NEODOSE

INDICATIONS

• Treatment of infections caused by aerobic gram-negative bacilli (eg, Pseudomonas, Klebsiella, E coli). Usually used in combination with a β-lactam antibiotic.
• 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:
  • 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 controlled 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%).

ADVERSE EFFECTS

Transient and reversible renal tubular dysfunction may occur, resulting in increased urinary losses of sodium, calcium, and magnesium. Vestibular and auditory ototoxicity may occur. The addition of other nephrotoxic and/or ototoxic medications (eg, furosemide, vancomycin) may increase these adverse effects. Increased neuromuscular blockade (ie, neuromuscular weakness and respiratory failure) may occur when used with pancuronium or other neuromuscular blocking agents and in patients with hypermagnesemia. The use of gentamicin ointment for newborn ocular prophylaxis has been associated with periocular ulcerative dermatitis.

BLACK BOX WARNING

Aminoglycoside therapy has been associated with potential neurotoxicity, ototoxicity, and nephrotoxicity. Patients with impaired renal function, dehydration, and those who receive high dosage or prolonged therapy are at an increased risk of toxicity. Discontinue therapy or adjust dose if there is evidence of ototoxicity or nephrotoxicity. Aminoglycoside ototoxicity is usually irreversible.

ADMINISTRATION

Infuse over a period of 30 to 120 minutes using a concentration of 2 mg/mL or 10 mg/mL. Administer as a separate infusion from penicillin-containing compounds. IM injection is associated with variable absorption, especially in the very small infant.

MONITORING

Measure serum concentrations when treating for more than 48 hours. Obtain peak concentration 30 minutes after end of infusion, and trough concentration just prior to the next dose. When treating patients with serious infections or significantly changing fluid or renal status consider measuring the serum concentration at 22- or 24-hours after a dose, and use the tables below for the suggested dosing interval. Blood samples obtained to monitor serum drug concentrations should be spun and refrigerated or frozen as soon as possible. Routine measurement of gentamicin concentrations are probably not necessary in full-term neonates without risk factors (low urine output, evidence of renal impairment, presence of shock, and/or concomitant use of nephrotoxic drugs).