Aminoglycoside Antibiotics: Clinical Uses

CLINICAL USES

Serious Gram-Negative Bacillary Infections

Gentamicin is the aminoglycoside antibiotic most com-monly used to treat serious infections due to gram-negative aerobic bacilli, such as Escherichia coli and Kleb-siella pneumoniae, and Proteus, Serratia, Acinetobacter, Citrobacter, and Enterobacter spp. Gentamicin also has significant activity against Staphylococcus aureus. The aminoglycosides are often used in combination with β-lactams in the initial empirical therapy of sepsis and of fever in immunocompromised patients. The combination is used both to ensure adequate antibiotic coverage in these seriously ill patients and to exploit the synergistic antibiotic activity that β-lactams and aminoglycosides have against many species. These drugs should not, how-ever, be injected simultaneously, since the β-lactams can chemically inactivate the aminoglycosides.

Aminoglycosides are often used in patients with gram-negative bacillary pneumonia. Single daily dosing may be of particular importance in patients with pneu-monia, since this regimen can increase the peak con-centration of the aminoglycosides in bronchial secre-tions.

Acute salpingitis (pelvic inflammatory disease) due to Neisseria gonorrhoeae, Chlamydia trachomatis, or both is often complicated by superinfection with gram-negative bacilli and anaerobes. A combination of gen-tamicin, clindamycin, and doxycycline has been shown to be an effective treatment for this polymicrobial in-fection.

The combination of gentamicin and clindamycin is useful in patients with an intraabdominal infection or an abscess secondary to penetrating trauma, diverticuli-tis, cholangitis, appendicitis, peritonitis, or postsurgical wound infection. These infections are often polymicro-bial, including gram-negative bacilli and anaerobes. Definitive treatment of these conditions may also re-quire surgical or other intervention to drain the abscess.

Choice of one aminoglycoside over another for the treatment of serious infections should be guided both by assessment of the antibiotic sensitivities of the spe-

cific bacterial strain causing the patient’s infection and by familiarity with local patterns of bacterial resistance. Pseudomonas aeruginosa is more likely than other gram-negative bacilli to exhibit resistance to genta-micin. However, Pseudomonas spp. resistant to gen-tamicin may be susceptible to amikacin or tobramycin. Streptomycin is the drug of choice for patients with pneumonia due to Yersinia pestis (plague) or Francisella tularensis (tularemia).

Eradication of Facultative Gut Flora

A combination of neomycin and nonabsorbable eryth-romycin base given orally prior to colorectal surgery can markedly reduce the incidence of postoperative wound infection. Orally administered neomycin is sometimes used to suppress the facultative flora of the gut in patients with hepatic encephalopathy. It is un-clear how this improves coma, but one theory is that it reduces systemic absorption of the bacterial metabo-lites that allegedly cause hepatic encephalopathy. Although more than 95% of an oral dose of neomycin is excreted unchanged in the stool of normal subjects, the bioavailability of neomycin may be much higher in patients with an abnormal gastrointestinal mucosa.

Neomycin is often combined with other antibiotics, such as polymyxin B and bacitracin, and applied as an ointment to prevent any infection of minor skin abra-sions, burns, and cuts.

Cystic Fibrosis

P. aeruginosa is commonly found in the bronchial secre-tions of patients with cystic fibrosis. In one study, daily inhalation of large doses of tobramycin decreased the colonization by this organism 100-fold and significantly improved pulmonary function.

Endocarditis

A combination of gentamicin and ampicillin is recom-mended as prophylaxis of endocarditis prior to surgery or instrumentation of the gastrointestinal or genitouri-nary tracts for patients at high risk for endocarditis. Gentamicin plus vancomycin is recommended as pro-phylaxis of endocarditis for high-risk patients with a his-tory of β-lactam allergy. Gentamicin or streptomycin will act synergistically with penicillin for the treatment of enterococcal endocarditis.

Meningitis

The degree of penetration of the aminoglycosides into cerebrospinal fluid is proportional to the degree of in-flammation of the meninges. However, aminoglycosides are best combined with the β-lactams or other antibi-otics in the treatment of meningitis.

Tuberculosis

In response to the increasing prevalence of mycobacte-rial resistance to standard antibiotic chemotherapy, the use of aminoglycosides is increasing in patients at high risk for having resistant infections. Inhaled aminoglyco-sides may also have a role in patients with persistently positive sputum despite therapy. Streptomycin is useful in the initial therapy of severe or disseminated tubercu-losis, which is most common in immunocompromised patients.

Ophthalmological Infection

Because of the very high concentrations of gentamicin achieved in the conjunctival sac, it is effective against nearly all of the typical bacterial pathogens that cause conjunctivitis. Special high-dose formulations of gentam-icin are necessary for treating bacterial ophthalmic ker-atitis. Gentamicin is not active against viral conjunctivitis, although it may prevent a secondary bacterial infection. Bacterial endophthalmitis, an infection of the vitreous humor, usually requires both vitreous aspiration and in-travitreal instillation of gentamicin and cefazolin.

Gonococcal Urethritis

Spectinomycin (Trobicin), an aminocyclitol antibiotic chemically related to the aminoglycosides, is occasion-ally used to treat uncomplicated gonococcal urethritis in patients who are allergic to β-lactam. Treatment fail-ures have occurred, however, when spectinomycin was used in gonococcal pharyngitis or systemic gonococcal infection.