The significance of sepsis markers among patients with positive blood cultures is paramount in enhancing early diagnosis and treatment within the ICU setting. Sepsis is the main reason for mortality in such settings, thus calling for fast and accurate diagnostic methods to improve the outcome of the patient. Of all the studied biomarkers, C-reactive protein (CRP) and serum procalcitonin (PCT) are the markers most important to diagnose bacterial sepsis in the early stage of the process than the methods applied traditionally.  Procalcitonin minimizes the risk of death, antibiotic consumption, and antibiotic-related side effects when it is used to guide the initiation and duration of antibiotic treatment. [1,2]. ICU patients with trauma and sepsis have considerably higher PCT levels, which could possibly distinguish sepsis from SIRS in critical illness. [3] The study thus assesses their efficacy, keeping in mind both the suspected and confirmed cases of sepsis. The research aims to unearth insights into their roles in facilitating timely and proper therapeutic interventions, ultimately reducing the high mortality rates that characterize sepsis in ICU patients by analyzing the potential of PCT and CRP. Blood culture remains the gold standard for diagnosing bacterial sepsis and provides direct proof of microbial infection in the bloodstream. However, the limitations of this method regarding time to result have prompted interest in biomarkers such as serum procalcitonin (PCT) and C-reactive protein (CRP) for earlier detection of bacteremia-related sepsis. Biomarkers can offer critical insights into the inflammatory response, thereby improving the timeliness of diagnosis and intervention [4]. This study specifically examines the effectiveness of PCT and CRP in patients with suspected and confirmed sepsis, aiming to determine their potential utility in clinical practice. Through such markers, this research seeks to improve diagnostic precision and predictive assessment for potential effective management in patients with sepsis.

METHODOLOGY

A retrospective study was conducted over a six-month period within the Microbiology department of a tertiary care hospital, focusing on patients with positive blood cultures. A total of 100 patient records were meticulously analyzed to assess the levels of inflammatory markers, specifically serum procalcitonin (PCT) and C-reactive protein (CRP).

Inclusion Criteria: Patient with both PCT and CRP requests along with blood culture

Exclusion Criteria: Patients with single marker request.

Assay method:

AGAPPE Mispa i3 nephelometry was used to determine the levels of serum PCT and serum CRP; a level of less than 6 mg/L for the latter and less than 0.3 ng/ml for the former was        considered normal.

Data collection: Institutional HIMS (Hospital Information Management System) software was used to procure data regarding the patients included in the study.

Statistical analysis: MS Excel was used for data compilation. The statistical software of SPSS 20.0 was used for data analysis. The measurements were expressed by mean and frequency distribution and the count data were expressed by rate of prevalence (%) among the different groups studied (Gram positive bacteria, Gram negative bacteria and fungi).

RESULTS

Prevalence of Gram Positive & Gram-Negative septicemia:

The study shows the prevalence of Gram-negative bacteremia to be 83% and Gram-positive bacteremia to be 17%, with Escherichia coli being the predominant pathogen isolated accounting to 50.6% followed by multidrug-resistant Klebsiella pneumoniae (22.8%), (19 cases) and Acinetobacter baumannii (9 cases). Other pathogens include Burkholderia pseudomallei (4 cases) and Enterobacter cloacae (6 cases), while Salmonella Typhi and Serratia marcescens each account for 2 and 1 case respectively. The data shows the prevalence of Gram-positive bacteraemia, with Staphylococcus aureus being the most common cause (9 cases), followed by Enterococcus faecalis (5 cases). Enterococcus faecium and Streptococcus pneumoniae are less prevalent, with 2 cases and 1 case respectively.

CRP and PCT: Of all the patients included, PCT was found to be positive in 91% cases, while CRP was 83% making PCT, a reliable marker for sepsis. The CRP and PCT values obtained were compared with the organisms isolated by blood culture. Fig 1 & Fig: 2 shows the frequency distribution of CRP and PCT among Gram Positive Bacteria, Gram Negative bacteria and Fungi isolated from clinical samples.

Fig:1 showing comparison of mean CRP levels (mg/L) among patients infected with Gram-positive bacteria, Gram-negative bacteria, and fungi.

Gram-positive bacteria (Streptococcus spp., Staphylococcus aureus) and Gram-negative bacteria (Burkholderia pseudomallei, Escherichia coli) tend to show high levels of CRP; this is compatible with the fact that they often cause more serious and invasive infections. Such infections would likely lead to significant inflammation, possibly as a result of factors such as bacterial virulence, the location of infection, or the nature of the immune response.

Fungal infections, such as Candida glabrata, Candida auris, show lower CRP values. It is possible that fungal infections, although serious (especially in immunocompromised patients), provoke a less pronounced inflammatory response compared to bacterial infections. Fungal infections, however, can be very debilitating and require prompt treatment.

Fig 2: Comparative analysis of serum procalcitonin (PCT) levels (ng/mL) across different microbial pathogens.

The elevated PCT values across these organisms suggest active and potentially severe infections, with Gram-negative bacteria such as Escherichia coli and Burkholderia pseudomallei posing the highest risk. Gram-positive bacteria, particularly Streptococcus spp. and Staphylococcus aureus, also show significantly elevated levels, indicating serious infections. Fungal infections, while generally showing lower PCT values, can still be significant, particularly when caused by invasive organisms like Candida glabrata or C. auris.

In our study, procalcitonin (PCT) showed a good diagnostic performance in identifying bacteraemia, with an AUC of 0.73 (95% CI: 0.65–0.81). At a cutoff value of 2.1 ng/mL, PCT achieved a positive predictive value of 72.5% and a negative predictive value of 67.9%, indicating its usefulness both in ruling in and ruling out bloodstream infection. In contrast, C-reactive protein (CRP) had a poor discriminatory value, with an AUC of 0.52 (95% CI: 0.43–0.62), which is close to random chance and statistically insignificant. These findings suggest that PCT is a more reliable biomarker than CRP for predicting bacteraemia among ICU patients with positive blood cultures.

DISCUSSION

Prevalence of Gram-Positive & Gram-Negative septicemia:

A larger proportion of Gram-negative organisms (87.3%) were isolated from culture-positive individuals, with Escherichia coli (27.3%) and Klebsiella (20%) being the most common. Gram-positive isolates accounted for 12.7% [5,6]. This finding is similar to our study. The study reveals that high levels of serum procalcitonin (PCT) are strongly linked to infections caused by extended-spectrum beta-lactamase (ESBL) producing and multidrug-resistant (MDR) bacteria. This suggests PCT could be a valuable tool for predicting sepsis outcomes, especially in infections involving resistant bacteria [7]. Since procalcitonin can indicate the early stages of multiple organ dysfunction syndrome (MODS), monitoring its levels daily could be beneficial for tracking the condition of critically ill patients. [8]. PCT concentrations of gram-negative (14.94 ng/mL, IQR 2.93 ~ 48.76) were significantly higher than gram-positive (4.74 ng/mL, IQR 1.22 ~ 17.5) and fungal (1.47 ng/mL, IQR 0.66 ~ 35.34). [9] C-reactive protein (CRP) is a sensitive parameter for diagnosing non-systemic infections, whereas procalcitonin (PCT) appears to be a useful parameter for improving the diagnosis and monitoring of therapy in patients with sepsis and septic shock [10,11,12,13]. In contrast, C-reactive protein (CRP), while elevated, did not exhibit the same level of specificity or prognostic value in these instances. The differential impact of these markers suggests that PCT may offer superior predictive capabilities in the early identification and management of sepsis, especially in complex cases involving resistance [14]. PCT levels were significantly higher in the GP group compared to the GN group, while CRP levels did not show any significant difference between the two groups [15]. Consequently, integrating PCT assessments into clinical protocols could significantly enhance the ability to stratify patients based on risk and tailor treatments more effectively, thereby improving the overall management of sepsis cases within intensive care settings.

The findings of this study underscore the critical role that serum procalcitonin (PCT) and C-reactive protein (CRP) play in the diagnostic and prognostic evaluation of sepsis. PCT has demonstrated substantial potential in identifying high-risk sepsis patients, allowing clinicians to make more informed decisions regarding treatment strategies. The accurate determination of PCT levels can significantly enhance patient outcomes by facilitating timely diagnoses and preventing unnecessary interventions. Moreover, the integration of CRP, despite its lower specificity compared to PCT, contributes to a more comprehensive understanding of the inflammatory response in sepsis cases [16]. Collectively, these biomarkers provide valuable tools for clinicians to improve the management of sepsis, ultimately reducing the associated morbidity and mortality rates.

CONCLUSION

In summary, the study reinforces the pivotal role that serum procalcitonin (PCT) and C-reactive protein (CRP) play in the diagnosis and management of sepsis, particularly among patients with positive blood cultures. Elevated levels of PCT, in particular, have been shown to correlate with a higher risk of severe sepsis, offering clinicians a reliable biomarker for identifying patients in need of urgent intervention. The ability of PCT to provide early prognostic insights surpasses that of CRP, making it a valuable tool for enhancing diagnostic accuracy and informing treatment strategies. As such, integrating PCT measurements into standard clinical protocols can significantly improve patient outcomes by ensuring timely diagnosis and reducing unnecessary treatments. These findings underscore the importance of adopting comprehensive biomarker analysis in sepsis management, ultimately advancing therapeutic approaches and reducing mortality rates in intensive care units.

These findings suggest that integrating PCT measurement in clinical practice could enhance the accuracy of sepsis diagnosis and improve patient management by facilitating timely interventions.

REFERENCES

1. Schuetz P, Müller B, Christ-Crain M, Stolz D, Tamm M, Bouadma L, Luyt CE, Wolff M, Chastre J, Tubach F, Kristoffersen KB, Burkhardt O, Welte T, Schroeder S, Nobre V, Wei L, Bhatnagar N, Bucher HC, Briel M. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2012 Sep 12;2012(9):CD007498. doi: 10.1002/14651858.CD007498.pub2. Update in: Cochrane Database Syst Rev. 2017 Oct 12;10:CD007498. doi: 10.1002/14651858.CD007498.pub3. PMID: 22972110; PMCID: PMC6464976.
2. Wacker C, Prkno A, Brunkhorst FM, Schlattmann P. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013 May;13(5):426-35. doi: 10.1016/S1473-3099(12)70323-7. Epub 2013 Feb 1. PMID: 23375419.
3. Sakran JV, Michetti CP, Sheridan MJ, Richmond R, Waked T, Aldaghlas T, Rizzo A, Griffen M, Fakhry SM. The utility of procalcitonin in critically ill trauma patients. J Trauma Acute Care Surg. 2012 Aug;73(2):413-8; discussion 418. doi: 10.1097/TA.0b013e31825ff5b7. PMID: 22846948.
4. Mierzchała-Pasierb M, Lipińska-Gediga M. Sepsis diagnosis and monitoring - procalcitonin as standard, but what next? Anaesthesiol Intensive Ther. 2019;51(4):299-305. doi: 10.5114/ait.2019.88104. PMID: 31550871.
5. Goyal PK, Sinha S, Saraf P. Comparison of Clinical Characteristics and Biomarkers in Culture-Positive and Culture-Negative Sepsis Patients. Cureus. 2024 Apr 21;16(4): e58682. doi: 10.7759/cureus.58682. PMID: 38774176; PMCID: PMC11107478.
6. Gutiérrez-Gutiérrez B, Morales I, Pérez-Galera S, Fernández-Riejos P, Retamar P, de Cueto M, Pascual Á, Rodríguez-Baño J. Predictive value of the kinetics of procalcitonin and C-reactive protein for early clinical stability in patients with bloodstream infections due to Gram-negative bacteria. Diagn Microbiol Infect Dis. 2019 Jan;93(1):63-68. doi: 10.1016/j.diagmicrobio.2018.07.019. Epub 2018 Aug 3. PMID: 30131239.
7. Verma N, Kapoor S, Rao D, Sharma S, Arora A. PCT as a Prognostic Marker in Cardiac Patients with Neutropenic Sepsis: Two Case Reports. Indian J Clin Biochem. 2014 Jan;29(1):107-11. doi: 10.1007/s12291-013-0382-4. Epub 2013 Oct 2. PMID: 24478560; PMCID: PMC3903924.
8. Giamarellos-Bourboulis EJ, Mega A, Grecka P, Scarpa N, Koratzanis G, Thomopoulos G, Giamarellou H. Procalcitonin: a marker to clearly differentiate systemic inflammatory response syndrome and sepsis in the critically ill patient? Intensive Care Med. 2002 Sep;28(9):1351-6. doi: 10.1007/s00134-002-1398-z. Epub 2002 Aug 7. PMID: 12209289.
9. Pan YP, Fang YP, Xu YH, Wang ZX, Shen JL. The Diagnostic Value of Procalcitonin Versus Other Biomarkers in Prediction of Bloodstream Infection. Clin Lab. 2017 Feb 1;63(2):277-285. doi: 10.7754/Clin.Lab.2016.160802. PMID: 28182347.
10. Santacroce E, D'Angerio M, Ciobanu AL, Masini L, Lo Tartaro D, Coloretti I, Busani S, Rubio I, Meschiari M, Franceschini E, Mussini C, Girardis M, Gibellini L, Cossarizza A, De Biasi S. Advances and Challenges in Sepsis Management: Modern Tools and Future Directions. Cells. 2024 Mar 2;13(5):439. doi: 10.3390/cells13050439. PMID: 38474403; PMCID: PMC10931424.
11. Schupp T, Weidner K, Rusnak J, Jawhar S, Forner J, Dulatahu F, Dudda J, Brück LM, Hoffmann U, Bertsch T, Akin I, Behnes M. C-reactive protein and procalcitonin during course of sepsis and septic shock. Ir J Med Sci. 2024 Feb;193(1):457-468. doi: 10.1007/s11845-023-03385-8. Epub 2023 May 19. PMID: 37204560; PMCID: PMC10196281.
12. Wu HN, Yuan EY, Li WB, Peng M, Zhang QY, Xie KL. Corrigendum: Microbiological and clinical characteristics of bloodstream infections in general intensive care unit: A retrospective study. Front Med (Lausanne). 2023 Mar 21; 10:1174935. doi: 10.3389/fmed.2023.1174935. Erratum for: Front Med (Lausanne). 2022 Apr 28; 9:876207. doi: 10.3389/fmed.2022.876207. PMID: 37025960; PMCID: PMC10071656.
13. Yang, X., Zeng, J., Yu, X. et al.PCT, IL-6, and IL-10 facilitate early diagnosis and pathogen classifications in bloodstream infection. Ann Clin Microbiol Antimicrob 22, 103 (2023).
14. Bassetti M, Russo A, Righi E, Dolso E, Merelli M, D'Aurizio F, Sartor A, Curcio F. Role of procalcitonin in predicting etiology in bacteremic patients: Report from a large single-center experience. J Infect Public Health. 2020 Jan;13(1):40-45. doi: 10.1016/j.jiph.2019.06.003. Epub 2019 Jun 24. PMID: 31248812.
15. Liu HH, Zhang MW, Guo JB, Li J, Su L. Procalcitonin and C-reactive protein in early diagnosis of sepsis caused by either Gram-negative or Gram-positive bacteria. Ir J Med Sci. 2017 Feb;186(1):207-212. doi: 10.1007/s11845-016-1457-z. Epub 2016 May 2. PMID: 27139197.
16. Anush MM, Ashok VK, Sarma RIN, Pillai SK. Role of C-reactive Protein as an Indicator for Determining the Outcome of Sepsis. Indian Journal of Critical Care Medicine, January 2019; 23(1):11-14.