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Neonatal Sepsis Nawaf M. Al-Dajani Neonatal sepsis is a leading cause of morbidity and mortality in Neonatal intensive care unit which leads to significant burden of health care cost. The incidence of neonatal sepsis varies according to gestational age, chronological age and NICU environment; 6-38 % in NICU setting (Health Care Associated) compared to 1-3/1000 in term neonate. There have been several changes on ecology of causative agents over the last decade or so. Major decline in early group B Streptococcus (GBS) sepsis and relative increase in E. coli sepsis has been noted. Coagulase negative Staphylococci (CoNS) remain the leading causative agents of late sepsis among hospitalized premature neonates. A new tend of pathogenesis of CoNS has been noticed in many NICUs across the world "persistent CoNS" which is associated with thrombocytopenia and other morbidities. Gram negative organisms with multi-drug resistance especially K. pneumoniae extended spectrum beta-lactamase (ESBL) producers becoming more prevalent and challenging. Other Gram negative; Enterobacter, Acinetobacter, Serratia, Pseudomonas etc…, are endemic in many NICUs. Methicillin resistant Staphylococcus aureus is becoming an evolving causative agent in both settings HCA and community acquired. Fungal infections occur in about 10% of all late sepsis. Candida species are becoming tolerant to various antifungal therapies (Amphotericin & Fluconazole). Many reports stated therapeutic failure with traditional antifungal drugs. In KSA, GBS sepsis is considered uncommon or even rare. Gram negative organisms are the predominant in many NICUs especially those not following appropriate infection control practice. In addition to sterile fluid culture various adjuvant tools are used to diagnose neonatal sepsis. C-reactive protein, procalcitonin and interleukins carry an important value for ocurrence of sepsis. They vary in term of sensitivity and specificity and cost. No specific antibiotic regimen is superior to other. Ampicillin and aminoglycoside or third generation cephalosporine (cefotaxime) is a regimen of choice for early sepsis. In general, the narrowest possible antibiotic spectrum should be used; a combination of cloxacillin and aminoglycoside seems to be reasonable and adequate in most occasions for late sepsis. This regimen has been very effective in treating non-persistent CoNS sepsis in most occasions (86%). Even if CoNS is resistant to cloxacillin, physicians are not obligated to change to vancomycin if patient shows clinical improvement. Guide lines for empiric therapy should be based on antibiogram data for each unit. Meropenem is considered the first durg of choice for late sepsis in many NICUs, the approach should be discouraged. Endemic Gram negative in many units has had lead to such approach. Linezolid is a relatively new antibiotic, is being used to treat persistent CoNS sepsis with adequate response. Caspofungin is an expensive antifungal drug considered a back up tool for treatment of candidal sepsis tolerant to conventional antifungals. Various adjuvant therapeutic modalities have been used for treatment of sepsis such as intravenous immunoglobulin, G-CSF, pentoxiphyline ….etc. IVIG can be used in Gram negative sepsis and pentoxiphyline carries promising results. Every effort should be directed toward sepsis prevention rather than treatment. This task is multifaceted and need collaboration form many health care workers.