PREDICTION OF CLINICAL

OUTCOMES OF NEONATAL SEPSIS

BY TIME TO POSITIVITY OF
BLOOD CULTURE

Dr SAURAV SHARMA
 INTRODUCTION

• Tremendous progress has been made in maternal and under-5 mortality over the last two decades. Neonatal
mortality is still a challenge in LMIC. 

• It accounts for more than two-thirds of all fatalities in children under the age of five. 

• One-fifth of global live births and more than a twenty five percent of neonatal deaths occur in India. The
current neonatal mortality rate (NMR) of India is 28 per 1000 live births. 

• A multisystem disease with a positive blood culture within the first month of life is characterized as neonatal
sepsis. It is one of the leading causes of newborn death worldwide including in India. 

• Neonatal sepsis has been related to increased medical costs, a longer hospital stay, and possibly poor long-
term neuro-developmental outcomes.
 INTRODUCTION contd

• Incidence of neonatal sepsis in tertiary care hospitals of Delhi is 2.2 % of live births and culture positive
sepsis is 0.95%. Reported mortality from all causes of sepsis is 25% and that from culture positive sepsis is
47% [DeNIS study].

• Blood culture is the gold standard for diagnosis of septicaemia and is performed in all cases of suspected
sepsis prior to starting antibiotics.  

• Now BACTEC and BACT/ALERT blood culture systems, it is now possible to identify bacterial growth
within 12-24 hours. Bacteria can be detected at a concentration of 1-2 colony forming unit (cfu) per mL using
these modern techniques.

• Time to positivity (TTP) is defined as the time period between blood incubation and the positive signal in the
blood culture system.
 INTRODUCTION contd
• Previous research underlined the importance of early laboratory diagnosis of bacteremia and shown that the
time to positive (TTP) of a blood culture can be used to predict clinical outcomes in adults with bacteremia.

• The correlation between TTP and clinical outcomes in neonatal sepsis patients, on the other hand, is
unknown.

• The goal of this study is to see if there's a correlation between TTP and clinical manifestations and outcomes
in newborn sepsis.
 OBJECTIVES
 Primary Objective:

•  To determine the correlation between time to positivity of blood culture and mortality in neonatal sepsis. 

 Secondary Objective:

• To determine the correlation between time to positivity of blood culture and septic shock, disseminated

intravascular coagulation(DIC) and meningitis in neonatal sepsis.

 METHODOLOGY
 Study design:

• Prospective Cohort Study 

 Study period:

• 18 months 

 Study population:

• Inborn neonates with culture positive sepsis

• 109 neonates 
 METHODOLOGY contd. 

 Inclusion criteria:

• All inborn neonates who have culture proven sepsis during neonatal period

 Definition of time to positivity:

• The time period between blood incubation and the positive signal in culture system, whereby all the individuals were
included only once.

• If multiple cultures came positive, the shortest TTP was recorded.

 Exclusion criteria

• Major congenital malformation

• Extreme prematurity (<28 weeks)

 SAMPLE SIZE

Considering the study by Yuanyuan Li et al with odds ratio of 17 for mortality in time to positivity (<17hrs), 95%
Confidence interval, 80% power, margin of error 5% and by using the formula, the sample size is 90. Formula
used is: - 

Where Zα is value of Z at two-sided alpha error of 5%, Z is a constant( set by convention according to the
accepted 'alpha' error and whether it is a one sided or two sided effect)In the above-mentioned formula σ is the
standard deviation (estimated) and Δ the difference in effect of two interventions which is required (estimated
effect size).
 RESULTS
• DEMOGRAPHICS:-

Gender Mode of delivery

100
60 80
80
55 60
40
50
20 29
45 0
Female Male LSCS VAGINAL ROUTE

                                                                                                                         
BIRTH WEIGHT:-
MINIMUM MAXIMUM MEDIAN
                   0.848 kg 4kg 2.1kg

GESTATION:-
MINIMUM MAXIMUM MEDIAN
                 28 weeks 39 weeks 35 weeks
 RESULTS contd.
Resusciatation MECONIUM
required STAINED LIQUOR
100 100
80
80
60
60
40
20 40
0 20
Not required Bag & Mask Bag & Tube 0
ventilation ventilation Negative Present

Risk factors for sepsis

100
80
60
40
20
0
Negative Present

        
 RESULTS contd.
DISTRIBUTION OF TYPE OF ORGANISMS:-
• Of the total 109 isolates, 57.74% were Gram negative and 42.26% were Gram positive pathogens.

FREQUENCY

   Klebsiella spp.
    Acinetobacter spp.
4%
7%    Escherichia coli
21%   Pseudomonas spp
    Burkholderia cepacia
16% Enterobacter
   Staphylococcus(MSSA)
  Staphylococcus(MRSA)
6% CONS
23%      Enterococcus
9% Streptococcus
2%
1%
1% 10%

                                                                              
 RESULTS contd. 
TIME TO POSITIVITY:-
• In the present study, the median time to positivity of blood culture of the 109 neonates was 16.5hrs (range 1.5hrs to
96hrs). For gram negative culture isolates, the median TTP was 12.5hrs (3 hrs to 70hrs) while for gram positive
culture isolates, the median TTP was 19hrs (1.5hrs to 96hrs).

TIME TO POSITIVITY MINIMUM MAXIMUM  MEDIAN

OVERALL 1.5 hrs 96 hrs 16.5hrs

GRAM NEGATIVE 3 hrs 70 hrs 12.5 hrs

BLOOD CULTURE

GRAM POSITIVE 1.5 hrs 96hrs 19 hrs

BLOOD CULTURE

                                           
 RESULTS contd. 
ROC curve of TTP to predict in- hospital mortality
 Sensitivity- 70.00%

 Specificity- 73.47%

 AUC(area under curve)- 0.731

                                
                                                                                                                      
 RESULTS contd.
We found 14hrs to be the optimal cut-off point (70% sensitivity, 73.47% specificity, area under curve= 0.731). Therefore
we selected 14 hrs as the standard cut-off. Based on this, patients were divided into two groups: Early detection group
(TTP≤ 14hrs) and Late detection group (TTP>14hrs).

                        
               
                                                                                            
RESULTS contd.

      
RESULTS contd.

      
 CONCLUSION
 Early Time to positivity (TTP ≤14hrs) in blood culture correlates with worse outcomes in neonatal sepsis
cases.

 Early time to positivity is associated with increased risk of in- hospital mortality in neonatal sepsis cases.

 Early TTP is also associated with increased risk of morbidities like septic shock and disseminated
intravascular coagulation.

 Gram negative organisms are significantly associated with early TTP.  

 Time to positivity of blood culture in neonates can be noted to anticipate and manage neonatal morbidity so
as to prevent mortality.