What is the approach to diagnosing and managing neonatal sepsis (Systemic Inflammatory Response Syndrome) in a newborn?

From the Guidelines

Neonatal sepsis requires prompt recognition and treatment to prevent serious complications, and the most recent evidence from 2024 supports the use of ampicillin plus gentamicin as first-line empirical treatment for early-onset sepsis, and vancomycin plus an aminoglycoside or third-generation cephalosporin for late-onset sepsis 1. The approach to diagnosing and managing neonatal sepsis involves identifying risk factors such as premature rupture of membranes, maternal fever, or prematurity, and watching for clinical signs including temperature instability, lethargy, poor feeding, respiratory distress, or hypotension. Some key points to consider in the diagnosis and management of neonatal sepsis include:

• Identifying risk factors and clinical signs of sepsis
• Obtaining a complete blood count with differential, blood culture, C-reactive protein, and possibly cerebrospinal fluid analysis and chest X-ray
• Beginning empiric antibiotics immediately after obtaining cultures
• Providing supportive care including respiratory support, fluid management, and hemodynamic stabilization with vasopressors if needed
• Monitoring vital signs, laboratory values, and clinical status closely
• Adjusting antibiotics based on culture results and continuing treatment for 7-14 days for bacteremia and 14-21 days for meningitis The aggressive approach is necessary because neonates have immature immune systems and can deteriorate rapidly, with sepsis carrying significant mortality risk if not treated promptly, as highlighted in a study from 2021 1. It is also important to note that the increasing prevalence of Gram-negative bacteria and multidrug-resistant infections in neonatal sepsis requires careful consideration of antibiotic resistance patterns and the need for robust antimicrobial stewardship, as emphasized in a study from 2021 1. Additionally, guidelines from reputable organizations such as the World Health Organization and the American Academy of Pediatrics provide recommendations for the prevention and management of neonatal sepsis, including the use of intrapartum antibiotic prophylaxis and empirical antibiotic therapy 1. Overall, the management of neonatal sepsis requires a comprehensive and multidisciplinary approach, taking into account the latest evidence and guidelines to ensure the best possible outcomes for these vulnerable patients.

From the FDA Drug Label

When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. Clinical studies have shown gentamicin injection to be effective in bacterial neonatal sepsis; Specimens for bacterial culture should be obtained to isolate and identify causative organisms and to determine their susceptibility to gentamicin. In the neonate with suspected bacterial sepsis or staphylococcal pneumonia, a penicillin-type drug is also usually indicated as concomitant therapy with gentamicin.

The approach to diagnosing and managing neonatal sepsis (Systemic Inflammatory Response Syndrome) in a newborn involves:

• Obtaining specimens for bacterial culture to identify causative organisms and determine their susceptibility to gentamicin 2
• Considering local epidemiology and susceptibility patterns in selecting empiric therapy
• Using gentamicin as initial therapy in suspected or confirmed gram-negative infections, and potentially in conjunction with a penicillin-type or cephalosporin-type drug
• Penicillin-type drug is usually indicated as concomitant therapy with gentamicin in neonates with suspected bacterial sepsis or staphylococcal pneumonia The decision to continue therapy with gentamicin should be based on the results of susceptibility tests, the severity of the infection, and other important considerations.

From the Research

Diagnosis of Neonatal Sepsis

• Neonatal sepsis is a clinical syndrome that may include systemic signs of infection, circulatory shock, and multisystem organ failure 3
• Blood culture remains the gold standard for diagnosis 3, 4
• The accurate and timely diagnosis of sepsis in neonates presents significant difficulties, since "culture negative" or "suspected" sepsis varies widely worldwide 4
• Various sepsis risk assessment tools have been developed to aid in the diagnosis of neonatal sepsis 4

Management of Neonatal Sepsis

• The optimal treatment of infants with suspected early-onset sepsis is broad-spectrum antimicrobial agents (ampicillin and an aminoglycoside) 5
• Once a pathogen is identified, antimicrobial therapy should be narrowed (unless synergism is needed) 5
• Antimicrobial therapy should be discontinued at 48 hours in clinical situations in which the probability of sepsis is low 5
• Immediate treatment with antibiotics is imperative in cases of suspected neonatal sepsis 3

Antibiotic Regimens for Neonatal Sepsis

• Current evidence is insufficient to support any antibiotic regimen being superior to another for late-onset neonatal sepsis 6
• The benefits and harms of different antibiotic regimens remain unclear due to the lack of well-powered trials and the high risk of systematic errors 6
• RCTs assessing different antibiotic regimens in late-onset neonatal sepsis with low risks of bias are warranted 6

Prevention of Antibiotic Overuse

• The abuse of antibiotics in inpatient and outpatient newborns is a public health problem of epidemiological and even epidemic proportions 7
• There is a need for evidence-based use of intrapartum antimicrobial therapy to reduce the risk of early-onset neonatal sepsis 5
• Recent data suggest an association between prolonged empirical treatment of preterm infants (≥5 days) with broad-spectrum antibiotics and higher risks of late onset sepsis, necrotizing enterocolitis, and mortality 5