Consenso de expertos para el tratamiento antimicrobiano de las infecciones causadas por bacilos gram negativos multirresistentes en pacientes adultos
Barra lateral del artículo
Contenido principal del artículo
Resumen
La resistencia bacteriana es un fenómeno de alto impacto para la salud pública mundial. A pesar de que se han construido redes de vigilancia y se han desarrollado nuevas tecnologías para la caracterización de este fenómeno; aún existen diferentes retos por abordar. El uso indiscriminado y desinformado de los antibióticos aporta de manera sustancial al fenómeno de la resistencia; por esta razón es indispensable que se desarrollen estrategias que favorezcan el aumento del conocimiento de los profesionales sanitarios para la prescripción de los antibióticos de acuerdo con diferentes factores entre ellos la epidemiología local, el sitio de infección, las condiciones clínicas de los pacientes y la mejor evidencia disponible. El objetivo de este documento es presentar recomendaciones para el tratamiento de infecciones causadas por microrganismos Gram negativos multirresistentes en el contexto hospitalario de Colombia. Se presenta una guía con 26 recomendaciones basadas en la evidencia; la metodología desarrollada se basó en la búsqueda de la literatura, evaluación de la evidencia, síntesis de información y consenso de expertos para asignar nivel de recomendación.
Detalles del artículo
Citas
Murray CJ, Shunji Ikuta K, Sharara F, Swetschinski L, Robles Aguilar G, Gray A, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis 2022. https://doi.org/10.1016/S0140-6736(21)02724-0.
Rosenthal VD, Bat-Erdene I, Gupta D, Belkebir S, Rajhans P, Zand F, et al. International Nosocomial Infection Control Consortium (INICC) report, data summary of 45 countries for 2012-2017: Device-associated module. Am J Infect Control 2020;48:423–32. https://doi.org/10.1016/J.AJIC.2019.08.023.
Sojo-Dorado J, López-Hernández I, Rosso-Fernandez C, Morales IM, Palacios-Baena ZR, Hernández-Torres A, et al. Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trial. JAMA Netw Open 2022;5:e2137277. https://doi.org/10.1001/JAMANETWORKOPEN.2021.37277.
Che H, Wang R, Wang J, Cai Y. Ceftazidime/avibactam versus carbapenems for the treatment of infections caused by Enterobacteriaceae: A metaanalysis of randomised controlled trials. Int J Antimicrob Agents 2019;54:809–13. https://doi.org/10.1016/J.IJANTIMICAG.2019.09.007.
Hu Q, Chen J, Sun S, Deng S. Mortality-Related Risk Factors and Novel Antimicrobial Regimens for Carbapenem-Resistant Enterobacteriaceae Infections: A Systematic Review. Infect Drug Resist 2022;15:6907. https://doi.org/10.2147/IDR.S390635.
Klein EY, van Boeckel TP, Martinez EM, Pant S, Gandra S, Levin SA, et al. Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. Proc Natl Acad Sci U S A 2018;115:E3463–70. https://doi.org/10.1073/PNAS.1717295115.
Carmeli Y, Armstrong J, Laud PJ, Newell P, Stone G, Wardman A, et al. Ceftazidime-avibactam or best available therapy in patients with ceftazidimeresistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): a randomised, pathogen-directed, phase 3 study. Lancet Infect Dis 2016;16:661–73. https://doi.org/10.1016/S1473-3099(16)30004-4.
Vista de Guía de práctica clínica para la infección de vías urinarias complicada n.d. https://www.revistainfectio.org/P_OJS/index.php/infectio/article/view/1120/1260 (accessed January 24, 2023).
Pranita Tamma AD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ, et al. Last updated March 30, 2022, and posted online at https://www.idsociety.org/practice-guideline/amrguidance-2.0n.d
Oxman AD. Grading quality of evidence and strength of recommendations. BMJ 2004;328:1490. https://doi.org/10.1136/BMJ.328.7454.1490.
Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52. https://doi.org/10.1093/CID/CIQ257.
Huttner A, Kowalczyk A, Turjeman A, Babich T, Brossier C, Eliakim-Raz N, et al. Effect of 5-Day Nitrofurantoin vs Single-Dose Fosfomycin on Clinical Resolution of Uncomplicated Lower Urinary Tract Infection in Women: A Randomized Clinical Trial. JAMA 2018; 319:1781–9. https://doi.org/10.1001/JAMA.2018.3627.
Gupta K, Hooton TM, Roberts PL, Stamm WE. Short-course nitrofurantoin for the treatment of acute uncomplicated cystitis in women. Arch Intern Med 2007;167:2207–12. https://doi.org/10.1001/ARCHINTE.167.20.2207.
Goodlet KJ, Benhalima FZ, Nailor MD. A Systematic Review of Single-Dose Aminoglycoside Therapy for Urinary Tract Infection: Is It Time To Resurrect an Old Strategy? Antimicrob Agents Chemother 2018;63. https://doi.org/10.1128/AAC.02165-18.
Agwuh KN, MacGowan A. Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines. J Antimicrob Chemother 2006;58:256–65. https://doi.org/10.1093/JAC/DKL224.
fda. label n.d.
fda, cder. MONUROL ® [mon ur ol] (fosfomycin tromethamine) Granules for Oral Solution Rx only n.d.
Hooton TM, Scholes D, Gupta K, Stapleton AE, Roberts PL, Stamm WE. Amoxicillin-clavulanate vs ciprofloxacin for the treatment of uncomplicated cystitis in women: a randomized trial. JAMA 2005;293:949–55. https://doi.org/10.1001/JAMA.293.8.949.
Tamma PD, Goodman KE, Harris AD, Tekle T, Roberts A, Taiwo A, et al. Comparing the Outcomes of Patients With Carbapenemase- Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia. Clin Infect Dis 2017;64:257–64. https://doi.org/10.1093/CID/CIW741.
Ito R, Mustapha MM, Tomich AD, Callaghan JD, McElheny CL, Mettus RT, et al. Widespread Fosfomycin Resistance in Gram-Negative Bacteria Attributable to the Chromosomal fosA Gene. MBio 2017;8. https://doi.org/10.1128/MBIO.00749-17.
Elliott ZS, Barry KE, Cox HL, Stoesser N, Carroll J, Vegesana K, et al. The Role of fosA in Challenges with Fosfomycin Susceptibility Testing of Multispecies Klebsiella pneumoniae Carbapenemase-Producing Clinical Isolates. J Clin Microbiol 2019;57. https://doi.org/10.1128/JCM.00634-19.
Wagenlehner FM, Umeh O, Steenbergen J, Yuan G, Darouiche RO. Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI). Lancet 2015;385:1949–56. https://doi.org/10.1016/S0140-6736(14)62220-0.
Kaye KS, Bhowmick T, Metallidis S, Bleasdale SC, Sagan OS, Stus V, et al. Effect of Meropenem-Vaborbactam vs Piperacillin-Tazobactam on Clinical Cure or Improvement and Microbial Eradication in Complicated Urinary Tract Infection: The TANGO I Randomized Clinical Trial. JAMA 2018;319:788–99. https://doi.org/10.1001/JAMA.2018.0438.
Portsmouth S, van Veenhuyzen D, Echols R, Machida M, Ferreira JCA, Ariyasu M, et al. Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial. Lancet Infect Dis 2018;18:1319–28. https://doi.org/10.1016/S1473-3099(18)30554-1.
Sims M, Mariyanovski V, McLeroth P, Akers W, Lee YC, Brown ML, et al. Prospective, randomized, double-blind, Phase 2 dose-ranging study comparing efficacy and safety of imipenem/cilastatin plus relebactam with imipenem/cilastatin alone in patients with complicated urinary tract infections. J Antimicrob Chemother 2017;72:2616–26. https://doi.org/10.1093/JAC/DKX139.
Bassetti M, Echols R, Matsunaga Y, Ariyasu M, Doi Y, Ferrer R, et al. Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogenfocused, descriptive, phase 3 trial. Lancet Infect Dis 2021;21:226–40. https://doi.org/10.1016/S1473-3099(20)30796-9.
Sorlí L, Luque S, Li J, Campillo N, Danés M, Montero M, et al. Colistin for the treatment of urinary tract infections caused by extremely drugresistant Pseudomonas aeruginosa: Dose is critical. J Infect 2019;79:253–61. https://doi.org/10.1016/J.JINF.2019.06.011.
Ren H, Li X, Ni ZH, Niu JY, Cao B, Xu J, et al. Treatment of complicated urinary tract infection and acute pyelonephritis by short-course intravenous levofloxacin (750 mg/day) or conventional intravenous/ oral levofloxacin (500 mg/day): prospective, open-label, randomized, controlled, multicenter, non-inferiority clinical trial. Int Urol Nephrol 2017;49:499–507. https://doi.org/10.1007/S11255-017-1507-0.
Wagenlehner FME, Cloutier DJ, Komirenko AS, Cebrik DS, Krause KM, Keepers TR, et al. Re: Once-daily plazomicin for complicated urinary tract infections. Journal of Urology 2019;202:641–2. https://doi.org/10.1056/NEJMoa1801467.
Bilinskaya A, Linder KE, Kuti JL. Plazomicin: an intravenous aminoglycoside antibacterial for the treatment of complicated urinary tract infections. Expert Rev Anti Infect Ther 2020;18:705–20. https://doi.org/10.1080/14787210.2020.1759419.
Coupat C, Pradier C, Degand N, Hofliger P, Pulcini C. Selective reporting of antibiotic susceptibility data improves the appropriateness of intended antibiotic prescriptions in urinary tract infections: a case-vignette randomised study. European Journal of Clinical Microbiology & Infectious Diseases 2013;32:627–36. https://doi.org/10.1007/s10096-012-1786-4.
de Jonge BLM, Karlowsky JA, Kazmierczak KM, Biedenbach DJ, Sahm DF, Nichols WW. In Vitro Susceptibility to Ceftazidime-Avibactam of Carbapenem-Nonsusceptible Enterobacteriaceae Isolates Collected during the INFORM Global Surveillance Study (2012 to 2014). Antimicrob Agents Chemother 2016;60:3163–9. https://doi.org/10.1128/AAC.03042-15.
Remolina G. SA, Conde M. CE, Escobar C. JC, Leal C. AL, Bravo O. JS, Saavedra R. SY, et al. Tipos de carbapenemasas expresadas en Klebsiella spp., y Pseudomonas aeruginosa resistente a carbapenémicos en seis hospitales de alta complejidad de la Ciudad de Bogotá - Colombia. Revista Chilena de Infectología 2021;38:720–3. https://doi.org/10.4067/S0716-10182021000500720.
García-Betancur JC, Appel TM, Esparza G, Gales AC, Levy-Hara G, Cornistein W, et al. Update on the epidemiology of carbapenemases in Latin America and the Caribbean. Expert Rev Anti Infect Ther 2021;19:197–213. https://doi.org/10.1080/14787210.2020.1813023.
Carvalhaes CG, Castanheira M, Sader HS, Flamm RK, Shortridge D. Antimicrobial activity of ceftolozane-tazobactam tested against gramnegative contemporary (2015-2017) isolates from hospitalized patients with pneumonia in US medical centers. Diagn Microbiol Infect Dis 2019;94:93–102. https://doi.org/10.1016/J.DIAGMICROBIO.2018.11.021.
Canver MC, Satlin MJ, Westblade LF, Kreiswirth BN, Chen L, Robertson A, et al. Activity of Imipenem-Relebactam and Comparator Agents against Genetically Characterized Isolates of Carbapenem-Resistant Enterobacteriaceae. Antimicrob Agents Chemother 2019;63. https://doi.org/10.1128/AAC.00672-19.
Kulengowski B, Burgess DS. Imipenem/relebactam activity compared to other antimicrobials against non-MBL-producing carbapenem-resistant Enterobacteriaceae from an academic medical center. Pathog Dis 2019;77.https://doi.org/10.1093/FEMSPD/FTZ040.
Castanheira M, Duncan LR, Mendes RE, Sader HS, Shortridge D. Activity of Ceftolozane-Tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae Isolates Collected from Respiratory Tract Specimens of Hospitalized Patients in the United States during 2013 to 2015. Antimicrob Agents Chemother 2018;62. https://doi.org/10.1128/AAC.02125-17.
Castanheira M, Doyle TB, Collingsworth TD, Sader HS, Mendes RE. Increasing frequency of OXA-48-producing Enterobacterales worldwide and activity of ceftazidime/avibactam, meropenem/vaborbactam and comparators against these isolates. Journal of Antimicrobial Chemotherapy 2021;76:3125–34. https://doi.org/10.1093/JAC/DKAB306.
Pfaller MA, Huband MD, Mendes RE, Flamm RK, Castanheira M. In vitro activity of meropenem/vaborbactam and characterisation of carbapenem resistance mechanisms among carbapenem-resistant Enterobacteriaceae from the 2015 meropenem/vaborbactam surveillance programme. Int J Antimicrob Agents 2018;52:144–50. https://doi.org/10.1016/J.IJANTIMICAG.2018.02.021.
Johnston BD, Thuras P, Porter SB, Anacker M, VonBank B, Vagnone PS, et al. Activity of imipenem-relebactam against carbapenem-resistant Escherichia coli isolates from the United States in relation to clonal background, resistance genes, coresistance, and region. Antimicrob Agents Chemother 2020;64. https://doi.org/10.1128/AAC.02408-19/SUPPL_FILE/AAC.02408-19-S0001.PDF.
Castanheira M, Doyle TB, Kantro V, Mendes RE, Shortridge D. Meropenem- Vaborbactam Activity against Carbapenem-Resistant Enterobacterales Isolates Collected in U.S. Hospitals during 2016 to 2018. Antimicrob Agents Chemother 2020;64. https://doi.org/10.1128/AAC.01951-19.
Spiliopoulou I, Kazmierczak K, Stone GG. In vitro activity of ceftazidime/avibactam against isolates of carbapenem-non-susceptible Enterobacteriaceae collected during the INFORM global surveillance programme (2015-17). J Antimicrob Chemother 2020;75:384–91. https://doi.org/10.1093/JAC/DKZ456.
Shaw E, Rombauts A, Tubau F, Padullés A, Cámara J, Lozano T, et al. Clinical outcomes after combination treatment with ceftazidime/avibactam and aztreonam for NDM-1/OXA-48/CTX-M-15-producing Klebsiella pneumoniae infection. J Antimicrob Chemother 2018;73:1104–6. https://doi.org/10.1093/JAC/DKX496.
Hobson CA, Bonacorsi S, Fahd M, Baruchel A, Cointe A, Poey N, et al. Successful Treatment of Bacteremia Due to NDM-1-Producing Morganella morganii with Aztreonam and Ceftazidime-Avibactam Combination in a Pediatric Patient with Hematologic Malignancy. Antimicrob Agents Chemother 2019;63. https://doi.org/10.1128/AAC.02463-18.
de la Calle C, Rodríguez O, Morata L, Marco F, Cardozo C, García-Vidal C, et al. Clinical characteristics and prognosis of infections caused by OXA-48 carbapenemase-producing Enterobacteriaceae in patients treated with ceftazidime-avibactam. Int J Antimicrob Agents 2019;53:520–4. https://doi.org/10.1016/J.IJANTIMICAG.2018.11.015
Biagi M, Wu T, Lee M, Patel S, Butler D, Wenzler E. Searching for the Optimal Treatment for Metallo- and Serine-Beta-Lactamase Producing Enterobacteriaceae: Aztreonam in Combination with Ceftazidimeavibactam or Meropenem-vaborbactam. Antimicrob Agents Chemother 2019;63. https://doi.org/10.1128/AAC.01426-19.
Sieswerda E, van den Brand M, van den Berg RB, Strater J, Schouls L, van Dijk K, et al. Successful rescue treatment of sepsis due to a pandrugresistant, NDM-producing Klebsiella pneumoniae using aztreonam powder for nebulizer solution as intravenous therapy in combination with ceftazidime/avibactam. J Antimicrob Chemother 2020;75:773–5. https://doi.org/10.1093/JAC/DKZ495.
Benchetrit L, Mathy V, Armand-Lefevre L, Bouadma L, Timsit JF. Successful treatment of septic shock due to NDM-1-producing Klebsiella pneumoniae using ceftazidime/avibactam combined with aztreonam in solid organ transplant recipients: report of two cases. Int J Antimicrob Agents 2020;55. https://doi.org/10.1016/J.IJANTIMICAG.2019.10.023.
Eckmann C, Montravers P, Bassetti M, Bodmann KF, Heizmann WR, Garcií MS, et al. Efficacy of tigecycline for the treatment of complicated intraabdominal infections in real-life clinical practice from five European observational studies. J Antimicrob Chemother 2013;68 Suppl 2. https://doi.org/10.1093/JAC/DKT142.
Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America 2022 Guidance on the Treatment of Extended-Spectrum Beta-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa). Clinical Infectious Diseases 2022;75:187–212. https://doi.org/10.1093/CID/CIAC268.
Díaz-Brochero C, Valderrama-Rios MC, Nocua-Báez LC, Cortés JA. Firstgeneration cephalosporins for the treatment of complicated upper urinary tract infection in adults: A systematic literature review. Int J Infect Dis 2022;116:403–10. https://doi.org/10.1016/J.IJID.2021.12.363.
Harris PNA, Tambyah PA, Lye DC, Mo Y, Lee TH, Yilmaz M, et al. Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance: A Randomized Clinical Trial. JAMA 2018;320:984–94. https://doi.org/10.1001/JAMA.2018.12163.
Babinchak T, Ellis-Grosse E, Dartois N, Rose GM, Loh E. The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infections: analysis of pooled clinical trial data. Clin Infect Dis 2005;41 Suppl 5. https://doi.org/10.1086/431676.
Solomkin J, Evans D, Slepavicius A, Lee P, Marsh A, Tsai L, et al. Assessing the Efficacy and Safety of Eravacycline vs Ertapenem in Complicated Intra-abdominal Infections in the Investigating Gram-Negative Infections Treated With Eravacycline (IGNITE 1) Trial: A Randomized Clinical Trial. JAMA Surg 2017;152:224–32. https://doi.org/10.1001/JAMASURG.2016.4237.
Walkty A, Karlowsky JA, Baxter MR, Adam HJ, Golden A, Lagace-Wiens P, et al. In vitro activity of imipenem-relebactam against various resistance phenotypes/genotypes of Enterobacterales and Pseudomonas aeruginosa isolated from patients across Canada as part of the CANWARD study, 2016-2019. Diagn Microbiol Infect Dis 2021;101:115418. https://doi.org/10.1016/J.DIAGMICROBIO.2021.115418.
Lob SH, Karlowsky JA, Young K, Motyl MR, Hawser S, Kothari ND, et al. In vitro activity of imipenem-relebactam against resistant phenotypes of Enterobacteriaceae and Pseudomonas aeruginosa isolated from intraabdominal and urinary tract infection samples - SMART Surveillance Europe 2015-2017. J Med Microbiol 2020;69:207–17. https://doi.org/10.1099/JMM.0.001142/CITE/REFWORKS.
Lapuebla A, Abdallah M, Olafisoye O, Cortes C, Urban C, Landman D, et al. Activity of Imipenem with Relebactam against Gram-Negative Pathogens from New York City. Antimicrob Agents Chemother 2015;59:5029–31. https://doi.org/10.1128/AAC.00830-15.
Pogue JM, Kaye KS, Veve MP, Patel TS, Gerlach AT, Davis SL, et al. Ceftolozane/Tazobactam vs Polymyxin or Aminoglycoside-based Regimens for the Treatment of Drug-resistant Pseudomonas aeruginosa. Clin Infect Dis 2020;71:304–10. https://doi.org/10.1093/CID/CIZ816.
Sader HS, Castanheira M, Shortridge D, Mendes RE, Flamm RK. Antimicrobial Activity of Ceftazidime-Avibactam Tested against Multidrug-Resistant Enterobacteriaceae and Pseudomonas aeruginosa Isolates from U.S. Medical Centers, 2013 to 2016. Antimicrob Agents Chemother 2017;61. https://doi.org/10.1128/AAC.01045-17.
Shortridge D, Pfaller MA, Arends SJR, Raddatz J, Depestel DD, Flamm RK. Comparison of the In Vitro Susceptibility of Ceftolozane-Tazobactam With the Cumulative Susceptibility Rates of Standard Antibiotic Combinations When Tested Against Pseudomonas aeruginosa From ICU Patients With Bloodstream Infections or Pneumonia. Open Forum Infect Dis 2019;6. https://doi.org/10.1093/OFID/OFZ240.
Fraile-Ribot PA, Zamorano L, Orellana R, del Barrio-Tofiño E, Sánchez- Diener I, Cortes-Lara S, et al. Activity of Imipenem-Relebactam against a Large Collection of Pseudomonas aeruginosa Clinical Isolates and Isogenic Beta-Lactam-Resistant Mutants. Antimicrob Agents Chemother 2020;64. https://doi.org/10.1128/AAC.02165-19.
Barnes MD, Taracila MA, Rutter JD, Bethel CR, Galdadas I, Hujer AM, et al. Deciphering the Evolution of Cephalosporin Resistance to Ceftolozane- Tazobactam in Pseudomonas aeruginosa. MBio 2018;9. https://doi.org/10.1128/MBIO.02085-18.
Tamma PD, Beisken S, Bergman Y, Posch AE, Avdic E, Sharara SL, et al. Modifiable Risk Factors for the Emergence of Ceftolozane-tazobactam Resistance. Clin Infect Dis 2021;73:e4599–606. https://doi.org/10.1093/CID/CIAA1306.
Golden AR, Adam HJ, Baxter M, Walkty A, Lagacé-Wiens P, Karlowsky JA, et al. In Vitro Activity of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacilli Isolated from Patients in Canadian Intensive Care Units. Diagn Microbiol Infect Dis 2020;97. https://doi.org/10.1016/J.DIAGMICROBIO.2020.115012.
Hackel MA, Tsuji M, Yamano Y, Echols R, Karlowsky JA, Sahma DF. In Vitro Activity of the Siderophore Cephalosporin, Cefiderocol, against a Recent Collection of Clinically Relevant Gram-Negative Bacilli from North America and Europe, Including Carbapenem-Nonsusceptible Isolates (SIDERO-WT-2014 Study). Antimicrob Agents Chemother 2017;61. https://doi.org/10.1128/AAC.00093-17.
Hackel MA, Tsuji M, Yamano Y, Echols R, Karlowsky JA, Sahm DF. In Vitro Activity of the Siderophore Cephalosporin, Cefiderocol, against Carbapenem-Nonsusceptible and Multidrug-Resistant Isolates of Gram- Negative Bacilli Collected Worldwide in 2014 to 2016. Antimicrob Agents Chemother 2018;62. https://doi.org/10.1128/AAC.01968-17.