Best Use of Antibiotics

I recently posted news from Pittsburgh in which outcomes for patients with KPC producers treated with ceftazidime-avibactam were superior to those in which polymyxins were used. This data was observational, not from an RCT, and so requires confirmation from larger, better designed studies. This week, results from the TANGO-2 study, were released in which a randomized trial comparing meropenem-vaborbactam with "best available therapy" (BAT) was stopped early by its DSMB because of the risk to patients in the BAT arm. The press release describing these results can be found here: http://www.themedicinescompany.com/investors/news/medicines-company-announces-tango-2-trial-meropenem-vaborbactam-formerly-carbavance Only 72 patients were enrolled, of which 43 had CRE infections. Clinical cure was significantly higher in patients treated with meropenem-vaborbactam. These patients also had lower mortality and lower rates of renal adverse events. This data has not yet been pu...

NDM is a metallo-beta-lactamase and provides a bigger treatment challenge than KPC. This is because avibactam (and vaborbactam and relebactam) does not inhibit it. Therefore, NDM producers are resistant to ceftazidime-avibactam. However, avibactam may still play a role in the treatment of infections with NDM producers. This is when it is combined with aztreonam. Aztreonam is a curious antibiotic because it is not inactivated by NDM. However, most NDM producing bacteria produce other beta-lactamases as well, some of which will inactivate aztreonam. So aztreonam alone will rarely be a useful option for NDM producers. Several years ago, David Livermore from the UK, hypothesized that combining avibactam with aztreonam would provide a useful treatment option for NDM producers. This is because the avibactam will inactivate all of the "other" beta-lactamases, allowing aztreonam to kill the bacteria because it is not destroyed by NDM. Development of the aztreonam-avibactam com...

MRSA is a killer but luckily we are seeing less of it in hospitals than we used to. Treatment of MRSA has been turned on its head with the advent of antibiotics like daptomycin and linezolid. But my guess is that we still turn to vancomycin in many situations, including MRSA bloodstream infections. Counterintuitively, adding an antistaphylococcal beta-lactam (eg, flucloxacillin or nafcillin) to vancomycin is synergistic in both in vitro and animal models. Could this add to vancomycin's effectiveness in patients? A pilot study ("CAMERA"), published in CID, showed that the mean duration of MRSA bacteremia was 3.0 days in patients assigned to vancomycin monotherapy and 1.94 days in those given vancomycin plus flucloxacillin. These findings can be found here: Combination of Vancomycin and β-Lactam Therapy for  Methicillin-Resistant Staphylococcus aureus  Bacteremia: A Pilot Multicenter Randomized Controlled Trial. Davis JS, Sud A, O'Sullivan MVN, Robinson JO,...

Is there still a role for colistin or polymyxin B in the treatment of KPC producers? There is a plethora of articles examining treatment of KPC producers. Most now conclude that a combination of a polymyxin with other antibiotics is more effective than use of a polymyxin alone. Based on a single center experience, recently made available online by Antimicrobial Agents and Chemotherapy , the place of polymyxins as firstline therapy for KPC producers is looking very doubtful . This article looked at treatment of bloodstream infection due to carbapenem resistant Klebsiella pneumoniae at the University of Pittsburgh Medical Center. Importantly, it was observational, not a RCT. Clinical success was defined at 30 days as survival, resolution of signs and symptoms of infection, sterilization of blood cultures within 7 days of treatment initiation, and absence of recurrent infections. A good choice of endpoints. 85% (11/13) patients treated with ceftazidime-avibactam had clinical succes...

The Nobel Prize website is full of absolute gems. In addition to a searchable list of "who won" and "what for", it also has bios of the winners, a listing of who nominated them and PDFs of both their Nobel lecture and their banquet speech. Bob Dylan's fabulous speech is found here: https://www.nobelprize.org/nobel_prizes/literature/laureates/2016/dylan-lecture.html Moving back to ID, Sir Alexander Fleming's Nobel lecture can be found here: https://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/fleming-lecture.pdf For those of you who are microbiologists, it is interesting to learn that Fleming used his newly discovered penicillin as a selective agent in culture medium to isolate Bordetella pertussis and "Pfeiffer's influenza bacillus" (presumably H. influenzae ) from respiratory samples. Famously Fleming delivered an important message to those of us who are antibiotic stewards or interested in antibiotic dosing: "I...

Please read no further if you are from Barcelona. You have made up your mind already on this topic! For those of you with an open mind, I would like to question the opinion that ampicillin and ceftriaxone should be first line therapy for enterococcal endocarditis. We have all seen the elderly patient with a prosthetic heart valve and Enterococcus faecalis in their blood. I love these consults because: (a) I know ID input can add a lot to the management of these infections, and (b) I know we are in the long haul and so I will get to know the patient well. But I also groan a little when I get the call because I know we are in for a difficult time - problems include "too old and sick for valve replacement surgery", there is real mortality associated with this infection, and yes, these are the patients in whom aminoglycoside use can be challenging. For those of you who had the pleasure of knowing Bob Moellering, you will recall he was the pioneer of understanding that ent...

Welcome! The purpose of this blog is to critically review new information on antibiotics of relevance to hospital based ID Physicians and Pharmacists. My emphasis is to get beyond data from FDA and EMA registration studies, to data that will really make a difference to ID practice. I don't care if a new antibiotic has data for complicated intra-abdominal infection, but really want to know if it will work in a sick patient with bloodstream infection due to a multiresistant organism. We are entering a fortunate time in which a host of new antibiotics against multiresistant organisms will soon be available. I want to look beyond "the spin" to ensure we use the best antibiotic for each individual patient. If that is a generic and "cheap" antibiotic, let's go for it. If it is a new and expensive antibiotic, let's critically examine the data. One of my interests is going beyond observational studies to ID physician/pharmacist led RCTs that are going to an...