In response to my previous post Claus Klingenberg wrote a comment in which he mentioned a recent systematic review that he had published with a group of colleagues. This review of a small number of RCTs (9) and a larger number of observational studies (38) examined the effects of prolonging or broadening the spectrum of antibiotic therapy on individual risks such as NEC and later fungal sepsis, and how those complications impact mortality. (Esaiassen E, et al. Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis. J Antimicrob Chemother. 2017;72(7):1858-70).

The RCTs were generally comparisons of different antibiotic regimes, apart from one of routine antibiotics vs no antibiotics. The observational studies were also mostly short vs long courses, and narrow vs broad spectrum. They found:

Prolonged antibiotic exposure in uninfected preterm infants is associated with an increased risk of NEC and/or death, and broad-spectrum antibiotic exposure is associated with an increased risk of IFI.

The authors of the review appropriately did not calculate a pooled Odds Ratio, as the studies are too heterogeneous, but the individual ORs for NEC and/or death range from 1.3 to 7.7, they include numerous observational studies with over 5,000 babies. The studies of invasive fungal infection show in most instances, and particularly in larger studies, an association with the use of third generation cephalopsorins or carbapenems. Specifically among preterm infants, there is an increase in all-cause mortality when antibiotics are given for longer periods in babies with negative cultures.