Treatment of Resistant Gram-negative bacilli in children

Infect Dis Now. 2023 Nov;53(8S):104794. doi: 10.1016/j.idnow.2023.104794. Epub 2023 Oct 5.

Abstract

Resistance of Gram-negative bacteria to the most widely used antibiotics, particularly β-lactams, is now considered as major public health problem. The main resistance mechanisms to β-lactams in Enterobacterales are the production of extended spectrum β-lactamases (ESBL) or carbapenemases, which hydrolyze virtually all β-lactams. However, a substantial proportion of carbapenem-resistant Gram-negative bacilli do not produce carbapenemase but combine overproduction of a cephalosporinase and/or ESBL with very low penem hydrolysis and reduced outer membrane permeability. The arrival of new antibacterial agents active on some of these multidrug-resistant strains, such as new β-lactam inhibitors, has marked a turning point in treatment and represents real progress. In-depth knowledge of resistance mechanisms is crucial to the choice of the most effective molecule, and their prescription requires close collaboration between microbiologists, infectious disease specialists and intensive care physicians. While these compounds are significantly more active against resistant strains than those previously available, their spectrum of activity does not cover all resistance mechanisms in Gram-negatives, nor in other bacterial species potentially involved in polymicrobial infections. The use of these new compounds does not alter antibiotic regimens in terms of duration and indication of combined antibiotic therapy, which remain very limited.

Keywords: Carbapenemases; Child; Enterobacteral antibiotic resistance; Extended Spectrum β-lactamases.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Carbapenems / pharmacology
  • Child
  • Gram-Negative Bacteria
  • Gram-Negative Bacterial Infections* / drug therapy
  • Humans
  • beta-Lactams

Substances

  • Anti-Bacterial Agents
  • beta-Lactams
  • Carbapenems