Strains of multidrug-resistant Mycobacterium tuberculosis, including streptomycin-resistant strains, are usually susceptible to amikacin. Kanamycin-resistant strains may be cross-resistant to amikacin. The dosage of amikacin for tuberculosis is 10–15 mg/kg/d as a once-daily or two to three times weekly injection and always in combination with other drugs to which the isolate is susceptible.
Like all aminoglycosides, amikacin is nephrotoxic and ototoxic (particularly for the auditory portion of the eighth nerve). Serum concentrations should be monitored. Target peak serum concentrations for an every-12-hours dosing regimen are 20–40 mcg/mL, and trough levels should be maintained between 4 and 8 mcg/mL.
Netilmicin shares many characteristics with gentamicin and tobramycin. However, the addition of an ethyl group to the 1-amino position of the 2-deoxystreptamine ring (ring II, Figure 45–2) sterically protects the netilmicin molecule from enzymatic degradation at the 3-amino (ring II) and 2-hydroxyl (ring III) positions. Consequently, netilmicin may be active against some gentamicinresistant and tobramycin-resistant bacteria.
The dosage (5–7 mg/kg/d) and the routes of administration are the same as for gentamicin. Netilmicin is largely interchangeable with gentamicin or tobramycin but is no longer available in the United States.
NEOMYCIN, KANAMYCIN, & PAROMOMYCIN
Neomycin, kanamycin, and paromomycin have similar pharmacologic properties.
Drugs of the neomycin group are active against Gram-positive and Gram-negative bacteria and some mycobacteria. P aeruginosa and streptococci are generally resistant. Mechanisms of antibacterial action and resistance are the same as with other aminoglycosides. The former widespread use of these drugs in bowel preparation for elective surgery contributed to the selection of resistant organisms and some outbreaks of enterocolitis in hospitals. Cross-resistance between kanamycin and neomycin is complete and may result in amikacin cross-resistance.
Like all aminoglycosides, drugs of the neomycin group are poorly absorbed from the gastrointestinal tract. After oral administration, the intestinal flora is suppressed or modified, and the drug is excreted in the feces. Excretion of any absorbed drug is mainly through glomerular filtration into the urine.
Neomycin is generally limited to topical and oral use due to toxicity associated with parenteral use and higher resistance rates compared to other aminoglycosides. Kanamycin use is limited to treatment of multi-drug-resistant tuberculosis, although alternate agents, such as amikacin, may be preferred. It is no longer available in the USA. Paromomycin has been shown to be effective against visceral leishmaniasis when given parenterally (see Chapter 52), and this serious infection may represent an important use for this drug. Paromomycin can be used for intestinal Entamoeba histolytica infection and is sometimes used for intestinal infections with other parasites.
A. Topical Administration