Serum Procalcitonin and Neutrophil Toxic Granules Guided Management of Post-Operative <i>K. pneumoniae</i> Septic-Shock in Laminectomy—A Case Report

doi:10.4236/aid.2012.23011

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Advances in Infectious Diseases, 2012, 2, 72-75

http://dx.doi.org/10.4236/aid.2012.23011 Published Online September 2012 (http://www.SciRP.org/journal/aid)

Serum Procalcitonin and Neutrophil Toxic Granules

Guided Management of Post-Operative K. pneumoniae

Septic-Shock in Laminectomy—A Case Report

Indira Chivukula1, Paul K. Marx1, Kamaraju S. Ratnakar2, G. Subbaiah3, Venkataraman Sritharan1*

1Molecular Diagnostics and Biomarkers Laboratory, Department of Laboratory Medicine, Global Hospitals, Hyderabad, India; 2Aca-

demic and Research, Global Hospitals, Hyderabad, India; 3Institute of Orthopedics and Spine Surgery, Hyderabad, India.

Email: *[email protected]

Received April 3rd, 2012; revised May 5th, 2012; accepted June 7th, 2012

ABSTRACT

Introduction: We still rely on clinical diagnosis for initiating empirical antibiotic therapy and await blood culture for

confirmation of infection, species identification and drug sensitivity. Differential blood cell count (WBC and neutro-

phils) and recording of toxic granules in the neutrophils are established methods for indirect diagnosis of infection

though they are not used in the diagnosis of sepsis per se. Serum Procalcitonin is considered as a good biomarker in the

management of sepsis. Materials and Methods: Whole blood and serum were used for laboratory analysis. We have

combined the detection of toxic granules in the peripheral blood smear and serum PCT levels for diagnosis and moni-

toring the recovery of a patient with septic shock. A 63 year old laminectomy patient was transferred 2 days after the

surgery to our hospital with several co-morbidities and complications. He was in septic shock and was put on Continu-

ous Renal Replacement Therapy, with ionotropic support and IV fluids via nasogastric feeding and administration of

Activated Protein C. Blood culture and daily measurements of serum Procalcitonin, differential blood cells count, and

observation of toxic granules in neutrophils were done. Results: The blood culture showed infection due to K. pneumo-

niae resistant to carbapenems. WBC and Neutrophil counts were quite variable and showed incoherent response to

treatment. Serum PCT was 24.57 ng/mL on the next day of admission and it peaked at 30.2 ng/mL on day 3. Its level

started decreasing from the 4th day. Toxic granules disappeared when serum PCT levels reached < 1 ng/mL. The patient

responded well to treatment and he was discharged on the 16th day upon request. Conclusion: This case is presented as

an example of managing sepsis with a combination of a conventional hematology marker and a modern biomarker. Re-

source poor hospitals with inadequate microbiology services, may evaluate and use these two biomarkers not only for

the total management of sepsis but also to reduce the cost of critical care.

Keywords: Sepsis; Procalcitonin; Toxic Granules

1. Introduction

Sepsis is the most common cause of death in nonco ron ary

Intensive Care Units (ICU) with a reported mortality of

29% in the US and 27% in Europe [1], particularly in

elderly, immuno compromised/suppressed and critically

ill patients. Approximately, 46% of critical care patients

and 53% of hospital based patients die due to severe sep-

sis in India [2].

Many laboratory results are indistinguishable between

patients with Systemic Inflammatory Response Syndrome

(SIRS) and sepsis or septic shock with multi organ fail-

ure. Differential diagnosis of infection and inflammation

is very difficult in the absence of cu lture results. Conv en-

tional laboratory indicators for infection, like WBC/ neu-

trophils count and serum C-reactive protein (CRP), are

non-specific and are often influenced by factors other

than infection. Therefore, their status may not directly

correlate to either progression or control of infection.

Recent reports indicate that absolute neutrophil counts

and morphological changes like toxic granules may be

better indicators of systemic infection than band count

[3]. Since it is desirable to have high sensitivity we used

two markers, a biomarker and hematology marker for

detecting and monitoring systemic infection (sepsis).

Resource poor countries may not have a well equipped

microbiology laboratory to do blood culture. Hence, there

is an urgent need for biomarkers for a cost-effective and

reliable management of sepsis.

Procalcitonin (PCT) has been pr oposed as a more spe-

cific and better prognostic mark er than differential blood

*Corresponding a uthor.

Serum Procalcitonin and Neutrophil Toxic Granules Guided Management of Post-Operative K. pneumoniae

Septic-Shock in Laminectomy—A Case Report 73

cell count and CRP in the management of sepsis [3-6].

Serum PCT based algorithm has been designed and used

to guide the management of sepsis in many countries in

Europe and the USA [7-10]. Several formats are avail-

able for the determination of serum PCT, 1) a semi quan-

titative lateral flow rapid test device called PCT-Q (> 0.5

ng·ml–1); 2) a fairly sensitive (>0.2 ng·ml–1) Lumino Im-

muno Assay (LIA) and 3) a highly sensi ti ve (<0.1 ng·m l –1)

KryptorTM Procalcitonin assay (all manufactured by

BRAHMS Diagnostica GmbH, Thermo Scientific Inc) in

several countries including India. Procalcitonin test has

been introduced in India only a couple of years ago and

there have not been many studies to evaluate its useful-

ness in the diagnosis or management or stratification of

sepsis in India. In India, quantitative serum PCT assay

(LIA) has been evalua ted in infectious pyelo nephritis [11]

in children, infective febrile conditions in intensive care

units [12] and a semi-quantitative rapid test device was

used in two other studies [13,14]. Though serum PCT

levels are not elevated in viral infections [15], it is sig-

nificant that this study demonstrates that serum PCT re-

sponds strongly in a HIV positive patient who had sec-

ondary bacterial infection.

2. Case Presentation

63-year-old male, was presented in the emergency of

Global Hospital, Hyderabad with hypotension (60/40

mmHg) and hypoglycemia (60 mg/dl), urinary retention

(dysuria), consciousness but with slurred speech. The pa-

tient had history of laminectomy + decompression C2 -

C7, Coronary Artery Disease with Tri Vascular Disease,

hypertension, Diabetes Mellitus, HIV + and he was being

transferred and admitted in ICCU of Global Hospitals

due to complications, for further evaluation and treatment.

The treatment included Continuous Renal Replacement

Therapy, with ionotropic support and IV fluids via na-

sogastric feeding and administration of Activated Protein

C. Regular monitoring was done for septic-shock. His

hospital stay was uneventful and he was discharged on

the 16th day.

Whole blood in EDTA was collected for hemogram

analysis. The WBC and neutrophil coun ts increased con-

tinuously and so did the serum creatinine during early

part of his stay. The blood culture showed K. pneumo-

niae resistant to carbapenams and he was treated with

antibiotics Tigecyclin, Colistin. Results of the laboratory

investigations are summarized in Table 1.

Serum was separated from clotted blood and serum

procalcitonin was assayed every 24 h by BRAHMS LIA

method. Hematology parameters like hemoglobin, he-

matocrit, MCV (mean corpuscular volume), MCH (mean

corpuscular hemoglobin), MCHC (mean corpuscular

hemoglobin concentration) were measured using auto-

mated 5 part hematology analyzer. Peripheral blood

smears were stained with Leishman Stain and the toxic

granules in the neutrophils viewed at 1000× magnifica-

tion. Serum PCT was assayed in 11 consecutive 24 h

samples (Figure 1). The patient was discharged on the

16th day on request and he was stable at the time of dis-

charge.

3. Discussion

Our intention was to determine the association (if any)

between serum PCT levels and neutrophil toxic granules

and their usefulness as surrogate biomarkers in the man-

agement of septic shock. This case study mainly focuses

on neutrophil toxic granules profile and the serum PCT

levels during the course of septic-shock in an immuno-

supressed (HIV +) patient. Our data suggest that there is

secondary systemic bacterial infection. Blood culture

done on day 3 of admission confirmed carbapenam re-

sistant K. penumoniae infection. Tigecyclin and Colistin

were administered from day 3. Blood culture was not

done on days 4 - 6. Blood cultur e done on 7th day showed

“no growth”. There was positive correlation between

serum PCT and toxic granules. The toxic granules were

present on all days and disappeared from 12th day when

PCT levels reached 0.5 ng·mL–1. Serum PCT increased

during first 3 days of admission and started decreasing

immediately after administration of Tigecyclin and

Colistin, indicating infection control (Figure 1). Serum

PCT peaked on the 3rd day (30.32 ng·mL–1) and was as-

sociated with severe leukocytosis, thrombocytopenia,

neutrophilia with shift to the left and increased levels of

blood urea and creatinine indicating multi organ in-

volvement. Clinical improvement in the patient from day

4 onwards was underlined by improvement in the PCT

Figure 1. Association between serum PCT levels and toxic

granules in septic shock (+) and (–) indicate presence and

absence of toxic granules in neutrophils (Indira C et al. 2011).

Serum Procalcitonin and Neutrophil Toxic Granules Guided Management of Post-Operative K. pneumoniae

Septic-Shock in Laminectomy—A Case Report

Table 1. Laboratory data.

BIO-MARKER HEMATOLOGY MICRO BIOCHEMISTRY

Day

in ICU sPCT

ng/ml Toxic

Granules Hb

(gm%) Platelets WBC Neut

(%) Culture Urea

(mg/dl) sCreat

mg/dl)

1 ND (+) 10.2 1.38 25060 92 K.p 136 2.1

2 24.57 (+) 11.4 0.6 26480 89 CR 90 1.9

3 30.32 (+) 9.8 0.31 32050 88 ND 119 3.6

4 26.86 (+) 8.5 0.51 20500 88 ND 124 3.6

5 16.35 (+) 9 0.65 9970 82 ND 110 3.4

6 7.27 (+) 9.3 0.55 11020 80 ND 106 3

7 5.62 (+) 9.6 0.54 16390 86 No growth 92 2.2

8 2.37 (+) 11.4 0.55 18360 86 No growth 110 2.1

9 2.21 (+) 11.8 0.66 16240 83 No growth 118 1.8

10 1.93 (+) 10.1 0.34 12520 80 No growth 101 1.9

11 0.71 (+) 8.3 0.97 7010 66 No growth 85 1.6

12 0.5 (–) 7.3 1.18 6160 54 No growth 110 1.9

13 ND (–) 7.5 1.59 6200 48 No growth 110 1.7

14 ND (–) 7.6 2.27 8200 65 No growth 110 1.9

15 ND (–) 7.7

2.85 7420 58 No growth 81 1.4

16 ND (–) 7.1 3.13 6130 54 No growth 73 1.3

ND: Not Done; (+) Toxic Granules Detected; (–) Toxic granules Not Detected; Hb = Hemoglobin; ICU = Intensive Care Unit; sPCT: serum Procaocitonin;

sCreat: serum creatinine; Hb: Hemog lobin; K.p: K. pneumoniae; Neut: Neutrophil.

levels, urea, creatinine and disappearance of the toxic

granules on the 12th day. Serum PCT was not done be-

yond 12th day as there was no fever and to reduce the

cost of investigations. The patient recovered completely

and was discharged on the 16th day on request.

4. Conclusion

Surrogate biomarkers help to monitor changes at mo-

lecular level during infections. We compared the toxic

granules in neutrophils with the levels of serum PCT

every 24 h. The changes in the levels of serum PCT and

the toxic granules represented more closely the status of

infection (severity) in the patient compared to WBC and

neutrophil counts. Toxic granules when scored and quan-

titated based on the density and distribution in the cyto-

plasm of neutrophils would enhance the predictive value.

Serum PCT levels and toxic granules may be considered

for early diagnosis, assessment of severity and for termi-

nating antibiotic treatment in sepsis. It will be useful to

investigate the outcome prediction for the patient when

serum PCT and toxic granules are used regularly every

24 h to monitor response to treatment instead of culture.

This may eventually help to improve outcome pred iction

and reduce the cost of critical care. Resource poor labo-

ratories/hospitals where good microbiology facility is not

available may find it viable to use serum PCT and toxic

granules in the management of sepsis and septic shock.

5. Acknowledgements

We acknowledge CPC Diagnostics, Chennai for supply-

ing us the PCT LIA kits at a discounted cost for the

study.

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