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WASHINGTON- (Nov. 6, 2018) -The majority of patients with cystic fibrosis may not achieve blood concentrations of antibiotics at the cause of pulmonary exacerbations, leading to worsening pulmonary function, National Health System. Additionally, the study findings show that it is impossible to predict which dosing regimens which patients will achieve therapeutically significant antibiotic concentrations in their blood.
The findings, published online in the Journal of Pediatric Pharmacology and Therapeuticssuggest that close monitoring blood pressure antibiotic concentrations could prove key to improving clinical outcomes.
Cystic fibrosis, a genetic condition that affects about 70,000 people worldwide, is characterized by a buildup of thick, sticky mucus in patients' lungs. There, the mucus traps bacteria, causes patients to develop lungs that progressively damage these vital organs and odd patients' ability to breathe.
These infections, which cause a host of symptoms of pulmonary exacerbations, are typically treated with a combination of at least two antibiotics with unique mechanisms. One of these drugs is typically a beta-lactam antibiotic, a member of a family of antibiotics that includes penicillin derivatives, cephalosporins, monobactams and carbapenems.
Beta-lactam antibiotics are time-dependent in their bactericidal activity. Their concentrations must exceed a minimum inhibitory concentration for a certain period. However, Andrea Hahn, M.D., MS, an infectious disease specialist at Children's National, blood concentrations of Beta-lactam antibiotics are not typically tracked while patients receive them.
Since antibiotic dosing often does not correlate with cystic fibrosis patients' clinical outcomes, Dr. Hahn and colleagues examine whether patients actually achieved serum antibiotic concentrations that are therapeutically effective.
The researchers collected data from 19 patients at Children's Cystic Fibrosis Center. For each patient,
When they were at the clinic for a well-visit
At the beginning of an acute pulmonary exacerbation that required intravenous antibiotic therapy
After treating that acute pulmonary exacerbation
More than 30 days after the patient completed the treatment course.
The researchers also checked plasma drug concentrations of beta-lactam antibiotics during each patient's treatment course. They collected samples at a minimum of four time points:
A trough of less than 30 minutes before a dose
A peak one hour after a dose was infused
A sample of three hours after the dose was infused
A repeat trough less than 30 minutes before another dose.
In addition, all patients underwent pulmonary function tests at the start of their exacerbations.
Using these data points, the researchers made a model to determine which patients had achieved therapeutic concentrations. They then correlated these findings with the results of patients' pulmonary function tests. Just 47 percent of patients had achieved therapeutic concentrations. Those who achieved significant improvement in their pulmonary function compared with patients who did not.
Paradoxically, they discovered that antibiotic doses, some patients had caused high serum antibiotic concentrations while others did not.
Dr. Hahn notes that real-time monitoring of antibiotic blood concentrations could help patients stay on top of whether patients are being adequately dosed. The research team is investigating this in a new study.
Another way to ensure that patients receive therapeutically meaningful levels of antibiotics is to develop new variables such as age, gender, and creatinine clearance – a measure of kidney function that can be a predictable predictor of metabolism – to predict drug pharmacokinetics. Using the findings of this research, Dr. Hahn adds, Children 's National Disease.
"Getting adequate treatment is crucial for getting better," she says. "At Children's National, we are implementing policies to make sure that our patients with cystic fibrosis, infusing new research insights into patients' ongoing clinical care.
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