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Little evidence for current optimal antibiotic therapy in febrile neonates.

Three Part Question

In [neonates with fever] is [empiric abx therapy of cefotaxime/amp better than gentamicin/amp] at [improving patient overall survival]?

Clinical Scenario

26 day-old male is transferred to OHSU ED for further work-up of 1 d h/o fever and a UA showing elevated WBC and bacteria. Blood cultures were drawn, and an LP was performed. The newborn was given tylenol for fever. He was admitted to the pediatric inpatient service for ROS. There was question as to whether to begin empiric therapy with either gentamicin/ampicillin or cefotaxime/ampicillin.

Search Strategy

1.Medline 1950 to July 2009 using the OVID interface [exp infant, newborn AND exp fever AND (exp ampicillin AND (exp gentamicin OR exp cefotaxime))].
2.Medline 1950 to July 2009 the OVID interface [exp infant, newborn AND exp fever AND anti-bacterial agents]
3.Medline 1950 to July 2009 using the OVID interface [exp infant, newborn AND exp fever AND (exp clinical trials/ or exp randomized controlled trials/ or randomized controlled
4.Medline 1950 to July 2009 using the OVID interface [exp infant, newborn AND (exp fever OR exp meningitis OR exp sepsis OR exp pneumonia) AND exp anti-bacterial agents AND (exp ampicillin AND (exp gentamicin OR exp cefotaxime)) AND (exp clinical trials or exp randomized controlled trials or randomized controlled trial).
5.Google. [empiric therapy cefotaxime gentamicin]

Search Outcome

1.5 Articles. None were relevant
2.0 Articles
3.33 Articles. None were relevant
4.16 Articles. Multiple trials comparing gent/amp and cefotax/amp to other regimens for newborn bacterial meningitis, but none comparing the two regimens to each other.
5.88,000 articles. 1 relevant article. Details shown in table 1.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Clark, RH, Bloom BT, Spitzer, AR, Gerstmann, DR.
-128,914 NICU patients empirically treated w/ abx. -24,111 treated w/ amp and ceftoax -104,803 patients treated w/ amp and gentamicinRetrospective cohortLikelihood of deathOR 1.5 w/ cefotax vs. gentamicin (CI 1.4-1.7)-only included NICU patients treated w/ abx <4 days after birth -didn't restrict to just babies with fever -retrospective study


In infants <30 days, it appears that no RCTs have actually been performed comparing the two empiric regimens w/ survival as an outcome. However, the 2006 study by Clark, et al suggests that, in neonates <3 days treated with empiric therapy in the NICU, survival is significantly improved with gentamicin/ampicillin vs. cefotaxime/ampicillin.

Clinical Bottom Line

There are no studies which address optimal empiric therapy for neonates aged 1-28 days with fever. However, a large study w/ NICU neonates <4 days of age supports the use of gentamicin/ampicillin in neonatal patients without contraindications to the regimen.


  1. Reese H. Clark, Barry T. Bloom, Alan R. Spitzer, and Dale R. Gerstmann Empiric Use of Ampicillin and Cefotaxime, Compared With Ampicillin and Gentamicin, for Neonates at Risk for Sepsis Is Associated With an Increased Risk of Neonatal Death