NEODOSE

INDICATIONS

Broad-spectrum antibiotic useful against group B streptococcus, Listeria monocytogenes, and susceptible E coli species.

• Anthreax:

• Group B Streptococcal (GBS) Disease:
  • Definitive: The preferred antibiotic for early-onset and late-onset, culture confirmed-GBS disease is penicillin G and the alternative is ampicillin.
  • Empiric:
    • Preterm Infants: The choice is based on multiple factors in those continuously hospitalized beyond 72 hours of age. Empirical choices include group B streptococci-susceptible antibiotics including a β-lactam, cephalosporin, or vancomycin.
      • 7 days or younger: The preferred empiric therapy is ampicillin plus an aminoglycoside. If there is compelling reason to suspect an ampicillin-resistant infection in a critically ill neonate, especially very-low-birth-weight neonates, then consider the addition of a broaderspectrum antibiotic.
      • 8 to 28 days: Ampicillin plus ceftazidime is preferred for previously healthy infants in the community when critical illness and meningitis are absent.
      • 29 to 90 days: Ceftriaxone is recommended for critically ill infants with meningitis.
      • 8 to 90 days: Adding vancomycin to empiric therapy is recommended for previously healthy infants in the community if there is evidence of meningitis or critical illness to expand coverage, including for β-lactam-resistant Streptococcus pneumoniae.
• Infective endocarditis: The following recommendations are based on a consensus of experts. The full pediatric guidelines can be found here:

• Meningitis: Empiric agents for the treatment of meningitis in neonates are ampicillin, gentamicin, and cefotaxime. Reassess therapy based on culture and sensitivity results
• Sepsis, Early-Onset: Ampicillin plus gentamicin are the agents of choice for empirical treatment of early-onset sepsis (EOS) in neonates at most risk for EOS. Broad-spectrum antibiotics may be necessary in neonates who are severely ill, particularly preterm neonates at high risk for EOS after prolonged antepartum maternal antibiotic treatment.
  • Gestational age 34 6/7 weeks or younger:
    • Highest Risk for EOS: Administer empirical antibiotics in those at highest risk; neonates born preterm because of maternal cervical incompetence, preterm labor, premature rupture of membranes, clinical concern for intraamniotic infection, or acute onset of unexplained nonreassuring fetal status.
    • Low Risk: Consider empirical antibiotics based on the risks and benefits. Those at low risk are those born preterm by cesarean delivery because of maternal noninfectious illness or placental insufficiency in the absence of labor, attempts to induce labor, or rupture of membranes before delivery.
  • Gestational age 35 0/7 weeks or older: Administer empirical antibiotics based on level of risk. Multiple approaches of determining risk may be used including categorical algorithms, multivariate risk assessments, or serial physical examinations.

Duration:

• Discontinue antibiotics by 36 to 48 hours when blood cultures are sterile, unless a sitespecific infection has been identified, for preterm and full term neonates.
• Procalcitonin values in addition to perinatal risk factors, signs and symptoms, and laboratory values may aid in the determination to discontinue antibiotic therapy in neonates with suspected early-onset sepsis. The duration of antibiotic therapy was reduced by 9.9 hours with a procalcitonin-guided algorithm compared with standard care in a multicenter randomized control trial of 1710 neonates born after 34 weeks of gestational age with possible or unlikely sepsis. Re-infection and mortality was not different between the groups (risk difference 0.1% (95% CI, -5.2% to 5.3%).

FDA APPROVED INDICATION

• Bacterial meningitis caused by E coli, group B streptococci, and other gram-negative bacteria (Listeria monocytogenes, N meningitides). Addition of an aminoglycoside may increase effectiveness against gram-negative bacteria.
• Septicemia caused by susceptible gram-positive organisms including Streptococcus species, penicillin G-susceptible staphylococci, and enterococci. Gram-negative sepsis caused by E coli, P mirabilis and Salmonella species. Addition of an aminoglycoside may enhance effectiveness.

ADVERSE EFFECTS

Very large doses may result in CNS excitation or seizure activity. Moderate prolongation of bleeding times (by approximately 60 seconds) has been reported after the third or fourth dose in neonates 33 to 41 weeks GA receiving 50 to 100 mg/kg every 12 hours. Prolongation of bleeding times (by approximately 2 minutes) has also been reported after at least 10 doses in preterm very low birth-weight neonates 23 to 30 weeks GA receiving 50 to 100 mg/kg every 12 hours. The clinical implications of the prolonged bleeding time is unknown. Hypersensitivity reactions (maculopapular rash, urticarial rash, or fever) are rare in neonates.

ADMINISTRATION

• Intravenous: Doses 500 mg or less should be administered slowly over 3 to 5 minutes IV and over at least 10 to 15 minutes for doses 1 g or greater. Recommended concentrations are 30, 40, 50, and 100 mg/mL for intermittent IV
• Intramuscular: Mix to a final concentration of 250 mg/mL for IM administration

MONITORING

• Periodic assessment of renal, hepatic, and hematopoietic function in patients receiving extended treatment.
• After 2 consecutive procalcitonin measurements within the normal range and when there is a low risk for infection (assessed by perinatal risk factors, clinical symptoms, and other laboratory findings), consider discontinuation of antibiotics for suspected early-onset sepsis in neonates (34 weeks or older) categorized as infection possible or unlikely. All neonates should receive a minimum of 24 hours of antibiotics before discontinuation.