Monograph of Neomycin

Introduction/Overview

Neomycin is a member of the aminoglycoside class of antibiotics, historically significant for its broad-spectrum activity against Gram-negative bacteria and certain Gram-positive organisms. The drug remains integral in topical formulations for skin and eye infections, as well as in some systemic preparations for localized infections. While systemic use has largely been supplanted by newer aminoglycosides with improved safety profiles, neomycin continues to be valuable in specific clinical contexts, particularly where resistance patterns or drug availability dictate its selection.

Learning objectives for this chapter include:

• Identify the chemical and pharmacological classification of neomycin.
• Explain the molecular basis of its antibacterial activity and potential cellular effects.
• Describe the key pharmacokinetic parameters that influence dosing and monitoring.
• Outline approved therapeutic indications and common off‑label applications.
• Recognize the spectrum of adverse reactions and strategies for minimizing toxicity.

Classification

Drug Class and Chemical Category

Neomycin falls within the aminoglycoside antibiotic group, characterized by the presence of amino-substituted sugars linked by glycosidic bonds. Chemically, it is a mixture of two major components, neomycin B and neomycin C, with additional minor analogues. The molecular formula for neomycin B is C₂₇H₅₃N₁₀O₁₇, and for neomycin C is C₂₈H₅₅N₁₀O₁₈. The mixture exhibits a high degree of glycosidic linkage diversity, contributing to its pharmacologic profile.

Pharmacological Subclass

As an aminoglycoside, neomycin is primarily bactericidal. It is frequently combined with other antibiotics, notably polymyxins and beta‑lactams, to broaden spectrum and mitigate resistance. Within topical preparations, neomycin is often paired with bacitracin and polymyxin B, forming a classically known triple combination antibiotic ointment.

Mechanism of Action

Pharmacodynamic Overview

Neomycin binds to the 30S subunit of bacterial ribosomes, disrupting the initiation complex of translation. This binding is mediated by the aminoglycoside’s 2,6-diaminopropionic acid residues, which recognize the A-site of the 30S subunit. The resultant misreading causes incorporation of incorrect amino acids, leading to the synthesis of nonfunctional proteins and eventual cell death. The bactericidal effect is concentration-dependent, and the post-antibiotic effect (PAE) is modest compared to other aminoglycosides.

Cellular Mechanisms and Resistance

Upon entry into bacterial cells via an energy-dependent, two-step transport process, neomycin accumulates in the cytoplasm. The drug’s affinity for the ribosomal RNA is enhanced by the presence of the 4,6-dihydroxylysine moiety, which facilitates protonation and membrane translocation. Resistance mechanisms include enzymatic modification (acetylation, adenylation, or phosphorylation), decreased permeability through porin channels, and active efflux pumps. The prevalence of aminoglycoside-modifying enzymes significantly limits the clinical utility of neomycin in systemic therapy.

Pharmacokinetics

Absorption

Topical administration results in limited systemic absorption, with reported plasma concentrations typically below 1 μg/mL when used on intact skin. Oral ingestion of neomycin leads to negligible systemic bioavailability (<1%) due to extensive first-pass metabolism and poor gastrointestinal permeability. Systemic exposure is therefore primarily derived from local application or accidental ingestion in vulnerable populations.

Distribution

When absorbed systemically, neomycin displays a low volume of distribution (V_d ≈ 0.3 L/kg). The drug demonstrates negligible penetration across the blood–brain barrier and the blood–ocular barrier, rendering it unsuitable for systemic treatment of central nervous system or ocular infections. Distribution to extracellular fluid is limited by its cationic nature and hydrophilicity.

Metabolism

Neomycin undergoes minimal hepatic metabolism. The primary route of elimination is renal excretion unchanged. Minor metabolites, such as dehydroneomycin, have been identified but are present at negligible levels and not clinically relevant.

Excretion

Renal clearance (CL_renal) accounts for the majority of neomycin elimination, with a half-life (t_1/2) ranging from 2 to 4 hours in individuals with normal renal function. The drug’s elimination follows first-order kinetics, and accumulation may occur in patients with impaired renal clearance.

Dosing Considerations

In topical formulations, the concentration is typically 0.5–1.0% w/v, which provides sufficient local bactericidal activity while minimizing systemic exposure. Systemic dosing, when historically employed, involved 15–20 mg/kg/day divided into multiple administrations, yet this approach is rarely used due to toxicity concerns. Dose adjustments are recommended in patients with creatinine clearance <40 mL/min, with a potential reduction in frequency or dose to prevent accumulation.

Therapeutic Uses/Clinical Applications

Approved Indications

Neomycin’s primary indications are topical, encompassing:

• Skin infections, including superficial abscesses, cellulitis, and minor burns.
• Ophthalmic infections, such as bacterial conjunctivitis, where it is formulated as eye drops or ointments.
• Intrauterine applications for prophylaxis of postoperative endometritis in certain obstetric protocols.

Off-Label and Emerging Uses

While systemic use is largely discontinued, neomycin has been employed in the following off-label contexts:

• As part of a triple antibiotic ointment for prophylactic treatment of surgical wounds with high contamination risk.
• In combination with nitrofurantoin for urinary tract infections, although data supporting efficacy are limited.
• In veterinary medicine for treating certain bacterial infections in livestock, where regulatory approvals differ from human medicine.

Adverse Effects

Common Side Effects

Topical application may lead to local irritation, pruritus, and transient erythema. Systemic exposure, though rare, can result in the following:

• Ototoxicity manifested as tinnitus, vertigo, or hearing loss, particularly with prolonged high-dose exposure.
• Nephrotoxicity characterized by acute tubular necrosis, presenting as increased serum creatinine and reduced glomerular filtration.
• Local anaphylactic reactions, including urticaria and angioedema.

Serious or Rare Adverse Reactions

Severe nephrotoxicity can occur in patients with pre-existing renal impairment or when combined with other nephrotoxic agents, such as loop diuretics or amphotericin B. Ototoxicity may be irreversible if exposure exceeds safe limits, and monitoring of auditory function is advised in susceptible individuals. Rarely, anaphylactic shock has been documented following intravenous administration, necessitating immediate cessation and supportive care.

Black Box Warnings

Given the potential for irreversible ototoxicity and nephrotoxicity, regulatory agencies require a black box warning for systemic use. The warning emphasizes the necessity of monitoring renal function and auditory thresholds, especially in patients with concurrent risk factors.

Drug Interactions

Major Drug-Drug Interactions

Neomycin’s aminoglycoside structure predisposes it to synergistic toxicity when combined with other agents:

• Loop diuretics (e.g., furosemide) can potentiate nephrotoxicity by promoting renal concentration of neomycin.
• Amphotericin B may lead to additive renal damage.
• Other aminoglycosides (gentamicin, tobramycin) can increase cumulative ototoxic risk.

Contraindications

Contraindications include known hypersensitivity to neomycin or any aminoglycoside, active intravascular contamination, and severe renal impairment (creatinine clearance <20 mL/min) when systemic therapy is contemplated. Topical use is contraindicated in patients with a history of severe allergic reactions to the drug.

Special Considerations

Pregnancy and Lactation

Neomycin is classified as pregnancy category C. Rodent studies have indicated potential fetal toxicity at high doses, though human data are limited. Consequently, systemic exposure should be avoided during pregnancy unless benefits outweigh risks. Topical use is considered relatively safe, with minimal transdermal absorption; however, caution is advised. The drug is excreted into breast milk at low levels, and the risk to nursing infants is low. Nonetheless, monitoring for signs of systemic absorption is prudent.

Pediatric and Geriatric Considerations

In children, especially infants, the risk of ototoxicity is heightened due to immature renal function and smaller body size. Dosing is typically weight-based, and serum drug levels are rarely measured unless prolonged therapy is required. Older adults exhibit decreased renal clearance, increasing the probability of accumulation; dosage adjustment based on creatinine clearance is recommended. In both populations, vigilance for auditory and renal adverse events is essential.

Renal and Hepatic Impairment

Renal dysfunction markedly prolongs t_1/2, raising the risk of nephrotoxicity and ototoxicity. Dose reductions or extended dosing intervals are advised when creatinine clearance falls below 40 mL/min. Hepatic impairment has minimal impact on neomycin pharmacokinetics due to the drug’s negligible hepatic metabolism; however, concurrent hepatic disease may exacerbate systemic absorption from the gastrointestinal tract, warranting caution.

Summary/Key Points

• Neomycin is an aminoglycoside antibiotic primarily used topically; systemic use is limited due to toxicity.
• Its bactericidal action involves interference with the 30S ribosomal subunit, leading to faulty protein synthesis.
• Pharmacokinetic properties include low systemic absorption, renal clearance as the main elimination route, and a half-life of 2–4 hours in healthy adults.
• Approved indications focus on topical skin and eye infections; systemic indications are rare and contraindicated in many patient populations.
• Adverse effects are dominated by nephrotoxicity and ototoxicity; monitoring renal function and auditory thresholds is crucial.
• Drug interactions that potentiate renal or auditory toxicity should be avoided or closely monitored.
• Special populations—pregnant women, nursing mothers, children, and elderly patients—require dose adjustments and careful monitoring due to altered pharmacokinetics and heightened susceptibility to toxicity.
• Clinical pearls: employ topical formulations whenever possible; avoid systemic exposure in patients with renal impairment; consider alternative aminoglycosides (e.g., gentamicin) when systemic therapy is unavoidable.

References

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8. Rang HP, Ritter JM, Flower RJ, Henderson G. Rang & Dale's Pharmacology. 9th ed. Edinburgh: Elsevier; 2020.