Prof. Paolo Manzoni

Prof. Paolo Manzoni

Neonatal sepsis are associated with a huge burden of morbidity and mortality.

Infections occurring in the neonatal period include bloodstream, urine, cerebrospinal, peritoneal, and lung infections as well as infections starting from burns and wounds, or from any other usually sterile sites.

For many pathogens, peripheral colonization usually precedes systemic infection, however many episodes of sepsis are actually caused by a breakthrough , pathogenic microorganism.

Sepsis in neonates, especially when preterms, are  associated with cytokine – and biomediator-induced disorders of respiratory, hemodynamic, and metabolic processes.

Neonates in the neonatal intensive care unit feature many specific risk factors for bacterial and fungal sepsis. Prematurity is the most important risk factor, since the incidence rates of sepsis are linearly associated with decreased gestational age and birth weight. In addition, loss of gut commensals such as Bifidobacteria and Lactobacilli spp, as occurs with prolonged antibiotic treatments, delayed enteral feeding, or nursing in incubators, translates into proliferation of pathogenic microflora and abnormal gut colonization.

Empirical antibiotic treatment is popular in preterm neonates because of severity of sepsis and in lack of early, reliable laboratory sepsis markers.

No conclusive data exist, though, on the appropriate duration of antibiotic courses. These two factors often determine an overuse of antibiotics (either in number of infants exposed, or in duration of exposure in single patients). This overuse is associated with a number of potential adverse outcomes, such as selection of multidrug-resistant organisms, invasive candidiasis, necrotising enterocolitis,  increased costs, modification and disruption of the normal development of the gut microbiota potentially impacting  on late gut health and immunity.

A wide range of measures can be implemented in order to prevent overuse of antibiotics nonetheless preventing neonatal infections.

Improvement in diagnostic skills is mandatory, and this goal can be pursued by implementing the use of novel diagnostic methodologies like the heart –rate frequency characteristics, and the gradient in central vs. peripheral body temperature. Moreover, skilled use of the existing biomarkers of infection can be of increasing help in better understanding when is possible to stop antibiotic courses.In fact, withdrawal of unnecessary exposure when empirical use has been performed is equally advisable, meaning that antibiotics may be suspended if the infection is not clinically and microbiologically confirmed after 48-72 hrs. Shorter courses may be also envisaged when infection is confirmed.

A wide range of preventative measures can be implemented, since overuse of antibiotics may obviously be limited by preventing infections.

Promotion of breast-feeding and – more generally – nutritional and feeding strategies enhancing the role of human fresh milk are of utmost importance. Hygiene measures are a key step, as the greatest proportion of infections in neonates are acquired nosocomially.

Adoption of a cautious central venous catheter policy, including CVC bundles, is critical to decrease the frequency of catheter-associated infections (CLABSI).

Enhancement of the enteric microbiota composition with the supplementation of probiotics, medical stewardship concerning H2blockers with restriction of their use, all of this translate into a better chance for the neonate host to develop a competent enteric microbiota thus enhancing some defensive mechanisms at gut level.

Use of drugs or bioactive substances in prevention is also important, and its usefulness has been consistently underlined in the last decade. Bovine lactoferrin supplementation can prevent late-onset sepsis by any agent in preterm neonates, whereas fluconazole  and (to a lesser extent) nystatin can prevent invasive systemic fungal infections.

Finally, specific measures are warranted to prevent ventilator associated pneumonia (VAP), and among them, early weaning from mechanical ventilation is the most impacting measure.

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