Get Permission Varshney, Shah, and Patel: Role of C-reactive protein in deciding duration of antibiotics therapy in neonatal bacterial infection in Maharashtra


Introduction

Neonatal bacterial infection (septicaemia) remains a significant cause of neonatal morbidity and mortality globally. The incidences of neonatal sepsis vary between 11 to 25 per thousand live births in India.1 Its clinical manifestations vary from being specific to subtle, testing the skills of a paediatrician. The inability to be certain of infection coupled with non-specific signs of the life threatening illness in neonates have resulted in wide spread use of antibiotics,2 aggravating the problem of antibiotics resistance. There is an increasing need for careful evaluation of indications and duration of treatment which in turn would shorten the length and cost of hospital stay and diminish the trauma and side effects of antibiotics.3

C-reactive protein (CRP) an acute phase reactant is synthesized in liver in response to inflammatory cytokines and may rise more than 1000 times during acute phase responses. It falls quickly after efficient elimination of microbial stimulus, due to its short half of life of 19 hours.4 Thus CRP may be used as parameter for the time period when antibiotic therapy can safely be discontinued in case of suspected neonatal septicaemia, which was the aim of present study in neonates <28 days.

Material and Method

60 (sixty) neonates admitted at paediatric ward of Vedanta Institute of Medical Science Palgarh, Maharashtra were studied.

Inclusive criteria

Neonates <28 days of life having birth weight more than 1500 grams with suspected septicaemia were included in the study.

Exclusion criteria

Neonates undergone surgery due to wound infection Neonates diagnosed as meningitis (because it requires longer treatment of antibiotics) were excluded from study.

Method

After admission bloodculture and sensitivity, Routine blood investigations, urine culture and sensitivity, chest x-ray, CRP were done. CRP was estimated within 24-48 hours of admission. Then neonates were classified as per the levels of CRP serum levels.

Neonates were kept up to 48 hours after stopping the antibiotics to observe the recurrence of clinical features of septicaemia. If there is no recurrence of symptoms of septicaemia within four weeks of discharge or the baby required antibiotics for different diagnosis other than septicaemia.

In the case of relapse the baby needed another course of antibiotics for suspected or proved septicaemia within 4 weeks after discharge.

To estimate the value of CRP as a parameter for guiding the duration of antibiotic therapy, the negative predictive value with respect to further treatment was determined.

The duration of study was about two years (July 2015 to August 2018).

Statistical analysis

Different clinical features, CRP levels, micro organisms were classified with percentage. The statistical analysis was made in SPSS software. The ratio of male and female were 2:1.

Results

Table 1: Clinical features of infected neonates – 48 (80%) born by vaginal delivery 4(6.6%) had history of maternal fever, 6(10%) had history of PROM, 23(38.3%) refusal of feeds, 20(33.3%) lethargy, 12(20%) poor cry, 12(20%) Tachypnea, 7(11.6%) Jaundice, 8(13.3%) Conjunctivitis, 7(11.6%) vomiting, 4(6.6%) excessive cry, 2(3.3%) pyoderma, 3(5%) abdominal distension, 3(5%) Hypothermia, 1(1.6%) fever, 2(3.3%) diarrhoea, 1(1.6%) umbilical sepsis.

Table 2: Study of organism observed in 26(43.3%). In the gram negative 20 (33.3%) neonates: 07(11.6%) klebesiella, 06(10%) E Coli, 05(8.33%) pseudomonas, 02(3.33%) Acinetobacter. 6(10%) neonates had gram positive bacilli – 4 (6.66%) staphylococcus aureus, 1(1.66%) Coagulase Negative Staphylococci (CoNS), 01(1.66%) had Haemolytic streptococci.

Table 3 : CRP guided distribution of treatment, relapse rate in two groups and correlation with blood culture. In group A (28) had CRP value was <6 -duration of therapy was <3 days and No. bacilli, No relapse was observed.In group B CRP value was >6 in 32 neonates, 2 patients treated for 5 days, 17 patients for 7 days and 13 patients for 11 days. Blood culture was positive for 14 neonateswith 7 days therapy, for 12 neonates with 11 days duration therapy and no relapse was observed.

Table 4: overall duration of treatment for<7 days observed in group I were 28, and group II were 2 and total number were 30. Duration of > 7 days therapy observed in group 1 were 17 and group 2 were 13 and total number were 30.

Table 1

Clinical features of suspected infected neonates

S.No.

Particular

No. of neonates

Percentage

1

Vaginal delivery

48

80

2

Material fever >100.4 F

4

6.6

3

PROM > 18 hrs (premature Rapture of Membrane)

6

10

4

Refusal feeds

23

38.3

5

Lethargy

20

33.3

6

Poor Cry

12

20

7

Tachypnea

12

20

8

Jaundice

7

11.6

9

Conjunctivitis

8

13.3

10

Vomiting

7

11.6

11

Excessive Cry

4

6.6

12

Pyoderma

2

3.3

13

Abdominal distension

3

5

14

Hypothermia

3

5

15

Fever

1

1.6

16

Diarrhoea

2

3.3

17

Umbilical sepsis

1

1.6

Table 2

Study of micro organism

Particular

Organism

No. of cases

Percentage

Gram Negative (n=20) (33.3%)

Kelbesiella

07

11.6

E. Coli

06

10

Pseudomonas

05

8.33

Acinetobacter

02

3.33

Gram Positive (n=6) (10%)

Staphylococcus

04

6.66

Aurous

01

1.66

CONS and αHemolytic streptococci

01

1.66

Total

26

Table 3

CRP guided distribution of treatment relapse rate in two groups and correlation with blood culture results

CRP Value

Groups

Duration of therapy No of cases

Blood culture +ve

Relapse

Nagative predicative value (%)

<6

Group A (28) 46.6

<3 days

Nil

Nil

100

>6

Group B

5 days (2)(3.3%)

Nil

Nil

100

(32)

7 days (17)(28.3%)

14

Nil

100

(53.3)

> 11 days (13)(21.6%)

12

Nil

100

Table 4

Over all durations of treatment with CRP guided treatment

Group

Duration of treatment

+

< 7 days

> 7 days

Group 1

28

17

Group 2

2

13

Total

30

30

Discussion

In the present study the role of CRP in deciding duration of antibiotic therapy in neonatal bacterial infection in Maharashtra region. The clinical features were 48 (80%) born by vaginal delivery, 4(6.6%) had history of maternal fever > 100.4 F, 6(10%) had history of Premature rupture of membranes (PROM) >18 hrs, 23(38.3) with refusal feeds, 20(33.3%) were lethargic, 12(20%) had poor cry, 12(20%) had tachypnea, 7(11.6%) had jaundice, 8(13.3%) had conjunctivitis, 7(11.6%) had vomiting, 4 (6.6%) had excessive cry, 2(3.3%) had pyoderma, 3(5%) had abdominal distension, 3(5%) had Hypothermia, 2 (3.3%) had diarrhoea, 1(1.6%) had fever, 1(1.6%) had umbilical sepsis (Table 1). In the study of organism 20 neonates (33.3%) had gram negative and 6 (10%) had gram positive organisms (Table 2). In CRP guided distribution of treatment In CRP value >6 group-1 had 28(46.6%) neonates duration of therapy was < 3 days No positively of blood culture and no relapse was observed.

In CRP level >6 32(53.3%) neonates were observed. Duration of therapy was 5 days for 2(3.3%) neonates and 7 days for 17(28.3%) and 11 days 13(21.6%) neonates (Table 3). The overall duration of treatment for <7 days observed in group I were 28, and group II were 2 and total number were 30. Duration of > 7 days therapy observed in group 1 were 17 and group 2 were 13 and total number were 30(Table 4). These findings were more or less in agreement with previous studies. 5, 6, 7

As Bacterial infections stimulate the hepatocytes to produce CRP a non-specific immune response, which is useful clinical marker for the individual host-pathogen interaction. Since the half-life of CRP is less than 3 days a rapid fall is seen with successful antibiotic therapy. 8 The diagnosis of neonatal septicaemia is difficult to establish based on the clinical criteria alone because of its subtle, variable and non-specific signs and symptoms. The use of safe and effective antibiotics has significantly contributed to decrease neonatal mortality.9 However, the fear of missing a case of neonatal septicaemia, with its serious outcome had led to overuse of antibiotics in this age group of neonates. It is also reported any bacterial infection may ultimately turned to septicaemia, if the mother was infected during pregnancy or before delivery. 10 Hence CRP plays vital role in duration of treatment.

Summary and Conclusion

The role of CRP is significant in deciding the duration of antibiotics therapy in neonates. It is safer as compared to other, but still further study is required for other marker because CRP cannot influence gestation age infections, non-infectious confounders. Moreover exact mechanism of elevation and decrease of CRP values during infections is still unclear.

Conflict of Interest

The authors declare no relevant conflicts of interest.

Source of Funding

None.

References

1 

V K Poul M Singh Singh M Neonatal sepsisMedical emergencies in children 2nd Edn.Sagar Publication New Delhi19981158

2 

AA Fanaroff BJ Stoll LL Wright WA Carlo RA Ehrenkranz AR Stark Trends in neonatal morbidity and mortality for very low birthweight infantsAm J Obstet Gynecol20071962147.e1810.1016/j.ajog.2006.09.014

3 

BE Murray Can antibiotic resistance be controlled?J Med19943301712293010.1056/NEJM199404283301710

4 

D Vigushin M Pepys PN Hawkins Metabolic and scintigraphicstudies of radio-iodinated human C-reactive protein in health and diseaseJ Clin Invest19931213515710.1172/JCI116336

5 

RD Feign JD Cherry Text book of paediatric infections disease 3rd Edn.Philadelphia WB Saunders 19941025

6 

Gb - Avery Diseases of New born infantPhiladelphia WB Saunders 199198105

7 

UK Namdeo HP Singh VJ Rajput KK Shrivastava S Namdeo Bacteriological profile of neonatal septicemiaInd Pediatr198724536

8 

RK Jaswal RK Kaushal A Goel K Pathania Role of C-reactive protein in deciding duration of antibiotic therapy in neonatal septicemiaIndian Pediatr20034098803

9 

S Ehi B Gering P Bartmann J Högel F Pohlandt C-reactive protein is a useful marker for guiding duration of antibiotic therapy in suspected neonatal bacterial infectionPediatrics19979922162110.1542/peds.99.2.216

10 

JS Gerdes RA Polin Sepsis screen in neonates with evaluation of plasma fibronectinPediatr Infect Dis J198765443610.1097/00006454-198705000-00005



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Article History

Received : 03-05-2022

Accepted : 23-05-2022


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https://doi.org/10.18231/j.ijmpo.2022.020


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