Efficacy and Treatment Duration: Where is the Tipping Point?

Development pf antibacterials differs in several important ways from drug development in other areas, and the lack of standard dose-finding is just one of them. Dose-finding in its most basic form involves ascending amounts of drug for efficacy and safety; Continue reading Efficacy and Treatment Duration: Where is the Tipping Point?

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

Eravacycline Conference Call: Unrevealing and Disappointing

Whatever has become of investigative journalism?  All we read after the Stifel conference call (11/17/2015) is descriptive rehash of information provided by Tetraphase at the conference.  No probing questions that we thought investors would ask who just lost 80% of Continue reading Eravacycline Conference Call: Unrevealing and Disappointing

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

Mme Erava and The Mysterious Case of Auto-Combustion

SH: My dear Watson, did you read the news of the astonishing debacle that befell Mme Erava and made the headlines, creating anxiety of hitherto unknown proportions in Tetraland? Dr.W.: A disaster of epic proportions, for sure, and a mystery, Continue reading Mme Erava and The Mysterious Case of Auto-Combustion

Brilacidin – QIDP Drug At a Critical Juncture

At around this time (July 2015), Cellceutix is expected to hammer out a Phase 3 program for brilacidin, its defensin-mimetic and host-defense protein (HDP) mimic structurally similar to magainin, with FDA. Brilacidin is certainly an interesting novel compound, coming from a Continue reading Brilacidin – QIDP Drug At a Critical Juncture

Treating GC in the Face of Dwindling Antibiotic Options – (2)

For GC antibiotics, the development path looks like a trip down the road less traveled, leading into some uncharted territory. Let’s take Melinta’s statement [1] at face value according to which the single 900 mg dose of delafloxacin failed because of Continue reading Treating GC in the Face of Dwindling Antibiotic Options – (2)

Commenting on Comments:  The Ceftaroline Trial Program in CABP

The ceftaroline (Teflaro®) program was executed at a time when FDA was debating a new CABP Guidance with new outcome measures: no longer was the time-honored TOC assessment acceptable, instead improvement on Day 3-5 was to become the new primary Continue reading Commenting on Comments:  The Ceftaroline Trial Program in CABP

Meropenem Dosing for VAP: High + Prolonged Beats Conventional Dosing

Sometimes an article pops up addressing a question we have been mulling over for quite some time.  It so happened with a recent publication which shed new light on penem dosing for ICU patients[1]. Conducted at a single Belgian centre Continue reading Meropenem Dosing for VAP: High + Prolonged Beats Conventional Dosing

Some Thoughts about Eravacycline Based on the Phase 2 cIAI Study

Solomkin et al. conclude that the efficacy and safety of eravacycline compares favorably to the control drug, ertapenem.[1]  This top-level assessment is made with the usual caveats (insufficient statistical power, small sample size), but a few points deserve comment. Eravacycline Continue reading Some Thoughts about Eravacycline Based on the Phase 2 cIAI Study

The Breakpoint Dilemma

As antibiotic resistance increases over the years, originally established susceptibility breakpoints (S-I-R) are becoming less relevant.   This ‘creep’ towards higher MICs over time is a unique but well-known feature of antimicrobials ultimately making these drugs obsolete. In the past, Continue reading The Breakpoint Dilemma