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Critically ill patients may not be receiving enough antibiotics
Recent data suggest that patients who are critically ill with infections may not be receiving adequate antibiotic exposure and are having adverse outcomes as a result.
“”We have shown on a large scale that current beta-lactam antibiotic dosing in critically ill patients does not consistently achieve therapeutic drug exposures,” Jason A. Roberts, PhD, BPharm, associate professor in the school of medicine at the University of Queensland in Brisbane, Australia, told Infectious Disease News. “Not only are there many patients with low concentrations who are 30% less likely to have a positive clinical outcome, but there are many that also have high and potentially toxic concentrations.”
Jason A. Roberts
Roberts and colleagues conducted the Defining Antibiotic Levels in Intensive care patients (DALI) study, a prospective, multinational pharmacokinetic point-prevalence study. Eight beta-lactam antibiotics were studied: amoxicillin, ampicillin, cefazolin, cefepime, ceftriaxone, doripenem, meropenem and piperacillin. The researchers identified 361 evaluable patients who were treated with one of these antibiotics. Each patient provided a mid-dose blood sample halfway through the dosing interval and a pre-dose blood sample at the end of a dosing interval.
The clinical cure rate was 66.5%. The total infection-related mortality was 8.9%. Among the 248 patients receiving antibiotics for an infection, 67% were given treatment by intermittent bolus dosing and 33% received prolonged infusion. Among those who received intermittent bolus dosing, 20% did not achieve concentrations above the minimum inhibitory concentrations (MICs) for 50% of the dosing interval, which is the minimum accepted antibiotic exposure, compared with 7% of those who received prolonged infusions.
Overall, 16% of the 248 patients did not reach the 50% dosing interval exposure time and these patients were 32% less likely to have a positive clinical outcome (OR=0.68; 95% CI, 0.52-0.91). The predictive value for a positive clinical outcome was similar using a concentration at 50% of the dosing interval and at 100% of the dosing interval.
“Given that current dosing regimens of antibiotics are derived from studies performed in non-critically ill patients where drug disposition is much different than in critically ill patients, it is unsurprising that those doses are not sufficient in the ICU,” Roberts said. “The data support a more personalized approach to beta-lactam dosing in critically ill patients, so that antibiotic exposures associated with clinical success are more consistently achieved.”
Roberts said that the results of this study should encourage clinicians to be more aware of the effects on antibiotic dosing requirements of augmented renal clearance, extracorporeal therapies, obesity and sickness severity. He said that future studies should evaluate ways to ensure patients achieve therapeutic antibiotic exposure and whether it will be possible to reduce the emergence of antibiotic resistance through dose optimization. — by Emily Shafer
Jason Roberts, PhD, B Pharm, can be reached at: Pharmacy department, Level 1 Ned Hanlon Building, Royal Brisbane and Women’s Hospital, Butterfield St., Herston, Queensland, Australia 4029; email: j.roberts2@uq.edu.au.
Disclosure: The researchers report no relevant financial disclosures.