Antibiotics in Neonatal Infections

Abstract

The bacteria most commonly responsible for early-onset (materno-fetal) infections in neonates are group B streptococci, enterococci, Enterobacteriaceae and Listeria monocytogenes. Coagulase-negative staphylococci, particularly Staphylococcus epidermidis, are the main pathogens in late-onset (nosocomial) infections, especially in high-risk patients such as those with very low birthweight, umbilical or central venous catheters or undergoing prolonged ventilation. The primary objective of the paediatrician is to identity all potential cases of bacterial disease quickly and begin antibacterial treatment immediately after the appropriate cultures have been obtained. Combination therapy is recommended for initial empirical treatment in the neonate. In early-onset infections, an effective first-line empirical therapy is ampicillin plus an aminoglycoside (duration of treatment 10 days). An alternative is ampicillin plus a third-generation cephalosporin such as cefotaxime, a combination particularly useful in neonatal meningitis (mean duration of treatment 14 to 21 days), in patients at risk of nephrotoxicity and/or when therapeutic monitoring of aminoglycosides is not possible. Another potential substitute for the aminoglycoside is aztreonam. Triple combination therapy (such as amoxicillin plus cefotaxime and an aminoglycoside) could also be used for the first 2 to 3 days of life, followed by dual therapy after the microbiological results. In late-onset infections the combination oxacillin plus an aminoglycoside is widely recommended. However, vancomycin plus ceftazidime (+/- an aminoglycoside for the first 2 to 3 days) may be a better choice. Teicoplanin may be a substitute for vancomycin. However, the initial approach should always be modified by knowledge of the local bacterial epidemiology. After the microbiological results, treatment should be switched to narrower spectrum agents if a specific organism has been identified, and should be discontinued if cultures are negative and the neonate is in good clinical condition. Penicillins and third-generation cephalosporins are generally well tolerated in neonates. There is controversy regarding whether therapeutic drug monitoring of aminoglycosides will decrease toxicity (particularly renal damage) in neonates, and on the efficacy and safety of a single daily dose versus multiple daily doses of these drugs. Toxic effects caused by vancomycin are uncommon, but debate still exists over the need for therapeutic drug monitoring of this agent. When antibacterials are used in neonates, accurate determination of dosage is required, particularly for compounds with a low therapeutic index and in patients with renal failure. Very low birthweight infants are also particularly prone to antibacterial-induced toxicity.

A Population and Developmental Pharmacokinetic Analysis To Evaluate and Optimize Cefotaxime Dosing Regimen in Neonates and Young Infants

“…These are mainly hypersensitivity and gastrointestinal effects (45). Cefotaxime very rarely causes nephrotoxicity or seizures in neonates (46). The favorable safety profile observed in our population is in agreement with these previous findings.…”

Pharmacokinetics of Cefotaxime and Desacetylcefotaxime in Infants during Extracorporeal Membrane Oxygenation

“…This need not be a problem with drugs that are as safe as cephalosporins are considered to be (11,16). Our standard dose regimen is based on studies of neonatal and pediatric patients that have identified the influence of gestational age (20), body weight (20), postnatal age (6), and renal function (28) on CTX pharmacokinetics.…”

Real-Time Polymerase Chain Reaction for Detecting Bacterial DNA Directly from Blood of Neonates Being Evaluated for Sepsis

“…[1][2][3][4] Infants admitted to the neonatal intensive care unit (NICU) for sepsis evaluation are usually managed clinically with bacterial cultures, a complete blood count (CBC), and combination antimicrobial therapy for presumed sepsis; for example, the antibiotics given to the term infant might include ampicillin and gentamicin, or ampicillin and cefotaxime. [5][6][7][8][9] Traditionally, infants are provided with antibiotic therapy for 72 hours pending negative culture results. 10 -12 Currently, there is no definitive test for diagnosing neonatal sepsis because even blood culturing techniques have unacceptably low sensitivities.…”