Introduction: Neonatal sepsis is a primary cause of newborn hospitalization, morbidity, and mortality. Common newborn sepsis symptoms are widely documented. Bacterial and non-bacterial sepsis in neonates may have different clinical presentations and laboratory characteristics. Again, newborn sepsis bacteria vary by region.

Objectives: This study investigated the current etiology of neonatal sepsis and the clinicopathological distinctions between bacterial and non-bacterial sepsis.

Materials & methods: This cross-sectional observational study was conducted in Bangladesh Shishu Hospital & Institute’s [former Dhaka Shishu (Children) Hospital] SCBU and NICU wards from May 2013 to June 2014. The study included 597 infants of both sexes who were diagnosed with clinical sepsis upon admission. We collected clinical and pathological data in all instances. Blood culture and susceptibility testing isolated and identified the microbial organism.

Results: After cultivation, only 20.6% of organisms were identified. The majority of bacteria were Klebsiella (30/63). Most identified Gram-negative bacteria were susceptible to Meropenem (100%), followed by Imipenem (75%) and Cefepime (75%). E. coli was the most delicate. All isolated S. aureus were vancomycin-sensitive (100%). Nearly all bacteria were resistant to ampicillin (93.7%), gentamicin (93.7%), and third-generation cephalosporins. Clinical characteristics of neonatal bacterial sepsis include lethargy (85.7%), poor feeding (81.0%), hyperthermia (71.4%), hypoperfusion (66.7%), and jaundice (66.7%). In bacterial sepsis, hemoglobin, lymphocyte, and platelet levels were significantly lower (p<0.05), whereas neutrophil and CRP levels were significantly greater (p<0.05).

Conclusion: Klebsiella dominates neonatal sepsis. The most sensitive antibiotics were meropenem and imipenem. Almost all gram-negative bacteria except E. coli were ampicillin, gentamicin, and third-generation cephalosporin-resistant. Bacterial sepsis caused greater lethargy, poor eating, heat, hypoperfusion, and jaundice. In bacterial sepsis, ANC, neutrophil, and CRP were greater, and hemoglobin, lymphocyte, and platelet were lower.

Neonatal sepsis is a clinical syndrome characterized by systemic signs of circulatory compromise caused by bacterial invasion of the bloodstream in the first four weeks of life,¹ and is more common in developing countries compared with developed countries.² In Bangladesh, the neonatal mortality rate (NMR) is 24 per 1000 live births, which accounts for about 60% of all under-five deaths.³ Neonatal sepsis is broadly divided into two types according to age of onset: early onset sepsis (<72 hours) and late onset sepsis (≥72 hours - 28 days). Early-onset sepsis is acquired during fetal life, delivery, or at the nursery. Late-onset sepsis is generally acquired by exposure to nosocomial pathogens (i.e., horizontal transmission).⁴ The reported incidence of neonatal sepsis varies from 7 to 38 per 1000 live births in Asia.⁵

The signs and symptoms of neonatal sepsis are nonspecific. These include fever or hypothermia, breathing problems like cyanosis and apnea, trouble feeding, drowsiness or irritability, hypotonia, seizures, a fontanel that bulges, poor perfusion, bleeding issues, abdominal distention, hepatomegaly, jaundice that can't be explained, and more.⁶ The complete white blood cell (WBC) count and differential count, the immature to total neutrophil (I/T) ratio, C-reactive protein (CRP), and the blood culture have all been used in the lab to diagnose neonatal sepsis.⁷ Blood culture has been considered the gold standard for confirmation of diagnosis.⁸ Since the spectrum of organisms that cause neonatal sepsis changes overtime and varies from region to region and hospital to hospital, even in the same city/country, it is necessary to conduct periodic surveillance to assess the changing pattern of organisms causing neonatal sepsis.² So, this study was undertaken to find out the etiologic pattern of neonatal sepsis in recent times, its susceptibility, and the clinicopathological differences between bacterial and nonbacterial sepsis in neonates.

This cross-sectional observational study was conducted from May 2013 to June 2014 in the ward, SCBU (Special Care Baby Unit), & NICU (Neonatal Intensive Care Unit) of Dhaka Shishu (Children) Hospital, Dhaka. The study looked at 597 admitted cases where the mother had things that put her at risk for sepsis, such as premature or prolonged rupture of the membranes for more than 18 hours, an intrapartum fever, a urinary tract infection, or foul-smelling vaginal discharge or liquor. The babies also had signs and symptoms of sepsis, such as low or high blood pressure, fatigue, apnea, bradycardia, tachycardia, hypoperfusion, trouble feeding, abdominal distension, tachypnea, and respiratory distress. All of the pathological tests, including Hb%, TLC & DC of WBC, platelet count, CRP, and RBS, as well as the isolation and identification of microbes, were done by cultured blood. Among which, 63 culture-positive bacterial isolates were identified and included in this study.

 Statistical analysis

Statistical analysis was done by using computer software SPSS (Statistical Package for Social Science) version 16.0. Laboratory data was analyzed by using an unpaired t-test. The level of significance was set at 0.05, and p < 0.05 was considered significant.

The preterm neonates comprised 56.8%. The male-to-female ratio was 2:1. Over one-third (36.2%) was delivered by lower uterine caesarian section (LUCS), and about one-third (32.2%) was delivered at home (Table 1).

Diagnosis of sepsis based on onset shows that the majority (84%) was late-onset sepsis (LOS). (Figure 1)

Figure 1 Diagnosis of sepsis based on onset.

During the study period, bacterial sepsis (positive blood cultures) was found in 63 (10.5%) of the 597 newborns who were thought to have clinical sepsis. 33 (52.4%) of these neonates were preterm, while 30 (47.6%) were term. Regarding clinical characteristics, lethargy in 54 (85.7%), poor feeding in 51 (81.0%), hyperthermia in 45 (71.4%), hypoperfusion in 42 (66.7%), jaundice in 42 (66.7%), cyanosis in 30 (47.6%), apnea in 27 (42.9%), abdominal distension in 27 (42.9%), tachycardia in 21 (33.3%), respiratory distress in 21 (33.3%), and bleeding in 12 (19.0%) cases were observed (Table 2).

Between the 63 neonatal sepsis cases where bacteria were found in the culture, the levels of hemoglobin, lymphocytes, and platelets were significantly lower (p<0.05), and the levels of neutrophils and CRP were significantly higher (p<0.05) in the bacterial group compared to the non-bacterial group. (Table 3)

Most of the isolated Gram-negative bacteria were sensitive to meropenem, followed by imipenem and cefepime. E. coli was the most sensitive organism. All of the isolated S. aureus were sensitive to vancomycin. (Table 4)

Neonatal infection is one of the major health problems in developing countries, including Bangladesh. Early diagnosis of neonatal sepsis is primarily based on clinical evaluation, but the diagnosis requires clinical-pathological-microbiological correlation.⁹

The present study was conducted to find out the common clinical characteristics of bacterial sepsis and make a comparative evaluation between bacterial and non-bacterial sepsis in terms of hematological, biochemical, and pathological characteristics along with the antimicrobial susceptibility of the isolated bacteria.

In this study, Gram-negative bacteria were responsible for most cases of neonatal sepsis. They were Klebsiella, Serratia, Acinetobacter, and E. coli in order of how common they were. Staphylococcus aureus was the most common Gram-positive organism. Similar findings were observed in a Bangladeshi study¹⁰ Klebsiella is emerging as a common bacterium in hospital settings.^11–13 But our study result slightly differs from the findings in a study in Iran¹⁴ and India,¹⁵ where Pseudomonas aeruginosa was the most common cause of neonatal sepsis, followed by Klebsiella pneumoniae and Escherichia coli.

In similar studies from Bangladesh, Nepal, and Pakistan, E. coli was the leading cause of neonatal sepsis, followed by Klebsiella pneumoniae.^9,12,15 Another study in India reported that more common causative organisms were Klebsiella, E. coli, Pseudomonas, Salmonella, and Staphylococcus aureus.⁴

The pattern of antibiotic sensitivity showed that Meropenem (100%) and Imipenem (81.2%) were the most sensitive antibiotics. Cefepime (75%), on the other hand, was the least sensitive. Most of the gram-negative bacteria isolates were resistant to ampicillin, gentamicin, and ceftriaxone. The other two studies in two tertiary care hospitals in Bangladesh showed similar results, with imipenem being the most sensitive antibiotic (91.6% & 79%, respectively) and ceftriaxone being the least sensitive one (25.3% & 22%, respectively).^16,17

A recent study in India also found imipenem being the most sensitive (93%) and ampicillin being the most resistant (97%) antibiotics.⁴ All of the Klebsiella species that were found to be resistant to ampicillin, gentamicin, and 3rd generation cephalosporin. This was in line with what another study in Bangladesh found.¹⁸

A study in Malaysia showed that 84% of Klebsiella and 69% of Acinetobacter were resistant to third- generation cephalosporin. The widespread use of cephalosporins within the last decade is believed to have selected resistant strains.⁵ Multidrug resistances of the causative organisms of sepsis are a rapidly emerging, potentially disastrous problem worldwide and has become a serious health problem in hospitals and the community. The situation worsens in developing countries due to the lack of control over antibiotic use.¹⁹

The current study found that the most common signs of bacterial sepsis were fatigue (86%), poor feeding (81%), high body temperature (72%), low blood flow (67%), and jaundice (67%). However, common features such as lethargy, poor feeding, hyperthermia, and jaundice were also observed. In India, a similar type of result was also observed.²⁰

There were big differences between the bacterial and non-bacterial groups in terms of hemoglobin, lymphocytes, platelets, and neutrophils and CRP (p<0.05 in each case). Again, measurement of serial CRP concentrations in serum may be useful in the treatment of suspected neonatal sepsis.²¹ However, a negative CRP can be useful in aiding the decision to discontinue antibiotics.²² A new study found that 83.5% of newborns had low platelet counts (<150×103/µl), which suggests that this is an important finding in neonatal bacterial sepsis. It was more severe in babies with gram-negative infections than gram-positive infections.²³ Among the gram-negative organisms, Klebsiella pneumoniae caused the maximum effect on various platelet parameters.²⁴

Klebsiella are now playing a dominant role in neonatal sepsis. Meropenem and imipenem were the most sensitive antibiotics. Almost all bacteria (gram-negative) were resistant to ampicillin, gentamicin, and third-generation cephalosporins except E. coli. Lethargy, poor feeding, hyperthermia, hypoperfusion, and jaundice were more prevalent in bacterial sepsis. Hemoglobin, lymphocyte, and platelet were significantly lower, and ANC, neutrophil, and CRP was significantly higher in bacterial sepsis.

During the treatment of neonatal sepsis due to Klebsiella spp., meropenem can be the first antibiotic of choice in a hospital setting.

Consent for publication

Not applicable.

Availability of data and materials

The dataset used in the current study is available from the corresponding author on reasonable request.

The authors are thankful to the reviewers for their thoughtful comments and suggestions that helped us to improve the paper.

The study is self-funded.

There was no conflict of interest.

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