Skip to main content

Advertisement

SpringerLink
Log in

Appropriateness of empirical antibiotics: risk factors of adult patients with sepsis in the ICU

  • Research Article
  • Published:
International Journal of Clinical Pharmacy Aims and scope Submit manuscript

Abstract

Background The appropriateness of antibiotics is the basis for improving the survival of patients with sepsis. Objective This study aimed to determine the appropriateness of empirical antibiotics, reasons for non-appropriate empirical antibiotics, risk factors of mortality, length of stay in intensive care unit (ICU-LOS) and Acute Physiology And Chronic Health Evaluation II (APACHE II) score predictors in adult patients with sepsis. Setting An adult ICU of a tertiary hospital in  Malaysia. Methods A retrospective cohort study was conducted amongst patients with sepsis. Data were retrieved from the patients’ files and computer system. Each case was reviewed for the appropriateness of empirical antibiotics based on ICU local guidelines, bacterial sensitivity, dose, frequency, creatinine clearance and time of administration of empirical antibiotics. Multivariable logistic and Cox regression modelling were performed to compute the adjusted association of receiving appropriate or inappropriate empirical antibiotics with ICU mortality. Multivariable linear regression modelling was performed using ICU-LOS and APACHE II scores. Main outcome measures were ICU mortality, severity score (APACHE II scores) and ICU-LOS. Results The total mortality rate amongst the 228 adult ICU patients was 84.6%. Males showed a higher mortality rate (119 [52.2%]) than females (74 [32.5%]). Inappropriate empirical antibiotics were significantly associated with mortality and ICU-LOS (P < 0.005). Results from multivariable logistic regression showed that the appropriateness of empirical antibiotics model was a potential predictor for survival (OR 0.395, 95% CI 0.184–0.850, P < 0.005). Results from simple linear regression indicated that the appropriateness of empirical antibiotics model was a remarkable predictor of decreasing ICU-LOS (R2 = 0.055, 95% CI − 7.184 to − 2.114, P < 0.001). Results from simple Cox regression suggested that the appropriateness of empirical antibiotics was a protective factor for ICU mortality (HR 0.610, 95% CI 0.433–0.858, P = 0.005). Multivariable Cox regression revealed that the administration of antibiotics exceeding the recommended dose based on creatinine clearance was a protective factor (HR 0.186, 95% CI 0.040–0.868, P = 0.032). Conclusion The appropriateness of empirical antibiotics is a good predictor for improving survival and decreasing ICU-LOS. Effective appropriateness of empirical antibiotics use and close adherence to the recommended dose can prevent the early mortality of patients with sepsis and acute renal failure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Retamar P, Portillo MM, López-Prieto MD, Rodríguez-López F, De Cueto M, García MV, et al. Impact of inadequate empirical therapy on the mortality of patients with bloodstream infections: a propensity score-based analysis. Antimicrob Agents Chemother. 2012;56(1):472–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Vincent J-L. Update on surgical sepsis syndrome. Br J Surg. 2017;104(2):e34–40.

    Article  PubMed  Google Scholar 

  3. Brusselaers N, Labeau S, Vogelaers D, Blot S. Value of lower respiratory tract surveillance cultures to predict bacterial pathogens in ventilator-associated pneumonia: systematic review and diagnostic test accuracy meta-analysis. Intensive Care Med. 2013;39(3):365–75.

    Article  PubMed  Google Scholar 

  4. Kollef MH, Sherman G, Ward S, Fraser VJ. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest. 1999;115(2):462–74.

    Article  CAS  PubMed  Google Scholar 

  5. Vaughan D, Pakyz A, Stevens M, Lee K, Bernard S. Adequacy of empiric gram-negative coverage for septic patients at an academic medical center. Am J Infect Control. 2019;47(10):1194–9.

    Article  PubMed  Google Scholar 

  6. Lee C-C, Lee C-H, Chuang M-C, Hong M-Y, Hsu H-C, Ko W-C. Impact of inappropriate empirical antibiotic therapy on outcome of bacteremic adults visiting the ED. Am J Emerg Med. 2012;30(8):1447–56.

    Article  PubMed  Google Scholar 

  7. Zhou X, Su L-X, Zhang J-H, Liu D-W, Long Y. Rules of anti-infection therapy for sepsis and septic shock. Chin Med J (Engl). 2019;132(5):589–96.

    Article  Google Scholar 

  8. Ling TL, Cheng TC, Har LC, Ismail NI. Malaysian registry of intensive care report for 2015. 2017.

  9. Levent T, Delfosse F, Lambiotte F, Dezorzi S, Gosteau L, Vasseur M. Does high antibiotic consumption still reflect bad practices? Méd Mal Infect. 2012;42(7):309–14.

    Article  CAS  PubMed  Google Scholar 

  10. Hartmann B, Junger A, Brammen D, Röhrig R, Klasen J, Quinzio L, et al. Review of antibiotic drug use in a surgical ICU: management with a patient data management system for additional outcome analysis in patients staying more than 24 hours. Clin Ther. 2004;26(6):915–24 (discussion 904).

    Article  PubMed  Google Scholar 

  11. SANLC. Geok JT, Ling TL, Cheng TC, Othman AS. Malaysian registry of intensive care report for 2012. 2013.

  12. Dean AG, Sullivan KM. OpenEpi: open source epidemiologic statistics for public health. Emory University, Rollins School of Public Health. 2013. www.OpenEpi.com. Accessed 07 July 2017.

  13. Journal O, The OF, Society I, Nephrology OF. Official journal of the international society of nephrology KDIGO clinical practice guideline for acute kidney injury. J Int Soc Nephrol. 2012;2(1):3.

    Google Scholar 

  14. Garnacho-Montero J, Garcia-Garmendia JL, Barrero-Almodovar A, Jimenez-Jimenez FJ, Perez-Paredes C, Ortiz-Leyba C. Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis. Crit Care Med. 2003;31(12):2742–51.

    Article  PubMed  Google Scholar 

  15. Allison MG, Heil EL, Hayes BD. Appropriate Antibiotic Therapy. Emerg Med Clin N Am. 2017;35:25–42.

    Article  Google Scholar 

  16. Rhodes A, Evans L, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med. 2017;45(3):486–552.

    Article  PubMed  Google Scholar 

  17. Kang C-I, Kim S-H, Park WB, Lee K-D, Kim H-B, Kim E-C, et al. Bloodstream infections caused by antibiotic-resistant gram-negative bacilli: risk factors for mortality and impact of inappropriate initial antimicrobial therapy on outcome. Antimicrob Agents Chemother. 2005;49(2):760–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Adrie C, Garrouste-Orgeas M, Essaied WI, Schwebel C, Darmon M, Mourvillier B, et al. Attributable mortality of ICU-acquired bloodstream infections: Impact of the source, causative micro-organism, resistance profile and antimicrobial therapy. J Infect. 2017;74(2):131–41.

    Article  PubMed  Google Scholar 

  19. Cardwell SM, Crandon JL, Nicolau DP, McClure MH, Nailor MD. Epidemiology and economics of adult patients hospitalized with urinary tract infections. Hosp Pract (1995). 2016;44(1):33–40.

    Article  Google Scholar 

  20. Sostarich AM, Zolldann D, Haefner H, Luetticken R, Schulze-Roebecke R, Lemmen SW. Impact of multiresistance of gram-negative bacteria in bloodstream infection on mortality rates and length of stay. Infection. 2008;36(1):31–5.

    Article  CAS  PubMed  Google Scholar 

  21. González AL, Leal AL, Cortés JA, Sánchez R, Barrero LI, Castillo JS, et al. Effect of adequate initial antimicrobial therapy on mortality in critical patients with Pseudomonas aeruginosa bacteremia. Biomedica. 2014;34(Suppl 1):58–66.

    PubMed  Google Scholar 

  22. Adrie C, Alberti C, Chaix-Couturier C, Azoulay É, de Lassence A, Cohen Y, et al. Epidemiology and economic evaluation of severe sepsis in France: age, severity, infection site, and place of acquisition (community, hospital, or intensive care unit) as determinants of workload and cost. J Crit Care. 2005;20(1):46–58.

    Article  PubMed  Google Scholar 

  23. Wichmann MW, Inthorn D, Andress HJ, Schildberg FW. Incidence and mortality of severe sepsis in surgical intensive care patients: the influence of patient gender on disease process and outcome. Intensive Care Med. 2000;26(2):167–72.

    Article  CAS  PubMed  Google Scholar 

  24. Mayr FB, Yende S, Angus DC. Epidemiology of severe sepsis. Virulence. 2014;5(1):4–11.

    Article  PubMed  Google Scholar 

  25. April MD, Aguirre J, Tannenbaum L, et al. Sepsis clinical criteria in emergency department patients admitted to an intensive care unit: an external validation study of quick. J Emerg Med. 2016;October:1–10.

    Google Scholar 

  26. Hall MJ, Williams SN, DeFrances CJ, Golosinskiy A. Inpatient care for septicemia or sepsis: a challenge for patients and hospitals. NCHS Data Brief. 2011;62:1–8.

    Google Scholar 

  27. van Vught LA, Klouwenberg PMK, Spitoni C, Scicluna BP, Wiewel MA, Horn J, et al. Incidence, risk factors, and attributable mortality of secondary infections in the intensive care unit after admission for sepsis. JAMA. 2016;315(14):1469–79.

    Article  PubMed  Google Scholar 

  28. Martin GS, Mannino DM, Moss M. The effect of age on the development and outcome of adult sepsis. Crit Care Med. 2006;34(1):15–21.

    Article  PubMed  Google Scholar 

  29. Bellou A, Israel B, Medical D, Blain H. Management of sepsis in older patients in the emergency department. In: Geriatric emergency medicine. © Springer International Publishing Switzerland 2018, 2018, p. 177–197.

  30. Papathanassoglou E, Middleton N, Benbenishty J, Williams G, Christofi M-D, Hegadoren K. Systematic review of gender-dependent outcomes in sepsis. Nurs Crit Care. 2017;22(5):284–92.

    Article  PubMed  Google Scholar 

  31. Kumar P, Renuka MK, Kalaiselvan MS, Arunkumar AS. Outcome of noncardiac surgical patients admitted to a multidisciplinary intensive care unit. Indian J Crit Care Med. 2017;21(1):17–22.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Asghar A, Hashmi M, Rashid S, Khan FH. Incidence, outcome and risk factors for sepsis—a two year retrospective study at surgical intensive care unit of a teaching hospital in pakistan. J Ayub Med Coll Abbottabad. 2016;28(1):79–83.

    PubMed  Google Scholar 

  33. Karvellas CJ, Abraldes JG, Arabi YM, Kumar A. Appropriate and timely antimicrobial therapy in cirrhotic patients with spontaneous bacterial peritonitis-associated septic shock: a retrospective cohort study. Aliment Pharmacol Ther. 2015;41(8):747–57.

    Article  CAS  PubMed  Google Scholar 

  34. Beumier M, Casu GS, Hites M, Seyler L, Cotton F, Vincent JL, et al. β-lactam antibiotic concentrations during continuous renal replacement therapy. Crit Care. 2014;18(3):R105.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Fuller BM, Mohr N, Skrupky L, Mueller K, McCammon C. Emergency department vancomycin use: dosing practices and associated outcomes. J Emerg Med. 2013;44(5):910–8.

    Article  PubMed  Google Scholar 

  36. Zhou J, Qian C, Zhao M, Yu X, Kang Y, Ma X, et al. Epidemiology and outcome of severe sepsis and septic shock in intensive care units in mainland China. PLoS ONE. 2014;9(9):e107181.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Badia M, Iglesias S, Servia L, Domingo J, Gormaz P, Vilanova J, et al. Mortality predictive factors in patients with urinary sepsis associated to upper urinary tract calculi. Med Intens. 2015;39(5):290–7.

    Article  CAS  Google Scholar 

  38. Boel J, Sogaard M, Andreasen V, Jarlov JO, Arpi M. Evaluating antibiotic stewardship programs in patients with bacteremia using administrative data: a cohort study. Eur J Clin Microbiol Infect Dis. 2015;34(7):1475–84.

    Article  CAS  PubMed  Google Scholar 

  39. 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(1):83.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Our deep appreciation goes to Mrs. Hartini Abul Hadi in the record department for providing the researchers with access to all facilities and her assistance during data collection in the hospital.

Funding

Not applicable.

Author information

Authors and Affiliations

  1. Faculty of Pharmacy-Universiti Teknologi Mara - Puncak Alam Campus, 42300, FF1, Level 10, Bandar Puncak Alam, Puncak Alam, Selangor, Malaysia

    Khalid Ahmad Al-Sunaidar, Noorizan Prof. Abd Aziz & Yahaya Prof. Hassan

Authors
  1. Khalid Ahmad Al-Sunaidar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Noorizan Prof. Abd Aziz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yahaya Prof. Hassan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Khalid Ahmad Al-Sunaidar.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflicts of interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Al-Sunaidar, K.A., Prof. Abd Aziz, N. & Prof. Hassan, Y. Appropriateness of empirical antibiotics: risk factors of adult patients with sepsis in the ICU. Int J Clin Pharm 42, 527–538 (2020). https://doi.org/10.1007/s11096-020-01005-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11096-020-01005-4

Keywords

Search

Navigation