Randomised controlled trial of fosfomycin in neonatal sepsis: pharmacokinetics and safety in relation to sodium overload

Antimicrobial resistance (AMR) disproportionally impacts populations in low-income and middle-income countries (LMICs). Reductions in mortality have been less in neonates than older children, and at least one-quarter of neonatal deaths are attributable to infection.1 AMR contributes to this burden, with multidrug-resistant (MDR) pathogens accounting for ~30% of global neonatal sepsis deaths.2

WHO recommends ampicillin, penicillin or cloxacillin (if Staphylococcus aureus infection is suspected) plus gentamicin (first-line), and third-generation cephalosporins (second-line) for empiric treatment of neonatal sepsis.3 With spread of extended spectrum β-lactamase (ESBL) and carbapenemase enzymes,4 clinical isolates are commonly reported non-susceptible to this regimen.5 Carbapenem-sparing is important in controlling MDR,6 and reintroduction of legacy antibiotics has been advocated to address the lack of new affordable antibiotics.7

Fosfomycin is an off-patent phosphonic acid derivative identified as ‘critically important’ by WHO.8 Fosfomycin is bactericidal9 and exhibits activity against Gram-positive and Gram-negative bacteria, including methicillin-resistant S. aureus, vancomycin-resistant Enterococcus spp, ESBL producers and may penetrate biofilms.10 Fosfomycin demonstrates in vitro synergy with aminoglycosides and carbapenems11 12 and is commonly used for MDR urinary tract infections in adults.13



Christina W Obiero, Phoebe Williams, Sheila Murunga, Johnstone Thitiri, Raymond Omollo, Ann Sarah Walker, Thaddaeus Egondi, Borna Nyaoke, Erika Correia, Zoe Kane, Silke Gastine, Karin Kipper, Joseph F Standing, Sally Ellis, Mike Sharland, James Alexander Berkley


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