Full-text of the article is available for this locale: Russian.
Abstract
INTRODUCTION: Creation of protocols for effective empiric antimicrobial therapy is impossible without the analysis of current antibiotic susceptibility data. OBJECTIVE: Analysis of changes in the etiological significance of the leading pathogens of bacteremia in the ICU (intensive care unit) in the period from 2003 to 2021, and their sensitivity to antibiotics; study of the types of carbapenemases in the most relevant pathogens — Klebsiella pneumoniae and Acinetobacter baumannii. MATERIALS AND METHODS: The analysis included all microorganisms isolated from the blood of patients who were in the medical 12-bed ICU in the emergency hospital of Moscow in the period from 2003 to 2021. Identification of microorganisms and determination of antibiotic sensitivity were carried out with an automatic PHOENIX analyzer and a standardized disco diffusion method. Detection of carbapenemases was carried out by PCR (polymerase chain reaction). RESULTS: In the period from 2003 to 2021, 17 034 blood samples were examined, from which 6372 microorganisms were isolated. During this period, the proportion of Gram-negative microorganisms increased from 21.0 to 52.8 %, mainly due to K. pneumoniae from 1.0 to 24.5 % and A. baumannii from 0 to 9.1 %. The resistance of these microorganisms to carbapenems increased significantly from 2008 to 2021: K. pneumoniae from 2.3 % to 70.3 %, A. baumannii — from 7.5 to 99.5 %. K. pneumoniae produced the following types of carbapenemases: OXA-48 (73.8 %), KPC (6.2 %), NDM 1.5 %, NDM + OXA-48 (15.4 %), KPC + OXA-48 (3.1 %). All A. baumannii strains produced OXA-40 type carbapenemase. OXA-48 carbapenemase producers were resistant to colistin and tigecycline in 14.6 and 44.8 %, and to ceftazidime/avibactam in 4.2 %. CONCLUSIONS: The increased level of antimicrobial resistance in recent years among Gram-negative microorganisms isolated from blood is a very significant problem in the ICU. Most K. pneumoniae strains are characterized as multi-drug resistant, about 10 % of the strains were categorized as extremely-drug resistant (XDR) or pan-drug resistant. All strains of A. baumannii belong to the category of XDR.
References
- Cunha B.A. Sepsis and septic shock: selection of empiric antimicrobial therapy. Crit Care Clin. 2008; 24(2): 313–34, ix. DOI: 10.1016/j.ccc.2007.12.015
- Funk D.J., Kumar A. Antimicrobial therapy for life-threatening infections: speed is life. Crit Care Clin. 2011; 27(1): 53–76. DOI: 10.1016/j.ccc.2010.09.008
- Seymour C.W., Gesten F., Prescott H.C., et al. Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. N Engl J Med. 2017; 376(23): 2235–44. DOI: 10.1056/NEJMoa1703058
- Capp R., Chang Y., Brown D.F. Effective antibiotic treatment prescribed by emergency physicians in patients admitted to the intensive care unit with severe sepsis or septic shock: where is the gap? J Emerg Med. 2011; 41(6): 573–80. DOI: 10.1016/j.jemermed.2010.10.024
- Zilberberg M.D., Nathanson B.H., Sulham K., et al. Carbapenem resistance, inappropriate empiric treatment and outcomes among patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia and sepsis. BMC Infect Dis. 2017; 17(1): 279. DOI: 10.1186/s12879-017-2383-z
- Borer A., Saidel-Odes L., Riesenberg K., et al. Attributable mortality rate for carbapenem-resistant Klebsiella pneumoniae bacteremia. Infect Control Hosp Epidemiol. 2009; 30(10): 972–6. DOI: 10.1086/605922
- А. Bykov, M. Suvorova, I. Sychev, I., et al. Infections in the intensive care unit caused by carbapenemase-producing Klebsiella pneumoniae and Acinetobacter baumannii: clinical and microbiological characteristics and outcome [abstract]. 29th European Conference on Clinical Microbiology and Infectious Diseases. Amsterdam, The Netherlands, April 13–16, 2019.
- Kohler P.P., Volling C., Green K., et al. Carbapenem Resistance, Initial Antibiotic Therapy, and Mortality in Klebsiella pneumoniae Bacteremia: A Systematic Review and Meta-Analysis. Infect Control Hosp Epidemiol. 2017; 38(11): 1319–28. DOI: 10.1017/ice.2017.197
- Cienfuegos-Gallet A.V., Ocampo de Los Ríos A.M., Sierra Viana P., et al. Risk factors and survival of patients infected with carbapenem-resistant Klebsiella pneumoniae in a KPC endemic setting: a case-control and cohort study. BMC Infect Dis. 2019; 19(1): 830. DOI: 10.1186/s12879-019-4461-x
- Chen Y., Chen Y., Liu P., et al. Risk factors and mortality for elderly patients with bloodstream infection of carbapenem resistance Klebsiella pneumoniae: a 10-year longitudinal study. BMC Geriatr. 2022; 22(1): 573. DOI: 10.1186/s12877-022-03275-1
- Weinstein M.P., Towns M.L., Quartey S.M., et al. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis. 1997; 24(4): 584–602. DOI: 10.1093/clind/24.4.584
- Pogue J.M., Kaye K.S., Cohen D.A., et al. Appropriate antimicrobial therapy in the era of multidrug-resistant human pathogens. Clin Microbiol Infect. 2015; 21(4): 302–12. DOI: 10.1016/j.cmi.2014.12.025
- Perez K.K., Olsen R.J., Musick W.L., et al. Integrating rapid diagnostics and antimicrobial stewardship improves outcomes in patients with antibiotic-resistant Gram-negative bacteremia. J Infect. 2014; 69(3): 216–25. DOI: 10.1016/j.jinf.2014.05.005
- Luyt C.E., Bréchot N., Trouillet J.L., et al. Antibiotic stewardship in the intensive care unit. Crit Care. 2014; 18(5): 480. DOI: 10.1186/s13054-014-0480-6
- Vora N.M., Kubin C.J., Furuya E.Y. Appropriateness of gram-negative agent use at a tertiary care hospital in the setting of significant antimicrobial resistance. Open Forum Infect Dis. 2015; 2(1):ofv009. DOI: 10.1093/ofid/ofv009
- Lai C.C., Shi Z.Y., Chen Y.H., et al. Effects of various antimicrobial stewardship programs on antimicrobial usage and resistance among common gram-negative bacilli causing health care-associated infections: A multicenter comparison. J Microbiol Immunol Infect. 2016; 49(1): 74–82. DOI: 10.1016/j.jmii.2015.05.011
- Campion M., Scully G. Antibiotic Use in the Intensive Care Unit: Optimization and De-Escalation. J Intensive Care Med. 2018; 33(12): 647–55. DOI: 10.1177/0885066618762747
- Программа СКАТ (Стратегия контроля антимикробной терапии) при оказании стационарной медицинской помощи. Российские клинические рекомендации. Под ред. С.В. Яковлева, Н.И. Брико, С.В. Сидоренко, Д.Н. Проценко. М.: Перо, 2018. 156 с. [AMS program (Strategy for the Control of Antimicrobial Therapy) in the provision of inpatient medical care. Russian clinical guidelines. Ed. S.V. Yakovlev, N.I. Briko, S.V. Sidorenko, D.N. Protsenko. M.: Pero, 2018. 156 p. (In Russ)]
- Журавлева М.В., Родионов Б.А., Лысенко М.А. и др. Изучение случаев бактериемии грамотрицательными патогенами с множественной и экстремальной устойчивостью к антибиотикам в реальной клинической практике. Антибиотики и Химиотерапия. 2021; 66(3–4): 27–34. DOI: 10.37489/0235-2990-2021-66-3-4-27-34 [Zhuravleva M.V., Rodionov B.A., Lysenko M.A., et al. Study of Cases of Bacteremia with Gram-Negative Pathogens with Multiple and Extreme Antibiotic Resistance in Real Clinical Practice. Antibiotics and Chemotherapy. 2021; 66(3–4): 27–34. DOI: 10.37489/0235-2990-2021-66-3-4-27-34 (In Russ)]
- Sanders C.C., Sanders W.E. Jr. Emergence of resistance to cefamandole: possible role of cefoxitin-inducible beta-lactamases. Antimicrob Agents Chemother. 1979; 15(6): 792–7. DOI: 10.1128/AAC.15.6.792
- Gazouli M., Sidorenko S.V., Tzelepi E., et al. A plasmid-mediated beta-lactamase conferring resistance to cefotaxime in a Salmonella typhimurium clone found in St. Petersburg, Russia. J Antimicrob Chemother. 1998; 41(1): 119–21. DOI: 10.1093/jac/41.1.119
- Сидоренко С.В., Страчунский Л.С., Ахмедова Л.И. и др. Результаты многоцентрового исследования сравнительной активности цефепима и других антибиотиков в отношении возбудителей тяжелых нозокомиальных инфекций (исследование «Micromax»). Антибиотики и химиотерапия. 1999; 11: 7. [Sidorenko S.V., Strachunsky L.S., Akhmedova L.I. Results of a multicenter study of the comparative activity of cefepime and other antibiotics against pathogens of severe nosocomial infections (Micromax study). Antibiotics and Chemotherapy. 1999; 11: 7. (In Russ)]
- Jones R.N., Pfaller M.A.; MYSTIC Study Group (Europe). Antimicrobial activity against strains of Escherichia coli and Klebsiella spp. with resistance phenotypes consistent with an extended-spectrum beta-lactamase in Europe. Clin Microbiol Infect 2003; 9(7): 708–12. DOI: 10.1046/j.1469-0691.2003.00555.x
- Решедько Г.К., Рябкова Е.Л., Кречикова О.И. и др. Резистентность к антибиотикам грамотрицательных возбудителей нозокомиальных инфекций в ОРИТ многопрофильных стационаров России. Клиническая Микробиология и Антимикробная Химиотерапия. 2008; 10(2): 96–112.
- Eucast.org [Internet]. The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 10.0, 2020. Available from: https://www.eucast.org
- Eucast.org [Internet]. Antimicrobial susceptibility tests on groups of organisms or agents for which there are no EUCAST breakpoints [updated 1 December 2021]. Available from: https://www.eucast.org
- Mic.eucast.org [Internet]. Antimicrobial wild type distributions of microorganisms. Mic distributions include collated data from multiple sources, geographical areas and time periods and can never be used to infer rates of resistance. Available from: https://mic.eucast.org/search/
- European Centre for Disease Prevention and Control/European Medicines Agency. ECDC/EMEA joint technical report: the bacterial challenge: time to react.: European centre for disease prevention and control & European medicines agency, Stockholm, Sweden & London, United Kingdom, 2009.
- Magiorakos A.P., Srinivasan A., Carey R.B., et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012; 18(3): 268–81. DOI: 10.1111/j.1469-0691.2011.03570.x
- Suvorova M., Sychev I., Bykov A., et al. Analysis of Gram-negative bacteraemia and sensitivity of blood isolates in the ICU department of Moscow (Russia) emergency hospital from 2003 to 2018 [abstract]. 29th European Conference on Clinical Microbiology and Infectious Diseases. Amsterdam, The Netherlands, April 13–16, 2019. Available from: https://www.escmid.org/fileadmin/eccmid/2019/media/documents/Final_Programme_web.pdf
- Timsit J.F., Ruppé E., Barbier F., et al. Bloodstream infections in critically ill patients: an expert statement. Intensive Care Med. 2020; 46(2): 266–84. DOI: 10.1007/s00134-020-05950-6
- Orsi G.B., Giuliano S., Franchi C., et al. Changed epidemiology of ICU acquired bloodstream infections over 12 years in an Italian teaching hospital. Minerva Anestesiol. 2015; 81(9): 980–8.
- Kim H., Kim E.S., Lee S.C., et al. Decreased Incidence of Methicillin-Resistant Staphylococcus aureus Bacteremia in Intensive Care Units: a 10-Year Clinical, Microbiological, and Genotypic Analysis in a Tertiary Hospital. Antimicrob Agents Chemother. 2020; 64(10): e01082–20. DOI: 10.1128/AAC.01082-20
- Gudiol C., Bodro M., Simonetti A., et al. Changing aetiology, clinical features, antimicrobial resistance, and outcomes of bloodstream infection in neutropenic cancer patients. Clin Microbiol Infect. 2013; 19(5): 474–9. DOI: 10.1111/j.1469-0691.2012.03879.x
- El-Sokkary R., Uysal S., Erdem H., et al. Profiles of multidrug-resistant organisms among patients with bacteremia in intensive care units: an international ID-IRI survey. Eur J Clin Microbiol Infect Dis. 2021; 40(11): 2323–34. DOI: 10.1007/s10096-021-04288-1
- Белобородов В.Б., Голощапов О.В., Гусаров В.Г. и др. Методические рекомендации Российской некоммерческой общественной организации «Ассоциация анестезиологов-реаниматологов», Межрегиональной общественной организации «Альянс клинических химиотерапевтов и микробиологов», Межрегиональной ассоциации по клинической микробиологии и антимикробной химиотерапии (МАКМАХ), общественной организации «Российский Сепсис Форум» «Диагностика и антимикробная терапия инфекций, вызванных полирезистентными штаммами микроорганизмов» (обновление 2022 г.). Вестник анестезиологии и реаниматологии. 2022; 19(2): 84–114. DOI: 10.21292/2078-5658-2022-19-2-84-114 [Beloborodov V.B., Goloschapov O.V., Gusarov V.G., et al. Guidelines of the Association of Anesthesiologists-Intensivists, the Interregional Non-Governmental Organization Alliance of Clinical Chemotherapists and Microbiologists, the Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (IACMAC), and NGO Russian Sepsis Forum "Diagnostics and antimicrobial therapy of the infections caused by multiresistant microorganisms" (update 2022). Messenger of ANESTHESIOLOGY AND RESUSCITATION. 2022; 19(2): 84–114. DOI: 10.21292/2078-5658-2022-19-2-84-114 (In Russ)]
- Antunes L.C., Visca P., Towner K.J. Acinetobacter baumannii: evolution of a global pathogen. Pathog Dis. 2014; 71(3): 292–301. DOI: 10.1111/2049-632X.12125
- Harding C.M., Hennon S.W., Feldman M.F. Uncovering the mechanisms of Acinetobacter baumannii virulence. Nat Rev Microbiol. 2018; 16(2): 91–102. DOI: 10.1038/nrmicro.2017.148
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Copyright (c) 2023 Annals of Critical Care