Adjunctive therapy to treat neonatal sepsis

ABSTRACT

Introduction: Neonatal sepsis (NS) is a very severe condition that causes significant morbidity and mortality.

Areas covered: To overcome the limits of antibiotic therapy and improve NS outcomes, measures chosen among those theoretically able to improve host defenses or positively interfere with deleterious immune responses could be suggested. This paper discusses the mechanisms of action of these measures, whether their efficacy in prophylaxis justifies use in NS therapy and their impact.

Expert opinion: NS remains a relevant problem despite the availability of antibiotics effective against the most common agents and the introduction of effective preventive measures such as group B Streptococcus prenatal screening and intrapartum antibiotic prophylaxis. This explains why attempts to introduce new prophylactic and therapeutic measures have been made. Unfortunately, none of the measures suggested and tested to date can be considered a definitive advance. It is highly likely that in the future, new measures will be proposed according to the increase in the knowledge of the characteristics of immune system function in preterm infants and the methods to modulate unproper immune responses.

KEYWORDS:

• Granulocyte colony stimulating factor
• granulocyte transfusion
• immunoglobulin
• lactoferrin
• melatonin
• minerals
• neonatal sepsis
• pentoxifylline
• probiotic

Article highlights

• Neonatal sepsis (NS) is a very severe condition that causes significant morbidity and mortality. Usually, NS is classified according to the age of onset: cases that appear within the first 3 days in neonates admitted to the neonatal intensive care unit and within the 7 days of life for term infants are defined as early-onset sepsis (EOS); NS diagnosed beyond 3 days of life in neonates observed in the NICU and beyond 7 days of life in term infants are classified as late onset sepsis (LOS).

• NS remains a relevant problem despite the availability of antibiotics effective against the most common pathogenetic agents and the introduction of highly effective preventive measures such as GBS prenatal screening and intrapartum antibiotic prophylaxis.

• The use of measures theoretically able to improve host defences (i.e. immunoglobulin, granulocyte transfusion, granulocyte/macrophage colony stimulating factors) and/or modulate the immune response (i.e. minerals, melatonin, pentoxifylline, probiotics) to prevent or treat NS seems very attractive. However, the available data are insufficient to draw firm conclusions, and presently, none of the suggested adjuvants is included in the official guidelines for the management of neonates at risk.

• Measures that are potentially effective can be used only for prophylaxis, as the time necessary for effective action is too long and incompatible with the need for an urgent intervention such as that required during NS. The best example in this regard is given by the use of PBT, which is presently largely prescribed for the prevention of NS in PT infants but is never used for NS therapy.

• For ML, the results of the use of NS therapy are promising, although insufficient to draw firm conclusions. These therapeutics may be effective for a short time and reduce damage due to inappropriate immune responses.

• Presently, traditional preventive measures, including human milk feeding and maternal prophylaxis against group B Streptococcus, remain the most effective solution to reduce the risk of NS. The rational use of antibiotics, together with nutritional, cardiovascular and respiratory support, are the most effective factors to assure the best outcome of children with NS.

• In the future, new antimicrobial proteins and peptides might be proposed for NS prevention and therapy. Moreover, new methods to improve the innate immune response and thereby reduce the risk of NS development will be developed. Finally, inhibition of the inflammasome might further improve NS outcomes.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.