AHFS Class:

• Antibacterials 84:04.04

Generic Name(s):

• Gentamicin Sulfate

Gentamicin is an aminoglycoside antibiotic.

Gentamicin is used topically in the treatment of superficial infections of the skin caused by susceptible bacteria. However, substantial evidence of effectiveness is lacking and some experts question the use of topical antibiotics in general. Minor skin infections and wounds usually heal without treatment, and systemic anti-infective therapy is required for the treatment of serious or extensive skin infections. In addition, indiscriminate use of topical gentamicin may result in the emergence of organisms resistant to the drug and other aminoglycosides.

For systemic uses of gentamicin, see 8:12.02. For use of gentamicin in infections of the eye, see 52:04.04.

Gentamicin sulfate is applied topically to the skin in the form of a cream or ointment containing 0.1% gentamicin. Because the ointment helps retain moisture, it has been used in the treatment of infections on dry, eczematous, or psoriatic skin. The cream is usually used for the treatment of wet, oozing primary infections and greasy secondary infections; the cream is also used if a water-washable preparation is desired.

A small amount of gentamicin cream or ointment should be applied gently to the cleansed affected area 3-4 times daily. The area may be covered with a sterile gauze dressing; infected stasis ulcers may be covered with gelatin packing. In the topical treatment of impetigo, crusts should be removed from the lesions to permit contact between the antibiotic and the infection. Care should be taken to avoid further contamination of the infected skin.

Adverse Effects

Gentamicin appears to have a low order of toxicity when applied to the skin; however, sensitization to the drug may occasionally result from topical application. In addition, commercially available gentamicin preparations contain other ingredients such as parabens which may also cause allergic contact dermatitis. Local irritation including erythema and pruritus occur rarely following topical application of gentamicin. Possible photosensitization has been reported in several patients treated with topical gentamicin, but the reaction could not be directly attributed to the drug.

Precautions and Contraindications

The use of gentamicin may result in overgrowth of nonsusceptible organisms including fungi. If superinfection occurs during gentamicin therapy, the drug should be discontinued and appropriate therapy instituted.

Serious adverse reactions including ototoxicity and nephrotoxicity have occurred in patients receiving systemic gentamicin therapy. (See Cautions in the Aminoglycosides General Statement 8:12.02.) The possibility of cumulative toxicity should be considered if gentamicin is applied topically to large skin lesions or large areas of denuded skin in combination with systemic aminoglycoside therapy.

Topical gentamicin is contraindicated in patients who are hypersensitive to the drug or any ingredients in the formulations. Patients who are hypersensitive to other topical antibiotics should be closely observed during treatment with gentamicin. If irritation or hypersensitivity occurs, the drug should be discontinued. Cross-allergenicity among the aminoglycosides has been demonstrated and the possibility that patients who become sensitized to topical gentamicin may also be sensitive to other topical and/or systemic aminoglycosides should be considered.

Mechanism of Action

Gentamicin is usually bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drug appears to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits.

Spectrum

In general, gentamicin is active against many aerobic gram-negative bacteria and some aerobic gram-positive bacteria. The drug is inactive against fungi, viruses, and most anaerobic bacteria. In vitro, gentamicin concentrations of 1-8 mcg/mL inhibit most susceptible strains of Escherichia coli, Haemophilus influenzae, Moraxella lacunata, Neisseria, indole-positive and indole-negative Proteus, Pseudomonas (including most strains of Ps. aeruginosa), Staphylococcus aureus, S. epidermidis, and Serratia. However, different species and different strains of the same species may exhibit wide variations in susceptibility in vitro. In addition, in vitro susceptibility does not always correlate with in vivo activity. Gentamicin is only minimally active against streptococci.

Resistance

Natural and acquired resistance to gentamicin have been demonstrated in both gram-negative and gram-positive bacteria. Gentamicin resistance may be the result of decreased permeability of the bacterial cell wall, alterations in the ribosomal binding site, or the presence of a plasmid-mediated resistance factor which is acquired by conjugation. Plasmid-mediated resistance enables the resistant bacteria to enzymatically modify the drug by acetylation, phosphorylation, or adenylylation and can be transferred between organisms of the same or different species. Resistance to other aminoglycosides and several other anti-infectives (e.g., chloramphenicol, sulfonamides, tetracycline) may be transferred on the same plasmid.

There is partial cross-resistance between gentamicin and other aminoglycosides.

Pharmacokinetics

Gentamicin sulfate is not usually absorbed following topical application to intact skin; however, the drug is readily absorbed through denuded areas of skin or skin that has lost the keratin layer as in wounds, burns, or ulcers. Greater absorption may occur with topical application of gentamicin cream than with topical application of gentamicin ointment.

Chemistry and Stability

Chemistry

Gentamicin is an aminoglycoside antibiotic obtained from cultures of Micromonospora purpurea. The commercially available drug is a mixture of the sulfate salts of gentamicin C₁, C₂, and C_1A; all 3 components appear to have similar antimicrobial activity. Gentamicin sulfate occurs as a white to buff powder and is soluble in water and insoluble in alcohol.

Stability

Topical gentamicin sulfate preparations should be stored at 2-30°C.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.