Treatment of Neonatal Sepsis
For early-onset neonatal sepsis, initiate ampicillin plus gentamicin immediately as first-line empiric therapy, targeting Group B Streptococcus, E. coli, and Listeria monocytogenes. 1
Early-Onset Sepsis: First-Line Empiric Therapy
Ampicillin plus gentamicin is the WHO-recommended standard for early-onset neonatal sepsis (onset within first 72 hours of life), providing coverage against the most common pathogens including Group B Streptococcus, E. coli, and Listeria monocytogenes. 1
This combination demonstrates approximately 92% susceptibility against Gram-negative isolates in early-onset disease, making it highly effective for initial empiric coverage. 1
The FDA labels both gentamicin and ampicillin as indicated for bacterial neonatal sepsis, with gentamicin specifically effective against Pseudomonas aeruginosa, Proteus species, E. coli, Klebsiella-Enterobacter-Serratia species, and Staphylococcus species. 2, 3
Recent surveillance data from 2022 confirms that all Gram-positive EOS isolates remain susceptible to either ampicillin or gentamicin, and only 8% of all EOS cases involve pathogens nonsusceptible to both agents. 4
Critical Timing Requirements
Initiate antibiotics within 1 hour for septic shock and within 3 hours for sepsis without shock. 1
Obtain blood cultures before antibiotic administration, but never delay treatment while waiting for culture results. 1
Discontinue antibiotics after 48 hours if cultures are negative and clinical probability of sepsis is low, as prolonged empirical treatment (≥5 days) in preterm infants increases risks of late-onset sepsis, necrotizing enterocolitis, and mortality. 5, 6
Late-Onset and Nosocomial Sepsis
For hospital-acquired infections (onset >72 hours), use amikacin plus cloxacillin as first-line therapy, providing coverage against resistant staphylococci and Gram-negative bacteria. 1, 5
The pathogen profile differs substantially from early-onset sepsis: nosocomial infections involve coagulase-negative staphylococci, Staphylococcus aureus (including MRSA), Gram-negative bacteria, and enterococci rather than GBS and Listeria. 5
Replace cloxacillin with vancomycin when methicillin-resistant organisms are suspected, particularly in infants with central venous catheters or prolonged NICU stays. 5
Use vancomycin plus ceftazidime when methicillin-resistant staphylococci or resistant Gram-negative bacteria are strongly suspected. 1, 5
Escalation Strategy
Add cefotaxime when there is evidence or strong suspicion of Gram-negative sepsis, as recommended by the American Academy of Pediatrics. 1
Escalate therapy immediately if no clinical improvement occurs after 48-72 hours of initial empiric therapy, or if blood cultures reveal organisms resistant to the initial regimen. 1, 5
For confirmed Gram-negative sepsis, third-generation cephalosporins, fourth-generation cephalosporins, piperacillin-tazobactam, and carbapenems demonstrate ≥95% susceptibility. 4
Carbapenem-Resistant Organisms
Initiate polymyxin therapy when cultures demonstrate carbapenem-resistant Gram-negative organisms such as Acinetobacter baumannii, Klebsiella pneumoniae, or Pseudomonas aeruginosa resistant to all beta-lactams. 7
Consider combination therapy with polymyxins plus aminoglycosides for pan-resistant organisms, though neonatal evidence is extremely limited. 7
Utilize therapeutic drug monitoring for polymyxins whenever available to optimize dosing and minimize toxicity. 7
Obtain follow-up cultures during treatment to detect resistance development, particularly for carbapenem-resistant organisms. 7
Regional Resistance Considerations
Modify empiric choices based on local bacterial epidemiology and resistance patterns, as less than one-quarter of neonates globally receive WHO-recommended antibiotics due to resistance. 1, 5
In low- and middle-income countries, 97% of Gram-negative isolates show ampicillin resistance, with similarly concerning rates of third-generation cephalosporin resistance. 1, 7
For late-onset sepsis caused by Enterobacteriaceae, recent systematic review data from 2022 shows alarmingly low sensitivity: for Klebsiella species, 100% of studies found <50% sensitivity to ampicillin, 68% found <50% sensitivity to gentamicin, and 63% found <50% sensitivity to third-generation cephalosporins. 8
Dosing Specifics for Neonates
For ampicillin in neonatal sepsis/meningitis: Dosing depends on gestational and postnatal age. For neonates ≤34 weeks gestational age and ≤7 days postnatal age, use 100 mg/kg/day divided every 12 hours. For those >34 weeks gestational age and ≤28 days postnatal age, use 150 mg/kg/day divided every 8 hours. 3
For gentamicin: The FDA label indicates effectiveness in bacterial neonatal sepsis, and recommends use in conjunction with a penicillin-type drug in neonates with suspected bacterial sepsis or staphylococcal pneumonia. 2
Common Pitfalls to Avoid
Delaying antibiotic escalation: If no clinical improvement occurs after 48-72 hours, broaden coverage immediately rather than continuing ineffective therapy. 5
Ignoring local antibiograms: Resistance patterns vary significantly between institutions and must guide empiric selection; using outdated protocols wastes critical time. 5, 7
Failing to narrow therapy: Once culture results return, de-escalate to the narrowest effective spectrum to reduce resistance development and adverse effects. 5
Continuing antibiotics unnecessarily: Discontinue after 48 hours if cultures are negative and clinical probability of sepsis is low, as prolonged empirical antibiotics increase morbidity and mortality in preterm infants. 5, 6
Using third-generation cephalosporins as initial empiric therapy: This practice accelerates emergence of drug-resistant organisms more rapidly than aminoglycosides and may cause antagonistic interactions when combined with penicillins. 9