Selective Digestive Decontamination in Hemato-Oncological Patients Colonized with Carbapenem-Resistant Enterobacterales
DOI:
https://doi.org/10.20344/amp.23139Keywords:
Carbapenems, Decontamination, Drug Resistance, Bacterial, Enterobacteriaceae, Enterobacteriaceae Infections, Gastrointestinal Tract, Hematologic NeoplasmsAbstract
Infections caused by multidrug-resistant Gram-negative bacteria, including carbapenem-resistant Enterobacterales, are a global threat and their gradual increase is alarming. They represent a major challenge to public health because of limited therapeutic options and high case-fatality rates. Hemato-oncological patients represent a high-risk subpopulation for these types of infections, more specifically in previous carbapenem-resistant Enterobacterales colonized patients, because of severe immunosuppression not only due to the disease itself but also due to treatment like intensive chemotherapy or allogeneic hematopoietic stem cell transplant. Selective digestive decontamination is a prophylactic intervention with the purpose of reducing or eliminating gut colonization by pathogenic agents, preserving beneficial endogenous flora but its application remains controversial due to great heterogeneity amongst studies. However, in this review we intend to examine the role of selective digestive decontamination in context of high-risk patients such as hemato-oncological carbapenem-resistant Enterobacterales carriers who will receive highly immunosuppressive treatments, as it appears to be an appealing short-term strategy for the prevention of difficult-to-treat infections.
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References
World Health Organization. WHO bacterial priority pathogens list, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. Geneva: WHO; 2024.
Gao S, Yan R, Zhang S, Li L, Zhang R, Fan J, et al. Rectal culture could predict carbapenem-resistant organism bloodstream infection and reduce the mortality in haematological patients: a retrospective cohort study. J Global Antimicrob Resist. 2024;36:96-104. DOI: https://doi.org/10.1016/j.jgar.2023.12.007
Girmenia C, Rossolini GM, Piciocchi A, Bertaina A, Pisapia G, Pastore D, et al. Infections by carbapenem-resistant Klebsiella pneumoniae in SCT recipients: a nationwide retrospective survey from Italy. Bone Marrow Transplant. 2015;50:282-8. DOI: https://doi.org/10.1038/bmt.2014.231
Amanati A, Sajedianfard S, Khajeh S, Ghasempour S, Mehrangiz S, Nematolahi S, et al. Bloodstream infections in adult patients with malignancy, epidemiology, microbiology, and risk factors associated with mortality and multi-drug resistance. BMC Infect Dis. 2021;21:636. DOI: https://doi.org/10.1186/s12879-021-06243-z
Wang S, Song Y, Shi N, Yin D, Kang J, Cai W, et al. Characteristics, outcomes, and clinical indicators of bloodstream infections in neutropenic patients with hematological malignancies: a 7-year retrospective study. Infect Drug Resist. 2023;16:4471-87. DOI: https://doi.org/10.2147/IDR.S413454
European Centre for Disease Prevention and Control. Carbapenem-resistant Enterobacteriaceae, second update. Stockholm: ECDC. 2019.
Pana ZD, Zaoutis T. Treatment of extended-spectrum β-lactamase-producing enterobacteriaceae (ESBLs) infections: what have we learned until now? F1000Res. 2018;7:F1000 Faculty Rev-1347. DOI: https://doi.org/10.12688/f1000research.14822.1
Suay-García B, Pérez-Gracia MT. Present and future of carbapenem-resistant enterobacteriaceae (CRE) Infections. Antibiotics. 2019;8:122. DOI: https://doi.org/10.3390/antibiotics8030122
Lutgring JD, Limbago BM. The problem of carbapenemase-producing-carbapenem-resistant-enterobacteriaceae detection. J Clin Microbiol. 2016;54:529-34. DOI: https://doi.org/10.1128/JCM.02771-15
Porreca AM, Sullivan KV, Gallagher JC. The epidemiology, evolution, and treatment of KPC-producing organisms. Curr Infect Dis Rep. 2018;20:13. DOI: https://doi.org/10.1007/s11908-018-0617-x
Cassini A, Högberg LD, Plachouras D, Quattrocchi A, Hoxha A, Simonsen GS, et al. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. Lancet Infect Dis. 2019;19:56-66. DOI: https://doi.org/10.1016/S1473-3099(18)30605-4
Web Annex C. WHO AWaRe (access, watch, reserve) classification of antibiotics for evaluation and monitoring of use, 2023. In: The selection and use of essential medicines 2023: Executive summary of the report of the 24th WHO Expert Committee on the Selection and Use of Essential Medicines, 24 – 28 April 2023. Geneva: World Health Organization; 2023.
Jean S-S, Harnod D, Hsueh P-R. Global threat of carbapenem-resistant gram-negative bacteria. Front Cell Infect Microbiol. 2022;12:823684. DOI: https://doi.org/10.3389/fcimb.2022.823684
European Centre for Disease Prevention and Control. Antimicrobial resistance in the EU/EEA (EARS-Net) - annual epidemiological report 2023. Stockholm: ECDC; 2024.
Pires D, Zagalo A, Santos C, Cota de Medeiros F, Duarte A, Lito L, et al. Evolving epidemiology of carbapenemase-producing enterobacteriaceae in Portugal: 2012 retrospective cohort at a tertiary hospital in Lisbon. J Hosp Infect. 2016;92:82-5. DOI: https://doi.org/10.1016/j.jhin.2015.11.006
Cattaneo C, Di Blasi R, Skert C, Candoni A, Martino B, Di Renzo N, et al. Bloodstream infections in haematological cancer patients colonized by multidrug-resistant bacteria. Ann Hematol. 2018;97:1717-26. DOI: https://doi.org/10.1007/s00277-018-3341-6
Campos-Madueno EI, Moradi M, Eddoubaji Y, Shahi F, Moradi S, Bernasconi OJ, et al. Intestinal colonization with multidrug-resistant enterobacterales: screening, epidemiology, clinical impact, and strategies to decolonize carriers. Eur J Clin Microbiol Infect Dis. 2023;42:229-54. DOI: https://doi.org/10.1007/s10096-023-04548-2
Luo H, Chen X, Jiang Z, Yan Q. Prevalence of and risk factors for intestinal colonisation by multidrug-resistant gram-negative bacteria in patients with haematological malignancies: a systematic review and meta-analysis. Int J Antimicrob Agents. 2024;63:107043. DOI: https://doi.org/10.1016/j.ijantimicag.2023.107043
Vehreschild MJ, Hamprecht A, Peterson L, Schubert S, Hantschel M, Peter S, et al. A multicentre cohort study on colonization and infection with ESBL-producing enterobacteriaceae in high-risk patients with haematological malignancies. J Antimicrob Chemother. 2014;69:3387-92. DOI: https://doi.org/10.1093/jac/dku305
Scheich S, Reinheimer C, Brandt C, Wichelhaus TA, Hogardt M, Kempf VAJ, et al. Clinical impact of colonization with multidrug-resistant organisms on outcome after autologous stem cell transplantation: a retrospective single-center study. Biol Blood Marrow Transplant. 2017;23:1455-62. DOI: https://doi.org/10.1016/j.bbmt.2017.05.016
Girmenia C, Bertaina A, Piciocchi A, Perruccio K, Algarotti A, Busca A, et al. Incidence, risk factors and outcome of pre-engraftment gram-negative bacteremia after allogeneic and autologous hematopoietic stem cell transplantation: an italian prospective multicenter survey. Clin Infect Dis. 2017;65:1884-96. DOI: https://doi.org/10.1093/cid/cix690
Giannella M, Trecarichi EM, De Rosa FG, Del Bono V, Bassetti M, Lewis RE, et al. Risk factors for carbapenem-resistant Klebsiella pneumoniae bloodstream infection among rectal carriers: a prospective observational multicentre study. Clin Microbiol Infect. 2014;20:13507-62. DOI: https://doi.org/10.1111/1469-0691.12747
Bar-Yoseph H, Cohen N, Korytny A, Andrawus ER, Even Dar R, Geffen Y, et al. Risk factors for mortality among carbapenem-resistant enterobacteriaceae carriers with focus on immunosuppression. J Infect. 2019;78:101-5. DOI: https://doi.org/10.1016/j.jinf.2018.10.003
Averbuch D, Cordonnier C, Livermore DM, Mikulska M, Orasch C, Viscoli C, et al. Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011). Haematologica. 2013;98:1836-47. DOI: https://doi.org/10.3324/haematol.2013.091330
Girmenia C, Viscoli C, Piciocchi A, Cudillo L, Botti S, Errico A, et al. Management of carbapenem resistant Klebsiella pneumoniae infections in stem cell transplant recipients: an Italian multidisciplinary consensus statement. Haematologica. 2015;100:e373-6. DOI: https://doi.org/10.3324/haematol.2015.125484
Patel G, Huprikar S, Factor SH, Jenkins SG, Calfee DP. Outcomes of carbapenem-resistant klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infect Control Hosp Epidemiol. 2008;29:1099-106. DOI: https://doi.org/10.1086/592412
Tamma PD, Heil EL, Justo JA, Mathers AJ, Satlin MJ, Bonomo RA. Infectious Diseases Society of America 2024 guidance on the treatment of antimicrobial-resistant gram-negative infections. Clin Infect Dis. 2024;ciae403. DOI: https://doi.org/10.1093/cid/ciae403
Garcia-Vidal C, Stern A, Gudiol C. Multidrug-resistant, gram-negative infections in high-risk haematologic patients: an update on epidemiology, diagnosis and treatment. Curr Opin Infect Dis. 2021;34:314-22. DOI: https://doi.org/10.1097/QCO.0000000000000745
Catho G, Huttner BD. Strategies for the eradication of extended-spectrum beta-lactamase or carbapenemase-producing enterobacteriaceae intestinal carriage. Expert Rev Anti Infect Ther. 2019;17:557-69. DOI: https://doi.org/10.1080/14787210.2019.1645007
Goldman L, Schafer AI, editors. Goldman-Cecil medicine. 25th ed. Philadelphia: Elsevier/Saunders; 2016.
Septimus EJ, Schweizer ML. Decolonization in prevention of health care-associated infections. Clin Microbiol Rev. 2016;29:201-22. DOI: https://doi.org/10.1128/CMR.00049-15
Sleijfer DTh, Mulder NH, De Vries-Hospers HG, Fidler V, Nieweg HO, van Der Waaij D, et al. Infection prevention in granulocytopenic patients by selective decontamination of the digestive tract. Eur J Cancer. 1980;16:859-69. DOI: https://doi.org/10.1016/0014-2964(80)90140-1
van der Waaij D, Berghuis-de Vries JM, Lekkerkerk Lekkerkerk-v null. Colonization resistance of the digestive tract in conventional and antibiotic-treated mice. J Hyg. 1971;69:405-11. DOI: https://doi.org/10.1017/S0022172400021653
Tacconelli E, Mazzaferri F, De Smet AM, Bragantini D, Eggimann P, Huttner BD, et al. ESCMID-EUCIC clinical guidelines on decolonization of multidrug-resistant Gram-negative bacteria carriers. Clin Microbiol Infect. 2019;25:807-17. DOI: https://doi.org/10.1016/j.cmi.2019.01.005
Saidel-Odes L, Polachek H, Peled N, Riesenberg K, Schlaeffer F, Trabelsi Y, et al. A randomized, double-blind, placebo-controlled trial of selective digestive decontamination using oral gentamicin and oral polymyxin e for eradication of carbapenem-resistant klebsiella pneumoniae carriage. Infect Control Hosp Epidemiol. 2012;33:14-9. DOI: https://doi.org/10.1086/663206
Oren I, Sprecher H, Finkelstein R, Hadad S, Neuberger A, Hussein K, et al. Eradication of carbapenem-resistant enterobacteriaceae gastrointestinal colonization with nonabsorbable oral antibiotic treatment: a prospective controlled trial. Am J Infect Control. 2013;41:1167-72. DOI: https://doi.org/10.1016/j.ajic.2013.04.018
Machuca I, Gutiérrez-Gutiérrez B, Pérez Cortés S, Gracia-Ahufinger I, Serrano J, Madrigal MD, et al. Oral decontamination with aminoglycosides is associated with lower risk of mortality and infections in high-risk patients colonized with colistin-resistant, KPC-producing Klebsiella pneumoniae. J Antimicrob Chemother. 2016;71:3242-9. DOI: https://doi.org/10.1093/jac/dkw272
Stoma I, Karpov I, Iskrov I, Krivenko S, Uss A, Vlasenkova S, et al. Decolonization of intestinal carriage of mdr/xdr gram-negative bacteria with oral colistin in patients with hematological malignancies: results of a randomized controlled trial. Mediterr J Hematol Infect Dis. 2018;10:2018030. DOI: https://doi.org/10.4084/mjhid.2018.030
Tascini C, Sbrana F, Flammini S, Tagliaferri E, Arena F, Leonildi A, et al. Oral gentamicin gut decontamination for prevention of KPC-producing Klebsiella pneumoniae infections: relevance of concomitant systemic antibiotic therapy. Antimicrob Agents Chemother. 2014;58:1972-6. DOI: https://doi.org/10.1128/AAC.02283-13
Ben-David D, Masarwa S, Navon-Venezia S, Mishali H, Fridental I, Rubinovitch B, et al. Carbapenem-resistant klebsiella pneumoniae in post-acute-care facilities in israel. Infect Control Hosp Epidemiol. 2011;32:845-53. DOI: https://doi.org/10.1086/661279
Gupta N, Limbago BM, Patel JB, Kallen AJ. Carbapenem-resistant enterobacteriaceae: epidemiology and prevention. Clin Infect Dis. 2011;53:60-7. DOI: https://doi.org/10.1093/cid/cir202
Schwaber MJ, Klarfeld-Lidji S, Navon-Venezia S, Schwartz D, Leavitt A, Carmeli Y. Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults and effect of acquisition on mortality. Antimicrob Agents Chemother. 2008;52:1028-33. DOI: https://doi.org/10.1128/AAC.01020-07
Lambelet P, Tascini C, Fortunato S, Stefanelli A, Simonetti F, Vettori C, et al. Oral gentamicin therapy for carbapenem-resistant klebsiella pneumoniae gut colonization in hematologic patients: a single center experience. New Microbiol. 2017;40:161-4.
Lübbert C, Faucheux S, Becker-Rux D, Laudi S, Dürrbeck A, Busch T, et al. Rapid emergence of secondary resistance to gentamicin and colistin following selective digestive decontamination in patients with KPC-2-producing klebsiella pneumoniae: a single-centre experience. Int J Antimicrob Agents. 2013;42:565-70. DOI: https://doi.org/10.1016/j.ijantimicag.2013.08.008
Pellicé M, Rodríguez-Núñez O, Rico V, Agüero D, Morata L, Cardozo C, et al. Factors associated with short-term eradication of rectal colonization by KPC-2 producing klebsiella pneumoniae in an outbreak setting. Front Microbiol. 2021;12:630826. DOI: https://doi.org/10.3389/fmicb.2021.630826
Zuckerman T, Benyamini N, Sprecher H, Fineman R, Finkelstein R, Rowe JM, et al. SCT in patients with carbapenem resistant Klebsiella pneumoniae: a single center experience with oral gentamicin for the eradication of carrier state. Bone Marrow Transplant. 2011;46:1226-30. DOI: https://doi.org/10.1038/bmt.2010.279
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