BNF for Children 2011-2012

BNFC 2011–2012 5.1.4 Aminoglycosides 277Most side-effects of this group of antibiotics are doserelated;therefore care must be taken with dosage andwhenever possible treatment should not exceed 7 days.The important side-effects are ototoxicity, and nephrotoxicity;they occur most commonly in children withrenal failure.Aminoglycosides may impair neuromuscular transmissionand should not be given to children with myastheniagravis; large doses given during surgery havebeen responsible for a transient myasthenic syndromein patients with normal neuromuscular function.Aminoglycosides should preferably not be given withpotentially ototoxic diuretics (e.g. furosemide); if concurrentuse is unavoidable, administration of the aminoglycosideand of the diuretic should be separated byas long a period as practicable.Renal impairment Excretion of aminoglycosides isprincipally via the kidney and accumulation occurs inrenal impairment. Ototoxicity and nephrotoxicity occurcommonly in patients with renal failure. If there isimpairment of renal function, the interval betweendoses must be increased; if the renal impairment issevere, the dose itself should be reduced as well.Serum-aminoglycoside concentrations must be monitoredin patients with renal impairment, see SerumConcentrations below; renal, auditory, and vestibularfunction should also be monitored. A once-daily, highdoseregimen of an aminoglycoside should be avoidedin children over 1 month of age with a creatinineclearance less than 20 mL/minute/1.73 m 2 .Once daily dosage Once daily administration ofaminoglycosides is more convenient, provides adequateserum concentrations, and has largely superseded multiple-dailydose regimens (given in 2–3 divided dosesduring the 24 hours). Local guidelines on dosage andserum concentrations should be consulted. A oncedaily,high-dose regimen of an aminoglycoside shouldbe avoided in children with endocarditis or burns ofmore than 20% of the total body surface area, or inchildren over 1 month of age with a creatinine clearanceof less than 20 mL/minute/1.73m 2 . The extended intervaldose regimen is used in neonates to reflect thechanges in renal function that occur with increasinggestational and postnatal age (see Neonates below).Serum concentrations Serum concentration monitoringavoids both excessive and subtherapeutic concentrationsthus preventing toxicity and ensuring efficacy.In children with normal renal function,aminoglycoside concentration should be measured initiallyafter 3 or 4 doses of a multiple daily dose regimen;children with renal impairment may require earlier andmore frequent measurement of aminoglycoside concentration.Blood samples should be taken just before the next doseis administered (‘trough’ concentration). If the pre-dose(‘trough’) concentration is high, the interval betweendoses must be increased. For multiple daily dose regimens,blood samples should also be taken approximately1 hour after intramuscular or intravenous administration(‘peak’ concentration). If the post-dose (‘peak’)concentration is high, the dose must be decreased.Serum-aminoglycoside concentration should be measuredin all children and must be determined in infants,in neonates, in obesity, and in cystic fibrosis, or if highdoses are being given, or if there is renal impairment.Cystic fibrosis A higher dose of parenteral aminoglycosideis often required in children with cystic fibrosisbecause renal clearance of the aminoglycoside isincreased. For the role of aminoglycosides in the treatmentof pseudomonal lung infections in cystic fibrosissee Table 1, section 5.1. Nebulised tobramycin is usedfor chronic pseudomonal lung infection in cystic fibrosis;however, resistance may develop, and some childrendo not respond to treatment.Endocarditis Gentamicin is used in combination withother antibiotics for the treatment of bacterial endocarditis(Table 1, section 5.1). Serum-gentamicin concentrationshould be determined twice each week (moreoften in renal impairment). Streptomycin may be usedas an alternative in gentamicin-resistant enterococcalendocarditis.Gentamicin is the aminoglycoside of choice in the UKand is used widely for the treatment of serious infections.It has a broad spectrum but is inactive againstanaerobes and has poor activity against haemolyticstreptococci and pneumococci. When used for the‘blind’ therapy of undiagnosed serious infections it isusually given in conjunction with a penicillin or metronidazole(or both). Gentamicin is used together withanother antibiotic for the treatment of endocarditis (seeabove and Table 1, section 5.1).Loading and maintenance doses may be calculated onthe basis of the patient’s weight and renal function (e.g.using a nomogram); adjustments are then made accordingto serum-gentamicin concentrations. High doses areoccasionally indicated for serious infections, especiallyin the neonate, children with cystic fibrosis or theimmunocompromised patient; whenever possible treatmentshould not exceed 7 days.Amikacin is more stable than gentamicin to enzymeinactivation. Amikacin is used in the treatment of seriousinfections caused by gentamicin-resistant Gramnegativebacilli.Tobramycin has similar activity to gentamicin. It isslightly more active against Ps. aeruginosa but showsless activity against certain other Gram-negative bacteria.Tobramycin may be administered by nebuliser for thetreatment of Ps. aeruginosa infection in cystic fibrosis(see Cystic Fibrosis, above).Neomycin is too toxic for parenteral administration andcan only be used for infections of the skin or mucousmembranes or to reduce the bacterial population of thecolon prior to bowel surgery or in hepatic failure. Oraladministration may lead to malabsorption. Smallamounts of neomycin may be absorbed from the gutin children with hepatic failure and, as these childrenmay also be uraemic, cumulation may occur with resultantototoxicity.Neonates As aminoglycosides are eliminated principallyvia the kidney, neonatal treatment must reflect thechanges in glomerular filtration that occur with increasinggestational and postnatal age. The extended intervaldose regimen is used in neonates, and serum-aminoglycosideconcentrations must be measured. In patients onsingle daily dose regimens it may become necessary toprolong the dose interval to more than 24 hours if thetrough concentration is high.5 Infections