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Confounding by indication of the safety of de-escalation in community-acquired pneumonia: A simulation study embedded in a prospective cohort


Autoři: Inger van Heijl aff001;  Valentijn A. Schweitzer aff002;  C. H. Edwin Boel aff003;  Jan Jelrik Oosterheert aff004;  Susanne M. Huijts aff005;  Wendelien Dorigo-Zetsma aff006;  Paul D. van der Linden aff001;  Marc J. M. Bonten aff002;  Cornelis H. van Werkhoven aff002
Působiště autorů: Department of Clinical Pharmacy, Tergooi hospital, Hilversum, The Netherlands aff001;  Julius Center for Health Sciences and Primary care, University Medical Centre Utrecht, Utrecht, The Netherlands aff002;  Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, The Netherlands aff003;  Department of Internal Medicine & Infectious Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands aff004;  Department of Pulmonary Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands aff005;  Department of Medical Microbiology, Tergooi hospital, Hilversum, The Netherlands aff006
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0218062

Souhrn

Observational studies have demonstrated that de-escalation of antimicrobial therapy is independently associated with lower mortality. This most probably results from confounding by indication. Reaching clinical stability is associated with the decision to de-escalate and with survival. However, studies rarely adjust for this confounder. We quantified the potential confounding effect of clinical stability on the estimated impact of de-escalation on mortality in patients with community-acquired pneumonia. Data were used from the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA). The primary outcome was 30-day mortality. We performed Cox proportional-hazards regression with de-escalation as time-dependent variable and adjusted for baseline characteristics using propensity scores. The potential impact of unmeasured confounding was quantified through simulating a variable representing clinical stability on day three, using data on prevalence and associations with mortality from the literature. Of 1,536 included patients, 257 (16.7%) were de-escalated, 123 (8.0%) were escalated and in 1156 (75.3%) the antibiotic spectrum remained unchanged. Crude 30-day mortality was 3.5% (9/257) and 10.9% (107/986) in the de-escalation and continuation groups, respectively. The adjusted hazard ratio of de-escalation for 30-day mortality (compared to patients with unchanged coverage), without adjustment for clinical stability, was 0.39 (95%CI: 0.19–0.79). If 90% to 100% of de-escalated patients were clinically stable on day three, the fully adjusted hazard ratio would be 0.56 (95%CI: 0.27–1.12) to 1.04 (95%CI: 0.49–2.23), respectively. The simulated confounder was substantially stronger than any of the baseline confounders in our dataset. Quantification of effects of de-escalation on patient outcomes without proper adjustment for clinical stability results in strong negative bias. This study suggests the effect of de-escalation on mortality needs further well-designed prospective research to determine effect size more accurately.

Klíčová slova:

Antibiotics – Antimicrobials – Death rates – Heart rate – Oxygen – Pneumonia – Randomized controlled trials – Observational studies


Zdroje

1. Davey P, Marwick CA, Scott CL, Charani E, McNeil K, Brown E, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev. 2017;2:CD003543. Epub 2017/02/09. doi: 10.1002/14651858.CD003543.pub4 28178770; PubMed Central PMCID: PMC6464541.

2. Schuts EC, Hulscher MEJL, Mouton JW, Verduin CM, Stuart JWTC, Overdiek HWPM, et al. Current evidence on hospital antimicrobial stewardship objectives: a systematic review and meta-analysis. The Lancet Infectious Diseases. 2016;16(7):847–56. doi: 10.1016/S1473-3099(16)00065-7 26947617

3. Kim JW, Chung J, Choi SH, Jang HJ, Hong SB, Lim CM, et al. Early use of imipenem/cilastatin and vancomycin followed by de-escalation versus conventional antimicrobials without de-escalation for patients with hospital-acquired pneumonia in a medical ICU: a randomized clinical trial. Crit Care. 2012;16(1):R28. Epub 2012/02/18. doi: 10.1186/cc11197 22336530; PubMed Central PMCID: PMC3396273.

4. Leone M, Bechis C, Baumstarck K, Lefrant JY, Albanese J, Jaber S, et al. De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial. Intensive Care Med. 2014;40(10):1399–408. Epub 2014/08/06. doi: 10.1007/s00134-014-3411-8 25091790.

5. Garnacho Montero J, Gutiérrez Pizarraya A, Escoresca Ortega A, Corcia Palomo Y, Fernández Delgado E, Herrera Melero I, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive care medicine. 2014;40(1):32–40. doi: 10.1007/s00134-013-3077-7 24026297

6. Bonten MJM, Huijts S, Bolkenbaas M, Webber C, Patterson S, Gault S, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. The New England journal of medicine. 2015;372(12):1114–25. doi: 10.1056/NEJMoa1408544 25785969

7. Postma D, van Werkhoven C, van Elden LJR, Thijsen SFT, Hoepelman AIM, Kluytmans JAJW, et al. Antibiotic treatment strategies for community-acquired pneumonia in adults. The New England journal of medicine. 2015;372(14):1312–23. doi: 10.1056/NEJMoa1406330 25830421

8. Wiersinga WJ, Bonten MJ, Boersma WG, Jonkers RE, Aleva RM, Kullberg BJ, et al. Management of community-acquired pneumonia in adults: 2016 guideline update from the Dutch Working Party on Antibiotic Policy (SWAB) and Dutch Association of Chest Physicians (NVALT). Netherlands journal of medicine. 2018;76(1):4–13. 29380739

9. Danish Society of Infectious Diseases. Behandling af samfundserhvervet pneumoni 2011 [August 13, 2019]. Available from: http://www.infmed.dk/guidelines.

10. Spindler C, Stralin K, Eriksson L, Hjerdt-Goscinski G, Holmberg H, Lidman C, et al. Swedish guidelines on the management of community-acquired pneumonia in immunocompetent adults—Swedish Society of Infectious Diseases 2012. Scandinavian journal of infectious diseases. 2012;44(12):885–902. Epub 2012/07/27. doi: 10.3109/00365548.2012.700120 22830356.

11. SWAB (The Dutch Working Party on Antibiotic Policy). A-teams Praktijkgids Antimicrobial Stewardship in Nederland. 2 ed. Leusden: Buro Hans; 2018. 21–2 p.

12. Niederman MS, Mandell LA, Anzueto A, Bass JB, Broughton WA, Campbell GD, et al. Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med. 2001;163(7):1730–54. Epub 2001/06/13. doi: 10.1164/ajrccm.163.7.at1010 11401897.

13. Halm EA, Fine MJ, Marrie TJ, Coley CM, Kapoor WN, Obrosky DS, et al. Time to clinical stability in patients hospitalized with community-acquired pneumonia: implications for practice guidelines. Jama. 1998;279(18):1452–7. Epub 1998/05/26. doi: 10.1001/jama.279.18.1452 9600479.

14. Castro-Guardiola A, Viejo-Rodriguez AL, Soler-Simon S, Armengou-Arxe A, Bisbe-Company V, Penarroja-Matutano G, et al. Efficacy and safety of oral and early-switch therapy for community-acquired pneumonia: a randomized controlled trial. Am J Med. 2001;111(5):367–74. Epub 2001/10/05. doi: 10.1016/s0002-9343(01)00868-3 11583639.

15. Kohno S, Yanagihara K, Yamamoto Y, Tokimatsu I, Hiramatsu K, Higa F, et al. Early switch therapy from intravenous sulbactam/ampicillin to oral garenoxacin in patients with community-acquired pneumonia: a multicenter, randomized study in Japan. Journal of infection and chemotherapy: official journal of the Japan Society of Chemotherapy. 2013;19(6):1035–41. Epub 2013/05/23. doi: 10.1007/s10156-013-0618-5 23695232.

16. Oosterheert JJ, Bonten MJ, Schneider MM, Buskens E, Lammers JW, Hustinx WM, et al. Effectiveness of early switch from intravenous to oral antibiotics in severe community acquired pneumonia: multicentre randomised trial. BMJ (Clinical research ed). 2006;333(7580):1193. Epub 2006/11/09. doi: 10.1136/bmj.38993.560984.BE 17090560; PubMed Central PMCID: PMC1693658.

17. Blum CA, Nigro N, Briel M, Schuetz P, Ullmer E, Suter-Widmer I, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet (London, England). 2015;385(9977):1511–8. Epub 2015/01/23. doi: 10.1016/S0140-6736(14)62447-8 25608756.

18. Carugati M, Franzetti F, Wiemken T, Kelley RR, Peyrani P, Blasi F, et al. De-escalation therapy among bacteraemic patients with community-acquired pneumonia. Clin Microbiol Infect. 2015;21(10):936 e11–8. Epub 2015/06/28. doi: 10.1016/j.cmi.2015.06.015 26115864.

19. Cremers AJ, Sprong T, Schouten JA, Walraven G, Hermans PW, Meis JF, et al. Effect of antibiotic streamlining on patient outcome in pneumococcal bacteraemia. J Antimicrob Chemother. 2014;69(8):2258–64. Epub 2014/04/15. doi: 10.1093/jac/dku109 24729585.

20. Viasus D, Simonetti AF, Garcia-Vidal C, Niubo J, Dorca J, Carratala J. Impact of antibiotic de-escalation on clinical outcomes in community-acquired pneumococcal pneumonia. J Antimicrob Chemother. 2017;72(2):547–53. Epub 2016/11/01. doi: 10.1093/jac/dkw441 27798219.

21. West DM, McCauley LM, Sorensen JS, Jephson AR, Dean NC. Pneumococcal urinary antigen test use in diagnosis and treatment of pneumonia in seven Utah hospitals. ERJ Open Res. 2016;2(4). Epub 2017/01/06. doi: 10.1183/23120541.00011–2016 28053969; PubMed Central PMCID: PMC5152836.

22. Yamana H, Matsui H, Tagami T, Hirashima J, Fushimi K, Yasunaga H. De-escalation versus continuation of empirical antimicrobial therapy in community-acquired pneumonia. J Infect. 2016;73(4):314–25. Epub 2016/07/11. doi: 10.1016/j.jinf.2016.07.001 27394401.

23. Joung MK, Lee JA, Moon SY, Cheong HS, Joo EJ, Ha YE, et al. Impact of de-escalation therapy on clinical outcomes for intensive care unit-acquired pneumonia. Crit Care. 2011;15(2):R79. Epub 2011/03/04. doi: 10.1186/cc10072 21366903; PubMed Central PMCID: PMC3219332.

24. Montravers P, Augustin P, Grall N, Desmard M, Allou N, Marmuse JP, et al. Characteristics and outcomes of anti-infective de-escalation during health care-associated intra-abdominal infections. Crit Care. 2016;20:83. Epub 2016/04/08. doi: 10.1186/s13054-016-1267-8 27052675; PubMed Central PMCID: PMC4823898.

25. Lee CC, Wang JL, Lee CH, Hung YP, Hong MY, Tang HJ, et al. Clinical benefits of antimicrobial de-escalation in adults with community-onset monomicrobial Escherichia coli, Klebsiella species and Proteus mirabilis bacteremia. Int J Antimicrob Agents. 2017;50(3):371–6. Epub 2017/07/12. doi: 10.1016/j.ijantimicag.2017.03.024 28694235.

26. Jones M, Fowler R. Immortal time bias in observational studies of time-to-event outcomes. J Crit Care. 2016;36:195–9. Epub 2016/11/05. doi: 10.1016/j.jcrc.2016.07.017 27546771.

27. Groenwold RH, Nelson DB, Nichol KL, Hoes AW, Hak E. Sensitivity analyses to estimate the potential impact of unmeasured confounding in causal research. International journal of epidemiology. 2010;39(1):107–17. Epub 2009/12/02. doi: 10.1093/ije/dyp332 19948779.

28. Hernan MA, Hernandez-Diaz S, Werler MM, Mitchell AA. Causal knowledge as a prerequisite for confounding evaluation: an application to birth defects epidemiology. Am J Epidemiol. 2002;155(2):176–84. Epub 2002/01/16. doi: 10.1093/aje/155.2.176 11790682.


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