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Chapter 45: Aminoglycosides & Spectinomycin

A 34-year-old patient is febrile (39.5°C [103.1°F]), with a white blood cell count that has risen from 8500 to 20,000/mm3. The ICU attending physician is concerned about a bloodstream infection and decides to treat with empiric combination therapy directed against Pseudomonas aeruginosa. The combination therapy includes tobramycin. Regarding the mechanism of action of aminoglycosides, the drugs

(A) Are bacteriostatic

(B) Bind to the 50S ribosomal subunit

(C) Cause misreading of the code on the mRNA template

(D) Inhibit peptidyl transferase

(E) Stabilize polysomes

Aminoglycosides are bactericidal inhibitors of protein synthesis binding to specific components of the 30S ribosomal subunit. Their actions include block of the formation of the initiation complex, miscoding, and polysomal breakup. Peptidyl transferase is inhibited by chloramphenicol, not aminoglycosides. The answer is C.

A 72-kg patient with creatinine clearance of 80 mL/min has a Gram-negative infection. Amikacin is administered intramuscularly at a dose of 5 mg/kg every 8 h, and the patient begins to respond. After 2 d, creatinine clearance declines to 40 mL/min. Assuming that no information is available about amikacin plasma levels, what would be the most reasonable approach to management of the patient at this point?

(A) Administer 5 mg/kg every 12 h

(B) Decrease the dosage to daily total of 200 mg

(C) Decrease the dosage to 180 mg every 8 h

(D) Discontinue amikacin and switch to gentamicin

(E) Maintain the patient on the present dosage and test auditory function

Monitoring plasma drug levels is important when aminoglycosides are used. In this case, the patient seems to be improving, so a decrease of the amikacin dose in proportion to decreased creatinine clearance is most appropriate. Because creatinine clearance is only one half of the starting value, a dose reduction should be made to one half of that given initially. The answer is C.

Which of the following statements about the clinical uses of the aminoglycosides is accurate?

(A) Effective in the treatment of infections caused by anaerobes such as Bacteroides fragilis

(B) Gentamycin is used with ampicillin for synergistic effects in the treatment of enterococcal endocarditis

(C) In the treatment of a hospital-acquired infection caused by Serratia marcescens, netilmicin is less effective than streptomycin

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