Sepsis Forum 2022: Uncomplicated infections – pros and cons of ultra-short term antibiotic treatment

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Exposure to antimicrobials is related to the emergence of resistance in microorganisms, which is a major challenge in clinical practice around the world. There is an increasing tendency to spend less time on antibiotics. However, the use of ultra-short times is still a matter of debate.

A session of the XVIII International Sepsis Forum discussed these points in terms of pros and cons.

Arguments against using ultra-short time

  • The duration of antimicrobial treatment should take into account some factors: host immune status, pathogen involved, site of infection, clinical response, whether there is still exposure to the risk factor, and whether focus has been removed.
  • Several strategies are used to determine shorter treatment times: based on de-escalation, based on biomarkers, based on clinical response associated with biomarkers and complexity, and based on fixed treatment times to which ultra-short-term treatments fall.
  • However, a single definition of what would be ultra-short can be difficult due to the heterogeneity of the infection types. Likewise, it is difficult to define what would be uncomplicated infections associated with septic patients.
  • To consider ultra-short treatment times, some requirements are necessary: ​​fully susceptible pathogens, bactericidal effect with Pk / Pd optimization, rapid onset of antibiotic effect, good penetration at the site of infection, antibiotic effect on non-dividing bacteria, antimicrobial effect, there is unaffected by conditions caused by infection, absence of foreign body, absence of abscesses and absence of signs of immune deficiency.
  • An important point to consider is the extent to which the results of studies showing benefits (or non-inferiority) of short antibiotic times can be extrapolated to other populations. The speaker cites two recent articles, CAP-IT published in JAMA (doi: 10.1001 / jama.2021.17843), which evaluated the treatment of bacterial pneumonia in children, and PTC published in The Lancet (doi.org/10.1016/S0140-6736(21)00313-5), which evaluated the discontinuation of beta-lactams in patients with community-acquired pneumonia after three days. In both cases, factors such as the exclusion of critically ill, immunosuppressed patients and patients with other severity factors must be taken into account when interpreting the results.

arguments for

  • Ultra-short antibiotic treatment times are not applicable to certain types of infections such as endocarditis, osteomyelitis, cystic fibrosis or pneumonia. legionella. In addition, it is necessary to have proper focus control and the absence of immunosuppression.
  • Antimicrobials are used to treat infections and not sepsis itself. For adequate treatment of sepsis, supportive measures are essential and there is still no specific treatment.
  • Following antibiotic exposure, bacterial death occurs in two phases: an initial rapid phase (bacteria with a normal phenotype) and a slower one (bacteria with a persistent phenotype), with an appropriate response to treatment when there is an effect in both phases.
  • Based on this dynamic model for the antimicrobial effect of the drugs used for invasive infections caused by Escherichia coli and for Staphylococcus aureus, two to four days and four to nine days of treatment, respectively, would be sufficient.
  • The risk of adverse events increases by 4% and the risk of developing antimicrobial resistance by 3% for each day of antibiotic treatment. This means that an increase in antibiotic exposure from three to five days represents a 9% increase in the operating room for side effects. When one considers a difference from three to seven days, it is an increase of 19%.

individualization

  • The duration of treatment has several variables: characteristics of the antimicrobial agent, the type of microorganism involved and host variables. The severity of the infection and the site of infection must also be considered.
  • Markers of improvement are important and widespread when they individualize therapy, especially in critically ill patients, even without much scientific evidence for their use. Among these are clinical improvement, blood counts and procalcitonine.
  • A multicenter study in Spain followed 312 patients with community-based PNM randomized to at least five days of treatment or discontinuation of treatment if there were more than 48 hours without fever and without clinical instability. There was no difference between the groups in mortality at 10 and 30 days, one year, nor in new admissions or cardiovascular events.
  • A systematic review of studies evaluating enterobacterial bacteremia without endocarditis and with catheter removal found no difference in mortality within 30 days between those treated for more or less ten days of treatment.
  • Another study also points to non-inferiority with treatment with 7 vs. 14 days for uncomplicated gram-negative bacteremia. It is noteworthy that most infections had a urinary focus.

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# Bielicki JA, Stöhr W, Barratt S, et al. Effect of Amoxicillin dose and duration of treatment on the need for re-treatment of antibiotics in children with community-acquired pneumonia: CAP-IT Randomized Clinical Trial. JAMA. 2021; 326 (17): 1713-1724. doi: 10.1001 / jama.2021.17843 # Jacques Ropers, et al. Discontinuation of β-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical wards (PTC): a double-blind, randomized, placebo-controlled, non-inferiority study. Published: March 27, 2021. doi: https://doi.org/10.1016/S0140-6736(21)00313-5

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