Three “new antibiotics” and two chapters in our textbooks that need to be rewritten. Six slam-dunk top publications, that was all (!) in the clinical trials late-breaker session at ECCMID2017. The “antibiotics” are a beta-lactamase that inactivates cephalosporins in the gut to prevent C. difficile infection (CDI), and two drugs with activity against CPE: a new aminoglycoside (plazomicin) and a ciderophore cephalosporin (cefiderocol). The antibiotic pipeline starts dripping again.
Abstracts of these studies are not available yet, and this is what I recall from the presentations (and a little help from internet).
The oral beta-lactamase (ribaxamase) was tested in a randomized double-blind placebo-controlled trial (RdBpCT) in patients receiving ceftriaxon (with/without a macrolide) and reduced the occurrence of CDI with 74%. A fascinating new approach: inactivating antibiotics where they only do harm: in the colon. More studies on this approach are under way and there also was a failure in a phase2 study presented in the same session (not ribaxamase).
Cefiderocol, a siderophore cephalosporin with activity against all Gram-negative bacteria (but not Gram-postives) was compared in a RdBCT to imipenem in 452 patients with complicated UTI. The primary efficacy endpoint (composite of clinical cure and microbiologic eradication) was met in 72.6% and 54.6% in patients receiving cefiderocol and imipenem, respectively. It also was non-inferior in other efficacy and safety endpoints.
Plazomicin was compared in the EPIC study to meropenem in 609 patients with cUTI, and also succeeded in being non-inferior in efficacy and safety, at all endpoints. In fact, it was associated with less recurrences of UTI. In the CARE study 39 patients with CRE infection (80% BSI) were treated with tigecyclin (60%) or meropenem (40%) and then randomized to adjunctive treatment with plazomicin (n=18) or colistin (n=21). All-cause day 28 mortality was 12% and 40% for plazomicin and colistin, respectively, and in survival analysis the hazard for death at day 60 was 0.37 (0.15-0.91) for plazomicin.
And finally two pearls of real-world pragmatic studies, both from the UK.
In the ARREST study about 750 patients with S.aureus bloodstream infection (SAB) were randomized to added therapy with rifampin or placebo, that started after an average of 68 hours antibiotic therapy. An impressive amount of data was presented (just 1 week after database lock!) and rifampicin failed to improve outcome on every thinkable endpoint. Discussion closed, I think.
In the OVIVO study 1054 patients with bone/joint infections were randomized to guideline recommended 6 weeks iv-treatment or the possibility to swith to oral therapy after 7 days of iv-treatment. Marvelously executed (including cost analyses an quality-of-life) and no differences in any outcome (only less catheter-associated infections in the oral therapy group). The new strategy would save 20M £££ per year in the UK (probably less than the funding). Again, discussion closed I think.
Looking forward to see the final scientific publications (also to see if my memory didn’t let me down), but these are 3 new kids on the block and another proof that Brexit will reduce the quality of EU-based clinical studies.