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| ORIGINAL ARTICLE |
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| Ahead of print publication |
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Environmental colonization and transmission of carbapenem-resistant Enterobacteriaceae and carbapenem-resistant acinetobacter baumannii in intensive care unit
Priyal P Trivedi, Shahzad Mirza, Nageswari R Gandham, Nikunja Kumar Das, Rabindra N Misra, Rashmi Kharel, Susan Joe
Department of Microbiology, Dr. D. Y. Patil Medical College Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pimpri, Maharashtra, India
| Date of Submission | 20-Mar-2021 |
| Date of Decision | 20-Aug-2021 |
| Date of Acceptance | 27-Aug-2021 |
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Correspondence Address:
Shahzad Mirza,
Dr. D. Y. Patil Medical College Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune - 411 018, Maharashtra
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/mjdrdypu.mjdrdypu_210_21
Background and Objectives: Health care-associated infections (HAI) are one of the most common adverse events in health-care delivery and an endemic burden as major health-care problem. Carbapenems have broad-spectrum antibacterial activity and thus known as Extended-spectrum β-lactamases. Therefore, the emergence of carbapenem-resistant bacteria poses great significance in HAI. Methods: The study was undertaken to see the prevalence of carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant enterobacteriaceae (CRE) in patient samples and surrounding environment. During the study, all the patients' clinical samples sent to the microbiology department for culture sensitivity were considered. All isolates were processed according to standard microbiological protocols and reported according to the Clinical and Laboratory Standards Institute guidelines. Environmental swabs were taken from HI-touch areas from all intensive care unit (ICU)-admitted patients' rooms. Results: Around 290 isolates were reported during the study from concerned ICUs. Out of which 80 samples were carbapenemase producers. Environmental samples were collected from ICUs from Hi-Touch areas showed growth in 23 samples out of a total of 270. Carbapenem-resistant isolates identified in the study belonged equally to Enterobacteriaceae (most common-Klebsiella pneumoniae and Escherichia coli) and nonfermenters classes (CRAB and Pseudomonas aeruginosa), were of similar concern and also difficult to treat, and further compounds the morbidity and mortality of associated infections. The majority of carbapenem-resistant pathogens in this study were resistant to extended-spectrum cephalosporins, fluoroquinolones, and piperacillin-tazobactam (multidrug-resistant [MDR]). Interpretation and Conclusions: In a setting where CRE and CRAB persist, environmental contamination is common. Screening of patients, ensuring strict contact precautions, and strictly following decontamination guidelines in ICUs can be a powerful tool in discerning HAI caused due to CRE and CRAB.
Keywords: Carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Enterobacteriaceae, health care-associated infection and infection control, intensive care unit
How to cite this URL:
Trivedi PP, Mirza S, Gandham NR, Das NK, Misra RN, Kharel R, Joe S. Environmental colonization and transmission of carbapenem-resistant Enterobacteriaceae and carbapenem-resistant acinetobacter baumannii in intensive care unit. Med J DY Patil Vidyapeeth [Epub ahead of print] [cited 2023 Mar 20]. Available from: https://www.mjdrdypv.org/preprintarticle.asp?id=339395 |
| Introduction | |  |
Hospital-acquired infections are of paramount importance as they cause increased rate of mortality and morbidity in an intensive care unit (ICU) admitted patients, and multidrug-resistant (MDR) bacteria isolates are second among the etiological agents.[1] Among MDR pathogens, carbapenem-resistant Klebsiella pneumoniae presents a critical danger to public and clinical health due to its elevated levels of resistance to most alternative antibiotics. Despite upgrades in hospital infection control practices and antibiotic stewardship programs carbapenem-resistant Enterobacteriaceae (CRE) is still on the rise.[2]
Carbapenem-resistant Acinetobacter baumannii (CRAB) has presented a challenge in critically ill patients.[3] It reckons to hospital outbreaks in ICU.[4] Sharp incline in the prevalence of CRAB since the past decade has been observed globally.[5] Once appraised insignificant[6] its high inferable mortality has been well illustrated nowadays.[7] Acinetobacter outbreak termination is arduous to achieve in hospitals.[5]
Carbapenems still play major role as a last resort for the treatment of MDR Gram-negative microbes.[8] Increasing resistance to carbapenems, besides economic burden, also compromises outcomes of patients.[9] The increased morbidity and mortality associated with antibiotic resistance are of major concern in high-risk patients.[10] Given the scenario, this possess serious risk to public health, the centers for disease control and prevention has recognized the threat posed by CRE and as an emergency threat[11] and the development of antibiotics against CRE, CRAB, and Pseudomonas aeruginosa has been emphasized by the World Health Organization.[12]
Knowing hospital antibiograms and susceptibility helps in treating patients with serious infection as the ecology of Gram-negative pathogens can be known, and appropriate empirical therapy can be administered in suspected cases of carbapenem resistance.[12]
Healthcare-associated infections (HAI) are of major concern in health-care systems.[1],[2] Carbapenem-resistant Gram-negative bacteria, namely, CRE, CRAB are a serious cause of HAIs and a rising global health concern.[13] Some strains have the capability to cause transmission which results in the carbapenemase productions.[14] This can increase infection rates and strain on infection prevention and control.[15] Various risk factors associated with acquisitions of these include prior antibiotic exposure, long ICU stays, devices in situ.[16] Surveillance carried out of several outbreaks of such pathogens have pointed out environmental contamination of the Hi-touch areas in hospital setting and contact transmission in the spread of these strains.[17] Diligent environmental decontamination and strict adherence to infection control practices are essential in disrupting transmission, but outbreaks still accounts for closure of complete units.[18]
| Methods | | |
Place of study
Tertiary care set up in Western Maharashtra, India.
Type of study
This was observational and cross-sectional study.
Period of study
Two months.
Surveillance was conducted by a two-way approach for environmental prevalence and surveillance of clinical cultures for CRE and CRAB in the medical ICU (MICU), surgical ICU (SICU), and pediatric ICU (PICU) in the tertiary care setup. The hospital has approximately 1800 beds and houses more than 100 beds in ICUs.
Study procedures
Inclusion criteria
All patients isolated with CRE and/or CRAB admitted to ICU for more than 48 h.
Exclusion criteria
Isolation from patients with hospitalization <48 h in ICUs.
The study comprised two components: The first component was a 5-month surveillance of clinical cultures of CRE and CRAB isolated from patients within the ICUs, while the second component was the culture-positive CRE and CRAB isolated from environmental samples collected from ICUs.
During the study, all the patient's clinical samples sent to the microbiology department for culture sensitivity were considered for the study such as blood, urine, pus, body fluids, endotracheal tube aspirates and swabs from nares, axillae, groin, wounds, and exit sites of drains, if any. Samples taken from patients who had been in the ICU for <24 h or who were known CRAB carriers were not considered for the study.
Environmental swabs were taken from Hi-touch areas from all the patient rooms in the ICU, regardless of whether they were occupied by patients at the time. The Hi-touch areas swabbed were: ventilator monitors, bedside rails, cardiac tables, IV stands, and bed lockers. Samples were collected from MICU, SICU, and PICU from bedside areas at different times of the day to check for bacterial loads at different time namely before routine cleaning and disinfection of ICUs. All the samples were collected randomly from different bedside areas and also retrospectively from bedside areas of patients with culture-positive reports.
Specimen collection and culture
All samples were collected by the student under the guidance of microbiologist and infection control nurses who were trained and supervised by the infection control officer. Sterile cotton swabs were moistened with sterile saline and were rolled over the surface. Each swab was collected from the environment (HI-touch areas) in Glucose broth media and transported to the microbiology department for processing at the earliest. The samples were inoculated onto MacConkey agar and incubated at 37°C for 48 h.
All Gram-negative bacteria that were isolated were further tested by various biochemical reactions characteristic of Enterobacteriaceae.[19] A meropenem disc (10 μg, Himedia) was placed on each plate to select for carbapenem-resistant organisms. Susceptibility testing was performed on all isolates of Enterobacteriaceae and A. baumannii using the Kirby–Bauer disc diffusion method, and those with a meropenem zone of ≤19 and ≤14 mm were interpreted as resistant respectively based on the Clinical Laboratory and Standards Institute criteria (M100).[20] Bact/Alert 3D system and VITEK 2C were used wherever required.
| Results | | |
The first component
Of the total 2187 samples received from the concerned ICU's total culture-positive samples reported were 290 (13.2%). One hundred and twenty were from SICU, 120 from MICU and 50 samples were from PICU. Out of these, 80 samples were carbapenemase producers and accounted for about 27.5% of the positive cultures. Most carbapenemase-producing organisms (46) were isolated from SICU followed by 28 from MICU and 6 from PICU [Figure 1]. | Figure 1: Distribution of carbapenemase-producing isolates from ICU.ICU: Intensive care unit, MICU: Medical ICU, SICU: Surgical ICU, PICU: Paediatric ICU
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Of all the samples reported for carbapenemase production maximum isolation was from urine samples (24) making it the most common source of carbapenemase-producing organisms in our study, followed by tracheal aspirate (19). Three isolates were reported from cerebrospinal fluid. The patient had craniotomy (all 3 samples were from the same patient but were included as were collected at three different admissions to the ICU) [Figure 2]. | Figure 2: Sample-wise distribution of carbapenemase producers. bl: Blood, fl: Fluids, fv: Urine, ps: Pus, sf: Cerebrospinal fluid, sp: Sputum, ta: Tracheal aspirate, ti: Tissue
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The most common organisms from Enterobacteriaceae (CRE) isolated was K. pneumoniae (28), followed by Escherichia More Details coli (11). Among nonfermenters the most common organism isolated was P. aeruginosa (24) followed by A. baumannii (CRAB) (16) [Figure 3].
Of the total carbapenem-resistant organisms isolated from MICU, the most common organism was Klebsiella pneumonia (13) followed by P. aeruginosa (8) and A. baumannii (5). From SICU it was P. aeruginosa (16) followed by K. pneumonia (15). Similarly, from PICU, E. coli was isolated in 4 samples followed by A. baumannii (CRAB) in 2 samples [Figure 4]. | Figure 4: Organism-wise distribution of carbapenemase producers in ICU setups. ICU: Intensive care unit, MICU: Medical ICU, SICU: Surgical ICU, PICU: Paediatric ICU
Click here to view |
Out of the total 80 carbapenem-resistant organisms isolated from clinical samples, 40 were CRE and rest 40 were carbapenem-resistant non fermenters such as A. baumannii (CRAB) and P. aeruginosa. CRE were resistant to majority of the drugs classes such as aminoglycosides, 2nd and 3rd generation cephalosporins, fluroquinolones, and carbapenems such as imipenem and meropenem. A similar sensitivity pattern was seen with the nonfermenters too which were also resistant to majority classes of antibiotics processed by disc diffusion (Kirby-Bauer method) using the Clinical and Laboratory Standards Institute guidelines.[21]
The second component
Total 270 samples were collected from ICUs from 75 visits. Samples were collected from bedside railings, cardiac table, patient locker IV stand, and ventilator monitor and showed 7 cultures positive for Bed-railing, 3 for cardiac table, 2 for locker, 6 for IV stand, and 5 cultures positive for ventilator monitor.
Of these 270 samples collected, 23 samples were culture positive for carbapenemase-producing organisms, the most common being K. pneumonia (10) followed by E. coli (6), P. aeruginosa (4) and A. baumannii (3) [Table 1] and rest 247 samples grew varied flora like Gram-positive commensal flora and sensitive strains of Gram-negative organisms. Some samples even showed no growth too. | Table 1: Organism-wise distribution in various intensive care units among environmental samples
Click here to view |
| Discussion | | |
Given their importance against MDR Gram-negative pathogens, carbapenem resistance is of serious concern.[1],[16] In this study, carbapenem resistance in 80 isolates accounting for 27.5% of 290 g negative reported isolates from the concerned ICUs with K. pneumoniae being the most frequent carbapenem pathogen followed by P. aeruginosa were found. Urine samples accounted as the major source of carbapenem-resistant pathogens, whereas tracheal aspirates isolates contributed for almost one-fourth of isolates.
CRE is of a significant clinical problem. They not only cause infections but also can reside and colonize which can lead to transfer of these pathogens between patients.[22] CRE frequently carries plasmid-mediated carbapenem resistance determinants, such as K. pneumonia carbapenemases, which can easily promulgate to different pathogens.[23] Due to the scarcity of treatment alternatives for CRE, Carbapenem resistance is of particular concern, which may lead to inept initial therapy.[22]
Carbapenem-resistant isolates identified in the study conducted belonged equally to Enterobacteriaceae and nonfermenters class, the most common pathogens from Enterobacteriaceae was K. pneumonia and E. coli. Both microbes have witnessed a sharp incline in carbapenem resistance in the previous years.[2] Similar findings were seen in a multi-centric study done in the United States.[24] In the United States, rates of carbapenem-resistant K. pneumonia increased from 0.1% in 2002 to 4.5% in 2010.[2]
Similarly, from the surveillance samples 23 isolates were carbapenemase producers and here too the most common pathogen isolated was K. pneumoniae followed by E. coli among Enterobacteriaceae and among nonfermenters P. aeruginosa was isolated from 4 samples and A. baumannii from 3 samples. Similar findings were seen in a study done by Ng et al.[25]
Among nonfermenters, particularly A. baumannii (CRAB) and P. aeruginosa were of similar concern which are also difficult to treat and worsens the morbidity and mortality of associated infections as carbapenem resistance is associated with increase in mortality for both P. aeruginosa and A. baumanii.[26] The majority of carbapenem-resistant pathogens in the study were MDR and resistant to broad-spectrum cephalosporins, fluoroquinolones, and piperacillin-tazobactam.
The major contributors to carbapenem-resistant isolates were isolated from urinary tract infections and respiratory tract infections.
The study also highlights urine samples and tracheal aspirates from patient infections as an important source of carbapenem-resistant pathogens leading to hospital infections such as catheter-associated urinary tract infection and ventilator-associated pneumonia. Recognition of this is important from both the patient management and infection prevention, as wounds can act as repositories for CRE and CRAB, thereby increasing their transmission through contact transfer if appropriate measures are not taken.
Environmental colonization by CRE and CRAB was evidence based on the study in ICUs. There could be a correlation to the proximity of the equipment to the patient with Hi touch areas (such as ventilators and bedrails) which were more likely to be contaminated. This may be due to aerosol-generating procedures like suctioning in intubated patients on ventilators. A recent study also found that nebulized medication administration (NMA) and bronchoscope with NMA generated significantly higher levels of aerosols compared to other activities such as bronchoscopy alone or noninvasive ventilation.[27] In addition, the areas positive for CRE and CRAB were also high-touch surface areas, as was also defined by Carling et al.[28] All environmental surfaces were cleaned with a high-level disinfectant on a daily basis. Reusable equipment such as infusion pumps and oximeter probes were wiped down with the high-level disinfectant after each patient use. As each patient had their own dedicated blood pressure cuff, they were cleaned with the same high-level disinfectant after the patient was transferred out of the ICU.
As per local infection control policy, staff members are required to don proper personal protective equipment prior to procedures and to doff after its completion regardless of whether the patient is known to have colonization or infection with any MDR organisms. In the ICUs, alcohol-based hand rub is placed at the foot of the patient's bed which facilitates the use of the hand rub prior to exiting the room. Staff was encouraged to do hand hygiene with alcohol-based hand rub.
Although A. baumannii is ubiquitous in the environment, it is known to have a predilection for water sources.[29] A study conducted in an ICU in Japan reported that an outbreak of A. baumannii had been caused by tap water from sinks colonized with the organism and was transmitted through oral care using tap water.[29] In the study concerned, water samples taken from washbasins during the study from ICUs were also negative for CRE and CRAB.
Similarly, the study also found that antibiotic susceptibility of organisms isolated from patient samples and those from the environment were similar. It is insufficient to rely on phenotypic patterns alone in determining the relatedness of the isolates and hence genotypic correlation is needed to confirm the transfer of these organisms from environment to the patients.
Also, not only were CRE and CRAB found but also other carbapenem-resistant Gram-negative nonfermenters like P. aeruginosa in the isolates from both components of the samples were reported.
| Conclusions | | |
A key limitation of all retrospective studies of antimicrobial resistance is that culturing of hospitalized patients relies on the clinician's assessment of the need for a clinical culture. Accordingly, our findings are based on culture-positive samples from ill patients who required clinical culture and surveillance samples. We therefore cannot infer the exact rates of carbapenem-resistant isolates in the hospital. We conclude from our findings that carbapenem-resistant Gram-negative bacteria continue to be an important problem in hospitals. Furthermore, screening of patients in an environment where patients are at high risk for acquisition of CRE and CRAB can be a powerful tool in discerning nosocomial infections from these pathogens and their transmission and also proposing infection control strategies.
Financial support and sponsorship
The study was selected, approved, and completed by the Indian Council of Medical Research as Short-Term Studentship research work.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Teerawattanapong N, Kengkla K, Dilokthornsakul P, Saokaew S, Apisarnthanarak A, Chaiyakunapruk N. Prevention and control of multidrug-resistant gram-negative bacteria in adult Intensive Care Units: A systematic review and network meta-analysis. Clin Infect Dis 2017;64:S51-60.  |
| 2. | Braykov NP, Eber MR, Klein EY, Morgan DJ, Laxminarayan R. Trends in resistance to carbapenems and third-generation cephalosporins among clinical isolates of Klebsiella pneumoniae in the United States, 1999-2010. Infect Control Hosp Epidemiol 2013;34:259-68. |
| 3. | Munoz-Price LS, Weinstein RA. Acinetobacter infection. N Engl J Med 2008;358:1271-81. |
| 4. | Kohlenberg A, Brümmer S, Higgins PG, Sohr D, Piening BC, de Grahl C, et al. Outbreak of carbapenem-resistant Acinetobacter baumannii carrying the carbapenemase OXA-23 in a German university medical centre. J Med Microbiol 2009;58:1499-507. |
| 5. | Blot S, Vandewoude K, Colardyn F. Nosocomial bacteremia involving Acinetobacter baumannii in critically ill patients: A matched cohort study. Intensive Care Med 2003;29:471-5. |
| 6. | Garnacho J, Sole-Violan J, Sa-Borges M, Diaz E, Rello J. Clinical impact of pneumonia caused by Acinetobacter baumannii in intubated patients: A matched cohort study. Crit Care Med 2003;31:2478-82. |
| 7. | Jones CL, Clancy M, Honnold C, Singh S, Snesrud E, Onmus-Leone F, et al. Fatal outbreak of an emerging clone of extensively drug-resistant Acinetobacter baumannii with enhanced virulence. Clin Infect Dis 2015;61:145-54. |
| 8. | Bartsch SM, McKinnell JA, Mueller LE, Miller LG, Gohil SK, Huang SS, et al. Potential economic burden of carbapenem-resistant Enterobacteriaceae (CRE) in the United States. Clin Microbiol Infect 2017;23:48.e9-16. |
| 9. | Thaden JT, Pogue JM, Kaye KS. Role of newer and re-emerging older agents in the treatment of infections caused by carbapenem-resistant Enterobacteriaceae. Virulence 2017;8:403-16. |
| 10. | |
| 11. | |
| 12. | Micek ST, Welch EC, Khan J, Pervez M, Doherty JA, Reichley RM, et al. Empiric combination antibiotic therapy is associated with improved outcome against sepsis due to gram-negative bacteria: A retrospective analysis. Antimicrob Agents Chemother 2010;54:1742-8. |
| 13. | |
| 14. | Tängdén T, Giske CG. Global dissemination of extensively drug-resistant carbapenemase-producing Enterobacteriaceae: Clinical perspectives on detection, treatment and infection control. J Intern Med 2015;277:501-12. |
| 15. | Otter JA, Burgess P, Davies F, Mookerjee S, Singleton J, Gilchrist M, et al. Counting the cost of an outbreak of carbapenemase-producing Enterobacteriaceae: An economic evaluation from a hospital perspective. Clin Microbiol Infect 2017;23:188-96. |
| 16. | El Shafie SS, Alishaq M, Leni Garcia M. Investigation of an outbreak of multidrug-resistant Acinetobacter baumannii in trauma Intensive Care Unit. J Hosp Infect 2004;56:101-5. |
| 17. | Zanetti G, Blanc DS, Federli I, Raffoul W, Petignat C, Maravic P, et al. Importation of Acinetobacter baumannii into a burn unit: A recurrent outbreak of infection associated with widespread environmental contamination. Infect Control Hosp Epidemiol 2007;28:723-5. |
| 18. | Simor AE, Lee M, Vearncombe M, Jones-Paul L, Barry C, Gomez M, et al. An outbreak due to multiresistant Acinetobacter baumannii in a burn unit: Risk factors for acquisition and management. Infect Control Hosp Epidemiol 2002;23:261-7. |
| 19. | Mirza SB, Misra RN, Gandham NR, Angadi KM, Dass NK, Savita J. β-Lactamase Producing Enterobacteriaceae: A Growing Concern in Community Acquired Infections. International Journal of Microbiology Research, 2018;10:1418-21. Available from: https://bioinfopublication.org/downpdf.php?artid=BIA0004692. [Last assessed on 2021 Sep 28]. |
| 20. | Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; CLSI Publication M100-S22. Wayne, PA: CLSI; 2019. Available from: https://clsi.org/media/2663/m100ed29_sample.pdf .[Last assessed on 2021 Sep 28]. |
| 21. | Carlet J, Jarlier V, Harbarth S, Voss A, Goossens H, Pittet D, et al. Ready for a world without antibiotics? The Pensières antibiotic resistance call to action. Antimicrob Resist Infect Control 2012;1:11. |
| 22. | Gupta N, Limbago BM, Patel JB, Kallen AJ. Carbapenem-resistant Enterobacteriaceae: Epidemiology and prevention. Clin Infect Dis 2011;53:60-7. |
| 23. | Bonomo RA, Burd EM, Conly J, Limbago BM, Poirel L, Segre JA, et al. Carbapenemase-producing organisms: A global scourge. Clin Infect Dis 2018;66:1290-7. |
| 24. | McCann E, Srinivasan A, DeRyke CA, Ye G, DePestel DD, Murray J, et al. Carbapenem-nonsusceptible gram-negative pathogens in ICU and non-ICU settings in US hospitals in 2017: A multicenter study. Open Forum Infect Dis 2018;5:ofy241. |
| 25. | Ng, Deborah H.L, Marimuthu K, Lee J.J, et al. Environmental colonization and onward clonal transmission of carbapenem-resistant Acinetobacter baumannii (CRAB) in a medical intensive care unit: the case for environmental hygiene. Antimicrob Resist Infect Control 7, 51 (2018). https://doi.org/10.1186/s13756-018-0343-z |
| 26. | Lemos EV, de la Hoz FP, Einarson TR, McGhan WF, Quevedo E, Castañeda C, et al. Carbapenem resistance and mortality in patients with Acinetobacter baumannii infection: Systematic review and meta-analysis. Clin Microbiol Infect 2014;20:416-23. |
| 27. | O'Neil CA, Li J, Leavey A, Wang Y, Hink M, Wallace M, et al. Characterization of aerosols generated during patient care activities. Clin Infect Dis 2017;65:1335-41. |
| 28. | Carling PC, Parry MF, Von Beheren SM, Healthcare Environmental Hygiene Study Group. Identifying opportunities to enhance environmental cleaning in 23 acute care hospitals. Infect Control Hosp Epidemiol 2008;29:1-7. |
| 29. | Umezawa K, Asai S, Ohshima T, Iwashita H, Ohashi M, Sasaki M, et al. Outbreak of drug-resistant Acinetobacter baumannii ST219 caused by oral care using tap water from contaminated hand hygiene sinks as a reservoir. Am J Infect Control 2015;43:1249-51. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1]
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