Effect of clinical risk factors on bacteriological profile in neonatal sepsis: A descriptive cross-sectional study at a tertiary care center, Nepal

Introduction

Neonatal sepsis is an important etiology of neonatal mortality and morbidity. The global incidence of neonatal infection in a study was 7.3 per 1000 live births.¹ At national level, 16% of total perinatal death was because of neonatal sepsis in Nepal.² The common organism of neonatal sepsis are Group B Streptococci, Escherichia coli, Listeria monocytogenes, Staphylococcus sp, Enterococci, Klebsiella, Enterobacter, and Pseudomonas.³ The responsible major factors associated with early-onset neonatal sepsis are foul-smelling amniotic fluid, premature rupture of membrane, meconium-stained amniotic fluid, prematurity (<37 weeks gestation), low birth weight(<2.5kg), low Apgar score (<7)⁴ and mode of deliveries. The risk factors for late onset neonatal sepsis are invasive mechanical ventilation, intravascular catheterization, delay of early enteral feeding with breast milk, prolonged parenteral nutrition, cardio-pulmonary diseases, and hospital admission.⁵ The beta-lactam antibiotic combined with an aminoglycoside are mainstay of the treatment of neonatal sepsis. However, cephalosporin (cefotaxime) and a glycopeptide (vancomycin) have been frequently used to treat late-onset sepsis.⁶ The aim of this study is to find the incidence and risk factors associated with culture-positive neonatal sepsis, and common bacterial agents responsible for it.

Methods

Results

Our study revealed 2.79 kg±0.55 kg as the mean birthweight of neonates (Table 1). Likewise, the mean age of neonates who participated in the study at the time of neonatal sepsis diagnosis was 6.19 days with a standard deviation of 3.87 days. The neonates had an average gestational age of 37.64±1.27 weeks at the delivery time. Among 385 participants, more than half 225 (58.4%) were male, and the remaining were female.

Moreover, neonates with a weight less than 2500 g (low Birth weight, LBW) were 107 (27.8%) (Table 2). Only 8.3% (32) neonates were born prematurely (<37 weeks). Premature rupture of membrane was reported in 11.4% of mothers. The record showed only 28 mothers had foul-smelling amniotic fluid at the time of delivery. Most women had a normal vaginal delivery (222, 57.7%) followed by cesarean section (153, 39.7%).

Most of the neonatal sepsis diagnoses were clinically diagnosed (283, 73.5%) (Table 3). The remaining cases (102, 26.5%) were culture-positive neonatal sepsis.

According to chronology (Table 4), late neonatal sepsis was the predominant diagnosis (85.5%. 329).

Out of 102 culture-positive neonatal sepsis, Staph aureus was found to be the predominant pathogen (40, 39.2%) in culture isolates followed by Klebsiella (25, 24.5%) and Acinetobacter (16, 15.7%) (Table 5).

There is a statistically significant association between culture-positive neonatal sepsis and prematurity and foul-smelling amniotic fluid. While association with gender, types of neonatal sepsis (early or late), low birth weight, prematurity, and mode of delivery were insignificant. The premature rupture of membrane was four times more likely to have associations with culture-positive neonatal sepsis (OR=4.32, 95% CI: 2.20–8.47). Similarly, mothers with foul-smelling amniotic fluid were three times more likely to have culture-positive neonatal sepsis (OR=3.03, 95% CI: 1.32–6.92) (Table 6).

Discussion

The incidence of culture-positive neonatal sepsis was low in our study (26.5%). The results were close to a study done in Ethiopia (29.3%)⁸ and Tamil Nadu, India (26.2%).⁹ A study based in Nepali, showed 42.7% of cases were blood culture positive and 57.3% (110 cases) had culture-negative but clinically suspected neonatal sepsis with features of sepsis.¹⁰ The late type neonatal sepsis was major category in our study and about four times the early type of neonatal sepsis (73.5%). The findings are similar to a study in Australia where an incidence of early-onset and late onset neonatal sepsis was 0.51% and 1.3% per 1000 live births (2.5 times that of early neonatal sepsis).¹¹ This may partly be due to the high prevalence of risk factors associated with late neonatal sepsis. At a global level, the early onset type is 2.6 times more common with respect to late-onset neonatal sepsis according to a study in a systematic review and meta-analysis.¹² The bacterial spectrum demonstrated Staphylococcus aureus as a common pathogen to cause neonatal sepsis followed by Klebsiella. The results are different in other similar studies. Similar studies found Escherichia coli and Streptococcus agalactiae were the most frequent organisms associated with early-onset neonatal sepsis whereas Coagulase-negative Staphylococcus (co-NS) was the main culprit of late-onset neonatal sepsis.¹³ Similarly, a Nepali hospital based study found Klebsiella pneumoniae (34%) and Enterobacter spp. (25%) as the most common bacterial isolates.¹⁴ A study concluded that Escherichia coli was the predominant organism in both early-onset and late-onset type neonatal sepsis, however, Staphylococcus aureus was common in late-onset sepsis.¹⁵ A hospital study done in Saudi Arabia reported that the proportion of neonatal sepsis (clinical and culture positive) was almost equivalent in both males (52%) and females (48%).¹⁶ However, males had a slightly higher association (59%) with culture-positive sepsis in our study. The current study demonstrated that late-onset neonatal sepsis is nine times more associated with culture-positive sepsis. The above findings are supported by a Myanmar based study that concluded that neonates with late-onset sepsis (LOS) were more probable to have bacteriologically confirmed sepsis (45%) versus early onset sepsis (38%) (aPR: 1.2 (95% CI: 1.1–1.4)).¹⁷ But in a similar study, positive blood culture was found in equal proportion in early (47.1%) and late-onset (51.4%) neonatal sepsis respectively.¹⁸ As per our study, neonates with low birth weight constitute 23.5% of culture-positive neonatal sepsis. Furthermore, prematurity was present in 7.8% of all culture-positive neonatal sepsis. A similar study based in USA, concluded that the incidence of sepsis is significantly higher in premature infants, as well as those with very low birth weight (<1000 grams).¹⁹ The current study also showed normal vaginal and cesarean delivery modes were equally prevalent in culture-positive sepsis. A study completed in Nepal revealed the highest incidence of positive bacterial growth in male newborns (52.3%); 72 hours or more age (71.2%); low birth weight (62.7%); preterm (31.4%); and post cesarean cases (63.3%).¹⁰ Our study has demonstrated a statistically significant association between premature rupture of membrane (PROM) and foul-smelling amniotic fluid with culture positive type neonatal sepsis. A significant association was seen between blood culture positivity with foul-smelling amniotic fluid (p = 0.025), PROM (p = 0.016), birth asphyxia, and low birth weight (p = 0.003) in other similar studies.²⁰ A hospital based study showed neonatal sepsis was present in 2.7% of mothers who had early rupture on membranes.²¹ Similarly, in a study done in B.P. Koirala Institute of Health Sciences (BPKIHS) institute, PROM, meconium-stained and foul-smelling amniotic fluid, low birth weight, prematurity, and low Apgar score were significant risk factors leading to neonatal sepsis.²² Another study established an association of early type Neonatal Sepsis with PROM, foul-smelling amniotic fluid, traditional midwife handling, and maternal urinary tract infection (p < 0.05).²³ The major perinatal factors for neonatal sepsis in a similar study were prolonged labor, PROM, maternal pyrexia within 2 weeks (>38°C), foul-smelling amniotic fluid (13%), low apgar score (20%) and unhygienic or >3 sterile per vaginal examinations.²⁴ A meta-analysis and systemic review study based in India, found that male sex, outborn neonates, mechanical ventilation, prematurity, and PROM as significant clinical factors for neonatal sepsis.²⁵

Conclusions

Neonatal sepsis is prevalent mostly in an underdeveloped countries like Nepal. The contributing factors for the high burden of neonatal sepsis are premature rupture of membrane, foul-smelling amniotic fluid, prematurity, and low birth weight, unhygienic home delivery practices. Addressing the factors above, the incidence and its impact can be avoided dramatically. The role of pediatricians, nurses, hospital administrations and general awareness among mothers about hygienic practices during parturition is essential to minimize overall neonatal mortality and morbidity.

Patient consent

Parents’ written informed consent was received after full explanation of research purposes and processes.