Basic & Clinical Pharmacology, 10th Edition

45. Aminoglycosides & Spectinomycin - Henry F. Chambers, MD

INTRODUCTION

The drugs described in this chapter are bactericidal inhibitors of protein synthesis that interfere with ribosomal function. These agents are useful mainly against aerobic gram-negative microorganisms.

AMINOGLYCOSIDES

Introduction

The aminoglycosides include streptomycin, neomycin, kanamycin, amikacin, gentamicin, tobramycin, sisomicin, netilmicin, and others. They are used most widely against gram-negative enteric bacteria, especially in bacteremia and sepsis, in combination with vancomycin or a penicillin for endocarditis, and for treatment of tuberculosis.

General Properties of Aminoglycosides

A. PHYSICAL AND CHEMICAL PROPERTIES
Aminoglycosides have a hexose ring, either streptidine (in streptomycin) or 2-deoxystreptamine (other aminoglycosides), to which various amino sugars are attached by glycosidic linkages (Figures 45-1 and 45-2). They are water-soluble, stable in solution, and more active at alkaline than at acid pH.

B. MECHANISM OF ACTION
The mode of action of streptomycin has been studied far more closely than that of other aminoglycosides, but probably all act similarly. Aminoglycosides are irreversible inhibitors of protein synthesis, but the precise mechanism for bactericidal activity is not known. The initial event is passive diffusion via porin channels across the outer membrane. Drug is then actively transported across the cell membrane into the cytoplasm by an oxygen-dependent process. The transmembrane electrochemical gradient supplies the energy for this process, and transport is coupled to a proton pump. Low extracellular pH and anaerobic conditions inhibit transport by reducing the gradient. Transport may be enhanced by cell wall-active drugs such as penicillin or vancomycin; this enhancement may be the basis of the synergism of these antibiotics with aminoglycosides.

Inside the cell, aminoglycosides bind to specific 30S-subunit ribosomal proteins (S12 in the case of streptomycin). Protein synthesis is inhibited by aminoglycosides in at least three ways (Figure 45-3): (1) interference with the initiation complex of peptide formation; (2) misreading of mRNA, which causes incorporation of incorrect amino acids into the peptide, resulting in a nonfunctional or toxic protein; and (3) breakup of polysomes into nonfunctional monosomes. These activities occur more or less simultaneously, and the overall effect is irreversible and lethal for the cell.

C. MECHANISMS OF RESISTANCE
Three principal mechanisms have been established: (1) production of a transferase enzyme or enzymes inactivates the aminoglycoside by adenylylation, acetylation, or phosphorylation. This is the principal type of resistance encountered clinically. (Specific transferase enzymes are discussed below.) (2) There is impaired entry of aminoglycoside into the cell. This may be genotypic, ie, resulting from mutation or deletion of a porin protein or proteins involved in transport and maintenance of the electrochemical gradient; or phenotypic, eg, resulting from growth conditions under which the oxygen-dependent transport process described above is not functional. (3) The receptor protein on the 30S ribosomal subunit may be deleted or altered as a result of a mutation.

D. PHARMACOKINETICS AND ONCE-DAILY DOSING
Aminoglycosides are absorbed very poorly from the intact gastrointestinal tract; almost the entire oral dose is excreted in feces after oral administration. However, the drugs may be absorbed if ulcerations are present. After intramuscular injection, aminoglycosides are well absorbed, giving peak concentrations in blood within 30-90 minutes. Aminoglycosides are usually administered intravenously as a 30- to 60-minute infusion; after a brief distribution phase, this results in serum concentrations that are identical to those following intramuscular injection.

Traditionally, aminoglycosides have been administered in two or three equally divided daily doses for patients with normal renal function. However, once-daily aminoglycoside dosing may be preferred in certain clinical situations. Aminoglycosides have concentration-dependent killing; that is, increasing concentrations kill an increasing proportion of bacteria and at a more rapid rate. They also have a significant postantibiotic effect, such that the antibacterial activity persists beyond the time during which measurable drug is present. The postantibiotic effect of aminoglycosides can reach several hours. Because of these properties, a given total amount of aminoglycoside may have better efficacy when administered as a single large dose than when administered as multiple smaller doses.

Aminoglycoside toxicity is both time- and concentration-dependent. Toxicity is unlikely to occur until a certain threshold concentration is achieved, but once that concentration is achieved the time above this threshold becomes critical. This threshold is not precisely defined, but a trough concentration above 2 mcg/mL is predictive of toxicity. At clinically relevant doses, the time above this threshold will be greater with multiple smaller doses of drug than with a single large dose.

Numerous clinical studies demonstrate that a single daily dose of aminoglycoside is just as effective¾and no more (and often less) toxic¾than multiple smaller doses. Therefore, many authorities now recommend that aminoglycosides be administered as a single daily dose in many clinical situations. The efficacy of once-daily aminoglycoside dosing in combination therapy of enterococcal, streptococcal, and staphylococcal endocarditis remains to be defined, and the standard low-dose, thrice-daily administration is still recommended. The role of once-daily dosing in pregnancy and in neonates also is not well-defined.

Once-daily dosing has potential practical advantages. For example, determination of serum concentrations is probably unnecessary unless aminoglycoside is given for more than 3 days. A drug administered once a day rather than three times a day saves time. And once-a-day dosing lends itself to outpatient therapy.

Once-daily dosing, however, does not eliminate responsibility for careful monitoring and dosage adjustment to minimize toxicity. Selection of the appropriate dose is particularly critical if renal function is impaired. Aminoglycosides are cleared by the kidney, and excretion is directly proportional to creatinine clearance. Rapidly changing renal function, which may occur with acute renal failure in the patient with septic shock, must be anticipated to avoid overdose. Provided these pitfalls are avoided, once-daily aminoglycoside dosing is safe and effective. If the creatinine clearance is 100 mL/min, gentamicin is given as a 5 mg/kg dose (15 mg/kg for amikacin) over 30-60 minutes. If the creatinine clearance is 80 mL/min, the dose is 4 mg/kg (12 mg/kg for amikacin); if creatinine clearance is 50 mL/min, the dose is 3 mg/kg (9 mg/kg for amikacin). If the creatinine clearance is less than 50 mL/min, a 2 mg/kg gentamicin loading dose is given and subsequent doses are adjusted as would normally be done. Serum concentrations need not be routinely checked until the second or third day of therapy, depending on the stability of renal function and the anticipated duration of therapy. It is probably unnecessary to check peak concentrations, because they will be high. The goal is to administer drug so that concentrations of less than 1 mcg/mL are present between 18 and 24 hours after dosing. This provides a sufficient period of time for washout of drug to occur before the next dose is given. This is most easily determined either by measuring serum concentrations in samples obtained 2 hours and 12 hours after dosing and then adjusting the dose based on the actual clearance of drug or by measuring the concentration in a sample obtained 8 hours after a dose. If the 8-hour concentration is between 1.5 mcg and 6 mcg/mL, the target trough will be achieved at 18 hours.

Aminoglycosides are highly polar compounds that do not enter cells readily. They are largely excluded from the central nervous system and the eye. In the presence of active inflammation, however, cerebrospinal fluid levels reach 20% of plasma levels, and in neonatal meningitis the levels may be higher. Intrathecal or intraventricular injection is required for high levels in cerebrospinal fluid. Even after parenteral administration, concentrations of aminoglycosides are not high in most tissues except the renal cortex. Concentration in most secretions is also modest; in the bile, it may reach 30% of the blood level. With prolonged therapy, diffusion into pleural or synovial fluid may result in concentrations 50-90% of that of plasma.

The normal half-life of aminoglycosides in serum is 2-3 hours, increasing to 24-48 hours in patients with significant impairment of renal function. Aminoglycosides are only partially and irregularly removed by hemodialysis¾eg, 40-60% for gentamicin¾and even less effectively by peritoneal dialysis.

Dosage adjustments must be made to avoid accumulation of drug and toxicity in patients with renal insufficiency. Either the dose of drug is kept constant and the interval between doses is increased, or the interval is kept constant and the dose is reduced. Nomograms and formulas have been constructed relating serum creatinine levels to adjustments in treatment regimens. The simplest formula divides the dose (calculated on the basis of normal renal function) by the serum creatinine value (mg/dL). Thus, a 60-kg patient with normal renal function might receive 300 mg/d of gentamicin (maximum daily dose of 5 mg/kg), whereas a 60-kg patient with a serum creatinine of 3 mg/dL would receive 100 mg/d. However, this approach fails to take into account the age and gender of the patient, both of which significantly affect creatinine clearance without necessarily being reflected as a change in serum creatinine. Because aminoglycoside clearance is directly proportional to the creatinine clearance, a better method for determining the aminoglycoside dose is to estimate creatinine clearance using the Cockcroft-Gault formula described in Chapter 61.

The daily dosage of aminoglycoside is calculated by multiplying the maximum daily dose by the ratio of estimated creatinine clearance to normal creatinine clearance, ie, 120 mL/min, which is a typical value for a 70-kg young adult male. For a 60-year-old female weighing 60 kg with a serum creatinine of 3 mg/dL, the corrected dosage of gentamicin would be approximately 50 mg/d, half the dose calculated by the simplest formula. There is considerable individual variation in aminoglycoside serum levels among patients with similar estimated creatinine clearance values. Therefore, it is mandatory, especially when using higher dosages for more than a few days or when renal function is rapidly changing, to measure serum drug levels to avoid severe toxicity. For a traditional twice- or thrice-daily dosing regimen, peak serum concentrations should be determined from a blood sample obtained 30-60 minutes after a dose and trough concentrations from a sample obtained just before the next dose.

E. ADVERSE EFFECTS
All aminoglycosides are ototoxic and nephrotoxic. Ototoxicity and nephrotoxicity are more likely to be encountered when therapy is continued for more than 5 days, at higher doses, in the elderly, and in the setting of renal insufficiency. Concurrent use with loop diuretics (eg, furosemide, ethacrynic acid) or other nephrotoxic antimicrobial agents (eg, vancomycin or amphotericin) can potentiate nephrotoxicity and should be avoided if possible. Ototoxicity can manifest itself either as auditory damage, resulting in tinnitus and high-frequency hearing loss initially, or as vestibular damage, evident by vertigo, ataxia, and loss of balance. Nephrotoxicity results in rising serum creatinine levels or reduced creatinine clearance, although the earliest indication often is an increase in trough serum aminoglycoside concentrations. Neomycin, kanamycin, and amikacin are the most ototoxic agents. Streptomycin and gentamicin are the most vestibulotoxic. Neomycin, tobramycin, and gentamicin are the most nephrotoxic.

In very high doses, aminoglycosides can produce a curare-like effect with neuromuscular blockade that results in respiratory paralysis. This paralysis is usually reversible by calcium gluconate (given promptly) or neostigmine. Hypersensitivity occurs infrequently.

F. CLINICAL USES
Aminoglycosides are mostly used against gram-negative enteric bacteria, especially when the isolate may be drug-resistant and when there is suspicion of sepsis. They are almost always used in combination with a b-lactam antibiotic to extend coverage to include potential gram-positive pathogens and to take advantage of the synergism between these two classes of drugs. Penicillin-aminoglycoside combinations also are used to achieve bactericidal activity in treatment of enterococcal endocarditis and to shorten duration of therapy for viridans streptococcal and staphylococcal endocarditis. Which aminoglycoside and what dose should be used depend on the infection being treated and the susceptibility of the isolate.

STREPTOMYCIN

Introduction

Streptomycin (Figure 45-1) was isolated from a strain of Streptomyces griseus. The antimicrobial activity of streptomycin is typical of that of other aminoglycosides, as are the mechanisms of resistance. Resistance has emerged in most species, severely limiting the current usefulness of streptomycin, with the exceptions listed below. Ribosomal resistance to streptomycin develops readily, limiting its role as a single agent.

Clinical Uses

A. MYCOBACTERIAL INFECTIONS
Streptomycin is mainly used as a second-line agent for treatment of tuberculosis. The dosage is 0.5-1 g/d (7.5-15 mg/kg/d for children), which is given intramuscularly or intravenously. It should be used only in combination with other agents to prevent emergence of resistance. See Chapter 47 for additional information regarding the use of streptomycin in mycobacterial infections.

B. NONTUBERCULOUS INFECTIONS
In plague, tularemia, and sometimes brucellosis, streptomycin, 1 g/d (15 mg/kg/d for children), is given intramuscularly in combination with an oral tetracycline.

Penicillin plus streptomycin is effective for enterococcal endocarditis and 2-week therapy of viridans streptococcal endocarditis. Gentamicin has largely replaced streptomycin for these indications. Streptomycin remains a useful agent for treating enterococcal infections, however, because approximately 15% of enterococcal isolates that are resistant to gentamicin (and therefore to netilmicin, tobramycin, and amikacin) will be susceptible to streptomycin.

Adverse Reactions

Fever, skin rashes, and other allergic manifestations may result from hypersensitivity to streptomycin. This occurs most frequently with prolonged contact with the drug either in patients who receive a prolonged course of treatment (eg, for tuberculosis) or in medical personnel who handle the drug. Desensitization is occasionally successful.

Pain at the injection site is common but usually not severe. The most serious toxic effect with streptomycin is disturbance of vestibular function¾vertigo and loss of balance. The frequency and severity of this disturbance are in proportion to the age of the patient, the blood levels of the drug, and the duration of administration. Vestibular dysfunction may follow a few weeks of unusually high blood levels (eg, in individuals with impaired renal function) or months of relatively low blood levels. Vestibular toxicity tends to be irreversible. Streptomycin given during pregnancy can cause deafness in the newborn and therefore is relatively contraindicated.

GENTAMICIN

Introduction

Gentamicin is an aminoglycoside (Figure 45-2) isolated from Micromonospora purpurea. It is effective against both gram-positive and gram-negative organisms, and many of its properties resemble those of other aminoglycosides. Sisomicin is very similar to the C_1a component of gentamicin.

Antimicrobial Activity

Gentamicin sulfate, 2-10 mcg/mL, inhibits in vitro many strains of staphylococci and coliforms and other gram-negative bacteria. It is active alone, but also as a synergistic companion with b-lactam antibiotics, against pseudomonas, proteus, enterobacter, klebsiella, serratia, stenotrophomonas, and other gram-negative rods that may be resistant to multiple other antibiotics. Like all aminoglycosides, it has no activity against anaerobes.

Resistance

Streptococci and enterococci are relatively resistant to gentamicin owing to failure of the drug to penetrate into the cell. However, gentamicin in combination with vancomycin or a penicillin produces a potent bactericidal effect, which in part is due to enhanced uptake of drug that occurs with inhibition of cell wall synthesis. Resistance to gentamicin rapidly emerges in staphylococci owing to selection of permeability mutants. Ribosomal resistance is rare. Among gram-negative bacteria, resistance is most commonly due to plasmid-encoded aminoglycoside-modifying enzymes. Gram-negative bacteria that are gentamicin-resistant usually are susceptible to amikacin, which is much more resistant to modifying enzyme activity. The enterococcal enzyme that modifies gentamicin is a bifunctional enzyme that also inactivates amikacin, netilmicin, and tobramycin, but not streptomycin; the latter is modified by a different enzyme. This is why some gentamicin-resistant enterococci are susceptible to streptomycin.

Clinical Uses

A. INTRAMUSCULAR OR INTRAVENOUS ADMINISTRATION
Gentamicin is used mainly in severe infections (eg, sepsis and pneumonia) caused by gram-negative bacteria that are likely to be resistant to other drugs, especially pseudomonas, enterobacter, serratia, proteus, acinetobacter, and klebsiella. It usually is used in combination with a second agent, as an aminoglycoside alone may not be effective for infections outside the urinary tract. For example, gentamicin should not be used as a single agent to treat staphylococcal infections because resistance develops rapidly. Aminoglycosides should not be used for single-agent therapy of pneumonia because penetration of infected lung tissue is poor and local conditions of low pH and low oxygen tension contribute to poor activity. Gentamicin 5-6 mg/kg/d traditionally is given intravenously in three equal doses, but once-daily administration is just as effective for some organisms and less toxic.

Serum gentamicin concentrations and renal function should be monitored if gentamicin is administered for more than a few days or if renal function is changing (eg, in sepsis, which often is complicated by acute renal failure). For patients receiving dosing every 8 hours, target peak concentrations are 5-10 mcg/mL, and trough concentrations should be less than 1-2 mcg/mL. Trough concentrations above 2 mcg/mL indicate accumulation of drug and are associated with toxicity; in this case, the dose should be lowered or the interval extended to achieve the target range.

B. TOPICAL ADMINISTRATION
Creams, ointments, and solutions containing 0.1-0.3% gentamicin sulfate have been used for the treatment of infected burns, wounds, or skin lesions and the prevention of intravenous catheter infections. Topical gentamicin is partly inactivated by purulent exudates. Ten milligrams can be injected subconjunctivally for treatment of ocular infections.

C. INTRATHECAL ADMINISTRATION
Meningitis caused by gram-negative bacteria has been treated by the intrathecal injection of gentamicin sulfate, 1-10 mg/d. However, neither intrathecal nor intraventricular gentamicin was beneficial in neonates with meningitis, and intraventricular gentamicin was toxic, raising questions about the utility of this form of therapy. Moreover, the availability of third-generation cephalosporins for gram-negative meningitis has rendered this therapy obsolete in most cases.

Adverse Reactions

Nephrotoxicity is usually reversible and mild. It occurs in 5-25% of patients receiving gentamicin for longer than 3-5 days. Such toxicity requires, at the very least, adjustment of the dosing regimen and should prompt reconsideration of the need for the drug, particularly if there is a less toxic alternative agent. Measurement of gentamicin serum levels is essential. Ototoxicity, which tends to be irreversible, manifests itself mainly as vestibular dysfunction. Loss of hearing can also occur. The incidence of ototoxicity is in part genetically determined, having been linked to point mutations in mitochondrial DNA, and occurs in 1-5% for patients receiving gentamicin for more than 5 days. Hypersensitivity reactions to gentamicin are uncommon.

TOBRAMYCIN

This aminoglycoside (Figure 45-2) has an antibacterial spectrum similar to that of gentamicin. Although there is some cross-resistance between gentamicin and tobramycin, it is unpredictable in individual strains. Separate laboratory susceptibility tests are therefore necessary.

The pharmacokinetic properties of tobramycin are virtually identical to those of gentamicin. The daily dose of tobramycin is 5-6 mg/kg intramuscularly or intravenously, traditionally divided into three equal amounts and given every 8 hours. Monitoring blood levels in renal insufficiency is an essential guide to proper dosing.

Tobramycin has almost the same antibacterial spectrum as gentamicin with a few exceptions. Gentamicin is slightly more active against serratia, whereas tobramycin is slightly more active against pseudomonas; Enterococcus faecalis is susceptible to both gentamicin and tobramycin, but E faecium is resistant to tobramycin. Gentamicin and tobramycin are otherwise interchangeable clinically. Gentamicin is much less expensive, however, and is preferred for this reason.

Like other aminoglycosides, tobramycin is ototoxic and nephrotoxic. Nephrotoxicity of tobramycin may be slightly less than that of gentamicin, but the difference is clinically inconsequential.

Tobramycin is also formulated in solution (300 mg in 5 mL) for inhalation for treatment of Pseudomonas aeruginosa lower respiratory tract infections complicating cystic fibrosis. The drug is recommended as a 300-mg dose regardless of the patient's age or weight for administration twice daily in repeated cycles of 28 days on therapy followed by 28 days off therapy. Serum concentrations 1 hour after inhalation average 1 mcg/mL; consequently, nephrotoxicity and ototoxicity rarely occur. Caution should be used when administering the tobramycin to patients with preexisting renal, vestibular, or hearing disorders.

AMIKACIN

Amikacin is a semisynthetic derivative of kanamycin; it is less toxic than the parent molecule (Figure 45-2). It is resistant to many enzymes that inactivate gentamicin and tobramycin, and it therefore can be used against some microorganisms resistant to the latter drugs. Many gram-negative enteric bacteria, including many strains of proteus, pseudomonas, enterobacter, and serratia, are inhibited by 1-20 mcg/mL amikacin in vitro. After injection of 500 mg of amikacin every 12 hours (15 mg/kg/d) intramuscularly, peak levels in serum are 10-30 mcg/mL.

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 7.5-15 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 troughs should be maintained at less than 2 mcg/mL.

NETILMICIN

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 gentamicin-resistant and tobramycin-resistant bacteria.

The dosage (5-7 mg/kg/d) and the routes of administration are the same as for gentamicin. It is completely therapeutically interchangeable with gentamicin or tobramycin and has similar toxicities.

NEOMYCIN & KANAMYCIN

Introduction

Neomycin and kanamycin are closely related. Paromomycin is also a member of this group. All have similar properties.

Antimicrobial Activity & Resistance

Drugs of the neomycin group are active against gram-positive and gram-negative bacteria and some mycobacteria. Pseudomonas and streptococci are generally resistant. Mechanisms of antibacterial action and resistance are the same as with other aminoglycosides. The widespread use of these drugs in bowel preparation for elective surgery has resulted in the selection of resistant organisms and some outbreaks of enterocolitis in hospitals. Cross-resistance between kanamycin and neomycin is complete.

Pharmacokinetics

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.

Clinical Uses

Neomycin and kanamycin are now limited to topical and oral use. Neomycin is too toxic for parenteral use. With the advent of more potent and less toxic aminoglycosides, parenteral administration of kanamycin has also been largely abandoned.

A. TOPICAL ADMINISTRATION
Solutions containing 1-5 mg/mL are 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 is 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 coma, coliform flora can be suppressed by giving 1 g every 6-8 hours together with reduced protein intake, thus reducing ammonia intoxication. Use of neomycin for hepatic coma has been almost entirely supplanted by lactulose, which is much less toxic. Paromomycin, 1 g every 6 hours orally for 2 weeks, has been effective in intestinal amebiasis (see Chapter 53).

Adverse Reactions

All members of the neomycin group have significant nephrotoxicity and ototoxicity. Auditory function is affected more than vestibular. Deafness has occurred, 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.

SPECTINOMYCIN

Spectinomycin is an aminocyclitol antibiotic that is structurally related to aminoglycosides. It lacks amino sugars and glycosidic bonds.



Spectinomycin is active in vitro against many gram-positive and gram-negative organisms, but it is used almost solely as an alternative treatment for drug-resistant gonorrhea or gonorrhea in penicillin-allergic patients. The majority of gonococcal isolates are inhibited by 6 mcg/mL of spectinomycin. Strains of gonococci may be resistant to spectinomycin, but there is no cross-resistance with other drugs used in gonorrhea. Spectinomycin is rapidly absorbed after intramuscular injection. A single dose of 40 mg/kg up to a maximum of 2 g is given. There is pain at the injection site and occasionally fever and nausea. Nephrotoxicity and anemia have been observed rarely.



PREPARATIONS AVAILABLE

Amikacin (generic, Amikin)

Parenteral: 50, 250 mg (in vials) for IM, IV injection

Gentamicin (generic, Garamycin)

Parenteral: 10, 40 mg/mL vials for IM, IV injection

Kanamycin (Kantrex)

Oral: 500 mg capsules
Parenteral: 500, 1000 mg for IM, IV injection; 75 mg for pediatric injection

Neomycin (generic, Mycifradin)

Oral: 500 mg tablets; 125 mg/5 mL solution

Netilmicin (Netromycin)

Parenteral: 100 mg/mL for IM, IV injection

Paromomycin (Humatin)

Oral: 250 mg capsules

Spectinomycin (Trobicin)

Parenteral: 2 g powder to reconstitute for 400 mg/mL IM injection

Streptomycin (generic)

Parenteral: 400 mg/mL for IM injection

Tobramycin (generic, Nebcin)

Parenteral: 10, 40 mg/mL for IM, IV injection; powder to reconstitute for injection
Solution for inhalation (TOBI): 300 mg in 5 mL sodium chloride solution



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