Antibiotic Article

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HEADLINE: Advantage to meropenem combo therapy for CF exacerbations:

effect not sustained long term; Women's Health; cystic fibrosis BYLINE:

Jancin, Bruce

The combination of meropenem and tobramycin was superior to ceftazidime

and tobramycin in treating acute pulmonary exacerbations of cystic

fibrosis, Dr. L. Blumer reported at the annual Interscience

Conference on Antimicrobial Agents and Chemotherapy.

The advantages, however, were confined to the short term. There was no

significant difference between the two combinations with regard to the

rate of additional exacerbations during the subsequent year, according

to Dr. Blumer, professor of pediatrics at Case Western Reserve

University, Cleveland.

One hundred two patients aged 5 years and up with acute pulmonary

exacerbations of cystic fibrosis due to meropenemand

ceftazidime-sensitive Pseudomonas aeruginosa were randomized to 14 days

of meropenem plus tobramycin or to ceftazidime plus tobramycin. Nineteen

additional patients with Burkholderia cepacia infection or

ceftazidime-resistant P. aeruginosa received open-label meropenem plus

tobramycin.

The proportion of patients with a satisfactory improvement in pulmonary

function on day 7 of treatment, as defined by at least a 15% gain in

forced expiratory volume in 1 second ([FEV.sub.1]), was 62% in patients

randomized to meropenem and tobramycin, compared with 44% in the

cefrazidime/tobramycin group. Median time to a satisfactory gain in

pulmonary function was 4 days in the meropenem arm and 6 days in the

ceftazidime arm.

At the end of treatment, those patients in the meropenem group showed a

mean 38.8% improvement in [FEV.sub.1], compared with baseline, while

those on ceftazidime had a mean 29.4% improvement.

Clinical response, as assessed by a standardized acute change score,

showed a mean 49.5% improvement in the meropenem group after 14 days of

therapy, which wasn't significantly different than the mean 55.6%

improvement in the ceftazidime arm. The score was comprised of six

domains: appetite, activity, weight loss, resting respiratory effort,

cough, as well as chest examination.

The two regimens also showed comparable significant reductions in sputum

bacterial burden, added Dr. Blumer, who is also director of the division

of pharmacology and critical care and director of the 'pediatric ICU at

Rainbow Babies and Children's Hospital in Cleveland.

Thirty-eight of 52 (73%) patients randomized to ceftazidime had an acute

exacerbation during 1 year of follow-up, as did 33 of 50 (66%) on

meropenem. There was no statistical difference between the two groups in

time to exacerbation.

In patients with infection due to B. cepacia or ceftazidime-resistant P.

aeruginosa, 2 weeks of open-label meropenem / tobramycin produced a mean

45.5% reduction in acute change score as well as a significant reduction

in sputum bacterial burden. However, it didn't result in significant

improvement in [FEV.sub.1], compared with baseline, he said at the

conference, sponsored by the American Society for Microbiology.

Only two patients in each arm of the randomized trial discontinued

therapy because of a drug-related adverse event.

Limited emergence of bacterial resistance was seen during treatment,

with isolates from only 1.3% of meropenem-treated patients and 3.2% of

ceftazidime-treated patients showing a fourfold rise in minimal

inhibitory concentration after 14 days of therapy. During the follow-up

period, however, these rates climbed to 12.9% and 22.8%, respectively.

Dr. Blumer explained that cystic fibrosis patients have a high rate of

chronic pulmonary colonization by non-fermenting gram-negative bacteria.

These bacteria can't be eradicated on a long-term basis using

anti-microbial therapy.

Indeed, the major cause of death in patients with cystic fibrosis is

progressive respiratory failure caused by repeated bacterial infections.

Dosing in the AstraZeneca-sponsored study consisted of intravenous

meropenem at 40 mg/kg up to 2 g every 8 hours; intravenous cefrazidime

at 50 mg/kg up to 2 g every 8 hours; and tobramycin titrated on the

basis of serum concentration monitoring.

Becki

Life is not measured by the number of breaths we take, but by the moments

that take our breath away.

Listed for Lungs 1/14/04

at

Mayo Clinic ville,Fla.

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