Efficacy and safety of switching from intravenous to oral antibiotics (amoxicillin–clavulanic acid) versus a full course of intravenous antibiotics in neonates with probable bacterial infection (RAIN): a multicentre, randomised, open-label, non-inferiority trial

Switch from intravenous-to-oral antibiotics in neonatal probable and proven early-onset infection: a prospective population-based real-life multicentre cohort study

“…In the RAIN study, readmission due to reinfection occurred in 1 of 252 (0.4%) neonates undergoing intravenous-to-oral switch therapy, which was non-inferior to 1 of 252 (0.4%) receiving intravenous-only. The safety of intravenous-to-oral switch in culture-negative EOI, as found in both our prospective cohort and in the RAIN study, is supported by pharmacological studies, which have shown that oral administration of amoxicillin in clinically stable neonates results in serum concentrations surpassing the minimal inhibitory concentrations of amoxicillin of GBS for more than 50% of the time of the dosing interval 12 16 18. The safety of the intravenous-to-oral switch is also in line with results from randomised controlled trials from low-income and middle-income countries, where first-line treatment with oral antibiotics was non-inferior to intravenous treatment 13 14.…”

“…The main limitation of this study was the inclusion of culture-negative cases. However, most neonates had clinical signs of infection, and those without had maternal risk factors and CRP above 50 mg/L, a higher cut-off value than those used in other countries (10–30 mg/L) 5 18 32. Another limitation was that the comparison of overall antibiotic use before and after the implementation of intravenous-to-oral switch therapy was based on estimates from the Danish Neonatal Database, which is non-validated 33.…”

“…However, intravenous therapy has disadvantages, including the need for hospitalisation and intravenous peripheral catheter reinsertions 9–11. There is emerging evidence to support the effectiveness and safety of switch from intravenous-to-oral administration of antibiotic therapy in neonates with EOI 12–18…”

Fighting Antimicrobial Resistance in Neonatal Intensive Care Units: Rational Use of Antibiotics in Neonatal Sepsis

“…Additionally, an ongoing trial by Dutta et al has been designed to examine whether a total of 7 days of antibiotics is not inferior compared to a total of 14 days of antibiotics among neonates with uncomplicated, culture-proven sepsis with respect to definite or probable relapse of sepsis within 21 days of observation after intravenous antibiotic completion [ 121 ]. Finally, Keij et al examined the efficacy and safety of early intravenous-to-oral antibiotic switch therapy compared with a 7 day course of intravenous antibiotics among neonates with probable bacterial infection [ 122 ]. After an initial 48–72 h of intravenous antibiotics, neonates were switched to an oral suspension of amoxicillin/clavulanic acid (intervention group) or continued on intravenous antibiotics, according to the local protocol, for a total of 7 days.…”

“…Neonates were included in the trial if they were of a postmenstrual age of 35 weeks or older and a postnatal age of 0–28 days with a body weight of at least 2 kg, whereas neonates with culture-proven bacterial sepsis or severe clinical sepsis were excluded. The authors reported that a cumulative reinfection rate at 28 days did not differ between the groups (<1%) [ 122 ]. Of note, the inclusion of neonates with specific gestational age and birthweight in the previous trials suggested that the studies applied to a selected group of neonates.…”