Page 847 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 45 Aminoglycosides & Spectinomycin 833

not recommended for treatment of pharyngeal gonococcal infec- children).There is pain at the injection site and, occasionally, fever
tions due to high failure rates regardless of in vitro susceptibility. and nausea. Nephrotoxicity and anemia have been observed rarely.
Spectinomycin is rapidly absorbed after intramuscular injection. Spectinomycin is no longer available for use in the USA but is still
The standard regimen is a single dose of 2–4 g/d (40 mg/kg in recommended elsewhere.

SUMMARY Aminoglycosides

Subclass, Mechanism of Pharmacokinetics, Toxicities,
Drug Action Effects Clinical Applications Interactions

AMINOGLYCOSIDES & SPECTINOMYCIN
• Gentamicin Prevents bacterial Bactericidal activity against Sepsis caused by aerobic IV • renal clearance (half-life 2.5 h) • conventional
protein synthesis susceptible bacteria • synergistic Gram-negative bacteria dosing 1.3–1.7 mg/kg q8h with goal peak levels
by binding to the effects against Gram-positive bacteria • synergistic activity in 5–8 mcg/mL • trough levels <2 mcg/mL
30S ribosomal when combined with β-lactams or endocarditis caused by • once-daily dosing at 5–7 mg/kg as effective and
subunit vancomycin • concentration- streptococci, staphylococci, may have less toxicity than conventional dosing
dependent killing and a significant and enterococci • Toxicity: Nephrotoxicity (reversible), ototoxicity
post-antibiotic effect (irreversible), neuromuscular blockade

• Tobramycin: Intravenous; more active than gentamicin versus Pseudomonas; may also have less nephrotoxicity
• Amikacin: Intravenous; resistant to many enzymes that inactivate gentamicin and tobramycin; higher doses and target peaks and troughs than gentamicin and
tobramycin
• Streptomycin: Intramuscular, widespread resistance limits use to specific indications such as tuberculosis and enterococcal endocarditis
• Neomycin: Oral or topical, poor bioavailability; used before bowel surgery to decrease aerobic flora
• Spectinomycin: Intramuscular; sole use is for treatment of antibiotic-resistant gonococcal infections or gonococcal infections in penicillin-allergic patients; not available
in the USA

PREP AR A TIONS Cheer SM, Waugh J, Noble S: Inhaled tobramycin (TOBI): A review of its use in
A V AIL ABLE the management of Pseudomonas aeruginosa infections in patients with cystic
fibrosis. Drugs 2003;63:2501.
Freeman CD et al: Once-daily dosing of aminoglycosides: Review and recommen-
dations for clinical practice. J Antimicrob Chemother 1997;39:677.
GENERIC NAME AVAILABLE AS
Jackson J et al: Aminoglycosides: How should we use them in the 21st century?
Amikacin Generic, Amikin Curr Opin Infect Dis 2013;26:516.
Gentamicin Generic Le T, Bayer AS: Combination antibiotic therapy for infective endocarditis. Clin
Kanamycin Generic, Kantrex Infect Dis 2003;36:615.
Neomycin Generic, Mycifradin Olsen KM et al: Effect of once-daily dosing vs. multiple daily dosing of tobramycin
on enzyme markers of nephrotoxicity. Crit Care Med 2004;32:1678.
Paromomycin Generic, Humatin
Paul M et al: Beta-lactam monotherapy versus beta-lactam-aminoglycoside combi-
Streptomycin Generic nation therapy in cancer patients with neutropenia. Cochrane Database Syst
Tobramycin Generic, Nebcin Rev 2013 Jun 29;6:CD003038.
Peña C et al: Effect of adequate single-drug versus combination antimicrobial
therapy on mortality in Pseudomonas aeruginosa bloodstream infections. Clin
REFERENCES Infect Dis 2013;57:208.
Baddour L et al: Infective Endocarditis in Adults: Diagnosis, Antimicrobial Poole K: Aminoglycoside resistance in Pseudomonas aeruginosa. Antimicrob Agents
Therapy, and Management of Complications. Circulation 2015;132:1435. Chemother 2005;49:479.
Busse H-J, Wöstmann C, Bakker EP: The bactericidal action of streptomycin: Zhanel G et al: Comparison of the next generation aminoglycoside plazomicin
Membrane permeabilization caused by the insertion of mistranslated pro- to gentamicin, tobramycin, and amikacin. Expert Rev Anti Infect Ther
teins into the cytoplasmic membrane of Escherichia coli and subsequent 2012;10:459.
caging of the antibiotic inside the cells due to degradation of these proteins.
J Gen Microbiol 1992;138:551.

C ASE STUD Y ANSWER

The patient has normal renal function and thus qualifies divided and administered every 8 hours, as a conventional
for once-daily dosing. Tobramycin could be administered dosing strategy. With conventional dosing, peak and trough
as a single once-daily injection at a dose of 350–490 mg concentrations should be monitored with the target peak
(5–7 mg/kg). A serum level between 1.5 and 6 mcg/mL mea- concentration of 5–10 mcg/mL and the target trough con-
sured 8 hours after infusion correlates with an appropriate centration of <2 mcg/mL.
trough level. Alternatively, the same total daily dose could be