Traumatology and Orthopedics of RussiaTraumatology and Orthopedics of RussiaТравматология и ортопедия России2311-29052542-0933Vreden National Medical Research Center of Traumatology and Orthopedics1672010.17816/2311-2905-16720CLINICAL STUDIESКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯClinical studiesResearch ArticleTwelve-Year Dynamics of Leading Pathogens Spectrum Causing Orthopedic Infection: A Retrospective StudyДвенадцатилетняя динамика спектра ведущих возбудителей ортопедической инфекции: ретроспективное исследованиеhttps://orcid.org/0000-0001-6284-7133KasimovaAlina R.КасимоваАлина Рашидовна
Russian Federation

Cand. Sci. (Med.)

канд. мед. наук

kasi-alina@yandex.ruhttps://orcid.org/0000-0003-4891-4963TufanovaOlga S.ТуфановаОльга Сергеевна
Russian Federation
katieva@mail.ruhttps://orcid.org/0000-0003-2326-7413GordinaEkaterina M.ГординаЕкатерина Михайловна
Russian Federation

Cand. Sci. (Med.)

канд. мед. наук

emgordina@win.rniito.ruhttps://orcid.org/0000-0001-8045-1220GvozdetskyAnton N.ГвоздецкийАнтон Николаевич
Russian Federation

Cand. Sci. (Med.)

канд. мед. наук

Gvozdetskiy_AN@hotmail.comhttps://orcid.org/0000-0003-2121-094XRadaevaKseniia S.РадаеваКсения Сергеевна
Russian Federation
xenrada@gmail.comhttps://orcid.org/0000-0003-3307-4674RukinaAnna N.РукинаАнна Николаевна
Russian Federation
anrukina@win.rniito.ruhttps://orcid.org/0000-0002-2083-2424BozhkovaSvetlana A.БожковаСветлана Анатольевна
Russian Federation

Dr. Sci. (Med.)

д-р мед. наук

clinpharm-rniito@yandex.ruhttps://orcid.org/0000-0003-0733-2414TikhilovRashid M.ТихиловРашид Муртузалиевич
Russian Federation

Dr. Sci. (Med.), Professor

д-р мед. наук, профессор, чл.-кор. РАН

rtikhilov@gmail.comVreden National Medical Research Center of Traumatology and OrthopedicsФГБУ «Национальный медицинский исследовательский центр травматологии и ортопедии им. Р.Р. Вредена» Минздрава РоссииPavlov First Saint Petersburg State Medical UniversityФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава РоссииMechnikov North-Western State Medical UniversityФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава РоссииVreden National Medical Research Center of Traumatology and OrthopedicsФГБУ «Национальный медицинский исследовательский центр травматологии и ортопедии им. Р.Р. Вредена» Минздрава России150220243103202430166750310202326122023Copyright ©; 2024, Eco-VectorCopyright ©; 2024, Эко-ВекторCopyright ©; 2024,2024Eco-VectorЭко-Векторhttps://creativecommons.org/licenses/by-nc-nd/4.0https://journal.rniito.org/jour/article/view/16720

Background. The number of surgeries on the musculoskeletal system is increasing every year. Along with the increasing access to orthopedic care, the number of patients with orthopedic infection, the etiological agents of which can be from various taxonomic groups, is also increasing. Staphylococcus aureus and different types of coagulase-negative staphylococci (CoNS), including S. epidermidis and S. lugdunensis, together are the causative agents in 70% of cases.

Aim of the study — to analyze the dynamics of the microbial spectrum isolated from patients of the septic surgery department for the period from 2011 to 2022.

Methods. We performed a retrospective analysis of the microbial spectrum isolated from patients who were treated in the septic surgery department from January 1, 2011 to December 31, 2022. The leading pathogens were microorganisms whose share in the spectrum exceeded 3.5%. Of the isolated pathogens, 48.8% were the only etiological agents, and microbial associations were detected in 51.2% of the isolated pathogens.

Results. A total of 10,327 bacteria strains were identified over the 12-year period. The leading microorganisms causing orthopedic infection were Staphylococcus spp., Enterococcus spp., Propionibacterium spp., Pseudomonas aeruginosa, Corynebacterium spp., Streptococcus spp., Klebsiella spp. and Acinetobacter spp. In the dynamics of isolated pathogens during the analyzed period, several trends were determined: a decrease in the shares of S. aureus, Enterococcus spp., P. aeruginosa, Acinetobacter spp. and an increase in the shares of CoNS and Corynebacterium spp.

Conclusion. During 12 years, in the microbial spectrum of orthopedic infection in patients of the septic surgery department of our Center, Gram-positive bacteria, in the majority representatives of the genus Staphylococcus, prevailed. At the same time, a significant decrease in the share of S. aureus strains and an increase in the frequency of isolation of various species of CoNS were registered. A significant decrease in the number of non-fermenting Gram-negative bacteria was also revealed.

Актуальность. Количество хирургических вмешательств на опорно-двигательном аппарате возрастает с каждым годом. Одновременно с ростом доступности ортопедической помощи увеличивается и количество пациентов с ортопедической инфекцией, этиологическими агентами которой могут быть представители различных таксономических групп. Staphylococcus aureus и различные виды коагулазонегативных стафилококков (CoNS), включая S. epidermidis и S. lugdunensis, в совокупности являются возбудителями в 70% случаев.

Цель исследования — проанализировать динамику спектра ведущих патогенов, выделенных от пациентов отделения гнойной остеологии, за период с 2011 по 2022 г.

Материал и методы. Выполнен ретроспективный анализ спектра микроорганизмов, изолированных от пациентов, находившихся на лечении в отделении гнойной хирургии с 1 января 2011 г. по 31 декабря 2022 г. К ведущим возбудителям относили микроорганизмы, доля которых в спектре превышала 3,5%. Из выделенных возбудителей 48,8% были единственными этиологическими агентами, в 51,2% определяли наличие микробных ассоциаций.

Результаты. За 12-летний период идентифицировано 10 327 штаммов различных видов бактерий. Ведущими микроорганизмами, выделенными от пациентов с ортопедической инфекцией, были Staphylococcus spp., Enterococcus spp, Propionibacterium spp., Pseudomonas aeruginosa, Corynebacterium spp., Streptococcus spp., Klebsiella spp. и Acinetobacter spp. В динамике выделенных возбудителей за анализируемый период определено несколько трендов: сокращение долей S. aureus, Enterococcus spp., P. aeruginosa, Acinetobacter spp. и увеличение доли СоNS и Corynebacterium spp.

Заключение. Выполненное исследование показало, что в течение 12 лет в спектре возбудителей ортопедической инфекции у пациентов отделения гнойной хирургии нашего Центра основными были грамположительные бактерии, в большинстве представители рода Staphylococcus. При этом регистрировали значимое снижение доли штаммов S. aureus и рост частоты выделения различных видов СоNS. Также выявлено значимое снижение количества неферментирующих грамотрицательных бактерий.

orthopedic infectionStaphylococcus aureusmicrobial spectrumperiprosthetic infectionosteomyelitisортопедическая инфекцияStaphylococcus aureusспектр возбудителейперипротезная инфекцияостеомиелитSamelis P., Papagrigorakis E., Sameli E., Mavrogenis A., Savvidou O., Koulouvaris P. Current concepts on the application, pharmacokinetics and complications of antibiotic-loaded cement spacers in the treatment of prosthetic joint infections. Cureus. 2022;14(1):e20968. doi: 10.7759/cureus.20968.1. Samelis P., Papagrigorakis E, Sameli E, Mavrogenis A, Savvidou O, Koulouvaris P. Current concepts on the application, pharmacokinetics and complications of antibiotic-loaded cement spacers in the treatment of prosthetic joint infections. Cureus. 2022 Jan 5;14(1):e20968. doi: 10.7759/cureus.20968.SIRIS Report 2019. Annual Report of the Swiss National Joint Registry, Hip and Knee, 2012–2018. November 2019. doi: 10.13140/RG.2.2.15632.56323.2. (SIRIS Report 2019. Annual Report of the Swiss National Joint Registry, Hip and Knee, 2012 – 2018.2019 November 2019. DOI: 10.13140/RG.2.2.15632.56323Akindolire J., Morcos M.W., Marsh J.D., Howard J.L., Lanting B.A., Vasarhelyi E.M. The economic impact of periprosthetic infection in total hip arthroplasty. Can J Surg. 2020;63(1):E52-E56. doi: 10.1503/cjs.004219.3. Akindolire J.; Morcos M.; Marsh J.; Howard L.; Lanting B.; Vasarhelyi, E. The economic impact of periprosthetic infection in total hip arthroplasty. Can. J. Surg. J. Can. Chir. 2020, 63 (1), E52–E56. https://doi.org/10.1503/cjs.004219.Drago L., De Vecchi E., Bortolin M., Zagra L., Romanò C., Cappelletti L. Epidemiology and Antibiotic Resistance of Late Prosthetic Knee and Hip Infections. J Arthroplasty. 2017;32(8):2496-2500. doi: 10.1016/j.arth.2017.03.005.4. Drago L.; De Vecchi E.; Bortolin M.; Zagra L.; Romanò C.; Cappelletti L. Epidemiology and antibiotic resistance of late prosthetic knee and hip infections. J. Arthroplasty 2017, 32 (8), 2496–2500. https://doi.org/10.1016/j.arth.2017.03.005.Masters E.A., Ricciardi B.F., Bentley K.L.M., Moriarty T.F., Schwarz E.M., Muthukrishnan G. Skeletal infections: microbial pathogenesis, immunity and clinical management. Nat Rev Microbiol. 2022;20(7):385-400. doi: 10.1038/s41579-022-00686-0.5. Masters E.; Ricciardi B.; Bentley K.; De M.; Moriarty T.; Schwarz E.; Muthukrishnan G. Skeletal infections: microbial pathogenesis, immunity and clinical management. Nat. Rev. Microbiol. 2022, 20 (7), 385–400. https://doi.org/10.1038/s41579-022-00686-0.Kheir M.M., Tan T.L., Ackerman C.T., Modi R., Foltz C., Parvizi J. Culturing Periprosthetic Joint Infection: Number of Samples, Growth Duration, and Organisms. J Arthroplasty. 2018;33(11):3531-3536.e1. doi: 10.1016/j.arth.2018.06.018.6. Kheir M.; Tan T.; Ackerman C.; Modi R.; Foltz C.; Parvizi J. Culturing periprosthetic joint infection: number of samples, growth duration, and organisms. J. Arthroplasty 2018, 33 (11), 3531-3536.e1. https://doi.org/10.1016/j.arth.2018.06.018.Akgün D., Maziak N., Plachel F., Siegert P., Minkus M., Thiele K. et al. The role of implant sonication in the diagnosis of periprosthetic shoulder infection. J Shoulder Elbow Surg. 2020;29(6):e222-e228. doi: 10.1016/j.jse.2019.10.011.7. Akgün D.; Maziak N.; Plachel F.; Siegert P.; Minkus M.; Thiele K. et al. The role of implant sonication in the diagnosis of periprosthetic shoulder infection. J. Shoulder Elbow Surg. 2020, 29 (6), e222–e228. https://doi.org/10.1016/j.jse.2019.10.011.Гордина Е.М., Божкова С.А. Бактериальные биопленки в ортопедии: проблема и возможные перспективы профилактики. РМЖ. 2021;29(8):29-32. Gordina E.M., Bozhkova S.A. Bacterial biofilms in orthopedics: the problem and possible prospects for prevention. RMJ. 2021;29(8):29-32. (In Russian).8. Гордина Е.М., Божкова С.А. Бактериальные биопленки в ортопедии: проблема и возможные перспективы профилактики. РМЖ. 2021(8):29-32. Gordina E.M., Bozhkova S.A. Bacterial biofilms in orthopedics: the problem and possible prospects for prevention. RMJ. 2021(8):29-32.Божкова С.А., Касимова А.Р., Тихилов Р.М., Полякова Е.М. Рукина А.Н., Шабанова В.В. и др. Неблагоприятные тенденции в этиологии ортопедической инфекции: результаты 6-летнего мониторинга структуры и резистентности ведущих возбудителей. Травматология и ортопедия России. 2018;24(4):20-31. doi: 10.21823/2311-2905-2018-24-4-20-31. Bozhkova S.A., Kasimova A.R., Tikhilov R.M., Polyakova E.M., Rukina A.N., Shabanova V.V. et al. Adverse Trends in the Etiology of Orthopedic Infection: Results of 6-Year Monitoring of the Structure and Resistance of Leading Pathogens. Traumatology and Orthopedics of Russia. 2018;24(4):20-31. (In Russian). doi: 10.21823/2311-2905-2018-24-4-20-31.9. Неблагоприятные тенденции в этиологии ортопедической инфекции: результаты 6-летнего мониторинга структуры и резистентности ведущих возбудителей / С. А. Божкова, А. Р. Касимова, Р. М. Тихилов [и др.] // Травматология и ортопедия России. – 2018 (4): – 20-31. – DOI 10.21823/2311-2905-2018-24-4-20-31. Bozhkova S.A., Kasimova A.R., Tikhilov R.M., Polyakova E.M., Rukina A.N., Shabanova V.V., Liventsov V.N. [Adverse Trends in the Etiology of Orthopedic Infection: Results of 6-Year Monitoring of the Structure and Resistance of Leading Pathogens.]. Travmatologiya i ortopediya Rossii [Traumatology and Orthopedics of Russia]. 2018;24(4): 20-31. (In Russ.). DOI: 10.21823/2311-2905-2018-24-4-20-31.Zeller V., Kerroumi Y., Meyssonnier V., Heym B., Metten M.A., Desplaces N. et al. Analysis of postoperative and hematogenous prosthetic joint-infection microbiological patterns in a large cohort. J Infect. 2018;76(4):328-334. doi: 10.1016/j.jinf.2017.12.016.10. Zeller V.; Kerroumi Y.; Meyssonnier V.; Heym B.; Metten M.; Desplaces N.; et al. Analysis of postoperative and hematogenous prosthetic joint-infection microbiological patterns in a large cohort. J. Infect. 2018, 76 (4), 328–334. https://doi.org/10.1016/j.jinf.2017.12.016.Wimmer M., Friedrich M., Randau T., Ploeger M., Schmolders J., Strauss A. et al. Polymicrobial infections reduce the cure rate in prosthetic joint infections: outcome analysis with two-stage exchange and follow-up two years. Int Orthop. 2016;40(7):1367-1373. doi: 10.1007/s00264-015-2871-y.11. Wimmer M.; Friedrich M.; Randau T.; Ploeger M.; Schmolders J.; Strauss A.; et al. Polymicrobial infections reduce the cure rate in prosthetic joint infections: outcome analysis with two-stage exchange and follow-up two years. Int. Orthop. 2016, 40 (7), 1367–1373. https://doi.org/10.1007/s00264-015-2871-y.Issa K., Pourtaheri S., Stewart T., Faloon M., Sahai N., Mease S. et al. Clinical differences between monomicrobial and polymicrobial vertebral osteomyelitis. Orthopedics. 2017;40(2):e370-e373. doi: 10.3928/01477447-20161108-05.12. Issa K.; Pourtaheri S.; Stewart T.; Faloon M.; Sahai N.; Mease S.; et al. Clinical differences between monomicrobial and polymicrobial vertebral osteomyelitis. Orthopedics 2017, 40 (2), e370–e373. https://doi.org/10.3928/01477447-20161108-05.Sebastian S., Malhotra R., Sreenivas V., Kapil A., Chaudhry R., Dhawan B. A Clinico-microbiological study of prosthetic joint infections in an indian tertiary care hospital: role of universal 16s rrna gene polymerase chain reaction and sequencing in diagnosis. Indian J Orthop. 2019;53(5):646-654. doi: 10.4103/ortho.IJOrtho_551_18.13. Sebastian S.; Malhotra R.; Sreenivas V.; Kapil A.; Chaudhry R.; Dhawan B. A Clinico-microbiological study of prosthetic joint infections in an indian tertiary care hospital: role of universal 16s rrna gene polymerase chain reaction and sequencing in diagnosis. Indian J. Orthop. 2019, 53 (5), 646–654. https://doi.org/10.4103/ortho.IJOrtho_551_18.Li H., Fu J., Niu E., Chai W., Xu C., Hao L. et al. The risk factors of polymicrobial periprosthetic joint infection: a single-center retrospective cohort study. BMC Musculoskelet Disord. 2021;22:780. doi: 10.1186/s12891-021-04664-0.14. Li H.; Fu J.; Niu E.; Chai W.; Xu C.; Hao L. et al. The risk factors of polymicrobial periprosthetic joint infection: a single-center retrospective cohort study. BMC Musculoskelet. Disord. 2021, 22, 780. https://doi.org/10.1186/s12891-021-04664-0.Valenzuela M., Averkamp B., Odum S., Rowe T., Fehring T.K. Polymicrobial colonization of prosthetic joint infections treated with open wound management. J Arthroplasty. 2022;37(7S):S653-S656. doi: 10.1016/j.arth.2022.03.016.15. Valenzuela M.; Averkamp B.; Odum S.; Rowe T.; Fehring T. K. Polymicrobial colonization of prosthetic joint infections treated with open wound management. J. Arthroplasty 2022, 37 (7S), S653–S656. https://doi.org/10.1016/j.arth.2022.03.016.Fröschen F.S., Randau T.M., Franz A., Molitor E., Hoerauf A., Hischebeth G.T.R. Microbiological Trends and Antibiotic Susceptibility Patterns in Patients with Periprosthetic Joint Infection of the Hip or Knee over 6 Years. Antibiotics (Basel). 2022;11(9):1244. doi: 10.3390/antibiotics11091244.16. Fröschen F.; Randau T.; Franz A.; Molitor E.; Hoerauf A.; Hischebeth G. Microbiological trends and antibiotic susceptibility patterns in patients with periprosthetic joint infection of the hip or knee over 6 years. Antibiot. Basel Switz. 2022, 11 (9), 1244. https://doi.org/10.3390/antibiotics11091244.Ull C., Yilmaz E., Baecker H., Schildhauer T.A., Waydhas C., Hamsen U. Microbial findings and the role of difficult-to-treat pathogens in patients with periprosthetic infection admitted to the intensive care unit. Orthop Rev (Pavia). 2020;12(3):8867. doi: 10.4081/or.2020.8867.17. Ull C.; Yilmaz E.; Baecker H.; Schildhauer T.; Waydhas C.; Hamsen U. Microbial findings and the role of difficult-to-treat pathogens in patients with periprosthetic infection admitted to the intensive care unit. Orthop. Rev. 2020, 12 (3), 8867. https://doi.org/10.4081/or.2020.8867.Abubakar U., Sulaiman S.A.S. Prevalence, trend and antimicrobial susceptibility of Methicillin Resistant Staphylococcus aureus in Nigeria: a systematic review. J Infect Public Health. 2018;11(6):763-770. doi: 10.1016/j.jiph.2018.05.013.18. Abubakar U.; Sulaiman S. Prevalence, trend and antimicrobial susceptibility of methicillin resistant staphylococcus aureus in nigeria: a systematic review. J. Infect. Public Health 2018, 11 (6), 763–770. https://doi.org/10.1016/j.jiph.2018.05.013.Hamdan E.M., Hassan A.A., Amin S.A., Ahmed H.A., Ataelmanan A.E., Elmakki M.A. et al. Increasing Prevalence of Methicillin-resistant Staphylococcus aureus among Hospital and Community acquired Infections in Khartoum State, Sudan. Infect Disord Drug Targets. 2022. doi: 10.2174/1871526523666221201101411.19. Hamdan E.; Hassan A.; Amin S.; Ahmed H.; Ataelmanan A.; Elmakki, M. A.; Elhassan, M. M. Increasing prevalence of methicillin-resistant staphylococcus aureus among hospital and community acquired infections in khartoum state, sudan. Infect. Disord. Drug Targets 2022. https://doi.org/10.2174/1871526523666221201101411.Arjyal C., Kc J., Neupane S. Prevalence of Methicillin-Resistant Staphylococcus aureus in Shrines. Int J Microbiol. 2020;2020:7981648. doi: 10.1155/2020/7981648.20. Arjyal C.; Kc J.; Neupane S. Prevalence of methicillin-resistant staphylococcus aureus in shrines. Int. J. Microbiol. 2020, 2020, 7981648. https://doi.org/10.1155/2020/7981648.França A., Gaio V., Lopes N., Melo L.D.R. Virulence Factors in Coagulase-Negative Staphylococci. Pathogens. 2021;10(2):170. doi: 10.3390/pathogens10020170.21. França A.; Gaio V.; Lopes N.; Melo L. D. R. Virulence factors in coagulase-negative staphylococci. Pathog. Basel Switz. 2021, 10 (2), 170. https://doi.org/10.3390/pathogens10020170.Винклер Т., Трампуш А., Ренц Н., Перка К., Божкова С.А. Классификация и алгоритм диагностики и лечения перипротезной инфекции тазобедренного сустава. Травматология и ортопедия России. 2016;22(1):33-45. doi: 10.21823/2311-2905-2016-0-1-33-45. Winkler T., Trampuz A., Renz N., Perka C., Bozhkova S. Classification and algorithm for diagnosis and treatment of hip prosthetic joint infection. Traumatology and Orthopedics of Russia. 2016;22(1):33-45. (In Russian). doi: 10.21823/2311-2905-2016-0-1-33-45.22. Винклер Т, Трампуш А, Ренц Н, Перка К, Божкова СА. Классификация и алгоритм диагностики и лечения перипротезной инфекции тазобедренного сустава. Травматология и ортопедия России. 2016;22(1):33-45. doi: 10.21823/2311-2905-2016-0-1-33-45. Winkler T, Trampuz A, Renz N, Perka C, Bozhkova S. Classification and algorithm for diagnosis and treatment of hip prosthetic joint infection. Traumatology and Orthopedics of Russia. 2016;22(1):33-45. doi: 10.21823/2311-2905-2016-0-1-33-45Widerström M., Stegger M., Johansson A., Gurram B.K., Larsen A.R., Wallinder L. et al. Heterogeneity of Staphylococcus epidermidis in prosthetic joint infections: time to reevaluate microbiological criteria? Eur J Clin Microbiol Infect Dis. 2022;41(1):87-97. doi: 10.1007/s10096-021-04352-w.23. Widerström M.; Stegger M.; Johansson A.; Gurram B.; Larsen A.; Wallinder L. et al.; Heterogeneity of staphylococcus epidermidis in prosthetic joint infections: time to reevaluate microbiological criteria? Eur. J. Clin. Microbiol. Infect. Dis. 2022, 41 (1), 87–97. https://doi.org/10.1007/s10096-021-04352-w.Hischebeth G.T., Randau T.M., Ploeger M.M., Friedrich M.J., Kaup E., Jacobs C. et al. Staphylococcus aureus versus Staphylococcus epidermidis in periprosthetic joint infection-Outcome analysis of methicillin-resistant versus methicillin-susceptible strains. Diagn Microbiol Infect Dis. 2019;93(2):125-130. doi: 10.1016/j.diagmicrobio.2018.08.012.24. Hischebeth G.; Randau T.; Ploeger M.; Friedrich M.; Kaup E.; Jacobs C.; et al. Staphylococcus aureus versus Staphylococcus epidermidis in periprosthetic joint infection-outcome analysis of methicillin-resistant versus methicillin-susceptible strains. Diagn. Microbiol. Infect. Dis. 2019, 93 (2), 125–130. https://doi.org/10.1016/j.diagmicrobio.2018.08.012.Rabaud C., Mauuary G. Infection and/or colonization by methicillin-resistant Staphylococcus epidermidis (MRSE). Pathol Biol (Paris). 2001;49(10):812-814. doi: 10.1016/s0369-8114(01)00221-8.25. Rabaud C.; Mauuary G. Infection and/or colonization by methicillin-resistant Staphylococcus epidermidis (MRSE). Pathol. Biol. (Paris) 2001, 49 (10), 812–814. https://doi.org/10.1016/s0369-8114(01)00221-8.Benito N., Franco M., Ribera A., Soriano A., Rodriguez-Pardo D., Sorlí L. et al. Group for the Study of Prosthetic Joint Infections. Time trends in the aetiology of prosthetic joint infections: a multicentre cohort study. Clin Microbiol Infect. 2016;22(8):732.e1-8. doi: 10.1016/j.cmi.2016.05.004.26. Benito N.; Franco M.; Ribera A.; Soriano A.; Rodriguez-Pardo D.; Sorlí L.; et al; REIPI (Spanish Network for Research in Infectious Disease) Group for the Study of Prosthetic Joint Infections. Time Trends in the Aetiology of Prosthetic Joint Infections: A Multicentre Cohort Study. Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis. 2016, 22 (8), 732.e1-8. https://doi.org/10.1016/j.cmi.2016.05.004.