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- BAEP: brainstem auditory evoked potential
- Cmax: peak serum concentration
- MIC: minimum inhibitory concentration
- NAG: N-acetyl-beta-glucosaminidase
- PAE: postantibiotic effect
- TEOAE: transient evoked otoacoustic emissions
- Vd: volume of distribution
Objectives
After completing this article, readers should be able to:
Describe the concept of concentration-dependent bactericidal activity seen with aminoglycosides.
Describe the postantibiotic effect of aminoglycosides.
Explain the concept of adaptive resistance.
Describe the effects of extended dosing intervals on potential aminoglycoside toxicities.
Apply concepts of extended-dosing intervals to gentamicin therapy in neonates.
Background
Aminoglycosides are among the most frequently used antibiotics in neonatology, usually for patients in whom sepsis is suspected. Despite the development of third- and fourth-generation cephalosporins and other new antibiotics, gentamicin, netilmicin, tobramycin, and amikacin continue to be important tools for treating serious infections in neonates. They are bactericidal, have a relatively low rate of bacterial resistance, and have a low cost. Aminoglycosides used concurrently with beta-lactam antibiotics yield synergistic activity against both gram-negative and gram-positive bacteria as well as reduced development of resistance. However, aminoglycosides have a narrow therapeutic window, and close monitoring is required to minimize potential nephrotoxicity and ototoxicity. In the past few years, dosing regimens have been changed in the hopes of increasing efficacy and decreasing toxicity. This review discusses the evidence supporting high-dose/extended-interval regimens and their application to neonates.
Aminoglycoside antibiotics have been used since the 1940s, initially developed by screening soil actinomycetes for antibacterial activity. All consist of a six-membered ring that has amino group constituents linked by glycosidic bonds to two or more sugars. The commonly used aminoglycosides in neonatology—gentamicin, tobramycin, netilmicin, and amikacin—differ in the number and type of sugars linked at various places on the aminocyclitol ring. Understanding of how the different structures relate to antibacterial activity is incomplete. All are highly active against most aerobic gram-negative bacteria. Tobramycin is most active against Pseudomonas sp, and amikacin usually is reserved for treatment of organisms such as Serratia sp that are resistant to other aminoglycosides. Synergism with antibiotics that disrupt …
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