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Table of Content - Volume 11 Issue 3 - September 2019

 

Procalcitonin in bacterial infections

 

Md Siddique Ahmed Khan1, Syed Arshaduddin Ahmed2*

 

1Professor and HOD, Department of Biochemistry, Shadan Institute of Medical Sciences, Hyderabad, INDIA.

2Associate Professor, Department of Pharmacology, Osmania Medical College, Hyderabad, INDIA.

Email: drarshadomc@gmail.com

 

Abstract               Background: Procalcitonin [PCT] is a protein which consists of 116 amino acids, is a peptide precursor of the hormone calcitonin. It exhibits greater specificity than other pro inflammatory markers like cytokines. PCT has short half-life (25–30 hours in plasma), coupled with its virtual absence in health and specificity for bacterial infections, gives it a clear advantage over the other markers of bacterial infection and is used in the diagnosis of bacterial infections and to guide antibiotic therapy since 1990’s. Currently patients treated with procalcitonin guided therapy have lower risk of antibiotic related side effects. Objective: The objective of this study was to prove that Procalcitonin is useful in early detection of acute bacterial infection. Design: This was a prospective descriptive study. Duration: One year i.e. November 2017 to November 2018. Setting: Shadan Institute of Medical Sciences, Hyderabad. Participants: 100 Sick patients above 18 years of age with a fever (temperature over 38°C) who were considered at risk of having a bacterial infection were included in the study. Methods: All the patients were subjected to detailed clinical examination and investigations. Patient’s clinical profile, progression of disease and outcome were recorded. PCT and various other relevant factors were measured in all study subjects. Data were presented in the form of statistical Tables and charts. SPSS software version 20 was used for statistical analysis. Results: Serum PCT level of patients with bacterial infection was significantly higher than that in the non-bacterial cases; serum PCT level of patients with bacterial infection, before and after treatment had statistical significance. Conclusion: These results suggest that PCT is a useful biomarker of bacterial infections, and it might serve as a strong tool to detect patients with sepsis.

Key Words: Procaclitonin, Bacterial Infections, Diagnosis, Marker.

 

 

INTRODUCTION

Procalcitonin (PCT) is a peptide (116 amino acids) precursor of the calcium-regulating thyroid hormone, calcitonin. The level of procalcitonin in the blood stream of healthy individuals is below the limit of detection (0.01 µg/L) of clinical assays. The level of procalcitonin rises in a response to a pro-inflammatory stimulus, especially of bacterial origin. It is therefore often classed as an acute phase reactant. The induction period for procalcitonin ranges from 4–12 hours with a half-life spanning anywhere from 22–35 hours. Due to PCT’s variance between microbial infections and healthy individuals, it has become a marker to improve identification of bacterial infection and guide antibiotic therapy. The isolation of causes is considered as the golden standard of diagnosing bacterial infections and sepsis. However, due to the time required for the implementation and interpretation of the results of blood and other bacterial cultures, insufficient sensitivity (blood culture) and low specificity caused by contamination (sputum), under the modern understanding of the definition, identification of bacterial pathogen today does not present the condition that determines the diagnosis of sepsis and bacterial infections. About 70% of radiologically proven pneumonia and up to 80% of clinically suspected bacteraemia remain microbiologically undifferentiated. The results of researches, which in recent years have been focused on the acute phase reactants of inflammation, indicate considerable diagnostic potential of procalcitonin (PCT) in the early detection of bacterial infection and its correlation with disease severity and outcome of treatment.

MATERIALS AND METHODS

Place of Study: Shadan Institute of Medical Sciences, Hyderabad.

Type of Study: This was a prospective descriptive study.

Sample Collection: Sample size: 100.

Sampling Methods: Consecutive sampling.

Inclusion Criteria: 100 Sick patients above 18 years of age with a fever (temperature over 38°C) who were considered at risk of having a bacterial infection were considered eligible for inclusion in the study.

Exclusion Criteria: Cases with recent surgeries, chronic disease, immunodeficiency or those who took antibiotics within 10 days of presentation were excluded from the study.

Statistical Methods: Data were presented in the form of statistical Tables and charts. SPSS software version 20 was used for statistical analysis.

Ethical Approval: Approval was taken from the Institutional Ethics Committee prior to commencement of the study.

 

OBSERVATIONS AND RESULTS

Table 1: Age and Sex Distribution

Age range (years)

Male

Female

No.

%

No.

%

20-40

22

22%

20

20%

41-60

20

20%

16

16%

61-80

20

20%

14

14%

Total

62

62%

38

38%

A total of 100 patients with age ranging from 20 to 80 years were undertaken for study and majority of them belonged to age group of 20 – 40 years.

 

Table 2: Symptomatology

Symptoms

No. of Patients

Percentage

Fever

96

96%

Breathlessness

32

32%

Cough

20

20%

Burning Micturition

18

18%

Headache

22

22%

Vomiting

22

22%

Pain abdomen

14

14%

Of all the patients undertaken for study majority were having fever around 96% and 1/3rd of them showed breathlessness symptoms, around 20% of the patients exhibited symptoms of cough, headache and vomiting and lesser number with burning micturation and pain abdomen.

Table 3: PCT and Blood Culture results

Patients

PCT Positive(46%)

PCT Negative(54%)

P Value

Blood Culture Positive

16(16%)

4(4%)

*p<0.05

Blood Culture Negative

30(30%)

50(50%)

The PCT results in blood culture positive patients read as follows - around 16% tested positive for PCT and 4% tested negative. In blood culture negative around 30% tested positive for PCT and 50% tested negative for the same.

DISCUSSION

A total of 100 patients were undertaken for the study of PCT in bacterial infections. We selected a random effects model that assumes that the included studies belong to a random sample of a universe of studies. A large spectrum of the population was covered in the meta-analysis, allowing generalization of the results. All age groups were included in this study, because kinetics of PCT follow similar pattern in children and adults, with some evidence that PCT levels vary in a similar way during the first 48 h of life. Fever was the most common symptom in 96% of the patients, around 1/3rd had breathlessness and around 20% had cough, headache and vomiting, few with burning micturition and abdominal pain. The PCT results. Procalcitonin is a reliable, consistently accurate biomarker of invasive bacterial infection with a high positive predictive value when plasma levels are elevated and a strong negative predictive value when plasma levels are low. Viral infections, collagen vascular diseases, inflammatory of infections is still a challenge for clinicians. The general consensus is not to provide antibiotics for every suspected infection because of emerging issues with bacterial resistance. Therefore, a marker specific for bacterial infection will be most helpful. Based on this meta-analysis, we observed that PCT levels were more accurate markers for bacterial infection than were CRP levels, both when differentiating bacterial infections from non - infective causes of inflammation and when differentiating bacterial infections from viral infections. The first commercial PCT assay (LUMI test) has a functional lower limit of sensitivity of 0.5 ng/mL. The second-generation Food and Drug Administration (FDA)-approved PCT assay is technically a time-resolved cryptate emission immunoassay. The assay quantifies both PCT and part of the N-terminal end of the PCT molecule. The functional lower limit of sensitivity is 0.05 ng/mL, and the assay has reliable linear quantitation to 1,000 ng/mL. Either serum or plasma is used, and results are available in 1 hour or less. The clinical evaluation of PCT levels continues. At present, there are four common uses of PCT levels. First, the current immunoassay was approved by the FDA for establishing the likelihood of mortality in critically ill septic patients. Second, PCT levels have been used to guide empirical antibacterial therapy in patients with acute exacerbations of chronic bronchitis, community-acquired pneumonia (CAP), and sepsis. Third, PCT levels, along with standard clinical parameters, can assist in determining whether the patient's empirical antibacterial therapy is effective. Finally, the most useful application is the use of sequential PCT levels to determine when there is no longer a need for antibacterial therapy. The clinical implications of the above mentioned observational studies may be limited by differences in disease definitions and patient groups, use of insensitive PCT assays, and different methodological issues such as observer bias, selection bias and issues of sample availability, co-infection and colonization. To overcome these limitations, several randomized-controlled studies have investigated the use of PCT to assist in decisions about initiation and/or duration of antibiotic therapy (antibiotic stewardship).

 

CONCLUSIONS

These results suggest that PCT is a useful biomarker of bacterial infections, and it might serve as a strong tool to detect patients with sepsis. The PCT assay was found to be a useful biomarker of bacteremia in this study. The assay could be performed and reported rapidly and provided valuable information before availability of culture results. This might assist in avoiding unwarranted antibiotic usage.

 

REFERENCES

  1. E. Bottieau, J. Clerinx, E. Van den Enden et al., “Fever after a stay in the tropics: diagnostic predictors of the leading tropical conditions,” Medicine, vol. 86, no. 1, pp. 18–25, 2007.
  2. V. Nobre, S. Harbarth, J.-D. Graf, P. Rohner, and J. Pugin, “Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial,” American Journal of Respiratory and Critical Care Medicine, vol. 177, no. 5, pp. 498–505, 2008.
  3. P. Linscheid, D. Seboek, E. S. Nylen et al., “In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue,” Endocrinology, vol. 144, no. 12, pp. 5578–5584, 2003.
  4. M. Christ-Crain, D. Jaccard-Stolz, R. Bingisser et al., “Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial,” The Lancet, vol. 363, no. 9409, pp. 600–607, 2004.
  5. M. Christ-Crain, D. Stolz, R. Bingisser et al., “Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial,” American Journal of Respiratory and Critical Care Medicine, vol. 174, no. 1, pp. 84–93, 2006.
  6. R.P. Peters, M.A. van Agtmael, S.A. Danner, et al. New developments in the diagnosis of bloodstream infections Lancet Infect Dis, 4 (2004), pp. 751-760.
  7. M. Christ-Crain, B. Muller Procalcitonin in bacterial infections –hype, hope, more or less? Swiss Med Wkly, 135 (2005), pp. 451-460.
  8. P. Schuetz, M. Christ-Crain, R. Thomann, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial.
  9. L. Bouadma, C.E. Luyt, F. Tubach, et al. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial Lancet, 375 (2010), pp. 463-474.
  10. M. Briel, P. Schuetz, B. Mueller, et al. Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care Arch Intern Med, 168 (2008), pp. 2000-2007.
  11. R.P. Dellinger, M.M. Levy, A. Rhodes, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012 Crit Care Med, 41 (2013), pp. 580-637.
  12. M. Pammi, D. Zhong, Y. Johnson, et al. Polymicrobial bloodstream infections in the neonatal intensive care unit are associated with increased mortality: a case-control study BMC Infect Dis, 14 (2014), p. 390.
  13. D.J. Diekema, S.E. Beekmann, K.C. Chapin, et al. Epidemiology and outcome of nosocomial and community-onset bloodstream infection J Clin Microbiol, 41 (2003), pp. 3655-3660.
  14. Cies, J.J. and Chopra, A. Procalcitonin use in a pediatric intensive care unit. Pediatr Infect Dis J. 2014; 33: 984–986.
  15. Downes, K.J., Weiss, S.L., Gerber, J.S., Klieger, S.B., Fitzgerald, J.C., Balamuth, F. et al. A pragmatic biomarker-driven algorithm to guide antibiotic use in the pediatric intensive care unit: the optimizing antibiotic strategies in sepsis (OASIS) study. (May 4. pii: piw023. [Epub ahead of print])J Pediatric Infect Dis Soc. 2016.
  16. Chiesa, C., Pacifico, L., Osborn, J.F., Bonci, E., Hofer, N., and Resch, B. Early-onset neonatal sepsis: still room for improvement in procalcitonin diagnostic accuracy studies. Medicine (Baltimore). 2015; 94: e123.