OncohematologyOncohematologyОнкогематология1818-83462413-4023Publishing House ABV Press37310.17650/1818-8346-2019-14-3-77-89INFECTION PROBLEMS IN ONCOHEMATOLOGYПРОБЛЕМЫ ИНФЕКЦИЙ В ОНКОГЕМАТОЛОГИИInfectious complications caused by carbapenemase-producing Enterobacterales in patients with hematological disordersИнфекционные осложнения, вызванные Enterobacterales с продукцией карбапенемаз, у пациентов с заболеваниями системы кровиhttps://orcid.org/0000-0003-3414-9316TandilovaK. S.ТандиловаK. C.
Russian Federation

4 Novyy Zykovskiy Proezd, Moscow 125167

Кристина Сергеевна Тандилова

125167 Москва, Новый Зыковский проезд, 4

 

kristina.tandilova@gmail.comhttps://orcid.org/0000-0001-5973-5763KlyasovaG. A.КлясоваГ. А.
Russian Federation

4 Novyy Zykovskiy Proezd, Moscow 125167

125167 Москва, Новый Зыковский проезд, 4

National Research Center for Hematology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России2010201914377892010201920102019https://oncohematology.abvpress.ru/ongm/article/view/373

Mortality rates approaching 60 % have been reported in hematological patients with infections caused by carbapenemase-producing Enterobacterales. The incidence of these infections is rapidly increasing, whereas the therapeutic options are limited. This review represents characteristics of infections caused by carbapenemase-producing Enterobacterales in patients with hematological disorders, highlights risk factors and management options of these infections.

Инфекции, вызванные Enterobacterales с продукцией карбапенемаз, характеризуются высокой летальностью, достигающей 60 % и более у пациентов с заболеваниями системы крови. Частота этих инфекций неуклонно возрастает, а возможности терапии остаются весьма ограниченными. В данном обзоре представлена характеристика инфекционных осложнений, вызванных Enterobacterales c продукцией карбапенемаз, выделены факторы риска возникновения этих инфекций, а также описан алгоритм их лечения.

carbapenemase-producing Enterobacteraleshemoblastosiscolonizationmultidrug-resistant bacteriainfectionEnterobacterales с продукцией карбапенемазгемобластозколонизацияполирезистентные бактерииинфекцияTrecarichi E.M., Pagano L., Martino B. et al. Bloodstream infections caused by Klebsiella pneumoniae in oncohematological patients: clinical impact of carbapenem resistance in a multicentre prospective survey. Am J Hematol 2016;91(11):1076–81. DOI: 10.1002/ajh.24489.Ambler R.P. The structure of beta-lactamases. Philos Trans R Soc Lond B Biol Sci 1980;289(1036):321–31.Lee C.R., Lee J.H., Park K.S. et al. Global dissemination of carbapenemase-producing Klebsiella pneumoniae: epidemiology, genetic context, treatment options, and detection methods. Front Microbiol 2016;7:895. DOI: 10.3389/fmicb.2016.00895.Chiu S.K., Ma L., Chan M.C. et al. Carbapenem nonsusceptible Klebsiella pneumoniae in Taiwan: dissemination and increasing resistance of carbapenemase producers during 2012–2015. Sci Rep 2018;8(1):8468. DOI: 10.1038/s41598-018-26691-z.Evans B.A., Amyes S.G. OXA β-lactamases. Clin Microbiol Rev 2014;27(2):241–63. DOI: 10.1128/CMR.00117-13.Nordmann P., Naas T., Poirel L. Global Spread of Carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis 2011;17(10):1791–8. DOI: 10.3201/eid1710.110655.Nordmann P., Mariotte S., Naas T. et al. Biochemical properties of a carbapenemhydrolyzing beta-lactamase from Enterobacter cloacae and cloning of the gene into Escherichia coli. Antimicrob Agents Chemother 1993;37(5):939–46. DOI: 10.1128/AAC.37.5.939.Naas T., Nordmann P. Analysis of a carbapenemhydrolyzing class A beta-lactamase from Enterobacter cloacae and of its LysR-type regulatory protein. PNAS 1994;91(16):7693–7.Yigit H., Queenan A.M., Anderson G.J. et al. Novel Carbapenem-Hydrolyzing β-Lactamase, KPC-1, from a CarbapenemResistant Strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 2001;45(4):1151–61. DOI: 10.1128/AAC.45.4.1151-1161.2001.Woodford N., Tierno P.M. Jr, Young K. et al. Outbreak of Klebsiella pneumoniae producing a new carbapenem-hydrolyzing class A beta-lactamase, KPC-3, in a New York Medical Center. Antimicrob Agents Chemother 2004;48(12):4793–9. DOI: 10.1128/AAC.48.12.4793-4799.2004.Leavitt A., Navon-Venezia S., Chmelnitsky I. et al. Emergence of KPC-2 and KPC-3 in carbapenem-resistant Klebsiella pneumoniae strains in an Israeli hospital. Antimicrob Agents Chemother 2007;51(8):3026–9. DOI: 10.1128/AAC.00299-07.Maltezou H.C., Giakkoupi P., Maragos A. et al. Outbreak of infections due to KPC2-producing Klebsiella pneumoniae in a hospital in Crete (Greece). J Infect 2009;58(3):213–9. DOI: 10.1016/j.jinf.2009.01.010Mezzatesta M.L., Gona F., Caio C. et al. Outbreak of KPC-3-producing, and colistinresistant, Klebsiella pneumoniae infections in two Sicilian hospitals. Clin Microbiol Infect 2011;17(9):1444–7. DOI: 10.1111/j.1469-0691.2011.03572.x.van Duin D., Doi Y. The global epidemiology of carbapenemase-producing Enterobacteriaceae. Virulence 2017;8(4):460–9. DOI: 10.1080/21505594.2016.1222343.French C.E., Coope C., Conway L. et al. Control of carbapenemase-producing Enterobacteriaceae outbreaks in acute settings: an evidence review. J Hosp Infect 2017;95(1):3–45. DOI: 10.1016/j.jhin.2016.10.006Pitout J.D.D., Nordmann P., Poirel L. Сarbapenemase-producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance. Antimicrob Agents Chemother 2015;59(10):5873–84. DOI: 10.1128/AAC.01019-15.Lazareva I.V., Ageevets V.A., Ershova T.A. et al. Prevalence and antibiotic resistance of carbapenemase-producing gram-negative bacteria in Saint Petersburg and some other regions of the Russian Federation. Antibiotiki i khimioterapiya = Antibiotics and Chemotherapy 2016;61;11–12;28–38. (In Russ.).Лазарева И.В., Агеевец В.А., Ершова Т.А. и др. Распространение и антибактериальная резистентность грамотрицательных бактерий, продуцентов карбапенемаз, в Санкт-Петербурге и некоторых других регионах Российской Федерации. Антибиотики и химиотерапия 2016;61;11–12;28–38.Sukhorukova M.V., Edelstein M.V., Skleenova E.Yu. et al. Antimicrobial resistance of nosocomial Enterobacteriaceae isolates in Russia: results of multicenter epidemiological study «MARATHON» 2013–2014 Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya = Clinical Microbiology and Antimicrobial Chemotherapy 2017;19;1:49–56. (In Russ.).Сухорукова М.В., Эйдельштейн М.В., Склеенова Е.Ю. и др. Антибиотикорезистентность нозокомиальных штаммов Enterobacteriaceae в стационарах России: результаты многоцентрового эпидемиологического исследования «МАРАФОН» 2013–2014. Клиническая микробиология и антимикробная химиотерапия 2017;19(1);49–56.Edelstein M.V., Zhuravlev V.S., Shek E.A. Prevalence of nosocomial strains Enterobacteriaceae have carbapenemases in Russia. Izvestiya Saratovskogo Universiteta. Njvaya seriya. Seriya: Khemiya. Biologiya. Ekologiya = Izvestiya of Saratov University. New Series. Series: Chemistry. Biology. Ecology 2017;17(1):36–41 (In Russ.). DOI: 10.18500/1816-9775-2017-17-1-36-41.Эйдельштейн М.В., Журавлев В.С., Шек Е.А. Распространенность карбапенемаз среди нозокомиальных штаммов Enterobacteriaceae в России. Известия Саратовского университета. Новая серия. Серия Химия. Биология. Экология 2017;17(1):36–41. DOI: 10.18500/1816-9775-2017-17-1-36-41.Shevchenko O.V., Mudrak D.Y., Skleenova E.Y. et al. First detection of VIM-4 metallo-β-lactamase-producing Escherichia coli in Russia. Clin Microbiol Infect 2012;18(7):E214–7. DOI: 10.1111/j.1469-0691.2012.03827.x.Sukhorukova M., Savochkina J., Alexandrova I. et al. First outbreak of carbapenemresistant OXA-48-producing Klebsiella pneumoniae in Russia. 22nd European Congress of Clin. Microbiol. Infect. Dis. 2012, March 31–Apr 3. London, United Kingdom. Available at: https://www.escmid.org/escmid_publications/escmid_elibrary/material/?mid=5700.Barantsevich E.P., Churkina I.V., Barantsevich N.E. et al. Emergence of Klebsiella pneumoniae producing NDM-1 carbapenemase in Saint Petersburg, Russia. J Antimicrob Chemother 2013;68(5):1204–6. DOI: 10.1093/jac/dks503.Ageevets V.A., Partina I.V., Lisitsyna E.S. et al. Emergence of carbapenemase-producing Gram-negative bacteria in Saint Petersburg, Russia. Int J Antimicrob Agents 2014;44(2):152–5. DOI: 10.1016/j.ijantimicag.2014.05.004.Edelstein M.V., Sukhorukova M.V., Skleenova E.Y. et al. In vitro activities of avibactam combinations with ceftazidime and aztreonam against clinical Enterobacteriaceae isolates recovered from hospitalized patients in Russia: results of the national surveillance. 27th European Congress of Clin. Microbiol. Infect. Dis. 2017, Apr 22–25. Vienna, Austria. Available at: https://www.escmid.org/escmid_publications/escmid_elibrary/material/?mid=51875.Girmenia C., Rossolini G.M., Piciocchi A. et al. Infections by carbapenem-resistant Klebsiella pneumoniae in SCT recipients: a nationwide retrospective survey from Italy. Bone Marrow Transplant 2015;50(2):282– 8. DOI: 10.1038/bmt.2014.231.Pouch S.M., Satlin M.J. Carbapenem-resistant Enterobacteriaceae in special populations: Solid organ transplant recipients, stem cell transplant recipients, and patients with hematologic malignancies. Virulence 2017;8(4):391–402. DOI: 10.1080/21505594.2016.1213472.Pagano L., Caira M., Trecarichi E.M. et al. Carbapenemase-producing Klebsiella pneumoniae and hematologic malignancies. Emerg Infect Dis 2014;20(7):1235–6. DOI: 10.3201/eid2007.130094.Balkan I.I., Aygün G., Aydın S. et al. Blood stream infections due to OXA-48like carbapenemase-producing Enterobacteriaceae: treatment and survival. Int J Infect Dis 2014;26:51–6. DOI: 10.1016/j.ijid.2014.05.012.Tofas P., Skiada A., Angelopoulou M. et al. Carbapenemase-producing Klebsiella pneumoniae bloodstream infections in neutropenic patients with haematological malignancies or aplastic anaemia: Analysis of 50 cases. Int J Antimicrob Agents 2016;47(4):335–9. DOI: 10.1016/j.ijantimicag.2016.01.011.Satlin M.J., Calfee D.P., Chen L. et al. Emergence of carbapenem-resistant Enterobacteriaceae as causes of bloodstream infections in patients with hematologic malignancies. Leuk Lymphoma 2013;54(4):799–806. DOI: 10.3109/10428194.2012.723210.Averbuch D., Orasch C., Cordonnier C. et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica 2013;98(12):1826–35. DOI: 10.3324/haematol.2013.091025.Papanicolas L.E., Gordon D.L., Wesselingh S.L., Rogers G.B. Not just antibiotics: is cancer chemotherapy driving antimicrobial resistance? Trends Microbiol 2018;26(5):393–400. DOI: 10.1016/j.tim.2017.10.009.Tischendorf J., de Avila R.A., Safdar N. Risk of infection following colonization with carbapenem-resistant Enterobacteriaceae: a systematic review. Am J Infect Control 2016;44(5):539–43. DOI: 10.1016/j.ajic.2015.12.005.Micozzi A., Gentile G., Minotti C. et al. Carbapenem-resistant Klebsiella pneumoniae in high-risk haematological patients: factors favouring spread, risk factors and outcome of carbapenem-resistant Klebsiella pneumoniae bacteremias. BMC Infect Dis 2017;17(1):203. DOI: 10.1186/s12879-017-2297-9.Giannella M., Trecarichi E.M., De Rosa F.G. et al. Risk factors for carbapenem-resistant Klebsiella pneumoniae bloodstream infection among rectal carriers: a prospective observational multicentre study. Clin Microbiol Infect 2014;20(12):1357–62. DOI: 10.1111/1469-0691.12747.Girmenia C., Viscoli C., Piciocchi A. et al. Management of carbapenem resistant Klebsiella pneumoniae infections in stem cell transplant recipients: an Italian multidisciplinary consensus statement. Haematologica 2015;100(9):e373–6. DOI: 10.3324/haematol.2015.125484.Forcina A., Baldan R., Marasco V. et al. Control of infectious mortality due to carbapenemaseproducing Klebsiella pneumoniae in hematopoietic stem cell transplantation. Bone Marrow Transplant 2017;52(1):114–9. DOI: 10.1038/bmt.2016.234.Zuckerman T., Benyamini N., Sprecher H. 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(9):1226–30. DOI: 10.1038/bmt.2010.279.Oren I., Sprecher H., Finkelstein R. et al. Eradication of carbapenem-resistant Enterobacteriaceae gastrointestinal colonization with nonabsorbable oral antibiotic treatment: a prospective controlled trial. Am J Infect Control 2013;41(12):1167–72. DOI: 10.1016/j.ajic.2013.04.018.Machuca I., Gutierrez-Gutierrez B., Perez Cortes S. 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(11):3242– 9. DOI: 10.1093/jac/dkw272.Tascini C., Sbrana F., Flammini S. 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(4):1972–6. DOI: 10.1128/AAC.02283-13.Tacconelli E., Mazzaferri F., Marie de Smet A. et al. ESCMID-EUCIC clinical guidelines on decolonisation of multidrugresistant Gram-negative bacteria carriers. Clin Microbiol Infect 2019. DOI: 10.1016/j.cmi.2019.01.005.Daikos G.L., Tsaousi S., Tzouvelekis L.S. et al. Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems. Antimicrob Agents Chemother 2014;58(4):2322–8. DOI: 10.1128/AAC.02166-13.Rodríguez-Baño J., Gutiérrez-Gutiérrez B., Machuca I., Pascual A. Treatment of infections caused by extended-spectrum-betalactamase-, AmpC-, and carbapenemaseproducing Enterobacteriaceae. Clin Microbiol Rev 2018;31(2). DOI: 10.1128/CMR.00079-17.de Maio Carrilho C.M.D., Marques de Oliveira L., Gaudereto J. et al. A prospective study of treatment of carbapenem-resistant Enterobacteriaceae infections and risk factors associated with outcome. BMC Infect Dis 2016;16(1):629. DOI: 10.1186/s12879-016-1979-z.Gutiérrez-Gutiérrez B., Salamanca E., de Cueto M. et al. A predictive model of mortality in patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae. Mayo Clin Proc 2016;91(10):1362–71. DOI: 10.1016/j.mayocp.2016.06.024.Hilf M., Yu V.L., Sharp J. et al. Antibiotic therapy for Pseudomonas aeruginosa bacteremia: outcome correlations in a prospective study of 200 patients. Am J Med 1989;87(5):540–6. DOI: 10.1016/S00029343(89)80611-4.Charlson M.E., Szatrowski T.P., Peterson J., Gold J. Validation of a combined comorbidity index. J Clin Epidemiol 1994;47(11):1245–51. DOI: 10.1016/0895-4356(94)90129-5.Cano A., Gutiérrez-Gutiérrez B., Machuca I. et al. Risks of infection and mortality among patients colonized with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: validation of scores and proposal for management. Clin Infect Dis 2018;66(8):1204–10. DOI: 10.1093/cid/cix991.Tumbarello M., Trecarichi E.M., De Rosa F.G. et al. Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study. J Antimicrob Chemother 2015;70(7):2133–43. DOI: 10.1093/jac/dkv086.Pea F., Della Siega P., Cojutti P. et al. Might real-time pharmacokinetic/pharmacodynamic optimisation of high-dose continuous-infusion meropenem improve clinical cure in infections caused by KPCproducing Klebsiella pneumoniae? Int J Antimicrob Agents 2017;49(2):255–8. DOI: 10.1016/j.ijantimicag.2016.10.018.Del Bono V., Giacobbe D.R., Marchese A. et al. Meropenem for treating KPC-producing Klebsiella pneumoniae bloodstream infections: should we get to the PK/PD root of the paradox? Virulence 2017;8(1):66–73. DOI: 10.1080/21505594.2016.1213476.Bulik C.C., Nicolau D.P. Double-carbapenem therapy for carbapenemase-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 2011;55(6):3002–4. DOI: 10.1128/AAC.01420-10.De Pascale G., Martucci G., Montini L. et al. Double carbapenem as a rescue strategy for the treatment of severe carbapenemaseproducing Klebsiella pneumoniae infections: a two-center, matched case-control study. Crit Care 2017;21(1):173. DOI: 10.1186/s13054-017-1769-z.Klyasova G.A., Okhmat V.A. Antimicrobial therapy. In: Program treatment of blood system disorders. 2nd edn. Ed.: V.G. Savchenko. Moscow: Praktika, 2018. Pp. 1067–1113. (In Russ.).Клясова Г.А., Охмат В.А. Антимикробная терапия. В кн.: Алгоритмы диагностики и протоколы лечения заболеваний системы крови. Том 2. Под ред. В.Г. Савченко. М.: Практика, 2018. C. 1067–1113.Kozlov R.S., Stetsyuk O.U., Andreeva I.V. Ceftazidime-avibactam: new rules for the game against multidrugresistant gram-negative bacteria. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya = Clinical Microbiology and Antimicrobial Chemotherapy 2018;20(1):24–34. (In Russ.).Козлов Р.С., Стецюк О.У., Андреева И.В. Цефтазидимавибактам: новые «правила игры» против полирезистентных грамотрицательных бактерий. Клиническая микробиология и антимикробная химиотерапия 2018;20(1):24–34.Castón J.J., Lacort-Peralta I., MartínDávila P. et al. Clinical efficacy of ceftazidime/ avibactam versus other active agents for the treatment of bacteremia due to carbapenemaseproducing Enterobacteriaceae in hematologic patients. Int J Infect Dis 2017;59:118–23. DOI: 10.1016/j.ijid.2017.03.021.Tumbarello M., Trecarichi E.M., Corona A. et al. Efficacy of ceftazidime-avibactam salvage therapy in patients with infections caused by Klebsiella pneumoniae carbapenemaseproducing K. pneumoniae. Clin Infect Dis 2019;68(3):355–64. DOI: 10.1093/cid/ciy492.