Little evidence for current optimal antibiotic therapy in febrile neonates.
Date First Published:
September 25, 2009
Last Updated:
September 25, 2009
Report by:
Paul Willis, Medical Student (Oregon Health and Science University)
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 trial.mp.)
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]
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 trial.mp.)
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]
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.
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):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| 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 Reese H. Clark, Barry T. Bloom, Alan R. Spitzer, and Dale R. Gerstmann 2006 USA | -128,914 NICU patients empirically treated w/ abx. -24,111 treated w/ amp and ceftoax -104,803 patients treated w/ amp and gentamicin |
Retrospective cohort | Likelihood of death | OR 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 |
Author Commentary:
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.
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.
References:
- 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