83932
document
Once versus thrice daily gentamicin in patients with serious infections . Aminoglycosides are usually given in two or three divided doses . A once-daily regimen might be more effective and less toxic . We have conducted a randomised trial in consecutive patients with serious infections for whom an aminoglycoside seemed warranted . Exclusion criteria were neutropenia or severely impaired renal function . 123 patients were enrolled . For efficacy analysis only those patients were considered in whom treatment with the aminoglycoside was not stopped within 72 h ( n = 67 ) ; toxicity was analysed on patients receiving aminoglycosides for more than 48 h and not using other nephrotoxic medication ( n = 85 ) . Gentamicin 4 mg/kg every day ( OD ) or gentamicin 1.33 mg/kg three times daily ( MD ) ( with dose-reduction in case of renal dysfunction ) were given intravenously . In almost all patients intravenous amoxycillin 1 g every 6 h was also started . Baseline characteristics were comparable in both arms . A good clinical response was observed in 32/35 ( 91 % ) of the OD and in 25/32 ( 78 % ) in the MD group ( difference 13 % , 95 % confidence interval -6.4 % to +26.9 % ) . 2 patients in each group died with uncontrolled infection . An insufficient bacteriological response ( persistent positive cultures , resistance , or superinfection ) was observed in 2 patients with OD and 3 patients with MD . In patients treated for more than 48 h duration of therapy and mean doses were 7.0 days ( 1590 mg ) and 7.4 days ( 1672 mg ) in OD and MD respectively . Mean first serum trough/peak levels were 0.6/10.2 mg/L and 1.4/5.2 mg/L . Nephrotoxicity ( a rise in serum creatinine of 45 mumol/L or more ) developed in 2/40 ( 5 % ) in OD and 11/45 ( 24 % ) in MD ( p = 0.016 ) . Risk factors for nephrotoxicity were duration of therapy and baseline creatinine clearance rate . High-tone audiometry was performed when possible ; no significant differences were found in hearing loss ( 3/12 and 3/11 ) or prodromal signs of ototoxicity ( 5/12 and 4/11 ) . A once-daily dosing regimen of gentamicin is at least as effective as and is less nephrotoxic than more frequent dosing .
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Intervention_Pharmacological
daily gentamicin
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Intervention_Pharmacological
aminoglycoside
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Intervention_Pharmacological
aminoglycosides
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Intervention_Pharmacological
Gentamicin 4 mg/kg every day ( OD ) or gentamicin 1.33 mg/kg three times daily ( MD ) ( with dose-reduction in case of renal dysfunction
83937
Intervention_Pharmacological
intravenous amoxycillin 1 g every 6 h
83938
Intervention_Pharmacological
OD
83939
Intervention_Pharmacological
MD
83940
Intervention_Pharmacological
OD
83941
Intervention_Pharmacological
MD
83942
Intervention_Pharmacological
once-daily dosing regimen of gentamicin
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Outcome_Physical
persistent positive cultures , resistance , or superinfection
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Outcome_Physical
Mean first serum trough/peak levels
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Outcome_Physical
Nephrotoxicity ( a rise in serum creatinine of 45 mumol/L or more )
83946
Outcome_Adverse-effects
nephrotoxicity
83947
Outcome_Physical
creatinine clearance rate
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Outcome_Other
High-tone audiometry
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Outcome_Physical
hearing loss
83950
Outcome_Physical
prodromal signs of ototoxicity
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Participant_Condition
infections
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Participant_Condition
infections
83953
Participant_Condition
neutropenia
83954
Participant_Condition
impaired renal function
83955
Participant_Sample-size
123