Evidence memo / Immune & thymic

Gramicidin

Also: gramicidin D · tyrothricin component · channel-forming peptide antibiotic

Gramicidin is a peptide antibiotic with a place in history: in 1939 it became the first antibiotic to be manufactured and used in the clinic, before penicillin was widely available. Today it survives as a topical and eye-drop antibiotic for minor infections, often combined with others. The Watchlist boundary is that it is strictly a surface treatment, never given into the body because it destroys red blood cells.

Approved for specific usesApproved specific use

The verdict

Our read at a glance.

Whether gramicidin is understood as a topical/eye-only peptide antibiotic with a distinct membrane-channel mechanism, of mainly historical and niche importance, rather than a systemic antibiotic.

The signal
Gramicidin reliably kills Gram-positive bacteria on contact and has decades of use as a topical and ophthalmic antibiotic, usually combined with other agents (such as neomycin and polymyxin B). Its evidence is established by long use for minor surface infections rather than by modern trials.
The unknown
Its place is settled and narrow; the main practical questions are formulation, local tolerance, and stewardship of topical antibiotics rather than any new use.
Our read
A historic, niche peptide antibiotic: gramicidin was the first antibiotic used in the clinic and is a classic membrane-channel-forming molecule, but its hemolytic toxicity confines it to topical and eye use. Read it as an approved surface antibiotic and a piece of antibiotic history, not a systemic treatment, and a real counterpart to unproven topical antimicrobial-peptide claims.

The mechanism

How it works.

Bacteria, like all cells, keep careful gradients of ions (like sodium and potassium) across their membrane, and need those gradients to live. Gramicidin is a small peptide that slips into the membrane and, by pairing up, forms an open channel that lets those ions pour freely across. The gradients collapse, the membrane loses its charge, and the Gram-positive bacterium dies. This channel-forming (ionophore) mechanism is different from antibiotics that block cell-wall building (like bacitracin or penicillin). The catch is that gramicidin does the same thing to human red blood cells, bursting them, which is why it can only ever be used on the surface of the body, never injected.

Safety & regulatory boundary

The consequential part.

Gramicidin cannot be given into the body because it ruptures red blood cells (it is hemolytic), so it is used only on the surface, on skin and in the eye. Topical use is generally well tolerated but can cause local irritation or allergy. It is an approved topical/ophthalmic antibiotic, not a systemic drug, and it is a real, approved peptide antibiotic, unlike the unproven antimicrobial-peptide skin claims tracked elsewhere here.

What's next

What we're watching.

Mainly stewardship of topical antibiotics; no new systemic or major role is expected given its hemolytic toxicity.

Context

Why this is discussed.

Gramicidin is a landmark: the first antibiotic put to clinical use, isolated by Rene Dubos in 1939, before penicillin reached patients. It is also a textbook example of a peptide that kills bacteria by punching ion channels through their membrane, and it still appears in some topical and eye antibiotic products.

The evidence base

9 cited references.

Regulatory & labels2

DailyMed label: NEOMYCIN AND POLYMYXIN B SULFATES AND GRAMICIDIN

A-S Medication Solutions (FDA label) · 2026

DailyMed label: NEOMYCIN AND POLYMYXIN B SULFATES AND GRAMICIDIN

Bausch & Lomb Incorporated (FDA label) · 2024

Indexed literature (PubMed)5

Over-the-counter antibiotics compromising aminoglycoside activity

Robertson A et al. · J Antimicrob Chemother · 2025

Peptide models for membrane channels

Marsh D · Biochem J · 1996

In vitro antibacterial activity of gramicidin and tyrothricin

Ruckdeschel G et al. · Arzneimittelforschung · 1983

Enhanced eryptosis following gramicidin exposure

Malik A et al. · Toxins (Basel) · 2015

Keep reading

Related published memos.