Translate this page into:
Carbapenem resistance and associated resistance genes in enterobacteriaceae and non-enterobacteriaceae in India: A systematic review and meta-analysis
For correspondence: Dr Aseem Rangnekar, Department of Microbiology, ICMR-Bhopal Memorial Hospital and Research Centre, Bhopal 462 038, Madhya Pradesh, India e-mail: aseem.rangnekar1603@gmail.com
-
Received: ,
Accepted: ,
How to cite this article: Khan Z, Bose P, Kumari S, Rangnekar A, Panwalkar N, Desikan P. Carbapenem resistance and associated resistance genes in enterobacteriaceae and non-enterobacteriaceae in India: A systematic review and meta-analysis. Indian J Med Res. 2026;163:505-19. doi: 10.25259/IJMR_2824_2025
Abstract
Background and objectives
Carbapenems are highly potent antibiotics, and the emergence and spread of carbapenem resistance is a major global public health challenge. This systematic review and meta-analysis investigated the prevalence of carbapenem resistance in Enterobacteriaceae and non-Enterobacteriaceae in India and delineated the spectrum of genes associated with carbapenem resistance in carbapenem-resistant organisms.
Methods
A comprehensive systematic review of available electronic databases was conducted in accordance with PRISMA guidelines. Studies on human samples from India reporting phenotypic and genotypic data for carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-resistant non-Enterobacteriaceae (CRNE) were included. Pooled prevalence rates were determined using a random effects model to account for heterogeneity. Data analyses were performed using Meta-Analysis Online software.
Results
A total of 45 studies met the inclusion criteria. The pooled prevalence of CRE was 9% (0.07–0.11) and CRNE was 16% (0.09–0.24), with marked heterogeneity (I2=99%, P<0.001). Within Enterobacteriaceae, Escherichia coli and Klebsiella spp. exhibited the highest levels of carbapenem resistance. Among non-Enterobacteriaceae, Acinetobacter spp. and Pseudomonas spp. were the predominant resistant organisms. Genotypic analysis revealed that, among metallo β-lactamases, blaNDM-1 and blaVIM-1 were the most frequently reported genes in CRE and CRNE, while blaOXA-48 was the major determinant in CRE, whereas blaOXA-23 and blaOXA-51 predominated in CRNE, among the serine β-lactamases.
Interpretation and conclusions
This meta-analysis identified diverse carbapenem-resistant organisms and genetic determinants in both CRE and CRNE. Regional variation in prevalence was evident, with a notable lack of data from Central India. The findings identify lacunae in reporting, emphasise on circulating genes, and highlight the urgent need for strengthening nationwide surveillance to help formulate robust evidence-based strategies for combating carbapenem resistance.
Keywords
Carbapenem resistant
Carbapenem resistant genes
Enterobacteriaceae
India
Non-Enterobacteriaceae
Prevalence
Antibiotic resistance is a growing global concern, with resistance now documented for all known antibiotics. Many organisms of the Enterobacteriaceae family have acquired the broadest range of resistance mechanisms, including structural adaptations and the production of beta-lactamase enzymes that break down antibiotics, specifically carbapenem.1,2 Such adaptations have also been seen in other microorganisms of the non- Enterobacteriaceae families, Acinetobacter baumannii and Pseudomonas aeruginosa, in particular. Carbapenems are broad-spectrum antibiotics, generally reserved for the treatment of multidrug resistant (MDR) pathogens. Indiscriminate antibiotic use, suboptimal infection prevention and control practices, and limited access to advanced diagnostic modalities collectively contribute to the increased transmission and recurrent outbreaks of carbapenem-resistant organisms.3
Carbapenem resistance is typically driven by mobile genetic elements carrying beta-lactamase genes. The epidemiology and molecular profiles of carbapenem-resistant organisms have been investigated across various regions of India. The most frequently reported carbapenemase genes include blaNDM-1, blaVIM, blaIMP, blaOXA-48, blaOXA-181, and blaKPC.4,5 The widespread dissemination of these resistance determinants across diverse bacterial species has contributed to a rising burden of infections, posing a significant threat to clinical care and hospital environments. Studies from India have reported concerning rates of carbapenem resistance among Gram-negative bacteria. However, consolidated evidence on the prevalence and molecular determinants of carbapenem-resistant pathogens remains limited. A systematic review and analysis of available data is essential to improve understanding of the burden and distribution of carbapenem resistance in India. We could not come across any comprehensive systematic review and meta-analysis to report the pooled prevalence of carbapenem resistance in India. This study aims to address the critical evidence gap and thus support the development of informed, country-specific public health strategies. In this systematic review and meta-analysis, we estimated the pooled prevalence (PPr) of carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-resistant non-Enterobacteriaceae (CRNE) in India and the genes associated with carbapenem resistance.
Methods
This systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement6 and was registered in the International Prospective Register of Systematic Reviews (PROSPERO ID-CRD420251119960).
Database search
Studies were identified through databases such as PubMed and Google Scholar. The combination of keywords used in the search included “prevalence”, “epidemiology”, “gram-negative bacilli”, “Acinetobacter baumannii, Pseudomonas, “carbapenem resistance”, “carbapenem-resistance genes”, blaNDM, blaVIM,blaKPC, blaOXA, “carbapenemase”, “Enterobacteriaceae”, “non-Enterobacteriaceae”, and “India”. Online searches were conducted between December 2023 and May 2024. The collected literature was saved in Zotero citation manager.
Inclusion and exclusion of studies
Studies were included that were conducted on human samples, reporting phenotypic and genotypic results, of carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-resistant non-Enterobacteriaceae (CRNE), and were exclusively published from India. Duplicate studies were removed.
Data extraction and quality assessment
Data from the selected studies were extracted into an Excel sheet, with the following variables chosen as input: publication year, sample size, proportion of CRE and CRNE, and the genes coding for carbapenem resistance. A table was created to present phenotypic and genotypic data related to carbapenem resistance, and these data were stratified by geographical zones. Carbapenem-resistance genes (CRG) reported from Enterobacteriaceae and non-Enterobacteriaceae in various studies were presented by a chord diagram using Rstudio (version 4.5.2) software. All authors independently verified the extracted data. A modified Downs and Black checklist7 was adopted to assess the quality of studies, as employed in similar reviews.8 These were: a clearly described objective of the study, study design, sample size, percentages, missing data management, and other characteristics explored/reported.
Group and subgroup analysis
Two main groups, Enterobacteriaceae and non-Enterobacteriaceae, were identified for group analysis. Variables for subgrouping were CRE, CRNE, different zones of India, CRG, and publication year.
Statistical analysis
Meta-analysis was performed using MetaAnalysis software (supported by ELIXIR Hungary). The statistics for each study were reported using the inverse variance method, along with proportions accompanied by 95% confidence intervals (CI). A random-effect meta-analysis was conducted using the DerSimonian-Laird method, which estimates the variance of effect sizes across studies (τ2). Q/χ2, known as Cochran’s heterogeneity, which measures the overall dispersion of studies around the grand mean, and I2, represent total variation across studies. Egger’s test was conducted to assess publication bias. A P value ≤0.05 was statistically significant.
Results
Overview of studies
Searches across different databases yielded a total of 300 studies, of which 150 were common between datasets. Preliminary screening based on title, abstract, and author affiliations led to the exclusion of 60 studies. Assessment of eligibility of studies excluded another 45 studies ( Fig. 1). The remaining 45 studies were selected for systematic review and meta-analysis.
Out of 45 studies, 15 studies solely represent CRE, 15 CRNE, and the remaining 15 studies included both CRE and CRNE. Among studies on CRE isolates, the highest number of studies were on Klebsiella spp. Followed by Escherichia coli. Among the CRNE, the highest number of studies were on Acinetobacter spp. Followed by Pseudomonas spp. Other CRE and CRNE isolates are presented in the Table9-53.
| S. No | Zone and authors | Sampling year | Sample Size | Carbapenem-resistant enterobacteriaceae (%) | Genes Studied (n) | Carbapenem-resistant non-enterobacteriaceae (%) | Genes studied (n) |
| North east zone | |||||||
| 1 | Shakil and Khan9, 2010 | Jan 2009 to Dec 2009 | 920 | Acinetobacter baumannii (0.6) | |||
| 2 | Garg et al10, 2019 | Aug 2014 to July 2016 | 8973 | Klebsiella pneumoniae (7.6) | blaNDM-1 (7), blaOXA-48 (8), blaIMP-1 (1), blaVIM-1 (5), and blaSPM (2) | Pseudomonas aeruginosa (24) | blaNDM-1 (53), blaVIM-1 (14), blaOXA-48 (8), and blaSPM (1) |
| Enterobacter spp. (5) | blaNDM-1 (4), blaOXA-48 (6) blaIMP-1 (1), blaVIM-1 (2), and blaSPM (1) | Acinetobacter spp. (22) | blaNDM-1 (51), blaOXA-48 (10), and blaVIM-1 (12) | ||||
| Proteus spp. (4.8) | blaNDM-1 (8), blaOXA-48 (2), and blaVIM-1 (3) | Stenotrophomonas maltophilia (1.6) | blaNDM-1 (4) | ||||
| Morganella morganii (2.8) | blaNDM-1 (6), and blaVIM-1 (2) | Alcaligenes faecalis (2.5) | blaVIM-1 (2) | ||||
| Providencia spp. (3.8) | blaNDM-1 (6), and blaVIM-1 (2) | ||||||
| Citrobacter spp. (5.7) | blaNDM-1 (10), blaOXA-48 (3), and blaVIM-1 (4) | ||||||
| Escherichia coli (16) | blaNDM-1 (25), blaIMP-1 (2), blaVIM-1 (6), and blaOXA-48 (11), and blaSPM (3) | ||||||
| 3 | Rahman et al11, 2014 | Jan 2013 to Dec 2014 | 464 | Klebsiella pneumoniae (45.4) | blaNDM-1 (20) | ||
| Escherichia coli (31.8) | blaNDM-1 (14) | ||||||
| Citrobacter spp. (9.09) | blaNDM-1 (4) | ||||||
| Enterobacter spp. (4.5) | blaNDM-1 (2) | ||||||
| Providencia spp. (12.3) | blaNDM-1 (4) | ||||||
| 4 | Naim et al12, 2017 | Jan 2015 to June 2015 | 116 | Citrobacter spp. (24.1) | blaNDM-1 (14) | Pseudomonas spp. (20.6) | blaNDM-1 (7) |
| Serratia spp. (14.6) | blaNDM-1 (8) | Acinetobacter spp. (4.3) | blaNDM-1 (2) | ||||
| Klebsiella spp. (7.75) | blaNDM-1 (7) | Aeromonas spp. (0.8) | |||||
| Proteus spp. (3.4) | blaNDM-1 (2) | ||||||
| Providencia spp. (1.7) | |||||||
| Escherichia coli (15.6) | blaNDM-1 (26) | ||||||
| 5 | Ahmad et al13, 2019 | Jan 2016 to Dec 2017 | 17 | Klebsiella pneumoniae (100) | blaNDM-1 (13), blaNDM-4 (1), blaNDM-5 (3), blaOXA-48 (7), and blaVIM-2 (7) | ||
| 6 | Kumari et al14, 2021 | June 2019 to May 2020 | 99 | Klebsiella pneumoniae (27.2) | blaNDM-1 (13), blaNDM-1 and blaVIM-1 (6), and blaVIM-1 (8) | Acinetobacter baumannii (37.3) | blaNDM-1 (15), blaNDM-1 and blaVIM-1 (8), and blaVIM-1 (18) |
| Escherichia coli (5.05) | blaNDM-1 (3) | Pseudomonas aeruginosa (25.8) | blaNDM-1 (5), blaNDM-1 and blaVIM-1 (1), and blaVIM-1 (3) | ||||
| Proteus mirabilis (2.02) | blaNDM-1 (1), and blaVIM-1 (1) | Pseudomonas spp. (2.02) | |||||
| Enterobacter spp.(1) | |||||||
| Citrobacter freundii (1) | |||||||
| 7 | Singh et al15, 2023 | Oct 2016 to Mar 2017 | 500 | Escherichia coli (58.2) | blaNDM-1 (98), blaVIM-1 (58), blaIMP-1 (49), blaNDM-1 and blaVIM-1 (49) and blaVIM-1 and blaIMP-1 (27) | ||
| Klebsiella pneumoniae (41.7) | blaNDM-1 (72), blaVIM-1 (25), blaIMP-1 (29), blaNDM-1 and blaVIM-1 (21) and blaVIM-1 and blaIMP-1(8) | ||||||
| 8 | Mohanty et al16, 2017 | Jan 2011 to Dec 2013 | 387 | Klebsiella pneumoniae (63.4) | blaNDM-1 (39), blaVIM-1 (4), blaOXA-48 (13), blaOXA-181 (18), and blaKPC (2) | ||
| Escherichia coli (36.5) | blaNDM-1 (22), blaOXA-48 (10), blaOXA-181 (4), and blaVIM-1 (2) | ||||||
| 9 | Ralte et al17, 2022 | Jan 2019 to Dec 2021 | 141 | Escherichia coli (43.9) | blaOXA-48 (4) | Pseudomonas aeruginosa (6.3) | blaOXA-48 (1) |
| Shigella sonnei (18.7) | |||||||
| Klebsiella pneumoniae (30.4) | |||||||
| 10 | Bora et al18, 2013 | Jan 2012 to Dec 2012 | 270 | Escherichia coli (100) | blaNDM-1 (14) | ||
| 11 | Bali et al19, 2013 | Jan 2012 to Dec 2012 | 165 | Acinetobacter spp. (60) | blaOXA-23 (47) and blaOXA-51 (47) | ||
| 12 | Niranjan et al20, 2013 | Jan 2012 to Dec 2012 | 30 | Acinetobacter baumannii (100) | blaVIM-1 (30), blaOXA-23 (14), blaOXA-51 (30), blaIMP-1 (30), blaVIM-2 (6), and blaIMP-2 (15) | ||
| 13 | Mohan et al21, 2015 | Jan 2008 to Dec 2012 | 166 | Klebsiella pneumoniae (7) | blaNDM-1 (17), blaIMP-1 (3), and blaVIM-1 (2) | Pseudomonas aeruginosa (29.5) | blaNDM-1 (4), blaIMP-1 (2), and blaVIM-1 (15) |
| Escherichia coli (14.4) | blaNDM-1 (16), blaVIM-1 (7), and blaKPC (1) | Acinetobacter baumannii (7) | blaIMP-1 (1), and blaVIM-1 (26) | ||||
| Enterobacter aerogenes (5.4) | blaNDM-1 (7) | ||||||
| Morganella morganii (0.6) | blaNDM-1 (1) | ||||||
| Proteus mirabilis (0.6) | blaNDM-1 (1) | ||||||
| Providencia stuartii (0.6) | blaNDM-1 (1) | ||||||
| 14 | Chatterjee et al22, 2017 | Jan 2015 to June 2015 | 1544 | Klebsiella pneumoniae (8.7) | blaVIM-1 (3) | Pseudomonas aeruginosa (15.9) | blaVIM-1 (20), and blaNDM-1 (31) |
| Escherichia coli (7.7) | BlaVIM-1 (1), and blaNDM-1 (49) | Acinetobacter spp. (53.6) | blaNDM-1 (104), and blaVIM-1 (3) | ||||
| Enterobacter cloacae (3.6) | Elizabethkingia meningoseptica (3.09) | ||||||
| Enterobacter aerogenes (2.5) | Stenotrophomonas maltophilia (2.06) | ||||||
| Citrobacter freundii (2.06) | |||||||
| Citrobacter koseri (1) | |||||||
| 15 | Gautam et al23, 2023 | Mar 2018 to Dec 2021 | 307 | Acinetobacter baumannii (100) | BlaVIM-1 (1), blaIMP-1 (4), blaOXA-58 (6), and blaOXA-23 (96) | ||
| South zone | |||||||
| 16 | Amudhan et al24, 2011 | Jan 2010 to Dec 2010 | 110 | Acinetobacter baumannii (77.4) | blaOXA-23 (95), blaOXA-24 (2), blaOXA-51 (99), blaIMP-1 (1), and blaVIM-1 (54) | ||
| 17 | Shenoy et al25, 2014 | July 2012 to Dec 2012 | 74 | Klebsiella pneumoniae (13.5) | blaNDM-1 (8) | Acinetobacter baumannii (27) | blaNDM-1 (4) |
| Escherichia coli (13.5) | blaNDM-1 (5) | Pseudomonas aeruginosa (5.4) | |||||
| Providencia rettgeri (25.6) | blaNDM-1 (8) | Burkholderia cepacia (1.3) | blaNDM-1 (1) | ||||
| Proteus vulgaris (2.7) | blaNDM-1 (2) | Pseudomonas putida (1.35) | blaNDM-1 (1) | ||||
| Citrobacter freundii (1.35) | Roultella ornitholytica (1.35) | blaNDM-1 (1) | |||||
| Enterobacter cloacae (5.4) | blaNDM-1 (4) | Alcaligenes fecalis (1.35) | |||||
| 18 | Aseem et al26, 2016 | Jan 2014 to Dec 2015 | 153 | Klebsiella pneumoniae (100) | blaKPC (25) | ||
| 19 | Bhaskar et al27, 2019 | July 2017 to Sep 2018 | 250 | Klebsiella pneumoniae (100) | blaNDM-1 (16) | ||
| 20 | Gantasala et al28, 2022 | Jan 2020 to June 2020 | 1602 | Escherichia coli (50) | blaNDM-1 (11), blaOXA-48 (8), blaVIM-1 (4), and blaKPC (1) | ||
| Klebsiella spp. (50) | |||||||
| 21 | Amudhan et al29, 2012 | Apr 2010 to Oct 2010 | 179 | Pseudomonas aeruginosa (34) | blaVIM-1 (34), and blaIMP-1 (2) | ||
| Acinetobacter baumannii (64) | blaVIM-1 (53), and blaIMP-1 (1) | ||||||
| Acinetobacter lwoffii (0.5) | blaVIM-1 (1) | ||||||
| Pseudomonas stutzeri (0.5) | |||||||
| 22 | Mohanam and Menon30, 2017 | Jan 2014 to Dec 2015 | 213 | Pseudomonas aeruginosa (100) | blaVIM-1 and blaIMP-1 (1), blaVIM-1 and blaNDM-1 (3), blaIMP-1 and blaNDM-1 (2), blaVIM-1 (7), and blaNDM-1 (6) | ||
| 23 | Girija et al31, 2018 | Jan 2016 to Dec 2017 | 1000 | Acinetobacter baumannii (100) | blaVIM-1 (25), and blaGIM (12) | ||
| 24 | Manohar et al32, 2021 | Jan 2015 and Dec 2016 | 151 | Escherichia coli (37.7) | blaNDM-1 (12), blaOXA-23 (4), blaOXA-181 (9), and blaIMP-1 (1) | Pseudomonas aeruginosa (6.6) | blaNDM-1 (1) |
| Klebsiella pneumoniae (26.4) | blaNDM-1 (5), blaOXA-23 (1), blaOXA-51 (2), and blaOXA-181 (7) | Acinetobacter baumannii (4.6) | blaOXA-23 (2), blaOXA-51 (7), and blaOXA-181 (2) | ||||
| Salmonella Typhi (5.2) | Achromobacter xylosoxidans (3.3) | blaNDM-1 (1) | |||||
| Enterobacter cloacae (5.2) | Elizabethkingia meningoseptica (0.6) | ||||||
| Proteus mirabilis (3.3) | |||||||
| Klebsiella oxytoca (3.3) | |||||||
| Serratia marcescens (3.3) | blaNDM-1 (1) | ||||||
| 25 | Nachimuthu et al33, 2015 | Jan 2014 to Dec 2014 | 93 | Escherichia coli (52) | blaNDM-1 (9) | Pseudomonas aeruginosa (10) | blaIMP-1 (4) |
| Klebsiella pneumoniae (11) | blaNDM-1 (4) and blaOXA-181 (3) | Providencia rettgeri (1) | blaNDM-1 (1) | ||||
| Enterobacter hormaechei (3) | blaNDM-1 (2) | Acinetobacter baumannii (3.2) | |||||
| 26 | Jayakaran et al34, 2019 | June and Aug 2018 | 101 | Klebsiella pneumoniae (26.3) | blaNDM-1 (4) | Pseudomonas spp. (15.8) | |
| Escherichia coli (24.2) | blaNDM-1 (2) | Acinetobacter spp. (4.2) | blaNDM-1 (1), blaOXA-23 (1) | ||||
| 27 | Vijayakumar et al35, 2016 | Jan 2014 to July 2015 | 103 | Acinetobacter baumannii (100) | blaNDM-1 (20), blaOXA-23 (82), blaOXA-24 (2), blaOXA-51 (103), and blaVIM-1 (6) | ||
| 28 | Veeraraghavan et al36 , 2017 | Jan 2015 to Sep 2016 | 115 | Klebsiella pneumoniae (100) | blaNDM-1 (22), blaOXA-48 (15) and blaNDM-1 and blaOXA-48 (32) | ||
| 29 | Uma Karthika et al37, 2009 | Jan 2007 to Apr 2007 | 55 | Acinetobacter baumannii (89) | blaIMP-1 (23) | ||
| 30 | Mohamuda Parveen et al38, 2012 | Jan 2011 to Mar 2011 | 179 | Klebsiella pneumoniae (39.2) | |||
| Escherichia coli (60.8) | |||||||
| 31 | Ramakrishnan et al39, 2014 | Nov 2009 to Oct 2010 | 75 | Pseudomonas aeruginosa (84) | blaVIM-1 (1), blaVIM-2 (10) | ||
| 32 | Vamsi et al40, 2022 | Mar 2018 to Dec 2021 | 1093 | Escherichia coli (28.4) | blaNDM-1 (12) | Pseudomonas spp. (8.2) | blaNDM-1 (9), blaNDM-1 and blaOXA-48 (2), blaNDM-1, blaOXA-48 and blaVIM-1 (2) |
| Klebsiella pneumoniae (58.2) | blaNDM-1 (47), blaNDM-1 and blaOXA-48 (1), blaNDM-1, blaOXA-48 and blaVIM-1 (4) | Acinetobacter spp. (9) | blaNDM-1 (10), blaNDM-1, blaOXA-48 and blaVIM-1 (9) | ||||
| Enterobacter spp. (2) | blaNDM-1 (4), blaNDM-1, blaOXA-48 and blaVIM-1 (3) | ||||||
| 33 | Solanki et al41, 2014 | Jan 2012 to Sep 2012 | 60 | Escherichia coli (25) | blaNDM-1 (12), blaVIM-1 (2), blaKPC (1), blaNDM-1 and blaKPC (2) | Acinetobacter baumannii (18) | blaNDM-1 (7), blaIMP-1 + blaNDM-1 (1) and blaNDM-1 and blaKPC (7) |
| Klebsiella pneumoniae (35) | blaNDM-1 (25), blaNDM-1 and blaKPC (5) | Pseudomonas aeruginosa (22) | BlaVIM-1 (3) | ||||
| East zone | |||||||
| 34 | Mohan et al42, 2017 | Jan 2014 to Dec 2015 | 232 | Escherichia coli (100) | blaNDM-1 (27) and blaVIM-1 (20) | ||
| 35 | Verma et al43, 2019 | Jul 2017 to Sep 2018 | 559 | Pseudomonas aeruginosa (100) | blaNDM-1 (29), blaNDM-1 and blaVIM-1 (6), blaGIM (7), blaVIM-1 (30) and blaSIM (7) | ||
| 36 | Kumari et al44, 2022 | Mar 2019 to Dec 2019 | 101 | Escherichia coli (12.7) | blaNDM-1 (7) | Pseudomonas aeruginosa (18.2) | |
| Klebsiella pneumoniae (41.7) | blaNDM-1 (4) | Acinetobacter baumannii (14.3) | blaNDM-1 (1) | ||||
| 37 | Castanheira et al45, 2009 | 2006 | 301 | Pseudomonas spp. (18.9) | BlaVIM-1 (57) | ||
| 38 | Datta et al46, 2014 | Jan 2007 to Dec 2011 | 1985 | Escherichia coli (26) | blaNDM-1 (6) | ||
| Klebsiella pneumoniae (65) | blaNDM-1 (6) | ||||||
| Enterobacter cloacae (7.6) | blaNDM-1 (3) | ||||||
| 39 | Das et al47, 2019 | July 2017 to Sep 2018 | 415 | Escherichia coli (20) | blaNDM-1 (25), blaOXA-48 (3), and blaNDM-1 and blaOXA-48 (4) | Acinetobacter baumannii (8.4) | blaNDM-1 (2), blaOXA-23 (4) and blaOXA-58 (2) |
| Klebsiella pneumoniae (53.5) | blaNDM-1 (3), blaOXA-48 (62), blaNDM-1 and blaOXA-48 (16) and blaKPC (2) | Acinetobacter spp. (2) | blaNDM-1 (1) | ||||
| Enterobacter spp. (4.5) | blaNDM-1 (6) | Pseudomonas aeruginosa (9.8) | blaNDM-1 (11) and blaVIM-1 (1) | ||||
| Citrobacter freundii (1) | blaNDM-1 (1) and blaOXA-48 (1) | Pseudomonas spp. (1) | blaVIM-1 (1) | ||||
| 40 | Longjam et al48, 2014 | Mar 2018- Dec 2021 | 289 | Acinetobacter baumannii (100) | blaNDM-1 (4) and blaOXA-23 (269), blaOXA-51 (277) | ||
| West zone | |||||||
| 41 | Prabhala et al49, 2024 | Jan 2022 to Dec 2022 | 10,632 | Escherichia coli (20.8) | blaNDM-1 (9), blaOXA-48 (6), blaNDM-1 and blaOXA-48 (9) and blaNDM-1, blaVIM-1 and blaOXA-48 (1) | Pseudomonas aeruginosa (12.2) | blaNDM-1 (4), blaOXA-48 (2), blaVIM-1 (1) and blaNDM-1, blaVIM-1 and blaOXA-48 (1) |
| Enterobacter spp. (0.32) | blaNDM-1 (1) | Acinetobacter baumannii (6.7) | blaNDM-1 (7) | ||||
| Klebsiella pneumoniae (59.9) | blaNDM-1 (43), blaOXA-48 (19), blaNDM-1 and blaOXA-48 (53) and blaNDM-1, blaVIM-1 and blaOXA-48 (2) | ||||||
| 42 | Purohit et al50, 2012 | Jan 2011-Dec 2011 | 130 | Acinetobacter baumannii (33) | blaVIM-1 (7) | ||
| 43 | Khajuria et al51, 2014 | Jan 2012 to Dec 2012 | 300 | Escherichia coli (100) | blaNDM-1 (300) and blaNDM-1 and blaOXA-48 (25) | ||
| 44 | Giri et al52, 2021 | Jan 2020 to June 2020 | 50 | Klebsiella pneumoniae (100) | blaNDM-1 (45), blaOXA-48 (30), blaVIM-1 (6) and blaNDM-1 and blaOXA-48 (25) | ||
| 45 | Rajni et al53, 2022 | Oct 2018 to Dec 2018 | 1240 | Escherichia coli (1.12) | blaNDM-1 (11), blaOXA-48 (12), blaIMP (2), blaVIM (1), blaAIM (8), blaGIM (1), blaSIM (3), blaBIC (8) and blaSPM (6) | ||
| Klebsiella pneumoniae (1.12) | blaNDM-1 (11), blaOXA-48 (12), blaIMP (2), blaAIM (8), blaSIM (3), blaBIC (8) and blaSPM (6) | ||||||
Of the 45 studies included, 43 studies reported carbapenem resistance genes. The Table presents the number of genes detected in CRE and CRNE. Within the CRE group, (i) five studies identified the blaKPC gene of Ambler Class A, (ii) 26 studies identified genes linked to Ambler Class B, including blaNDM-1, blaNDM-4, blaNDM-5, blaIMP, blaVIM, blaIMP-1, blaVIM-1, blaVIM-2, blaAIM, blaGIM, blaSIM, blaBIC, and blaSPM. Co-occurrence of genes includes blaVIM-1 + blaNDM-1, blaVIM-1 + blaIMP-1, blaOXA-48 + blaNDM-1,blaKPC + blaNDM-1,blaVIM-1 + blaNDM-1 +blaOXA-48, and (iii) 15 studies identified genes linked to Ambler Class D, specifically blaOXA-23, blaOXA-28, blaOXA-48, blaOXA-51, and blaOXA-181.
In the CRNE group, (i) only one study reported blaKPC gene with co-occurrence of blaNDM-1(Ambler Class A), (ii) twenty-five studies identified genes linked to Ambler Class B, including blaNDM-1, blaIMP-1, blaVIM-1, blaVIM-2, blaGIM, blaSIM, and blaSPM. Co-occurrence of genes includes blaVIM-1 + blaNDM-1, blaVIM-1 + blaIMP-1, blaNDM-1 + blaIMP-1, blaNDM-1 + blaOXA-48, and blaNDM-1 + blaOXA-48 + blaVIM-1, (iii) Seventeen studies identified genes linked to Ambler Class D, specifically blaOXA-23, blaOXA-24, blaOXA-28, blaOXA-48, blaOXA-51, blaOXA-58, and blaOXA-181 as shown in the Table9-53. Phenotypic studies were distributed across various geographical regions in India: 18 studies from the South zone, 15 from the North and Northeast zone, 7 from the East zone, and 5 from the West zone. Genotypic studies encompass 19 studies from the South zone, 14 from the North and Northeast zone, 7 from the East zone, and 5 from the West zone. No study was reported in the literature from the Central zone.
Meta-analysis findings
Phenotypic pooled prevalence
According to the meta-analysis results, the PPr of carbapenem resistance (CR) in Enterobacteriaceae was 0.09% (0.7–0.11), with a considerable heterogeneity (τ2=0.026: Q/χ2=9078.75; I2=99%; P<0.001) (Supplementary Fig. 1), and publication bias (Egger’s test, P<0.001). The PPr of CR in non-Enterobacteriaceae was 0.16% (0.09–0.24), with a considerable heterogeneity (τ2=0.016: Q/χ2=7537.3; I2=99%; P<0.001) (Supplementary Fig. 2) and publication bias (Egger’s test, P< 0.001). The authors considered a meta-analysis to be appropriate, as it generated robust pooled prevalence estimates, i.e., 9% for carbapenem resistance in Enterobacteriaceae and 16% in non-Enterobacteriaceae, based on high-quality studies, despite substantial heterogeneity (I2=99%). These findings underscore the critical need to understand existing evidence on the prevalence of carbapenem resistance in India.
High CR in Enterobacteriaceae was observed in Klebsiella pneumoniae and Escherichia coli with PPr 0.21% (0.15-0.28) and 0.14% (0.08-0.20), respectively. The PPr values for other subgroups among CRE include Providencia spp. (0.03%, 0.00-0.06), Proteus spp. (0.02%, 0.01-0.04), Enterobacter spp. (0.01%,0.00-0.02), Citrobacter spp. (0.01%, 0.00-0.03). Some microorganisms that were very few in number were grouped as group 7 (Morganella morganii, Salmonella typhi, Shigella sonnei, and Serratia spp.) with PPr 0.03% (0.01-0.07) as shown in the forest plot (Supplementary Fig. 1). High CR in non-Enterobacteriaceae was observed in Acinetobacter spp. and Pseudomonas spp. with PPr 0.30% (0.15-0.49) and 0.12% (0.06-0.20), respectively. Limited studies have documented additional CRNE, including Achromobacter xylosoxidans, Elizabethkingia meningoseptica, Alcaligenes faecalis, Stenotrophomonas maltophilia, Roultella ornitholytica, Burkholderia cepacia, and Aeromonas spp., which were categorised as group 3 in the forest plot and subsequently analysed. The PPr for group 3 was 0.01% (0.00-0.01) as depicted in Supplementary Figure 2.
The CRE dataset spanned studies from 2013 to 2023, exhibiting a high degree of heterogeneity (τ2=0.076: Q/χ2=6422.78; I2=99.5%; P=0.001) and a PPr of 0.40 (0.31-0.50). High prevalence of CRE was noted during the years 2016-17 and 2020-21, with PPr of 0.58 (0.25-0.88) and 0.58 (0.23-0.89), respectively. This was followed by PPr of 0.48 (0.10-0.87), 0.43 (0.001-1.00), 0.34 (0.14-0.57), and 0.14 (0.07-0.23) for the years 2014-15, 2012-13, 2018-19, and 2022-23, respectively. The CRNE included studies from 2008 to 2023, exhibiting a high level of heterogeneity (τ2=0.109; Q/χ2=7,000.71; I2=99.6%; P=0.001). The PPr was 0.38 (0.27-0.50). High CRNE with PPr 0.86 (0.43-1.0) was observed during the year 2012–13 (n=04), and the lowest was observed in 2018-19 with PPr 0.12 (0.03-0.27).
Studies on CRE were sourced from 17 Indian States exhibiting a high level of heterogeneity (τ2=0.03; Q/χ2=3755.68; I2=99.2%; P=0.001). The highest prevalence of CRE was observed in the southern zone of India with a PPr of 0.33 (0.17-0.51), followed by the west zone (n=4), the north and north-east zone (n=11), and the east zone (n=4), which had PPr of 0.23 (0.00-0.78), 0.19 (0.04-0.39), and 0.16 (0.05-0.30), respectively. The highest PPr in the CRNE group was from the south zone (n=14) of India, with a PPr of 0.47 (0.2-0.75), followed by the west zone (n=2) with a PPr of 0.35 (0.00-1.0), the east zone (n=4) with a PPr of 0.32 (0.01-0.80), and the north-north-east zone (n=9) with a PPr of 0.14 (0.03-0.31). However, the PPr difference in CRE (χ2=3.29, P=0.34) and CRNE (χ2=5.74, P=0.12) in zones is not found to be statistically significant after subgroup analysis.
Genotypic pooled prevalence
Ambler class A carbapenemases
Serine-β-lactamases: Among Ambler class A carbapenemases, the blaKPC gene was reported by 6 studies (n=30) and was primarily identified in Klebsiella spp. and Escherichia coli. The blaKPC gene with the blaNDM-1 gene (n=7) was reported by one study in Klebsiella spp. and Escherichia coli. One study reported the co-occurrence of blaNDM-1and blaKPC genes in Acinetobacter baumannii in the CRNE group. The association of genes with the organisms is illustrated through a chord diagram in Figure 2. The PPr of carbapenem resistance genes encoding serine-β-lactamases in CRE was 0.19 (0.03-0.44), exhibiting heterogeneity (τ2=0.115: Q/χ2=133.29; I2=95.5%; P<0.01).
Ambler class B carbapenemases
Metallo-β-lactamases: Among metallo-β-lactamases producing CRE, blaNDM-1 was the most frequently reported gene (n=1175) in Escherichia coli and Klebsiella spp, followed byblaIMP-1 (n=88) and blaVIM-1 (n=68). Additional carbapenem resistance genes identified include blaAIM (n=16), blaBIC (n=16), blaSPM (n=3), blaVIM-2 (n=7), blaSIM (n=6), blaNDM-5 (n=3), blaIMP (n=2), blaGIM (n=1), blaVIM (n=1), and blaNDM-4 (n=1).Some CRE harboured more than one carbapenem resistance genes include blaNDM-1 and blaOXA-48 (n=165), blaNDM-1 and blaVIM-1 (n=76), blaIMP-1 and blaVIM-1 (n=35), and blaNDM-1, blaVIM-1 and blaOXA-48 (n=10). The number of genes present in CRE was presented through a chord diagram ( Fig. 2).
Among metallo-β-lactamases producing CRNE, the blaNDM-1gene was predominantly reported (n=440), followed by blaVIM-1(n=309), blaIMP-1 (n=289), blaIMP-2 (n=15), blaGIM (n=19), blaVIM-2 (n=16), blaSIM (n=7), and blaSPM (n=1). Some CRNE harboured more than one carbapenem resistance genes include blaNDM-1 and blaVIM-1 (n=18) and blaNDM-1, blaVIM-1 and blaOXA-48 (n=11), blaIMP-1 and blaNDM-1 (n=3), blaNDM-1 and blaOXA-48 (n=2) and blaIMP-1 and blaVIM-1 (n=1), as illustrated in Figure 2. The PPr of carbapenem resistance genes encoding metallo-β-lactamases in CRE and CRNE was 0.42 (0.31-0.54), exhibiting heterogeneity (τ2=0.149: Q/χ2=2432.35; I2=98%; P=0.001), and 0.26 (0.17-0.36), with heterogeneity (τ2=0.118: Q/χ2=1754.01; I2=97%; P=0.001), respectively.
Ambler class D carbapenemases
Serine-β-lactamases: Among the serine-β-lactamases, Class D carbapenemase-producing CRE, the most frequently reported gene was blaOXA-48 (n=209). The blaOXA-181 (n=19), blaOXA-23 (n=5) and blaOXA-51 (n=2) were also reported. In CRNE, the predominant blaOXA gene variants identified were blaOXA-23 (n = 610) and blaOXA-51 (n=563) in Acinetobacter spp. The other identified genes were blaOXA-48 (n=21), blaOXA-58 (n=8), blaOXA-24 (n=4), and blaOXA-181 (n=2) in the respective CRE and CRNE were shown in Figure 2.
The PPr of the examined CRG encoding for serine-β-lactamases in CRE and CRNE was 0.28 (0.18-0.41), exhibiting heterogeneity (τ2=0.0561: Q/χ2=309.46; I2=95.2%; P<0.0001), and 0.63 (0.38-0.85), also with heterogeneity (τ2=0.3025: Q/χ2=1957.24; I2=99%; P=0.001), respectively.
Discussion
This study included publications that were reported from India to generalise the findings for the proportion of carbapenem resistance among gram negative bacilli. Carbapenem resistance was present in a significant proportion of CRE and CRNE in this study. The estimate of CRE is comparable to the data from Kuwait54 and the United Arab Emirates,55 but higher than that reported by European nations56 and Afghanistan,57 and lower than that reported from Saudi Arabia and Egypt.58,59 Likewise, our result of CRNE is consistent with the observation reported from sub-Saharan Africa.60 In contrast, Iran and Pakistan estimated a higher prevalence of CRNE.61,62 The findings of our study indicate a significant level of variability in the overall prevalence of CRE and CRNE. Subgroup analysis was therefore conducted by organisms, geographical zone, and publication year of the study. Carbapenem resistance in Klebsiella spp. and Escherichia coli was notably high, as compared to the data reported from Pakistan and East Africa62,63 and lower estimated from West Africa64. We found that the PPr of Enterobacter spp., Proteus spp., Citrobacter spp., Providencia spp., Morganella morganii, Salmonella typhi, Shigella sonnei, and Serratia spp. was lower than that reported from Pakistan and West Africa62,64. Among the CRNE, a higher carbapenem resistance was observed in Acinetobacter spp. followed by Pseudomonas spp. This aligns with a study from the Sub-Saharan region60 and found slightly lower from West Africa64. This variability in the PPr of CRE and CRNE across various countries worldwide may reflect differences in study design, population examined, sampling methods, lab practices, and healthcare settings. Differences in antibiotic availability and utilisation, together with antibiotic stewardship initiatives, may further influence the discrepancies in outcomes.
In this review, although pooled prevalence of CRE and CRNE varied across geographical zones, subgroup analysis did not show statistically significant inter-zonal differences, likely due to high heterogeneity among studies. This result is likely influenced by the extremely high heterogeneity observed among the included studies, a challenge frequently encountered in meta-analyses of antimicrobial resistance due to methodological variation and diverse clinical settings.65 A relatively higher burden observed in the southern region may be attributed to greater healthcare density, leading to increased antibiotic pressure, colonisation, and patient movement. Karnataka (from the south zone) had the highest number of health facilities registered under the Ayushman Bharat Digital Mission (ABDM) in March 2024.66-68 In contrast, lower prevalence in the northeastern region may reflect limited healthcare access and comparatively lower antibiotic use. Additionally, regional publication bias may have influenced the pooled estimates.
Temporal fluctuations in carbapenem resistance in CRE and CRNE were observed across the study period. Periods of higher prevalence may be attributed to increased carbapenem use in tertiary-care settings, expansion of high-risk clones, and dissemination of key carbapenemase genes such as blaNDM, blaOXA-48–like, and blaKPC.69,70 The surge during the pandemic period can also be linked to the COVID-19 pandemic, which was associated with inappropriate empirical antibiotic use, disruption of antimicrobial stewardship, and increased hospitalisation71-73. Variations in prevalence across years may be explained by differences in study period, population characteristics, environmental factors, sample types, and the diversity and number of isolates studied. These fluctuations highlight the need for continuous surveillance to monitor evolving resistance trends and guide effective control strategies.
In this review, the prevalent genes among CRE were blaKPC, blaNDM-1, blaVIM-1, blaIMP-1, blaOXA-48, and frequently reported in Klebsiella spp., Escherichia coli, and Enterobacter spp. Upon reviewing the literature, it was also found that the blaKPC, blaNDM-1, blaVIM-1, blaIMP-1, and blaOXA-48 genes were reported by other studies as common genes responsible for carbapenem resistance in Enterobacteriaceae. 66,67
In CRNE, the blaNDM-1, blaVIM-1, blaIMP-1, blaOXA-23, and blaOXA-51 genes were commonly reported in Acinetobacter spp. and Pseudomonas spp. Global clones of Acinetobacter baumannii (such as GC1 and GC2) often harbour blaNDM-1, blaVIM-1, blaOXA-23, and blaOXA-51 genes. These clones have been implicated in nosocomial outbreaks across various regions, including India, Southeast Asia, the Middle East, Europe, and Latin America.74-77 This widespread distribution may account for the high frequency of CRG in CRNE.
This meta-analysis highlights the diversity of organisms and carbapenem-resistance genes among CRE and CRNE, with heterogeneity driven by variations in specimen types, study settings, and laboratory methods. Predominant pathogens included Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, while blaNDM-1, blaVIM, and OXA-type enzymes were key resistance determinants. Notable regional data gaps, particularly from central India, were observed, underscoring the need for regular surveillance, pharmacovigilance, and implementation of strict antibiotic stewardship programs across India for generating sufficient data so that appropriate guidelines for the control of carbapenem resistance can be formulated. Limitations include uneven regional representation of studies and persistent heterogeneity due to methodological differences, which may affect the precision of pooled estimates. Additionally, limited data on sequence types and plasmid profiles restricted deeper molecular epidemiological insights.
Author contributions
ZK: Conceptualisation, data extraction, study segregation, analysis, manuscript writing; PB: Data collection, validation, manuscript writing; SK: Manuscript writing; AR: manuscript writing; NP: Manuscript writing; PD: Manuscript writing. All the authors have read and approved the final printed version of the manuscript.
Financial support and sponsorship
None.
Conflicts of Interest
None.
Use of Artificial Intelligence (AI)-Assisted Technology for manuscript preparation
The authors confirm that there was no use of AI-assisted technology for assisting in the writing of the manuscript and no images were manipulated using AI.
References
- Overview of antimicrobial resistance and mechanisms: The relative status of the past and current. The Microbe.. 2024;3:100083.
- [CrossRef] [Google Scholar]
- JMM profile: Carbapenems—a broad-spectrum antibiotic. J Med Microbiol.. 2021;70:001462.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Global threat of carbapenem-resistant gram-negative bacteria. Front Cell Infect Microbiol.. 2022;12:823684.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Carbapenem-resistant enterobacteriaceae in the community: A scoping review. Int J Antimicrob Agents.. 2017;50:127-34.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Global spread of carbapenem-resistant enterobacteriaceae: Epidemiological features, resistance mechanisms, detection and therapy. Microbiol Res.. 2023;266:127249.
- [CrossRef] [PubMed] [Google Scholar]
- The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Syst Rev.. 2021;10:89.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- The feasibility of creating a checklist for the assessment of the methodological quality both of randomized and non-randomized studies of health care interventions. J Epidemiol Community Health.. 1998;52:377-84.
- [CrossRef] [PubMed] [Google Scholar]
- Prevalence of hepatitis B and hepatitis C virus co-infection in India: A systematic review and meta-analysis. Indian J Med Microbiol.. 2017;35:332-9.
- [CrossRef] [PubMed] [Google Scholar]
- Detection of CTX-m-15-producing and carbapenem-resistant Acinetobacter baumannii strains from urine from an Indian hospital. J Chemother.. 2010;22:324-7.
- [CrossRef] [PubMed] [Google Scholar]
- Molecular epidemiology and therapeutic options of carbapenem-resistant gram-negative bacteria. Indian J Med Res.. 2019;149:285-89.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Prevalence and molecular characterisation of new Delhi metallo-β-lactamases NDM-1, NDM-5, NDM-6 and NDM-7 in multidrug-resistant enterobacteriaceae from India. Int J Antimicrob Agents.. 2014;44:30-7.
- [CrossRef] [PubMed] [Google Scholar]
- Alarming emergence, molecular characterization, and outcome of blaNDM-1 in patients infected with multidrug-resistant Gram-negative bacilli in a tertiary care hospital. J Lab Physicians.. 2017;9:170-6.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Molecular characterization of novel sequence type of carbapenem-resistant New Delhi metallo-β-lactamase-1–producing klebsiella pneumoniae in the neonatal intensive care unit of an Indian hospital. Int J Antimicrob Agents.. 2019;53:525-29.
- [CrossRef] [PubMed] [Google Scholar]
- Emergence of blaNDM-1 and blaVIM producing gram-negative bacilli in ventilator-associated pneumonia at AMR surveillance regional reference laboratory in India. PLoS One.. 2021;16:e0256308.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Characterisation of OXA-48-like carbapenemases in escherichia coli and klebsiella pneumoniae from North India. 3 Biotech.. 2023;13:134.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Identification of carbapenemase-mediated resistance among enterobacteriaceae bloodstream isolates: A molecular study from India. Indian J Med Microbiol.. 2017;35:421-5.
- [CrossRef] [PubMed] [Google Scholar]
- The emergence of carbapenem-resistant gram-negative bacteria in Mizoram, Northeast India. Microbiol Res.. 2022;13:342-9.
- [CrossRef] [Google Scholar]
- Incidence of blaNDM-1 gene in escherichia coli isolates at a tertiary care referral hospital in Northeast India. Indian J Med Microbiol.. 2013;31:250-6.
- [CrossRef] [PubMed] [Google Scholar]
- Emergence of carbapenem-resistant acinetobacter in a temperate north Indian state. Br J Biomed Sci.. 2013;70:156-60.
- [CrossRef] [PubMed] [Google Scholar]
- Multiple carbapenem hydrolyzing genes in clinical isolates of acinetobacter baumannii. Indian J Med Microbiol.. 2013;31:237-41.
- [CrossRef] [PubMed] [Google Scholar]
- Occurrence of blaNDM-1 and absence of blaKPC genes encoding carbapenem resistance in uropathogens from a tertiary care centre from north India. Indian J Med Res.. 2015;142:336-43.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Universal presence of blaNDM-1 gene in carbapenem-resistant gram-negative bacilli in an Indian hospital in 2015. J Clin Diagn Res.. 2017;11:DL01-2.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Acinetobacter baumannii in suspected bacterial infections: association between multidrug resistance, virulence genes, and biofilm production. Indian J Med Res.. 2023;158:439-46.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- OXA beta-lactamase–mediated carbapenem resistance in acinetobacter baumannii. Indian J Med Microbiol.. 2011;29:269-74.
- [CrossRef] [PubMed] [Google Scholar]
- Phenotypic identification and molecular detection of blaNDM-1 gene in multidrug-resistant gram-negative bacilli in a tertiary care centre. Indian J Med Res.. 2014;139:625-31.
- [PubMed] [PubMed Central] [Google Scholar]
- Approach to carbapenemase detection in klebsiella pneumoniae in routine diagnostic laboratories. J Clin Diagn Res.. 2016;10:DC24-7.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Molecular characterization of extended spectrum β-lactamase and carbapenemase producing klebsiella pneumoniae from a tertiary care hospital. Indian J Crit Care Med.. 2019;23:61-6.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Genotypic and phenotypic expression of antibiotic resistance patterns of uropathogenic enterobacteriaceae. Infect Drug Resist.. 2022;15:3991-9.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- blaIMP and blaVIM mediated carbapenem resistance in pseudomonas and acinetobacter species in India. J Infect Dev Ctries.. 2012;6:757-62.
- [CrossRef] [PubMed] [Google Scholar]
- Coexistence of metallo-β-lactamase–encoding genes in pseudomonas aeruginosa. Indian J Med Res.. 2017;146:S46-S52.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Prevalence of VIM- and GIM-producing acinetobacter baumannii from patients with severe urinary tract infection. Acta Microbiol Immunol Hung.. 2018;65:539-50.
- [CrossRef] [PubMed] [Google Scholar]
- Dissemination of carbapenem resistance and plasmids encoding carbapenemases in gram-negative bacteria isolated in India. JAC Antimicrob Resist.. 2021;3:dlab015.
- [CrossRef] [PubMed] [Google Scholar]
- Characterization of carbapenem-resistant gram-negative bacteria from Tamil Nadu. J Chemother.. 2016;28:371-4.
- [CrossRef] [PubMed] [Google Scholar]
- Phenotypic and genotypic characterization of multidrug-resistant isolates from patients with catheter-associated urinary tract infection in a tertiary care hospital. J Lab Physicians.. 2019;11:206-11.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Molecular characterization of invasive carbapenem-resistant acinetobacter baumannii from a tertiary care hospital in south India. Infect Dis Ther.. 2016;5:379-87.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Carbapenem resistant klebsiella pneumoniae isolated from bloodstream infection: Indian experience. Pathog Glob Health.. 2017;111:240-6.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Phenotypic and genotypic assays for detecting the prevalence of metallo-β-lactamases in clinical isolates of acinetobacter baumannii from a south Indian tertiary care hospital. J Med Microbiol.. 2009;58:430-5.
- [CrossRef] [PubMed] [Google Scholar]
- Study of CTX-M type of extended spectrum β-lactamase among nosocomial isolates of escherichia coli and klebsiella pneumoniae in south India. Indian J Microbiol.. 2012;52:35-40.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Molecular characterization of metallo β-lactamase–producing multidrug-resistant pseudomonas aeruginosa from clinical samples. Indian J Pathol Microbiol.. 2014;57:579-82.
- [CrossRef] [PubMed] [Google Scholar]
- Phenotypic and genotypic detection of carbapenemase production among gram negative bacteria isolated from hospital acquired infections. Saudi Med J.. 2022;43:236-43.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Comparative evaluation of multiplex PCR and routine phenotypic methods for detection of carbapenemases among gram-negative bacilli. J Clin Diagn Res.. 2014;8:DC23-DC26.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Fecal carriage of carbapenem-resistant Enterobacteriaceae and risk factor analysis in hospitalized patients: A single-centre study from India. Indian J Med Microbiol.. 2017;35:555-62.
- [CrossRef] [PubMed] [Google Scholar]
- Detection of carbapenemase-producing pseudomonas aeruginosa by phenotypic and genotypic methods in a tertiary care hospital of east India. J Lab Physicians.. 2019;11:287-91.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Genome-wide identification of carbapenem-resistant gram-negative bacterial isolates retrieved from hospitalized patients in Bihar, India. Sci Rep.. 2022;12:8477.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Carbapenem resistance among pseudomonas aeruginosa strains from India: evidence for nationwide endemicity of multiple metallo-β-lactamase clones (VIM-2, -5, -6, -11, and newly characterized VIM-18) Antimicrob Agents Chemother.. 2009;53:1225-30.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- A five-year experience of carbapenem resistance in enterobacteriaceae causing neonatal septicaemia: Predominance of NDM-1. PLoS One.. 2014;9:e112101.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Rapid and economical detection of eight carbapenem-resistance genes in enterobacteriaceae, pseudomonas spp, and acinetobacter spp directly from positive blood cultures using an internally controlled multiplex-PCR assay. Infect Control Hosp Epidemiol.. 2019;40:737-9.
- [CrossRef] [PubMed] [Google Scholar]
- Molecular characterization of class A ESBLs, class B MBLs, class C AmpC, and class D OXA carbapenemases in multidrug-resistant acinetobacter baumannii clinical isolates in a tertiary care hospital, West Bengal, India. Cureus.. 2024;15:e43656.
- [Google Scholar]
- Prevalence and molecular characterization of carbapenem resistant gram-negative bacilli in a tertiary care hospital in Mumbai. IJMMTD.. 2023;9:150-4.
- [CrossRef] [Google Scholar]
- Detection of metallo-β-lactamase–producing acinetobacter baumannii using microbiological assay, disc synergy test, and PCR. Indian J Med Microbiol.. 2012;30:456-61.
- [CrossRef] [PubMed] [Google Scholar]
- Emergence of escherichia coli co-producing NDM-1 and OXA-48 carbapenemases in urinary isolates at a tertiary care centre in central India. J Clin Diagn Res.. 2014;8:DC01-DC04.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Genotypic characterization of carbapenem resistant enterobacterales in clinical isolates from western Maharashtra. Indian J Med Microbiol.. 2021;39:500-3.
- [CrossRef] [PubMed] [Google Scholar]
- First report of molecular epidemiology of carbapenem resistant enterobacteriaceae from a tertiary level hospital in Rajasthan, Western India. JMSH.. 2022;8:200-8.
- [CrossRef] [Google Scholar]
- emergence of new sequence type OXA-48 carbapenemase-producing enterobacteriaceae in kuwait. Microb Drug Resist.. 2015;21:329-34.
- [CrossRef] [PubMed] [Google Scholar]
- Clonal emergence of klebsiella pneumoniae ST14 co-producing OXA-48-type and NDM carbapenemases with high rate of colistin resistance in Dubai, United Arab Emirates. Int J Antimicrob Agents.. 2018;52:90-5.
- [CrossRef] [PubMed] [Google Scholar]
- Tigecycline activity tested against carbapenem-resistant enterobacteriaceae from 18 European nations: results from the SENTRY surveillance program (2010–2013) Diagn Microbiol Infect Dis.. 2015;83:183-6.
- [CrossRef] [PubMed] [Google Scholar]
- Antimicrobial susceptibility data from a network of 13 lebanese hospitals reflecting the national situation during 2015–2016. Antimicrob Resist Infect Control.. 2019;8:1-17.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Trends in the annual incidence of carbapenem resistance among gram-negative bacilli in a large teaching hospital in Makkah city, Saudi Arabia. J Tuberc Res.. 2017;5:229-36.
- [Google Scholar]
- Epidemiology of carbapenem-resistant enterobacteriaceae in Egyptian intensive care units using national healthcare-associated infections surveillance data, 2011-2017. Antimicrob Resist Infect Control.. 2020;9:2.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Prevalence of carbapenem resistance in acinetobacter baumannii and pseudomonas aeruginosa in Sub-Saharan Africa: A systematic review and meta-analysis. PLoS One.. 2023;18:e0287762.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Prevalence and mechanisms of carbapenem resistance in acinetobacter baumannii: A comprehensive systematic review of cross-sectional studies from Iran. Microb Drug Resist.. 2020;26:270-83.
- [CrossRef] [PubMed] [Google Scholar]
- Carbapenem resistance and treatment options in clinical enterobacteriaceae: A systematic review and meta-analysis from Pakistan. Heliyon.. 2024;10:e28052.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- The current status of carbapenem resistance in East Africa: A systematic review. BMC Res Notes.. 2018;11:629.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Carbapenem-resistant enterobacteriaceae in West Africa: A systematic review and meta-analysis. BMC Med Genomics.. 2024;17:267.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Statistical heterogeneity in meta-analyses. In: Higgins JPT, green, s, eds. Cochrane handbook for systematic reviews of interventions. Cochrane Collaboration; 2011. Version 5.1.0
- [Google Scholar]
- Statista. Number of health facilities under Ayushman Bharat digital mission in India as of march 27, 2024, by State. Available from: https://www.statista.com/statistics/1458989/india-health-facilities-under-abdm-by-state/, accessed on December 25, 2025.
- Antibiotic resistance-the need for global solutions. Lancet Infect Dis.. 2013;13:1057-98.
- [CrossRef] [PubMed] [Google Scholar]
- Global trends in antibiotic consumption during 2016–2023 and future projections through 2030. Proc Natl Acad Sci USA.. 2024;121:e2411919121.
- [Google Scholar]
- The epidemiology of carbapenem-resistant enterobacteriaceae. J Infect Dis.. 2017;215:S28-S36.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Structure, epidemiology and resistance mechanisms of carbapenemases. J Med Microbiol.. 2017;66:1087-97.
- [Google Scholar]
- Global antibiotic use during the COVID-19 pandemic: Analysis of pharmaceutical sales data from 71 countries, 2020-2022. EClinicalMedicine.. 2023;57:101848.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- COVID-19: Impact on prescribing and antimicrobial resistance. Rev Esp Quimioter.. 2021;34:63-8.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Surveillance of carbapenem resistance in Asian countries: A systematic review and meta-analysis. BMJ Open.. 2024;14:e088597.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Update on the epidemiology of carbapenemases in Latin America and the Caribbean. Expert Rev Anti Infect Ther.. 2021;19:197-213.
- [CrossRef] [PubMed] [Google Scholar]
- International and regional spread of carbapenem-resistant Klebsiella pneumoniae in Europe. Nat Commun.. 2024;15:5092.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Global spread of carbapenem-resistant Enterobacteriaceae: Epidemiological features, resistance mechanisms, detection and therapy. Microbiol Res.. 2023;266:127249.
- [CrossRef] [PubMed] [Google Scholar]
- Subtypes, resistance and virulence platforms in extended-drug resistant Acinetobacter baumannii Romanian isolates. Sci Rep.. 2021;11:13288.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]