from each of the following countries: Austria [81], Belgium [82], Bulgaria [83], Denmark [84], Finland [85], France [86], Ireland [87], the Netherlands [88], Norway [89], Romania [90], and Spain [91], as well as 5 including multiple European countries [11,92,93,94,95]). A total of 14 studies were from North America (12 from the USA [96,97,98,99,100,101,102,103,104,105,106,107] and 2 from Canada [108,109]). A total of 11 studies were from South America (6 from Brazil [110,111,112,113,114,115], from 2 Colombia [116,117], and 1 from each of the following countries: Argentina [118], Chile [119], and Ecuador [120]). Three studies were from Africa (one each from Egypt [121], Nigeria [122], and Uganda [123]). Additionally, four global surveillance studies [124,125,126,127] and nine studies spanning multiple continents [128,129,130,131,132,133,134,135,136] were included.
The isolation period of strains ranged from 1997 [96] to 2024 [73,74] across the included studies. Among the 83 out of the 118 studies (70.3%) that reported sample sources, bloodstream isolates were most common (72 studies), followed by urine (58), respiratory tract (33), sputum (27), wound swabs (25), rectal swabs (17), skin or soft tissue (18), catheter-related (13), abdominal (14), bile (9), pus (8), and ascitic fluid (5).
In terms of isolated organisms, K. pneumoniae was reported in 96 studies, Escherichia coli in 52, Enterobacter cloacae in 31, Citrobacter spp. in 24, Klebsiella oxytoca in 23, Serratia spp. in 15, Enterobacter spp. in 15, Acinetobacter baumannii complex in 13, Providencia spp. in 11, Morganella spp. in 11, Klebsiella aerogenes in 9, Pseudomonas aeruginosa in 8, Raoultella spp. in 8, Proteus spp. in 8, and Enterobacter aerogenes in 6 studies. A few studies also isolated other genera (e.g., Salmonella spp., Cronobacter sakazakii, Achromobacter denitrificans, Klebsiella quasipneumoniae, Klebsiella variicola, Pantoea spp., Kluyvera spp., Pluralibacter gergoviae, Hafnia alvei).
Fifty-eight studies included data on the detection of specific blaKPC genes. The majority [53/58 (91%)] reported the isolation of blaKPC-2. About half [27/58 (47%)] reported the isolation of blaKPC-3. Other blaKPC genes were also detected, such as blaKPC-4, blaKPC-6, blaKPC-8, blaKPC-9, blaKPC-11, blaKPC-12, blaKPC-17, blaKPC-18, blaKPC-20, blaKPC-29, blaKPC-30, blaKPC-31, blaKPC-36, blaKPC-46, and blaKPC-66.
In Table 2 and the Supplementary Table S2, the antimicrobial resistance of KPC-producing isolates is presented. According to the included studies that provided relevant data, resistance was lowest for polymyxins (colistin or polymyxin B) (ranging from 4 to 80% across studies) and for ceftazidime–avibactam (ranging from 0 to 4%). Some studies also reported relatively low resistance rates for tigecycline (ranging from 0 to 73%) and for trimethoprim–sulfamethoxazole in some others (ranging from 5.6 to 100%). However, antimicrobial resistance is high for other classes of antimicrobial agents, including third-generation cephalosporins (cefotaxime, ceftriaxone, and ceftazidime), cefepime (a fourth-generation cephalosporin), piperacillin–tazobactam (an antipseudomonal antimicrobial agent), carbapenems (imipenem, meropenem, and ertapenem), and fluoroquinolones (ciprofloxacin and levofloxacin), reaching up to 100% (Table 2 and Supplementary Table S2).

4. Discussion

The results of our study demonstrate the widespread occurrence of infections caused by KPC-producing pathogens in most parts of the world. The first published case of infection due to a KPC-producing organism was from the US in 2001, describing the molecular characterization of KPC-1, a novel group 2f, class A, carbapenem-hydrolyzing β-lactamase, from a pathogen isolated from a patient in 1996 [138,139]. Infections due to KPC-producing pathogens have now been disseminated globally.
Infection control deficiencies and pressure for the emergence of antimicrobial resistance, combined with frequent international travel, have led to this new global public health problem [140]. Infections by KPC-producing pathogens are now common in Europe, Asia [including India and China, frequently in conjunction with the metallo-β-lactamase (MBL) antimicrobial resistance mechanism, especially the presence of the New Delhi metallo-β-lactamase (NDM)], North America, South America (especially in Brazil and Colombia), the Middle East (frequently in conjunction with the OXA-48 antimicrobial resistance mechanism), and Africa. There are at least 150 blaKPC gene variants, with the blaKPC-2 gene being the most prevalent in several countries [141,142].
Infections caused by KPC-producing bacteria have already become endemic in most areas of the world, including Europe (especially Poland and southern Europe countries, such as Italy, Greece, and Spain), Latin America, the US, and Asia [143]. In addition, there have already been sporadic cases of such infections in many additional countries worldwide, including European countries (such as France, Germany, the UK, Ireland, Belgium, the Netherlands, Hungary, Finland, and Sweden), Asia (including South Korea), and Oceania (Australia) [143]. Also, there are reported cases from most remaining countries with a substantial overall record of publications [143]. Finally, there is a paucity of relevant publications from sub-Saharan African countries [143].
In addition to their broad geographic spread, specific KPC-producing lineages have acquired enhanced virulence or additional resistance mechanisms. Recent reports have described hypervirulent K. pneumoniae clones (associated with community-acquired invasive disease) that have acquired blaKPC-harboring plasmids. These plasmids are considered mobile genetic elements (MGEs) and can transfer horizontally between bacterial clones and species. They contain the blaKPC genes inside transposons, with the most prevalent of them being the transposon Tn4401, although other elements, such as non-Tn4401, have been reported to contain the genes as well [144]. The plasmids that harbor blaKPC genes are categorized as plasmid incompatibility groups, with the two main groups being the IncF plasmids (mainly associated with intra-clonal transfer, or between K. pneumoniae and E. coli) and the IncN plasmids (transfer between other bacterial species) [145,146]. The hypervirulent K. pneumoniae strains are called convergent, as they combine multidrug-resistance with hypervirulence. These cases highlight the possibility of KPC-producing strains causing severe community infections, although their true virulence relative to classical strains is still under investigation. At the same time, strains co-producing KPC together with other carbapenemases (specifically NDM-type metallo-β-lactamases) are increasingly emerging in different parts of the world. The co-production of KPC and NDM in the same isolate has been associated with outbreaks of pan-drug-resistant infections and poses a serious therapeutic challenge [147,148].
Infections due to KPC-producing pathogens usually occur in patients who receive care in the hospital or long-term care facilities. They are more common in patients in intensive care units. KPC-producing pathogens can cause infections in all human systems and organs, including healthcare-associated pneumonia (HAP), such as ventilator-associated pneumonia (VAP), urinary tract infections (UTIs), septicemia, abdominal infections, skin and soft tissue infections (SSTIs), and device-associated infections. In healthcare settings, there is pressure for colonization with KPC-producing pathogens, and opportunities for subsequent cross-infection between patients exist. Invasive medical devices and inadequate infection control measures among healthcare personnel significantly contribute to the transmission and dissemination of infections caused by KPC-producing pathogens in healthcare settings [149]. Adherence to strict infection control practices helps control the dissemination of infections caused by KPC-producing pathogens [150].
Based on the results presented above, the antimicrobial resistance of KPC-producing microorganisms was high in most studied antibiotics, reaching up to 100% (third-generation cephalosporins, cefepime, piperacillin–tazobactam, carbapenems, and fluoroquinolones). Among the antimicrobial agents with potential antimicrobial activity against KPC-producing pathogens (polymyxins, ceftazidime–avibactam, tigecycline, and trimethoprim–sulfamethoxazole), polymyxins may cause nephrotoxicity [151], while tigecycline is not indicated for bacteremia, healthcare-associated pneumonia (due to the presence of adverse events) [152], and urinary tract infections. Ceftazidime–avibactam is a costly drug, especially compared to carbapenems, that has limited availability in low-resource countries [153]. Notably, ceftazidime–avibactam has demonstrated sustained antimicrobial activity against KPC-producing pathogens, with resistance often below 5% in both our analysis and external surveillance data. However, recent evidence highlights the emergence of KPC variants with mutations that impact susceptibility to newer β-lactam/β-lactamase inhibitor (BL/BLI) combinations [154,155]. As described by Hobson et al. [154], specific amino acid substitutions in the Ω-loop region of the KPC enzyme—most notably D179Y—can confer resistance to ceftazidime–avibactam while simultaneously restoring susceptibility to carbapenems. These mutations alter the enzyme’s structure in a way that reduces inhibitor binding but also impairs carbapenem hydrolysis [154,156]. Clinically, this presents a diagnostic and therapeutic challenge, as such variants may not be detected by conventional carbapenemase assays and may respond unpredictably to β-lactam treatment [155,156].
Furthermore, there are limited microbiological and clinical data on the potential use of fosfomycin against KPC-producing pathogens [15]. Thus, the comprehensive evaluation of the published evidence on the susceptibility of KPC-producing bacteria in studies included in our article is of potential clinical interest, particularly in considering the use of various antibiotics for infections caused by such bacteria. In addition, cefiderocol has demonstrated activity against KPC-producing Enterobacterales, with MIC50s ranging from 0.15 to 1 mg/L, and could be an option for treating patients with infections caused by KPC-producing bacteria in the absence of other available alternatives [107].
The strength of this review lies in its extensive systematic search of six resources, which evaluates the most recent available data on the epidemiology of KPC-producing pathogens worldwide. Also, the documentation of the implemented search strategy ensures the study’s reproducibility.
However, some limitations need to be addressed. The isolated species refer to all the strains tested for KPC production, and do not represent the exact number of those with positive results via the PCR method. Additionally, not all studies provided relevant data regarding the antimicrobial susceptibility of KPC-producing pathogens; therefore, the results may underrepresent the actual antimicrobial resistance worldwide for these types of bacteria. Last but not least, the included studies were heterogeneous in design and geographic focus. Many regions (particularly lower-income countries) lack adequate surveillance programs for antimicrobial resistance, including for carbapenemase-producing organisms, resulting in potential gaps and biases in the global data. This variability and under-reporting may limit the generalizability of our findings.

5. Conclusions

The evaluation of the available and most recent literature shows that KPC-producing pathogens have disseminated worldwide in all continents, with a predominance in Asian countries. Antimicrobial resistance is high in most of the examined antibiotics, with a few exceptions, including polymyxins, ceftazidime–avibactam, tigecycline, and trimethoprim-sulfamethoxazole. However, novel therapeutic options provide hope. New β-lactam/β-lactamase inhibitor combinations, such as meropenem–vaborbactam, imipenem–cilastatin–relebactam, and ceftazidime–avibactam, have demonstrated excellent antimicrobial activity against KPC producers. Additionally, cefiderocol offers an alternative option for treating difficult-to-treat cases. Last but not least, global surveillance and reporting, rigorous infection control practices, and prudent antimicrobial stewardship are crucial to curb the further spread of these highly drug-resistant pathogens [157].

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/microorganisms13071697/s1, Table S1: Search strings used for each resource to identify relevant articles, done on 20 February 2025. Table S2: Antimicrobial resistance percentages (%) of Klebsiella pneumoniae carbapenemase (KPC)-producing Gram-negative isolates in the included studies.

Author Contributions

M.E.F. had the idea for the article. All authors contributed to the methodology used in the article. C.-M.A., M.Z. and D.S.K. conducted the literature search, data extraction, and tabulation. M.E.F. and D.S.K. contributed to the first version of the manuscript. C.-M.A., M.Z. and C.F. revised the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

CLSIClinical and Laboratory Standards Institute
EUCASTEuropean Committee on Antimicrobial Susceptibility Testing
HAPhealthcare-associated pneumonia
KPCKlebsiella pneumoniae carbapenemase
MBLmetallo-β-lactamase
NDMNew Delhi metallo-β-lactamase
PCRpolymerase chain reaction
SSTIskin and soft tissue infection
STsequence type
UTIurinary tract infection
VAPventilator-associated pneumonia

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Microorganisms 13 01697 g001
Figure 1. a There were 5120 results in total but only the first 1000 results could be accessed with Google Scholar. * Consider, if feasible, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). ** If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools.
Figure 1. a There were 5120 results in total but only the first 1000 results could be accessed with Google Scholar. * Consider, if feasible, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). ** If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools.
Microorganisms 13 01697 g001
Table 1. Detection of Klebsiella pneumoniae carbapenemase (KPC) in Gram-negative bacteria isolated from various regions globally.
Table 1. Detection of Klebsiella pneumoniae carbapenemase (KPC) in Gram-negative bacteria isolated from various regions globally.
First Author, Year [ref.] *ContinentCountryIsolation PeriodPopulation, n/N (%)Sources of Isolation (n)Species (n)KPC Detection, n/N (%)Types of KPC
Hassan, 2021 [121]AfricaEgypt12/2018–12/2019Clinical isolates, 154/206 (75) ICUWound swabs (77), respiratory secretions (56), blood (37), urine (27), and other (9)Carbapenem-resistant A. baumannii22/206 (11)blaKPC
Odewale, 2023 [122]AfricaNigeria2/2018–8/2019Clinical isolatesNRK. pneumoniae17/128 (13)blaKPC
Ssekatawa, 2021 [123]AfricaUganda1/2019–12/2019Clinical isolatesUrine (128), pus swabs (48), blood (23), rectal swabs (16), vaginal swabs (7), tracheal aspirate (3), and sputum (2)K. pneumoniae18/227 (8)blaKPC-type
Fang, 2019 [20]AsiaChina1/2015–1/2017Inpatient, 41/47, (87) colonization, 6/47 (13) infectionRespiratory (20), urine (12), blood (6), ascites (3), bile (2), skin (1), and other (3)CRE; K. pneumoniae (35), E. cloacae (4), Citrobacter freundii (3), E. coli (3), and K. oxytoca (2)38/47 (81)blaKPC-2
Ge, 2024 [21]AsiaChina2021–2022InpatientBAL, blood, sputum, and urineCRKP; K. pneumoniae30/31 (97)blaKPC-2
Han, 2020 [22]AsiaChina1/2016 –12/2018Inpatient, 498/935 (53) childrenAscites, bile, blood, catheter, drainage, other aseptic body fluids, pus, sputum, and urineCRE; K. pneumoniae (709), E. coli (149), E. cloacae (36), Citrobacter freundii (14), Serratia marcescens (8), E. aerogenes (7), K. oxytoca (7), Morganella morganii (3), Proteus vulgaris (1), and Providencia rettgeri (1)482/935 (52); 307/935 (70) in adults, 175/935 (35) in childrenblaKPC
Hu, 2020 [23]AsiaChina2008–2018Clinical isolatesNRCRKP; K. pneumoniae504/534 (94)blaKPC-2
Jin, 2022 [24]AsiaChina1/2019–12/2021Inpatient, childrenSputum, urine, blood, catheter, BAL, gastric fluid, and othersK. pneumoniae21/34 (62)blaKPC-2
Jing, 2022 [25]AsiaChina07/2019–10/2019NRRespiratory tract (129), blood (45), urine (17), wounds (8), ascitic fluid (6), pleural effusion (5), cerebrospinal fluid (4), and other (24)K. pneumoniae (184), E. cloacae (11), K. oxytoca (6), Citrobacter freundii (5), K. aerogenes (2), and Serratia marcescens (1)175/238 (74)blaKPC-2
Kang, 2020 [26]AsiaChina1/2016–12/2016ICUBlood, CSF, lower respiratory tract, urine, and woundsCRKP; K. pneumoniae120/128 (94)blaKPC-2
Li, 2021 [27]AsiaChina2015–2018NRLower respiratory tract (249), urine (33), secretion (25), blood (14), catheter (13), puncture fluid (7), pleural fluid (7), drainage fluid (4), ascitic fluid (3), cerebral spinal fluid (2), pus (2), and bile (1)K. pneumoniae (350), E. coli (26), E. cloacae (15), and other (8)119/399 (30)blaKPC-2
Liang, 2024 [28]AsiaChina1/2013–12/2022InpatientBloodstream infectionsCRE; K. pneumoniae, E. coli, E. cloacae, and K. oxytoca, Salmonella spp.8/35 (23)blaKPC
Liao, 2023 [29] AsiaChina01/2018–02/2021Clinical isolatesSputum (17), bronchoalveolar lavage fluid (8), urine (7), blood (3), secretion (3), and others (4)K. pneumoniae35/42 (83)blaKPC-2
Liu, 2021 [30]AsiaChina2004–2018Clinical isolatesNRE. cloacae complex 14/113 (12)blaKPC-2
Ma, 2024 [31]AsiaChina1/2021–12/2021Inpatient, childrenSputum (63), blood (11), urine (10), BAL (9), ascites (5), CSF (3), joint fluid (1), hydrothorax (1), and other (2) CRKP; K. pneumoniae93/108 (86)blaKPC
Peng, 2022 [32]AsiaChina1/2015–12/2018Inpatient, 36/89 (40) ICUSputum (86), urine (31), blood (13), lung tissue (9), and bile (7)CRE; K. pneumoniae (89), E. coli (28), E. cloacae (20), Citrobacter freundii (5), K. aerogenes (3), and Cronobacter sakazakii (1)73/146 (50)blaKPC-2
Shen, 2023 [33]AsiaChina01/2018–12/2020Clinical isolatesNRK. pneumoniae23/94 (24)blaKPC
Shi, 2024 [34]AsiaChina2018–2019Clinical isolatesNRCRKP; K. pneumoniae (708)563/708 (80)blaKPC-2
Tian, 2018 [35]AsiaChina1/2016–12/2017Inpatient, childrenNRCRKP; K. pneumoniae30/169 (18)blaKPC-2
Tian, 2020 [36]AsiaChina2002–2017Clinical isolatesUrine (18), blood (16), drainage (11), and other (13)E. coli13/58 (22)blaKPC-2
Wang, 2018 [37]AsiaChina1/2012 –12/2016Clinical isolatesRespiratory tract (858), blood (304), urine (303), abdominal fluid (117), and other (219)CRE; K. pneumoniae (1201), E. coli (282), E. cloacae (179), Citrobacter freundii (44), K. oxytoca (29), Serratia marcescens (28), E. aerogenes (24), Raoultella ornithinolytica (6), Citrobacter braakii (3), Citrobacter koseri (3), and Raoultella planticola (2)961/1801 (53)blaKPC-2
Wang, 2020 [39]AsiaChina10/2016–3/2019InpatientSputum (12), drainage fluid (4), blood (3), wound (2), urine/urinary catheter (7), and bronchial perfusate (1)CRKP; K. pneumoniae12/30 (40)blaKPC
Wang, 2022 [38]AsiaChina3/2018–6/2018InpatientSputum (18), blood (16), pus (6), ascites (2), CSF (1), bile (1), and secretions (1)CRKP; K. pneumoniae42/45 (93)blaKPC-2
Wei, 2022 [40]AsiaChina1/2020–12/2020ICUBlood, pus, puncture fluid, respiratory tract, and urineCRKP; K. pneumoniae79/80 (99)blaKPC-2
Wu, 2024 [41]AsiaChina2021InpatientBlood, CNS, gastrointestinal tract, genital tract, peritoneum, respiratory tract, skin/soft tissue, and urinary tractCarbapenem-resistant: A. baumannii, Enterobacterales, E. coli, K. pneumoniae, and P. aeruginosa203/1257 (16)blaKPC
Yan, 2021 [42]AsiaChina2018–2019Clinical isolatesSputum (142), blood (82), urine (21), ascites (11), wound (9), CSF (5), and other (35)CRE; K. pneumoniae, E. coli, E. cloacae, Citrobacter freundii, K. oxytoca, Providencia rettgeri, K. aerogenes, and Serratia marcescens215/305 (70)blaKPC
Yang, 2013 [43]AsiaChina2/2009–11/2011Inpatient, ICUSputum (25), blood (8), urine (7), venous cannula (3), drainage fluid (3), and bile (2)K. pneumoniae2/2009–11/2011: 48/1636 (3)
12/2012–6/2012: 41/351 (12)		blaKPC-2
Zhang, 2021 [44]AsiaChina4/2018–7/2019Inpatient, 102/133 (77) ICUSputum (81), bile (12), urine (12), blood (8), and CSF and BAL (7)CRKP; K. pneumoniae133/133 (100)blaKPC-2
Patil, 2023 [63]AsiaIndia1/2020–12/2021Inpatients, outpatientBlood, urine, wound, sputum, and CSFK. pneumoniae13/60 (22)blaKPC
Darabi, 2019 [64]AsiaIran12/2013–9/2016Inpatient, 107/182 (59) outpatientUrine (137) and sputum (26), wounds (10), blood (8), and stool (1)K. pneumoniae7/182 (4)blaKPC
Haji, 2021 [137]AsiaIraq2019–2020Clinical isolates, inpatient and outpatientUrine, sputum, swabs, and bloodE. coli, A. baumannii, and Achromobacter dentrificans4/53 (7)blaKPC
Adler, 2011 [46]AsiaIsrael8/2008–4/2009InpatientRectal swabsCRE; K. pneumoniae, K. oxytoca, and E. aerogenes32/33 (97)blaKPC
Adler, 2015 [45]AsiaIsrael1/2009–6/2012InpatientSurveillance cultures (76) and blood (12)E. coli88/88 (100)blaKPC-2, blaKPC-3
Ben-David, 2015 [47]AsiaIsrael1/2006–5/2007InpatientBlood and urineCRKP; K. pneumoniae120/120 (100)blaKPC-3
Hussein, 2022 [48]AsiaIsrael1/2005–12/2020InpatientRectal swabsCPE; Citrobacter spp., E. coli, E. cloacae, K. oxytoca, K. pneumoniae, Morganella spp., Proteus spp., Providencia spp., and Raoultella spp.2014: 89/95 (94)
2015: 100/109 (92)
2016: 51/59 (84)
2017: 58/65 (88)
2018: 58/88 (66)
2019: 71/141 (51)
2020: 75/134 (56)
2014–2020: 502/691 (73)		blaKPC
Manandhar, 2020 [49]AsiaNepal6/2012–12/2018Inpatient, 295/2153 (14) childrenNRE. coli (719), Klebsiella spp. (532), and Enterobacter spp. (520), and A. baumannii (383)E. coli: 0/719 (0)
Klebsiella spp.: 22/532 (4)
Enterobacter: 201/337 (60) a
A. baumannii: not tested		blaKPC
Sah, 2021 [50]AsiaNepal1/2016–12/2016Inpatient, ICU, children, neonatesBloodA. baumannii complex, E. coli, E, aerogenes, and K. pneumoniae8/50 (16)blaKPC
Takahashi, 2021 [51]AsiaNepal10/2018–1/2020Hospital samplesNRP. aeruginosa4/43blaKPC-2
AlAmri, 2019 [62]AsiaSaudi Arabia9/2017–5/2018Clinical isolatesRespiratory tract (41), wound swabs (18), rectal swabs (13), blood (10), urine (6), and other (15)A. baumannii103/103 (100)blaKPC-like
Ling, 2015 [52]AsiaSingapore1/2011–12/2013InpatientStool, urine, wound, blood, sputum, bile, catheter, peritoneal fluid, mephrostomy fluid, tracheal aspirate, and ulcerCRE; K. pneumoniae, E. coli, and E. cloacae complex107/268 (40)blaKPC
Teo, 2014 [53]AsiaSingapore9/2010–5/2013Clinical isolatesNRCRE; E. coli, Klebsiella spp., Citrobacter spp., and Enterobacter spp.31/400 (8)blaKPC-type
Teo, 2022 [54]AsiaSingapore2009–2020InpatientNRCRKP; K. pneumoniae sensu stricto (500), K. quasipneumoniae subsp. similipneumoniae (55), K. quasipneumoniae subsp. quasipneumoniae (55), and K. variicola subsp. variicola (9)235/575 (41)blaKPC
Lim, 2024 [1]AsiaSouth Korea2018–2022Clinical isolatesNRCPE; K. pneumoniae, E. coli, Enterobacter spp., Citrobacter freundii, K. oxytoca, Serratia marcescens, Citrobacter koseri, Raoultella ornitholytica, Providencia rettgeri, Proteus spp., and Morganella morganii47,313/63,513 (74)blaKPC
Yoo, 2023 [59]AsiaSouth Korea01/2016–12/2021Inpatients from ICU NRK. pneumoniae (253), E. cloacae complex (44), E. coli (15), and others (15)164/327 (50)blaKPC
Chiu, 2013 [55]AsiaTaiwan2010–2012Clinical isolatesNRCRKP; K. pneumoniae41/347 (12)blaKPC-2
Huang, 2023 [56]AsiaTaiwan2013–2021NRUrine (68), blood (50), sputum (37), skin/pus/wound (14), body fluids (5), and catheter tip (1)CPE; K. pneumoniae (79), E. coli (56), E. cloacae complex (44), Citrobacter freundii (9), K. oxytoca (6), and K. aerogenes (1)38/195 (19)blaKPC
Lee, 2021 [57]AsiaTaiwan2017–2020InpatientNRCRE; K. pneumoniae (175), E. coli (26)2017: 64/83 (77)
2018: 27/36 (75)
2019: 37/43 (85)
2020: 32/39 (82)
2017–2020: 69/201 (34)		blaKPC
Falco, 2016 [65]AsiaVenezuela4/2014–7/2014Inpatient, children, 2/19 (11) ICUBlood (15), bronchial secretion (2) catheter (1), and lesion secretion (1)CRKP; K. pneumoniae19/19 (100)blaKPC-2
Berglund, 2019 [60]AsiaVietnam2/2015–9/2015InpatientTracheal fluid, nasopharynx, blood, and otherK. pneumoniae57/57 (100)blaKPC-2
Linh, 2021 [61]AsiaVietnam2010–2015InpatientBronchial fluid (92), blood (18), sputum (6), urine (4), pleural fluid (1), abdominal fluid (1)CRE; K. pneumoniae (305), E. coli (186), Klebsiella spp. (54), Enterobacter spp. (29), and Citrobacter spp. (25)122/599 (20) bblaKPC-2, blaKPC-12
Miriagou, 2010 [13]Asia/EuropeRussia1/2020–12/2021InpatientBlood, cerebrospinal fluid, urine, BAL, endotracheal aspirate, biopsies, and wound swabsK. pneumoniae (2503) and E. coli (2055)410/4558 (9)blaKPC-3
Yürek, 2023 [66]Asia/EuropeTurkey12/2020–3/2021Inpatient, outpatientUrine (27), blood (6), respiratory tract (6), abscess or wound (3), and other (3)K. pneumoniae5/35 (14)blaKPC c
David, 2019 [93]Europe31 countries d11/2013–4/2014NRNRK. pneumoniae spp.311/1649 (18)blaKPC-2, blaKPC-3, blaKPC-12
Grundmann, 2017 [95]EuropeAlbania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Israel, Italy, Kosovo, Latvia, Lithuania, Luxembourg, Malta, Montenegro, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Macedonia, Turkey, the UK—England and Northern Ireland, and the UK—Scotland11/2013–4/2014InpatientAll clinical specimens were accepted, except for stool and surveillance screening samplesK. pneumoniae (850), E. coli (77)393/927 (42)blaKPC
Hoenigl, 2012 [81]EuropeAustria10/2010–2/2011InpatientNRK. oxytoca31/31 (100)blaKPC
Kazmierczak, 2020 [94]EuropeAustria, Belgium, Denmark, France, Germany, the Netherlands, Sweden, the UK, Greece, Italy, Portugal, Spain, Turkey, the Czech Republic, Hungary, Poland, Romania, and Russia2013–2017NRLower respiratory tract, skin and soft tissue, urinary tract, intra-abdominal, bloodstream, or other infectionsCRE; K. pneumoniae, E. cloacae, and E. coli570/1231blaKPC
De Laveleye, 2017 [82] EuropeBelgium1/2013–12/2014NRNRE. coli and K. pneumoniae2013: 13/35 (37)
2014: 25/35 (71)		blaKPC
Dobreva, 2022 [83]EuropeBulgaria2014–2018NRUrine (4), blood (3), wound (2), cerebrospinal fluid (1), tracheobronchial aspirate (1), and rectal swab (1)K. pneumoniae12/12 (100)blaKPC-2
Hammerum, 2020 [84]EuropeDenmark1/2014–6/2018Clinical isolatesNRK. pneumoniae, Klebsiella quasipneumoniae, and Klebsiella variicola8/103 (8)blaKPC-2, blaKPC-3
Räisänen, 2020 [85]EuropeFinland2012–2018Clinical isolatesUrine, wound swabs, blood, respiratory tractCPE; K. pneumoniae, E. coli, and Citrobacter freundii, E. cloacae 71/231 (31)blaKPC-like
Carbonne, 2010 [86]EuropeFrance9/2009–10/2009Inpatient, 4/13 (31) infection, 9/13 (69) colonization cBile, blood, bronchial aspirate, and rectal swabK. pneumoniae13/295 (4)blaKPC-2
Bonnin, 2024 [92]EuropeGermany, Belgium, England, Austria, Netherlands, Poland, and Czech Republic1/2013–3/2021NRNRCarbapenemase-producing Morganella morganii 26/247 (11)blaKPC-2
Kontopidou, 2014 [68]EuropeGreece9/2009–6/2010ICUNRCPKP; K. pneumoniae52/82 (63)blaKPC
Pournaras, 2013 [69]EuropeGreece9/2010–2/2012InpatientRectal swabCPE; K. pneumoniae, E. coli56/97 (58)blaKPC
Sorovou, 2023 [70]EuropeGreece1/2019–12/2022Inpatient, 26/212 (12) ICUUrine (154), rectal swab (12), BAL (11), wound swabs (8), sputum (7), central venous catheter (5), and other (15)K. pneumoniae2019: 10/51 (20)
2020: 8/42 (19)
2021: 9/54 (17)
2022: 38/65 (58)
2019–2022: 65/212 (31)		blaKPC
Zarras, 2022 [71]EuropeGreece3/2018–3/2021ICU, 34/150 (23) pediatric/neonatalBlood, bronchial secretions, rectal swabs, trauma, and urine eCRKP; K. pneumoniae56/150 (37), 24/34 (71) in children and neonatesblaKPC
Budia-Silva, 2024 [11]EuropeGreece, Italy, Romania, Serbia, Spain, and Turkey2016–2018InpatientBlood (334), urine (213), and other (140)CRKP; K. pneumoniae384/683 (56)blaKPC-2, blaKPC-3, blaKPC-36
Buzgó, 2025 [79]EuropeHungary3/2021–4/2023InpatientNRK. pneumoniae53/420 (13)blaKPC-2, blaKPC-3
Toth, 2010 [80]EuropeHungary9/2008–4/2009InpatientWound (2), lower respiratory tract (2), upper respiratory tract (2), stool (2), and central venous catheter (1)K. pneumoniae9/9 (100)blaKPC-2
Morris, 2012 [87]EuropeIreland2011InpatientBlood, central venous catheter, rectal swab, and urineCRKP; K. pneumoniae19/19 (100)blaKPC-2
Agodi, 2011 [72]EuropeItaly3/2009–5/2009ICUSputum (7), blood (6), urine (5), tonsillar swab (3), catheter tip (2), and peritoneal fluid (1)CRKP; K. pneumoniae24/24 (100)blaKPC-3
Orena, 2024 [73]EuropeItaly1/2024–6/2024InpatientRectal swabsCRE; E. coli, E. cloacae, K. oxytoca, and K. pneumoniae30/118 (25)blaKPC
Piazza, 2024 [74]EuropeItaly10/2021–3/2022Inpatient, infection, colonizationBlood (14), rectal swabs (3), respiratory tract (3), urine (1)Ceftazidime-resistant; K. pneumoniae21/21 (100)blaKPC
Santino, 2013 [75]EuropeItaly1/2012–6/2012Clinical isolatesUrine (5), wound (3), sputum (3), BAL (1), skin swab (l), blood (1), and pharyngeal swab (1)K. pneumoniae15/15 (100)blaKPC-3
Jamin, 2024 [88]EuropeNetherlands2011–2023Clinical isolatesNRK. pneumoniae107/2985 (4)blaKPC-3
Samuelsen, 2017 [89]EuropeNorway2007–2014Inpatient, traveling abroadUrine and fecal screeningCPE; K. pneumoniae and E. cloacae20/59 (34)blaKPC-2, blaKPC-3
Guzek, 2019 [76]EuropePoland1/2009–12/2016InpatientsUrine (46), cloacal swabs for fecal carriage (43), blood (11), wounds (9), bronchial tree aspirates collected via an endotracheal tube (8), abscesses (3), and fluid collected from the abdominal cavity (2)K. pneumoniae, E. coli, and C. freundii73/122 (60)blaKPC
Kuch, 2020 [77]EuropePoland1/2000–1/2017NRUrine, blood, and other clinical specimens (bronchial secretions, cerebrospinal fluid, peritoneal fluid, pleural fluid, pus, skin lesions, sputum, and wounds)K. pneumoniae, K. oxytoca, P. mirabilis, P. penneri, P. vulgaris, C. freundii, C. braakii, E. cloacae, E. aerogenes, E. amnigenus, S. marcescens, M. morganii, and P. rettgeri40/400 (10)blaKPC
Mrowiec, 2019 [78]EuropePoland2008–2015InpatientChildren: stool (69) and perianal swabs (12); adults: respiratory system (39), urine (23), and blood (10)K. pneumoniae14/170 (8)blaKPC
Baicus, 2018 [90]EuropeRomania2016Inpatient, ICULower respiratory tract (20), urine (30), blood (4), peritoneum (1), wound (5), and sputum (1)K. pneumoniae6/20 (30)blaKPC
Gracia-Ahufinger, 2023 [91]EuropeSpain1/2014–12/2018InpatientNRCPE; K. pneumoniae, E. cloacae complex, E. coli, and K. aerogenes313/2280 (14)blaKPC
Kazmierczak, 2016 [126]Global40 countries2012–2014Inpatient, 195/586 (33) ICU fRespiratory tract (189), urinary tract (137), skin/soft tissue (132), and wounds (71) fCRE; Enterobacterales (38,266) and P. aeruginosa (8010)586/46,276 (1)blaKPC-2, blaKPC-3, blaKPC-9, blaKPC-12, blaKPC-18
Nobrega, 2023 [127]Global56 countries2015–2017NRNRCitrobacter freundii (51), Citrobacter portucalensis (20), Citrobacter koseri (10), Citrobacter farmeri (3), Citrobacter amalonaticus (1), and Citrobacter braakii (1)29/91 (32)blaKPC-2, blaKPC-3
Estabrook, 2023 [125]GlobalNR2018–2019NRNRMeropenem-resistant; K. pneumoniae, E. cloacae, E. coli, Providencia spp., Serratia marcescens, Klebsiella spp., Citrobacter spp., Enterobacter spp., Proteus spp., and Morganella morganii568/2228 (26)blaKPC-2, blaKPC-3, blaKPC-4, blaKPC-6, blaKPC-31, blaKPC-46, blaKPC-66
Castanheira, 2012 [124]GlobalNR g1999–2008InpatientNRCPE; E. coli and Klebsiella spp.56/69 (81)blaKPC
Issac, 2023 [108]North AmericaCanada2013–2020InpatientUrine (917), axilla/groin/rectum (343), wounds (197), respiratory tract (163), blood (84), other (91), and unknown (10)CRE; K. pneumoniae (542), E. cloacae (508), E. coli (238), others (512), and unknown (5)406/1805 (22)blaKPC
Mataseje, 2016 [109]North AmericaCanada1/2010–12/2014Inpatient, outpatientStool or rectal swab, urine, sputum, blood, skin or soft tissue, surgical site, and otherCPE; K. pneumoniae,
Enterobacter spp., Serratia spp., Citrobacter spp., K. oxytoca, Morganella morganii, Providencia rettgeri, Pantoea spp., and Kluyvera spp.		169/261 (65)blaKPC-2, blaKPC-3, blaKPC-4
Bradford, 2004 [96]North AmericaUSA11/1997–7/2001InpatientUrine (9), sputum (8), blood (1), and miscellaneous sources (3) hCPE; K. pneumoniae (18) and K. oxytoca (1)19/19 (100)blaKPC-2
Castanheira, 2017 [97]North AmericaUSA2012–2015InpatientPneumonia, urinary tract infections, skin/soft tissue infections, bloodstream infections, and intra-abdominal infectionsCRE; K. pneumoniae, E. cloacae species complex, E. coli, K. oxytoca, Serratia marcescens, Citrobacter freundii, and E. aerogenes456/525 (87)blaKPC-2, blaKPC-3, blaKPC-4,
blaKPC-17 i
Endimiani, 2009 [98]North AmericaUSA3/2008–4/2008InpatientBlood, respiratory tract, and urineK. pneumoniae10/241 (4) (total), 10/10 (100) (CRKP)blaKPC-2, blaKPC-3
Fitzpatrick, 2022 [99]North AmericaUSA1/2013–12/2018Inpatient, outpatientUrine (1163), respiratory tract (235), blood (189), rectal (28), and other (290)Carbapenemase-producing CRE; E. coli, K. pneumoniae, K. oxytoca, and Enterobacter spp.914/1047 (87)blaKPC
Gomez-Simmonds, 2021 [100]North AmericaUSA3/2020–4/2020InpatientRespiratory tract (14), blood (5), and urine (1)CPE; K. pneumoniae27/31 (87)blaKPC-2, blaKPC-3
Jacobs, 2019 [107]North AmericaUSANRNRNRK. pneumoniae (794), E. coli (35), Enterobacter spp. (4), and Citrobacter freundii (1)737/834 (88)blaKPC-2, blaKPC-3, blaKPC-4, blaKPC-4-like
Kaiser, 2013 [101]North AmericaUSA2007–2009InpatientBlood, skin and soft tissue, respiratory tract, urinary tractK. pneumoniae113/2049 (6)blaKPC
Karlsson, 2022 [106]North AmericaUSA2011–2015InpatientUrine (349), blood (58), and other normally sterile sites (14)CPE; K. pneumoniae (265), E. cloacae complex (77), E. coli (50), K. aerogenes (26), and K. oxytoca (3)299/307 (97)blaKPC
Logan, 2019 [102]North AmericaUSA1/2008–12/2014Inpatient, childrenUrine (9), blood (9), respiratory tract (8), and other (10)K. pneumoniae, E. coli, and E. cloacae18/36 (50)blaKPC
Precit, 2020 [103]North AmericaUSA10/2010–12/2017Clinical isolatesUrine (45), bronchial wash or sputum (7), wound (6), blood (3), stool or rectal swab (5), and other (7)E. coli and Klebsiella spp.35/74 (47)blaKPC
Shortridge, 2023 [104]North AmericaUSA2016–2020InpatientBloodstream infections, pneumonia, and urinary tract infectionsCRE; E. coli, K. pneumoniae, and E. cloacae184/222 (83)blaKPC-2, blaKPC-3, blaKPC-4, blaKPC-6
van Duin, 2020 [105]North AmericaUSA4/2016–8/2017InpatientUrine (404), respiratory tract (268), blood (130), wound (130), intra-abdominal (58), and other (50)K. pneumoniae, Enterobacter spp., E. coli, non-K. pneumoniae Klebsiella spp., and other573/1040 (55)blaKPC-2, blaKPC-3, blaKPC-4, blaKPC-6, blaKPC-8, blaKPC-18
Echegorry, 2024 [118]South AmericaArgentina11/2021Clinical isolatesUrine, blood, respiratory tract, abdominal tract, and othersK. pneumoniae (628), Morganellaceae (57), Enterobacter cloacae complex (51), E. coli (38), and other (47) j327/821 (40)blaKPC
Borghi, 2023 [110]South AmericaBrazil4/2015–11/2015InpatientBlood, bone fragment, catheter, nasal swab, rectal swab, secretions, tracheal aspirate, urine, and wound swabCRKP; K. pneumoniae40/40 (100)blaKPC
Campos, 2017 [111]South AmericaBrazil3/2013–3/2014ICUUrine, swab surveillance, tracheal aspirate, blood, surgical wound, catheter tip, biological fluids, CSF, and skin biopsyK. pneumoniae149/165 (90)blaKPC
Fochat, 2024 [112]South AmericaBrazil1/2020–8/2023Inpatient, ICUNRCRE; K. pneumoniae, Serratia marcescens, E. cloacae, K. aerogenes, and E. coli9/46 (20)blaKPC
Kiffer, 2023 [113]South AmericaBrazil2015–2022InpatientNREnterobacterales, P. aeruginosa, and A. baumanniiEnterobacterales: 41,282/60,205 (68)
P. aeruginosa: 1065/12,625 (8)
A. baumannii: 52/10,452 (0.5)		blaKPC
Tavares, 2015 [114]South AmericaBrazil1/2009–12/2011NRSurveillance swabs (26), urine (13), respiratory tract (12), skin and soft tissue (10), blood (5), other (10), and NR (7) kCRE; E. aerogenes (121), E. coli (104), E. cloacae (100), Serratia marcescens (19), Providencia stuartii (11), Pantoea agglomerans (10), Citrobacter freundii (8), K. oxytoca (9), and Morganella morganii (5)83/387 (21)blaKPC-2
Tolentino, 2019 [115]South AmericaBrazil2011–2014Inpatient, 48/48 (100)NRK. pneumoniae48/48 (100)blaKPC-2
Quesille-Villalobos, 2025 [119]South AmericaChile1/2019–12/2022InpatientBiopsies, blood, bone tissue, sterile fluids, and otherCPE; K. pneumoniae, E. cloacae complex, E. coli, Citrobacter spp., and K. oxytoca2019: 8/12 (67)
2020: 35/60 (58)
2021: 69/168 (41)
2022: 87/190 (46)
2019–2020: 199/430 (46)		blaKPC-2, blaKPC-3
Ibáñez-Prada, 2024 [116]South AmericaColombia7/2017–7/2021Inpatient, 189/248 (76) ICUNRCRE; K. pneumoniae, Enterobacter hormaechei, Klebsiella variicola subsp. variicola, Providencia rettgeri, and P. aeruginosa171/228 (75)blaKPC-2, blaKPC-3
Ocampo, 2016 [117]South AmericaColombia6/2012–6/2014Inpatient, 28/193 (15) children, 55/193 (29) ICUNRK. pneumoniae166/193 (86)blaKPC
Soria-Segarra, 2024 [120]South AmericaEcuador1/2022–5/2022Clinical isolatesNRCPE; K. pneumoniae, K. aerogenes, E. cloacae, E. coli, A. baumannii, and P. aeruginosa52/60 (87)blaKPC
Lascols, 2012 [135]Various; Africa, Asia, Europe, Latin
America, the Middle East, North America, South Pacific		NR2008–2009Clinical isolatesIntra-abdominal infectionsE. coli, K. oxytoca, K. pneumoniae, and Proteus mirabilis28/1093 (3)blaKPC-2, blaKPC-3, blaKPC-11
Wise, 2023 [136]Various; Africa/Middle East, Asia, Eurasia, Latin America27 countries l2019–2021Inpatient, 6632/24,937 (27) ICUUrinary tract (6408), bloodstream (5921), lower respiratory tract (4907), skin/soft tissue (4400), intra-abdominal (3263), and other (38)Enterobacterales705/7446 m (9)blaKPC
Hawser, 2009 [131]Various; America, Asia, EuropeIsrael, Puerto Rico, Colombia, and Greece2005–2008Clinical isolatesNRNR26/86 (30)blaKPC
Doyle, 2012 [129]Various; Asia, Europe, Latin America, Middle East, North America, the South PacificNR2008–2009Clinical isolatesNRCPE; Klebsiella spp., E. coli, Citrobacter freundii, and Enterobacter spp.49/142 (35)blaKPC
Karlowsky, 2022 [132]Various; Asia, Europe, Latin America, North America52 countries2018–2020NRUrinary tract (1210), respiratory tract (998), blood (823), intra-abdominal (409), and skin/soft tissue (449)Enterobacterales230/1265 (18)blaKPC
Gales, 2023 [130]Various; Asia/Pacific, Europe, Latin America, Middle East/Africa, North AmericaNR n2017–2019InpatientBlood, intra-abdominal, other (nervous system, reproductive system, head, ears, eyes, nose and throat), respiratory tract, skin/musculoskeletal, urinary tract, and instrumentsE. coli (20,047), P. aeruginosa (20,643), K. pneumoniae (17,229), and E. cloacae (6866)830/64,785 (1)blaKPC-2, blaKPC-3
Castanheira, 2019 [128]Various; Asia/Pacific, Europe, Latin America, North America42 countries2007–2016NRNRCRE; K. pneumoniae (997), E. cloacae species complex (69), E. coli (52), Serratia marcescens (44), K. oxytoca (30), K. aerogenes (27), Citrobacter freundii species complex (9), Proteus mirabilis (6), Enterobacter spp. (4), Raoultella ornithinolytica (3), Pluralibacter gergoviae (2), Providencia stuartii (2), Raoultella planticola (2), Serratia spp. (2), Hafnia alvei (1), Morganella morganii (1), Pantoea agglomerans (1), and Raoultella spp. (1)2007–2009: 186/1298 (50)
2014–2016: 501/1298 (54)		blaKPC-2, blaKPC-3, blaKPC-4, blaKPC-6, blaKPC-12, blaKPC-17, blaKPC-20, blaKPC-like o
Kazmierczak, 2021 [133]Various; Asia/South Pacific, Europe, Latin America, Middle East/Africa, North America34 countries p2012–2017InpatientLower respiratory tract (778), urinary tract (631), skin and soft tissue (581), intra-abdominal (408), bloodstream (266), and other (2)Meropenem non-susceptible; K. pneumoniae (2046), E. cloacae (177), E. coli (136), Klebsiella spp. (101), Citrobacter spp. (79), Proteeae (70), Serratia marcescens (31), Enterobacter spp. (18), and Raoultella spp. (8)1263/2666 (47)blaKPC-2, blaKPC-3, blaKPC-9, blaKPC-12, blaKPC-17, blaKPC-18, blaKPC-29, blaKPC-30
Kazmierczak, 2019 [134]Various; Europe, North AmericaCanada, Czech Republic, France, Germany, Greece, Hungary, Italy, Russia, Spain, Sweden, Turkey, and the United Kingdom2014InpatientNRA. baumannii, E. cloacae, K. oxytoca, K. pneumoniae, P. aeruginosa, and Serratia marcescens75/1272 (6)blaKPC
Abbreviations: A. baumannii, Acinetobacter baumannii; BAL, bronchoalveolar lavage; CPE, carbapenemase-producing Enterobacterales; CRE, carbapenem-resistant Enterobacterales; CNS, central nervous system; CRKP, carbapenem-resistant Klebsiella pneumoniae; CSF, cerebrospinal fluid; E. aerogenes, Enterobacter aerogenes; Enterobacter cloacae, E. cloacae; E. coli, Escherichia coli; K. aerogenes, Klebsiella aerogenes; K. oxytoca, Klebsiella oxytoca; K. pneumoniae, Klebsiella pneumoniae; K. pneumoniae; CRPA, carbapenem-resistant P. aeruginosa. * Studies are presented in alphabetical order first by continent and then by country. If multiple counties are included in a study, then the sorting is based on the first country according to alphabetical order. a 183 Enterobacter spp. isolates were not tested. b Of the 122 isolates, 109 were K. pneumoniae, and 13 were E. coli. c All isolates co-carried the bla KPC and blaOXA-48 genes. d Austria, Belgium, Bulgaria, Croatia, Cyprus, the Czech Republic, Denmark, Estonia, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Latvia, Lithuania, Luxembourg, Malta, Montenegro, North Macedonia, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Turkey, and the UK. e Rectal swabs were collected as part of colonization screening. f Data available for KPC-positive isolates. g Not specifically reporting countries; SENTRY and MYSTIC surveillance programs. h Seven isolates collected from urine, three from sputum, and three from miscellaneous sources were considered as colonization. i Only 371 isolates were tested for the specific blaKPC-producing genes. j Proteus mirabilis (n = 29), Providencia stuartii (n = 25), and Morganella morganii (n = 2). k For 7 isolates, the source of isolation is not reported (NR). l Argentina, Brazil, Cameroon, Chile, Colombia, Costa Rica, Dominican Republic, Guatemala, Hong Kong, India, Ivory Coast, Jordan, Kuwait, Malaysia, Mexico, Morocco, Nigeria, Panama, the Philippines, Qatar, Russia, Saudi Arabia, South Africa, Taiwan, Thailand, Turkey, and Venezuela. m 7446 isolates were eligible for beta-lactamase gene screening. n Not specifically reporting countries; ATLAS surveillance program. o Amplicon sequencing was not performed in the blaKPC-like isolates. These isolates were tested using a multiplex reaction and reamplified using singleplex. p Austria, Belgium, the Czech Republic, Denmark, France, Germany, Greece, Hungary, Italy, Netherlands, Poland, Portugal, Romania, Russia, Spain, Sweden, Turkey, the United Kingdom, Australia, China, Hong Kong, Japan, Malaysia, the Philippines, South Korea, Taiwan, Thailand, Israel, Kenya, Kuwait, Nigeria, South Africa, and the United States of America.
Table 2. Antimicrobial resistance percentages (%) of Klebsiella pneumoniae carbapenemase (KPC)-producing Gram-negative isolates in the included studies.
Table 2. Antimicrobial resistance percentages (%) of Klebsiella pneumoniae carbapenemase (KPC)-producing Gram-negative isolates in the included studies.
Study, Year/% [ref.]CAZP/TATMGENIMPMERCOLTGC
Campos, 2017 a [111]90.7nana6278.792.2nana
Castanheira, 2012 b [124]na94|100 cna45|51 cna84|53nana
Endimiani, 2009 [98]100nanana100100nana
Fang, 2019 [20]100100100na100nanana
Ge, 2024 [21]100100nanana100nana
Gracia-Ahufinger, 2023 [91]96957274778514na
Han, 2020 [22]989999849998na0.4
Hawser, 2009 [131]nananana80.880.8na0
Kaiser, 2013 [101]991001004110099161
Karlowsky, 2022 [132]97|100 cnanana94|91 c97|78 cnana
Kazmierczak, 2019 [134]nanananana10040na
Logan, 2019 [102]na18 [2/11]0 [0/8]7211 d11nana
Nobrega, 2023 [127]9297nanana96nana
Santino, 2013 [75]100nana801001008073
Shortridge, 2023 [104]92.296.1na3598.986.1na2.2
Sorovou, 2023 e [70]nana186nana210
Sorovou, 2023 f [70]nana172nana010
Sorovou, 2023 g [70]nana1711nana711
Sorovou, 2023 h [70]nana5949nana343
Tavares, 2015 [114]87na9842nanana47 i
Tian, 2018 [35]100nana8010010000
Tolentino, 2019 [115]100100na91.797.9100nana
Wang, 2020 [39]nananananananana
Wang, 2022 [38]nananana100100nana
Wise, 2023 [136]nana99509896na5
Abbreviations: ATM, aztreonam; CAZ, ceftazidime; COL, colistin; GEN, gentamycin; IMP, imipenem; MER, meropenem; P/T, piperacillin–tazobactam; TGC, tigecycline. a Percentages are a result of the average resistance percentage taken from 3 different hospitals, namely BACG—Beneficent Association of Campo Grande, RHMS—Regional Hospital of Mato Grosso do Sul, and UH/FUMS—Maria Aparecida Pedrossian University Hospital of Federal University of Mato Grosso do Sul. b Resistance of carbapenemase-producing Enterobacteriaceae. c The first value refers to the percentage of antimicrobial resistance as defined by the CLSI criteria; the second value refers to the percentage of antimicrobial resistance as defined by the EUCAST criteria. d Antimicrobial resistance reported at 11% as a sum for carbapenems (either imipenem or meropenem). e Isolates collected in 2019. f Isolates collected in 2020. g Isolates collected in 2021. h Isolates collected in 2022. i MIC50 = 1 mg/L.
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Falagas, M.E.; Asimotou, C.-M.; Zidrou, M.; Kontogiannis, D.S.; Filippou, C. Global Epidemiology and Antimicrobial Resistance of Klebsiella Pneumoniae Carbapenemase (KPC)-Producing Gram-Negative Clinical Isolates: A Review. Microorganisms 2025, 13, 1697. https://doi.org/10.3390/microorganisms13071697

AMA Style

Falagas ME, Asimotou C-M, Zidrou M, Kontogiannis DS, Filippou C. Global Epidemiology and Antimicrobial Resistance of Klebsiella Pneumoniae Carbapenemase (KPC)-Producing Gram-Negative Clinical Isolates: A Review. Microorganisms. 2025; 13(7):1697. https://doi.org/10.3390/microorganisms13071697

Chicago/Turabian Style

Falagas, Matthew E., Christina-Maria Asimotou, Maria Zidrou, Dimitrios S. Kontogiannis, and Charalampos Filippou. 2025. "Global Epidemiology and Antimicrobial Resistance of Klebsiella Pneumoniae Carbapenemase (KPC)-Producing Gram-Negative Clinical Isolates: A Review" Microorganisms 13, no. 7: 1697. https://doi.org/10.3390/microorganisms13071697

APA Style

Falagas, M. E., Asimotou, C.-M., Zidrou, M., Kontogiannis, D. S., & Filippou, C. (2025). Global Epidemiology and Antimicrobial Resistance of Klebsiella Pneumoniae Carbapenemase (KPC)-Producing Gram-Negative Clinical Isolates: A Review. Microorganisms, 13(7), 1697. https://doi.org/10.3390/microorganisms13071697

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