• Milagros P Reyes, Ammar Ali, Rodrigo E Mendes, and Douglas J Biedenbach.
• Division of Infectious Diseases, Harper University Hospital, 3990 John R., Detroit, MI 48201, USA. mreyes@med.wayne.edu
• Medicine (Baltimore). 2009 Sep 1;88(5):294-301.

AbstractA resurgence of endocarditis due to Pseudomonas aeruginosa was seen in 10 injection drug users (IDUs) in Detroit between 2006 and 2008 (6 men, 4 women; mean age, 48.1 yr). All patients tested negative for the human immunodeficiency virus (HIV). Five patients had left-sided endocarditis of the mitral valve and/or the aortic valve; 3 of 5 patients had prosthetic valve endocarditis. Four of 10 patients had right-sided endocarditis of the tricuspid valve alone. One patient had bilateral involvement of the aortic and tricuspid valves. Nine patients had Pseudomonas endocarditis (PsE); 1 patient had mixed endocarditis with P. aeruginosa and Candida parapsilosis. Seven of 10 patients were treated with a combination of intravenous cefepime, 4-6 g/d, plus high-dose tobramycin (HDT) for at least 6 weeks. Tobramycin, 8 mg/kg per day, was given as a single daily dose intravenously, aiming for peak serum levels of 18-22 microg/mL and trough levels of <1 microg/mL. The patient with mixed endocarditis was also treated with fluconazole. Two patients initially treated with other antipseudomonal regimens, including cefepime alone and piperacillin/tazobactam plus tobramycin, failed treatment and were switched to cefepime and HDT. A third patient was switched to cefepime and ciprofloxacin because of nephrotoxicity. Two patients developed nephrotoxicity to tobramycin; 1 patient developed ototoxicity. The overall medical cure rate for both left-sided and right-sided disease was 80% (4/5). All 5 patients who required surgery survived (5/5; 100%). Overall outcome was 90% (9/10). Indications for valve replacement were recurrent Pseudomonas bacteremia (n = 3), recurrent bacteremia and congestive heart failure (n = 1), and persistent bacteremia and fungemia (n = 1). Tricuspid valvulectomy with valve replacement was successful in 2 patients and in a third patient who had successful replacement of both the tricuspid and the aortic valve for recurrent bacteremia and congestive heart failure. Two patients with pure left-sided prosthetic valve endocarditis underwent successful repeat valve replacements. Although this is a small series, the overall mortality rate (1/10; 10%) was low. The patient who did not survive had left-sided involvement of the aortic valve and could not undergo surgery because of a large embolic cerebral infarct. The mortality rate of left-sided disease in the current series was 16.7% (1/6 including the patient with tricuspid and aortic valve PsE) compared to 60% in a series of 15 patients reported in 1990.Our current antimicrobial regimen for PsE consists of a combination of cefepime, 6 g/d, in 3 divided doses, plus HDT, 8 mg/kg per day, given as a single daily dose for 6 weeks. For cefepime-resistant Pseudomonas, imipenem, 4-6 g/d, or meropenem, 6 g/d, plus HDT has been successful. For right-sided disease refractory to medical therapy, surgical intervention is recommended if Pseudomonas bacteremia persists for 2 weeks on appropriate antimicrobial therapy or if bacteremia recurs after a 6-week course of treatment. Tricuspid repair/reconstruction or valvulectomy with valve replacement plus combined antipseudomonal regimen may be the optimal therapy for refractory right-sided endocarditis. This approach not only may prevent the development of severe and permanent impairment of right ventricular function, which is a complication of valvulectomy alone without valve replacement, but also may cure the infection. For left-sided disease, surgery is recommended if blood cultures remain positive for 7 days on appropriate antimicrobial therapy or if Pseudomonas bacteremia recurs after completion of a 6-week course of the combined regimen.

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