Solutions containing 1–5 mg/mL neomycin have been used on infected surfaces or injected into joints, the pleural cavity, tissue spaces, or abscess cavities where infection is present. The total amount of drug given in this fashion must be limited to 15 mg/kg/d because at higher doses enough drug may be absorbed to produce systemic toxicity. Whether topical application for active infection adds anything to appropriate systemic therapy is questionable. Ointments, often formulated as a neomycin-polymyxin-bacitracin combination, can be applied to infected skin lesions or in the nares for suppression of staphylococci but they are largely ineffective.
B. Oral Administration
In preparation for elective bowel surgery, 1 g of neomycin may be given orally every 6–8 hours for 1–2 days, often combined with 1 g of erythromycin base. This reduces the aerobic bowel flora with little effect on anaerobes. In hepatic encephalopathy, coliform flora can be suppressed by giving 1 g every 6–8 hours together with reduced protein intake, thus reducing ammonia production. Use of neomycin for hepatic encephalopathy has been largely supplanted by lactulose and other medications that are less toxic. Use of paromomycin in the treatment of protozoal infections is discussed in Chapter 52.
C. Intravenous and Intramuscular Administration
When used intravenously, the standard dose for kanamycin is 15 mg/kg/day in two to three divided doses, whereas for treatment of tuberculosis, 15 mg/kg is usually given intramuscularly as a single daily dose. In the case of once daily administration, kanamycin peak concentrations are typically between 35 and 45 mcg/mL, while trough concentrations should be undetectable.
All members of the neomycin group have significant nephrotoxicity and ototoxicity. Auditory function is affected more than vestibular function. Deafness may occur, especially in adults with impaired renal function and prolonged elevation of drug levels.
The sudden absorption of postoperatively instilled kanamycin from the peritoneal cavity (3–5 g) has resulted in curare-like neuromuscular blockade and respiratory arrest. Calcium gluconate and neostigmine can act as antidotes.
Although hypersensitivity is not common, prolonged application of neomycin-containing ointments to skin and eyes has resulted in severe allergic reactions.
Plazomicin is a new aminoglycoside under development and is expected to undergo review by the U.S. Food and Drug Administration in 2017. It has been studied in phase II clinical trials for treatment of urinary tract infections; phase III clinical trials are underway for treatment of carbapenem-resistant Enterobacteriaceae. It is a synthetic molecule derived from sisomicin, an aminoglycoside no longer available,. Various structural modifications have yielded a compound less susceptible to most aminoglycoside modifying enzymes, thus retaining activity against aminoglycoside-resistant pathogens. It appears to have similarly potent in vitro activity against Enterobacteriaceae and displays twoto four-fold lower MICs against nonfermenting Gram-negative bacilli (eg, P aeruginosa) when compared with gentamicin, tobramycin, and amikacin. It has activity similar to gentamicin against staphylococci. A 15-mg/kg dose yields mean peak and trough concentrations of 113 mcg/mL and 0.43 mcg/mL, respectively. The half-life is about 4 hours, and it is being studied as a single daily dose. Due to limited clinical experience, it is unclear whether the toxicity profile will be similar to other aminoglycosides; however, no ototoxicity or nephrotoxicity has been observed in early trials.