Pseudomonas aeruginosa

Pseudomonas aeruginosa NVE is a rare disease which usually affects right-sided heart valves in IVDUs [52,322] and is further discussed in chapter 3. Left-sided P. aeruginosa NVE in non-IVDUs has also been described [323]. The major risk factors identified were underlying valvular heart disease, hemodialysis, cardiac catheteriza-tion/ surgery, gastrointestinal and genitourinary tract procedures. Left-sided disease is characterized by an aggressive infection poorly responsive to antimicrobial therapy and is associated with mortality rates higher than isolated right-sided involvement [52]. Treatment failure may be attributed to the lack of correlation between in vitro and in vivo susceptibilities (e.g., as a result of biofilm formation), extremely large numbers of organisms present in infected vegetations, the phenotypic heterogeneity of the pathogen, and the frequent development of resistance on therapy [324-326]. In the absence of randomized controlled studies, but on the basis of clinical experience, the suggested management of left-sided P. aeruginosa endocarditis consists of immediate valve replacement, accompanied by a six-week course of high-dose, combined (P-lactam plus aminoglycoside) antimicrobial therapy [327]. The AHA recommends high-dose tobramycin (8 mg/kg/day IV in once-daily doses), with maintenance of peak and trough concentrations of 15-20 |g/mL and < 2 |g/mL, respectively, in combination with either an extended-spectrum penicillin (e.g., ticarcillin, piperacillin) or ceftazidime or cefepime in full doses [52]. Carbapenems, however, have rapid bactericidal action against P. aeruginosa [326], with low intrinsic resistance rates [328]. Thus, they may be potentially considered in place of an extended-spectrum penicillin, in combination with an aminoglyco-side. It should be mentioned, however, that the use of combination anti-pseudomonal therapy remains controversial. In the setting of suspected infection by P. aeruginosa, the use of more than one drug empirically is desirable to assure susceptibility to at least one antimicrobial agent. However, once susceptibility-testing results are available, it is unclear if combination therapy remains necessary, provided that pharmacokinetic parameters are optimized. Although there is no adequately powered, direct study of the effect of combination therapy on P. aeruginosa endocarditis, a recent meta-analy-sis favored the use of combination therapy for P. aeruginosa bacteremia, with an approximately 50% mortality reduction [329]. The authors caution, however, that the studies in the systematic review varied considerably in the types of antimicrobial used and there was considerable clinical heterogeneity.

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