Research Article
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Can high procalcitonin levels be a biomarker for detecting multidrug-resistant Gram-negative bacteremia?

Year 2023, Volume: 6 Issue: 6, 1162 - 1169, 29.10.2023
https://doi.org/10.32322/jhsm.1351860

Abstract

Aims: Clinicians prefer broad-spectrum empirical antibiotic therapy in patients with suspected bloodstream infection (BSI) due to long test turnaround times of conventional methods. We aimed to assess the contribution of procalcitonin (PCT) to the selection of antibiotics to be used in empirical treatment.
Methods: The results of inpatients whose blood cultures and samples for PCT tests had been sent simultaneously between 2018 and 2022 were analyzed retrospectively. Antibiotic susceptibility results of Enterobacteriaceae, Acinetobacter baumannii complex and Pseudomonas aeruginosa, were evaluated for multidrug-resistance (MDR).
Results: Results of 1206 patients who met the inclusion criteria were included in the study. The PCT median value in BSIs caused by the Gram-negative bacteria found to be statistically significantly higher than those caused by the Gram-positive bacteria, fungal and polymicrobial infections (p<0.05). The best cutoff value of ROC, with an AUC value of 0.607 (CI: 95%: 0.578-0.635, p< .0001), a sensitivity of 72.1%, and a specificity of 55.4%, for distinguishing GN BSIs from other BSIs was determined as 2.5 ng/ml. The PCT median value of MDR pathogens was found to be statistically significantly higher than that of non-MDR pathogens (p < 0.05). A ROC analysis was performed, and the AUC distinguishing MDR pathogens from non-MDR was found as 0.633(CI: 95%, 0.586-0.681; p <0.0001), with a best PCT cutoff of 11.4 ng/mL, a sensitivity of 54.8%, and a specificity of 66.3%
Conclusion: High levels of PCT can guide empirical antibiotic treatments, with its property to predict GN bacteria and that they might be MDR GN BSIs.

Supporting Institution

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References

  • Kibe S, Adams K, Barlow G. Diagnostic and prognostic biomarkers of sepsis in critical care. J Antimicrob Chemother. 2011;66(Supplement 2):ii33-ii40.
  • Grant MJC, Olson J, Gerber A. Clinician response time for positive blood culture results in a pediatric ICU. Heart & Lung. 2015;44(5):426-429.
  • Zanon F, Caovilla JJ, Michel RS, et al. Sepse na unidade de terapia intensiva: etiologias, fatores prognósticos e mortalidade. Rev Bras Ter Intensiva. 2008;20(2):128-134
  • Marshall JC, Vincent J, Guyatt G, et al. Outcome measures for clinical research in sepsis: a report of the 2nd Cambridge Colloquium of the International Sepsis Forum. Crit Care Med. 2005;33(8):1708-1716.
  • Marik PE, Taeb AM. SIRS, qSOFA and new sepsis definition. J Thorac Dis. 2017;9(4):943-945.
  • Lai L, Lai Y, Wang H, et al. Diagnostic accuracy of procalcitonin compared to C-reactive protein and interleukin 6 in recognizing Gram-negative bloodstream infection: a meta-analytic study. Dis Markers. 2020;2020:1-14.
  • Hausfater P, Garric S, Ayed SB, Rosenheim M, Bernard M, Riou B. Usefulness of procalcitonin as a marker of systemic infection in emergency department patients: a prospective study. Clin Infect Dis. 2002;34(7):895-901.
  • Panico C, Nylen E. Procalcitonin beyond the acute phase: novel biomediator properties? BMC Med. 2013;11(1): 89.
  • Bassetti M, Russo A, Righi E, et al. Role of procalcitonin in bacteremic patients and its potential use in predicting infection etiology. Exp Rev Anti-infective Ther. 2019;17(2):99-105.
  • Lin J, Chen Z, Chen X. Elevated serum procalcitonin predicts Gram-negative bloodstream infections in patients with burns. Burns. 2020;46(1):182-189.
  • Luo X, Chen S, Zhang J, et al. Procalcitonin as a marker of Gram-negative bloodstream infections in hematological patients with febrile neutropenia. Leukemia & Lymphoma. 2019;60(10):2441-2448.
  • Yan ST, Sun LC, Jia HB, Gao W, Yang JP, Zhang GQ. Procalcitonin levels in bloodstream infections caused by different sources and species of bacteria. Am J Emerg Med. 2017;35(4):579-583.
  • 13 Kirn T, Weinstein M. Update on blood cultures: how to obtain, process, report, and interpret. Clin Microbiol Infect. 2013;19(6):513-520.
  • European Committee on Antimicrobial Susceptibility Testing (EUCAST). Archive of EUCAST tables and documents. 2023 Available at: https://www.eucast.org/ast_of_bacteria/previous_versions_of_documents
  • Magiorakos A, Srinivasan A, Carey R, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18(3):268-281.
  • World Health Organization. WHO publishes list of bacteria for which new antibiotics are urgently needed. 2017. Available at: https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgentlyneeded. Accessed 25 January 2023
  • WHO. Central Asian and European surveillance of antimicrobial resistance: annual report 2020. Available at: https://iris.who.int/handle/10665/345873?&locale-attribute=es
  • Tamma PD, Avdic E, Keenan JF, et al. What is the more effective antibiotic stewardship intervention: pre-prescription authorization or post-prescription review with feedback?.Clinid. 2016; 537–543.
  • Schuetz P, Beishuizen A, Broyles M, et al. Procalcitonin (PCT)-guided antibiotic stewardship: an international experts consensus on optimized clinical use. Clin Chem Lab Med (CCLM). 2019;57(9):1308-1318.
  • Schuetz P, Albrich W, Mueller B. Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future. BMC Med. 2011;9(1).
  • Hoeboer S, van der Geest P, Nieboer D, Groeneveld A. The diagnostic accuracy of procalcitonin for bacteraemia: a systematic review and meta-analysis. Clin Microbiol Infect. 2015;21(5):474-481.
  • Oussalah A, Ferrand J, Filhine-Tresarrieu P, et al. Diagnostic accuracy of procalcitonin for predicting blood culture results in patients with suspected bloodstream infection. Medicine. 2015;94(44):e1774.
  • Lin C, Lu J, Chen Y, Kok VC, Horng J. Diagnostic value of serum procalcitonin, lactate, and high-sensitivity C-reactive protein for predicting bacteremia in adult patients in the emergency department. Peer J. 2017;5:e4094.
  • Bassetti M, Russo A, Righi E, et al. Comparison between procalcitonin and C-reactive protein to predict blood culture results in ICU patients. Crit Care. 2018;22(1):1-2
  • Schuetz P, Christ-Crain M, Müller B. Procalcitonin and other biomarkers to improve assessment and antibiotic stewardship in infections--hope for hype. Swiss Med Wkly. 2009;139(23-24):318-326
  • Linscheid P, Seboek D, Zulewski H, Keller U, Müller B. Autocrine/paracrine role of inflammation-mediated calcitonin gene-related peptide and adrenomedullin expression in human adipose tissue. Endocrinology. 2005;146(6):2699-2708.
  • Chirouze C, Schuhmacher H, Rabaud C, et al. Low serum procalcitonin level accurately predicts the absence of bacteremia in adult patients with acute fever. Clin Infect Dis. 2002;35(2):156-161.
  • Saeed K, González del Castillo J, Backous C, et al. Hot topics on procalcitonin use in clinical practice, can it help antibiotic stewardship?. Int J Antimicrob Agents. 2019;54(6):686-696.
  • He C, Wang B, Wang YF, Shen YC. Can procalcitonin be used to diagnose Gram-negative bloodstream infection? Evidence based on a meta-analysis. Eur Rev Med Pharmacol Sci. 2017;21(14):3253-3261.
  • 30 Wu H, Yuan E, Li W, Peng M, Zhang Q, Xie K. Microbiological and clinical characteristics of bloodstream infections in general intensive care unit: a retrospective study. Front Med. 2022;9: 876207.
  • Yang J, Li S, Rong H, Guo Q, Chen Y, Zhang G. Serum procalcitonin levels distinguish Gram-negative bacterial sepsis from Gram-positive bacterial and fungal sepsis. J Res Med Sci. 2016;21(1):39.
  • Rodríguez AH, Avilés-Jurado FX, Díaz E, et al. Procalcitonin (PCT) levels for ruling-out bacterial coinfection in ICU patients with influenza: a chaid decision-tree analysis. J Infect. 2016;72(2):143-151.
  • Dandona P. Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab. 1994;79(6):1605-1608.
  • Seki M, Watanabe Y, Oikawa N, Hariu M, Fuke R. Ability of procalcitonin to diagnose bacterial infection and bacteria types compared with blood culture findings. IJGM. 2016;9:325-331.
  • Sakan S, Kralik K, Mihelčić A, et al. Correlation between inflammatory parameters and bloodstream infections caused by multidrug resistant Gram-negative bacteria in critically ill COVID-19 patients–retrospective single-center study. Liječ Vjesn. 2022; 144(Supp 3):31-36.
  • Mera FSC, Chacón JAR, Lupercio ANC, et al. Marcadores hematológicos y bioquímicos para el diagnóstico precoz de bacteriemias causadas por Enterobacteriaceae resistentes a los carbapenémicos. Revista Médica-Científica CAMbios HECAM. 2021;20(2):67-73.
  • Goodman KE, Baghdadi JD, Magder LS, et al. Patterns, predictors, and intercenter variability in empiric Gram-negative antibiotic use across 928 United States hospitals. Clin Infect Dis. 2023;76(3):e1224-e1235.
  • Chambliss AB, Patel K, Colón-Franco JM, et al. AACC Guidance Document on the Clinical Use of Procalcitonin. J Appl Lab Med 2023;8(3):598-634.
  • Chirouze C, Schuhmacher H, Rabaud C, et al. Low serum procalcitonin level accurately predicts the absence of bacteremia in adult patients with acute fever. Clin Infect Dis. 2002;35(2):156-161.
  • Popov DA, Ovseenko ST, Vostrikova TY. [Procalcitonin as a predictor of bacteremia in postoperative cardiosurgery patients]. Anesteziol Reanimatol. 2014; (2):4-9.
  • Routsi C, Gkoufa A, Arvaniti K, et al. De-escalation of antimicrobial therapy in ICU settings with high prevalence of multidrug-resistant bacteria: a multicentre prospective observational cohort study in patients with sepsis or septic shock. J Antimicrob Chemother. 2020;75(12):3665-3674.
  • Wang X, Long Y, Su L, Zhang Q, Shan G, He H. Using Procalcitonin to Guide Antibiotic Escalation in Patients With Suspected Bacterial Infection: A New Application of Procalcitonin in the Intensive Care Unit. Front Cell Infect Microbiol. 2022;12: 844134
  • Paudel R, Dogra P, Montgomery-Yates AA, Coz Yataco A. Procalcitonin: A promising tool or just another overhyped test?. Int J Med Sci. 2020;17(3):332-337.
  • Xu H, Tian M, Pan S. Clinical utility of procalcitonin and its association with pathogenic microorganisms. Crit Rev Clin Lab Sci. 2022;59(2):93-111.
  • Garlasco J, Beqiraj I, Bolla C, et al. Impact of septic episodes caused by Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa in a tertiary hospital: clinical and economic considerations in years 2018–2020. J Infect Public Health. 2023;16(4):475-482.
  • Franeková J, Sečník P, Lavríková P, et al. Serial measurement of presepsin, procalcitonin, and C-reactive protein in the early postoperative period and the response to antithymocyte globulin administration after heart transplantation. Clin Transplant. 2017;31(1):e12870.
Year 2023, Volume: 6 Issue: 6, 1162 - 1169, 29.10.2023
https://doi.org/10.32322/jhsm.1351860

Abstract

References

  • Kibe S, Adams K, Barlow G. Diagnostic and prognostic biomarkers of sepsis in critical care. J Antimicrob Chemother. 2011;66(Supplement 2):ii33-ii40.
  • Grant MJC, Olson J, Gerber A. Clinician response time for positive blood culture results in a pediatric ICU. Heart & Lung. 2015;44(5):426-429.
  • Zanon F, Caovilla JJ, Michel RS, et al. Sepse na unidade de terapia intensiva: etiologias, fatores prognósticos e mortalidade. Rev Bras Ter Intensiva. 2008;20(2):128-134
  • Marshall JC, Vincent J, Guyatt G, et al. Outcome measures for clinical research in sepsis: a report of the 2nd Cambridge Colloquium of the International Sepsis Forum. Crit Care Med. 2005;33(8):1708-1716.
  • Marik PE, Taeb AM. SIRS, qSOFA and new sepsis definition. J Thorac Dis. 2017;9(4):943-945.
  • Lai L, Lai Y, Wang H, et al. Diagnostic accuracy of procalcitonin compared to C-reactive protein and interleukin 6 in recognizing Gram-negative bloodstream infection: a meta-analytic study. Dis Markers. 2020;2020:1-14.
  • Hausfater P, Garric S, Ayed SB, Rosenheim M, Bernard M, Riou B. Usefulness of procalcitonin as a marker of systemic infection in emergency department patients: a prospective study. Clin Infect Dis. 2002;34(7):895-901.
  • Panico C, Nylen E. Procalcitonin beyond the acute phase: novel biomediator properties? BMC Med. 2013;11(1): 89.
  • Bassetti M, Russo A, Righi E, et al. Role of procalcitonin in bacteremic patients and its potential use in predicting infection etiology. Exp Rev Anti-infective Ther. 2019;17(2):99-105.
  • Lin J, Chen Z, Chen X. Elevated serum procalcitonin predicts Gram-negative bloodstream infections in patients with burns. Burns. 2020;46(1):182-189.
  • Luo X, Chen S, Zhang J, et al. Procalcitonin as a marker of Gram-negative bloodstream infections in hematological patients with febrile neutropenia. Leukemia & Lymphoma. 2019;60(10):2441-2448.
  • Yan ST, Sun LC, Jia HB, Gao W, Yang JP, Zhang GQ. Procalcitonin levels in bloodstream infections caused by different sources and species of bacteria. Am J Emerg Med. 2017;35(4):579-583.
  • 13 Kirn T, Weinstein M. Update on blood cultures: how to obtain, process, report, and interpret. Clin Microbiol Infect. 2013;19(6):513-520.
  • European Committee on Antimicrobial Susceptibility Testing (EUCAST). Archive of EUCAST tables and documents. 2023 Available at: https://www.eucast.org/ast_of_bacteria/previous_versions_of_documents
  • Magiorakos A, Srinivasan A, Carey R, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18(3):268-281.
  • World Health Organization. WHO publishes list of bacteria for which new antibiotics are urgently needed. 2017. Available at: https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgentlyneeded. Accessed 25 January 2023
  • WHO. Central Asian and European surveillance of antimicrobial resistance: annual report 2020. Available at: https://iris.who.int/handle/10665/345873?&locale-attribute=es
  • Tamma PD, Avdic E, Keenan JF, et al. What is the more effective antibiotic stewardship intervention: pre-prescription authorization or post-prescription review with feedback?.Clinid. 2016; 537–543.
  • Schuetz P, Beishuizen A, Broyles M, et al. Procalcitonin (PCT)-guided antibiotic stewardship: an international experts consensus on optimized clinical use. Clin Chem Lab Med (CCLM). 2019;57(9):1308-1318.
  • Schuetz P, Albrich W, Mueller B. Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future. BMC Med. 2011;9(1).
  • Hoeboer S, van der Geest P, Nieboer D, Groeneveld A. The diagnostic accuracy of procalcitonin for bacteraemia: a systematic review and meta-analysis. Clin Microbiol Infect. 2015;21(5):474-481.
  • Oussalah A, Ferrand J, Filhine-Tresarrieu P, et al. Diagnostic accuracy of procalcitonin for predicting blood culture results in patients with suspected bloodstream infection. Medicine. 2015;94(44):e1774.
  • Lin C, Lu J, Chen Y, Kok VC, Horng J. Diagnostic value of serum procalcitonin, lactate, and high-sensitivity C-reactive protein for predicting bacteremia in adult patients in the emergency department. Peer J. 2017;5:e4094.
  • Bassetti M, Russo A, Righi E, et al. Comparison between procalcitonin and C-reactive protein to predict blood culture results in ICU patients. Crit Care. 2018;22(1):1-2
  • Schuetz P, Christ-Crain M, Müller B. Procalcitonin and other biomarkers to improve assessment and antibiotic stewardship in infections--hope for hype. Swiss Med Wkly. 2009;139(23-24):318-326
  • Linscheid P, Seboek D, Zulewski H, Keller U, Müller B. Autocrine/paracrine role of inflammation-mediated calcitonin gene-related peptide and adrenomedullin expression in human adipose tissue. Endocrinology. 2005;146(6):2699-2708.
  • Chirouze C, Schuhmacher H, Rabaud C, et al. Low serum procalcitonin level accurately predicts the absence of bacteremia in adult patients with acute fever. Clin Infect Dis. 2002;35(2):156-161.
  • Saeed K, González del Castillo J, Backous C, et al. Hot topics on procalcitonin use in clinical practice, can it help antibiotic stewardship?. Int J Antimicrob Agents. 2019;54(6):686-696.
  • He C, Wang B, Wang YF, Shen YC. Can procalcitonin be used to diagnose Gram-negative bloodstream infection? Evidence based on a meta-analysis. Eur Rev Med Pharmacol Sci. 2017;21(14):3253-3261.
  • 30 Wu H, Yuan E, Li W, Peng M, Zhang Q, Xie K. Microbiological and clinical characteristics of bloodstream infections in general intensive care unit: a retrospective study. Front Med. 2022;9: 876207.
  • Yang J, Li S, Rong H, Guo Q, Chen Y, Zhang G. Serum procalcitonin levels distinguish Gram-negative bacterial sepsis from Gram-positive bacterial and fungal sepsis. J Res Med Sci. 2016;21(1):39.
  • Rodríguez AH, Avilés-Jurado FX, Díaz E, et al. Procalcitonin (PCT) levels for ruling-out bacterial coinfection in ICU patients with influenza: a chaid decision-tree analysis. J Infect. 2016;72(2):143-151.
  • Dandona P. Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab. 1994;79(6):1605-1608.
  • Seki M, Watanabe Y, Oikawa N, Hariu M, Fuke R. Ability of procalcitonin to diagnose bacterial infection and bacteria types compared with blood culture findings. IJGM. 2016;9:325-331.
  • Sakan S, Kralik K, Mihelčić A, et al. Correlation between inflammatory parameters and bloodstream infections caused by multidrug resistant Gram-negative bacteria in critically ill COVID-19 patients–retrospective single-center study. Liječ Vjesn. 2022; 144(Supp 3):31-36.
  • Mera FSC, Chacón JAR, Lupercio ANC, et al. Marcadores hematológicos y bioquímicos para el diagnóstico precoz de bacteriemias causadas por Enterobacteriaceae resistentes a los carbapenémicos. Revista Médica-Científica CAMbios HECAM. 2021;20(2):67-73.
  • Goodman KE, Baghdadi JD, Magder LS, et al. Patterns, predictors, and intercenter variability in empiric Gram-negative antibiotic use across 928 United States hospitals. Clin Infect Dis. 2023;76(3):e1224-e1235.
  • Chambliss AB, Patel K, Colón-Franco JM, et al. AACC Guidance Document on the Clinical Use of Procalcitonin. J Appl Lab Med 2023;8(3):598-634.
  • Chirouze C, Schuhmacher H, Rabaud C, et al. Low serum procalcitonin level accurately predicts the absence of bacteremia in adult patients with acute fever. Clin Infect Dis. 2002;35(2):156-161.
  • Popov DA, Ovseenko ST, Vostrikova TY. [Procalcitonin as a predictor of bacteremia in postoperative cardiosurgery patients]. Anesteziol Reanimatol. 2014; (2):4-9.
  • Routsi C, Gkoufa A, Arvaniti K, et al. De-escalation of antimicrobial therapy in ICU settings with high prevalence of multidrug-resistant bacteria: a multicentre prospective observational cohort study in patients with sepsis or septic shock. J Antimicrob Chemother. 2020;75(12):3665-3674.
  • Wang X, Long Y, Su L, Zhang Q, Shan G, He H. Using Procalcitonin to Guide Antibiotic Escalation in Patients With Suspected Bacterial Infection: A New Application of Procalcitonin in the Intensive Care Unit. Front Cell Infect Microbiol. 2022;12: 844134
  • Paudel R, Dogra P, Montgomery-Yates AA, Coz Yataco A. Procalcitonin: A promising tool or just another overhyped test?. Int J Med Sci. 2020;17(3):332-337.
  • Xu H, Tian M, Pan S. Clinical utility of procalcitonin and its association with pathogenic microorganisms. Crit Rev Clin Lab Sci. 2022;59(2):93-111.
  • Garlasco J, Beqiraj I, Bolla C, et al. Impact of septic episodes caused by Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa in a tertiary hospital: clinical and economic considerations in years 2018–2020. J Infect Public Health. 2023;16(4):475-482.
  • Franeková J, Sečník P, Lavríková P, et al. Serial measurement of presepsin, procalcitonin, and C-reactive protein in the early postoperative period and the response to antithymocyte globulin administration after heart transplantation. Clin Transplant. 2017;31(1):e12870.
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Details

Primary Language English
Subjects Medical Bacteriology
Journal Section Original Article
Authors

Şölen Daldaban Dinçer 0000-0003-0627-5817

Ülkü Oral 0000-0002-6870-9628

Meltem Ayaş 0000-0003-1920-9261

Sebahat Aksaray 0000-0002-0552-1337

Early Pub Date October 28, 2023
Publication Date October 29, 2023
Published in Issue Year 2023 Volume: 6 Issue: 6

Cite

AMA Daldaban Dinçer Ş, Oral Ü, Ayaş M, Aksaray S. Can high procalcitonin levels be a biomarker for detecting multidrug-resistant Gram-negative bacteremia?. J Health Sci Med / JHSM. October 2023;6(6):1162-1169. doi:10.32322/jhsm.1351860

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