Insufficient Antibiotic Therapy for Patients With Cystic Fibrosis: A Study

Washington DC – It turns out that the majority of patients with cystic fibrosis may not reach a high enough blood concentration of antibiotics to effectively fight the bacteria responsible for pulmonary exacerbations resulting in deterioration of lung function.

Cystic fibrosis, a genetic disorder affecting approximately 70,000 people worldwide, is characterized by thick, sticky mucus build-up in patients' lungs. There, the mucus traps bacteria, causing patients to develop frequent lung infections that progressively damage these vital organs and impair their ability to breathe.

A recent study by researchers from the National Child Health System shows that it is impossible to predict only from dosing regimens patients who will reach therapeutically significant antibiotic concentrations in their blood. The results were published online in the Journal of Pediatric Pharmacology and Therapeutics

. These infections, which cause a host of symptoms collectively called pulmonary exacerbations, are usually treated with a combination of at least two antibiotics with unique mechanisms. One of these drugs is usually a beta-lactam antibiotic, a member of a family of antibiotics including penicillin derivatives, cephalosporins, monobactams and carbapenems.

Although all antibiotics have a minimal threshold of concentration required to treat infections, beta-lactam antibiotics are time-dependent in their bactericidal activity. Their concentrations must exceed a minimum inhibitory concentration for a certain period. However, the study's lead author, Andrea Hahn, explained that blood levels of beta-lactam antibiotics are usually not monitored while patients receive them.

Since the dosage of antibiotics often does not match the clinical results of the investigators examined whether patients had actually achieved serum concentrations of therapeutically effective antibiotics

. Furthermore, all patients had experienced pulmonary function tests at the beginning of their exacerbations and about once a week until the end of their antibiotic treatment.

Using data points, researchers constructed a model to determine which patients had reached therapeutic concentrations for bacteria present in their respiratory secretions. They then correlated these results with the results of pulmonary function tests of patients. Only 47% of patients had reached therapeutic concentrations. Those who had achieved significantly higher antibiotic exposure had further improved their lung function tests compared to unaffected patients.

Paradoxically, they discovered that even though each patient was receiving the recommended doses, some patients had serum levels of antibiotics high enough,

Another way to ensure that patients receive Therapeutically significant antibiotic levels involves developing new models incorporating variables such as age, bad, and creatinine clearance – a measure of renal function that can be a valuable predictor of metabolism– predicting the pharmacokinetics of drugs

Based on the results of this research, Dr. Hahn adds that Children's National has already implemented an algorithm using different variables to determine the dosage of antibiotics in patients treated at the hospital.

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