Neonatal Sepsis

Early-onset sepsis (EOS) is generally defined as infection presenting before 72 hours of life, although some surveillance definitions use the first 7 days. It is usually vertically acquired. In the United States, group B streptococcus (GBS) predominates in term infants, whereas Escherichia coli is relatively more important in preterm and very-low-birth-weight infants. PubMed+2PubMedNeonatal Sepsis: A Comprehensive ReviewPubMedNeonatal Sepsis - StatPearls - NCBI BookshelfCDCEarly-Onset Neonatal Sepsis Surveillance and Trends | ABCs | CDC

Late-onset sepsis (LOS; 72 hours or later) is commonly healthcare-associated in hospitalized preterm infants. Coagulase-negative staphylococci, Staphylococcus aureus, Gram-negative bacilli, and Candida are relevant pathogens, but the empiric choice should follow unit-specific susceptibility data and the infant's device, operative, and colonization history. ScienceDirect+2ScienceDirectNeonatal Sepsis - an overviewPubMedNeonatal Sepsis: A Comprehensive ReviewPubMedNeonatal Sepsis - StatPearls - NCBI Bookshelf

For infants born at 35 weeks' gestation or later, the American Academy of Pediatrics recognizes three EOS risk-assessment approaches: categorical maternal and neonatal risk thresholds, multivariate assessment using the Neonatal EOS Risk Calculator, and serial physical examination based on the infant's evolving condition. Each requires a local protocol defining vital-sign frequency, escalation criteria, and documentation. PubMed+1PubMedQuality assessment of clinical practice guidelines for neonatal sepsis using the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument: A systematic review of neonatal guidelinesPubMedNeonatal Sepsis: A Comprehensive Review

The EOS calculator incorporates gestational age, highest maternal intrapartum temperature, maternal GBS status, rupture-of-membranes duration, and intrapartum antibiotics, then combines these with the infant's clinical examination. In one prospective implementation cohort of 204,685 infants, calculator-guided care reduced blood-culture testing by 66% and empiric antibiotic treatment by 48% compared with a categorical CDC-based strategy. PubMedPubMedNeonatal Sepsis: A Comprehensive Review

Calculator-derived risk of at least 1 per 1,000 births supports blood culture plus clinical observation; a risk of at least 3 per 1,000 supports empiric antibiotics in the cited review. This tool is not a substitute for reassessment: an infant who becomes ill during observation requires immediate evaluation and treatment. PubMedPubMedNeonatal Sepsis: A Comprehensive Review

Blood culture remains the reference test for bacterial sepsis. Obtain it before the first antibiotic dose whenever feasible. A minimum 1 mL blood volume improves detection of low-density bacteremia. Modern continuously monitored systems detect more than 90% of untreated bacteremia by 36 hours in one review, supporting early antibiotic reassessment when the infant improves and cultures remain negative. ScienceDirect+2ScienceDirectNeonatal Sepsis - an overviewPubMedNeonatal Sepsis: A Comprehensive ReviewPubMedNeonatal Sepsis - StatPearls - NCBI Bookshelf

CBC abnormalities have limited positive predictive value. Leukopenia below 5,000/mm3 and severe neutropenia are more concerning than leukocytosis, but normal values do not exclude sepsis. An elevated immature-to-total neutrophil ratio is nonspecific; CBC findings should not independently justify prolonged empiric therapy. PubMed+2PubMedQuality assessment of clinical practice guidelines for neonatal sepsis using the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument: A systematic review of neonatal guidelinesPubMedNeonatal Sepsis: A Comprehensive ReviewPubMedNeonatal Sepsis - StatPearls - NCBI Bookshelf

CRP rises after infection onset and has limited utility at initial presentation. Serial rather than single measurements can contribute to a decision to stop therapy when cultures are negative and the infant is clinically well. Procalcitonin rises earlier but is also affected by noninfectious neonatal physiology and should not independently diagnose infection. ScienceDirect+2ScienceDirectNeonatal Sepsis - an overviewPubMedNeonatal Sepsis: A Comprehensive ReviewPubMedNeonatal Sepsis - StatPearls - NCBI Bookshelf

For suspected EOS, intravenous ampicillin plus gentamicin provides coverage for GBS, E. coli, enterococci, and Listeria and remains the recommended empiric combination in AAP-derived guidance. The supplied sources do not provide a U.S. neonatal dosing table sufficient to safely specify ampicillin or gentamicin dose intervals across gestational and postnatal ages; use an institutional neonatal dosing reference and therapeutic drug monitoring protocol. PubMed+2PubMedQuality assessment of clinical practice guidelines for neonatal sepsis using the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument: A systematic review of neonatal guidelinesPubMedNeonatal Sepsis: A Comprehensive ReviewPubMedNeonatal Sepsis - StatPearls - NCBI Bookshelf

Avoid routine empiric third-generation cephalosporins for uncomplicated EOS because broader exposure is associated with antimicrobial resistance and invasive fungal infection. Consider expanded Gram-negative coverage for an infant who is critically ill despite ampicillin-gentamicin, has credible resistant Gram-negative risk, or has suspected Gram-negative meningitis; obtain infectious diseases or microbiology input and use local susceptibility data. PubMed+1PubMedNeonatal Sepsis: A Comprehensive ReviewPubMedNeonatal Sepsis - StatPearls - NCBI Bookshelf

For hospital-acquired LOS, empiric regimens should cover local Gram-positive and Gram-negative epidemiology. Narrow-spectrum antistaphylococcal therapy plus an aminoglycoside is a reasonable approach where methicillin-resistant S. aureus prevalence is low; reserve empiric vancomycin for units or infants with a credible resistant Gram-positive risk. Suspected necrotizing enterocolitis requires anaerobic coverage, such as metronidazole. ScienceDirect+2ScienceDirectNeonatal Sepsis - an overviewPubMedNeonatal Sepsis: A Comprehensive ReviewPubMedNeonatal infection: antibiotics for prevention and treatment - NCBI Bookshelf

For suspected EOS, discontinue empiric therapy by 36 to 48 hours of sterile culture incubation unless there is clear site-specific infection or compelling persistent clinical evidence. Persistent cardiorespiratory instability in very-low-birth-weight infants, or isolated laboratory abnormalities, should not alone drive prolonged empirical treatment. ScienceDirect+3ScienceDirectNeonatal Sepsis - an overviewPubMedQuality assessment of clinical practice guidelines for neonatal sepsis using the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument: A systematic review of neonatal guidelinesPubMedNeonatal Sepsis: A Comprehensive ReviewPubMedNeonatal Sepsis - StatPearls - NCBI Bookshelf

For suspected LOS, NICE recommends reassessment at 48 hours and discontinuation when cultures are negative, initial suspicion was not strong, the infant is clinically reassuring, and CRP trends are reassuring. If antibiotics continue despite sterile cultures, review daily for a stop decision. PubMedPubMedNeonatal infection: antibiotics for prevention and treatment - NCBI Bookshelf

For uncomplicated culture-positive bacteremia without meningitis, 7 days is recommended in NICE guidance for EOS and LOS, with longer treatment for incomplete recovery, Gram-negative or S. aureus infection, central-line infection, osteomyelitis, intra-abdominal disease, or other focal infection. Duration must be individualized to organism, infection site, source control, CSF findings, and clearance cultures. PubMedPubMedNeonatal infection: antibiotics for prevention and treatment - NCBI Bookshelf

GBS screening and intrapartum antibiotic prophylaxis have substantially reduced GBS-associated EOS. ACOG-based recommendations cited in the supplied review support maternal rectovaginal screening at 36 0/7 to 37 6/7 weeks' gestation and intrapartum prophylaxis when indicated. PubMedPubMedNeonatal Sepsis: A Comprehensive Review

For LOS prevention, reduce invasive-device exposure, adhere to central-line insertion and maintenance practices, practice hand hygiene, and use antimicrobial stewardship to limit selection pressure and invasive candidiasis risk. PubMed+1PubMedNeonatal Sepsis: A Comprehensive ReviewPubMedNeonatal Sepsis - StatPearls - NCBI Bookshelf

In NICUs with substantial invasive candidiasis risk, antifungal prophylaxis may be considered for high-risk preterm infants. NICE recommends oral nystatin for infants receiving antibiotics for suspected LOS who weigh 1,500 g or less or were born before 30 weeks; intravenous fluconazole is an off-label alternative when enteral administration is not possible. Applicability to U.S. practice depends on local invasive candidiasis incidence and formulary policy. PubMedPubMedNeonatal infection: antibiotics for prevention and treatment - NCBI Bookshelf