Treatment options for neonatal infections in the post-cefotaxime era

ABSTRACT

Introduction

Cefotaxime has been used for the management of neonatal infections since the 1990s for suspected meningitis and to mitigate gentamicin-associated renal injury. Its shortage in 2015 and subsequent removal from the U.S. pharmaceutical market forced providers to consider alternatives. Ceftriaxone, a cephalosporin with an identical antibacterial spectrum of activity to cefotaxime, is contraindicated in neonates due to its risk of biliary pseudolithiasis. Ceftazidime was recommended as an alternative by the American Academy of Pediatrics but is inequivalent.

Areas covered

This article addresses indications for cephalosporin use and considerations when selecting an alternative to cefotaxime. Differences among cefotaxime, ceftriaxone, ceftazidime, and cefepime are discussed and compared to the standard-of-care presumptive regimen, ampicillin, and gentamicin. The authors consider the data behind the neonatal contraindication to ceftriaxone and provide recommendations for their application to practice.

Expert opinion

The data against ceftriaxone use in neonates remain poor, particularly in the context of the cefotaxime shortage and lack of an equivalent alternative. Ceftriaxone could be considered in low-risk neonates without hyperbilirubinemia or exposure to calcium-containing fluids on a case-by-case basis. Ceftazidime monotherapy for presumptive management of neonatal infections is inappropriate; cefepime should be more frequently utilized in neonates who are poor candidates for ceftriaxone.

KEYWORDS:

• Biliary pseudolithiasis
• ceftriaxone
• cefotaxime
• cephalosporins
• neonatal sepsis
• CSF penetration

Article highlights

• Cefotaxime has an important place in neonatal sepsis and meningitis management due to its superior penetration into cerebral spinal fluid and activity against gram-negative organisms versus gentamycin, but cefotaxime has been unavailable in the United States since 2015.

• Ceftriaxone, the most therapeutically equivalent agent to cefotaxime, is contraindicated in neonates because of reported biliary sludging and pseudolithiasis in children, but neonatal data are poor. Ceftazidime and cefepime are not equivalent to cefotaxime in bacterial coverage, urging the consideration for ceftriaxone use in low-risk neonates.

• Ceftriaxone use should be considered in NICUs unable to obtain cefotaxime in low-risk neonates without exposure to calcium-containing fluids for more than 48 hours and whose bilirubin levels are closely monitored and remain below 8 mg/dL.

• The decision to use ceftriaxone, ceftazidime, or cefepime in place of ampicillin and gentamicin or cefotaxime should be thoughtfully made based on comorbidities, concern for meningitis, and suspected bacterial pathogens.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was not funded.