Evaluation of Carba NP for Rapid Detection of Carbapenem Resistance in Routine Diagnostic Laboratories: A Retrospective Validation Study

Introduction: Carbapenem-resistant Gram-negative Bacilli (CR-GNB) cause many serious infections, resulting in increased treatment costs, prolonged hospitalisation, and a high mortality rate among infected patients. The survival of carbapenemaseproducing Gram-negative organisms is enhanced by mechanisms such as the presence of carbapenemases, reduced expression, and porin mutations. Accurate tests for rapid detection of bacterial antibiotic resistance are crucial for tracking, preventing, and containing the spread of resistant genes within hospitals and communities, as well as for guiding therapy. Aim: To evaluate the performance of the ‘Carba M test’ compared to phenotypic Carba NP tests, Carbapenem Inactivation Method (mCIM/eCIM) tests, and genotypic Carba R tests for the phenotypic detection and characterisation of various types of carbapenemase-producing GNB. Materials and Methods: A cross-sectional study was conducted in the Department of Microbiology at PSG Hospitals, Coimbatore, Tamil Nadu, India which has 1400 beds. The study was carried out over a period of 15 months (from June 2022 to August 2023). A total of 250 CR-GNB were included as the study population. A comparative evaluation of the Carba M test, Carba NP test, Carbapenem Inactivation Method (mCIM/eCIM), and Carba R test for the rapid detection of carbapenemase-producing GNB using standard methods was done. The data were analysed, and odds ratios and p-values were calculated for statistical significance at a 95% Confidence Interval (CI). Results: A total of 250 CR-GNB were isolated during the study period, of which 83 (33.2%) were from the Medical Intensive Care Unit (MICU), followed by the Medicine department with 24 (9.6%). Enterobacteriaceae accounted for the majority of the isolates, with 229 (91.6%), followed by Pseudomonas aeruginosa with 17 (6.8%) and Acinetobacter species with 4 (1.6%). Klebsiella pneumoniae was the most common isolate among Enterobacteriaceae, accounting for 216 (86.4%). Out of the 250 CR isolates tested by the Carba R test, 100 (40%) were positive for the Oxacillinase (OXA)-48 enzyme, 35 (14%) for the New Delhi Metallobetalactamase (NDM) enzyme, 4 (1.6%) for Verona Integron-encoded Metallobetalactamase (VIM), and all were negative for Imipenemase (IMP), and Oxacillinase (OXA), and Klebsiella pneumoniae Carbapenemase (KPC) genotypes. The sensitivity of mCIM/eCIM observed in the study was 67.12%, and specificity was 85.71% when compared to the molecular genotype (GeneXpert® Carba R test). The modified Carba NP test detected carbapenemases in 229 isolates, yielding an overall sensitivity of 95.07% and a specificity of 74.07%. The overall sensitivity and specificity of the Carba M test for detecting carbapenemase-producing GNB were 97.31% and 70.37%, respectively. The isolates producing Class A/D (OXA-48-like) enzymes were identified with sensitivities of 98% and specificities of 73.68%, while those producing Class B (NDM, VIM) enzymes showed sensitivities of 94.87% and specificities of 87.5%. Conclusion: The Carba M test is a cost-effective, feasible, and rapid phenotypic test for detecting and differentiating Class B from Class A/D carbapenemases. The Carba M test could serve as a supplemental test alongside the Carba R, Carba NP test, or mCIM/eCIM for diagnosing carbapenemase production in GNB.

Comparison of the carbapenem inactivation method (CIM) and modified carbapenem inactivation method (mCIM) for the detection of carbapenemase-producing organisms

PURPOSE:Detection of carbapenemases among Gram-negative bacteria (GNB) is important for both clinicians and infection control practitioners. The Clinical and Laboratory Standards Institute recommends Carba NP (CNP) as confirmatory test for carbapenemase production. The reagents required for CNP test are costly and hence the test cannot be performed on a routine basis. The present study evaluates modifications of CNP test for rapid detection of carbapenemases among GNB.MATERIALS AND METHODS:The GNB were screened for carbapenemase production using CNP, CarbAcineto NP (CANP), and modified CNP (mCNP) test. A multiplex polymerase chain reaction (PCR) was performed on all the carbapenem-resistant bacteria for carbapenemase genes. The results of three phenotypic tests were compared with PCR.RESULTS:A total of 765 gram negative bacteria were screened for carbapenem resistance. Carbapenem resistance was found in 144 GNB. The metallo-β-lactamases were most common carbapenemases followed by OXA-48-like enzymes. The CANP test was most sensitive (80.6%) for carbapenemases detection. The mCNP test was 62.1% sensitive for detection of carbapenemases. The mCNP, CNP, and CANP tests were equally sensitive (95%) for detection of NDM enzymes among Enterobacteriaceae. The mCNP test had poor sensitivity for detection of OXA-48-like enzymes.CONCLUSION:The mCNP test was rapid, cost-effective, and easily adoptable on routine basis. The early detection of carbapenemases using mCNP test will help in preventing the spread of multidrug-resistant organisms in the hospital settings.

Objective Carbapenems are last resort antibiotics for multidrug-resistant Enterobacteriaceae . However, resistance to carbapenem is increasing at an alarming rate worldwide leading to major therapeutic failures and increased mortality rate. Early and effective detection of carbapenemase producing carbapenem-resistant Enterobacteriaceae (CRE) is therefore key to control dissemination of carbapenem resistance in nosocomial as well as community-acquired infection. The aim of present study was to evaluate efficacy of Modified strip Carba NP (CNP) test against Modified Hodge test (MHT) for early detection of carbapenemase producing Enterobacteriaceae (CPE). Material and Methods Enterobacteriaceae isolated from various clinical samples were screened for carbapenem resistance. A total of 107 CRE were subjected to MHT and Modified strip CNP test for the detection of CPE. Statistical Analysis It was done on Statistical Package for the Social Sciences (SPSS) software, IBM India; version V26. Nonparametric test chi-square and Z -test were used to analyze the results within a 95% level of confidence. Results Out of 107 CRE, 94 (88%) were phenotypically confirmed as carbapenemase producer by Modified strip CNP test and 46 (43%) were confirmed by Modified Hodge Test (MHT). Thirty-eight (36%) isolates showed carbapenemase production by both MHT and CNP test, 56 isolates (52%) were CNP test positive but MHT negative, eight (7%) isolates were MHT positive but CNP test negative and five (5%) isolates were both MHT and CNP test negative. There is statistically significant difference in efficiency of Modified CNP test and MHT ( p < 0.05). Conclusion Modified strip CNP test is simple and inexpensive test which is easy to perform and interpret and gives rapid results in less than 5 minutes. It has high degree of sensitivity and specificity. Modified strip CNP test shows significantly higher detection capacity for carbapenemase producers as compared with MHT.

PURPOSE:Resistance to carbapenems due to carbapenemases has been increasingly noticed in Enterobacteriaceae. Clinical and Laboratory Standards Institute (CLSI) has recommended the latest Carba NP (CNP) test as a confirmatory test for carbapenemase production in Enterobacteriaceae. Low sensitivity of disk diffusion (DD) and modified Hodge test (MHT) may result in missing out of resistant strains which can adversely affect clinical management. The present study compares three phenotypic tests - CNP test, DD, and MHT for detection of carbapenemase production.MATERIALS AND METHODS:Four hundred consecutive, nonduplicate Enterobacteriaceae isolates were tested for carbapenem resistance using ertapenem disc (10 μg) by Kirby–Bauer DD method, MHT, and CNP. These tests were performed and interpreted as per the CLSI standards. CNP was considered to be the reference test for comparison. Sensitivity, specificity, and accuracy rates for ertapenem DD and MHT were calculated.RESULTS:One hundred and six out of 400 strains were positive by CNP test. Of the 294 CNP-negative strains, 28 were resistant by DD and 18 were resistant by MHT. Of the 106 CNP-positive strains, 82 were resistant and 16 were intermediate by DD while 76 were positive by MHT ertapenem DD had a sensitivity and specificity of 66.04% and 90.48%, respectively. Sensitivity and specificity of MHT were 54.72% and 93.88%, respectively. There was considerable discordance between all the three tests.CONCLUSION:As a rapid, simple, and cost-effective test with a greater capability greater to detect carbapenemase producers, CNP can be implemented in routine diagnostic laboratories, thereby benefiting patient care and antimicrobial stewardship.

Carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) poses a public health issue. Rapid detection of CP-CRE colonization is challenging; existing methods are either expensive or time-consuming. We evaluated an immunochromatographic test (ICT) for detecting carbapenemases directly from broth-enriched rectal swabs. One hundred intensive care patients provided 178 pairs of rectal swabs. One swab was tested using the GeneXpert Carba-R PCR assay; the other was inoculated into brain-heart infusion broth. After 4 and 6 h of incubation at 37°C, the broth was tested with the RESIST-5 O.K.N.V.I. ICT for Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), oxacillinase-48 (OXA-48), Verona integron-encoded metallo-β-lactamase (VIM), and imipenemase (IMP) carbapenemases. Broths were subcultured after overnight incubation, and recovered carbapenem-resistant Enterobacterales isolates were tested using GeneXpert Carba-R PCR. Sensitivity, specificity, and accuracy were calculated in comparison to culture positive for CP-CRE, confirmed by PCR for KPC, NDM, OXA-48, VIM, and IMP. Of the 178 swabs, 60 were culture positive for CP-CRE. After 6 h, the ICT demonstrated a sensitivity of 65%, specificity of 97.5%, and accuracy of 86.8%. Among heavily soiled swabs, sensitivity reached 81.8% for ICT after 6 h, and the specificity was 100%. The mean execution time for carbapenemase detection using ICT was reduced by 60 h compared to culture. The ICT after 6 h incubation offers reduced execution time for detecting CP-CREs. This method may serve as a valuable rapid screening tool, especially in resource-limited settings.IMPORTANCEThe rapid spread of multidrug-resistant bacteria requires innovative solutions for early detection and prevention measures. In this study, we present a simple protocol for the direct detection of carbapenemases in rectal swabs using an immunochromatographic assay. By optimizing the assay conditions, we achieved rapid and high-accuracy identification of five clinically important carbapenemases. This method can broaden access to rapid CP-CRE detection of fecal colonization-even in laboratories with limited resources-enabling the implementation of faster and more effective infection control measures, potentially reducing the spread of resistance.

Background: Carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) pose a serious public health threat. The CDC guidelines for combating CP-CRE include a recommendation to screen selected high-risk patients. Objective: We describe a program to identify and screen patients at risk for CP-CRE. Setting: An academic, tertiary-care center with 1,297 licensed beds and 62,071 admissions per year. Methods: A report was created in the electronic medical record (EMR) to identify adult patients admitted in the previous 24 hours from countries and states with known CP-CRE transmission based on address and ZIP code. Patients with a known travel history outside the United States were also reviewed, but these data were inaccurate. Initially, a physician from Infection Prevention and Control (IPAC) placed orders for CP-CRE screening of these patients. Subsequently, a nursing protocol was developed to facilitate infection preventionists placing orders for CP-CRE screening earlier in the eligible patient’s hospital stay. An electronic communication is sent via the EMR alerting the patient care team to the order, the rationale for the order, and links to a tool kit with resources to help answer patient questions. A single perirectal swab is obtained by the nurse caring for the patient and is tested for Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), oxacillinase-48 (OXA-48), and Verona integron-encoded metallo-β-lactamase (VIM) by polymerase chain reaction (PCR). Results: From May 2018 to November 2019, 688 patients were screened for CP-CRE using the case-finding report and the nursing protocol. Overall, 9 patients with CP-CRE were identified: 1 KPC, 2 NDM, and 5 OXA-48, and 1 patient was identified to have both NDM and OXA-48. The yield of 1.3% from this screening is higher than that reported previously in the literature. Use of the nursing protocol has enabled IPAC to complete timely CP-CRE surveillance and prevent transmission to other patients. We are currently using a similar process to identify and screen persons at risk for the emerging infection Candida auris.Conclusions: The EMR can be leveraged for early identification and screening of patients with epidemiologically significant pathogens. Protocols within the EMR can be effectively replicated and modified to respond to emerging infections and changing surveillance guidelines.Funding: NoneDisclosures: Consulting fee-—Merck (Priya Sampathkumar)

Objectives:To identify the carbapenemase producing Gram-negative bacteria (GNB) by phenotypic methods and to confirm the presence of resistant genes using real-time polymerase chain reaction (PCR).Methods:This was a prospective study carried out at the Department of Microbiology, Sri Venkata Sai Medical College and Hospital, Mahabubnagar, India, from March 2018-2021. All samples were screened for carbapenem resistance by disc diffusion method and the VITEK®2 compact system (bioMérieux, France). Detection of carbapenemase was carried out using RAPIDEC®CARBA NP test (Biomeriux Private Limited, South Delhi, India), screening for metallo-β-lactamases (MBL) was carried out by double disk synergy test (DDST), and genotypic characterization by real-time PCR.Results:Among the 1093 Gram-negative bacilli identified, 220 (17.0%) were resistant to carbapenems by both tested methods. Carbapenemase detection using the RAPIDEC®CARBA NP test indicated that 207 (94.0%) were carbapenemase producers, of which 189 (91.2%) were MBL producers. The most common carbapenemase genes identified were New Delhi metallo-β-lactamase (NDM; 47.3%), followed by the co-existence of genes in combination of NDM, with Verona integron-mediated metallo-β-lactamase (VIM; 39.6%), VIM and oxacillin hydrolyzing enzymes-48 (OXA-48; 4.3%), and OXA-48 (1.4%).No gene of active on imipenem, Klebsiella pneumonia carbapenemase, VIM, or OXA-48 alone was detected.Conclusion:This study suggests routine carbapenem resistance testing among multi-drug resistant-GNBs, as most of these infections occur in hospitals. In addition, there is a possibility that these highly antibiotic-resistant genes could spread to other bacteria resulting in further dissemination.

Detection of carbapenamase production by rapid carba NP test among Enterobacteriaceae isolates in tertiary care hospital - IJMR- Print ISSN No: - 2394-546X Online ISSN No:- 2394-5478 Article DOI No:- 10.18231/j.ijmr.2019.059, Indian Journal of Microbiology Research-Indian J Microbiol Res

Background and Objectives:RESİST-4 O.K.N.V. assay is a lateral immunochromatocraphic test for the identification of oxacillinase (OXA)-48-like, Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), and Verona integron-encoded metallo-β-lactamase (VIM) producing strains. It was aimed to evaluate the performance of the RESIST-4 O.K.N.V. test and to compare it with the reference method polymerase chain reaction (PCR). Also, the objective was to determine the distribution of carbapenemase types of CRE strains isolated in our hospital.Materials and Methods:Between January 2016–October 2019, 187 strains isolated from clinical samples were included in this study. Bacterial identification was done using MALDI-TOF MS. Antibiotic susceptibility tests were studied with the VITEK-2 automated system. Meropenem minimum inhibitory concentrations (MICs) were determined by the gradient test. All strains were studied with the RESIST-4 O.K.N.V. test and then the strains were selected for the PCR test. blaOXA-48, blaNDM, blaKPC, and blaVIM were investigated with PCR. K. pneumoniae NCTC® 13438 (KWIKSTIKTM, Microbiologics®, USA) was used as the positive control, E. coli ATTC® 25922 TM (Microbiologics®, USA) and three carbapenem-sensitive clinical isolates were also used as the negative control.Results:Meropenem MIC50 and MIC90 values were determined to be >32 mg/L. With PCR blaOXA-48, blaNDM, blaKPC and blaVIM were detected in 79, 63, 20, and 4 strains, respectively. blaOXA-48 and blaNDM were found together in 51 of the isolates. blaOXA-48, blaNDM, blaKPC, and blaVIM were not detected in two strains with carbapenem resistance in susceptibility tests. The sensitivity of the immunochromatographic test was 100% for OXA-48, KPC, and VIM but 84.1% for NDM. Specificity was determined as 100% for OXA-48, NDM, KPC, and VIM.Conclusion:RESIST-4 O.K.N.V. test showed high sensitivity and specificity in detecting OXA-48, KPC, NDM, and VIM type carbapenemases. However, it should be kept in mind that there may be false-negative results related to NDM.

A rapid, practical, and accurate identification of carbapenemase-producing Enterobacteriaceae isolates is crucial for the implementation of appropriate infection control measures and proper treatment of the infections. For this purpose, a large number of phenotypic test methods have been developed, although none has 100% sensitivity and specificity. Variations in sensitivity and specificity of these tests based on the type of beta-lactamase enzymes carried by that isolates might result in differences between regions and countries. The aim of this study was to compare the performances of widely used modified Hodge test (MHT) and Carbapenemase Nordmann-Poirel (Carba NP) test in the detection of carbapenemases in Enterobacteriaceae family members. A total of 65 Enterobacteriaceae isolates (43 bla(OXA-48), 10 bla(VIM), 9 bla(IMP), 1 bla(NDM-1), 1 bla(KPC-2) and 1 bla(OXA-48)+bla(VIM) carrying strains) that showed decreased sensitivity to at least one carbapenem (ertapenem, imipenem or meropenem), and carriage of carbapenemase gene confirmed by polymerase chain reaction (PCR), were included in the study. Seventy-eight isolates showing decreased susceptibility to carbapenems but lacking carbapenemase genes were used as controls. All isolates were identified by using conventional methods as well as automated BD Phoenix System (Becton Dickinson, USA). The antimicrobial susceptibility testing was performed using the same automated system, and was confirmed by disk diffusion method. Results were evaluated according to the CLSI criteria. MHT was performed in accordance with the CLSI guideline, and Carba NP test was carried out by a modified protocol. Instead of imipenem monohydrate, which was used in the original protocol, 6 mg/ml imipenem/cilastatin was used in the modified protocol. In the study, MHT identified 90.8% (59/65) of carbapenemase-producing isolates, while 93.9% (61/65) of the isolates were identified by Carba NP test. With MHT, four Klebsiella pneumoniae producing OXA-48, one Escherichia coli producing IMP, and one K.pneumoniae producing NDM-1, and with Carba NP test, one E.coli and one K.pneumoniae producing OXA-48, one E.coli producing IMP, and one Enterobacter cloacae producing VIM could not de detected. Three OXA-48-producing isolates (two K.pneumoniae and one E.coli) yielded late and weak positive results with Carba NP test. MHT had false positivity for 31 isolates, while Carba NP test showed no false positivity. In comparison of the sensitivity and specificity of the two tests, sensitivities were found to be similar although the Carba NP has a slightly higher sensitivity than the MHT (93.9% versus 90.8%, respectively; p= 0.754), Carba NP was found more specific (100% versus 60.3%, respectively; p< 0.0001). With Carba NP test, 26% of the isolates (n= 16) were positive within 15 minutes, and 85% (n= 52) were positive within the first hour. It was concluded that, Carba NP test showed high sensitivity and specificity than the MHT and the results can be obtained more rapidly for the presence of carbapenemases in Enterobacteriaceae. The use of MHT alone is not recommended to confirm the presence of carbapenemases produced by Enterobacteriaceae. On the other hand Carba NP test can be used for this purpose, however molecular analysis should be considered for suspicious negative results.

The rise in carbapenemases-producing organisms has challenged the scientific community. Infections caused by these bacteria have limited treatment options. There are various types such as Klebsiella pneumoniae carbapenemase (Ambler class A), metallo-beta-lactamases of VIM-type, IMP-type, NDM-type (Ambler class B), and OXA-48-types (Ambler class D). An efficient strategy for detection of carbapenemase producers is important to determine the appropriate therapeutic modalities. In this study, four methods - Carba NP test, modified Carba NP (MCNP) test, carbapenem inactivation method (CIM) test, and Rapidec Carba NP kit test were evaluated. We evaluated an in-house MCNP test to detect carbapenemase production using a single protocol which gave reliable results. Furthermore, CIM using routine antibiotic discs gives good results. Both these tests were found to be cost-effective.

This study applied two phenotypic tests, namely "Carbapenemase Nordmann-Poirel" (CarbaNP) test and "Carbapenem Inactivation Method" (CIM), against the isolates carrying the carbapenem resistance genes. The study included 83 carbapenem-resistant Enterobacteriaceae isolates producing oxacillinase-48 (OXA-48) and 30 carbapenem-sensitive Enterobacteriaceae isolates. Out of the total isolates studied, 77 isolates (92.77%) were identified as Klebsiella pneumoniae and six isolates (7.23%) were identified as Escherichia coli by Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry. Polymerase chain reaction (PCR) method used to detect resistance genes found that 74 isolates (89.16%) produced OXA-48 carbapenemase, whereas nine isolates (10.84%) produced both OXA-48 and New Delhi metallo-beta-lactamase-1 (NDM-1). The isolates producing both OXA-48 and NDM-1 were found to be positive by both phenotypic tests. Among isolates carrying only blaOXA-48 gene alone, nine isolates (13.04%) for CarbaNP test and two isolates for CIM test (2.90%) displayed false negative results, respectively. The sensitivity of CarbaNP and CIM tests was found to be 89.16% and 97.59%, respectively, whereas the specificity was determined to be 100% for both tests. These findings suggest that CarbaNP and CIM tests are useful tools to identify the carbapenemase producers. Molecular methods like PCR are recommended to verify false negative tests predicted to have OXA-48 activity.

The objective of this study is to evaluate the performance of the Xpert CARBA-R Test and the phenotyping confirmation tests (MHT, CIM, Mastdiscs, and Carba NP) for the detection of carbapenemases in multidrug resistant (MDR) Klebsiella pneumoniae isolates. A total of 68 MDR K. pneumoniae isolates isolated from various clinical samples, were included in the study. The identification and antibiotic susceptibility tests of these isolates were performed using the VITEK®2 (BioMérieux, France) automated system. The Xpert CARBA-R test was used as the molecular method. The combined disc method was performed using Mastdiscs Combi-D70C that includes four antibiotic discs with specific in-hibitors. The modified Hodge test was performed on all isolates. Carbapenemase inactivation method (CIM) and Carba NP test was used for carbapenemase enzyme production. Of the 50 isolates detected to produce carbapenemase by the molecular method (Xpert CARBA-R Test), 45 (90%) were detected by MHT, 39 (78%) were detected by CIM, and 42 (84%) were detected by Mastdiscs, while all the 50 isolates were detected by the Carba NP test. When the Xpert CARBA-R Test was taken as a reference, significant differences were found between the Carba NP and Xpert CARBA-R Test. There was no significant difference between the other phenotypic methods and Xpert CARBA-R Test. The sensitivity of the MHT, CIM, combined disc, and Carba NP tests was calculated as 0.90, 0.78, 0.84, and 1 and their specificity was calculated as 0.83, 0.83, 0.83 and 0, respectively. According to the gold standard, the predictive power of MHT, CIM, and MAST methods was found to be statistically significant. There are various methods of carbapenemase detection, including phenotypic and molecular methods. There is no single detection method that is valid and usable in all conditions. Laboratories should choose a suitable carbapenemase detection and confirmation method in line with their needs, economic conditions, and infrastructures. Although the detection of the presence of carbapenemase by molecular methods is fast and reliable, low-cost phenotypic tests can be used in laboratories that do not have this possibility. It is an important advantage that the combined disc method can also determine the enzyme type.

BackgroundCarbapenem‐resistant Klebsiella pneumoniae (CRKP) has become a global public health threat, with significantly increased morbidity and mortality among high‐risk inpatients. High‐risk genotypes of CRKP, primarily including K. pneumoniae carbapenemase (KPC), oxacillinase‐48–like (OXA‐48–like), New Delhi metallo‐β‐lactamase (NDM), imipenemase (IMP), and Verona integron–encoded metallo‐β‐lactamase (VIM) types (hereafter referred to as KPC, OXA‐48–like, NDM, IMP, and VIM, respectively) as defined by international consensus due to their association with enhanced transmission, drug resistance, and mortality risk, have emerged as key challenges in clinical practice. However, the impact of different genotypic types of CRKP on mortality risk and their regional epidemiology remain unclear.MethodsThis systematic review and meta‐analysis were conducted according to the PRISMA guidelines and registered in PROSPERO (CRD420251150672). PubMed, Embase, and Web of Science were systematically searched for original studies up to September 9, 2025. Eligible studies reported genotypic types of CRKP (such as KPC, OXA‐48–like, NDM, IMP, and VIM) and patient mortality. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random‐effects model. Subgroup analyses were performed by the genotype and region. Risk of bias was assessed using the ROBINS‐I tool.ResultsA total of 58 studies involving various countries and regions were included. The pooled analysis showed that CRKP infection with high‐risk genotypes—defined in this study primarily as KPC and OXA‐48–like types due to their strong association with increased transmission, drug resistance, and mortality—was significantly associated with increased all‐cause mortality (pooled OR = 3.08, 95% CI: 2.44–3.88, p < 0.0001; I2 = 63.4%). Subgroup analysis revealed that KPC‐type CRKP infection had a higher mortality risk (pooled OR = 3.57, 95% CI: 2.82–4.53), with the effect more pronounced in China (OR = 3.85) than in other countries (OR = 3.04). The OXA‐48–like genotype also showed increased mortality risk (OR = 2.57, 95% CI: 1.47–4.50), while evidence for other genotypes such as NDM, IMP, and VIM was limited. Sensitivity analysis and publication bias tests supported the robustness of the results. GRADE assessment indicated moderate evidence for KPC but lower quality for other genotypes.ConclusionsHigh‐risk genotypes of CRKP—defined in this study as KPC and OXA‐48–like due to their strong association with increased transmission, drug resistance, and mortality—are associated with significantly increased mortality risk in infected patients, especially in China. These findings support risk stratification and personalized management of high‐risk patients and provide evidence for regional prevention and control strategies. Further multicenter and mechanistic studies are warranted to improve clinical management and patient outcomes.