By Benedikt Huttner
This is the first ESGAP summary on antimicrobial stewardship activities at ASM Microbe 2016, that is being held in Boston, and deals with the symposium “Controversies in Antimicrobial Stewardship” (see here) purpose of this session according to the program was to discuss “current controversies / challenges / hot topics in antimicrobial stewardship“.
The first two presentations were a Pro-Con debate on de-escalation of antimicrobial therapy in the ICU setting:
– The „Pro“ side was presented by Marc Leone from France, the first author of probably the best randomized controlled trial so far on de-escalation of antibiotic therapy in the ICU setting (this multicenter trial failed to demonstrate non-inferiority of a de-escalation strategy compared to continuation of therapy in patients with severe sepsis with regard to the primary outcome „length of ICU stay“) Marc argued that de-escalation should be part of a comprehensive antibiotic stewardship strategy that includes stopping antibiotics if an infection is unlikely since it reduces exposure to broad-spectrum antibiotics and is unlikely to negatively impact patient outcomes (indeed most studies have shown an association of de-escalation with improved survival – although Marc admitted that this association is biased by „confounding by indication“).
– Jeroen Schouten from the Netherlands presented the CON part (as he had already done at ECCMID in Amsterdam in April; the PRO part at that time was presented by Jean-Francois Timist). Jeroen argued that not only there is no clear definition of de-escalation (see the recently published paper in CID of which both Marc and Jeroen are co-authors but he also nicely demonstrated that the evidence for an impact of de-esclation on favourable patient outcomes, overall antibiotic exposure and antimicrobial resistance is weak and hampered by major methodological limitations of the studies (severity of diseases at the time of de-escalation is eg rarely taken into account). He also mentioned a recent Belgian retrospective study which failed to show an impact of de-escalation on the emergence of resistance. Jeroen argued that shortening of duration of therapy may be a more promising approach and he mentioned the recent Dutch procalcitonin trial (of which he is a co-author. Yet, he failed to convince the audience (this was an interactive session with polling) that de-escalation should not be an integral part of antibiotic stewardship and he had to admit that he would also „de-escalate“ in certain situations… The debate is thus likely to go on until we have more high-quality RCTs.
The next presentation by Bojana Beovic (the current ESGAP president) from Slovenia was entitled „iv-oral switch: are published criteria relevant?”.
– Bojana reviewed the literature and showed that few criteria have really been validated. Except for the Pneumonia guidelines, most ID guidelines do not even mention any criteria for evaluating when oral switch is possible.
– She also mentioned the we might also face a paradigm shift for infections like left-sided endocarditis where the currently accepted dogma that iv treatment for the entire treatment period is the only valid approach is currently being challenged (see the recent retrospective study from France; in addition two RCTs are currently going on).
– While at the beginning of her presentation the audience mostly felt that iv-po switch was not done because physicians forgot about it, at the end most agreed that the problem is also a lack of validated criteria.
The fourth presenter, was Jason Roberts from Australia and he talked about optimization of PK/PD and whether it can prevent resistance.
– He argued that the many critically-ill patients, especially the young with hyper-filtration, are probably under dosed and Jason argued for the importance of therapeutic drug monitoring of beta-lactams.
– Jason also argued for the importance to consider the “Mutant Prevention Concentration (MPC)” for PK/PD targets rather than just the Minimal Inhibitory Concentration (MIC).
He also mentioned the potential interest of combination therapy to prevent emergence of resistance. This was the topic addressed by the last speaker Mical Paul from Tel Aviv, but she mostly argued against the use of combination therapy.
– She particularly focused on the evidence supporting the use of combination therapy for multidrug resistant organisms such as carbapenemase producing Klebsiella pneumonia or Acinetobacter species.
– She nicely illustrated that the studies suggesting a superiority of combination therapy suffer from major methodological limitations (eg by including infections with strains still susceptible or with low-level resistance to carbapenems). She argued that treating all infections caused by carbapenemase producing Enterobacteriaceae (CPE) with colistin and a carbapenem would massively increase carbapenem use in settings with a high endemicity of CPE, increasing selection pressure for CPE. In her hospital these infections are treated with colistin monotherapy (a RCT examining this question, led by Mical, is scheduled to finish recruitment by this fall.
In summary, the session showed again how much there is still to learn in antibiotic stewardship and that there is plenty material for future “controversies” sessions (with hopefully new evidence).