All Smiles at the Press Conference: Plazo+Levo Delivers

This December, Achaogen released much data on 2 plazomicin trials[1]: the pivotal EPIC study comparing plazomicin / levofloxacin with meropenem / levofloxacin in cUTI is the one we want to look at today because it is interpretable, while the other trial Continue reading All Smiles at the Press Conference: Plazo+Levo Delivers

Antibiotic Inhalers Galore (Part 1):  More Combinations and Permutations than a Rubik’s Cube

There is much interest in inhaled antibiotics these days.  Prima facie, the logic for this approach is compelling: Getting the antibiotic (and a lot of it) directly to the site of infection, while avoiding systemic toxicity, sounds like optimized efficacy Continue reading Antibiotic Inhalers Galore (Part 1):  More Combinations and Permutations than a Rubik’s Cube

Timely New Information on Next-Generation Tetracyclines – Part 2: Eravacycline and Protein Binding

A recent paper by Thabit describes a curious finding [1]. The authors measured total and free (i.e., nonprotein-bound) eravacycline levels at ascending doses in a mouse model. They found strikingly small increases in free drug levels when titrating up total doses. The Continue reading Timely New Information on Next-Generation Tetracyclines – Part 2: Eravacycline and Protein Binding

Choose your Outcome: How Design Minutiae Affect Trial Results

When you search for ‘ceftidoren’ on Wikipedia, you will get a surprise: there is no entry. However, a search on the web tells us that Spectracef (ceftidoren pivoxil) still exists. Gee, now the drug is spelled ‘cefditoren’ and – looking Continue reading Choose your Outcome: How Design Minutiae Affect Trial Results

The FDA AMDAC on Fluoroquinolones (Part 2): Where Were the FQ Advocates?

Any FDA meeting is a high-stakes game for industry:  One never knows how the discussions will go. Some oddball issue may take center stage and usurp much time, creating an unbalanced perspective.  At other times, simple issues seem to create Continue reading The FDA AMDAC on Fluoroquinolones (Part 2): Where Were the FQ Advocates?

AMDAC November 5, 2015 on Fluoroquinolones in ABS, ABECB, uUTI  – Part 1

Only now, a few days before the actual AMDAC meeting, the FDA’s Briefing Document becomes available to the public.  The topic of the December 5th meeting:  Reappraisal of the risk/benefit of fluoroquinolones (FQ) in approved but “mild, self-limiting” disease indications in Continue reading AMDAC November 5, 2015 on Fluoroquinolones in ABS, ABECB, uUTI  – Part 1

After ICAAC: Some More Thoughts on Eravacycline in cUTI and IGNITE-2

When a well-designed pivotal Phase 3 trial fails to show NI, it demands an explanation.  While awaiting the company’s analysis of the data, many possible explanations are bandied about.  So it was not surprising that the eravacycline cUTI study (IGNITE-2) Continue reading After ICAAC: Some More Thoughts on Eravacycline in cUTI and IGNITE-2

MRSA Fluoroquinolones – An Interesting Bunch Playing a High-Stakes Game

Fluoroquinolones (FQ) of the ofloxacin/ciprofloxacin generation were mainly active against Gram-negative bacteria, distinguishing themselves as cidal IV/PO drugs with high potency against most lactose- and non-lactose fermenters.  They were excellent against problem pathogens like P. aeruginosa, had excellent efficacy against Salmonellae, the Gonococcus Continue reading MRSA Fluoroquinolones – An Interesting Bunch Playing a High-Stakes Game

Most Anti-Infective Guidelines Don’t Get No Respect (Let Alone Use!)

It is no secret that most existing antibiotic guidelines are not getting much use these days.  The only indications pursued with any regularity are the feasible ones: ABSSSI, cUTI, and cIAI, much less CABP.  Yes, the occasional HABP/VABP trial is Continue reading Most Anti-Infective Guidelines Don’t Get No Respect (Let Alone Use!)

Why Moxifloxacin’s Approval for Plague Is So Disturbing

PLEASE SHARE YOUR OPINION AND VOTE BELOW On May 8th, 2015 moxifloxacin/Avelox was approved for treatment of inhalational plague.[1]   We learn that the approval followed the ‘animal rule’ process, and that treatment with moxifloxacin was 100% effective in the African Green Continue reading Why Moxifloxacin’s Approval for Plague Is So Disturbing

Aerosolized Antibiotics & Selling Nebulizers

“The medicine comes for free, just pay us for the inhaler” should be the marketing slogan for this group of therapeutics.  Nebulizers are good business: hard to copy as a delivery system, they are a great opportunity to ‘evergreen’ off-patent Continue reading Aerosolized Antibiotics & Selling Nebulizers

The Futile Quest of Proofing a Negative in the Presence of Overwhelming Absence of Harm

The cartilage damage caused by fluoroquinolones in juvenile beagle dogs is not subtle:  blister formation and erosions occur in a dose-dependent fashion resulting in reversible cartilage damage.  These lesions can be seen not just histologically but even macroscopically.  The animals Continue reading The Futile Quest of Proofing a Negative in the Presence of Overwhelming Absence of Harm

QT Prolongation with Azithromycin and Levofloxacin

Several antibiotic classes are associated with QTc prolongation: macrolides, quinolones, the antimalarials that share the quinine structure, and many azole antifungals.  FDA warned about the proarrhythmic effects of azithromycin in 2013 [i] but it is a recent publication by Rao Continue reading QT Prolongation with Azithromycin and Levofloxacin