Abstract
Objective – to assess the risk factors for colonization of non-sterile loci by gram-negative carbapenem-resistant bacteria, to analyze its effect and the effect of other factors of the perioperative period on the development of infectious complications in initially colonized patients with congenital heart defects (CHD).
Material and methods. Screening for colonization with Gram-negative carbapenem-resistant bacteria was performed in 549 children aged 0 to 12 months with risk factors for infectious complications (emergency hospitalization, transfer from other hospitals, antibiotic therapy in the previous 90 days) admitted for surgical treatment for CHD. Swabs from the pharynx and rectum were taken from each patient for microbiological examination no later than 72 hours after admission (a total of 1098 samples). The study group included 51 colonized patients; the control group included an equal number of matched non-colonized patients with risk factors randomly selected in the same time interval.
Results. A history of antibacterial therapy increased the chance of developing pathological colonization (odds ratio (OR) 1.41; 95% confidencial interval (CI) 1.78–9.42, p<0.01). Infectious complications in the study group developed in 32 (62.7%) patients, in the control group – in 17 (33.3%) patients (p=0.005). Initial colonization by Gram-negative carbapenem-resistant bacteria (OR 3.37; 95% CI 1.49– 7.59, p=0.005), presence of CHD with enrichment of pulmonary blood flow (OR 2.87; 95% CI 1.28–6.42, p=0.011), stay in the intensive care unit (ICU) over 5.5 days (OR 8,52; 95% CI 3.49–20.78, p<0.001), artificial lung ventilation over 68.5 hours (OR 5.7; 95% CI 2.39– 13.62, p<0.001), the presence of a central venous catheter (CVC) over 8.5 days (OR 28.83; 95% CI 9.91–83.83, p<0.001) increased the risk of infectious complications. The median development of infectious complications in patients of the study group was 4 (3–7) days, and in the control group 7.5 (4–13.5) days, p=0.02. In colonized patients, the duration of stay in the ICU and the duration of ventilation before the development of infectious complications were less than in patients without initial colonization (cut-off points of 4.5 days and 56.3 hours, respectively, versus 6.5 days and 97.4 hours, respectively). The threshold values of the duration of CVC standing before the development of infectious complications did not differ in initially colonized patients and patients without colonization (cut-off point of 8.5 days).
Conclusion. The main risk factor for colonization with Gram-negative carbapenem-resistant bacteria is a history of antibacterial therapy. Colonization with carbapenem-resistant Gram-negative bacteria, the presence of CHD with enrichment of the pulmonary blood flow, prolonged stay in the ICU, prolonged mechanical ventilation, and prolonged use of the CVC increases the risk of developing infectious complications of any etiology.
References
- Stiller B., Grundmann S., Höhn R., Kari F.A., Berger F., Baumgartner H. Adults with congenital heart disease – a new, expanding group of patients. Dtsch. Arztebl. Int. 2023; 120 (12): 195–202. DOI: 10.3238/arztebl.m2023.0006
- Cındık N., Gökdemir M., Çelik M., Günaydın A.Ç. Risk factors for and incidence of hospital-acquired infections after cardiac surgery in children with congenital heart disease: a single center experience. Turk. J. Pediatr. 2023; 65: 769–777. DOI: 10.24953/turkjped.2022.169
- Bianchini S., Nicoletti L., Monaco S., Rigotti E., Corbelli A., Colombari A. et al. On behalf of the peri-operative prophylaxis in neonatal and paediatric age pop-neoped study group. Peri-operative prophylaxis in patients of neonatal and pediatric age subjected to cardiac and thoracic surgery:ARAND/UCLAAppropriateness Method Consensus Study. Antibiotics (Basel). 2022; 21; 11 (5): 554. DOI: 10.3390/antibiotics11050554
- Yu X., Chen M., Liu X., Chen Y., Hao Z., Zhang H. et al. Risk factors of nosocomial infection after cardiac surgery in children with congenital heart disease. BMC Infect. Dis. 2020: 21; 20 (1): 64. DOI: 10.1186/s12879-020-4769-6
- Kelleher S.T., McMahon C.J., James A. Necrotizing enterocolitis in children with congenital heart disease: a literature review. Pediatr. Cardiol. 2021; 42 (8): 1688–1699. DOI: 10.1007/s00246-021-02691-1
- Kashif H., Abuelgasim E., Hussain N., Luyt J., Harky A. Necrotizing enterocolitis and congenital heart disease. Ann. Pediatr. Cardiol. 2021; 14 (4): 507–515. DOI: 10.4103/apc.apc_30_21
- Massart N., Mansour A., Ross J.T., Piau C., Verhoye J.P., Tattevin P. et al. Mortality due to hospital-acquired infection after cardiac surgery. J. Thorac. Cardiovasc. Surg. 2022; 163 (6): 2131–2140.e3. DOI: 10.1016/j.jtcvs.2020.08.094
- World Health Organization Bacterial Priority Pathogens List, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. https://www.who.int/publications/i/item/9789240093461
- Popov D.A. Prevalence of carriage of multidrug-resistant microflora in children of the first year of life, admitted for cardiac surgery. Children’s Heart and Vascular Diseases. 2021; 18 (2): 123–128 (in Russ.). DOI: 10.24022/1810-0686-2021-18-2-123-128
- Van der Zwaluw K., de Haan A., Pluister G.N., Bootsma H.J., de Neeling A.J., Schouls L.M. The carbapenem inactivation method (CIM), a simple and low-cost alternative for the Carba NP test to assess phenotypic carbapenemase activity in gram-negative rods. PLoS One. 2015; 10(3): e0123690. DOI: 10.1371/journal.pone.0123690
- Попов Д.А. Сравнительная характеристика современных методов определения продукции карбапенемаз. Клиническая микробиология и антимикробная химиотерапия. 2019; 2: 125–133. DOI: 10.36488/cmac.2019.2.125-133
- Popov D.A. Comparative review of the modern methods for carbapenemases detection. Clinical Mikrobiology and Antimicrobial Chemotherapy. 2019; 2: 125–133 (in Russ.). DOI: 10.36488/cmac.2019.2.125-133
- Cai S., Wang Z., Han X., Hu H., Quan J., Jiang Y. et al. The correlation between intestinal colonization and infection of carbapenem-resistant Klebsiella pneumoniae: A systematic review. J. Glob. Antimicrob. Resist. 2024; 38: 187–193. DOI: 10.1016/j.jgar.2024.04.013
- Li Q., Zhou X., Yang R., Shen X., Li G., Zhang C. et al. Carbapenem-resistant Gram-negative bacteria (CR-GNB) in ICUs: resistance genes, therapeutics, and prevention – a comprehensive review. Front. Public. Health. 2024: 27; 12: 1376513. DOI: 10.3389/fpubh.2024.1376513
- Souverein D., Euser S.M., Herpers B.L., Kluytmans J., Rossen J.W.A., Den Boer J.W. Association between rectal colonization with Highly Resistant Gram-negative Rods (HR-GNRs) and subsequent infection with HR-GNRs in clinical patients: A one year historical cohort study. PLoS One. 2019: 25; 14 (1): e0211016. DOI: 10.1371/journal.pone.0211016
- Du Q., Xu Q., Pan F., Shi Y., Yu F., Zhang T. et al. Association between intestinal colonization and extraintestinal infection with carbapenem- resistant Klebsiella pneumoniae in children. Microbiol. Spectr. 2023; 11 (2): e0408822. DOI: 10.1128/spectrum.04088-22
- Pawłowska I., Ziółkowski G., Jachowicz-Matczak E., Stasiowski M., Gajda M., Wójkowska-Mach J. Colonization and healthcare-associated infection of carbapenem-resistant Enterobacteriaceae, data from Polish hospital with high incidence of carbapenem-resistant Enterobacteriaceae, does active target screening matter? Microorganisms. 2023: 9; 11 (2): 437. DOI: 10.3390/microorganisms11020437
- Tesfa T., Mitiku H., Edae M., Assefa N. Prevalence and incidence of carbapenem-resistant K. pneumoniae coloni-zation: systematic review and meta-analysis. Syst. Rev. 2022; 11: 240. DOI: 10.1186/s13643-022-02110-3
- Tischendorf J., de Avila R.A., Safdar N. Risk of infection following colonization with carbapenem-resistant Entero-bactericeae: A systematic review. Am. J. Infect. Control. 2016; 1: 44 (5): 539–543. DOI: 10.1016/j.ajic.2015.12.005
- Giannella M., Freire M., Rinaldi M., Abdala E., Rubin A., Mu-laroni A. et al. Development of a risk prediction model for carbapenem-resistant Enterobacteriaceae infection after liver transplantation: a multinational cohort study. Clin. Infect. Dis. 2021; 16: 73 (4): e955–e966. DOI: 10.1093/cid/ciab109
- Qin X., Wu S., Hao M., Zhu J., Ding B., Yang Y. et al. The colonization of carbapenem-resistant Klebsiella pneumoniae: epidemiology, resistance mechanisms, and risk factors in patients admitted to intensive care units in China. J. Infect. Dis. 2020; 16: 221 (Suppl. 2): S206– S214. DOI: 10.1093/infdis/jiz622
- Liu J., Zhang S., Pei H., Tu F., Liu B., Yan J. et al. Klebsiella pneumoniae activates the TGF-β signaling pathway to adhere to and invade intestinal epithelial cells via enhancing TLL1 expression. Int. J. Med. Microbiol. 2022; 312 (6): 151561. DOI: 10.1016/j.ijmm.2022.151561
- Palacios-Baena Z.R., Giannella M., Manissero D., Rodríguez-Baño J., Viale P., Lopes S. et al. Risk factors for carbapenem-resistant Gram- negative bacterial infections: a systematic review. Clin. Microbiol. Infect. 2021; 27 (2): 228–235. DOI: 10.1016/j.cmi.2020.10.016
- Ferrer R., Soriano A., Cantón R., Del Pozo J.L., García-Vidal C., Garnacho-Montero J. et al. A systematic literature review and expert consensus on risk factors associated to infection progression in adult patients with respiratory tract or rectal colonisation by carbapenem-resistant Gram- negative bacteria. Rev. Esp. Quimioter. 2022; 35 (5): 455–467. DOI: 10.37201/req/062.2022
- García H., Cervantes-Luna B., González-Cabello H., Miran-da-Novales G. Risk factors for nosocomial infections after cardiac surgery in newborns with congenital heart disease. Pediatr. Neonatol. 2018; 59 (4): 404–409. DOI: 10.1016/j.pedneo.2017.11.014-21
- Popov D.A., Osokina R.A., Vostrikova T.Yu. Carriage of K. pneumoniae and molecular structure of produced carba-penemases in infants with congenital heart defects. Clinical Microbiology and Antimicrobial Chemotherapy. 2023; 2: 202–210 (in Russ.). DOI: 10.36488/cmac.2023.2.202- 210
- Golukhova E.Z. Report on the scientific and clinical activity of Bakoulev National Medical Research Center for Cardiovascular Surgery for 2023 and development prospects. The Bulletin of Bakoulev Center. Cardiovascular Diseases. 2024; 25 (Special Issue) (in Russ.). DOI: 10.24022/1810-0694-2024-25S
- Meng L., Li J., He Y., Xiong Y., Li J., Wang J. et al. The risk factors analysis and establishment of an early warning model for healthcare- associated infections after pediatric cardiac surgery: A STROBE-compliant observational study. Medicine (Baltimore). 2020; 99 (49): e23324. DOI: 10.1097/MD.0000000000023324
- Righi E., Mutters N.T., Guirao X., Del Toro M.D., Eckmann C., Friendrich A.W. et al. ESCMID/EUCIC clinical practice guidelines on perioperative antibiotic prophylaxis in patients colonized by multidrug-resistant Gram-negative bacteria before surgery. Clin. Microbiol. Infect. 2023; 29 (4): 463–479. DOI: 10.1016/j.cmi.2022.12.012
- Ippolito M., Cortegiani A. Empirical decision-making for antimicrobial therapy in critically ill patients. BJA Educ. 2023; 23 (12): 480–487. DOI: 10.1016/j.bjae.2023.09.001
- Bruns N., Dohna-Schwake C. Antibiotics in critically ill children – a narrative review on different aspects of a rational approach. Pediatr. Res. 2022; 91 (2): 440–446. DOI: 10.1038/s41390-021-01878-9
- Li J., Guo W., Wang J., Feng X., Lin Q., Zheng Y. et al. Strong homology between colonizing and bloodstream carbapenem-resistant Acinetobacter Spp.: implications for empiric antibiotic therapy in hematological patients. Infect. Drug. Resist. 2024; 17: 1827–1838. DOI: 10.2147/IDR.S458427
- Cano A., Gutiérrez-Gutiérrez B., Machuca I., Gracia-Ahufinger I., Pérez-Nadales E., Causse M. et al. Risks of infection and mortality among patients colonized with Klebsiella pneumoniae carbapenemase-producing K. pneu-moniae: validation of scores and proposal for management. Clin. Infect. Dis. 2018; 66 (8): 1204–1210. DOI: 10.1093/cid/cix991
About the authors
- Dmitry A. Popov, Dr. Med. Sci., Professor RAS, Head of Laboratory; ORCID
- Regina A. Osokina, Clinical Pharmacologist; ORCID
- Tatyana Yu. Vostrikova, Cand. Med. Sci., Clinical Microbiologist; ORCID
- Vyacheslav Yu. Beketovskiy, Anesthesiologist & Intensivist, Head of Department; ORCID
- Anton A. Atmashkin, Junior Researcher, Cardiovascular Surgeon; ORCID
- Nadezhda M. Shishkina, Cardiologist; ORCID