Eric Scholar , in xPharm: The Comprehensive Pharmacology Reference, 2007
Therapeutics
Neomycin is most often used topically to treat superficial infections. This includes treatment of superficial infections from staphylococci and gram-negative bacilli, either alone or in combination with bacitracin, chlorhexidine, or polymyxin. It has also been used orally in combination with other agents for patients prior to abdominal surgery or, in those at special risk from opportunistic infections, with gastrointestinal bacteria. It can also be used to decrease ammonia in encephalopathic patients suffering from hepatic coma.
Indications
Value
Units
Prep. and Route of Admin.
Reference
Comments
Respiratory infections
Dosage
100
mg/day, maximum dose
Aerosol
Kucers and Bennett (1979)
Bladder irrigation
Dosage
1000
ml
Diluted neosporin solution (1 ml ampule of neosporin GU irrigant added to 1000 ml isotonic saline) over 24 hrs.
Kucers and Bennett (1987)
Also contains polymyxin B sulfate.
Peritonitis
Dosage
0.5
%
Instilled into the peritoneal cavity after surgery.
Kucers and Bennett (1987)
Daily dose should not exceed 1 gm.
Preoperative Prophylaxis for Elective Colorectal Surgery
Dosage
1
gm
p.o. on third day of preparation. Starting in the afternoon, 1gm, then 1gm 1 hour later, then 1 gm at bedtime (3gm total).
Given on the third day after day 1, bisacodyl; day 2, magnesium sulfate; and in combination with erythromycin on day 3.
Hepatic Coma
Dosage
4-12
gm/day
Divide doses
Usually given for 5-6 days, however, it can be indefinite.
Contraindications
Hypersensitivity to neomycin or to other aminoglycosides. Neomycin oral solution is contraindicated in patients with inflammatory or ulcerative gastrointestinal disease, or patients who are at risk of increased absorption, or patients with intestinal obstruction.
Adverse Effects
Neomycin can cause irreversible deafness, which is a main reason it is no longer used parenterally. It is considerably more ototoxic than kanamycin. Sufficient absorption may occur after prolonged oral administration to cause ototoxicity, especially in the presence of renal impairment. Neomycin may also cause reversible renal damage if given parenterally. Like other aminoglycosides, it can cause neuromuscular blockade, especially when given intraperitoneally. Large oral doses may cause vomiting or diarrhea Kucers et al (1997).
Agent-Agent Interactions
Agent Name
Mode of Interaction
Ascorbic acid
Ascorbic acid decreases the effectiveness of the aminoglycosides by acidifying the urine.
Bumetanide
Loop diuretics increase the liklihood of ototoxicity with the aminoglycosides.
Furosemide
Loop diuretics increase the liklihood of ototoxicity with the aminoglycosides.
Ethacrynic acid
Loop diuretics increase the liklihood of ototoxicity with the aminoglycosides.
Calcium
High amounts of calcium and aminoglycosides concurrently in coronary bypass prime solutions showed an increased incidence of renal failure Schneider et al (1996).
Carboplatin
Carboplatin has an additive ototoxic effect with the aminoglycosides.
Cephalosporins
These drugs have potentially additive nephrotoxic effects with the aminoglycosides.
Cidofovir
This drug has potentially additive nephrotoxic effects with the aminoglycosides.
Cyclosporine
This drug has potentially additive nephrotoxic effects with the aminoglycosides.
Methoxyflurane
This drug has potentially additive nephrotoxic effects with the aminoglycosides.
Tacrolimus
This drug has potentially additive nephrotoxic effects with the aminoglycosides.
Indomethacin
When given i.v. concurrently with gentamicin or amikacin indomethacin, decreases gentamicin clearance.
Magnesium
Concomitant magnesium and aminoglycosides can produce neuromuscular weakness and, possibly, paralysis as a result of a decrease in acetylcholine release Watson et al (1983).
Nondepolarizing neuromuscular blocking agents used in anesthesia (e.g., succinylcholine)
These agents produce additive or synergistic neuromuscular blockade.
Penicillins
When penicillins and aminoglycosides are mixed together, there may be a chemical inactivation of both compounds.
Colton Nielson , ... Kiran Motaparthi , in Comprehensive Dermatologic Drug Therapy (Fourth Edition), 2021
Clinical Use
Dermatologic Uses
Neomycin is useful for treating minor wounds and cutaneous infections. It is used in combination with bacitracin to achieve optimal staphylococcal and streptococcal coverage.
Adverse Effects
As with other aminoglycosides, systemic toxicity to neomycin includes ototoxicity and nephrotoxicity. Systemic absorption and toxicity do not occur when the antibacterial agent is used topically on minor skin lesions. Neomycin-related deafness has been reported, usually involving a neomycin solution to irrigate a large wound.33 There have been rare reported cases of deafness from using ear drops containing neomycin. Ear drops containing an ototoxic agent should not be used in patients with tympanic membrane perforation.34 To reduce the potential for sensitization, resistance, or toxicity, it is recommended that no more than 1 g per day of a topical preparation containing neomycin be used, for a maximum of 7 days.32
Q41.2 The overall prevalence of allergic contact sensitivity to neomycin in the United States has been reported to range from 0.09% to 1.1%,35,36 but 10% of patients with ACD have positive patch testing to neomycin.12 In dermatologic surgery, neomycin is the most common cause of postoperative ACD and should be avoided.18 Regarding chronic use, studies indicate that in patients suffering from leg ulcers, between 9% and 13% of patients patch-tested positive to neomycin.15,37 Patch testing is done by applying 20% neomycin sulfate in petrolatum under occlusion for 48 hours (see Table 41.4). Although the majority of tests are positive in 96 hours, it may take 7 days to become positive.32 Neomycin potentially cross-reacts with streptomycin, kanamycin, gentamicin, paromomycin, spectinomycin, and tobramycin.38Q41.4 As previously mentioned, neomycin often co-reacts, but does not cross-react, with bacitracin. Therefore, patch testing to both may uncover a bacitracin allergy, and this co-reaction represents coincidental sensitization.25
Judith A. O'Donnell , ... Amar Safdar , in Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (Eighth Edition), 2015
Clinical Uses.
Neomycin is widely used in combination with other antibiotics, antifungals, and corticosteroids because of its availability, relatively low cost, and perceived efficacy.10,71 There are few well-controlled clinical trials documenting the efficacy and safety of topical neomycin.72 Neomycin has been shown to enhance reepithelialization in wound healing.11 However, in view of its well-documented contact sensitivity, possible systemic toxicity, and cross-reactivity with other antibiotics and because of the emergence of resistance, it is difficult to recommend the use of topical neomycin in the treatment of superficial skin infections.91
Nihar Ranjan , Dev P. Arya , in Methods in Enzymology, 2019
3.1 The assay
The F-Neo probe is fluorescent in water and several other types of buffer systems that have pH close to 7.0. Addition of the bacterial rRNA A-site oligonucleotide sequence causes fluorescence quenching of the fluorescein moiety. A titration experiment revealed that this quenching is complete when the F-Neo probe and the bacterial rRNA A-site oligonucleotide sequence are at equimolar ratio (Watkins et al., 2013). Further addition of the RNA oligonucleotide to excess amounts (sevenfold higher RNA concentration than the F-Neo probe) caused negligible change in the fluorescence emission signal intensity. Therefore, a 1:1 probe to RNA ratio can be used in the assay. The premise of the assay is that when the F-Neo probe is complexed with the bacterial rRNA A-site sequence at 1:1 ratio, large quenching of the fluorescence emission signal will occur which can be regained by successive displacement of the probe with a competing ligand. Neomycin was chosen as a test ligand from which the probe is derived. As expected, successive addition of neomycin to F-Neo complexed with the rRNA A-site completely displaced the F-Neo probe and brought back the fluorescence emission levels close to the level found in the unbound state (Watkins et al., 2013). The applicability of this assay in distinguishing the strong and weak binders was then checked with a small set of aminoglycoside antibiotics (neomycin, paromomycin, gentamycin, neamine, ribostamycin and streptomycin). The competition displacement assay was done by addition a threefold excess of test ligands (at 0.3 μM) to a 1:1 complex of F-Neo with the rRNA A-site (at 0.1 μM). The displacement assay produced a ranking in the order neomycin > gentamycin > paromoycin > neamine > ribostamycin > streptomycin which was very much in line with the independently generated thermodynamic parameters (ITC generated Ka values in the range of 4.9 × 109–1.6 × 106 M− 1 (Kaul & Pilch, 2002). These results established that both strong and moderate binders can be ranked rapidly and reliably with this assay.
Tak W. Mak , Mary E. Saunders , in The Immune Response, 2006
Neomycin-resistant clones are then isolated by positive drug selection, in which neomycin treatment kills all cells that have failed to incorporate neo. Among the neomycin-resistant clones will be both cells that have integrated neo randomly and a small number of cells in which neo has been integrated into the gene of interest, disrupting it. These latter cells are correctly gene-targeted cells or homologous recombinants. Homologous recombinants can then be distinguished from random integrants by restriction mapping and Southern blot screening. However, it is more efficient to distinguish between these two groups of neomycin-resistant cells by including a gene in the targeting plasmid outside the arms of homology that confers sensitivity to a second drug. This drug selection gene is then deleted from the ES cell only if homologous recombination occurs. Thus, if the targeting plasmid is randomly integrated, the second drug selection marker is retained in the ES cell and the cell dies in the presence of the second drug (negative selection). However, homologous recombination of the targeting vector into the gene of interest deletes the second drug selection marker, rendering correctly gene-targeted ES cells resistant to the second drug. The gene-targeted ES cells are then cultured to establish cell lines mutated at one allele of a single gene.
Mohamed M. Amin , in Dietary Interventions in Liver Disease, 2019
7.2.3 Antibiotics
Neomycin and different antiinfection agents, for example, metronidazole, oral vancomycin, paromomycin, and oral quinolones, are regulated with an end goal to diminish the colonic grouping of ammoniagenic microbes. Introductory neomycin dosing is 250 mg orally 2–4 times each day. Therapies as high as 4000 mg/d might be managed. Neomycin is normally held as a second-line agent, after start of treatment with lactulose. Long-time treatment with this oral aminoglycoside runs the dangers of inciting ototoxicity and nephrotoxicity on account of some foundational ingestion.
Rifaximin (Xifaxan), a nonabsorbable subordinate of rifampin, has been utilized in Europe for over 20 years for a wide assortment of gastrointestinal signs. Numerous clinical trials have shown that rifaximin at a measurement of 400 mg taken orally three times each day was as compelling as lactulose or lactitol at enhancing HE side effects.22 Similarly, rifaximin was as successful as neomycin and paromomycin. Rifaximin had a bearablility profile tantamount to fake treatment. It was preferably endured over both the cathartics and the other nonabsorbable antiinfection agents. A potential component for rifaximin's clinical action is its impacts on the metabolic capacity of the gut microbiota, as opposed to an adjustment in the relative bacterial availability.23
Peripheral edema and nausea are portrayed in some rifaximin-treated patients. There are additional addresses whether long-time treatment with rifaximin can actuate microbial protection. So far, microbial protection has not been accounted for in patients using the drug. It stays misty whether loose bowels caused by Clostridium difficile happens at a higher rate in rifaximin-treated patients than untreated patients. In the investigation by Bass et al., two rifaximin-treated patients and no placebo-treated patients created C. difficile disease.23
Thomas G. Boyce , Karthik Balakrishnan , in Principles and Practice of Pediatric Infectious Diseases (Fifth Edition), 2018
Management
Mild cases of otitis externa can be treated with instillation of topical otic antibiotic drops. Culture of otorrhea is usually unnecessary. The patient can enter the swimming pool as long as prolonged submersion is avoided. Excess water should be drained from the ear canal and the ear canal dried thoroughly with a hair dryer.
In addition to adequate analgesia, moderate or severe otitis externa usually requires aural lavage of the ear canal to permit contact of the antibiotic drops with infected skin. This is best accomplished by referring the patient to an otorhinolaryngologist. Lavage may be performed daily in some cases, and close follow-up is essential. A wick sometimes is inserted into the canal to allow topical antibiotic drops to remain in contact with the wall, particularly if canal edema makes instillation of drops difficult. Individuals with moderate or severe otitis externa should avoid swimming and maintain dry ear precautions until inflammation subsides, although formal data on the effect of water precautions are lacking.
Available topical otic antibiotic drops include ofloxacin, ciprofloxacin with hydrocortisone or dexamethasone, and polymyxin B–neomycin–hydrocortisone. The use of corticosteroids is empiric. Topical steroid alone is inferior to antibiotic-steroid combinations.18 A Cochrane database review found that the topical antibiotic preparations available were equally effective and that all were superior to placebo.19 Systemic antibiotics are unnecessary for uncomplicated cases.20
Neomycin, Neosporin
Neomycin is an aminoglycoside and is ototoxic. It should not be administered unless the tympanic membrane is known to be intact. It may also cause a contact dermatitis in some patients. However, in a trial comparing ciprofloxacin-dexamethasone with polymyxin B–neomycin–hydrocortisone, adverse events were uncommon and were not different in the two groups.21 Polymyxin B–neomycin–hydrocortisone is administered three to four times daily, ciprofloxacin-containing drops are administered twice daily, and ofloxacin drops can be administered once daily with equivalent cure rates.22 Most patients can be treated with a 7-day course. Symptoms improve within 3 to 6 days of starting therapy. For patients who do not respond, physicians should consider the possibility of necrotizing otitis externa, particularly in immunocompromised hosts. Guidelines for the management of acute otitis externa have been published by the American Academy of Otolaryngology–Head and Neck Surgery Foundation.23
For the patient who fails to respond to empiric therapy, fungal infection should be considered. Otomicroscopic examination may reveal fungal elements, and a Gram stain of exudate may reveal the hyphae of Aspergillus spp. or the budding yeast of Candida spp. A 1% solution of clotrimazole is the most commonly used agent for otomycosis.24 It has excellent activity against Aspergillus and Candida.25 Nontuberculous mycobacteria may rarely be the cause of persistent tympanostomy tube otorrhea.26 Furunculosis and local cellulitis respond best to the application of warm compresses and an orally administered antibiotic directed against S. aureus.
Andrew M. Lovering , David S. Reeves , in Antibiotic and Chemotherapy (Ninth Edition), 2011
Toxicity and side effects
Neomycin is the most likely of all the aminoglycosides to damage the kidneys and the auditory branch of the eighth nerve (Table 12.3). This has almost entirely restricted it to topical and oral use.
Irreversible deafness may develop even if the drug is stopped at the first sign of damage. Loss of hearing may occur as a result of topical applications to wounds or other denuded areas, particularly if renal excretion is impaired. Instillation of ear drops containing neomycin can result in deafness. This generally develops in the second week of treatment and is usually reversible.
Rashes have been described in 6–8% of patients treated topically and these patients may be rendered allergic to other aminoglycosides. Nausea and protracted diarrhea may follow oral administration. Sufficient drug may be absorbed from the gut on prolonged oral administration to produce deafness but not renal damage. Intestinal malabsorption and superinfection have been seen in patients receiving 4–9 g per day and may develop in patients receiving as little as 3 g of the drug per day. Precipitation of bile salts by the drug may impair the hydrolysis of long-chain triglycerides. Large doses instilled into the peritoneal cavity at operation may be absorbed, with resultant systemic toxicity, and patients concurrently exposed to anesthetics and muscle relaxants are liable to suffer neuromuscular blockade, which is reversible by neostigmine.
Rockford K. Draper , ... Tonghuan Hu , in Methods in Enzymology, 2001
Inhibition by CBM of Neomycin-Induced Precipitation of Coatomer
Neomycin, a multivalent (three pairs of amino groups) KKXX mimetic, precipitates coatomer from solution and the basis of the assay described here is the ability of monovalent (one amino group pair) KKXX mimetics to inhibit this precipitation by competing with neomycin for binding sites on coatomer.13 Two compounds tested here are dilysine (a positive control) and CBM. The assay can be used to calibrate the activity of commercially available CBM, to screen other compounds for their ability to interact with KKXX binding sites of coatomer, or to study the effect of KKXX mimetics on aspects of membrane traffic amenable to analysis with Golgi membranes in vitro.
Procedures
Solutions and Materials
Neomycin (Sigma, St. Louis, MO) stock solution: 100 mM in water adjusted to pH 7.4
1,3-Cyclohexanebis(methylamine) (CBM) (Acros Organics, Pittsburgh, PA) stock solution: 500 mM in water adjusted to pH 7.4
Dilysine (Sigma, St. Louis, MO) solution: 500 mM in water adjusted to pH 7.4
10× HM-S buffer: 250 mM HEPES, pH 7.4, 500 mM KCl, 25 mM magnesium acetate
10× H buffer: 250 mM HEPES, pH 7.4, 250 mM sucrose
Phosphate-buffered saline (PBS): 10 mM Na2HPO4/NaH2PO4, pH 7.4
Reagents and apparatus for polyacrylamide gel electrophoresis
Reagents and apparatus for electrophoretic transfer of proteins from a polyacrylamide gel to nitrocellulose
Mouse monoclonal antibody M3A5 to β-COP15
Horseradish peroxidase-conjugated goat anti-mouse
Supersignal chemiluminescence system for detecting horseradish peroxidase in immunoblots (Pierce Biochemical, Rockford, IL)
Preparation of CHO Cell Cytosol.
CHO cells from 20 (15-cm-diameter) plates grown to confluency are trypsinized to detach the cells. Further treatments are all at 4°. The cells are centrifuged, washed once with PBS and once with H buffer, and resuspended in five times the cell pellet volume of H buffer. After 30 min, the cells are homogenized in a 15-ml stainless steel Dounce homogenizer. The homogenate is centrifuged at 100,000g for 1 hr at 4° in a Beckman SW50.1 rotor. The supernatants, which contain soluble coatomer, are pooled and recentrifuged using the same conditions. The final supernatant is desalted over a Sephadex G-25 column equilibrated with HM-S buffer. Protein concentration should be in the range of 5–7.5 mg/ml. The cytosol is quickly frozen with liquid nitrogen in 400-μl aliquots.
Inhibition by CBM of Neomycin-Induced Precipitation of Coatomer from Cytosol.
Assays are at 4° in a final volume of 100 μl. To 1.5-ml conical centrifuge tubes are added 10 μl of 10× HM-S, 1 μl of stock neomycin, and volumes of either the dilysine or CBM stock solutions to give the desired concentration ranges. Enough water is added to give a final volume of 100 μl after the cytosol is added and the contents of the tube are mixed. Prior to addition, the CHO cell cytosol is centrifuged at 14,000 rpm for 30 min in the Eppendorf microfuge (about 16,000g in an F-45-18-11 rotor) to remove coatomer that may have precipitated on freezing and thawing. A volume of cytosol is added to give 1.5 mg/ml of protein, which should bring the final volume to 100 μl, and the contents are mixed again. The samples are incubated for 2 hr at 4° to allow precipitation and then centrifuged again for 30 min at 4° in the microfuge to separate supernatants from precipitates. The supernatant is carefully removed and to the pellets is added 120 μl of Laemmli sample buffer.16 If desired, the supernatant can also be analyzed for the presence of coatomer, which should decline as coatomer is precipitated. The samples are heated to boiling and electrophoresed in an 8% polyacrylamide gel with sodium dodecyl sulfate. Proteins are transferred to nitrocellulose by electrophoresis and the nitrocellulose is incubated with 0.1% Tween 20 as a blocking agent. Immunodetection of β-COP is with monoclonal antibody M3A5 to β-COP15 and the secondary antibody is horseradish peroxidase-conjugated goat anti-mouse. The blots are developed with the Pierce Biochemical Supersignal system according to manufacturer instructions. Inhibition by both dilysine and CBM of neomycin-induced precipitation of β-COP is illustrated in Fig. 2.
Fig. 2. The inhibition by dilysine and CBM of neomycin-induced precipitation of β-COP from cytosol. Cytosol was treated with neomycin in the presence of dilysine or CBM and precipitated as described in the text. β-COP was detected by immunoblotting.
Comments
The ratio of neomycin concentration (1 mM) to cytosol protein (1.5 mg/ml) used in these assays was empirically determined to give maximal precipitation of coatomer.13 Changing either the neomycin or protein concentrations will require recalibration of the concentration ratio. The precipitation reaction is sensitive to salt concentration and will need to be recalibrated if the salt is changed.13 We have been unable to solubilize neomycin-precipitated coatomer with either high salt concentrations or 0.1% Triton X-100, suggesting that the precipitation reaction is unsuitable for facile purification of coatomer.
Transgenic Cloned Goats and Cows for the Production of Therapeutic Proteins
William Gavin , ... Harry Meade , in Principles of Regenerative Medicine, 2008
Neomycin Selection and Stable Donor Cell Lines
The neomycin (neo) resistance selection procedure (G418 selection) allows for isolation of stable transfectants and is introduced into cells either linked in cis to genes of interest as one DNA fragment, or it can be introduced in trans by co-transfection. G418 selection is applied 48 h post-transfection and maintained thereafter. It is interesting to observe that in the initial phase of G418 selection, the apparent rate of rearrangement of the neo resistance gene and the gene of interest can differ significantly. This could result in the occurrence of multiple integrations of the neo gene independent of the gene of interest within a single colony, or resistant colonies that carry the neo cassette but not the gene of interest, even if the two were linked in cis in the transgene construct. This makes careful genotyping of each individual candidate donor cell line essential. In our experience, once the stable integration has been established however, the rearrangement of the transgene seems to be greatly reduced either in the presence (donor cells grown in culture) or in absence of G418 selection (the transgenic animals themselves). For transgenic animal lines produced by SCNT to date, we have not observed transgene rearrangement either within the lifespan of a transgenic animal or from one generation to another.
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