Renal function declines with age and dosage of drugs that are renally excreted– such as levofloxacin–should be administered in doses appropriate to specific patient subgroups.   Current dosage recommendations are based on a creatinine clearance of >50mL/min, and adjustments should be considered in those with reduced function, particularly elderly patients with renal disease. However, creatinine clearance measurement is not always available, and therefore dosage should be based on expected age-specific renal function.

To help clarify appropriate dosage in acutely hospitalized older patients treated with levofloxacin, researchers conducted a large, retrospective pharmacokinetic (PK) and pharmacodynamic (PD) study. Analysis identified the cutoff 24-hour area under the concentration-time curve (AUC24)/MIC ratio that best correlated with clinical outcome. Researchers then calculated the probability of attaining this value against different pathogens (PTA).

168 patients were enrolled, with trough (330) and peak (239) levels measured. Levofloxacin was administered in doses ranging from 500mg every 2 days, to a maximum of 500mg twice day.

Results confirmed that creatinine clearance (CrCL) was the only factor associated with a better model fit, and cutoff AUC24/MIC ratio (≥95.7) was the only factor that correlated with a favorable clinical outcome. In regard to PTA, optimal values were reported against E. coli and H. influenzae, borderline against S. aureus, and suboptimal against P. aeruginosa. The researchers concluded that levofloxacin doses used in the study were effective for treating pathogens with an MIC of ≤0.5 mg/liter in older patients with various degrees of renal function.  It is also expected that using optimal doses based on expected renal function will reduce any unwanted toxicity.

PMID: 28031199

Antimicrob Agents Chemother. 2017 Feb 23;61(3). pii: e02134-16. doi: 10.1128/AAC.02134-16.

Source: https://www.ncbi.nlm.nih.gov /pubmed/28031199?dopt=Abstract