During many years dosage of aminoglycosides have generated resistance
in several microorganisms through biochemical pathways that began to be
understand recently, although more suitable dose scheme must be
dilucidated. (1)
Meta-Analysis of Cantopoulus-Ioannidis is a very interesting work
mainly because it shows a general tendency of these years about once daily
dose (ODD) of aminoglycosides in pediatric and neonate patients.
Difficulties of this type of analysis are well known but, instead of
that, some of analyzed groups of patients show an also well known
different pharmacokinetics behavior for several drugs, and specifically
for aminoglycosides. This analysis includes only three studies with
tobramycin and netilmicin in cystic fibrosis (CF) patients, and we think
that some points would need to be clarified:
A - Amikacin and gentamicin were used in 21 of 24 groups studied.
Others three assays used tobramycin (one of them also netilmicin). These
three groups were the only ones with CF patients. This means that
Cantopoulus-Ioannidis et. al. did not find trials that, using amikacin and
gentamicin to treat pulmonary exacerbations in cystic fibrosis, could be
considered for this meta-analysis. Both drugs are very useful, even today,
for that pathology in some countries like, for instance, France and
Argentina. We should study the utility to including this sort of patients,
with so different pharmacokinetic parameters in these narrow therapeutic
range drugs.
B - Some papers published (but not included in meta-analysis
referred) used amikacin 35 mg/kg/day ODD, obtaining extremely high peaks
(85 - 150 mcg/mL). But these studies have not been actualized or
replicated again, so we do not know if those levels are sure, although
they could be clinically effective. (2) (3)
C - On the other hand, our experience show us that traditional dose
schemes can underdosage, which can be complicated for infectological
treatment, in the long term.
For those reasons we suggest to be cautious when CF patients are
included in this sort of meta-analysis because it can generate the use of
aminoglycoside ODD and, at this time, it could be dangerous, at least with
lack of evidence published. (4)
Very well designed clinical trials are needed to conclude if ODD can
be useful and sure in this pediatric CF patients.
References:
1 - Hoffman et al. Aminoglycoside antibiotics induce bacterial
biofilm formation. Nature. 2005 Aug 25;436(7054):1171-5.
2 - Canis F et al Pharmacokinetics and bronchial diffusion of single
daily dose amikacin in cystic fibrosis patients. J Antimicrob Chemother
1997 Mar;39(3):431-3
3 - Vic P et al. Tolerance, pharmacokinetics and efficacy of once
daily amikacin for treatment of Pseudomonas aeruginosa pulmonary
exacerbations in cystic fibrosis patients. Eur J Pediatr 1996
Nov;155(11):948-53
4 - Castaños C et al. Ensayo piloto sobre evaluación farmacocinética
y estimación de dosis de amikacina en fibrosis quística. Congreso
Argentino de Neumonología 2005. Sociedad Argentina de Pediatría. Trabajo
Libre D028.
http://www.sap.org.ar/staticfiles/actividades/congresos/congre2005/neumo/tl_neumo.pdf
Conflict of Interest:
None declared
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