Neomycin

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Continuing Education Activity

Neomycin is a medication used to treat and manage hepatic coma and perioperative prophylaxis. Neomycin belongs to a group of antibiotics known as aminoglycosides, which works by inhibiting bacterial protein synthesis leading to its bactericidal effect on gram-negative bacteria. This activity reviews the indications, contraindications, activity, adverse drug reactions, and other key elements (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) of neomycin therapy in the clinical setting related to the essential points needed by members of an interprofessional team managing the care of patients with hepatic coma, perioperative prophylaxis, constipation dominant inflammatory bowl syndrome, related conditions, and sequelae.

Objectives:

  • Identify the mechanism of action of neomycin.
  • Identify the most common adverse events associated with neomycin therapy.
  • Review the toxicology associated with neomycin therapy.
  • Outline some interprofessional team strategies for improving care coordination and communication to advance treatment with neomycin and improve outcomes.

Indications

Neomycin belongs to a group of antibiotics known as aminoglycosides. Like others in the aminoglycoside family, neomycin works by inhibiting bacterial protein synthesis leading to its bactericidal effect. This group of medications is particularly effective in killing gram-negative organisms allowing for good coverage of enteric organisms.[1] neomycin is poorly absorbed into the systemic circulation, making its use particularly useful within the Gastrointestinal tract. 

FDA-approved Indications

  • Hepatic Coma (portal-systemic encephalopathy): Neomycin is used to manage hepatic encephalopathy (i.e., hepatic coma). Its use is recommended in the acute setting of hepatic encephalopathy rather than chronic due to its side effect profile.[2] 
  • Surgical (perioperative) Prophylaxis: Neomycin is commonly combined with erythromycin or metronidazole as part of Nichols and Condon's bowel preparation a day before surgery to decrease the likelihood of surgical site infection.[3]

Off-label Use

  • Constipation predominant irritable bowel syndrome (IBS-C).[4]

Mechanism of Action

Mechanism of Action

Neomycin's mechanism of action is very similar to most aminoglycosides as it binds to the 30s ribosomal subunit interfering with bacterial protein synthesis. The initial steps needed for peptide synthesis are uninterrupted, but elongation fails to occur due to disruption of translational precision. This action thereby disrupts bacteria's translation process, leading to the medication's bactericidal effects.[1][5]

The pathogenesis of hepatic coma is often due to underlying liver disease leading to elevated ammonia levels in the blood. At high levels, ammonia can cross the blood-brain barriers leading to many of the neurologic manifestations of hepatic coma. In addition, ammonia within the brain leads to increased levels of glutamine and lactate, resulting in neuronal edema.[6] Therefore, therapies aim to decrease ammonia levels by either decreasing ammonia production or increasing ammonia excretion.

Neomycin's bactericidal effects decrease ammonia-producing bacteria residing in the gastrointestinal(GI) tract, thereby decreasing the burden of ammonia on the patient.[2] neomycin is often reserved for patients that cannot tolerate rifaximin. Neomycin is less commonly used due to its more significant side effect profile associated with long-term use.[7] Additionally, one should note that the use of poorly-absorbed antibiotics like rifaximin and neomycin is second-line to synthetic disaccharides (e.g., lactulose, lactitol). In practice, these antibiotics and synthetic disaccharides are often combined.

Due to neomycin's poor GI absorption, it is an effective choice for perioperative bowel prep with the minimal systemic circulation. Neomycin is often combined with erythromycin a day before surgery to decrease bacterial load in the colon to reduce the possibility of surgical site infections. Metronidazole may be an option due to its better tolerability than erythromycin. These antibiotics are part of a regimen in conjunction with mechanical bowel prep and standard IV antibiotic prophylaxis.[3]

There is some controversy about whether these methods of bowel preparation are effective and whether clinicians should use them. A multicentered, randomized, parallel, single-blinded trial conducted in Finland found that when compared to no bowel prep at all, there was no significant reduction in surgical site infections or morbidity when using mechanical and oral bowel preparation for elective colectomies.[8] A 2015 retrospective study found that oral antibiotic bowel preparation significantly reduced surgical site infections, decreased length of stay, and decreased readmission rates.[9]

Pharmacokinetics

Absorption: The lack of absorption from the gastrointestinal tract is the basis of the main use of neomycin as an oral agent to suppress intestinal bacterial flora.[10]

Distribution: As with other aminoglycosides, the quantity of absorbed neomycin transferred to the tissues increases cumulatively with each dose administered until a steady-state concentration is obtained. The kidney is the primary excretory path of the absorbed drug, and the highest concentration is found in the renal cortex. With cumulative dosings, progressive accumulation also occurs in the inner ear. The release of tissue-bound neomycin occurs slowly over several weeks after discontinued dosing.

Metabolism: There is limited information available on the metabolism of neomycin. It has limited systemic absorption following the drug administration, and metabolism is deemed to be negligible.

Excretion: Neomycin sulfate is excreted primarily through feces (97% of oral dose as unchanged drug).

Administration

Neomycin has various routes of administration but has poor GI absorption, like most aminoglycosides.[1] Oral administration functions to act within the GI tract itself. Alternative preparations include topical use.

Hepatic Coma

One gram of neomycin is administered every six hours for up to six days to treat hepatic encephalopathy.[2]

Surgical (Perioperative) Prophylaxis

One gram of oral neomycin is given with 1 gram of erythromycin base at 2 pm, 3 pm, and 10 pm the day before surgery.[3]

Use in Special Population

Patients with Hepatic Impairment

No dosage adjustments are provided in the manufacturer’s labeling.

Patients with Renal Impairment

No dosage adjustments are provided in the manufacturer’s labeling. Patients with renal insufficiency can develop toxic blood levels unless doses are properly regulated. If renal insufficiency develops during treatment, the clinician should reduce the dosage or discontinue antibiotics.

Pregnancy Considerations

Neomycin being an aminoglycoside, can cross the placenta. It may cause teratogenicity if administered to a pregnant woman. Hence, neomycin should be given to pregnant women only if needed. It is classified as FDA Pregnancy Category C medicine.[11]

Breastfeeding Considerations

There is a lack of data about the excretion of neomycin into milk; however, other aminoglycoside antibiotics are poorly excreted into breastmilk. In addition, newborn infants absorb small amounts of aminoglycosides; hence systemic effects of neomycin are unlikely. However, monitor the infant for possible effects on the gastrointestinal flora, such as candidiasis, diarrhea, and colitis.[12]

Adverse Effects

According to the package insert, neomycin's common adverse drug reaction is irritation or soreness of the mouth and rectal area. In addition, the side effect profile for the specific drug involves nausea, diarrhea, and clostridium difficile-related colitis. More serious adverse events include nephrotoxicity, auditory ototoxicity, and vestibular ototoxicity (usually irreversible).[13] Neuromuscular blockade is a rare but severe adverse drug reaction induced by neomycin therapy. Therefore neomycin should be avoided in patients with myasthenia gravis.[14] Methods of decreasing the frequency of such adverse events, especially nephrotoxicity, include once-daily dosing and maintaining adequate hydration status.[15]

Contraindications

  • Oral neomycin is contraindicated in intestinal obstruction and patients with a prior history of hypersensitivity. Patients with a history of hypersensitivity and serious toxic reactions to other aminoglycosides may have cross-sensitivity to neomycin.
  • Neomycin is also contraindicated in patients with inflammatory or ulcerative gastrointestinal disease because of the potential for enhanced gastrointestinal absorption of neomycin.[13]

Boxed Warnings

  • Nephrotoxicity
  • Ototoxicity
  • Neuromuscular blockade and respiratory paralysis
  • Neurotoxicity manifested by numbness, muscle twitching, and seizures
  • Concurrent use with other aminoglycosides and potent diuretics

Monitoring

A baseline serum BUN/creatinine should be obtained with subsequent periodical follow-up blood tests during chronic therapy to monitor for effects on renal function. Since elderly patients may have impaired renal function, which may not be evident in the results of routine screening tests like BUN or serum creatinine, a creatinine clearance determination is more advantageous.

Prompt discontinuation of the drug should occur with any signs of renal or otologic damage.[15][16]

Toxicity

Nephrotoxicity with the use of aminoglycoside antibiotics occurs primarily through renal tubular toxicity. Additional mechanisms are a decrease in glomerular filtration and a reduction of blood flow to the kidneys. If discontinued, this damage is usually temporary. Patient-specific risk factors for increased toxicity include age, impaired renal function, and dehydration. In contrast, treatment-specific risk factors are often related to prolonged therapy or high dosage, and they should always merit consideration before administering neomycin. It is also essential to consider concurrent medications that impair renal function, such as NSAIDs, diuretics, iodine contrast media, and other aminoglycosides.[15]

The possibility of ototoxicity is a serious consideration with neomycin, as hearing loss is often permanent. The feared complication is bilateral; high-frequency sensorineural hearing loss is secondary to cochleotoxicity.[17] The clinician should discontinue therapy with neomycin at the earliest sign of changes in hearing to reduce the extent of cochlear damage. Therefore, it is imperative to inform patients and raise their awareness about the potential side effects of this medication use.[18]

According to the manufacturer's labeling, there is no antidote for neomycin, but hemodialysis can remove neomycin from the blood.

Enhancing Healthcare Team Outcomes

Neomycin plays an important role in the management of hepatic encephalopathy, as well as for perioperative prophylaxis. Due to its potential for various toxicities, it is essential to gather a thorough medical history focusing on renal, otologic, and neurologic conditions before prescribing neomycin. Patients must understand well the benefits and possible risks associated with the medication. Additionally, baseline and recurrent laboratory workups are necessary to monitor for any signs of end-organ damage. Hence, recommended course of action for the patient receiving neomycin is as follows:

  • Clinicians(MD, NP, PA) usually prescribe the medicine.
  • The internist is responsible for identifying the proper indication of neomycin in hepatic coma. 
  • The surgeon is responsible for identifying the proper indication of neomycin in surgical prophylaxis.
  • Consultation with a nephrologist if the patient develops nephrotoxicity.
  • Consultation with otorhinolaryngologist if the patient develops ototoxicity. 
  • Consultation with a neurologist if the patient develops neurotoxicity and neuromuscular blockade.
  • Consultation with the intensivist is required for ICU care and need for mechanical ventilation in severe toxicity.
  • Pharmacists are accountable for medication reconciliation, checking for potential drug-drug interactions, and ensuring proper drug dosing.
  • Specially trained nurses administer neomycin at appropriate timing and ensure proper charting and care of the hospitalized patients.
  • Residents play an important role in the continuity of care and patient education.
  • Nocturnists should receive all the important information during the signout process.

As illustrated above, communication between clinicians (MDs, NPs, PAs), hospital pharmacists and nursing staff, and other healthcare professionals is required. Therefore, an interprofessional team approach is essential for patients receiving neomycin therapy to maximize efficacy and minimize adverse drug reactions associated with neomycin use, enhancing patient outcomes. [Level 5]


Article Details

Article Author

Niel Veirup

Article Editor:

Chris Kyriakopoulos

Updated:

5/8/2022 8:56:35 AM

PubMed Link:

Neomycin

References

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