What is Nafithromycin?

• Nafithromycin (development code WCK 4873) is an orally bioavailable ketolide developed by Wockhardt Limited with broad spectrum antibacterial activity against respiratory pathogens: Gram-positive bacteria such as S. pneumoniae and S. aureus and Gram-negatives such as Haemophilus influenzae, Moraxella catarrhalis, Legionella pneumophila, Mycoplasma pneumoniae and Chlamydophila pneumoniae.
• Nafithromycin (brand name Miqnaf^®) was approved by India’s CDSCO on January 2, 2025, for the treatment of community-acquired bacterial pneumonia (CABP).
• Nafithromycin is the second ketolide ever approved globally, the first was telithromycin (approved in 2001), which is no longer in use.

Table: Differences between 14-membered macrolides such as erythromycin and clarithromycin and the ketolides nafithromycin and telithromycin – see structures in the figure below.

Why It Matters

• Nafithromycin targets drug-resistant CABP, a major killer with over 3 million deaths globally yearly with India bearing ~25% of this burden.
• Nafithromycin is India’s first ‘home grown’ antibiotic to be granted approved.
• For over 25 years, Wockhardt has focused its drug discovery efforts on the discovery and development of new antibiotics to treat MDR infections.
• The company previously introduced levonadifloxacin (IV) and alalevonadifloxacin (oral) in 2019 and continues to build an impressive antibiotic pipeline.
• This is a proud milestone for Indian drug discovery and a timely addition in the fight against antimicrobial resistance. It will be fascinating to watch how the launch unfolds in India, and whether this innovation finds its way to global markets.

Linezolid, an oxazolidinone-class protein synthesis inhibitor, has been approved since 2000 and is used to treat Gram-positive infections like MRSA. But now, it’s stepping into an entirely new arena: chronic lower back pain.

Why antibiotics?
Emerging research suggests that bacterial infections in herniated disc tissue—think Cutibacterium acnes or coagulase-negative Staphylococcus—is an underlying driver of pain for some patients. The problem? Discs are poorly vascularized, making it difficult for systemic antibiotics to reach therapeutic levels. Past studies with oral amoxicillin alone and in combination with clavulanic acid showed modest pain relief, but directly delivering antibiotics to the infected disc could be a game-changer.

Enter PP353 from Persica Pharmaceuticals
This injectable formulation of linezolid, iohexol (for imaging), and a thermosensitive gel is designed to target degenerate lumbar discs. Once injected, it provides prolonged, high-concentration linezolid exposure at the infection site. Persica’s recent Phase 1b trial results in patients with Modic Type 1 changes (a marker of disc inflammation) are promising—hinting at a future where we treat the root cause of bacterially mediated pain, not just the symptoms. If successful, this approach could also reduce reliance on long-term opioid use.

See Persica’s publications here.

Could this approach transform how we treat chronic back pain worsened by infection?

A breakthrough in the fight against antimicrobial resistance: The US FDA has approved gepotidacin (Blujepa), a first-in-class triazaacenaphthylene oral antibiotic from GSK, on 25 March 2025 for uncomplicated urinary tract infections (uUTIs) in women and girls aged 12+. GSK plans a US launch in the second half of 2025.

What excites me most?
🔹A long-awaited innovation – The first new oral antibiotic for uUTIs in nearly 30 years, introducing a novel bacterial Type II topoisomerase inhibitor chemotype.
🔹Broad-spectrum activity – Targets problematic pathogens like Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, and Enterococcus faecalis.
🔹A model for public-private collaboration – Developed with support from BARDA and the Defense Threat Reduction Agency, highlighting the power of partnerships in tackling urgent health challenges.
🔹Bonus potential – Also in late-stage development for treating uncomplicated urogenital gonorrhoea.

With over half of women facing a uUTI in their lifetime and resistance eroding existing options, Blujepa could be a game-changer. How do you see this approval impacting patient care and the fight against AMR?

I am delighted to share that I have been named a Clarivate Analytics Highly Cited Researcher for 2024, marking the sixth time I have received this honour: Pharmacology & Toxicology in 2016, 2017, 2022, 2023 and 2024, and Cross-Field in 2021.

This achievement would not have been possible without the invaluable contributions of my colleagues, both past and present. Your insights, dedication, and support have been instrumental in shaping our research and amplifying its influence on the field. Thank you for being an integral part of this journey!

This recent letter in Antimicrobial Agents and Chemotherapy from authors from Paratek Pharma on the purity and/or stability of commercially purchased omadacycline tosylate was of interest. Omadacycline is a semi-synthetic tetracycline derivative approved for the treatment of bacterial infections (CABP and CSSSI). In this study, powder from a commercial vender was found to ~53% (wt/wt) omadacycline tosylate when compared to the authentic Paratek omadacycline tosylate drug substance. The purchased material was also amorphous and not crystalline. The remaining material was composed primarily of known impurities without microbiological activity. While this could change an MIC one-fold (not ideal), it could have consequences in other studies.

In another recent publication in Journal of Pharmaceutical and Biomedical Analysis, which was recently discussed by Derek Lowe, workers at Genentech highlighted the importance of investigating drug substance mass balance. They found that azetidine oligomers were present in the drug batch that were not observable by standard NMR, LC, ICP and GC methods. Metal impurities also well known and can cause issues in bioassays, potential toxicity and cause mayhem with drug batch reproducibility.

The most egregious issues can occur when the compound label does not correspond to what’s in the container. Probably the most (in)famous case was when an MDMA (‘ecstasy’) bottle was mislabelled as methamphetamine. This led to a 2003 retraction of a 2002 Science paper that initially claimed that MDMA was as toxic to primates as methamphetamine (also see commentary). There are also residual effects of the initial reports, as the retraction was not as visible in mainstream newspapers – see this article in Journal of Psychoactive Drugs. If you want to delve deeper, Retraction Watch has a specific category devoted to ‘wrong reagents’.

So, it’s always advisable to look for data anomalies, even if they are slight. Also, don’t 100% rely on what is written on the label.

Have you ever wondered what the new antibacterial strategies are?

As part of my work with the Institute for Molecular Bioscience at UQ, we have just published an open access review in ACS Infectious Diseases of antibacterial candidates in clinical trials published , as well as selected compounds still in the early stages of development, that have modes of action (MoAs) not found in marketed antibacterial drugs (antibiotics). Our hope is that this review will encourage further research into new treatment options for drug-resistant infections.