Neomycin

Article Author:
Niel Veirup
Article Editor:
Chris Kyriakopoulos
Updated:
8/2/2020 4:29:41 PM
For CME on this topic:
Neomycin CME
PubMed Link:
Neomycin

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 GI tract itself. 

FDA ιndications for oral neomycin include:

  • Hepatic coma (portal-systemic encephalopathy)
  • Surgical (perioperative) prophylaxis

Hepatic coma - Also commonly known as hepatic encephalopathy, oral neomycin has FDA indications for the management of 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 can be a bowel preparation for colorectal surgery. Neomycin is commonly combined with erythromycin or metronidazole as part Nichols and Condon prep a day before surgery to decrease the likelihood of surgical site infection.[3]

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. This action thereby disrupts the process of translation by bacteria leading to the medication's bactericidal effects.[1] 

The pathogenesis of hepatic coma is often due to underlying liver disease leading to elevated levels of ammonia in the blood. At high levels, ammonia can cross the blood-brain barriers leading to many of the neurologic manifestations of hepatic coma. Ammonia within the brain leads to increased levels of glutamine and lactate, resulting in neuronal edema.[4] Therefore therapies aim to decrease the ammonia levels be either decreasing ammonia production or increasing ammonia excretion. 

Neomycin's bactericidal effects decrease ammonia producing bacteria residing in the 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.[5] 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, the use of these antibiotics and synthetic disaccharides is often in combination with each other. 

Due to neomycin's poor GI absorption, it is an effective choice for perioperative bowel prep with minimal systemic circulation. Neomycin is often combined with erythromycin a day before surgery to decrease bacterial load in the colon with the intention of reducing 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 they should be used. A multicentre, 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[6]. A 2015 retrospective study found that using oral antibiotic bowel preparation significantly reduced the number of surgical site infections, decreased length of stay, and decreased readmission rates.[7] 

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.

For the treatment of acute hepatic coma, neomycin is 1000 mg administered every six hours for up to six days.[2] 

For surgical (perioperative) prophylaxis, 1 gram of oral neomycin with 1 gram of erythromycin base should be given at 2 pm, 3 pm, and 10 pm the day prior to surgery.[3]

Adverse Effects

The side effect profile for the specific drug involves nausea, diarrhea, and C. difficile related colitis. More serious adverse events include nephrotoxicity, auditory ototoxicity, and vestibular ototoxicity (usually irreversible).[8] Methods of decreasing the frequency of such adverse events, specifically nephrotoxicity include once-daily dosing and maintaining adequate hydration status.[9]

Contraindications

Contraindications include any history of hypersensitivity to neomycin or any component of the product formulation. Neomycin should not be utilized in individuals with bowel obstruction or inflammatory bowel disease. Avoid use in patients with a history of hypersensitivity reaction to aminoglycosides due to the possibility of cross-reactivity.

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. Prompt discontinuation of the drug should occur with any signs of renal or otologic damage. 

Toxicity

Black box warnings include:

  • Nephrotoxicity
  • Ototoxicity
  • Neuromuscular blockade and respiratory paralysis
  • Concurrent use with other aminoglycosides and potent diuretics

Nephrotoxicity with the use of aminoglycoside antibiotics occurs mainly through renal tubular toxicity. Additional mechanisms include a decrease in glomerular filtration and reduction of blood flow to the kidneys. If discontinued, this damage is usually temporary. Patient-specific risk factors for increased toxicity include patient's age, impaired renal function, and dehydration, while 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.[9]

The possibility of ototoxicity is a serious consideration with the use of neomycin as the hearing loss is often permanent. The feared complication is bilateral; high-frequency sensorineural hearing loss is secondary to cochleotoxicity.[10] 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.[11]

Enhancing Healthcare Team Outcomes

Neomycin plays an important role in the management of hepatic coma, 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 labs are necessary to monitor for any signs of end-organ damage. Decreasing the potential for adverse reactions can be achieved by minimizing the duration of therapy and maintaining adequate hydration status. Excellent communication between physicians, nurses, and pharmacists are essential to positive patient outcomes. 


References

[1] Jana S,Deb JK, Molecular understanding of aminoglycoside action and resistance. Applied microbiology and biotechnology. 2006 Mar;     [PubMed PMID: 16391922]
[2] Patidar KR,Bajaj JS, Antibiotics for the treatment of hepatic encephalopathy. Metabolic brain disease. 2013 Jun;     [PubMed PMID: 23389621]
[3] Kumar AS,Kelleher DC,Sigle GW, Bowel Preparation before Elective Surgery. Clinics in colon and rectal surgery. 2013 Sep;     [PubMed PMID: 24436665]
[4] Wijdicks EF, Hepatic Encephalopathy. The New England journal of medicine. 2016 Oct 27;     [PubMed PMID: 27783916]
[5] Jawaro T,Yang A,Dixit D,Bridgeman MB, Management of Hepatic Encephalopathy: A Primer. The Annals of pharmacotherapy. 2016 Jul;     [PubMed PMID: 27126547]
[6] Koskenvuo L,Lehtonen T,Koskensalo S,Rasilainen S,Klintrup K,Ehrlich A,Pinta T,Scheinin T,Sallinen V, Mechanical and oral antibiotic bowel preparation versus no bowel preparation for elective colectomy (MOBILE): a multicentre, randomised, parallel, single-blinded trial. Lancet (London, England). 2019 Sep 7;     [PubMed PMID: 31402112]
[7] Morris MS,Graham LA,Chu DI,Cannon JA,Hawn MT, Oral Antibiotic Bowel Preparation Significantly Reduces Surgical Site Infection Rates and Readmission Rates in Elective Colorectal Surgery. Annals of surgery. 2015 Jun;     [PubMed PMID: 25607761]
[8] Aminoglycosides 2012;     [PubMed PMID: 31643557]
[9] Wargo KA,Edwards JD, Aminoglycoside-induced nephrotoxicity. Journal of pharmacy practice. 2014 Dec;     [PubMed PMID: 25199523]
[10] Guthrie OW, Aminoglycoside induced ototoxicity. Toxicology. 2008 Jul 30;     [PubMed PMID: 18514377]
[11] Leis JA,Rutka JA,Gold WL, Aminoglycoside-induced ototoxicity. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2015 Jan 6;     [PubMed PMID: 25225217]