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Antibiotic modification versus withhold in febrile patients without evidence of bacterial infection, unresponsive to initial empiric regimen: a multicentre retrospective study conducted in Israel

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Abstract

Prescribing antibiotics for febrile patients without proof of bacterial infection contributes to antimicrobial resistance. Lack of clinical response in these patients often leads to antibiotic escalation, although data supporting this strategy are scarce. This study compared outcomes of modifying, withholding, or continuing the same antibiotic regimen for such patients. Febrile or hypothermic stable patients with suspected infection, unresponsive to empiric antibiotic treatment, admitted to one of 15 internal medicine departments in three hospitals during a 5-year study period, were included. Patients with a definitive clinical or microbiological bacterial infection, malignancy, immunodeficiency, altered mental status, or need for mechanical ventilation were excluded. Participants were divided into groups based on treatment strategy determined 72 h after antibiotic initiation: antibiotic modified, withheld or continued. Outcomes measured included in-hospital and 30-day post-discharge-mortality rates, length of hospital stay (LOS) and days of antimicrobial therapy (DOT). A total of 486 patients met the inclusion criteria: 124 in the Antibiotic modified group, 67 in the Antibiotic withheld group and 295 in the Initial antibiotic continued group. Patient characteristics were similar among groups with no differences in mortality rates in-hospital (23% vs. 25% vs. 20%, p = 0.58) and within 30 days after discharge (5% vs. 3% vs. 4%, p = 0.83). Changing antibiotics led to longer LOS (9.0 ± 6.8 vs. 6.2 ± 5.6 days, p = 0.003) and more DOT (8.6 ± 6.0 vs. 3.2 ± 1.0 days, p < 0.001) compared to withholding treatment. Withholding as compared to modifying antibiotics, in febrile patients with no clear evidence of bacterial infection, is a safe strategy associated with decreased LOS and DOT.

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Data availability

The datasets generated during and analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services (2019) Antibiotic resistance threats in the United States 2019. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf. Accessed 18 Mar 2019

  2. Barnes SL, Rock C, Harris AD et al (2017) The impact of reducing antibiotics on the transmission of multidrug-resistant organisms. Infect Control Hosp Epidemiol 38:663–669. https://doi.org/10.1017/ice.2017.34

    Article  PubMed  PubMed Central  Google Scholar 

  3. Schechner V, Temkin E, Harbarth S et al (2013) Epidemiological interpretation of studies examining the effect of antibiotic usage on resistance. Clin Microbiol Rev 26(2):289–307. https://doi.org/10.1128/CMR.00001-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tamma PD, Avdic E, Li DX et al (2017) Association of adverse events with antibiotic use in hospitalized patients. JAMA Intern Med 177(9):1308–1315. https://doi.org/10.1001/jamainternmed.2017.1938

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lin S, Xiaoyan Z, Yuxiao Z et al (2019) Antibiotic-induced disruption of gut microbiota alters local metabolomes and immune responses. Front Cell Infect Microbiol 9:99. https://doi.org/10.3389/fcimb.2019.00099

    Article  CAS  Google Scholar 

  6. Willmann M, Vehreschild MJGT, Biehl LM et al (2019) Distinct impact of antibiotics on the gut microbiome and resistome: a longitudinal multicenter cohort study. BMC Biol 17:76. https://doi.org/10.1186/s12915-019-0692-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Brown K, Valenta K, Fisman D et al (2015) Hospital ward antibiotic prescribing and the risks of Clostridium difficile infection. JAMA Intern Med 175:626–633. https://doi.org/10.1001/jamainternmed.2014.8273

    Article  PubMed  Google Scholar 

  8. Zilberberg MD, Nathanson BH, Sulham K et al (2016) Multidrug resistance, inappropriate empiric therapy, and hospital mortality in Acinetobacter baumannii pneumonia and sepsis. Crit Care 20:221. https://doi.org/10.1186/s13054-016-1392-4

    Article  PubMed  PubMed Central  Google Scholar 

  9. Iregui M, Ward S, Sherman G et al (2002) Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest 122(1):262–268. https://doi.org/10.1378/chest.122.1.262

    Article  PubMed  Google Scholar 

  10. Shorr AF, Micek ST, Welch EC et al (2011) Inappropriate antibiotic therapy in gram-negative sepsis increases hospital length of stay. Crit Care Med 39:46–51. https://doi.org/10.1097/CCM.0b013e3181fa41a7

    Article  CAS  PubMed  Google Scholar 

  11. Grossman C, Keller N, Bornstein G et al (2016) Factors associated with suitability of empiric antibiotic therapy in hospitalized patients with bloodstream infections. Chemother 9(3):159–163. https://doi.org/10.1080/1120009X.2016.1182770

    Article  CAS  Google Scholar 

  12. Zilberberg MD, Shorr AF, Micek ST et al (2008) Antimicrobial therapy escalation and hospital mortality among patients with HCAP: a single center experience. Chest 134:963–968. https://doi.org/10.1378/chest.08-0842

    Article  PubMed  Google Scholar 

  13. Kumar A, Ellis P, Arabi Y et al (2009) Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 136(5):1237–1248. https://doi.org/10.1378/chest.09-0087

    Article  PubMed  Google Scholar 

  14. Alvarez-Lerma F (1996) Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit. Intensive Care Med 22(5):387–394. https://doi.org/10.1007/BF01712153

    Article  CAS  PubMed  Google Scholar 

  15. Pardo J, Klinker KP, Boger SJ et al (2014) Time to positivity of blood cultures supports antibiotic de-escalation at 48 hours. Ann Pharmacother 48:33–40. https://doi.org/10.1177/1060028013511229

    Article  PubMed  Google Scholar 

  16. Seymour CW, Liu VX, Iwashyna TJ et al (2016) Assessment of clinical criteria for Sepsis: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315(8):762–774. https://doi.org/10.1001/jama.2016.0288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Barlam TF, Cosgrove SE, Abbo LM et al (2016) Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis 62:e51–e77. https://doi.org/10.1093/cid/ciw118

    Article  PubMed  PubMed Central  Google Scholar 

  18. Charlson ME, Pompei P, Ales KL et al (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383. https://doi.org/10.1016/0021-9681(87)90171-8

    Article  CAS  PubMed  Google Scholar 

  19. Rodrigues CMC, Groves H (2018) Acquired pneumonia in children: the challenges of microbiological diagnosis. J Clin Microbiol 56(3):e01318–e01317. https://doi.org/10.1128/JCM.01318-17

    Article  PubMed  PubMed Central  Google Scholar 

  20. Chanu R (2017) Using procalcitonin to guide antibiotic therapy. Open Forum Infect Dis 4(1):249. https://doi.org/10.1093/ofid/ofw249

    Article  CAS  Google Scholar 

  21. Christ-Crain M, Jaccard-Stolz D, Bingisser R et al (2004) Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet 363(9409):600–607. https://doi.org/10.1016/s0140-6736(04)15591-8

    Article  CAS  PubMed  Google Scholar 

  22. Carratala J, Garcia-Vidal C, Ortega L et al (2012) Effect of a 3-step critical pathway to reduce duration of intravenous antibiotic therapy and length of stay in community-acquired pneumonia: a randomized controlled trial. Arch Intern Med 172:922–928. https://doi.org/10.1001/archinternmed.2012.1690

    Article  PubMed  Google Scholar 

  23. Fine MJ, Stone RA, Lave JR et al (2003) Implementation of an evidence-based guideline to reduce duration of intravenous antibiotic therapy and length of stay for patients hospitalized with community-acquired pneumonia: a randomized controlled trial. Am J Med 15:343–351. https://doi.org/10.1016/s0002-9343(03)00395-4

    Article  Google Scholar 

  24. Avdic E, Cushinotto LA, Hughes AH et al (2012) Impact of an antimicrobial stewardship intervention on shortening the duration of therapy for community-acquired pneumonia. Clin Infect Dis 54:1581–1587. https://doi.org/10.1093/cid/cis242

    Article  PubMed  Google Scholar 

  25. Hauck LD, Adler LM, Mulla ZD (2004) Clinical pathway care improves outcomes among patients hospitalized for community-acquired pneumonia. Ann Epidemiol 14:669–675. https://doi.org/10.1016/j.annepidem.2004.01.003

    Article  PubMed  Google Scholar 

  26. Ibrahim EH, Ward S, Sherman G et al (2001) Experience with a clinical guideline for the treatment of ventilator-associated pneumonia. Crit Care Med 29:1109–1115. https://doi.org/10.1097/00003246-200106000-00003

    Article  CAS  PubMed  Google Scholar 

  27. Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services (2019) Core elements of hospital antibiotic stewardship programs. https://www.cdc.gov/antibiotic-use/core-elements/hospital.html. Accessed 25 Mar 2019

  28. Thom AT, Tamma PD, Harris AD et al (2019) Impact of a prescriber-driven antibiotic time-out on antibiotic use in hospitalized patients. Clin Infect Dis 68(9):1581–1584. https://doi.org/10.1093/cid/ciy852

    Article  PubMed  Google Scholar 

  29. Lee TC, Frenette C, Jayaraman D et al (2014) Antibiotic self-stewardship: trainee-led structured antibiotic time-outs to improve antimicrobial use. Ann Intern Med 161(10):s53–s58. https://doi.org/10.7326/M13-3016

    Article  PubMed  Google Scholar 

  30. Lesprit P, Landelle C, Girou E et al (2010) Reassessment of intravenous antibiotic therapy using a reminder or direct counselling. J Antimicrob Chemother 65:789–795. https://doi.org/10.1093/jac/dkq018

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Faye Schreiber for editorial assistance and Navah Jelin for statistical consultation.

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Authors and Affiliations

  1. Department of Internal Medicine A, Meir Medical Center, 59 Tchernichovsky St, 4428164, Kfar Saba, Israel

    Hadar Mudrik-Zohar, Gideon Y. Stein, Abd El-Haleem Natour & Danny Alon

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Hadar Mudrik-Zohar, Gideon Y. Stein & Danny Alon

  3. Pharmacy Services, Beilinson Campus, Rabin Medical Center, Petach Tikvah, Israel

    Ran Nissan

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  1. Hadar Mudrik-Zohar
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Correspondence to Hadar Mudrik-Zohar.

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The authors declare that they have no conflict of interest.

Ethics approval, consent to participate and consent for publication

The study was approved by Institutional Helsinki Committees at each of the two participating medical centres (approval numbers: RMC-0814-17 and MMC-0219-18). Informed consents to participate and for publication were not required due to the retrospective study design.

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Mudrik-Zohar, H., Nissan, R., Stein, G.Y. et al. Antibiotic modification versus withhold in febrile patients without evidence of bacterial infection, unresponsive to initial empiric regimen: a multicentre retrospective study conducted in Israel. Eur J Clin Microbiol Infect Dis 39, 2027–2035 (2020). https://doi.org/10.1007/s10096-020-03957-x

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