Cystic fibrosis (CF) patients are stuck between a rock
and a hard place. On one side there's the chronic bacterial
pulmonary infection that spurs on progressive lung damage.
On the other, the thrice-daily diet of aminoglycoside
antibiotics that can quell the infection, but only at
the expense of kidney damage and hearing loss. A study
published in the February 12 issue of The Lancet
softens the blow and details a more moderate approach.
It shows that antibiotic treatment is just as effective
and does less harm when administered only once a day.
The double-blind study involved
219 CF patients — 125 were children. The patients
were randomly picked to get a 30-minute IV infusion
of the antibiotic tobramycin in combination with ceftazidime
either once a day or thrice daily for 14 consecutive
days.
Volume of air forcefully expired
in one second (FEV1) was used to gauge lung function.
These measurements were expressed as a percentage of
the predicted normal value for a given patient's age,
sex and height.
The researchers, headed by Dr Alan
Smyth of the University of Nottingham and Nottingham
City Hospital, found lung function was similarly affected
by the once- or thrice-daily drug treatments. Mean change
in FEV1 was 10.4% and 10% for the once-daily crowd and
the thrice-daily folks, respectively. Moreover, the
mean change in FEV1 from baseline values was similar
for the once-daily treatment (21.9%) and three-times-daily
treatment (22.1%).
KIND
TO THE KIDNEYS
Best of all, those lucky once-a-day folks had markedly
less kidney perturbation, as measured by creatinine
change. "In children, we saw about a 4% fall in creatinine
after 14 days of treatment, compared to baseline, with
once daily. We saw a 4% rise with three times daily,"
says Dr Smyth.
"If this rise were sustained until
the next course of treatment and if it were cumulative
then we might see longterm toxicity," he cautions. "We
are aware of a number of patients with CF who have developed
acute renal failure on aminoglycosides, so this isn't
just a theoretical risk."
The researchers hope that their
findings will affect clinical practice. Indeed, they
say in their study that "once daily treatment may be
preferred by patients receiving intravenous antibiotics
because of its convenience."
But Dr Smyth's optimistic view
may not materialize overnight. The multi-application
strategy for tobramycin aims to keep the effective levels
of the drugs lethal for bacteria as less aggressive
treatment may help spawn resistance - a highly undesirable
effect.
Lancet Feb 12, 2005;365(9459):573-8
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