An endless one-sided confidence in Pip-tazo?

This weeks’ publication of the highly controversial results of the MERINO trial in JAMA caused quite a stir on social media. The paper has been viewed >50,000 times and the unexpected outcome has been challenged by many. But what was the conclusion in JAMA? “Among patients with E. coli or K. pneumoniae bloodstream infection (BSI) and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a non-inferior 30-day mortality.” Not and  in the same sentence, a doubled denial, is confusing. More important, as formulated, the study was inconclusive, which nobody seems to accept. We dived into the depths of the reporting and then tried to explain it. Continue reading

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A POET with a sledgehammer

Imagine, the look on the face of that ambitious PhD student, each day screening six hospitals for patients with S. aureus endocarditis, opening the NEJM and seeing that the Danes randomized 400 patients with Infective endocarditis (IE). And then his supervisor rubbing in that these 400 all underwent two extra transoesphageal echocardiograms for study purposes, that there were zero losses to follow-up and telling him how many samples of blood were collected to analyze antibiotic concentrations. Luckily, he was scheduled for our Journal club, which allowed him to apply the “trias scientifica”. Continue reading

Gaming with non-inferiority in antibiotic stewardship

An early switch from IV to oral treatment is one of the pillars of antibiotic stewardship. Oral antibiotics are mostly cheaper, hospital stay shortens and thus also the risk of healthcare-associated infections. One problem: before we change our current practice, we must demonstrate that the new strategy is safe. The best evidence comes from a non-inferiority trial. Yet, that usually implies enrolment of many patients. The solution to that problem: put on your poker face when drafting your sample size calculation and hope for the best. Our Danish colleagues show how.  Continue reading

Procalcitonin-guided antibiotics for respiratory tract infections (part 2)

Two weeks ago I posted a blog about an impeccable NEJM study on the effects of procalcitonin (PCT) on antibiotic use in patients with lower respiratory tract infection. I stated that this RCT was one of the first diagnostic studies in this disease area targeting the correct patients and ended by an invitation to identify the fatal flaw. Last week one of the PhD students (Valentijn Schweitzer, absent when the paper was discussed in our journal club) told me that searching a fatal flaw was not needed; as the RCT was unnecessary in the first place. Here is why. Continue reading

Procalcitonin-guided antibiotics for respiratory tract infections

Every day thousands of physicians worldwide are facing the dilemma whether “to treat or not to treat this coughing patient with antibiotics”. A test that safely discriminates a bacterial from a non-bacterial cause is the holy grail, and some feel that procalcitonin (PCT) is just that. Results from multiple – mostly European – studies and meta-analyses pushed them in that direction. Yet, we are not that often sure of the causative pathogen, and diagnostic research in the absence of a gold standard is tricky business. And now there is this marvelous study that perfectly addresses that uncertainty and questions all prior PCT evidence, and that was discussed in our PhD journal club. Continue reading

The antipathy against SDD explained

With the first paper on Selective Digestive Decontamination in ICU patients published in 1983, this year marks the 35th anniversary of one the fiercest controversies in intensive care medicine, infection prevention and clinical microbiology. To celebrate this, Intensive Care Medicine published 3 editorials called the “Antipathy against SDD is justified”: 1 arguing Pro, 1 Con and 1 wasn’t sure. If the contents of these editorials had been patients, a (good) physician would have called them “diagnostic”. SDD is where clinical epidemiology becomes psychology and sociology. Continue reading

Fosfomycin: the hottest drug in town!? News from ECCMID 2018

In our team Thijs ten Doesschate does a PhD in clinical epidemiology addressing some clinical aspects on fosfomycin; An old antibiotic, active against Enterobacteriaceae, and surfacing as promising alternative to beta-lactams and fluoroquinolones in times of antibiotic resistance. He is currently coordinating a multi-center double-blind placebo-controlled randomized trial to determine non-inferiority of fosfomycin (against ciprofloxaxin) in the step-down oral treatment of complicated Urinary Tract Infections (UTI). If non-inferior, we could reduce cipro usage. For himself (and now for us) he summarized fosfomycin news at ECCMID. Most presentations (O) and posters (P) can also be found on http://www.eccmidlive.org/ .

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