What is the role of antibiotics in the treatment of neonatal sepsis?

Updated: Jun 13, 2019
  • Author: Nathan S Gollehon, MD, FAAP; Chief Editor: Muhammad Aslam, MD  more...
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Answer

In the United States and Canada, the current approach to the treatment of early-onset neonatal sepsis includes the administration of combined intravenous (IV) aminoglycoside and expanded-spectrum penicillin antibiotic therapy. This regimen provides coverage for gram-positive organisms, especially group B Streptococcus (GBS), and gram-negative bacteria, such as E coli. The specific antibiotics to be used are chosen on the basis of maternal history and prevalent trends of organism colonization and antibiotic susceptibility in individual hospitals.

Antimicrobial resistance is increasing in the general population worldwide, and infections are rising in neonatal units due to multidrug- and extensively multidrug-resistant bacteria, posing a significant treatment dilemma. [56]  Reserving broad-spectrum therapy for high-risk infants and quickly de-escalating once culture results are available is one strategy for improving neonatal outcomes. [57]

If an infection appears to be nosocomial, as is common in late-onset sepsis, antibiotic coverage should be directed at organisms implicated in hospital-acquired infections, including S aureus, S epidermidis, and Pseudomonas  species. Most strains of S aureus produce beta-lactamase, which makes them resistant to penicillin G, ampicillin, carbenicillin, and ticarcillin. Vancomycin has been favored for this coverage; however, concern exists that overuse of this drug may lead to vancomycin-resistant organisms, thereby eliminating the best response to penicillin-resistant organisms. For this reason, some clinicians prefer oxacillin or nafcillin therapy in this setting.

Cephalosporins are attractive in the treatment of nosocomial infection because of their lack of dose-related toxicity and their ability to reach adequate serum and cerebrospinal fluid (CSF) concentrations. However, their use has led to the rapid induction of antibiotic resistance in gram-negative organisms. Ceftriaxone displaces bilirubin from serum albumin and should be used with caution in infants with significant hyperbilirubinemia due to the risk of kernicterus or bilirubin encephalopathy. Selection of the most effective drug is based on resistance and sensitivities for the organism isolated from cultures. Studies linking early cefotaxime exposure to an increased risk of neonatal death support the practice of limiting cephalosporin use to case-specific, targeted circumstances, such as in infants with findings concerning for concomitant meningitis. [58]

Zaidi et al compared the failure rates of three clinic-based antibiotic regimens in 0- to 59-day-old infants with possible serious bacterial infections in Karachi, Pakistan. [59] In a randomized study, the researchers found that outpatient therapy with injectable antibiotics is an effective alternative when hospitalization is not possible. Procaine penicillin/gentamicin was superior to oral trimethoprim-sulfamethoxazole, whereas ceftriaxone was more expensive and less effective than penicillin/gentamicin. [59]

Aminoglycosides and vancomycin both have the potential to produce ototoxicity and nephrotoxicity and should therefore be used with caution. Monitor serum drug levels during treatment to minimize the risk of these complications. The drug dosage or interval may have to be adjusted to achieve therapeutic drug serum levels. Infants who received aminoglycosides should undergo audiology and renal function screening before discharge to determine whether any short- or long-range toxic effects of these drugs have occurred.

If culture results are negative but the infant is at significant risk for or has clinical signs of sepsis, the clinician must decide whether to provide continued treatment. In most cases, 36-48 hours of negative culture results should allow the clinician to be confident that sepsis is absent; however, a small number of infants shown to have had sepsis by postmortem examination had negative culture results during their initial sepsis evaluation.

Although there remains concern that intrapartum maternal antibiotic administration may decrease the reliability of neonatal culture results, studies have failed to demonstrate a change in culture sensitivity or time to positive culture. [40, 60]  With this in mind, the need for continued therapy should be based not on a single test, but on a review of all diagnostic data, including the following:

  • Culture results

  • Maternal and intrapartum risk factors

  • CSF results

  • Complete blood cell (CBC) count and differential

  • C-reactive protein (CRP) trends

  • Radiographs

  • Clinical progress


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