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Research Article | Open Access2023|Volume 5|Issue 1| https://doi.org/10.37191/Mapsci-2582-4937-5(1)-034

Risk Factors and Microbiological Outcome in Neonatal Sepsis: A Clinical Study

Venugopal Reddy I1* and Vuppu Dinesh Kumar2

1Medical Director and Consultant Paediatrician, Ovum Hospital, Bangalore, India

2Consultant Paediatrician, Ovum Hospital, Bangalore, India

*Corresponding Author: Venugopal Reddy I, Medical Director and Consultant Paediatrician, Ovum Hospital, Bangalore, India.

ReceivedMar 20, 2023RevisedMar 31, 2023AcceptedApr 10, 2023PublishedApr 30, 2023
Abstract

Infection is the predominant cause of neonatal deaths universally. Neonatal deaths (30-50%) every year is caused due to sepsis. Due to nosocomial infections and their associated morbidities, cost and mortality, betterment of neonatal outcomes is complicated as hospitals in developing countries are at major risk for the transmission of infection. The present study aimed to analyse sepsis risk factors and microbiological outcome in the NICU and post-natal ward.

The study diagnosed the affected neonates as earliest possible so that suitable antibiotic treatment can be done without adding to the burden of antibiotic resistance. In this study, 94% of babies with neonatal sepsis were discharged and 6% of babies succumbed to the illness. Low birth weight between 1500-2500 grams was noted as an important contributing factor to sepsis in babies. PROM was found to be greater than 18 hours in (46%) of cases. Klebsiella pneumoniae was the common pathogen amongst gram negative bacteria in the present study and thus was the common cause of septicemia in neonates, and Coagulase negative Staphylococcus and Staphylococcus aureus were common bacteria among the gram-positive bacteria. A higher mortality rate in cases of late onset sepsis was observed and was explained probably due to prolonged NICU stay, multiple interventions such as mechanical ventilation, umbilical venous catheterization, and central lines.

Keywords

Neonatal Sepsis; Infection; Microbiological analysis; Antibiotics; Neonatal intensive care unit

Introduction

Infection is the predominant cause of neonatal deaths universally. Neonatal deaths (30-50%) every year are caused due to sepsis; thus, sepsis is most common factor contributing to the neonatal mortality. The common reason of is the and is responsible for about [1]. In neonatal syndrome the causes and reasons of infection are analyzed for the characterization of clinical syndrome either with or without protecting bacteremia during the neonatal period [2]. It includes multiple systemic infections such as osteomyelitis, urinary tract infections, septicemia, pneumonia, meningitis, and arthritis [3]. Clinical presentations of sepsis have been recognized in two forms. An early onset sepsis, which shows from 0-3 days of life, exhibiting pneumonia and respiratory distress. The perinatal risk factors are mostly the same. After 3 days of life is presents by late onset sepsis, which is similar to infections in hospital and commonly presents with pneumonia and septicemia [1]. Evaluation for neonatal sepsis and its medication remains a common practice in a newborn nursery. The ‘Rule out Sepsis’ in neonatology remains persistently unpleasant during diagnosis. It is certainly the second usual neonatal diagnosis after ‘well baby’ [4]. Despite the new advances in antibiotic therapy, neonatal sepsis is a main reason for high morbidity and mortality rates [5]. Due to nosocomial infections and their associated morbidities, cost and mortality, betterment of neonatal outcomes is complicated as hospitals in developing countries is at major risk for the transmission of infection [6,7]. Thus, it is imperative to closely monitor the antibiotic sensitivity pattern of pathogens and pattern of microbial growth in the NICU so as to rationale the antibiotic policy that suits every neonatal intensive care unit. In India, increasing issue of use and abuse of antibiotic in newborn care resulting in the increase of resistant bacteria [8]. Multi-drug resistance has been reported in developing countries and some of the developed countries such as Europe and Australia, North America [8]. The present study aimed to analyse sepsis risk factors and microbiological outcome in the NICU and post-natal ward. The study was done to diagnose the affected neonates as earliest possible so that suitable antibiotic treatment can be done without adding to the burden of antibiotic resistance.

Aims and objective

1. To Assess the neonatal sepsis profile pattern microbiologically

2. To assess the neonatal sepsis associated risk factors rationally.

Historical aspects

Gueinot was the first to consider the dangers of infection in 1872. Budin discovered the importance of defective organization of nursing service in preterm lead to sepsis. It was affirmed by the end of the 19th century that four chief infection sources respiratory system, gastrointestinal tract and skin, umbilicus [9]. In the early 1900s there were high mortalities and morbidities in neonates due to diarrhea and respiratory infections. With the discovery of antibiotics, mortality and morbidity came down from 90% in mid 1900s to 18% in the late 1900s [9].

Neonatal sepsis classification

Neonatal sepsis is classified into following:

1. Early onset sepsis: It is present within 72 hours of life as a fulminant, multisystem illness because of the acquired bacteria before and during delivery [10]. Gram-negative bacteria and Group B organisms including Listeria monocytogenes Haemophilus influenzae, Escherichia coli, Streptococcus are the common bacteria. Low birth weight, premature rupture of membranes (>18 hours), meconium-stained liquor, foul smelling liquor, prematurity, prolonged labour and perinatal asphyxia are the major factors responsible for increased risk in case of early onset of sepsis. The important infection source is the mother’s genital tract. Organisms usually are gram-negative organisms and group B Escherichia coli, Streptococci.

2. Late onset sepsis: It occurs due to acquired bacteria post-delivery (community sources or nosocomial) and is fulminant present with an aggressive infection. Late onset sepsis has a varied presentation. Organisms involved include Escherichia coli, Coagulase Negative Staphylococcus, Staphylococcus aureus. Factors associated with late onset sepsis include prelacteal feeds, poor cord care, poor hygiene, bottle feeding, and Nosocomial infections are associated with prematurity, mechanical ventilation, invasive procedures [1].

Epidemiology

The occurrence of neonatal sepsis depends on the geographic area that differs within the country and from one country to another country [10]. In the developed countries neonatal sepsis cases occur 1-4 cases per 1000 live births [3]. In India, the incidence of neonatal sepsis as per the National Neonatal Perinatal Database 2002-03 is 30 cases per 1000 live births [11]. Klebsiella is the major organism responsible for sepsis in India, followed by Staphylococcus aureus and E. Coli [11]. The survival of babies of lower birth rate and gestational age, nosocomial infections are on the rise due to prolonged NICU stay and multiple interventions.

Risk factors

Risk factors of neonatal sepsis include maternal and neonatal factors.

Maternal risk factors

1. Premature rupture of membranes (PROM): A history of PROM in mother greater than 18 hours increases sepsis risk in neonates by 10-fold to a rate of 2% for suspected sepsis and 1% for proven [12]. In mothers with premature membranes rupture, the invasion rate of microbial invasion may be as high as 75% [13]. The neonatal sepsis attack rate can be as more than 20% if the pathogen is recovered from amniotic fluid [14]. When intrapartum prophylaxis is not given, Infants born to women with PROM that has Group B Streptococci colonization have of 33% to 50% of estimated attack rate [15].

2. Chorioamnionitis: It is one of the main causes of neonatal sepsis. Chorioamnionitis in the mother increases the risk of sepsis by 3-30% [16]. Septicemia in utero is initiated when infected amniotic fluid is inhaled or swallowed by a fetus. Contaminated skin and mucosal surfaces are also sources of neonatal sepsis. Chorioamnionitis includes following maternal fever >100.4 °F with ≥ 2 with:

• Maternal leukocytosis

• Foul smelling vaginal discharge

• Uterine tenderness

• Fetal tachycardia

Meconium-stained amniotic fluid, many digital vaginal examinations with ruptured membranes, Low parity, spontaneous labor, uterine monitoring or internal fetal, longer length of labor and membrane rupture, and presence of genital tract microorganisms such as mycoplasma are major risk factors of Chorioamnionitis [17].

3. Maternal UTIs: Antepartum UTI has been implicated as a major risk factor for low birth weight or premature birth and perinatal death [18]. Emamghorashi, et al., study showed that In Iran, maternal urinary tract infection and neonatal septicemia are associated [19].

Neonatal factors

1. Prematurity: There is a 3-10-fold increase in the incidence of infection with prematurity. Prematurity predisposes the neonate to infections from maternal genital tract. Low immunity and immunoglobulin levels of premature neonate is the major reason behind decreased transplacental maternal IgG transfer, thus increasing the sepsis risk in preterm infants [14].

2. Low birth weight: Sepsis is an important cause of morbidity and mortality especially in infants with low birth weight [20]. 25% of VLBW infants are affected with sepsis internationally. Birth weight and gestational age are inversely proportional to the sepsis cases. Multiple episodes of sepsis are observed in infants of lower gestational age and birth weight probably due to reduced immune response [21,22].

3. Sex: Sepsis is more common in males than in females. As females exhibit larger genetic diversity than males, one of the X chromosomes in females gets inactivated that is involved in controlling thymic function and immunoglobulin synthesis which further results in a greater heterozygosity of antibody response.

Environmental factors

Following the birth canal, the baby gets exposed to flora in nursery, at home and of individual care takers [22]. Hence, environmental factors include:

1. Place and mode of delivery

2. Interventions done in the NICU

3. Prolonged NICU stay

4. Harmful cultural and social practices

Laboratory diagnosis

Neonatal sepsis can be evaluated using two types of tests:

1. Non-specific screening test

2. Specific diagnostic test

Non-specific screening test

This screening test is done to identify a septic neonate may not specifically identify the organism, but the result promptly indicates the possibility of infection.

These includes:

1. Total WBC count: It has been found that leucopenia <5000 cells/mm3, Absolute neutrophil count <1500/mm is associated with sepsis [23]. In a study done by Hornik, et al., it was found that high WBC counts were responsible for EOS. Sensitivity was poor with high specificity for WBC counts <5000/mm3 and sensitivity was poor for WBCs <1000/mm3 [24].

2. Immature to total neutrophil count ratio: It is the ratio of immature cells/total of mature and immature cells. Immature cells include band forms, metamyelocytes, myelocytes. Value above 27% in term babies and values of greater than 20% in preterm newborns is indicative of sepsis [25].

3. Micro-ESR: It is not a very reliable marker of infection. To do, Micro ESR capillary blood is collected in a pre-heparinized micro hematocrit tube and after one hour reading is calculated. Value >3 in the first week of life and >10 after 7 days is indicative of sepsis [10].

4. C-Reactive Protein: CRP (C-Reactive Protein) test is an easily available automated test. CRP are acute phase reactant proteins that are synthesized in the liver as an inflammation response. An elevated CRP suggests sepsis [26]. CRP of more than 10mg/dl suggests sepsis. 70-93% is the Sensitivity and 41-98% Specificity. 6-83% and 97-99% are Positive and negative predictive values respectively. Poor specificity is because it can be positive in perinatal asphyxia, fetal distress, maternal fever, intraventricular hemorrhage and meconium aspiration [27].

5. Platelet count: Thrombocytopenia is used as a non-specific marker for sepsis in neonates [28,29]. Guida, et al., study observed that 54% of cases of neonatal sepsis were associated with thrombocytopenia [30].

6. Acute phase reactants: In relation to neonatal sepsis, acute phase proteins Orosomucoid, Haptoglobin, Neopterin, Lactoferrin, Fibronectin, and α1 antitrypsin were analyzed. Most of the markers evaluated showed a significant increase in infected infants. However, clinically none of the marker is used in a routine basis due to their limited accuracy in diagnostics or due to presence of better and more sophisticated tests [31].

Sepsis screen

In the year 1980 Philip, and in the year 1987, Gerdes proposed a combination of tests which could predict neonatal sepsis (Table 1) [32]. Currently, the practical sepsis1 screen is being followed (Table 2) (Figure 1 and 2).

The combination of these tests gives almost 100% sensitivity with 83% specificity, 27%, and 100% of positive and negative predictive value respectively [23].

Therefore, if two or more test parameters are not in range, neonate should be considered as a positive screen started on antibiotic medication [1].

Author

Year

Test

Sensitivity

Specificity

Philip et al [32]

1980

Any two test of the following:

M.ESR >15 mm3

CRP >8mg/l

WCC <5000

ITR >0.2

Haptoglobin >25 mg/dl

93%

88%

Gerdes et al [33]

1987

Any two positive test of the following:

WBC<5000/mm3

I/T ratio >0.2

CRP >10mg/l

100%

83%

Table 1: Combination of tests to predict neonatal sepsis.

Absolute neutrophil count

Mouzinho’s chart for VLBW infants [25]

Low counts as per Manroe chart for term [23] (Figure 1 and 2)

I/T ratio

>20% in preterm babies, >27% in term babies

Micro ESR

Age in days +3 in the First week

>10 following 1st week of life

CRP

>10 mg/dl

Table 2: Currently followed the practical sepsis screen [1].

Picture 1.png

Figure 1: Absolute Neutrophil Count reference range [24].

Picture 2.png

Figure 2: Absolute Neutrophil Count reference range for very low birth weight neonates [26].

Specific diagnostic tests

Specific diagnostic test includes the isolation of bacteria from the central body fluid. This standard method is mostly used to diagnose neonatal sepsis because of its high specificity [32]. To improve the specificity and sensitivity of blood cultures, skin disinfection before collection should be done and proportionate volume of blood should be cultured per culture [34].

Detection of organism

1. Blood culture: This is the gold standardized diagnostic method for diagnosing neonatal sepsis. Sensitivity lies between 50% to 80% [35]. For detecting low bacterial density sepsis, volume of blood may not be sufficient [36]. The probability of effective growth of an organism highly increases post-inoculation with venous blood (0.5ml) in paediatric blood culture bottle [37]. However, a of the blood culture is negative, neonatal sepsis is not ruled out [38].

Bact/Alert Automated Blood Culture System

pH changes derived by CO2 is measured calorimetrically. Carbon dioxide is released when organism grows that is diffused across the membrane. The CO2 gets dissolved in water and this releases hydrogen ions and cause colour changes in the sensor, that is measured instrumently. Subcultures are done when positive results come [35].

2. Urine culture: Urine cultures have low yield in early onset sepsis. Urine cultures are collected by bladder catheterization or suprapubic puncture in most cases of late onset sepsis. A routine urine culture septic neonates is not recommended because the procedure is painful with a low yield.

Diagnosis of Urinary Tract Infections is confirmed when:

• 10 ml of centrifuged sample has >10 WBC/mm3

• Bladder catheterization obtained urine has >104 organisms/ml

• Suprapubic aspiration obtained urine has organisms [1].

3. Tracheal aspirate culture: Serial endotracheal aspirates are used to detect the flora in NICU. These are used to detect only respiratory tract infections that hospital acquired [39]. Thus, this test is unreliable for predicting sepsis [40].

4. CSF culture: The incidence of meningitis in neonatal sepsis varies from 0.3-3% in various studies [41]. In Early Onset Sepsis, clinical picture with septicemia and positive blood culture indicates lumbar puncture. Lumber culture is recommended in all neonates before any antibiotic treatment. In critically sick infant, LP is postponed till the infant is stabilized [1]. The newborn has specific CSF characteristics during initial period and values are shown in Table 3 [42].

CSF Components

Normal range

CSF/Blood Glucose (%)

5 (44-248)

Glucose (mg/dl)

52 (34-119)

CSF Protein (mg/dl)

90 (20-170)

PMN (%)

60%

Cells/mm3

8 (0-30 cells)

Table 3: CSF characteristics during initial period and values.

Clinical features

Neonatal sepsis manifested as either meningitis, pneumonia, generalized sepsis, or asymptomatic bacteremia [43]. Sepsis is generally manifests in specific and non-specific features:

Non-specific features

• Temperature instability

• Hypothermia or hyperthermia (temperature >39 ° C) [30]

• Lethargy

• Poor feeding

• Poor cry

• Refusal to suck

• Hypotonia

• Bradycardia/tachycardia

• Apneas

• Respiratory distress

Special features associated with different systems [1]

• CNS-Seizures, Stupor, High pitched cry and bulging anterior fontanelle

• CVS-Shock, hypotension

• GI-Feed intolerance, vomiting, abdominal distension, increased gastric residues

• Hepatic-Hepatomegaly, icterus

• Urinary-Acute renal failure

• Hematology-petechia, purpura, Bleeding

Associated conditions

Meningitis

About 33% of the neonates with sepsis have co-existing meningitis. Meningitis in neonate is devastating and secondary to severe parenchymal involvement, pulmonary problems, hypoxia, septic shock are observed in surviving infants. The signs of meningeal irritation are generally absent in the newborn. Hence, outcome is highly influenced by a high index of suspicion to early diagnosis of meningitis [44]. In a baby with sepsis, presence of seizures, staring episodes, bulging anterior fontanelle, high pitched cry should arouse the suspicion of meningitis. Group B beta haemolytic Streptococci, Listeria monocytogene, E. Coli are major organisms responsible for meningitis [45].

Pneumonia

Pneumonia is usually associated with early onset sepsis. Based on infection route and age of presentation, Pneumonia can be categorized into three categories [46]:

1. Transplacental pneumonitis: It is present in early hours of life and is in utero. It is usually associated with hepatosplenomegaly and neurological abnormalities.

2. Aspiration pneumonia: It occurs during the perinatal period and illness begins within the first few hours of birth. It is caused by aspiration of maternal flora from the maternal cervix before or during delivery.

3. Pneumonia acquired during delivery or in the postpartum period due to interventions after birth such as intubation, orotracheal suctioning. Organisms that commonly cause pneumonia include Staphylococcus aureus, Coliforms, Viruses, and Candida spp.

Septic arthritis and osteomyelitis

Spread of skin infection after 1-3 weeks of birth, results in septic arthritis and Neonatal osteomyelitis [47]. It is caused most by Staphylococcus aureus.

Bacteriology

Neonatal sepsis is caused mainly by Candida species and Gram-negative and Gram-positive bacteria [48]. There are diverse organisms that cause sepsis that differs based on the region and time [49,50]. Septic infections also vary based on the infant nursery and NICU conditions [51]. Maternal birth canal has highly prevalent coliform organisms and the newborns get colonized during delivery or soon after.

The common gram-negative organisms are:

1. Klebsiella: It is the most common organism implicated in neonatal sepsis especially in India. It accounts for 27.52 % of culture positive infections [52].

2. Escherichia coli: In India, about 11.6% cases of neonatal sepsis occur due to E. coli [52].

3. Pseudomonas aeruginosa: It is a contaminant of respirators, humidifiers, suction tubes etc. it is responsible for 9.3% of all septic cases [52].

Gram positive organisms

1. Staphylococcus spp: Both Staphylococcus aureus and Staphylococcus epidermidis colonize the skin and mucous membranes. Staphylococcus aureus is responsible for 13.6% cases of neonatal sepsis [52].

2. Coagulase negative Staphylococcus (CONS): It constitutes 10-27% of cases of sepsis in the NICU and 48% of cases of sepsis in VLBW babies.

3. Listeria monocytogenes: Listeria invades the placenta and infects the fetus by hematogenous spread, direct tissue invasion or ascending infection or. It is associated with hospital cross infection and involves meningitis [52].

Antibiotic sensitivity

The organisms causing sepsis in infant are rapidly diversifying due to region variation and different pattern of antibiotic treatment [53]. Combination of Gentamicin with Penicillin or Ampicillin is considered as the best choice antibiotic treatment for first line therapy [52]. For resistant pathogens that are hospital acquired combination of Amikacin or Gentamicin with Ampicillin or Cloxacillin is administered [52].

Third generation of antibiotics (cephalosporin (Cefotaxime or Ceftazidime)) is instituted in nurseries where multiple drug resistant organisms like Klebsiella and gram-negative bacilli are prevalent [52]. In case of Pseudomonas sepsis, amikacin in combination with Piperacillin-Tazobactam is be considered for effective treatment whereas amikacin in combination with Ciprofloxacin or Vancomycin is used against Methicillin resistant Staphylococcus aureus (MRSA). Addition of an aminoglycoside is useful in therapy against Staphylococcus [59]. New antibiotics like Imipenem, Meropenem and Aztreonam available in the market are effective against gram-negative organisms [53].

Adjunctive therapy

Exchange transfusion

This has shown to be effective in removal of bacteria and endotoxins from the circulation in septic neonates. Elimination of the vasoconstrictive action of the endotoxin results in improved tissue perfusion producing immediate improvement in cardiac output, urine output, acid-base imbalances [54,55].

Sadana et al demonstrated that mortality due to sepsis gets reduced to 50% in neonates when treated with double volume exchange transfusion [55].

Granulocyte-colony stimulating factor

G-CSF promotes the development and maturation of granulocyte by increasing bone marrow neutrophil storage pool and stimulating myeloid progenitor proliferation. Granulocyte adjuncts therapy have proven to be safe and feasible among the septic neonate in the existing clinical trials. However, data is insufficient to know its long-term effects G-CSF therapy is recommended in low weight septic neonates with neutropenia [56,57].

Materials and methods

Place of study

This study was conducted in the Neonatal Intensive Care Unit of Narayana Hrudayalaya Hospital.

Study design

It was a prospective cross-sectional observational hospital research.

Duration of study

This study was carried in a span of 12 months from April 2014 to March 2015.

Study population

Study included that the 50 neonates that fulfilled the inclusion criteria.

Inclusion criteria

In Narayana Hrudayalaya NICU, all the neonates were positive for sepsis.

Exclusion criteria

Neonates with no sepsis symptoms and features. Babies greater than 28 days were excluded.

Consent and ethical clearance

All the details in regional specific language were explained to the parents included the procedures and method involved in the study. Ethical clearance and Informed consent of parents was obtained.

Collection of data

A proforma was used to collect the data.

Method of study

Babies exhibiting the features of sepsis were analyzed including the detailed history and clinical examination. Possible risk factors were also analyzed and noted thoroughly. The investigations were done for the above babies shown in Table 4.

Absolute neutrophil count

As per Manroes charts

I/T ratio

> 20% in preterm, > 27% in terms

CRP

>10 mg/dl

Table 4: The investigation (I/T ratio and CRP test) done on babies.

ANC (absolute neutrophil counts)

• The ANC was derived from total WBC counts done by automated analyzer which used impedence method.

• The minimum cut off for significance in sepsis was read as per Manroe’s charts [23].

Immature/Total neutrophil count ratio

• A peripheral smear examination was done and the band forms and any early forms such as metamyelocytes were identified which gave the number of total immature cells.

• Subsequently, I/T ratio is defined as the total number of immature cells by the total neutrophil count.

• A ratio of 0.2 in preterm and 0.27 in term babies was counted as significant.

C-reactive protein

• The quantitative determination of CRP was done by extended range method.

• A value >10mg/L considered positive for sepsis.

• The presence of two or more abnormal parameters in infants are septic, and empirical antibiotic treatment is started, based on previous antibiotic sensitivity pattern.

Blood culture and sensitivity (BAcT/Alert blood culture)

1. Method of blood collection for blood culture: Under all aseptic precautions, the venipuncture site was identified and cleaned with spirit and Betadine. Using a sterile syringe, 0.5ml of blood was taken, and special culture bottle was used to inoculate the blood for Bact/Alert. The media contains trypticase soya broth (TSIB). At the bottom of the bottle, a calorimetric sensor was used analysis. As soon as the bottle showed a positive result, subculture was done on MacConkey’s agar and blood agar for the identification of organisms. Based on blood culture reports, the neonate was termed to have:

• Probable sepsis (blood culture negative).

• Culture positive sepsis (blood culture positive).

2. After monitoring the Clinical response antibiotic medication was changed to another antibiotic in case the patient condition was deteriorating.

3. The second line treatment was analyzed by the isolated organism susceptibility pattern and thus was used in case of positive blood culture.

Statistical analysis

For the statistical analysis, following methods were used in this study. Tables 5-25 and Figures 3-22 present the results (% and numbers) for each parameter discrete data and Mean and Standard deviation for continuous data are presented, and Chi-square test of significance was used to compare proportions: Chi-Square (2) test for (r x c tables)

Table 4.png

Table 5: N is the Grand Total. a,b…..h are the observed numbers.

Equation.png

DF=(r-1)*(c-1), where r=rows and c=columns. DF=Degrees of Freedom (Number of observations that are free to vary after certain Restriction have been placed on the data). The “p” value of less than 0.05 was accepted as indicating statistical significance. Statistical Package for Social Science (SPSS version 10.5) package was used for the Data analysis.

Observations and results

The following observations were made:

Sex

No. of case

Percentage

Female

12

24%

Male

38

76%

Total

50

100%

Table 6: Distribution of study population based on gender.

Picture 3.png

Figure 3: Pie graph showing gender distribution of study population.

Type of Sepsis

Number

Percentage

Late Onset (>72 Hours)

10

20%

Early onset (<72 hours)

40

80%

Table 7: Table describing different onset of neonatal sepsis cases.

Picture 4.png

Figure 4: Pie graph describing distribution of onset of neonatal sepsis.

Gestational age

Number of cases

Percentage

28-<32 WKS

7

14%

32-<37 WKS

14

28%

>=37 WKS

29

58%

Total

50

100%

Table 8: Distribution of cases based on to the gestational age of the neonate.

Picture 5.png

Figure 5: Pie graph showing distribution of cases according to the gestational age of the neonate.

Birth weight

Number

Percentage

<1000 grams

1

2%

1000-<1500 grams

9

18%

1500-<2500 grams

21

42%

≥ 2500 grams

19

38%

Total

50

100%

Table 9: Distribution of neonates based on the birth weight.

Picture 6.png

Figure 6: Pie graph describing Distribution of neonates based on the birth weight.

PROM >18 Hours

Number of cases

Percentage

Yes

23

46%

No

27

54%

Total

50

100%

Table 10: Table showing the distribution of cases with history of PROM >18 hours.

PROM

Total

value

‘p’ value

Yes

No

Late onset sepsis

2

8

10

3.402

0.065

20.00%

80.00%

100.00%

Early onset sepsis

21

19

40

52.50%

47.50%

100.00%

Total

23

27

50

46.00%

54.00%

100.00%

Table 11: Table showing relationship between the onset of sepsis and PROM >18 hours.

Picture 7.png

Figure 7: Pie graph showing distribution of cases with history of PROM >18 hours.

Picture 8.png

Figure 8: Bar graph showing relationship between the onset of sepsis and the PROM >18 hours.

Chorioamnionitis

Number of cases

Percentage

Absent

47

94%

Present

3

6%

Total

50

100%

Table 12: Table showing the distribution of cases based on the presence of chorioamnionitis.

Picture 9.png

Figure 9: Pie graph showing distribution of cases based on the presence of chorioamnionitis.

Chorioamnionitis

Total

value

‘p’ value

Yes

No

Late onset sepsis

0

10

10

0.798

0.372

0.00%

100.00%

100.00%

Early onset sepsis

300.00%

37

40

7.50%

92.50%

100.00%

Total

300.00%

47

50

6.00%

94.00%

100.00%

Table 13: Table showing the relationship between late and early onset of sepsis with chorioamnionitis.

Foul Smelling Liquor

No. of cases

Percentage

Absent

49

98%

Present

1

2%

Total

50

100%

Table 14: Distribution of cases based on the presence of foul-smelling liquor.

Picture 10.png

Figure 10: Bar graph showing association between chorioamnionitis and onset of sepsis.

Picture 11.png

Figure 11: Pie graph showing rationing of cases in accordance to the presence of foul smelling liquor.

Maternal UTI

No. of cases

Percentage

Absent

49

98%

Present

1

2%

Total

50

100%

Table 15: Table showing rationing of cases in accordance to the presence of maternal UTI.

Picture 12.png

Figure 12: Pie graph showing rationing of cases in accordance to the presence of maternal UTI.

Resuscitation required

Number of cases

Percentage

Required

16

32%

Not required

34

68%

Total

50

100%

Table 16: Table showing rationing of cases in accordance to the presence of requirement of resuscitation at birth.

Picture 13.png

Figure 13: Pie graph showing distribution of cases based on the presence of requirement of resuscitation at birth.

Interventions

Number of cases

Percentage

Intervention required

17

34%

Intervention not required

33

66%

Total

50

100%

Table 17: Table describing the case based on requirement of interventions such as mechanical ventilation, umbilical venous catheterization.

Picture 14.png

Figure 14: Pie graph showing distribution of cases based on requirement of interventions such as mechanical ventilation, umbilical venous catheterization.

Intervention

Total

Required

Did not require

Early onset sepsis

13

27

40

32.50%

67.50%

100%

Late onset sepsis

4

6

10

40%

60%

100%

Total

17

33

50

34%

66%

100%

Table 18: Onset of sepsis and requirement of NICU interventions-based case distribution.

Blood culture

Number of cases

Percentage

Positive

12

24%

No growth

38

76%

Total

50

100%

Table 19: Distribution of culture positive cases.

Picture 15.png

Figure 15: Bar graph describing distribution based on the onset of sepsis and requirement of NICU interventions.

Picture 16.png

Figure 16: Pie graph showing distribution of culture positive cases.

Organism

Number

Percentage

Gram positive bacteria

6

50%

Gram negative bacteria

4

33%

Candida spp

2

17%

Table 20: Table showing distribution of culture positive cases according to results on gram staining.

Picture 17.png

Figure 17: Pie graph showing distribution of culture positive cases according to results on gram staining.

Name of organism

Number of cases

Percent

Burkholderia cepacia

1

8%

Candida

2

17%

CONS.

2

17%

E. Coli

1

8%

Enterobacter cloaca

1

8%

Klebsiella

2

17%

MSSA

2

17%

Pseudomonas aeruginosa

1

8%

Total

12

100%

Table 21: Table showing the distribution of organisms grown in culture positive cases.

Picture 18.png

Figure 18: Pie graph showing distribution of organisms grown in culture positive cases.

Blood Culture Sensitivity

Total

Burkholderia cepacia

Candida spp.

CONS

E. coli spp.

Enterobacter cloacae

Klebsiella spp.

MSSA

Pseudomonas aeruginosa

Early onset sepsis

0

2

2

0

0

0

1

0

5

0%

40%

40%

0%

0%

0%

20%

0%

100%

Late onset Sepsis

100%

0

0

1

1

2

1

1

7

14%

0%

0%

14%

14%

30%

14%

14%

100%

Total

100%

2

2

1

1

2

2

1

12

Table 22: Table showing the relation between the onset of sepsis and organism.

Picture 19.png

Figure 19: Pie graph showing early onset of sepsis.

Picture 20.png

Figure 20: Pie graph showing late onset of sepsis.

Outcome

Number of cases

Percentage

Discharged

47

94%

Deceased

3

6%

Total

50

100%

Table 23: Outcome based distribution of cases.

Picture 21.png

Figure 21: Pie graph showing distribution of cases based on the outcome.

Age of Presentation

Total

valve

‘p’ value

<72 hours

>72 hours

Discharged

40

7

47

12.766

<0.001

85%

14%

100%

Deceased

0

3

3

0%

100%

100%

Total

40

10

50

80%

20%

100%

Table 24: Table showing the association between onset of sepsis and mortality.

Picture 22.png

Figure 22: Bar graph showing association between onset of sepsis and mortality.

Organisms No. Amikacin Cefepime Cefoperazone Ciprofloxacin Cefotaxime Cloxacillin Colistin Imipenem Linezolid Meropenem Penicillin Piptaz Vancomycin


Table 25: Table showing the antibiotic sensitivity of each organism.

Discussion

In the present study, 3.1:1 is the male to female ratio and males were more affected than with a 76% than females with 24% for females (Table 6). The result of the study was found to be comparable with Shrestha, et al., and NJ Begum S, et al., studies [52,57]. The results were highly in concurrence with Shashikala Tallur, et al., study where 67% males were affected that were more than the affected females (33%) [58]. Varsha, et al., [59] also showed similar results where males (66%) were more affected than females (34%). Early onset septicemia was found to be more prevalent than Late onset septicemia with a percentage of 80 and 20 respectively (Table 7). One study by Khinchi, et al., showed similar results with 60% and 40% of early and late onset sepsis [60]. The present study results were also shown to be in consistent with of Aletayab, et al., [61], Waseem R, et al., [62] and Al-Shamahy, et al., [63] studies.

The incidence of sepsis in current study showed that term babies had greater sepsis than that of preterm babies with a percentage of 58% and 42% (Table 8). Naushaduddin Ahmed ASM, et al., study results demonstrated increase in sepsis incidence in preterm infants as compared to term infants with a percentage of 52 in preterm and 48 in term infants [64,65]. However, studies by Khatua, et al., showed similar results as preterm babies had more sepsis than the term infants [66]. The pre-term infants showed a higher prevalence of sepsis than term infants due to the prolonged NICU stay. As shown in the Table 9, low birth weight is also one of the predominant factors contributing to sepsis in neonates with average ranging between 1500 grams to 2499 grams (Table 9). Meenu, et al., also showed that low birth weight is responsible for sepsis and infants with low weight are more prevalent to sepsis than normal birth weight infants [67]. Sepsis in neonates with molecular weight <2 kg is highly prevalent [64]. In the present study, it was seen that premature rupture of membranes greater than 18 hours was associated with (46%) of the babies (Table 10). Similar results were observed by Meenu, et al., infants from mothers with membrane premature rupture history had higher incidence of sepsis (45%) [67]. PROM caused early and late onset sepsis in 52.5% and 20% neonates. However, the results of were statistically insignificant (p=0.065) (Table 11).

Chorioamnionitis was observed in only early onset sepsis with a percentage of 6 respectively (Table 12) and these results were also statistically insignificant (p=0.372) (Table 13). Foul smelling liquor and Maternal UTI was present in 2% of the cases (Table 14,15). The study showed that 32% of babies were asphyxiated at birth and required some form of resuscitation in the form of bag and mask, bag and tube, chest compressions (Table 16). In our study, it was seen that 34% of cases were subjected to interventions such as mechanical ventilation, umbilical venous catheterization (Table 17). 40 percent of cases of late onset sepsis had required multiple intervention in the NICU such as mechanical ventilation, umbilical catheterization (Table 18). In this study, 24% of the patients yielded growth while 76% were culture negative (Table 19). In the study done by Naushadudin, 35% were culture yielded growth [65]. In a study by Varsha, et al., only 14% showed growth [59]. In our study, gram positive bacteria (50%) were more commonly the cause of septicemia in neonates than gram negative bacteria (33%) (Table 20). In a study done by Begum Sharifun Naher, et al., gram negative bacteria were isolated in 78% of cases [73]. Amongst the isolates, Klebsiella (17%), Methicillin sensitive Staphylococcus aureus (17%), Candida Spp (17%), Coagulase negative Staphylococcus spp (17%) were more common (Table 21). In a study done by Awoniyi, et al., Staphylococcus aureus grew in 28% of cases, Klebsiella in 13%, and Pseudomonas in 13% of cases [68]. In a study done by Sugandhi Rao, et al., gram negative organism sepsis was the most common (Pseudomonas is the most predominant bacteria after Klebsiella) followed by Staphylococcus aureus [69]. In a study done by Maimoona Mustafa, Klebsiella was the most common organism causing neonatal sepsis [70]. Shanti Ananthkrishnan, et al., showed Klebsiella as the major organism causing sepsis followed by CONS [71]. In our study, one baby grew E. coli in the CSF culture. In this study, amongst the culture positive cases, Candida, Coagulase Negative Staphylococcus grew in babies with early onset sepsis. E. coli, Klebsiella, Burkholdieria, Enterobacter, Pseudomonas, grew in babies with late onset sepsis. MSSA grew in both late and early onset sepsis (Table 22).

Clinical Outcome

In this study, 94% of babies with neonatal sepsis were discharged and 6% of babies succumbed to the illness (Table 23). In this study, there was a higher mortality rate in cases of late onset sepsis ( value=12.76, p<0.001) (Table 24). This can be explained probably due to prolonged NICU stay, multiple interventions such as mechanical ventilation, umbilical venous catheterization, and central lines.

Antibiotic sensitivity

In this study (Table 25), Klebsiella showed sensitivity against Amikacin, Cefoperazone, Ciprofloxacin, Colistin, Imipenem, Meropenem, and Piperacillin. According to NNPD 2002-03 [11], Klebsiella pneumoniae strains showed poor sensitivity to antibiotics Amikacin, Ceftazidime, Ciprofloxacin, Cefotaxime and Gentamicin. In a study done by Mainmoona Mustafa, Klebsiella was resistant to Gentamicin (45%), third generation cephalosporins such as Ceftazidime, and Cefotaxime [71]. Pseudomonas aeruginosa was sensitive to Ciprofloxacin, Cloxacillin, Linezolid, Piperacillin, and Vancomycin. In Mainmoona Mustafa’s study Pseudomonas was sensitive to Amikacin, Meropenem, and Colistin [75]. In current study, Staphylococcus aureus showed sensitivity to Ciprofloxacin, Cefotaxime, Linezolid, and Vancomycin.

According to The NNPD [11], among the Staphylococcus aureus isolates, most were sensitive to Vancomycin, Ciprofloxacin, Amikacin, but not to Penicillin. In this study E. coli was sensitive to Amikacin, Cefoperazone, Ciprofloxacin and Meropenem. According to NNPD [11], E. Coli was sensitive to Amikacin, Gentamycin, Cefoperazone, and Ciprofloxacin. In this study, Coagulase negative Staphylococcus was sensitive to Cefotaxime, Ciprofloxacin, Cloxacillin, Linezolid, and Vancomycin.

Recommendations

The following recommendations are made based on the results of the study:

1. Proper aseptic precautions should be ensured while handling the neonate.

2. NICU interventions should be limited to minimum and should be carried out in aseptic conditions.

3. Cefotaxime and Amikacin may be used for empirical treatment till blood culture reports are available.

4. For MDR gram-negative bacteria, Meropenem and Ciprofloxacin antibiotics are used for treatment.

5. For drug resistant gram-positive organisms, Linezolid and Vancomycin may be reserved.

Limitations of the study

Micro-ESR was not done while conducting study. Larger studies like the present study are required for comparison of the results.

Conclusion

The study was conducted in the NICU of Narayana Hrudayalaya, Bangalore on 50 neonates. The study concluded that sepsis incidence in preterm and term babies was comparable with the male babies showing more sepsis than the female babies. Low birth weight between 1500-2500 grams was noted as an important contributing factor to sepsis in babies.

PROM was found to be greater than 18 hours in (46%) of cases. Other important contributing factors includes maternal UTI, foul smelling liquor, Chorioamnionitis, Birth asphyxia and requirement of resuscitation were also seen in most cases. 24% of cases showed positive cultures of which, 50% were gram-negative organisms. Klebsiella pneumoniae was the common pathogen amongst gram negative bacteria in the present study and thus was the common cause of septicemia in neonates, and Coagulase negative Staphylococcus and Staphylococcus aureus were common bacteria among the gram-positive bacteria.

Fline antibiotics like Cefotaxime, Amikacin and higher antibiotics like Ceftazidime, and Piperacillin were reactive against gram negative bacteria whereas gram-positive organism showed sensitivity to Cefotaxime and higher antibiotics like Linezolid and Vancomycin.

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