Antibiotic regimens for suspected late onset sepsis in newborn infants

Editorial note: 

The review question has been addressed in a newer review with an up to date methodology (Korang 2021:

Antibiotics for newborn infants that might have blood infections when more than 48 hours old. Blood infection (sepsis) can make newborn infants seriously ill or even kill them. Sepsis in newborns more than 48 hours old is called late onset neonatal sepsis; it is usually caused by bacteria, and sometimes by fungal infection. Doctors often give antibiotics if they suspect this dangerous condition as it can be difficult to tell if a newborn has late onset neonatal sepsis. Certain antibiotics given for this condition can have serious side effects, including antibiotic resistance, which can result in worse infection. This Cochrane review examined which antibiotics are best for treating late onset neonatal sepsis, in terms of effectiveness and side effects. The authors searched the medical literature and found only one study that met all the criteria the authors were looking for. This study, from 1988, enrolled 28 newborn infants. Some of the newborns received a beta lactam antibiotic by itself while others got the beta lactam plus another antibiotic, an aminoglycoside. There were no significant differences between the two kinds of antibiotic treatment in this study. The Cochrane review authors concluded that there is not enough research to recommend one kind of antibiotic treatment over another for late onset neonatal sepsis.

This review has been superseded by a new Cochrane Review (Korang 2021).

Authors' conclusions: 

There is inadequate evidence from randomised trials in favour of any particular antibiotic regimen for the treatment of suspected late onset neonatal sepsis. The available evidence is not of high quality. Although suspected sepsis and antibiotic use is common, quality research is required to specifically address both narrow and broad spectrum antibiotic use for late onset neonatal sepsis. Future research also needs to assess cost effectiveness and the impact of antibiotics in different settings such as developed or developing countries and lower gestational age groups.

Read the full abstract...

Late onset neonatal sepsis (systemic infection after 48 hours of age) continues to be a significant cause of morbidity and mortality. Early treatment with antibiotics is essential as infants can deteriorate rapidly. It is not clear which antibiotic regimen is most suitable for initial treatment of suspected late onset sepsis.

This review has been superseded by a new Cochrane Review (Korang 2021).


To compare the effectiveness and adverse effects of different antibiotic regimens for treatment of suspected late onset sepsis in newborn infants.

Search strategy: 

The standard search strategy of the Cochrane Neonatal Review Group was used. This includes electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2004), MEDLINE (1966 - Dec 2004), EMBASE (1980 - Dec 2004) and CINAHL (1982 - Dec 2004), electronic abstracts of Pediatric Academic Society meetings (1996 - Dec 2004) and previous reviews including cross references (all articles referenced).

Selection criteria: 

Randomised and quasi randomised controlled trials comparing different initial antibiotic regimens in neonates with suspected late onset sepsis were evaluated.

Data collection and analysis: 

Both reviewer authors screened abstracts and papers against the inclusion criteria, appraised the quality of and extracted data from papers. For dichotomous outcomes, treatment effect was expressed as relative risk and risk difference with 95% confidence intervals. NNT was calculated for outcomes for which there was a statistically significant reduction in risk difference.

Main results: 

Thirteen studies were identified as possibly eligible for inclusion. The majority of studies were excluded as they did not separate data for early and late onset infection. Two studies are still awaiting assessment. Only one small study, in 24 neonates, was included in this review. It compared beta-lactam therapy with a combination of beta lactam plus aminoglycoside. The study did not meet our prespecified criteria for good methodological quality. In babies with suspected infection there was no significant difference in mortality (RR 0.17, 95% CI 0.01 to 3.23) or treatment failure (RR 0.17, 95% CI 0.01 to 3.23). Antibiotic resistance was assessed and there were no cases in either group.