الفهرس 
Aim of The WorkOnly 14 pages are availabe for public view
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Abstract
Neonatal sepsis (NS) is a major cause of morbidity and mortality; the incidence of early onset of sepsis (EOS) in developed countries is 0.9–1.5 per 1000 live births while the incidence of late onset of sepsis (LOS) is 3–3.7 per 1000 live births. The incidence of neonatal deaths in Egypt dropped to 13 per 1000 live births in 2020.
The signs and symptoms of NS are non-specific, which makes the diagnosis difficult despite the outstanding development of neonatology in recent years. The routinely used laboratory tests are extremely non-specific and often cause inappropriate use of antibiotics.
Blood culture is the gold standard for diagnosis of NS although it has many disadvantages because blood culture techniques usually take longer duration to detect blood stream infections, there is a possibility of contamination of the culture and false negative results may occur due to: low concentration of bacteria in the patient’s blood. Moreover, the sensitivity of blood cultures depends on the volume sampled. In addition, pathogens in blood cultures are only detected in approximately 25% of cases.
The triggering receptor expressed on myeloid cells-1 (TREM-1) is a family of receptors expressed on polymorph nuclear neutrophils (PMNs) and mature monocytes. It acts as an inflammatory trigger and amplifier after exposure to extracellular fungal and bacterial pathogens. It mediates the acute inflammatory response to microbial products that occur in sepsis.
This study aimed to determine the incidence of Gram-negative and Gram-positive organisms isolated from EOS and LOS in NICU of EL-Menshawy Hospital, to determine the antimicrobial susceptibility patterns among the isolated strains, to study the role of TREM-1 gene expression as an early biomarker for NS and to find out its relation to clinical disease severity compared with conventional blood culture and other markers.
This study was carried out at the Microbiology and Immunology Department, Faculty of Medicine, Menoufia University, in collaboration with the Medical Microbiology Department, El-Menshawy General Hospital, Ministry of Health and Population, Tanta, during the period from June 2019 to July 2020. The study involved 75 neonates (41 males & 34 females) from those admitted to the NICU of Neonates Department, El-Menshawy General Hospital and 25 apparently healthy neonates (14 males & 11 females) with no evidence of sepsis or any other medical illness as a control group.
The studied neonates were categorized into four groups: group I involved 25 neonates with an EOS (14 males & 11 females) that occurred within the first 72 hours after birth. group II involved 25 neonates with a LOS (13 males & 12 females) that occurred 72 hours after birth. group III involved 25 neonates with septic shock (14 males & 11 females). group IV involved 25 apparently healthy neonates (14 males & 11 females) with no evidence of sepsis or any other medical illness as a control group.
All neonates and controls included in this study were subjected to complete history taking, physical examination, assessment of disease severity according to the WHO young infant study group and integrated management of childhood illness (IMCI)
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group. Laboratory investigations, which included routine complete blood picture [total leucocytic count (TLC), platelet count, absolute neutrophil count (ANC), immature lymphocytes/total leucocytes (I/T ratio) and immature lymphocytes/mature leucocytes (I/M ratio)], C-reactive protein (CRP), liver enzymes (ALT & AST) and kidney function tests [blood urea nitrogen (BUN) & creatinine], were performed. Blood samples were synchronically collected for conventional blood culture for isolation and identification of the causative organisms as well as for estimation of TREM-1 gene expression level by Real Time PCR (RT- PCR).
The results revealed that premature rupture of membranes (PROM), diabetes mellitus, urinary tract infection (UTI), eclampsia, development of fever during labour, type of delivery, place of delivery and gestational age were significant maternal risk factors for NS in the studied neonatal patient groups (I, II and III) as compared to the control group (P<0.05 for each). However, no statistically significant difference was detected between neonates in groups I, II and III as regards maternal age and socio-economic status.
Low birth weight (LBW), prematurity and prolonged hospitalization were significant neonatal risk factors for NS in the studied neonatal patient groups as compared to the control group (P<0.05 for each). On the other hand, no statistically significant difference was detected among the studied neonates regarding development of meconium-stained liquor, ammnionitis and gender.
Regarding the clinical signs of NS in the studied groups, the body temperature, suckling reflex status, degree of activity and consciousness level were more significantly encountered among the patient groups (P <0.05 for each).
The mean values of I/T ratio, I/M ratio and absolute neutrophil count were significantly higher among EOS neonates than those of other groups (P< 0.001), while, the mean values of TLC, platelet count and CRP were significantly higher among septic shock neonates than those of other groups (P< 0.001).
The mean values of AST, blood urea, serum creatinine, serum level of Na+, serum level of K+, PaCO2 and capillary refill time were significantly higher among septic shock neonates than those of other groups (P< 0.001), while, the mean values of ALT, pH, HCO3- and PaO2 were significantly higher among LOS neonates than those of other groups (P< 0.001).
The total culture-proven cases represented 24% (18/75) of all the studied neonates with NS with no statistically significant difference among the three studied groups.
Regarding antimicrobial resistance pattern, about 50.0%, 62.5%, 18.2%, 20.0%, 75.0% and 50.0% of the isolated Klebsiella spp., E. coli, Pseudomonas spp., Acinetobacter spp., Staph. aureus and coagulase-negative staphylococci were multi-drug resistant (MDR); while 40.0%, 25.0%, 63.6%, 40.0%, 25.0% and 50.0% of the isolated Klebsiella spp., E. coli, Pseudomonas spp., Acinetobacter spp., Staph. aureus and coagulase-negative staphylococci were extreme-drug resistant (XDR); meanwhile 10.0%, 12.5%, 18.2% and 40.0% of the isolated Klebsiella spp., E. coli, Pseudomonas spp. and Acinetobacter spp. were pan-drug resistant (PDR).
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Regarding the mean values of TREM-1 gene expression, a significant difference was detected between groups I and III (P2=0.004), groups II and III (P4=0.038) and groups III and IV (P6<0.001) neonates.
Significant differences were detected among the studied neonatal groups as regards the relations between the mean values of TREM-1 gene expression and suckling reflex status, degree of activity, consciousness level, stage of respiratory distress and existence of respiratory tract infections (P<0.05).
As regards the correlation between mean values of TREM-1 gene expression and routine laboratory investigations for diagnosis of NS; In group I, a significant negative correlation was detected between the mean values of TREM-1 gene expression level and each of TLC and platelet count (P< 0.005 for each); on the other hand, a significant positive correlation was detected between the mean values of TREM-1 gene expression level and all of ALT, AST, urea, creatinine, K+, HCO3, PaO2 and capillary refill time (P< 0.05 for each). In group II, a highly significant negative correlation was detected between the mean values of TREM-1 gene expression level and platelet count (P<0.001); on the other hand, a significant positive correlation was detected between the mean values of TREM-1 gene expression level and all of ALT, AST, urea, creatinine, K+, HCO3, PaO2 and capillary refill time (P< 0.005 for each). In group III, a non-significant positive correlation was detected between the mean values of TREM-1 gene expression level and each of TLC, I/T ratio and CRP (P= 0.114, 0.555 and 0.97 respectively). No significant relation was detected between the mean values of TREM-1 gene expression fold changes and blood culture results (positive or negative) in neonates of groups I, II and III (P>0.05).
About 56.0%, 36.0% and 72.0% of neonates in groups I, II and III respectively died; a significant statistical difference was detected among the studied groups (P=0.037).
Regarding the relation between blood culture results and clinical sequel in each neonatal group, no significant statistical difference was detected among the studied groups (P>0.05); however, a highly significant statistical difference was detected among the studied groups as regards the relation between TREM-1 gene expression fold changes and clinical outcomes in groups I and III (P2<0.001) and between groups II and III (P4<0.001).
At a cutoff point of ≤0.631, TREM-1 mRNA could be considered as a potential marker for diagnosis of NS with sensitivity, specificity, PPV, NPV and 95% C.I of 65.33%, 96.0%, 98.0%, 48.0% and 0.609 – 0.808 respectively with a significant statistical difference (P= 0.002). Also, at a cutoff point of >0.369, TREM-1 gene expression could be considered as a potential prognostic marker for prediction of mortality associated with NS with sensitivity, specificity, PPV, NPV and 95% C.I of 87.8%, 97.06%, 97.3%, 86.8% and 0.811 – 0.993 respectively with a highly significant statistical difference (P<0.001).