Successful use of higher-than-recommended dosage of imipenem in Pseudomonas aeruginosa endocarditis

OBJECTIVE: To report a case of Pseudomonas aeruginosa endocarditis that was successfully treated with high-dose imipenem/cilastatin and to discuss dosage modification based on individual pharmacokinetic parameters. DATA SOURCES: Clinical studies, review articles, and relevant laboratory and pharmacokinetic information. CASE SUMMARY: A 27-year-old man with right-sided P. aeruginosa endocarditis was successfully treated with long-term imipenem/cilastatin and tobramycin. The imipenem dose required to achieve therapeutic serum concentrations and cidal activity was 6 g/d. The manufacturer's recommended maximum dose is 4.0 g/d or 50 mg/kg/d. Because of the patient's large apparent volume of distribution, low serum imipenem concentrations, and lack of serum cidal activity, the clinical decision was made to increase the dose to 6 g/d or 54 mg/kg/d. Treatment was tolerated for seven weeks without any adverse effects. The patient remains free of symptoms 24 months after the diagnosis. CONCLUSIONS: Careful and discriminate use of larger-than-recommended doses of imipenem may be indicated in certain clinical situations. Dosage may need to be adjusted to body size in order to obtain optimal serum concentrations and activity.