Treatment option for sepsis in children in the era of antibiotic resistance

Abstract

Sepsis caused by multidrug-resistant microorganisms is one of the most serious infectious diseases of childhood and poses significant challenges for pediatricians involved in management of critically ill children. This review discusses the use of pharmacokinetic/dynamic principles (i.e., prolonged infusion of β-lactams and vancomycin, once-daily administration of aminoglycosides and rationale of therapeutic drug monitoring) when prescribing antibiotics to critically ill patients. The potential of ‘old’ agents (i.e., colistin, fosfomycin) and newly approved antibiotics is critically reviewed. The pros and cons of combination antibacterial therapy are discussed and finally suggestions for the treatment of sepsis caused by multidrug-resistant organisms are provided.

Keywords::

• antibiotic
• MDR gram-negatives
• MDR gram-positives
• PK/PD
• TDM

Financial & competing interests disclosure

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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Efficacy data on the treatment of sepsis caused by multidrug-resistant (MDR) organisms in children are largely extrapolated from adult studies, as evidence-based pediatric studies are very limited. Pharmacokinetic/pharmacodynamic studies can partly overcome existing gaps.

• The number of new antibiotics for treatment of MDR infections in children is still low.

• Old agents (i.e., colistin, fosfomycin) could be potentially used after appropriate dosing regimen for all pediatric age groups have been defined.

• Advanced generation β-lactams for MDR gram-negative organisms and vancomycin for methicillin-resistant Staphylococcus aureus/methicillin-resistant S. epidermidis remains the cornerstone of therapy.

• Prolonged or continuous infusion of time-dependent antibiotics for pathogens with increased MICs is supported by the pharmacokinetic/pharmacodynamic modeling studies, but existing clinical evidence is still too limited to recommend its routine use.

• When prolonged infusion is applied, a loading dose should be used to achieve timely bactericidal concentrations.

• ODD doses of aminoglycosides have been safely used in neonates and children with sepsis.

• For vancomycin and aminoglycosides, high inter-individual and inter-microbial variability mandates the use of therapeutic drug monitoring to ensure safety and efficacy. The role of β-lactam therapeutic drug monitoring remains to be established.

• Combination therapy should be reserved for situations with high risk of resistance and/or severe disease. When considered, increased adverse event rates compared to monotherapy need to be borne in mind.

Notes